3. ITC
⢠âcancer infectionâ
⢠Described first by Christopherson
⢠ITC â Micro metastasis
⢠ONLY 0.05% of circulating tumor cells survive & initiate a metastatic
focus
6. ⢠FALSE POSITIVE : cases in which ITC are detected but metastasis
cannot be found & never develops
⢠MORPHOLOGIC = DIFFICULT TO REPORT = LOW FALSE POSITIVE
⢠NONMORPHOLOGIC = EASY TO REPORT = HIGHER FALSE POSITIVE
7. POSSIBLE CLINICAL RELEVANCE
⢠May have prognostic value
⢠May be used as selection criteria for more aggressive treatment options
⢠To monitor the efficacy of adjuvant treatment
⢠Majority of ITC are in nonproliferating phase, may be a target for antibody
therapy
⢠Role yet to be proven
8.
9. Proposed classification & coding
⢠lymph node metastasis is not found histologically
⢠morphologic examination for isolated tumor cells, the symbol âiâ is used in
parentheses after pN0.
⢠nonmorphological examinations the symbol âmolâ (for molecular) is used.
⢠In the case of sentinel lymph nodes, the additional symbol â(sn)â may be
used e.g., pN0(i1) (sn)
10.
11.
12. ITC & BREAST CANCER : YES/NO/MAY BE?
⢠Detailed examination of sentinel nodes by serial sectioning and
immunohistochemical staining can result in the detection of
extremely small tumors.
⢠AJCC :
⢠isolated tumor cells (ITC) = tumor cell clusters that are â¤0.2 mm
⢠micro metastases (MM) = >0.2 mm in diameter but â¤2 mm, denoted as
pN1mi.
⢠It was initially reported that the presence of ITC or MM is not an
adverse prognostic factor in breast cancer.
13. ⢠In 2009, Hansen et al.
⢠8-year overall and disease-free survival of patients with negative nodal status, ITC, or MM were not
significantly different.
⢠They concluded that patients with ITC or MM do not have a worse prognosis than node-negative
patients. However, they also showed that patients with ITC or MM underwent adjuvant
chemotherapy and axillary LN dissection more often than node-negative patients.
14. ⢠Conversely, de Boer et al.
⢠assessed a large amount of data from the Netherlands Cancer Registry
⢠early-stage breast cancer patients with ITC or MM in regional LNs who had
not received adjuvant therapy had a reduced 5-year disease-free survival rate.
⢠They also performed a meta-analysis that showed that the presence
of metastases of â¤2 mm in regional LNs is associated with poor
survival.
15. ⢠Andersson et al. reported that MM have a negative impact on survival
whereas ITC do not. However, they also found that patients with ITC
underwent axillary LN dissection significantly more often than those
with no detected LN deposits.
⢠Leidenius et al. reported that the presence of ITC is an adverse
prognostic factor in early breast cancer.
⢠These reports suggest that small tumor deposits have a negative
impact on survival; however, the difference in survival between ITC or
MM and node-negative cases is small and might be eliminated by
adjuvant treatment.
16. BREAST: ITC, MICROMETS & AJCC 8TH
⢠Isolated tumor cell clusters (ITC) are defined as small clusters o f cells not larger
than 0.2 mm, or single tumor cells, or fewer than 200 cells in a single histologic
cross-section.
⢠ITCs may be detected by routine histology or by IHC methods.
⢠Nodes containing only ITCs are excluded from the total positive node count for
purposes of N categorization but should be included in the total number of nodes
evaluated.
⢠the number of nodes with only ITCs should be noted in the pathology report.
18. ⢠significantly higher rate of deep myometrial invasion
⢠no significant differences between the two groups in
⢠tumor histology
⢠cervical involvement
⢠peritoneal cytology
⢠number of LNs assessed
⢠type of adjuvant therapy.
⢠ITC or MM may be a predictor of extra pelvic recurrence, especially para-
aortic node recurrence when implementation of para-aortic
lymphadenectomy is not considered.
20. ⢠It recently became evident that isolated tumor cells undetectable by conventional tumor staging are
frequently present in bone marrow of patients with apparently localized non-small cell lung cancer (NSCLC).
⢠Cytokeratin-18-positive cells in bone marrow were demonstrated in 59.7% patients at the time of primary
surgery and in 6 of 12 representative patients analysed twice 3 to 18 months after surgery.
⢠In patients without histopathological lymph node metastases (Pn0) the occurrence of 2 or more tumor cells
in bone marrow at primary surgery was a strong and independent predictor for overall survival (p =0.007) in
univariate analysis.
⢠The multivariate analysis showed a 2.8 times increased risk for shorter survival in patients with disseminated
tumor cells versus patients without such cells.
⢠Four of the 6 patients with a positive cytokeratin status after surgery developed a tumor recurrence 11 to 44
months after the operation, while none of the patients with a negative bone marrow at all time intervals
showed a tumor relapse.
21. ⢠Minimal residual bone marrow involvement is an independent
prognostic factor for overall survival in patients with node-negative
NSCLC, which may help to identify patients in need of an adjuvant
systemic therapy.
⢠The postoperative persistence or reappearance of tumor cells in bone
marrow indicates that these are not only shedded cells but rather
represent true metastasis.
22. ⢠At multivariate analysis, only T status resulted to be a factor significantly
influencing long-term disease-free (p = 0.0022) and disease-related survival
(p = 0.013); in particular the presence of lymph nodes micro metastatic
tumor cells (ITC or pN1mi) was confirmed not to affect long-term survival.
23. ITCs in Colorectal Ca : Devita
⢠Sirop et al. found only 8 papers that reported definitely poorer outcomes, whereas the remainder were
either equivocal in their conclusions or demonstrated no influence on outcome at all.
⢠Jeffers et al. evaluated LNs from 77 patients who were found to have negative LNs by routine examination
with immunocytochemical staining for cytokeratin AE1:AE3. Nineteen patients (25%) were found to have
immunohistochemical evidence of micrometastases; however, there was no difference in survival between
the microscopically positive and negative patients.
⢠Although the actual TNM staging is not altered by the presence of micrometastases, many clinicians choose
to regard the presence of such a finding as a poor prognostic variable in their consideration of adjuvant
treatment.
24. ⢠Immunohistochemistry showed that 5% of pts had micro metastases and 26%
had isolated tumor cells. A median of 5 years of follow-up revealed local or distant
recurrence in 23% of stage I/II patients with micro metastases or isolated tumor cells,
compared with 7% without micro metastases or isolated tumor cells (P = .010).
⢠Five-year disease-free survival for patients with and without micro
metastases or isolated tumor cells was 75% and 93%, respectively (P = .012). When
analysed separately, patients with isolated tumor cells (excluding micro metastases) had
also lower survival than node-negative patients (P = .012).
⢠CONCLUSION: The presence of micro metastases and isolated tumor cells was found to
be a prognostic factor for recurrence and disease-free survival.
25. ITCs in Colorectal Ca
⢠Immunohistochemical staining with an ant cytokeratin antibody is
useful in identifying isolated tumor cells in lymph nodes missed in
routine haematoxylin-eosin staining, but clinically it seems to be of
little prognostic value in patients with Dukes B colorectal carcinoma.
26.
27. ⢠â In CRC, In bone marrow and peritoneal cavity samples, the
detection rate increased in parallel with the tumor stage.
Interestingly, already 19% of patients with a stage I tumor had
positive cells within the peritoneal cavity. â
⢠After 4 years, 28% of patients with positive immunocytologic findings
in the peritoneal cavity were alive versus 60% of patients with
negative findings (p = 0.0079). No correlation was found by evaluating
the results of bone marrow samples.
⢠Similar impact was noticed in gastric cancer subjects.
28. ⢠Strongly indicated that in gastrointestinal cancer, the investigation of
peritoneal cavity cells is more relevant than the bone marrow
approach.
⢠The cumulative survival rates significantly correlated with the
immunocytologic findings.
⢠Patients with small tumors (stage I or II) and positive peritoneal cavity
samples showed a worse prognosis.
⢠Strongly suggested that the immunocytologic staining of peritoneal
lavage samples serves as a new prognostic marker.
29. ⢠Proven role in carcinoma breast
⢠Equivocal data for role in CRC
⢠Inconclusive evidence for role of itc in Ca endometrium, GI
Malignancy & cutaneous malignancies.
⢠May be viewed as a means for targeted therapy.