SlideShare ist ein Scribd-Unternehmen logo
1 von 9
Downloaden Sie, um offline zu lesen
Original Articles




    An Immunohistochemical Panel to Differentiate
Metastatic Breast Carcinoma to Skin From Primary Sweat
  Gland Carcinomas With a Review of the Literature
Marian Rollins-Raval, MD, MPH; Mamatha Chivukula, MD; George C. Tseng, ScD; Drazen Jukic, MD, PhD; David J. Dabbs, MD

N Context.—Approximatelymetastases. Sweat gland breast
cancer develop cutaneous
                         25% of patients with
                                                carci-
                                                                            neoplasm cases, and 2 primary breast cancer cases were
                                                                            retrieved and analyzed with the following IHC panel:
nomas (SGCs) account for about 0.05% of all cutaneous                       mammaglobin, gross cystic disease fluid protein (GCDFP)
neoplasms. Cutaneous metastases of breast carcinoma                         15, p63, basal cytokeratins (CK5, CK14, and CK17),
(CMBCs) (especially the ductal type) can be difficult to                    androgen receptor, and PAX5.
distinguish from SGCs. Treatment and prognoses for these                      Results.—The p63 was only weakly expressed in 1 of 12
2 types of tumors differ radically, making accurate                         CMBC cases (8.3%), whereas it was strongly expressed in
histologic diagnosis crucial. Although a few studies attempt                10 of 11 SGC cases (90.9%) (P , .001). Basal cytokeratins
to differentiate these entities employing immunohisto-                      demonstrated a similar immunoprofile in the SGC group,
chemical (IHC) studies (some of which we review here), to                   with 10 of 11 cases (90.9%) expressing all 3 markers, and a
date, no panel of IHC stains exists, to our knowledge, to                   variable immunoprofile in the CMBC group with 0%
distinguish these entities.                                                 (CK14) (P , .001) to 16.7% (2 of 12 cases; CK5 and CK17)
  Objective.—To devise a panel of IHC stains to distin-                     (P , .001) expression. Mammaglobin was expressed in 8 of
guish CMBC from SGC.                                                        12 cases (66.7%) of CMBC.
  Design.—Twelve cases of ductal CMBCs (11 not                                Conclusions.—Together, these 5 IHC stains were com-
otherwise specified type, and 1 basal phenotype), 11 cases                  bined to make a panel that was 100% sensitive and 91%
of SGCs (5 eccrine carcinomas, 3 porocarcinomas, and 3                      specific in distinguishing between CMBC and SGC.
microcystic adnexal carcinomas), 2 benign sweat gland                         (Arch Pathol Lab Med. 2011;135:975–983)


Approximately accountmetastases. Sweat gland carci-
               25% of patients with breast cancer may
   develop cutaneous
nomas (SGCs)
                                             1,2

                       for 0.05% of all cutaneous
                                                                            reports continue to demonstrate this potential diagnostic
                                                                            pitfall.4,5 We recently received 2 diagnostically challenging
                                                                            cases presenting similar challenges.
neoplasms.3 Clinically, the presentation of these 2 entities
is often distinct. Ductal cutaneous metastases of breast
carcinoma (CMBCs) present as multiple lesions in patients
with a previous diagnosis of primary breast carcinoma
(PBC), whereas SGC presents as a single cutaneous lesion
in patients with no known history of breast cancer.
However, CMBCs can be difficult to distinguish from
SGCs histologically, and complex clinical circumstances
can further complicate a diagnosis. Several recent case



   Accepted for publication October 12, 2010.
   From the Department of Pathology, University of Pittsburgh Medical
Center, Pittsburgh, Pennsylvania (Drs Rollins-Raval, Chivukula, Jukic,
and Dabbs); and the Department of Biostatistics, University of Pittsburgh
(Dr Tseng). Dr Jukic is now with the Division of Dermatopathology,
Department of Pathology and Laboratory Medicine, James A. Haley
Veterans’ Hospital, Tampa, Florida.
   The authors have no relevant financial interest in the products or
companies described in this article.
   Presented in part at the annual meeting of the United States and
Canadian Academy of Pathology, Denver, Colorado, March 5, 2008.             Figure 1. Eccrine carcinoma ex spiradenocylindroma with inset
   Reprints: Marian Rollins-Raval, MD, MPH, Department of Pathology,        showing the eccrine carcinoma ex spiradenocylindroma at higher
University of Pittsburgh Medical Center, A711 Scaife Hall, 3550 Terrace     power (hematoxylin-eosin, original magnifications 3100 and 3400
St, Pittsburgh, PA 15261 (e-mail: rollinsravalma@upmc.edu).                 [inset]).

Arch Pathol Lab Med—Vol 135, August 2011                                             IHC Panel of CMBC Versus SGC—Rollins-Raval et al   975
Figure 2. Infiltrating carcinoma shown with hematoxylin-eosin stain (A), as well as immunohistochemical stains for p63 (B), AE1/AE3 (C), CK5/6
(D), epithelial membrane antigen (E), and CK7 (F) (original magnifications 3200).


                              Case 1                                     7 years after her bilateral mastectomies. Although the
                                                                         morphology of the PBC and the skin lesions was similar,
  A 75-year-old woman with a history of bilateral                        immunohistochemical (IHC) studies were performed on
mastectomies for infiltrating ductal carcinoma of both                   all lesions. For the right PBC, the tumor cells demonstrat-
breasts, colectomy for carcinoma of the rectum, and                      ed strong positivity for cytokeratin (CK) 7, estrogen
hysterectomy with bilateral salpingo-oophorectomy for                    receptor (ER), and ERBB2 (formerly HER2/neu) and focal
benign disease presented with skin lesions on her back                   positivity for progesterone receptor (PR). For the left PBC,
976   Arch Pathol Lab Med—Vol 135, August 2011                                           IHC Panel of CMBC Versus SGC—Rollins-Raval et al
Table 1. Demographics of Cutaneous Metastatic                                   in Figures 2, B through F, respectively), and were negative
      Breast Carcinoma (CMBC) and Sweat Gland Carcinoma                                 for S100, ER, PR, CK20, GCDFP-15, and mammaglobin.
                         (SGC) Cases                                                    Based on this information alone, it was unclear whether
                                                               Mean Age
                                                                                        the lesion was a CMBC or an SGC, making the devel-
    Case Group          No. of Cases     % Female            (Age Range), y             opment of a treatment plan difficult.
                                                                                           As the treatment and prognosis for CMBC and SGC
      PBC                    2            100                 68    (53–83)
      CMBC                  12            100                 57    (40–80)a
                                                                                        differ significantly, developing a panel of IHC markers to
      BAN                    2             50                48.5   (34–63)             differentiate these 2 entities would be of high clinical
      SGC                   11             58.3              73.6   (49–93)             value. Numerous studies have evaluated these entities
Abbreviations: BAN, benign adnexal neoplasm; PBC, primary breast
                                                                                        either individually6–15 or comparatively using various
carcinoma.                                                                              (IHC) stains,16–23 but there has been no study, to our
a
    Age at presentation of metastatic lesion, not primary breast lesion.
                                                                                        knowledge, to determine the most useful IHC panel for
                                                                                        differentiating CMBC from SGC.
                                                                                           Several IHC stains have shown promise in their ability
the tumor cells were strongly positive for CK7, ER, and PR.                             to differentiate CMBC and SGC. Mammaglobin, a protein
Both PBCs were negative for CK903, S100, cross cystic fluid                             frequently overexpressed in breast cancer,11 has not been
protein–15 (GCDFP-15), and CK20. On hematoxylin-eosin                                   thoroughly examined in either CMBC or SGC. GCDFP-15,
stain, the skin lesion, which demonstrated areas of tight                               a glycoprotein originally isolated in human breast gross
intermingling between carcinoma and a spiradenocylin-                                   cystic fluid, although present in most primary and
droma, was more compatible with a malignant neoplasm                                    metastatic breast cancers, has also been reported to be
arising in the background of a benign mixed tumor rather                                expressed in a few cases of SGC.16,24 Androgen receptor
than metastasis to the benign tumor (Figure 1). In the                                  (AR), although often found in high-grade invasive breast
benign component, CK7 was positive only in the internal                                 cancer, has also been identified in some SGCs.7–9,13
mature cells and negative in basal cells, ERBB2 demon-                                     The basal cytokeratin stains (CK5, CK14, and CK17),
strated weak and less than 1+ positivity, and CK903 was                                 recently shown to be expressed in the basal phenotype of
strongly positive. CK20, ER, PR, and S100 were all negative                             breast carcinoma, were not present in most other types of
in the tumor cells. In the malignant component, CK903 was                               PBC.25,26 These stains have also been shown to be present
strongly positive, whereas CK7 and S100 were focally                                    in a few SGC cases.14,19,20 However, with the exception of
positive. CK20, GCDFP-15, ER, PR, and ERBB2 were all                                    CMBC with a basal phenotype, these markers are more
negative. Although these findings supported the diag-                                   likely to be seen in SGC; p63, a homologue of the p53 gene
nosis of a primary eccrine carcinoma (EC) arising in a                                  and expressed primarily by basal and myoepithelial cells
spiradenocylindroma, the possibility of a CMBC to the                                   of the skin, would be more likely to be seen in cases of SGC
benign neoplasm could not be ruled out. Molecular studies                               than in cases of CMBC.10,21,22
performed on the paraffin-embedded tissues showed                                          In addition, 1 of the authors (M.R.-R.) noticed a strong
multiple allelic losses in the PBC and no genetic alterations                           cytoplasmic and/or membranous staining with PAX5, a
in the EC. The patient subsequently developed additional                                B-cell–specific activator protein of the basal layer of
metastases to lymph nodes and additional skin sites from                                healthy epithelium, in an unrelated research study and
the EC. Although a definitive diagnosis was rendered in                                 decided to use the antibody in the current study,
this case, a simplified IHC panel would have benefited                                  hypothesizing that the staining pattern might be similar
both the pathologist and patient.                                                       in SGC. The PAX5 expression has been previously studied
                                                                                        in B lymphocytes, in most small cell carcinomas, and in
                           Case 2                                                       Merkel cell carcinomas.27,28
  An 84-year-old woman with a history of bilateral PBC                                     The goal of this study was to construct a panel of IHC
20 years earlier presented with a skin lesion of the right                              stains that would be highly sensitive and specific in
breast. The morphology of the previous PBC was not                                      distinguishing these 2 morphologically similar entities.
consistent with the new skin lesion, which showed an
infiltrating carcinoma (Figure 2, A). Numerous IHC stains                                              MATERIALS AND METHODS
were performed with the following results: the tumor cells                                                 Literature Review
were positive for p63, AE1/AE3, CK5/6, and epithelial                                    A MEDLINE (US National Library of Medicine, Bethesda,
membrane antigen, were focally positive for CK7 (shown                                  Maryland) search was performed from 1995 to 2009 to identify

                                            Table 2.         Immunohistochemistry Antibody Information
                    a
         Antibody                Clone            Dilution                     Vendor                    Location                Pretreatment
      GCDFP                23A3                   1:25               Vector Labs                Burlingame, California     CC1b mild and standard
      AR                   AR441                  1:100              Dako North America         Carpinteria, California    CC1 mild and standard
      Mammaglobin          304-1A5 and 31A5       Predilute          Zeta Corporation           Sierra Madre, California   CC1 mild
      p63                  4A4                    1:200              Neomarkers Inc             Fremont, California        CC1 mild and standard
      PAX5                 24                     1:25               BD Biosciences             San Jose, California       CC1 mild and standard
      CK5                  XM26                   1:25               Novocastra                 Newcastle Upon Tyne,       CC1 standard
                                                                       Laboratories Ltd           United Kingdom
      CK14                 LL002                  Predilute          Ventana Medical            Tucson, Arizona            CC1 standard
                                                                       Systems Inc
      CK17                 E3                     1:20               Dako North America         Carpinteria, California    CC1 mild and protease 3
a
  All immunostains were performed on the BenchMark XT using the iView/DAB detection system (Ventana Medical Systems, Tucson, Arizona).
b
  Ventana Medical Systems, Tucson, Arizona.

Arch Pathol Lab Med—Vol 135, August 2011                                                        IHC Panel of CMBC Versus SGC—Rollins-Raval et al     977
Table 3.    Comparative Review of Additional Similar Studies and the Immunohistochemical Results
              Study             Wallace et al,16 1995    Wick et al,17 1998                 Busam et al,18 1999                 Plumb et al,19 2004
                                                               a           b
         IHC Marker              MAC        CMBC          EC         PBC          MAC         PC          EC        CMBC        MAC        CMBCc
   ER                             2/8        1/15         9/27      31/59         2/8         0/4        2/13       10/30
   PR                             5/8       15/15          1/4      27/59         2/8         0/4        2/13        8/30
   c-erbB-2(HER2/neu)                                     9/27      12/59
   AR
   GCDFP                          1/6         7/15       5/27       41/59
   CEA                                                  21/27        5/59
   EGF-R                                                                          5/8         4/4       11/13        5/30
   CK5/6                                                                                                                         3/3        2/17
   CK5
   CK7
   CK14
   CK17
   CK20
   p63 (nuclear)
   S100                                                 12/27       27/59
   Podoplanin
   PAX5 (C/M)g
   Mammaglobin

Abbreviations: 1A, 1 apocrine case; 1N, 1 not otherwise specified case; AR, androgen receptor; CEA, carcinoembryonic antigen; CK, cytokeratin; C/
M, cytoplasmic/membranous; CMBC, cutaneous metastatic breast carcinoma (ductal); EC, eccrine carcinoma; EGF-R, epidermal growth factor
receptor; ER, estrogen receptor; ES, ex spiradenocylindroma; GCDFP, gross cystic disease fluid protein; IHC, immunohistochemistry; MAC,
microcystic adnexal carcinoma; PBC, primary breast carcinoma; PC, porocarcinoma; PR, progesterone receptor.
a
  In this study, EC refers to 23 eccrine carcinomas, as well as 4 apocrine lesions in the same category that were only separated by their staining for
  GCDFP-15, where 1 of 23 cases of eccrine carcinoma was positive whereas 4 of 4 cases of the apocrine lesions were positive for GCDFP.
b
  These authors looked at primary breast carcinomas as opposed to cutaneous metastases.
c
  There were 6 cases with weak staining, considered negative, for CK5/6.
d
  Of the 3, 1 was mucinous and stained only 1+ for p63 and was thus counted as negative here; the other 2 were strongly positive.
e
  There were 5 cases: 2N, 1A, 2ES.
f
  Two of 3 were graded as 1+.
g
  PAX5 showed a strong C/M staining pattern noted previously in normal epithelium which is reported here.


studies similar to our own, comparing primary SGC to CMBC (or                  paraffin-embedded tissues; and samples were analyzed with the
in 1 study, to PBC) using IHC stains. We selected a panel of 8 IHC             following IHC stains: mammaglobin, GCDFP-15, p63, CK5, CK14,
stains to investigate their staining patterns in CMBC and SGC.                 CK17, AR, and PAX5.
We did not repeat IHC studies that appeared in previous studies                   All IHC stain analysis was performed on the Ventana
to be less useful.                                                             BenchMark, XT (Ventana Medical Systems, Inc, Tucson, Arizona)
                                                                               using the iView DAB Detection System (Ventana Medical) with
                        Case Identification                                    commercially available antibodies according to standard proto-
   A retrospective search for CMBC and SGC cases using a Natural               cols (Table 2). All negative and positive controls demonstrated
Language Search was performed in the University of Pittsburgh                  appropriate immunolabeling.
Medical Center (Pittsburgh, Pennsylvania) CoPath Plus database                    The IHC stain results were semiquantitated as follows: AR,
(Cerner DHT, Inc, Waltham, Massachusetts) for the 9 years from 1998            PAX5, and p63 were nuclear stains, and strong nuclear positivity
to 2007. Based on the results of the database search, 27 cases were            was considered positive staining. The intensity of immunostain-
retrieved from the University of Pittsburgh Medical Center archives            ing was graded as negative (0), weak (1), moderate (2), and
for the study: 12 cases of ductal CMBC (44%), which included 11                strong (3), and the proportion of positive staining cells was
cases with morphologies not otherwise specified and 1 case of basal            recorded as 0% through 5% (1), 6% through 20% (2), 21% through
phenotype; 11 cases of SGC (41%), which included 5 cases of EC, 3              80% (3), and greater than 80% (4).
cases of porocarcinoma (PC), and 3 cases of microcystic adnexal                   Cytoplasmic staining was considered positive for GCDFP-15
carcinoma (MAC); and 4 additional, randomly selected cases (15%),              and mammaglobin, and the intensity of immunostaining was
which included 2 primary cutaneous adnexal benign neoplasms (a                 graded as weak, moderate, or strong.
poroma and an apocrine adenoma) and 2 cases of PBC.                               Basal cytokeratins—CK5, CK14, and CK17—were scored as
                                                                               positive if any cytoplasmic or membranous staining was
                           Demographics                                        observed in the tumor cells.
   The patients in PBC and metastatic breast cancer groups were all               A strong cytoplasmic and/or membranous staining pattern
women, whereas the SGC group consisted of both men and women.                  was considered positive for PAX5.
The mean ages for patients with ductal CMBC and SGC were
57 years and 73.6 years, respectively (Table 1). The difference in ages                               Statistical Analysis
was significantly different. Although all the patients with CMBC (12             A statistical analysis of the positive and negative results was
of 12; 100%) had documented PBCs, only 1 (case 1, described above)             performed with R statistical software 2.10.1 (R Project for
of the 11 patients with SGC (9%) had a history of PBC.                         Statistical Computing, Wien, Austria). The SGCs were all
                                                                               compiled into one group for the statistical analysis. Comparisons
                                                                               of the IHC staining profiles in the CMBC and SGC groups were
                      Immunohistochemistry                                     performed using a z test to calculate the P values for each
  Hematoxylin-eosin slides were reviewed; a representative tumor               IHC stain. Subsequently, a simple computer algorithm was
block was selected; sections were obtained on formalin-fixed,                  created to examine the effectiveness of a combination of
978   Arch Pathol Lab Med—Vol 135, August 2011                                                 IHC Panel of CMBC Versus SGC—Rollins-Raval et al
Table 3.        Extended
                                    20                            22
          Study         Qureshi et al, 2004         Ivan et al, 2005           Liang et al,23 2007                 This Study
                                                              d
      IHC Marker         PC       CMBC        MAC        EC            CMBC    PC         CMBC       MAC     PC            ECe       CMBC
   ER
   PR
   c-erbB-2(HER2/neu)
   AR                                                                                                0/3     2/3     0/5             5/12
   GCDFP                                                                                             0/3     0/3     1/5 (ES)        5/12
   CEA
   EGF-R
   CK5/6                 3/3        0/6
   CK5                                                                                               3/3     3/3     4/5             2/12
   CK7                   2/3f       6/6
   CK14                                                                                              3/3     3/3     4/5             0/12
   CK17                                                                                              3/3     3/3     4/5             2/12
   CK20                  0/3        0/6
   p63 (nuclear)         3/3        0/6       4/4        2/3           0/12                          3/3     3/3     4/5             1/12
   S100
   Podoplanin                                                                  6/6        0/11
   PAX5 (C/M)g                                                                                       3/3     2/3     2/5 (1A + 2N)   0/12
   Mammaglobin                                                                                       0/3     0/3     2/5 (ES)        7/12



the near statistically significant and statistically significant          with CK5/6, with 6 cases (35%) having weak positive
biomarkers.                                                               staining, whereas all 3 MACs (100%) expressed strong
                                                                          positive staining. This difference, although not evaluated
                           RESULTS
                                                                          specifically in the study,19 revealed the diagnostic poten-
                      Literature Review                                   tial of CK5/6 in differentiating these lesions.
   Wallace et al16 investigated the IHC staining character-                  Qureshi et al20 also examined the diagnostic potential of
istics of 15 cases (from 12 patients) of CMBC and                         several IHC stains, including p63, CK5/6, CK7, and CK20,
compared them to a series of primary eccrine tumors,                      to differentiate metastatic carcinomas from primary
including 8 MACs. The authors16 concluded that using                      cutaneous adnexal neoplasms. Several benign adnexal
standard IHC markers, such as ER, PR and GCDFP-15,                        neoplasms as well as malignant neoplasms, such as
would not reliably distinguish these 2 populations.                       hidradenocarcinoma, adenoid cystic carcinoma, seba-
   Wick et al17 examined 59 cases of ductal PBCs and                      ceous carcinoma, digital papillary adenocarcinoma, syr-
compared them with 27 cases of ductal SGC, which were                     ingomatous carcinoma, and mucinous carcinoma, were
further described as demonstrating eccrine morphology                     included in their study.20 Only their examinations of PCs
(23 cases; 85%) and apocrine differentiation (4 cases; 15%).              and CMBCs were included in Table 3. Three cases of PC
Using pancytokeratins, carcinoembryonic antigen, S100                     were all strongly positive for CK5/6 and p63, whereas
protein, GCDFP-15, ER, PR, and c-erbB-2 protein (ERBB2)                   CK7 demonstrated positivity in less that 10% of cells for 2
IHC stains, their findings17 concluded that the infrequency               cases, and CK20 was completely negative in all cases. The
of GCDFP-15 in eccrine sweat gland tumors as well as the                  6 CMBC cases were diffusely positive for CK7 and were
paucity of carcinoembryonic antigen in breast carcinomas                  negative for CK5/6, p63, and CK20. This study20 demon-
could be useful in predefined differential diagnostic                     strated the diagnostic potential of CK5/6 and p63 in
settings involving these 2 entities with the appropriate                  differentiating these 2 entities.
clinicopathologic information provided. We included this                     Ivan et al22 assessed the utility of p63 antibody for
study in our review because of its similarity to the current              differentiating primary cutaneous adnexal neoplasms and
study, even though it focused on distinguishing PBC from                  adenocarcinoma metastatic to the skin. In addition to
SGC, rather than distinguishing CMBC from SGC.                            several benign adnexal tumors, the authors22 analyzed 4
   Busam et al18 studied 30 cases of CMBC compared with                   MACs and 3 ECs (1 of the latter with mucinous
42 primary SGC cases for their expression of ER, PR, and                  differentiation) as well as a case of hidradenocarcinoma
epidermal growth factor receptor (EGFR). Several addi-                    and 2 cases of trichilemmal carcinomas. Of the MACs and
tional histologic types of SGC were examined in this                      ECs, only the ECs with mucinous differentiation were
study,18 including apocrine, hidradenocarcinoma, mucin-                   negative for nuclear positivity of p63, and none of the
ous, and basaloid carcinomas, which were not included in                  CMBCs demonstrated nuclear positivity, confirming the
our study. Only the 3 types of tumors included in our                     usefulness of this marker in distinguishing SGC from
study—MAC, PC, and EC—are presented in Table 3.                           CMBC.
Their results18 suggested that the expression of EGFR may                    Finally, Liang et al23 investigated the use of podoplanin
be diagnostically helpful in differentiating these 2 groups               to differentiate metastases to skin from various organ
of tumors, whereas ER and PR continued to show no                         sites, including the breast, from primary skin adnexal
significant difference between the 2 groups.                              carcinomas. In their study,23 the authors examined 11
   Plumb et al19 used CK5/6 to differentiate primary                      cases of metastatic breast cancer to the skin, all of which
cutaneous adnexal neoplasms, including 3 MACs, from                       (100%) were completely negative for podoplanin. They
cutaneous metastatic lesions, including 17 CMBCs. Only 2                  also examined a total of 40 primary skin adnexal
of 17 CMBC cases (12%) displayed strong positive staining                 carcinomas, only 2 of which (5%; a case of adenoid cystic
Arch Pathol Lab Med—Vol 135, August 2011                                             IHC Panel of CMBC Versus SGC—Rollins-Raval et al   979
Table 4.   Summary of Immunohistochemistry (IHC) Profile Staining Pattern in Cutaneous Metastatic Breast Carcinoma
                                        (CMBC) and Sweat Gland Carcinoma (SGC)
                        Mammaglobin,                                                                                          PAX5 (C/M),b
        IHC Staina        % (No.)             p63, % (No.)       CK5, % (No.)       CK14, % (No.)       CK17, % (No.)           % (No.)
   CMBC, N 5 12            66.7 (8)             8.3 (1)            16.7 (2)             0 (0)              16.7 (2)               0 (0)
   SGC, N 5 11             18.2 (2)            90.9 (10)           90.9 (10)           90.9 (10)           90.9 (10)             54.5 (6)
   P value                   .06c              ,.001               ,.001               ,.001               ,.001                   .01
Abbreviation: CK, cytokeratin; C/M, cytoplasmic/membranous.
a
  The differences in staining between CMBC and SGC with androgen receptor (P 5 .25) and gross cystic disease fluid protein–15 (P 5 .19) were not
  statistically significant.
b
  PAX5 did not show nuclear staining in either tumor but did show strong C/M staining, which is reported here.
c
  Marginally significant.



and a case of poorly differentiated adnexal carcinoma)                                  Immunohistochemical Analysis
were negative for podoplanin. However, because the                           Table 4 provides a summary of IHC profile staining
distinction between SGC and metastatic adenocarcinomas                    pattern in CMBC and SGC. The p63 was only weakly
may be equivocal in many cases, the only SGCs included                    expressed in 8.3% (1 of 12) of the CMBC cases, whereas it
in their study were the 6 PCs, which were all (100%)                      was strongly expressed in 90.9% (10 of 11) of the SGC cases
positive for podoplanin. The authors23 suggest that                       (P , .001). All 3 basal CKs were expressed in 90.9% (10 of
additional studies may be necessary in the future to                      11) of the SGC cases. In comparison, CMBC cases
evaluate more SGCs for podoplanin. From that limited                      demonstrated a staining profile of 0% (0 of 12) for CK14
study,23 podoplanin appeared to show promise in distin-                   and 16.7% (2 of 12) for CK5 and CK17. One case of CMBC
guishing SGC from CMBC.                                                   (8.3%) expressed both CK and CK17, whereas 2 more cases
  In our study, the only 2 SGCs that were positive for AR                 of CMBC (16.7%) were positive for either CK5 or CK17. The
were 2 of the 3 PCs (67% of the PCs; 18% of all SGCs).                    difference in basal CK staining among the SGC cases and
Although most adnexal carcinomas were negative for                        the CMBC cases was statistically significant for all 3 stains (P
GCDFP-15, only 1 of the 2 ECs (50%), ex spiradenocylin-                   , .001). Mammaglobin expression was seen in 66.7% (8 of
droma,29 was positive. That same carcinoma was positive                   12) of the CMBC cases, compared with 18.2% (2 of 11) of the
for mammaglobin as well, while staining negative for all                  SGC group (P 5 .06), which was marginally statistically
other stains. The second EC ex spiradenocylindroma was                    significant. The difference in expression for both AR or
positive for mammaglobin, while also staining positive for                GCDFP-15 in the 2 groups was not statistically significant.
p63, CK5, CK14, and CK17.                                                    The appearance of a typical CMBC is demonstrated in
  Although most of the CMBC cases in this study were                      Figure 3, A, whereas a typical SGC (a PC) is demonstrated
negative for the basal CK markers, 3 of the 12 cases (25%)                in Figure 3, B. Using these 2 cases as examples, the most
were positive for either or both CK5 and CK17. One case                   prominent staining pattern for each group is represented
that was positive for both of these immunostains was                      in Figure 4. The CMBCs were generally positive for
morphologically of a basal phenotype.                                     mammaglobin and negative for p63, CK5, CK14, and


Figure 3. Examples of ductal cutaneous
metastatic breast carcinoma (A) and sweat
gland carcinoma (porocarcinoma) (B) (hema-
toxylin-eosin, original magnifications 3100
[A and B] and 3400 [insets]).




980     Arch Pathol Lab Med—Vol 135, August 2011                                           IHC Panel of CMBC Versus SGC—Rollins-Raval et al
Figure 4. Immunohistochemical panel applied to ductal cutaneous metastatic breast carcinoma: mammaglobin (A), p63 (B), CK5 (C), CK14 (D),
and CK17 (E); and to sweat gland carcinoma (porocarcinoma): mammaglobin (F), p63 (G), CK5 (H), CK14 (I), and CK17 (J) (original magnifications
3100 [A through J] and 3400 [insets]).

CK17 (Figure 4, A through E, respectively), whereas SGCs                 (left inset), as well as the benign basal layer epithelium
(represented in the figure by a PC) were generally                       showing strong cytoplasmic/membranous staining (right
negative for mammaglobin and positive for p63, CK5,                      inset).
CK14, and CK17 (Figure 4, F though J, respectively).                        Only 5 out of the 8 stains (63%) examined by accepted
   None of the CMBC or SGC tumor cells (0%) demon-                       criteria demonstrate statistically significant, or near
strated nuclear staining for PAX5 (as shown in the right                 statistically significant, results. Incorporating those 5
inset of Figure 5, B). However, 54.5% (5 of 11) of the cases             IHC markers into a sum score system, we constructed a
of SGC expressed a distinct cytoplasmic and/or membra-                   panel to predict the disease represented in each case. The
nous staining pattern (Figure 5, B). Figure 5, A, demon-                 conditions set were based on the assumption that breast
strates the faint cytoplasmic blush seen in ductal CMBC                  cancer was usually expected to demonstrate the following


                                                                                                  Figure 5. PAX5 cytoplasmic/membranous
                                                                                                  staining. A, Ductal cutaneous metastatic
                                                                                                  breast carcinoma showing only faint cyto-
                                                                                                  plasmic blush (left inset) and a benign basal
                                                                                                  layer of epithelium showing strong cytoplas-
                                                                                                  mic/membranous staining (right inset). B,
                                                                                                  Sweat gland carcinoma (porocarcinoma)
                                                                                                  showing diffuse cytoplasmic/membranous
                                                                                                  pattern (left inset) with scattered B lympho-
                                                                                                  cytes showing the classic nuclear pattern
                                                                                                  (right inset) (original magnifications 3100 [A
                                                                                                  and B] and 3400 [insets]).




Arch Pathol Lab Med—Vol 135, August 2011                                           IHC Panel of CMBC Versus SGC—Rollins-Raval et al         981
Table 5.    Immunohistochemistry Condition Panela
      Case ID                Diagnosis                   MGB+        p632         CK52         CK142      CK172      Score      Groupb
    CMBC-1         Ductal, NOS type                        1           0           0             0          0          1          1
    CMBC-2         Ductal, NOS type                        1           0           0             0          0          1          1
    CMBC-3         Ductal, NOS type                        0           0           0             0          0          0          1
    CMBC-4         Ductal, NOS type                        0           0           0             0          0          0          1
    CMBC-5         Ductal, NOS type                        0           0           0             0          0          0          1
    CMBC-6         Ductal, basal phenotype                 0           0           1             0          1          2          1
    CMBC-7         Ductal, NOS type                        1           0           0             0          0          1          1
    CMBC-8         Ductal, NOS type                        0           0           0             0          0          0          1
    CMBC-9         Ductal, NOS type                        0           0           0             0          0          0          1
    CMBC-10        Ductal, NOS type                        1           1           0             0          0          2          1
    CMBC-11        Ductal, NOS type                        0           0           0             0          1          1          1
    CBMC-12        Ductal, NOS type                        0           0           1             0          0          1          1
    SGC-1          Eccrine carcinoma                       1           1           1             1          1          5          2
    SGC-2          Eccrine carcinoma, ex                   0           0           0             0          0          0          1
                     spiradenocylindroma
    SGC-3          Porocarcinoma                           1           1           1             1          1          5          2
    SGC-4          Porocarcinoma                           1           1           1             1          1          5          2
    SGC-5          Microcystic adnexal carcinoma           1           1           1             1          1          5          2
    SGC-6          Eccrine carcinoma                       1           1           1             1          1          5          2
    SGC-7          Porocarcinoma                           1           1           1             1          1          5          2
    SGC-8          Microcystic adnexal carcinoma           1           1           1             1          1          5          2
    SGC-9          Microcystic adnexal carcinoma           1           1           1             1          1          5          2
    SGC-10         Eccrine carcinoma                       1           1           1             1          1          5          2
    SGC-11         Eccrine carcinoma, ex                   0           1           1             1          1          4          2
                     spiradenocylindroma
Abbreviations: CK, cytokeratin; CMBC, cutaneous metastatic breast carcinoma; ID, identification; MGB, mammaglobin; NOS, not otherwise
specified; SGC, sweat gland carcinoma.
a
  Condition is the presumed result for metastatic breast carcinoma given the significant difference between CMBC and SGC for each of the 5
  immunohistochemistry stains (see Table 4).
b
  Group 1, ,3 conditions not met 5 CMBC; group 2, $3 conditions not met 5 SGC.

IHC staining profile: mammaglobin+, p632, CK52, CK142,                 patterns of CMBC and SGC. Ultimately, combining
CK172.                                                                 mammaglobin, p63, CK5, CK14, and CK17, we construct-
   For each condition that was not met, 1 point was added.             ed the IHC panel described above that consistently
If the score was less than 3 of 5 (0, 1, or 2; ,60%), the case         differentiates CMBC from SGC in our cases.
was defined as CMBC; if it was greater than or equal to 3 of              Numerous difficulties have hindered researchers in the
5 (3, 4, or 5; $60%), it was defined as SGC. Using this sum            identification of a clinically useful IHC panel to distin-
score system with these conditions, 12 of 12 patients with             guish these entities: the paucity of material, varying
CMBC (100% sensitivity) were correctly identified as were              morphologic appearances of the entities, and differences
10 of 11 patients with SGC (91% specificity) (Table 5).                in IHC staining techniques across laboratories are only a
                                                                       few. At the outset of this study, the number of cases
                         COMMENT                                       identified was few and reflected the rarity of these
   After reviewing several studies that also attempted to              neoplasms. In addition, there was considerable heteroge-
differentiate breast cancer and SGC, we attempted to                   neity among the groups of tumors examined. Within the
identify the most specific antibodies to differentiate these           classifications of CMBC and SGC, rare subtypes existed
2 neoplasms. The ER, PR, CK7, and CK20 stains were not                 that were challenging to evaluate. For example, only one
effective in differentiating these entities. The GCDFP-15,             case of basal-phenotype CMBC was included in our study.
carcinoembryonic antigen, EGFR, CK5/6, podoplanin,                     The IHC staining pattern of that CMBC subtype included
and p63 stains all showed potential based on previous                  known positivity for the basal cytokeratins (CK5, CK14,
studies. We further investigated 3 of these 6 IHC stains               and CK17).26 Although that one case expressed positivity
(GCDFP-15, CK5/6, and p63). In addition, we incorporat-                for both CK5 and CK17, it still fulfilled the criteria of the
ed 5 additional IHC stains (CK14, CK17, AR, mammaglo-                  panel for classification of the neoplasm as a CMBC.
bin, and PAX5), which had not been previously employed,                Another rare entity with possible confounding IHC
to our knowledge, in differentiating these lesions. Our                staining would be metaplastic breast carcinoma. Although
limited panel did not include carcinoembryonic antigen,                its morphologic characteristics can be quite distinct, it has
EGFR, or podoplanin. Carcinoembryonic antigen and                      been reported to be positive for p63.10 The staining pattern
EGFR had not shown as much promise in the studies                      of that entity for basal CK has not been extensively
reviewed as other IHC stains we wished to include. The                 evaluated. Both of these subtypes of breast cancer warrant
promising utility of podoplanin (published after the                   further investigation of their unique IHC staining pat-
completion of our study) was unknown during our                        terns.
investigation.                                                            For SGC, 2 cases of EC ex spiradenocylindroma were
   Our study demonstrated a sustained potential of CK5/6               included. These extremely rare neoplasms demonstrated
(or CK5 in our study) and p63 in distinguishing CMBC                   areas of apocrine differentiation. Undoubtedly, further
from SGC. The GCDFP-15 stain did not reveal a                          study of a larger cohort of SGC cases with apocrine
statistically significant difference between the staining              differentiation would be desirable. However, of these 2 EC
982    Arch Pathol Lab Med—Vol 135, August 2011                                          IHC Panel of CMBC Versus SGC—Rollins-Raval et al
ex spiradenocylindroma, only 1 did not fulfill enough                                                     References
conditions to be defined as an SGC by our immunopanel                    1. Krathen RA, Orengo IF, Rosen T. Cutaneous metastasis: a meta-analysis of
                                                                      data. South Med J. 2003;96(2):164–167.
(see Table 5, SGC-2). The other EC ex spiradenocylin-                    2. Spencer PS, Helm TN. Skin metastases in cancer patients. Cutis. 1987;39(2):
droma (case 1, described above) fulfilled the criteria of the         119–121.
IHC panel and was correctly identified as an SGC (see                    3. Cooper PH. Carcinomas of sweat glands. Pathol Annu. 1987;22(pt 1):83–
                                                                      124.
Table 5, SGC-11). The 5-stain IHC panel would have                       4. Cangelosi JJ, Nash JW, Prieto VG, Ivan D. Cutaneous adnexal tumor with an
significantly reduced the diagnostic difficulty initially             unusual presentation—discussion of a potential diagnostic pitfall. Am J
encountered by the pathologists involved with that case.              Dermatopathol. 2009;31(3):278–281.
                                                                         5. McLean SR, Shousha S, Francis N, et al. Metastatic ductal eccrine
Although these rare subtypes of CMBC and SGC have                     adenocarcinoma masquerading as an invasive ductal carcinoma of the male
slightly different IHC staining patterns compared with                breast. J Cutan Pathol. 2007;34(12):934–938.
most cases within these categories, the IHC panel correctly              6. Bayer-Garner IB, Smoller B. Androgen receptors: a marker to increase
                                                                      sensitivity for identifying breast cancer in skin metastasis of unknown primary
classified the entities in all but one case.                          site. Mod Pathol. 2000;13(2):119–122.
   Applying the conditions of the IHC panel to case 2                    7. Riva C, Dainese E, Caprara G, et al. Immunohistochemical study of
(described above) also pointed to a more definitive                   androgen receptors in breast carcinoma: evidence of their frequent expression in
                                                                      lobular carcinoma. Virchows Arch. 2005;447(4):695–700.
diagnosis. Mammaglobin was negative, whereas p63                         8. Narita D, Raica M, Suciu C, Cimpean A, Anghel A. Immunohistochemical
and CK5/6 were positive, which fulfilled 3 of the                     expression of androgen receptor and prostate-specific antigen in breast cancer.
conditions of the IHC panel and identified the lesion as              Folia Histochem Cytobiol. 2006;44(3):165–172.
                                                                         9. Moinfar F, Okcu M, Tsybrovskyy O, et al. Androgen receptors frequently are
an SGC. The case pathologist commented that the                       expressed in breast carcinomas: potential relevance to new therapeutic strategies.
morphology of this new lesion was not completely                      Cancer. 2003;98(4):703–711.
consistent with primary breast lesion but agreed that                    10. Koker MM, Kleer CG. p63 expression in breast cancer: a highly sensitive
because breast carcinomas may progress into poorly                    and specific marker of metaplastic carcinoma. Am J Surg Pathol. 2004;28(11):
                                                                      1506–1512.
differentiated forms over time, a breast carcinoma could                 11. Bhargava R, Beriwal S, Dabbs DJ. Mammaglobin vs GCDFP-15: an
not be completely ruled out. With the addition of the IHC             immunohistologic validation survey for sensitivity and specificity. Am J Clin
panel to the morphologic examination and clinicopatho-                Pathol. 2007;127(1):103–113.
                                                                         12. Smith KJ, Williams J, Corbett D, Skelton H. Microcystic adnexal
logic information, the case pathologist was more confident            carcinoma: an immunohistochemical study including markers of proliferation
in favoring a diagnosis of SGC. The IHC panel was useful              and apoptosis. Am J Surg Pathol. 2001;25(4):464–471.
in distinguishing CMBC from SGC in cases with classic                    13. Kariya Y, Moriya T, Suzuki T, et al. Sex steroid hormone receptors in
                                                                      human skin appendage and its neoplasms. Endocr J. 2005;52(3):317–325.
morphologies as well as those with unique characteristics                14. Hoang MP, Dresser KA, Kapur P, High WA, Mahalingam M. Microcystic
that yielded broader differential diagnoses.                          adnexal carcinoma: an immunohistochemical reappraisal. Mod Pathol. 2008;
   In addition to organizing a diagnostically useful IHC              21(2):178–185.
                                                                         15. Hiatt KM, Pillow JL, Smoller BR. Her-2 expression in cutaneous eccrine
panel, we present other interesting findings. The basal-              and apocrine neoplasms. Mod Pathol. 2004;17(1):28–32.
phenotype CMBC cases have the potential to metastasize                   16. Wallace ML, Longacre TA, Smoller BR. Estrogen and progesterone
to the skin, apart from other known metastatic sites, such            receptors and anti-gross cystic disease fluid protein 15 (BRST-2) fail to distinguish
                                                                      metastatic breast carcinoma from eccrine neoplasms. Mod Pathol. 1995;8(9):
as brain and bone. Furthermore, the percentage of                     897–901.
mammaglobin expression in CMBC appeared similar to                       17. Wick MR, Ockner DM, Mills SE, Ritter JH, Swanson PE. Homologous
its previously reported expression in PBC.11 This finding             carcinomas of the breasts, skin, and salivary glands: a histologic and
                                                                      immunohistochemical comparison of ductal mammary carcinoma, ductal sweat
may indicate preservation of this marker from PBC to the              gland carcinoma, and salivary duct carcinoma. Am J Clin Pathol. 1998;109(1):
metastases.                                                           75–84.
   Also, the novel interpretation of PAX5 in a cytoplas-                 18. Busam KJ, Tan LK, Granter SR, et al. Epidermal growth factor, estrogen,
                                                                      and progesterone receptor expression in primary sweat gland carcinomas and
mic and/or membranous staining pattern may provide                    primary and metastatic mammary carcinomas. Mod Pathol. 1999;12(8):786–793.
a specific marker for tumors of adnexal origin. The                      19. Plumb SJ, Argenyi ZB, Stone MS, De Young BR. Cytokeratin 5/6
known role of PAX5 as a transcription factor was                      immunostaining in cutaneous adnexal neoplasms and metastatic adenocarcino-
functionally consistent with its commonly described                   ma. Am J Dermatopathol. 2004;26(6):447–451.
                                                                         20. Qureshi HS, Ormsby AH, Lee MW, Zarbo RJ, Ma CK. The diagnostic utility
nuclear localization in B lymphocytes. However, the                   of p63, CK5/6, CK 7, and CK 20 in distinguishing primary cutaneous adnexal
cytoplasmic and/or membranous staining pattern was                    neoplasms from metastatic carcinomas. J Cutan Pathol. 2004;31(2):145–152.
striking and raises the possibility of alternative func-                 21. Ivan D, Nash JW, Prieto VG, et al. Use of p63 expression in distinguishing
                                                                      primary and metastatic cutaneous adnexal neoplasms from metastatic adenocar-
tions in cellular pathways. This staining pattern war-                cinoma to skin. J Cutan Pathol. 2007;34(6):474–480.
rants further investigation.                                             22. Ivan D, Hafeez Diwan A, Prieto VG. Expression of p63 in primary
                                                                      cutaneous adnexal neoplasms and adenocarcinoma metastatic to the skin. Mod
                    CONCLUSIONS                                       Pathol. 2005;18(1):137–142.
                                                                         23. Liang H, Wu H, Giorgadze TA, et al. Podoplanin is a highly sensitive and
   We formed a highly sensitive and specific IHC panel,               specific marker to distinguish primary skin adnexal carcinomas from adenocar-
composed of mammaglobin, p63, and 3 basal cytokeratins,               cinomas metastatic to skin. Am J Surg Pathol. 2007;31(2):304–310.
                                                                         24. Ormsby AH, Snow JL, Su WP, Goellner JR. Diagnostic immunohisto-
with sufficient power to aid in the differentiation between           chemistry of cutaneous metastatic breast carcinoma: a statistical analysis of the
CMBC and SGC. We recommend the use of this panel to                   utility of gross cystic disease fluid protein-15 and estrogen receptor protein. J Am
differentiate most cases of these 2 entities in routine               Acad Dermatol. 1995;32(5, pt 1):711–716.
                                                                         25. Bhargava R, Beriwal S, McManus K, Dabbs DJ. CK5 is more sensitive than
clinical practice.                                                    CK5/6 in identifying the ‘‘basal-like’’ phenotype of breast carcinoma. Am J Clin
                                                                      Pathol. 2008;130(5):724–730.
  We thank Cary Sipos, HT (ASCP) and Kim McManus, HT                     26. Dabbs DJ, Chivukula M, Carter G, Bhargava R. Basal phenotype of ductal
(ASCP) for their technical assistance. We would also like to          carcinoma in situ: recognition and immunohistologic profile. Mod Pathol. 2006;
thank Jay S. Raval, MD (Department of Pathology, University of        19(11):1506–1511.
Pittsburgh Medical Center) and Darice Y. Wong, PhD (Depart-              27. Feldman AL, Dogan A. Diagnostic uses of Pax5 immunohistochemistry.
ment of Bioengineering, University of California, Los Angeles)        Adv Anat Pathol. 2007;14(5):323–334.
for thoughtful discussions and critical reviews of earlier versions      28. Mhawech-Fauceglia P, Saxena R, Zhang S, et al. Pax-5 immunoexpression
                                                                      in various types of benign and malignant tumours: a high-throughput tissue
of this manuscript. Financial support for this article was            microarray analysis. J Clin Pathol. 2007;60(6):709–714.
provided through the University of Pittsburgh Medical Center’s           29. Carlsten JR, Lewis MD, Saddler K, et al. Spiradenocylindrocarcinoma: a
Department of Pathology.                                              malignant hybrid tumor. J Cutan Pathol. 2005;32(2):166–171.

Arch Pathol Lab Med—Vol 135, August 2011                                          IHC Panel of CMBC Versus SGC—Rollins-Raval et al                    983

Weitere ähnliche Inhalte

Was ist angesagt?

Am 7.15 shulman
Am 7.15 shulmanAm 7.15 shulman
Am 7.15 shulmanplmiami
 
Identification Of Pancreatic Cancer Stem Cells
Identification Of Pancreatic Cancer Stem CellsIdentification Of Pancreatic Cancer Stem Cells
Identification Of Pancreatic Cancer Stem Cellsbegelfer
 
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"Immunohistochemistry is an important complimentary tool for diagnosis of cancer"
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"Lawrence Richards
 
Rozenchan_et_al-2009-International_Journal_of_Cancer
Rozenchan_et_al-2009-International_Journal_of_CancerRozenchan_et_al-2009-International_Journal_of_Cancer
Rozenchan_et_al-2009-International_Journal_of_CancerPatricia Rozenchan
 
16. identification and characterization of cancer stem cells in liver cancer ...
16. identification and characterization of cancer stem cells in liver cancer ...16. identification and characterization of cancer stem cells in liver cancer ...
16. identification and characterization of cancer stem cells in liver cancer ...Dr. Wilfred Lin (Ph.D.)
 
Affy (1)
Affy (1)Affy (1)
Affy (1)arnimat
 
The connection between germline risk variants and somatic mutation patterns i...
The connection between germline risk variants and somatic mutation patterns i...The connection between germline risk variants and somatic mutation patterns i...
The connection between germline risk variants and somatic mutation patterns i...David Goode
 
Patología Molecular Del Cáncer De Mama
Patología Molecular Del Cáncer De MamaPatología Molecular Del Cáncer De Mama
Patología Molecular Del Cáncer De Mamalalfaro
 
Immuno histo chemistry in gyn oncology
Immuno histo chemistry in gyn oncologyImmuno histo chemistry in gyn oncology
Immuno histo chemistry in gyn oncologyShruthi Shivdas
 
Kurrey_et_al-2009-STEM_CELLS
Kurrey_et_al-2009-STEM_CELLSKurrey_et_al-2009-STEM_CELLS
Kurrey_et_al-2009-STEM_CELLSSwati Jalgaonkar
 
Fiona McKay-Diagnóstico prenatal no invasivo y diagnóstico genético reproductivo
Fiona McKay-Diagnóstico prenatal no invasivo y diagnóstico genético reproductivoFiona McKay-Diagnóstico prenatal no invasivo y diagnóstico genético reproductivo
Fiona McKay-Diagnóstico prenatal no invasivo y diagnóstico genético reproductivoFundación Ramón Areces
 
Paneles genómicos en tumores sólidos
Paneles genómicos en tumores sólidosPaneles genómicos en tumores sólidos
Paneles genómicos en tumores sólidosMauricio Lema
 

Was ist angesagt? (18)

Zeine et al. Modern Pathology 2009
Zeine et al. Modern Pathology 2009Zeine et al. Modern Pathology 2009
Zeine et al. Modern Pathology 2009
 
Am 7.15 shulman
Am 7.15 shulmanAm 7.15 shulman
Am 7.15 shulman
 
Identification Of Pancreatic Cancer Stem Cells
Identification Of Pancreatic Cancer Stem CellsIdentification Of Pancreatic Cancer Stem Cells
Identification Of Pancreatic Cancer Stem Cells
 
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"Immunohistochemistry is an important complimentary tool for diagnosis of cancer"
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"
 
Rozenchan_et_al-2009-International_Journal_of_Cancer
Rozenchan_et_al-2009-International_Journal_of_CancerRozenchan_et_al-2009-International_Journal_of_Cancer
Rozenchan_et_al-2009-International_Journal_of_Cancer
 
Sciencecafe Zeist 10 Dec 2009
Sciencecafe Zeist 10 Dec 2009Sciencecafe Zeist 10 Dec 2009
Sciencecafe Zeist 10 Dec 2009
 
16. identification and characterization of cancer stem cells in liver cancer ...
16. identification and characterization of cancer stem cells in liver cancer ...16. identification and characterization of cancer stem cells in liver cancer ...
16. identification and characterization of cancer stem cells in liver cancer ...
 
Affy
AffyAffy
Affy
 
Affy (1)
Affy (1)Affy (1)
Affy (1)
 
The connection between germline risk variants and somatic mutation patterns i...
The connection between germline risk variants and somatic mutation patterns i...The connection between germline risk variants and somatic mutation patterns i...
The connection between germline risk variants and somatic mutation patterns i...
 
Patología Molecular Del Cáncer De Mama
Patología Molecular Del Cáncer De MamaPatología Molecular Del Cáncer De Mama
Patología Molecular Del Cáncer De Mama
 
Immuno histo chemistry in gyn oncology
Immuno histo chemistry in gyn oncologyImmuno histo chemistry in gyn oncology
Immuno histo chemistry in gyn oncology
 
Kurrey_et_al-2009-STEM_CELLS
Kurrey_et_al-2009-STEM_CELLSKurrey_et_al-2009-STEM_CELLS
Kurrey_et_al-2009-STEM_CELLS
 
Berta Casar
Berta CasarBerta Casar
Berta Casar
 
Fiona McKay-Diagnóstico prenatal no invasivo y diagnóstico genético reproductivo
Fiona McKay-Diagnóstico prenatal no invasivo y diagnóstico genético reproductivoFiona McKay-Diagnóstico prenatal no invasivo y diagnóstico genético reproductivo
Fiona McKay-Diagnóstico prenatal no invasivo y diagnóstico genético reproductivo
 
MCC 2011 - Slide 4
MCC 2011 - Slide 4MCC 2011 - Slide 4
MCC 2011 - Slide 4
 
CDD 2015
CDD 2015CDD 2015
CDD 2015
 
Paneles genómicos en tumores sólidos
Paneles genómicos en tumores sólidosPaneles genómicos en tumores sólidos
Paneles genómicos en tumores sólidos
 

Ähnlich wie An immunohistochemical panel to differentiate

GROUP 1 Case 967-- A Teenage Female with an Ovarian MassCLI.docx
GROUP 1 Case 967-- A Teenage Female with an Ovarian MassCLI.docxGROUP 1 Case 967-- A Teenage Female with an Ovarian MassCLI.docx
GROUP 1 Case 967-- A Teenage Female with an Ovarian MassCLI.docxgilbertkpeters11344
 
Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...
Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...
Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...Mădălin Margan
 
Neoadjuvant therapy for HER-2 positive acantholytic squamous cell carcinoma o...
Neoadjuvant therapy for HER-2 positive acantholytic squamous cell carcinoma o...Neoadjuvant therapy for HER-2 positive acantholytic squamous cell carcinoma o...
Neoadjuvant therapy for HER-2 positive acantholytic squamous cell carcinoma o...komalicarol
 
Fine needle aspiration cytology of neuroendocrine carcinoma of the breast
Fine needle aspiration cytology of neuroendocrine carcinoma of the breastFine needle aspiration cytology of neuroendocrine carcinoma of the breast
Fine needle aspiration cytology of neuroendocrine carcinoma of the breastAbKadir Rifaei Rashid Khairi
 
Journel club presentation
Journel club presentationJournel club presentation
Journel club presentationimrana tanvir
 
Review and Updates of Immunohistochemistry in Selected Salivary Gland and Hea...
Review and Updates of Immunohistochemistry inSelected Salivary Gland and Hea...Review and Updates of Immunohistochemistry inSelected Salivary Gland and Hea...
Review and Updates of Immunohistochemistry in Selected Salivary Gland and Hea...imrana tanvir
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateJohnJulie1
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Datedaranisaha
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateEditorSara
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Datesemualkaira
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Datesemualkaira
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateEditorSara
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Datesemualkaira
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateNainaAnon
 
EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...
EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...
EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...ANCA MARIA CIMPEAN
 
Allelic Variation In BRCA Genes Could Be The Key To...
Allelic Variation In BRCA Genes Could Be The Key To...Allelic Variation In BRCA Genes Could Be The Key To...
Allelic Variation In BRCA Genes Could Be The Key To...Lynn Weber
 
New grading system for SCC.pdf
New grading system for SCC.pdfNew grading system for SCC.pdf
New grading system for SCC.pdfWajiha Alamgir
 
Properties of cancer
Properties of cancer Properties of cancer
Properties of cancer shakilaseran
 

Ähnlich wie An immunohistochemical panel to differentiate (20)

GROUP 1 Case 967-- A Teenage Female with an Ovarian MassCLI.docx
GROUP 1 Case 967-- A Teenage Female with an Ovarian MassCLI.docxGROUP 1 Case 967-- A Teenage Female with an Ovarian MassCLI.docx
GROUP 1 Case 967-- A Teenage Female with an Ovarian MassCLI.docx
 
Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...
Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...
Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...
 
Neoadjuvant therapy for HER-2 positive acantholytic squamous cell carcinoma o...
Neoadjuvant therapy for HER-2 positive acantholytic squamous cell carcinoma o...Neoadjuvant therapy for HER-2 positive acantholytic squamous cell carcinoma o...
Neoadjuvant therapy for HER-2 positive acantholytic squamous cell carcinoma o...
 
Fine needle aspiration cytology of neuroendocrine carcinoma of the breast
Fine needle aspiration cytology of neuroendocrine carcinoma of the breastFine needle aspiration cytology of neuroendocrine carcinoma of the breast
Fine needle aspiration cytology of neuroendocrine carcinoma of the breast
 
Journel club presentation
Journel club presentationJournel club presentation
Journel club presentation
 
Review and Updates of Immunohistochemistry in Selected Salivary Gland and Hea...
Review and Updates of Immunohistochemistry inSelected Salivary Gland and Hea...Review and Updates of Immunohistochemistry inSelected Salivary Gland and Hea...
Review and Updates of Immunohistochemistry in Selected Salivary Gland and Hea...
 
Carcinoma of unknown primary
Carcinoma of unknown primaryCarcinoma of unknown primary
Carcinoma of unknown primary
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Date
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Date
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Date
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Date
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Date
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Date
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Date
 
Screening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-DateScreening Tests for Cervical Cancer Up-To-Date
Screening Tests for Cervical Cancer Up-To-Date
 
EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...
EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...
EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...
 
Allelic Variation In BRCA Genes Could Be The Key To...
Allelic Variation In BRCA Genes Could Be The Key To...Allelic Variation In BRCA Genes Could Be The Key To...
Allelic Variation In BRCA Genes Could Be The Key To...
 
賴雨欣.ppt
賴雨欣.ppt賴雨欣.ppt
賴雨欣.ppt
 
New grading system for SCC.pdf
New grading system for SCC.pdfNew grading system for SCC.pdf
New grading system for SCC.pdf
 
Properties of cancer
Properties of cancer Properties of cancer
Properties of cancer
 

Kürzlich hochgeladen

High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)kishan singh tomar
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project reportNARMADAPETROLEUMGAS
 
Pregnacny, Parturition, and Lactation.pdf
Pregnacny, Parturition, and Lactation.pdfPregnacny, Parturition, and Lactation.pdf
Pregnacny, Parturition, and Lactation.pdfMedicoseAcademics
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionkrishnareddy157915
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptPradnya Wadekar
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.kishan singh tomar
 
Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxkomalt2001
 
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfSGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfHongBiThi1
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentsaileshpanda05
 
Microbiology lecture presentation-1.pptx
Microbiology lecture presentation-1.pptxMicrobiology lecture presentation-1.pptx
Microbiology lecture presentation-1.pptxkitati1
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxNaveenkumar267201
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024EwoutSteyerberg1
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfDolisha Warbi
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsMedicoseAcademics
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
Moving Forward After Uterine Cancer Treatment: Surveillance Strategies, Testi...
Moving Forward After Uterine Cancer Treatment: Surveillance Strategies, Testi...Moving Forward After Uterine Cancer Treatment: Surveillance Strategies, Testi...
Moving Forward After Uterine Cancer Treatment: Surveillance Strategies, Testi...bkling
 
The Importance of Mental Health: Why is Mental Health Important?
The Importance of Mental Health: Why is Mental Health Important?The Importance of Mental Health: Why is Mental Health Important?
The Importance of Mental Health: Why is Mental Health Important?Ryan Addison
 
Good Laboratory Practice (GLP) in Pharma-LikeWays.pptx
Good Laboratory Practice (GLP) in Pharma-LikeWays.pptxGood Laboratory Practice (GLP) in Pharma-LikeWays.pptx
Good Laboratory Practice (GLP) in Pharma-LikeWays.pptxLikeways
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...Shubhanshu Gaurav
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyMedicoseAcademics
 

Kürzlich hochgeladen (20)

High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project report
 
Pregnacny, Parturition, and Lactation.pdf
Pregnacny, Parturition, and Lactation.pdfPregnacny, Parturition, and Lactation.pdf
Pregnacny, Parturition, and Lactation.pdf
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung function
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.ppt
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.
 
Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptx
 
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfSGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing student
 
Microbiology lecture presentation-1.pptx
Microbiology lecture presentation-1.pptxMicrobiology lecture presentation-1.pptx
Microbiology lecture presentation-1.pptx
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functions
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
Moving Forward After Uterine Cancer Treatment: Surveillance Strategies, Testi...
Moving Forward After Uterine Cancer Treatment: Surveillance Strategies, Testi...Moving Forward After Uterine Cancer Treatment: Surveillance Strategies, Testi...
Moving Forward After Uterine Cancer Treatment: Surveillance Strategies, Testi...
 
The Importance of Mental Health: Why is Mental Health Important?
The Importance of Mental Health: Why is Mental Health Important?The Importance of Mental Health: Why is Mental Health Important?
The Importance of Mental Health: Why is Mental Health Important?
 
Good Laboratory Practice (GLP) in Pharma-LikeWays.pptx
Good Laboratory Practice (GLP) in Pharma-LikeWays.pptxGood Laboratory Practice (GLP) in Pharma-LikeWays.pptx
Good Laboratory Practice (GLP) in Pharma-LikeWays.pptx
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before Pregnancy
 

An immunohistochemical panel to differentiate

  • 1. Original Articles An Immunohistochemical Panel to Differentiate Metastatic Breast Carcinoma to Skin From Primary Sweat Gland Carcinomas With a Review of the Literature Marian Rollins-Raval, MD, MPH; Mamatha Chivukula, MD; George C. Tseng, ScD; Drazen Jukic, MD, PhD; David J. Dabbs, MD N Context.—Approximatelymetastases. Sweat gland breast cancer develop cutaneous 25% of patients with carci- neoplasm cases, and 2 primary breast cancer cases were retrieved and analyzed with the following IHC panel: nomas (SGCs) account for about 0.05% of all cutaneous mammaglobin, gross cystic disease fluid protein (GCDFP) neoplasms. Cutaneous metastases of breast carcinoma 15, p63, basal cytokeratins (CK5, CK14, and CK17), (CMBCs) (especially the ductal type) can be difficult to androgen receptor, and PAX5. distinguish from SGCs. Treatment and prognoses for these Results.—The p63 was only weakly expressed in 1 of 12 2 types of tumors differ radically, making accurate CMBC cases (8.3%), whereas it was strongly expressed in histologic diagnosis crucial. Although a few studies attempt 10 of 11 SGC cases (90.9%) (P , .001). Basal cytokeratins to differentiate these entities employing immunohisto- demonstrated a similar immunoprofile in the SGC group, chemical (IHC) studies (some of which we review here), to with 10 of 11 cases (90.9%) expressing all 3 markers, and a date, no panel of IHC stains exists, to our knowledge, to variable immunoprofile in the CMBC group with 0% distinguish these entities. (CK14) (P , .001) to 16.7% (2 of 12 cases; CK5 and CK17) Objective.—To devise a panel of IHC stains to distin- (P , .001) expression. Mammaglobin was expressed in 8 of guish CMBC from SGC. 12 cases (66.7%) of CMBC. Design.—Twelve cases of ductal CMBCs (11 not Conclusions.—Together, these 5 IHC stains were com- otherwise specified type, and 1 basal phenotype), 11 cases bined to make a panel that was 100% sensitive and 91% of SGCs (5 eccrine carcinomas, 3 porocarcinomas, and 3 specific in distinguishing between CMBC and SGC. microcystic adnexal carcinomas), 2 benign sweat gland (Arch Pathol Lab Med. 2011;135:975–983) Approximately accountmetastases. Sweat gland carci- 25% of patients with breast cancer may develop cutaneous nomas (SGCs) 1,2 for 0.05% of all cutaneous reports continue to demonstrate this potential diagnostic pitfall.4,5 We recently received 2 diagnostically challenging cases presenting similar challenges. neoplasms.3 Clinically, the presentation of these 2 entities is often distinct. Ductal cutaneous metastases of breast carcinoma (CMBCs) present as multiple lesions in patients with a previous diagnosis of primary breast carcinoma (PBC), whereas SGC presents as a single cutaneous lesion in patients with no known history of breast cancer. However, CMBCs can be difficult to distinguish from SGCs histologically, and complex clinical circumstances can further complicate a diagnosis. Several recent case Accepted for publication October 12, 2010. From the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Drs Rollins-Raval, Chivukula, Jukic, and Dabbs); and the Department of Biostatistics, University of Pittsburgh (Dr Tseng). Dr Jukic is now with the Division of Dermatopathology, Department of Pathology and Laboratory Medicine, James A. Haley Veterans’ Hospital, Tampa, Florida. The authors have no relevant financial interest in the products or companies described in this article. Presented in part at the annual meeting of the United States and Canadian Academy of Pathology, Denver, Colorado, March 5, 2008. Figure 1. Eccrine carcinoma ex spiradenocylindroma with inset Reprints: Marian Rollins-Raval, MD, MPH, Department of Pathology, showing the eccrine carcinoma ex spiradenocylindroma at higher University of Pittsburgh Medical Center, A711 Scaife Hall, 3550 Terrace power (hematoxylin-eosin, original magnifications 3100 and 3400 St, Pittsburgh, PA 15261 (e-mail: rollinsravalma@upmc.edu). [inset]). Arch Pathol Lab Med—Vol 135, August 2011 IHC Panel of CMBC Versus SGC—Rollins-Raval et al 975
  • 2. Figure 2. Infiltrating carcinoma shown with hematoxylin-eosin stain (A), as well as immunohistochemical stains for p63 (B), AE1/AE3 (C), CK5/6 (D), epithelial membrane antigen (E), and CK7 (F) (original magnifications 3200). Case 1 7 years after her bilateral mastectomies. Although the morphology of the PBC and the skin lesions was similar, A 75-year-old woman with a history of bilateral immunohistochemical (IHC) studies were performed on mastectomies for infiltrating ductal carcinoma of both all lesions. For the right PBC, the tumor cells demonstrat- breasts, colectomy for carcinoma of the rectum, and ed strong positivity for cytokeratin (CK) 7, estrogen hysterectomy with bilateral salpingo-oophorectomy for receptor (ER), and ERBB2 (formerly HER2/neu) and focal benign disease presented with skin lesions on her back positivity for progesterone receptor (PR). For the left PBC, 976 Arch Pathol Lab Med—Vol 135, August 2011 IHC Panel of CMBC Versus SGC—Rollins-Raval et al
  • 3. Table 1. Demographics of Cutaneous Metastatic in Figures 2, B through F, respectively), and were negative Breast Carcinoma (CMBC) and Sweat Gland Carcinoma for S100, ER, PR, CK20, GCDFP-15, and mammaglobin. (SGC) Cases Based on this information alone, it was unclear whether Mean Age the lesion was a CMBC or an SGC, making the devel- Case Group No. of Cases % Female (Age Range), y opment of a treatment plan difficult. As the treatment and prognosis for CMBC and SGC PBC 2 100 68 (53–83) CMBC 12 100 57 (40–80)a differ significantly, developing a panel of IHC markers to BAN 2 50 48.5 (34–63) differentiate these 2 entities would be of high clinical SGC 11 58.3 73.6 (49–93) value. Numerous studies have evaluated these entities Abbreviations: BAN, benign adnexal neoplasm; PBC, primary breast either individually6–15 or comparatively using various carcinoma. (IHC) stains,16–23 but there has been no study, to our a Age at presentation of metastatic lesion, not primary breast lesion. knowledge, to determine the most useful IHC panel for differentiating CMBC from SGC. Several IHC stains have shown promise in their ability the tumor cells were strongly positive for CK7, ER, and PR. to differentiate CMBC and SGC. Mammaglobin, a protein Both PBCs were negative for CK903, S100, cross cystic fluid frequently overexpressed in breast cancer,11 has not been protein–15 (GCDFP-15), and CK20. On hematoxylin-eosin thoroughly examined in either CMBC or SGC. GCDFP-15, stain, the skin lesion, which demonstrated areas of tight a glycoprotein originally isolated in human breast gross intermingling between carcinoma and a spiradenocylin- cystic fluid, although present in most primary and droma, was more compatible with a malignant neoplasm metastatic breast cancers, has also been reported to be arising in the background of a benign mixed tumor rather expressed in a few cases of SGC.16,24 Androgen receptor than metastasis to the benign tumor (Figure 1). In the (AR), although often found in high-grade invasive breast benign component, CK7 was positive only in the internal cancer, has also been identified in some SGCs.7–9,13 mature cells and negative in basal cells, ERBB2 demon- The basal cytokeratin stains (CK5, CK14, and CK17), strated weak and less than 1+ positivity, and CK903 was recently shown to be expressed in the basal phenotype of strongly positive. CK20, ER, PR, and S100 were all negative breast carcinoma, were not present in most other types of in the tumor cells. In the malignant component, CK903 was PBC.25,26 These stains have also been shown to be present strongly positive, whereas CK7 and S100 were focally in a few SGC cases.14,19,20 However, with the exception of positive. CK20, GCDFP-15, ER, PR, and ERBB2 were all CMBC with a basal phenotype, these markers are more negative. Although these findings supported the diag- likely to be seen in SGC; p63, a homologue of the p53 gene nosis of a primary eccrine carcinoma (EC) arising in a and expressed primarily by basal and myoepithelial cells spiradenocylindroma, the possibility of a CMBC to the of the skin, would be more likely to be seen in cases of SGC benign neoplasm could not be ruled out. Molecular studies than in cases of CMBC.10,21,22 performed on the paraffin-embedded tissues showed In addition, 1 of the authors (M.R.-R.) noticed a strong multiple allelic losses in the PBC and no genetic alterations cytoplasmic and/or membranous staining with PAX5, a in the EC. The patient subsequently developed additional B-cell–specific activator protein of the basal layer of metastases to lymph nodes and additional skin sites from healthy epithelium, in an unrelated research study and the EC. Although a definitive diagnosis was rendered in decided to use the antibody in the current study, this case, a simplified IHC panel would have benefited hypothesizing that the staining pattern might be similar both the pathologist and patient. in SGC. The PAX5 expression has been previously studied in B lymphocytes, in most small cell carcinomas, and in Case 2 Merkel cell carcinomas.27,28 An 84-year-old woman with a history of bilateral PBC The goal of this study was to construct a panel of IHC 20 years earlier presented with a skin lesion of the right stains that would be highly sensitive and specific in breast. The morphology of the previous PBC was not distinguishing these 2 morphologically similar entities. consistent with the new skin lesion, which showed an infiltrating carcinoma (Figure 2, A). Numerous IHC stains MATERIALS AND METHODS were performed with the following results: the tumor cells Literature Review were positive for p63, AE1/AE3, CK5/6, and epithelial A MEDLINE (US National Library of Medicine, Bethesda, membrane antigen, were focally positive for CK7 (shown Maryland) search was performed from 1995 to 2009 to identify Table 2. Immunohistochemistry Antibody Information a Antibody Clone Dilution Vendor Location Pretreatment GCDFP 23A3 1:25 Vector Labs Burlingame, California CC1b mild and standard AR AR441 1:100 Dako North America Carpinteria, California CC1 mild and standard Mammaglobin 304-1A5 and 31A5 Predilute Zeta Corporation Sierra Madre, California CC1 mild p63 4A4 1:200 Neomarkers Inc Fremont, California CC1 mild and standard PAX5 24 1:25 BD Biosciences San Jose, California CC1 mild and standard CK5 XM26 1:25 Novocastra Newcastle Upon Tyne, CC1 standard Laboratories Ltd United Kingdom CK14 LL002 Predilute Ventana Medical Tucson, Arizona CC1 standard Systems Inc CK17 E3 1:20 Dako North America Carpinteria, California CC1 mild and protease 3 a All immunostains were performed on the BenchMark XT using the iView/DAB detection system (Ventana Medical Systems, Tucson, Arizona). b Ventana Medical Systems, Tucson, Arizona. Arch Pathol Lab Med—Vol 135, August 2011 IHC Panel of CMBC Versus SGC—Rollins-Raval et al 977
  • 4. Table 3. Comparative Review of Additional Similar Studies and the Immunohistochemical Results Study Wallace et al,16 1995 Wick et al,17 1998 Busam et al,18 1999 Plumb et al,19 2004 a b IHC Marker MAC CMBC EC PBC MAC PC EC CMBC MAC CMBCc ER 2/8 1/15 9/27 31/59 2/8 0/4 2/13 10/30 PR 5/8 15/15 1/4 27/59 2/8 0/4 2/13 8/30 c-erbB-2(HER2/neu) 9/27 12/59 AR GCDFP 1/6 7/15 5/27 41/59 CEA 21/27 5/59 EGF-R 5/8 4/4 11/13 5/30 CK5/6 3/3 2/17 CK5 CK7 CK14 CK17 CK20 p63 (nuclear) S100 12/27 27/59 Podoplanin PAX5 (C/M)g Mammaglobin Abbreviations: 1A, 1 apocrine case; 1N, 1 not otherwise specified case; AR, androgen receptor; CEA, carcinoembryonic antigen; CK, cytokeratin; C/ M, cytoplasmic/membranous; CMBC, cutaneous metastatic breast carcinoma (ductal); EC, eccrine carcinoma; EGF-R, epidermal growth factor receptor; ER, estrogen receptor; ES, ex spiradenocylindroma; GCDFP, gross cystic disease fluid protein; IHC, immunohistochemistry; MAC, microcystic adnexal carcinoma; PBC, primary breast carcinoma; PC, porocarcinoma; PR, progesterone receptor. a In this study, EC refers to 23 eccrine carcinomas, as well as 4 apocrine lesions in the same category that were only separated by their staining for GCDFP-15, where 1 of 23 cases of eccrine carcinoma was positive whereas 4 of 4 cases of the apocrine lesions were positive for GCDFP. b These authors looked at primary breast carcinomas as opposed to cutaneous metastases. c There were 6 cases with weak staining, considered negative, for CK5/6. d Of the 3, 1 was mucinous and stained only 1+ for p63 and was thus counted as negative here; the other 2 were strongly positive. e There were 5 cases: 2N, 1A, 2ES. f Two of 3 were graded as 1+. g PAX5 showed a strong C/M staining pattern noted previously in normal epithelium which is reported here. studies similar to our own, comparing primary SGC to CMBC (or paraffin-embedded tissues; and samples were analyzed with the in 1 study, to PBC) using IHC stains. We selected a panel of 8 IHC following IHC stains: mammaglobin, GCDFP-15, p63, CK5, CK14, stains to investigate their staining patterns in CMBC and SGC. CK17, AR, and PAX5. We did not repeat IHC studies that appeared in previous studies All IHC stain analysis was performed on the Ventana to be less useful. BenchMark, XT (Ventana Medical Systems, Inc, Tucson, Arizona) using the iView DAB Detection System (Ventana Medical) with Case Identification commercially available antibodies according to standard proto- A retrospective search for CMBC and SGC cases using a Natural cols (Table 2). All negative and positive controls demonstrated Language Search was performed in the University of Pittsburgh appropriate immunolabeling. Medical Center (Pittsburgh, Pennsylvania) CoPath Plus database The IHC stain results were semiquantitated as follows: AR, (Cerner DHT, Inc, Waltham, Massachusetts) for the 9 years from 1998 PAX5, and p63 were nuclear stains, and strong nuclear positivity to 2007. Based on the results of the database search, 27 cases were was considered positive staining. The intensity of immunostain- retrieved from the University of Pittsburgh Medical Center archives ing was graded as negative (0), weak (1), moderate (2), and for the study: 12 cases of ductal CMBC (44%), which included 11 strong (3), and the proportion of positive staining cells was cases with morphologies not otherwise specified and 1 case of basal recorded as 0% through 5% (1), 6% through 20% (2), 21% through phenotype; 11 cases of SGC (41%), which included 5 cases of EC, 3 80% (3), and greater than 80% (4). cases of porocarcinoma (PC), and 3 cases of microcystic adnexal Cytoplasmic staining was considered positive for GCDFP-15 carcinoma (MAC); and 4 additional, randomly selected cases (15%), and mammaglobin, and the intensity of immunostaining was which included 2 primary cutaneous adnexal benign neoplasms (a graded as weak, moderate, or strong. poroma and an apocrine adenoma) and 2 cases of PBC. Basal cytokeratins—CK5, CK14, and CK17—were scored as positive if any cytoplasmic or membranous staining was Demographics observed in the tumor cells. The patients in PBC and metastatic breast cancer groups were all A strong cytoplasmic and/or membranous staining pattern women, whereas the SGC group consisted of both men and women. was considered positive for PAX5. The mean ages for patients with ductal CMBC and SGC were 57 years and 73.6 years, respectively (Table 1). The difference in ages Statistical Analysis was significantly different. Although all the patients with CMBC (12 A statistical analysis of the positive and negative results was of 12; 100%) had documented PBCs, only 1 (case 1, described above) performed with R statistical software 2.10.1 (R Project for of the 11 patients with SGC (9%) had a history of PBC. Statistical Computing, Wien, Austria). The SGCs were all compiled into one group for the statistical analysis. Comparisons of the IHC staining profiles in the CMBC and SGC groups were Immunohistochemistry performed using a z test to calculate the P values for each Hematoxylin-eosin slides were reviewed; a representative tumor IHC stain. Subsequently, a simple computer algorithm was block was selected; sections were obtained on formalin-fixed, created to examine the effectiveness of a combination of 978 Arch Pathol Lab Med—Vol 135, August 2011 IHC Panel of CMBC Versus SGC—Rollins-Raval et al
  • 5. Table 3. Extended 20 22 Study Qureshi et al, 2004 Ivan et al, 2005 Liang et al,23 2007 This Study d IHC Marker PC CMBC MAC EC CMBC PC CMBC MAC PC ECe CMBC ER PR c-erbB-2(HER2/neu) AR 0/3 2/3 0/5 5/12 GCDFP 0/3 0/3 1/5 (ES) 5/12 CEA EGF-R CK5/6 3/3 0/6 CK5 3/3 3/3 4/5 2/12 CK7 2/3f 6/6 CK14 3/3 3/3 4/5 0/12 CK17 3/3 3/3 4/5 2/12 CK20 0/3 0/6 p63 (nuclear) 3/3 0/6 4/4 2/3 0/12 3/3 3/3 4/5 1/12 S100 Podoplanin 6/6 0/11 PAX5 (C/M)g 3/3 2/3 2/5 (1A + 2N) 0/12 Mammaglobin 0/3 0/3 2/5 (ES) 7/12 the near statistically significant and statistically significant with CK5/6, with 6 cases (35%) having weak positive biomarkers. staining, whereas all 3 MACs (100%) expressed strong positive staining. This difference, although not evaluated RESULTS specifically in the study,19 revealed the diagnostic poten- Literature Review tial of CK5/6 in differentiating these lesions. Wallace et al16 investigated the IHC staining character- Qureshi et al20 also examined the diagnostic potential of istics of 15 cases (from 12 patients) of CMBC and several IHC stains, including p63, CK5/6, CK7, and CK20, compared them to a series of primary eccrine tumors, to differentiate metastatic carcinomas from primary including 8 MACs. The authors16 concluded that using cutaneous adnexal neoplasms. Several benign adnexal standard IHC markers, such as ER, PR and GCDFP-15, neoplasms as well as malignant neoplasms, such as would not reliably distinguish these 2 populations. hidradenocarcinoma, adenoid cystic carcinoma, seba- Wick et al17 examined 59 cases of ductal PBCs and ceous carcinoma, digital papillary adenocarcinoma, syr- compared them with 27 cases of ductal SGC, which were ingomatous carcinoma, and mucinous carcinoma, were further described as demonstrating eccrine morphology included in their study.20 Only their examinations of PCs (23 cases; 85%) and apocrine differentiation (4 cases; 15%). and CMBCs were included in Table 3. Three cases of PC Using pancytokeratins, carcinoembryonic antigen, S100 were all strongly positive for CK5/6 and p63, whereas protein, GCDFP-15, ER, PR, and c-erbB-2 protein (ERBB2) CK7 demonstrated positivity in less that 10% of cells for 2 IHC stains, their findings17 concluded that the infrequency cases, and CK20 was completely negative in all cases. The of GCDFP-15 in eccrine sweat gland tumors as well as the 6 CMBC cases were diffusely positive for CK7 and were paucity of carcinoembryonic antigen in breast carcinomas negative for CK5/6, p63, and CK20. This study20 demon- could be useful in predefined differential diagnostic strated the diagnostic potential of CK5/6 and p63 in settings involving these 2 entities with the appropriate differentiating these 2 entities. clinicopathologic information provided. We included this Ivan et al22 assessed the utility of p63 antibody for study in our review because of its similarity to the current differentiating primary cutaneous adnexal neoplasms and study, even though it focused on distinguishing PBC from adenocarcinoma metastatic to the skin. In addition to SGC, rather than distinguishing CMBC from SGC. several benign adnexal tumors, the authors22 analyzed 4 Busam et al18 studied 30 cases of CMBC compared with MACs and 3 ECs (1 of the latter with mucinous 42 primary SGC cases for their expression of ER, PR, and differentiation) as well as a case of hidradenocarcinoma epidermal growth factor receptor (EGFR). Several addi- and 2 cases of trichilemmal carcinomas. Of the MACs and tional histologic types of SGC were examined in this ECs, only the ECs with mucinous differentiation were study,18 including apocrine, hidradenocarcinoma, mucin- negative for nuclear positivity of p63, and none of the ous, and basaloid carcinomas, which were not included in CMBCs demonstrated nuclear positivity, confirming the our study. Only the 3 types of tumors included in our usefulness of this marker in distinguishing SGC from study—MAC, PC, and EC—are presented in Table 3. CMBC. Their results18 suggested that the expression of EGFR may Finally, Liang et al23 investigated the use of podoplanin be diagnostically helpful in differentiating these 2 groups to differentiate metastases to skin from various organ of tumors, whereas ER and PR continued to show no sites, including the breast, from primary skin adnexal significant difference between the 2 groups. carcinomas. In their study,23 the authors examined 11 Plumb et al19 used CK5/6 to differentiate primary cases of metastatic breast cancer to the skin, all of which cutaneous adnexal neoplasms, including 3 MACs, from (100%) were completely negative for podoplanin. They cutaneous metastatic lesions, including 17 CMBCs. Only 2 also examined a total of 40 primary skin adnexal of 17 CMBC cases (12%) displayed strong positive staining carcinomas, only 2 of which (5%; a case of adenoid cystic Arch Pathol Lab Med—Vol 135, August 2011 IHC Panel of CMBC Versus SGC—Rollins-Raval et al 979
  • 6. Table 4. Summary of Immunohistochemistry (IHC) Profile Staining Pattern in Cutaneous Metastatic Breast Carcinoma (CMBC) and Sweat Gland Carcinoma (SGC) Mammaglobin, PAX5 (C/M),b IHC Staina % (No.) p63, % (No.) CK5, % (No.) CK14, % (No.) CK17, % (No.) % (No.) CMBC, N 5 12 66.7 (8) 8.3 (1) 16.7 (2) 0 (0) 16.7 (2) 0 (0) SGC, N 5 11 18.2 (2) 90.9 (10) 90.9 (10) 90.9 (10) 90.9 (10) 54.5 (6) P value .06c ,.001 ,.001 ,.001 ,.001 .01 Abbreviation: CK, cytokeratin; C/M, cytoplasmic/membranous. a The differences in staining between CMBC and SGC with androgen receptor (P 5 .25) and gross cystic disease fluid protein–15 (P 5 .19) were not statistically significant. b PAX5 did not show nuclear staining in either tumor but did show strong C/M staining, which is reported here. c Marginally significant. and a case of poorly differentiated adnexal carcinoma) Immunohistochemical Analysis were negative for podoplanin. However, because the Table 4 provides a summary of IHC profile staining distinction between SGC and metastatic adenocarcinomas pattern in CMBC and SGC. The p63 was only weakly may be equivocal in many cases, the only SGCs included expressed in 8.3% (1 of 12) of the CMBC cases, whereas it in their study were the 6 PCs, which were all (100%) was strongly expressed in 90.9% (10 of 11) of the SGC cases positive for podoplanin. The authors23 suggest that (P , .001). All 3 basal CKs were expressed in 90.9% (10 of additional studies may be necessary in the future to 11) of the SGC cases. In comparison, CMBC cases evaluate more SGCs for podoplanin. From that limited demonstrated a staining profile of 0% (0 of 12) for CK14 study,23 podoplanin appeared to show promise in distin- and 16.7% (2 of 12) for CK5 and CK17. One case of CMBC guishing SGC from CMBC. (8.3%) expressed both CK and CK17, whereas 2 more cases In our study, the only 2 SGCs that were positive for AR of CMBC (16.7%) were positive for either CK5 or CK17. The were 2 of the 3 PCs (67% of the PCs; 18% of all SGCs). difference in basal CK staining among the SGC cases and Although most adnexal carcinomas were negative for the CMBC cases was statistically significant for all 3 stains (P GCDFP-15, only 1 of the 2 ECs (50%), ex spiradenocylin- , .001). Mammaglobin expression was seen in 66.7% (8 of droma,29 was positive. That same carcinoma was positive 12) of the CMBC cases, compared with 18.2% (2 of 11) of the for mammaglobin as well, while staining negative for all SGC group (P 5 .06), which was marginally statistically other stains. The second EC ex spiradenocylindroma was significant. The difference in expression for both AR or positive for mammaglobin, while also staining positive for GCDFP-15 in the 2 groups was not statistically significant. p63, CK5, CK14, and CK17. The appearance of a typical CMBC is demonstrated in Although most of the CMBC cases in this study were Figure 3, A, whereas a typical SGC (a PC) is demonstrated negative for the basal CK markers, 3 of the 12 cases (25%) in Figure 3, B. Using these 2 cases as examples, the most were positive for either or both CK5 and CK17. One case prominent staining pattern for each group is represented that was positive for both of these immunostains was in Figure 4. The CMBCs were generally positive for morphologically of a basal phenotype. mammaglobin and negative for p63, CK5, CK14, and Figure 3. Examples of ductal cutaneous metastatic breast carcinoma (A) and sweat gland carcinoma (porocarcinoma) (B) (hema- toxylin-eosin, original magnifications 3100 [A and B] and 3400 [insets]). 980 Arch Pathol Lab Med—Vol 135, August 2011 IHC Panel of CMBC Versus SGC—Rollins-Raval et al
  • 7. Figure 4. Immunohistochemical panel applied to ductal cutaneous metastatic breast carcinoma: mammaglobin (A), p63 (B), CK5 (C), CK14 (D), and CK17 (E); and to sweat gland carcinoma (porocarcinoma): mammaglobin (F), p63 (G), CK5 (H), CK14 (I), and CK17 (J) (original magnifications 3100 [A through J] and 3400 [insets]). CK17 (Figure 4, A through E, respectively), whereas SGCs (left inset), as well as the benign basal layer epithelium (represented in the figure by a PC) were generally showing strong cytoplasmic/membranous staining (right negative for mammaglobin and positive for p63, CK5, inset). CK14, and CK17 (Figure 4, F though J, respectively). Only 5 out of the 8 stains (63%) examined by accepted None of the CMBC or SGC tumor cells (0%) demon- criteria demonstrate statistically significant, or near strated nuclear staining for PAX5 (as shown in the right statistically significant, results. Incorporating those 5 inset of Figure 5, B). However, 54.5% (5 of 11) of the cases IHC markers into a sum score system, we constructed a of SGC expressed a distinct cytoplasmic and/or membra- panel to predict the disease represented in each case. The nous staining pattern (Figure 5, B). Figure 5, A, demon- conditions set were based on the assumption that breast strates the faint cytoplasmic blush seen in ductal CMBC cancer was usually expected to demonstrate the following Figure 5. PAX5 cytoplasmic/membranous staining. A, Ductal cutaneous metastatic breast carcinoma showing only faint cyto- plasmic blush (left inset) and a benign basal layer of epithelium showing strong cytoplas- mic/membranous staining (right inset). B, Sweat gland carcinoma (porocarcinoma) showing diffuse cytoplasmic/membranous pattern (left inset) with scattered B lympho- cytes showing the classic nuclear pattern (right inset) (original magnifications 3100 [A and B] and 3400 [insets]). Arch Pathol Lab Med—Vol 135, August 2011 IHC Panel of CMBC Versus SGC—Rollins-Raval et al 981
  • 8. Table 5. Immunohistochemistry Condition Panela Case ID Diagnosis MGB+ p632 CK52 CK142 CK172 Score Groupb CMBC-1 Ductal, NOS type 1 0 0 0 0 1 1 CMBC-2 Ductal, NOS type 1 0 0 0 0 1 1 CMBC-3 Ductal, NOS type 0 0 0 0 0 0 1 CMBC-4 Ductal, NOS type 0 0 0 0 0 0 1 CMBC-5 Ductal, NOS type 0 0 0 0 0 0 1 CMBC-6 Ductal, basal phenotype 0 0 1 0 1 2 1 CMBC-7 Ductal, NOS type 1 0 0 0 0 1 1 CMBC-8 Ductal, NOS type 0 0 0 0 0 0 1 CMBC-9 Ductal, NOS type 0 0 0 0 0 0 1 CMBC-10 Ductal, NOS type 1 1 0 0 0 2 1 CMBC-11 Ductal, NOS type 0 0 0 0 1 1 1 CBMC-12 Ductal, NOS type 0 0 1 0 0 1 1 SGC-1 Eccrine carcinoma 1 1 1 1 1 5 2 SGC-2 Eccrine carcinoma, ex 0 0 0 0 0 0 1 spiradenocylindroma SGC-3 Porocarcinoma 1 1 1 1 1 5 2 SGC-4 Porocarcinoma 1 1 1 1 1 5 2 SGC-5 Microcystic adnexal carcinoma 1 1 1 1 1 5 2 SGC-6 Eccrine carcinoma 1 1 1 1 1 5 2 SGC-7 Porocarcinoma 1 1 1 1 1 5 2 SGC-8 Microcystic adnexal carcinoma 1 1 1 1 1 5 2 SGC-9 Microcystic adnexal carcinoma 1 1 1 1 1 5 2 SGC-10 Eccrine carcinoma 1 1 1 1 1 5 2 SGC-11 Eccrine carcinoma, ex 0 1 1 1 1 4 2 spiradenocylindroma Abbreviations: CK, cytokeratin; CMBC, cutaneous metastatic breast carcinoma; ID, identification; MGB, mammaglobin; NOS, not otherwise specified; SGC, sweat gland carcinoma. a Condition is the presumed result for metastatic breast carcinoma given the significant difference between CMBC and SGC for each of the 5 immunohistochemistry stains (see Table 4). b Group 1, ,3 conditions not met 5 CMBC; group 2, $3 conditions not met 5 SGC. IHC staining profile: mammaglobin+, p632, CK52, CK142, patterns of CMBC and SGC. Ultimately, combining CK172. mammaglobin, p63, CK5, CK14, and CK17, we construct- For each condition that was not met, 1 point was added. ed the IHC panel described above that consistently If the score was less than 3 of 5 (0, 1, or 2; ,60%), the case differentiates CMBC from SGC in our cases. was defined as CMBC; if it was greater than or equal to 3 of Numerous difficulties have hindered researchers in the 5 (3, 4, or 5; $60%), it was defined as SGC. Using this sum identification of a clinically useful IHC panel to distin- score system with these conditions, 12 of 12 patients with guish these entities: the paucity of material, varying CMBC (100% sensitivity) were correctly identified as were morphologic appearances of the entities, and differences 10 of 11 patients with SGC (91% specificity) (Table 5). in IHC staining techniques across laboratories are only a few. At the outset of this study, the number of cases COMMENT identified was few and reflected the rarity of these After reviewing several studies that also attempted to neoplasms. In addition, there was considerable heteroge- differentiate breast cancer and SGC, we attempted to neity among the groups of tumors examined. Within the identify the most specific antibodies to differentiate these classifications of CMBC and SGC, rare subtypes existed 2 neoplasms. The ER, PR, CK7, and CK20 stains were not that were challenging to evaluate. For example, only one effective in differentiating these entities. The GCDFP-15, case of basal-phenotype CMBC was included in our study. carcinoembryonic antigen, EGFR, CK5/6, podoplanin, The IHC staining pattern of that CMBC subtype included and p63 stains all showed potential based on previous known positivity for the basal cytokeratins (CK5, CK14, studies. We further investigated 3 of these 6 IHC stains and CK17).26 Although that one case expressed positivity (GCDFP-15, CK5/6, and p63). In addition, we incorporat- for both CK5 and CK17, it still fulfilled the criteria of the ed 5 additional IHC stains (CK14, CK17, AR, mammaglo- panel for classification of the neoplasm as a CMBC. bin, and PAX5), which had not been previously employed, Another rare entity with possible confounding IHC to our knowledge, in differentiating these lesions. Our staining would be metaplastic breast carcinoma. Although limited panel did not include carcinoembryonic antigen, its morphologic characteristics can be quite distinct, it has EGFR, or podoplanin. Carcinoembryonic antigen and been reported to be positive for p63.10 The staining pattern EGFR had not shown as much promise in the studies of that entity for basal CK has not been extensively reviewed as other IHC stains we wished to include. The evaluated. Both of these subtypes of breast cancer warrant promising utility of podoplanin (published after the further investigation of their unique IHC staining pat- completion of our study) was unknown during our terns. investigation. For SGC, 2 cases of EC ex spiradenocylindroma were Our study demonstrated a sustained potential of CK5/6 included. These extremely rare neoplasms demonstrated (or CK5 in our study) and p63 in distinguishing CMBC areas of apocrine differentiation. Undoubtedly, further from SGC. The GCDFP-15 stain did not reveal a study of a larger cohort of SGC cases with apocrine statistically significant difference between the staining differentiation would be desirable. However, of these 2 EC 982 Arch Pathol Lab Med—Vol 135, August 2011 IHC Panel of CMBC Versus SGC—Rollins-Raval et al
  • 9. ex spiradenocylindroma, only 1 did not fulfill enough References conditions to be defined as an SGC by our immunopanel 1. Krathen RA, Orengo IF, Rosen T. Cutaneous metastasis: a meta-analysis of data. South Med J. 2003;96(2):164–167. (see Table 5, SGC-2). The other EC ex spiradenocylin- 2. Spencer PS, Helm TN. Skin metastases in cancer patients. Cutis. 1987;39(2): droma (case 1, described above) fulfilled the criteria of the 119–121. IHC panel and was correctly identified as an SGC (see 3. Cooper PH. Carcinomas of sweat glands. Pathol Annu. 1987;22(pt 1):83– 124. Table 5, SGC-11). The 5-stain IHC panel would have 4. Cangelosi JJ, Nash JW, Prieto VG, Ivan D. Cutaneous adnexal tumor with an significantly reduced the diagnostic difficulty initially unusual presentation—discussion of a potential diagnostic pitfall. Am J encountered by the pathologists involved with that case. Dermatopathol. 2009;31(3):278–281. 5. McLean SR, Shousha S, Francis N, et al. Metastatic ductal eccrine Although these rare subtypes of CMBC and SGC have adenocarcinoma masquerading as an invasive ductal carcinoma of the male slightly different IHC staining patterns compared with breast. J Cutan Pathol. 2007;34(12):934–938. most cases within these categories, the IHC panel correctly 6. Bayer-Garner IB, Smoller B. Androgen receptors: a marker to increase sensitivity for identifying breast cancer in skin metastasis of unknown primary classified the entities in all but one case. site. Mod Pathol. 2000;13(2):119–122. Applying the conditions of the IHC panel to case 2 7. Riva C, Dainese E, Caprara G, et al. Immunohistochemical study of (described above) also pointed to a more definitive androgen receptors in breast carcinoma: evidence of their frequent expression in lobular carcinoma. Virchows Arch. 2005;447(4):695–700. diagnosis. Mammaglobin was negative, whereas p63 8. Narita D, Raica M, Suciu C, Cimpean A, Anghel A. Immunohistochemical and CK5/6 were positive, which fulfilled 3 of the expression of androgen receptor and prostate-specific antigen in breast cancer. conditions of the IHC panel and identified the lesion as Folia Histochem Cytobiol. 2006;44(3):165–172. 9. Moinfar F, Okcu M, Tsybrovskyy O, et al. Androgen receptors frequently are an SGC. The case pathologist commented that the expressed in breast carcinomas: potential relevance to new therapeutic strategies. morphology of this new lesion was not completely Cancer. 2003;98(4):703–711. consistent with primary breast lesion but agreed that 10. Koker MM, Kleer CG. p63 expression in breast cancer: a highly sensitive because breast carcinomas may progress into poorly and specific marker of metaplastic carcinoma. Am J Surg Pathol. 2004;28(11): 1506–1512. differentiated forms over time, a breast carcinoma could 11. Bhargava R, Beriwal S, Dabbs DJ. Mammaglobin vs GCDFP-15: an not be completely ruled out. With the addition of the IHC immunohistologic validation survey for sensitivity and specificity. Am J Clin panel to the morphologic examination and clinicopatho- Pathol. 2007;127(1):103–113. 12. Smith KJ, Williams J, Corbett D, Skelton H. Microcystic adnexal logic information, the case pathologist was more confident carcinoma: an immunohistochemical study including markers of proliferation in favoring a diagnosis of SGC. The IHC panel was useful and apoptosis. Am J Surg Pathol. 2001;25(4):464–471. in distinguishing CMBC from SGC in cases with classic 13. Kariya Y, Moriya T, Suzuki T, et al. Sex steroid hormone receptors in human skin appendage and its neoplasms. Endocr J. 2005;52(3):317–325. morphologies as well as those with unique characteristics 14. Hoang MP, Dresser KA, Kapur P, High WA, Mahalingam M. Microcystic that yielded broader differential diagnoses. adnexal carcinoma: an immunohistochemical reappraisal. Mod Pathol. 2008; In addition to organizing a diagnostically useful IHC 21(2):178–185. 15. Hiatt KM, Pillow JL, Smoller BR. Her-2 expression in cutaneous eccrine panel, we present other interesting findings. The basal- and apocrine neoplasms. Mod Pathol. 2004;17(1):28–32. phenotype CMBC cases have the potential to metastasize 16. Wallace ML, Longacre TA, Smoller BR. Estrogen and progesterone to the skin, apart from other known metastatic sites, such receptors and anti-gross cystic disease fluid protein 15 (BRST-2) fail to distinguish metastatic breast carcinoma from eccrine neoplasms. Mod Pathol. 1995;8(9): as brain and bone. Furthermore, the percentage of 897–901. mammaglobin expression in CMBC appeared similar to 17. Wick MR, Ockner DM, Mills SE, Ritter JH, Swanson PE. Homologous its previously reported expression in PBC.11 This finding carcinomas of the breasts, skin, and salivary glands: a histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat may indicate preservation of this marker from PBC to the gland carcinoma, and salivary duct carcinoma. Am J Clin Pathol. 1998;109(1): metastases. 75–84. Also, the novel interpretation of PAX5 in a cytoplas- 18. Busam KJ, Tan LK, Granter SR, et al. Epidermal growth factor, estrogen, and progesterone receptor expression in primary sweat gland carcinomas and mic and/or membranous staining pattern may provide primary and metastatic mammary carcinomas. Mod Pathol. 1999;12(8):786–793. a specific marker for tumors of adnexal origin. The 19. Plumb SJ, Argenyi ZB, Stone MS, De Young BR. Cytokeratin 5/6 known role of PAX5 as a transcription factor was immunostaining in cutaneous adnexal neoplasms and metastatic adenocarcino- functionally consistent with its commonly described ma. Am J Dermatopathol. 2004;26(6):447–451. 20. Qureshi HS, Ormsby AH, Lee MW, Zarbo RJ, Ma CK. The diagnostic utility nuclear localization in B lymphocytes. However, the of p63, CK5/6, CK 7, and CK 20 in distinguishing primary cutaneous adnexal cytoplasmic and/or membranous staining pattern was neoplasms from metastatic carcinomas. J Cutan Pathol. 2004;31(2):145–152. striking and raises the possibility of alternative func- 21. Ivan D, Nash JW, Prieto VG, et al. Use of p63 expression in distinguishing primary and metastatic cutaneous adnexal neoplasms from metastatic adenocar- tions in cellular pathways. This staining pattern war- cinoma to skin. J Cutan Pathol. 2007;34(6):474–480. rants further investigation. 22. Ivan D, Hafeez Diwan A, Prieto VG. Expression of p63 in primary cutaneous adnexal neoplasms and adenocarcinoma metastatic to the skin. Mod CONCLUSIONS Pathol. 2005;18(1):137–142. 23. Liang H, Wu H, Giorgadze TA, et al. Podoplanin is a highly sensitive and We formed a highly sensitive and specific IHC panel, specific marker to distinguish primary skin adnexal carcinomas from adenocar- composed of mammaglobin, p63, and 3 basal cytokeratins, cinomas metastatic to skin. Am J Surg Pathol. 2007;31(2):304–310. 24. Ormsby AH, Snow JL, Su WP, Goellner JR. Diagnostic immunohisto- with sufficient power to aid in the differentiation between chemistry of cutaneous metastatic breast carcinoma: a statistical analysis of the CMBC and SGC. We recommend the use of this panel to utility of gross cystic disease fluid protein-15 and estrogen receptor protein. J Am differentiate most cases of these 2 entities in routine Acad Dermatol. 1995;32(5, pt 1):711–716. 25. Bhargava R, Beriwal S, McManus K, Dabbs DJ. CK5 is more sensitive than clinical practice. CK5/6 in identifying the ‘‘basal-like’’ phenotype of breast carcinoma. Am J Clin Pathol. 2008;130(5):724–730. We thank Cary Sipos, HT (ASCP) and Kim McManus, HT 26. Dabbs DJ, Chivukula M, Carter G, Bhargava R. Basal phenotype of ductal (ASCP) for their technical assistance. We would also like to carcinoma in situ: recognition and immunohistologic profile. Mod Pathol. 2006; thank Jay S. Raval, MD (Department of Pathology, University of 19(11):1506–1511. Pittsburgh Medical Center) and Darice Y. Wong, PhD (Depart- 27. Feldman AL, Dogan A. Diagnostic uses of Pax5 immunohistochemistry. ment of Bioengineering, University of California, Los Angeles) Adv Anat Pathol. 2007;14(5):323–334. for thoughtful discussions and critical reviews of earlier versions 28. Mhawech-Fauceglia P, Saxena R, Zhang S, et al. Pax-5 immunoexpression in various types of benign and malignant tumours: a high-throughput tissue of this manuscript. Financial support for this article was microarray analysis. J Clin Pathol. 2007;60(6):709–714. provided through the University of Pittsburgh Medical Center’s 29. Carlsten JR, Lewis MD, Saddler K, et al. Spiradenocylindrocarcinoma: a Department of Pathology. malignant hybrid tumor. J Cutan Pathol. 2005;32(2):166–171. Arch Pathol Lab Med—Vol 135, August 2011 IHC Panel of CMBC Versus SGC—Rollins-Raval et al 983