pendekatan pola histopatologi dalam limfoma

1. Pendekatan Pola Histopatologi
Dalam Diagnosis
Limfadenopati Reaktif
Ridholia
Departemen/KSM Patologi Anatomik
FK Universitas Airlangga / RSUD Dr. Soetomo

2. Outline
1. Gambaran makroskopis kelenjar getah bening normal
2. Gambaran mikroskopis kelenjar getah bening normal
3. Cortex : folikel primer dan sekunder
4. Paracortex
5. Medulla
6. Sinus
7. Riwayat klinis dan lokasi limfonodi yang terlibat
8. Pola histopatologi dalam diagnosis limfadenopati reaktif

3. Gambaran makroskopis kelenjar getah bening normal
1. Kecil, bulat, seperti ginjal
2. Diameter < atau = 1 cm
3. Penampang pada pembelahan: “pink brown”, homogen
Reaksi imun atau keganasan
1. Membesar, bila diameter > 3 cm maka mencurigakan
suatu keganasan
2. Putih (fish meat), nodularitas → limfoma
Sui C, et al., 2020

4. Gambaran mikroskopis kelenjar getah bening normal
Kompartemen:
• Area korteks (zona sel B)
• Folikel
• Parakorteks (zona sel T)
• high endothelial venules
• Medulla
• Area gelap (anyaman
medulla)
• Area terang (sinus medulla) Lymph Node. SpringerLink

5. Cortex (Folikel)
• Sel dendritic folikuler
• Sel limfosit B(centroblast,
centrocytes), TFH
• Tingible-body macrophages
Centroblasts (large non-cleaved cells) : sel B berukuran besar
dengan sitoplasma sedikit-sedang, inti bulat-oval, vesikuler,
anak inti kecil – jelas berada dekat membran inti (panah)
Centrocytes (cleaved cells) : sel B berukuran kecil – besar,
inti iregular dan berlekuk , seperti terpuntir, memanjang, anak
inti (-), sitoplasma sedikit (arrow head)
Mitosis (panah berlekuk)

6. Folikel primer dan sekunder
Bcl 2 Bcl 6
Diagnostic lymphoid pathology, 2011

7. Paracortex
• Epithelioid (or
Postcapillary or High
Endothelial) Venules
Sel endotel silindris, nucleus
oval besar, kromatin
vesicular, nucleoli tidak jelas.
• Interdigitating Dendritic
Cells
• Lymphoid Cells Histology for pathologist, 4th edition, 2021

8. Medulla
Medulla: area gelap dan terang
• Area gelap (anyaman medulla):
sel plasma, sel limfosit, sel
limfosit plasmasitoid,
plasmablast
• Area terang (sinus medulla):
monosit, makrofag, sel plasma,
sel mast
UGM

9. Sinus
• Makrofag
• Beberapa limfosit
Histology for pathologist, 4th edition, 2021

10. Historical clues Suggested diagnoses Initial testing
Fever, night sweats, weight loss, node
located in supraclavicular, popliteal, ilian,
bruishing, splenomegaly
Leukemia, lymphoma, solid tumor
metastasis
CBC, nodal biopsy or bone marrow biopsy,
imaging USG or CT
Fever, chills, malaise, sore throat, nausea,
vomiting, diarrhea, no other red flag
symptoms
Bacterial or viral pharyngitis, hepatitis,
influenza, mononucleosis, tuberculosis,
rubella
Limited illnesses may not require any
additional testing, depend on clinical
assessment, consider CBC, monospot test,
liver function tests, cultures, & disease
specific serologies as needed
High risk sexual behavior Chancroid, HIV infection, lymphogranuloma
venereum, syphillis
HIV1/HIV2 immunoassay, rapid plasma
reagen, culture of lesions, nucleic acid
amplification for chlamydia, migration
inhibitory factor test
Cats Cat scratch disease, toxoplasmosis Serology, PCR
Rabbits, or sheep or cattle wool, hair, or
hides
Anthrax, brucellosis, tularemia Serology, PCR
Undercooked meat Anthrax, brucellosis, toxoplasmosis Serology, PCR
Recent travel, insect bites Diagnoses based on endemic region Serology and test indicated by suspected
exposure
Arthralgias, rash, joint stiffness, fever, chills,
muscle weakness
Rheumatoid arthritis, Sjogren syndrome,
dermatomyositis, SLE
ANA, ESR, CBC, rheumatoid factor,
creatine kinase, electromyography, muscle
biopsy
Gaddey and Riegel, 2016

11. Involved lymph node(s) Etiology
Occipital scalp infection; insect bite, ringworm;very rarely lymphoma/metastatic tumors
Posterior auricular Rubella
Anterior auricular Infections of eyelids&conjunctivae;epidemic keratoconjunctivities
Posterior cervical Toxoplasmosis
Posterior cervical and submental Scalp infections;dental infections;tuberculosis
Anterior cervical Infections of oral cavity and pharynx
Cervical (suppurative) Tuberculosis
Supraclavicular (hard & fixed) Metastases from intrathoracic or intraabdominal Ca; rarely infections
Axillary Infections of upper extremities; cat scratch diseases; brucellosis; sporothrichosis, NHL
Epitrochlear : - Unilateral
- Bilateral
- Infections of hands
- Viral diseases in children; sarcoidosis, tularemia
Inguinal: - Unilateral
- Bilateral
- Lymphogranuloma venereum; syphilis
- Gonococcal, Herpetic veneral infections; mycoplasmal infection; urethritis
Progressively enlarged without infection Lymphoma; metastatic carcinoma
Pulmonary hilar : Unilateral
Bilateral
- Metastatic lung carcinoma
- Sarcoidosis; TB; histoplasmosis; coccidioidomycosis
Mediastinal, asymmetric Hodgkin lymphoma, nodular sclerosis; NHL
Intra-abdominal and retroperitoneal, palpable or displacing
viscera
Lymphoma; metastatic carcinoma; TB in mesenteric lymph node
Regional involvement in systemic infections Infectious mononucleosis; viral hepatitis;CMV; rubella; influenza
Generalized lymphadenopathy Sarcoidosis; hyperthyroidism; autoimmune hemolytic anemia; lymphoma

12. Follicular/Nodular Interfollicular/Para-
cortical
Diffuse Sinus Mixed/other
Reactive follicular
hyperplasia
Explosive follicular
hyperplasia (HIV)
PTGC
Castleman disease
Rheumatoid
lymphadenopathy
Luetic lymphadenitis
Kimura disease
Immunoblastic
proliferations
Viral lymphadenitis
(EBV, CMV, herpes)
Post vaccination
lymphadenitis
Drug sensitivity (eg.
Diphenylhydantoin
(Dilantin)
Immunoblastic
proliferations
Viral lymphadenitis
(EBV, CMV, herpes)
Post vaccination
lymphadenitis
Drug sensitivity (eg.
Diphenylhydantoin
(Dilantin)
Sinus hyperplasia
Rosai Dorfman
disease
Lymphangiogram
effect
Whipple disease
Vascular
transformation of
sinuses
Hemophagocytic
syndrome
Mixed hyperplasia
Dermatopathic
lymphadenopathy
Toxoplasmosis
Cat scratch disease
SLE
Kawasaki disease
Kikuchi
lymphadenitis
Granulomatous
lymphadenitis
Inflammatory
pseudotumor
Pola Histopatologi Dalam Diagnosis Limfadenopati Reaktif
Rosai and Ackerman’s Surgical Pathology, 11th ed, 2018

13. Histology for pathologist, 4th edition, 2021

14. Pola Histopatologi Dalam Diagnosis Limfadenopati Reaktif
Follicular/
Nodular Mixed/Others
Diffuse Sinus
Interfollicular/
paracortical

15. Pola Follicular/nodular

16. Kasus 1. Diagnosis ?
RSUD Dr. Soetomo
Reactive follicular hyperplasia Follicular lymphoma

17. Reactive follicular hyperplasia (Unspecified)
RSUD Dr. Soetomo
Tingible body macrophages (starry sky)

18. Follicular Lymphoma vs Reactive Follicular Hyperplasia

20. Castleman disease hyaline-vascular type Castleman disease plasma cell type
Kasus 2. Diagnosis?

21. Castleman Disease
Dr Amos Tay, 2023

22. HYALINE-VASCULAR VARIANT
Morfologi
• Hiperplasia folikel limfoid
(>>depleted follicles)
• GCs mengandung sedikit limfosit,
digantikan oleh sel dendritic folikel
• Folikel limfoid dipenetrasi oleh
arteriol sklerotik (lollipop)
• Deposit hyaline pada germinal center
• expanded mantle zone (onion skin)
Castleman Disease
• Interfollicular proliferation of vasculature,
often sclerotic, increased fibrosis
• Sinuses compressed and obliterated
• Capsule fibrotic and thickened
• Stromal rich variants with marked
“angiomyoid” interfollicular stromal
proliferation

23. Reactive Follicular Hyperplasia Mantle cell lymphoma mantle zone
growth pattern
Clinical >> Children and young adults Median age 60 yo
Morphology Normal mantle zone Expanded mantle zone with uniform
moderately atypical population
(centrocyte-like)
Immunohistochemistry Cyclin D1-, SOX11-.
No clonal Ig gene rearrangement
Cyclin D1+, SOX11+
Clonal Ig gene rearrangement
(translocation Ig gene and CCND1)
NEOPLASTIC COUNTERPART
Yuan et al, 2019

24. AITL
NEOPLASTIC COUNTERPART
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Pattern 1
Pattern 2 Pattern 3
CD AITL (pattern 1 &2)
Clinical Good Very ill, advanced stage
Follicular
hiperplasia
+ + (pattern 1)
Atrophic follicles + + (pattern 2)
Inflammatory
cells
+(sel
plasma
domi-
nan)
+ (a range of reactive
cell types including
eosinophiles,histiocy-
tes)
Cluster of
atypical TFH
cells (CD10+,
BCL6+,PD1+,
ICOS+,
CXCL13)
- +
Swerdlow et al., 2016

25. PLASMA CELL VARIANT
Morfologi
• Hiperplasia folikel limfoid
dengan germinal center reaktif
• Sebukan sel plasma pada
interfolikuler
• Sinus patent
Castleman Disease
Lyapichev K, et al. 2020
IOACHIM’S Lymph Node Pathology, 5th edition, 2022

26. NEOPLASTIC COUNTERPART
Castleman Disease
plasma cell variant
B-cell lymphoma with
plasmacytic differentiation
(Lymphoplasmacytic
Lymphoma, Marginal zone
Lymphomas)
Plasmacytoma dan
plasma cell myeloma
Autoimmune
lymphadenopathy (RA,
SLE)
Arsitektur normal Arsitektur terganggu Arsitektur terganggu • Arsitektur normal
• Gejala klinis,
physical findings?
• Waldenstorm
macroglobulinemia
–
• Dutcher bodies -
Russell bodies -
• Regio interfolikuler
kaya vaskuler
• Sel plasma:
Polyclonal
• Lymphoplasmacytic
Lymphoma: Waldenstorm
macroglobulinemia;
Dutcher bodies+; Russell
bodies +
• Regio interfolikuler tidak
kaya vaskuler
• Sel plasma: Monoclonal
• End organ
damage (CRAB?)
• Dutcher bodies+;
Russell bodies +
• Regio interfolikuler
tidak kaya
vaskuler
• Sel plasma atipik,
monoclonal
Lab: Rheumatoid
factor?, ANA test?

27. RSUD Dr. Soetomo
Laki-laki,
20 th.
Lokasi
dorsum
nasi.
Diagnosis?
Kasus 3.
Benign
lymphoproliferative
lesion dapat dijumpai
pada Kimura disease

28. Iranian Journal of Otorhinolaryngology, Vol.28(3), Serial No.86, May 2016
Case Report
Kimura’s Disease – An Unusual Presentation
Praveer Kumar Banerjee1
,
*
Abhineet Jain1
, Manjunath D2
Abstract
Introduction:
Kimura’s disease is a rare chronic inflammatory disease of unknown etiology, presenting as
painless subcutaneous nodules with lymphadenopathy and peripheral eosinophilia, mainly
disturbing the head and neck region. It mainly affects Asian males in their 2nd
to 4th
decade of
life. One such case of Kimura’s disease, which is uncommon in Indian natives, is reported.
Case Report:
A male patient presented with an insidious onset of a progressive painless disfiguring swelling
over his nose since four years, which was associated with nasal obstruction and post aural
swelling with a history of an inconclusive incisional biopsy. Clinical examination showed a
bilobed subcutaneous swelling present over the nose and a collapsed nasal valve area on
anterior rhinoscopy. FNAC was non-diagnostic and CT scan showed a mildly enhancing mass
lesion over the external nose. Complete surgical excision was performed. Diagnosis was
confirmed upon postoperative histopathology. During his 2nd week follow up, the patient had
a small nasal recurrence, which was treated medically with oral steroids, cetirizine, and

29. Inflamasi kronis yang mengenai jaringan subkutan dan kelenjar getah bening. >> usia dekade 3 dan 4,
laki-laki >>
• Lokasi paling sering: kepala dan leher, infra atau retroauricula.
• Etiologi: tidak diketahui
• Eosinophilia dalam darah ( >0,5x109/L)
• Peningkatan level Imunoglobulin E (IgE) dalam serum
• Morfologi:
➢ Hiperplasia folikel dengan germinal center reaktif
➢ Infiltrasi eosinofil luas, folicullolysis +/-
➢ Proliferasi vaskuler dengan sel endotel yang prominent
➢ warthin-finkeldey type polykaryocytes
Kimura Disease

30. Hiperplasia folikel
Sebukan luas
eosinofil di
regio
paracortex /
interfollicular
Warthin-finkeldey type
polykaryoyte (arrow),
eosinofil dan proliferasi
kapiler IOACHIM’S Lymph Node Pathology, 5th edition, 2022

31. DIAGNOSIS BANDING
Buder et al., 2013

32. Angiolymphoid Lymphoid Hyperplasia With Eosinophilia (ALHE)

33. DIAGNOSIS BANDING
Diagnosis Kimura Disease Drug reactions Parasitic infection
History - Riwayat
penggunaan
obat2an
-
Morfologi Eosinofilia Eosinofilia Eosinofilia
Folikel
hiperplastik
dengan GC
reaktif
Hiperplasia
folikular dan
parakortikal
Folikel hiperplastik
disertai granuloma,
terdeteksi sisa parasit
ResearchGate

34. NEOPLASTIC COUNTERPART
Kimura disease Classical Hodgkin Lymphoma Mixed Cellularity
Type
Age >> young adults Bimodal age distribution
location >> head and neck region (infra or
retroauriculer)
>> Nodal
Clinical features No B symptoms, peripheral blood
eosinophilia and elevated IgE
B symptoms, no peripheral blood eosinophilia and
elevated IgE
atlasgeneticsoncology.org

35. Langerhans Cell Histiocytosis (histiocytosis x)
Kimura disease Langerhans Cell Histiocytosis
Age >> young adults & male (3-4th decade of life),
Asians
Any age, mainly in children 1-4 yo
location >> head and neck region (infra or
retroauriculer)
>> bone and soft tissue, any site
Clinical features Involving subcutanous tissue or lymph nodes,
peripheral blood eosinophilia and elevated
IgE
Diabetes insipidus -
Localized LCH: simplex rash, bone damage, lymph nodes
involvement; disseminated LCH: internal organs were
involved, w/wo dysfunction of lung, liver or hemopoietic
system
Diabetes insipidus +/-
Lian et al., 2016

36. Pola
parakortikal/interfolikular
dan diffuse

37. Paracortical Hyperplasia
Partial architecture effacement.
Expansion of the paracortical
area
The admixture of different cell
types. Lymphocytes, histiocytes,
plasma cells, eosinophils,
immunoblasts
Increase vascularities w/
prominent high endothelial
venules

38. Pola parakortikal / interfolikular dan diffuse
• Immunoblastic proliferations
• Viral lymphadenitis
• Post vaccination
• Drug sensitivity
Sel limfosit T CD3+ di paracortex >> Sel immunoblast CD30+
Rosai and Ackerman’s Surgical Pathology, 11th ed, 2018

39. Infectious Mononucleosis lymphadenitis
Proliferasi sel immunoblast tersusun dalam
lembaran. Sel limfosit dengan ukuran bervariasi
Sel immunoblast dengan inti basophilic dan terdapat
paranuclear hof (RS?)
IOACHIM’S Lymph Node Pathology, 5th edition, 2022
Kasus 4. laki-laki, 12 th. Limfadenopati leher posterior.
Riwayat klinis px: tonsillopharyngitis. Diagnosis?

40. Infectious Mononucleosis lymphadenitis
➢ Limfadenitis akut yang disebabkan oleh infeksi Epstein-Barr Virus (EBV)
Klinis
• Usia anak2, remaja dan dewasa muda
• Triad: demam, faringitis, limfadenopati
• Limfositosis dengan sel atipik (Downey cells)
• Dibuktikan dengan : tes monospot +, tes serologi antibodi EBV, molekuler
(EBER ISH)

41. Infectious Mononucleosis lymphadenitis
Populasi sel heterogen di paracortex. Mottled
appearance. 2 sinus yang masih intak (panah)
Sel immunoblast CD20+ Sel immunoblast CD30+
IOACHIM’S Lymph Node Pathology, 5th edition, 2022

42. Viral lymphadenitis

43. NEOPLASTIC COUNTERPART
Infectious Mononucleosis Classical Hodgkin
Lymphoma
DLBCL ALCL
Arsitektur KGB terganggu
sebagian (masih tampak
folikel intak)
Arsitektur KGB terganggu
sebagian (masih tampak
folikel intak) +/-
Arsitektur KGB terganggu Sel neoplastik menginvasi
sinus dan menggantikan
arsitektur normal
Sinus + dilatasi, proliferasi
vaskuler +
Sinus -/+, proliferasi
vaskuler -
Sinus -, proliferasi
vaskuler -
Sinus diinvasi oleh sel
neoplastik, proliferasi
vaskuler -
Populasi sel
heterogen; spektrum sel
limfosit dari kecil ke besar;
Sel immunoblast dengan
inti basophilic dan
terdapat paranuclear hof
(RS-like cells)
Sel HRS diantara sel
inflamasi
Populasi homogen sel
immunoblast
Sel neoplastik tersu-
sun padat, sinusoidal
- Hallmark cells:
seperti ginjal
EBV + Sel HRS: CD30+, CD15+,
CD45-, marker sel B-/+,
sel T-, EBV+/-
5% DLBCL EBV+, usually
in elderly person
CD20+, CD30+
Marker sel T +/-, CD30+
strong, compact
ALK+/-, EMA+, EBV-

44. Kasus 5. Second opinion
Ny. s/36 tahun
Dx. klinis : tumor colli kanan
Dx. PA luar: kesan Hodgkin
Lymphoma. Diagnosis?
RSUD Dr. Soetomo

45. Diagnosis?
Area padat sel→ sel berukuran besar,kromatin
kasar.
Area pucat →nekrosis, debris karyorrhexis
RSUD Dr. Soetomo

46. Diagnosis?
Area padat sel CD3 40x CD3 400x
RSUD Dr. Soetomo

47. Diagnosis?
Area padat sel . CD20 400x Area padat sel . CD30 400x
RSUD Dr. Soetomo

48. RSUD Dr. Soetomo
Diagnosis?

49. Kikuchi-fujimoto disease (histiocytic necrotizing
lymphadenitis)
PAX5. 400x ZN negatif. 1000x
RSUD Dr. Soetomo
Diagnosis?

50. Kikuchi-fujimoto disease
(histiocytic necrotizing lymphadenitis)
• Etiologi: tidak diketahui
• >> Usia dewasa muda, women > men, Asia >>
• Limfadenopati di leher>>, unilateral
• Klinis:
• Asymptomatic, subfebris, penurunan berat badan, keringat malam, skin
rash, sakit tenggorokan, nyeri persendian
• Umumnya remisi spontan

51. Kikuchi-fujimoto disease (histiocytic
necrotizing lymphadenitis)
Morfologi
• Arsitektur KGB Normal masih dapat
dievaluasi
• Lokasi parakorteks
• Patchy areas of necrosis
• Apoptosis luas, debris inti luas
• Nonphagocytic histiocytes dengan crescent-
shaped nuclei
• Plasmacytoid dendritic cells
• Sel limfosit dan immunoblast
• Tidak ada neutrofil dan eosinofil
Clue:Fokus pucat yang terdiri dari kumpulan histiosit,
lokasi di antara GC kiri dan kanan. Deaver, et al., 2014

52. Kikuchi-fujimoto disease (histiocytic necrotizing
lymphadenitis)
Nonphagocytic histiocytes dengan crescent-shaped nuclei, debris inti
Deaver, et al., 2014

54. DIAGNOSIS BANDING
SLE

55. DIAGNOSIS BANDING
SLE
lymphadenitis
Necrotizing
granulomatous
lymphadenitis (TB,
histoplasmosis,
Cat-scratch
Disease (CSD))
Syphilis Infectious
mononucleo
-sis
Herpes simplex
lymphadenitis
Lymphoma
Sel
plasma,
hemato-
xylin
bodies;
vasculitis
dengan
deposit
DNA
pada
dinding
P.D(Azzo
pardi)
CSD, fungal:
Neutrofil,
granuloma, giant
cells.
TB: nekrosis
kaseosa+/-,
langhans giant cell
Special stain: PAS,
GMS,ZN, Warthin-
starry
Banyak sel
plasma
mengelilingi
pembuluh
darah,
terutama di
kapsul
Spirochetes+
(warthin-
starry silver
stained);
IHK,PCR
EBV+ Cowdry type A
intranuclear viral
inclusion
Distribusi patchy
parakorteks - ;
single-cell
apoptosis luas -
Jika perlu:
pemeriksaan
lanjutan (IHK),
molekuler

56. Pola Sinus

57. Diagnosis?
Expansion of sinuses due to the increased number of histiocytes. Non
spesific reaction of lymph nodes to infections and neoplasia. Tzankov
and Dirnhofer, 2017
Sinus Histiocytosis

58. Kasus 6. Laki-laki, usia 35 th. Limfadenopati
leher, bilateral, ukuran > 10 cm
Reddy, et al. 2014 Tzankov and Dirnhofer, 2017

59. Rosai Dorfman Disease
Diagnosis?

60. Sinus Histiocytosis With Massive Lymphadenopathy
(Rosai Dorfman Disease)
• Etilogi: tidak diketahui
• Lokasi : Nodal dan ekstranodal (>> nasal cavity dan sinus paranasal)
• Massive lymphadenopathy (KGB leher >>)
• >> tanpa gejala, 1/3 pasien: demam, penurunan BB yang signifikan,
keringat malam
Reddy, et al. 2014

61. Sinus Histiocytosis With Massive Lymphadenopathy
(Rosai Dorfman Disease)
Morfologi
• Dilatasi sinus KGB berisi sel limfosit, sel plasma dan histiosit
• Proliferasi histiosit dan mempunyai ciri khas intracelluar engulfment of
lymphocytes (emperipolesis)
• Lipid-laden macrophages (xanthoma cells): oil red O stain +
• Plasmacytosis
• Capsular fibrosis

62. NEOPLASTIC COUNTERPART

63. RDD VS LCH
Rosai Dorfman Disease Langerhans Cell Histiocytosis
Large nuclei Small to medium sized nuclei
Round, vesicular nuclei Grooved, folded nuclei
Prominent nucleoli Inconspicious nuclei
Prominent emperipolesis No emperipolesis
Eosinophils infrequent Eosinophils frequent
Capsular fibrosis frequent Capsular fibrosis infrequent
Plasmacytosis frequent Plasmacytosis infrequent
CD1a- CD1a+
Both are S100+

64. Pola Kombinasi

65. toxoplasmosis

66. Kasus 7. Diagnosis?
RSUD Dr. Soetomo

67. Diagnosis?
Limfadenitis Tuberculosis
RSUD Dr. Soetomo
ZN+

68. Area nekrosis (kanan atas), kumpulan sel
epitheloid dengan multinucleated giant cells (kiri
bawah)
Pulasan Ziehl-Nielsen. Single, slender, acid-fast
bacillus
IOACHIM’S Lymph Node Pathology, 5th edition, 2022
Limfadenitis Tuberculosis

69. Diagnostic lymphoid pathology, 2011
Kasus 8.
wanita, 25
th.
Limfadeno-
pati leher
posterior.
Diagnosis?

70. Diagnostic lymphoid pathology, 2011
Limfadenitis
Granulomatous
dapat dijumpai
pada
limfadenitis
toxoplasmosis.
Saran ?

71. Limfadenitis Toxoplasmosis
• Lymphadenitis caused by infection with the protozoan Toxoplasma gondii
Triad :
1. Marked follicular hyperplasia
2. Small granulomas, located within the hyperplastic follicles & at the periphery
3. Distention of marginal and cortical sinus by monocytoid B-cells
• Rare: observation of Toxoplasma organisms in lymph node
Serologic test:
• Sabin-feldman dye test (highly sensitive&specific)
• IgG & IgM anti Toxoplasma
Rosai and Ackerman’s Surgical Pathology, 11th ed, 2018

72. DIAGNOSIS BANDING
Tzankov and Dirnhofer, 2017
A. poorly-formed granuloma located at the
periphery hyperplastic follicle; B. monocytoid B-
cell hyperplasia
Limfadenitis Toxoplasmosis
Rosai and Ackerman’s Surgical Pathology, 11th ed, 2018
Sarcoidosis

73. UGM
Kasus 9.
Diagnosis?

74. UGM

75. UGM
Limfadenopati
dermatopatik.
Apakah
terdapat lesi
kulit kronis
pada pasien?
Mycosis
Fungoides?

76. Limfadenopati Dermatopatik
• A form of nodal hyperplasia usually secondary to a generalized dermatitis,
particularly those w/ exfoliative features
• A T-cell response to skin antigens processed and presented by interdigitating
dendritic cells
• Cut surface of node may show subcapsular rim of pigment
• Paracortical expansion with aggregates of Interdigitating reticulum cells,
histiocytes and Langerhans cells
• Scattered macrophages containing lipid and melanin

77. Multiple nodul berwarna pucat di regio paracortex .
Tampak pula hyperplasia folikel
IOACHIM’S Lymph Node Pathology, 5th edition, 2022
IDCs, sel Langerhans: membran inti pucat, inti
bengkok/berlipat, linear groove, sitoplasma luas,
melanophages
Dermatopathic Lymphadenopathy (lipomelanotic reticulosis)

78. NEOPLASTIC
COUNTERPART
Langerhans
cell
histiocytosis
Dermatopathic
lymphadenopat
hy
Garces et al., 2019

79. Kasus 10. Laki-laki, 40 th. Limfadenopati inguinal. Dx: Suspect Hodgkin Lymphoma
Diagnosis?
RSUD Dr. Soetomo
Cat-Scratch Disease
CD30 Ki67

80. Cat-scratch disease
• Limfadenitis yang disebabkan oleh bakteri gram negatif yaitu Bartonella
henselae .
• Suatu penyakit zoonosis. Reservoir bakteri terdapat pada kucing. 50%
dari kucing terinfeksi oleh Bartonella henselae
• Riwayat pasien: kontak dengan kucing (namun organismenya sulit untuk
dikultur)
• Klinis: limfadenopati unilateral, tanpa gejala

81. Cat-scratch disease
Morfologi:
• Necrotizing Granuloma (stellate)
• Central Microabscess
• Sel histiosit epitheloid tersusun palisading
• Multinucleated giant cells (rare)
• Capsular & perinodal involvement
• Pengecatan dengan Warthin-Starry silver dan Giemsa +
• IHK
• PCR (the most sensitive)

82. Apoptotic bodies, neutrofil (kanan atas). Sel
plasma dan limfosit (kiri bawah)
Warthin-starry stain
IOACHIM’S Lymph Node Pathology, 5th edition, 2022

83. Cat-scratch disease
IOACHIM’S Lymph Node Pathology, 5th edition, 2022

84. Lymph Node Inclusions
Salivary Gland Inclusion Composed
of Ductal Structures in a High
Cervical Lymph Node
Pelvic Lymph Node Involved by
Endosalpingiosis. Glands lined by
cuboidal cells with a müllerian
appearance and lacking atypical figures
are present in the capsule of the node.
Inklusi ini sulit dibedakan dengan
metastasis yang berasal dari low-grade
ovarian neoplasms.
Inklusi ini juga dapat ditemukan pada
KGB mediastinum laki-laki dan axilla
wanita
Nevus cells inclusion. Blue nevus involving
lymph node capsule.
Rosai and Ackerman’s Surgical Pathology, 11th ed, 2018

85. Lymph Node Inclusions
Inklusi lainnya:
• Epitel squamous: KGB colli. Disebut juga “benign lymphoepithelial cyst”. DD:
Metastatic well differentiated squamous cell carcinoma
• Folikel tiroid: KGB colli anterior tengah. Tidak ditemukan kondisi patologis dari
kelenjar tiroid
• Sel desidua: KGB pelvis. Selama kehamilan, hormonal, sel stroma dari endometriosis
• Sel mesothel: Diagnosis banding adalah metastatis occult malignant mesothelioma dari
rongga peritoneum atau pleura. !!!tidak ditemukan malignant mesothelioma
• Breast tissue : KGB Axilla, ektopik jaringan normal mamma

86. Pendekatan pola histopatologi lesi limfoid reaktif
Pattern Descriptive differential
diagnosis
Differential
diagnosis
Ancillary
techniques
Neoplastic
counterpart
Notes
1. Pola
Folikular
Follicular Hyperplasia Unspecific FH,
HIV-LA type A,
Autoimmune LA (RA),
Luetic LA,
IgG4-LA type II
IHC, serology, p24
staining, rheumatoid
factor, Warthin-
Starry staining,
IgG/IgG4 staining
Follicular
lymphoma, Mantle
cell lymphoma with
mantle zone
growth pattern,
lymphocyte-rich
classical hodgkin
lymphoma nodular
pattern
-
PTGC IgG4-LA type IV IgG4/IgG staining NLPHL Look for L&H cells
(LP cells)
Castleman disease IgG4-LA type I, HIV-
associated LA type C
IHC, serology, p24
staining, IgG/IgG4
staining
Mantle cell
lymphoma with
mantle zone
pattern,
Angioimmunoblasti
c T-cell lymphoma
(AITL)
Look for kaposi
sarcoma

87. Pendekatan pola histopatologi lesi limfoid reaktif
Pattern Descriptive
differential diagnosis
Differential
diagnosis
Ancillary
techniques
Neoplastic
counterpart
Notes
Kimura disease Parasitic disorder,
drug reaction
IgE staining ALHE
(Epitheloid
hemangioma),
LCH, CHL, AITL
-
2. Pola
Parakortikal
Nodular paracortical
T-cell hyperplasia
Dermatophatic
lymphadenopathy
IHC Mycosis
Fungoides,
Langerhans cell
histiocytosis
-
Diffuse
(immunoblastic)
paracortical
hyperplasia
Drug reaction,
vaccination
reaction, Herpes-
family-virus
infections, IgG4-LA
type III
Serology,
IgG/IgG4 staining,
in situ hybridization
(ISH)
AITL, DLBCL,
CHL
-

88. Pattern Descriptive
differential
diagnosis
Differential diagnosis Ancillary
techniques
Neoplastic
counterpart
Notes
3. Pola
kombinasi
Granulomatous-LA - -
Non necrotizing
granulomatous LA
Toxoplasmosis Sabin-feldman dye
test,
IgG & IgM anti
Toxoplasma
Sarcoidosis, whipple
disease
PAS Masked malignant
tumors (carcinomas,
germ cell tumors,
lymphomas)
-
Necrotizing
granulomatous LA
Mycobacteriosis
(Tuberculosis), fungal
infection (e.g.
histoplasmosis)
Ziehl-Neelsen,
grocott
methenamin sliver,
PAS stain
- -
Pendekatan pola histopatologi lesi limfoid reaktif

89. Pattern Descriptive
differential
diagnosis
Differential
diagnosis
Ancillary
techniques
Neoplastic
counterpart
Notes
Microabscess or
supurative
granulomatous
LA
cat-scratch
disease,
chronic(septic)
granulomatous
disease (CSG),
Lymphogranulo
ma Venereum,
tularemia,
yerseniosis,
Mycobacteriosis
Warthin-starry,
ZN, the nitro
blue tetrazolium
test (CSG), frei
test (LV)
Hodgkin
Lymphoma with
stellate necrosis
-
Histiocytic
necrotizing LA
Kikuchi-
Fujimoto
Disease, SLE
IHC; ANA/DS-
DNA test
High grade
lymphoma
Pendekatan pola histopatologi lesi limfoid reaktif

90. Pattern Descriptive
differential diagnosis
Differential
diagnosis
Ancillary
techniques
Neoplastic
counterpart
Notes
4. Pola sinus Sinus Histiocytosis - - Metastatic
carcinomas
-
Histiocytic reactions
with foamy histiocytes
Draining of
prostheses
Histochemistry,
polarized light
examination
- -
Hereditary storage
disease
Histochemistry,
genetics,
biochemistry
- -
Sinus histiocytosis with
massive LA
Rosai Dorfman
disease
IHC LCH -
Histiocytic increase
with
hemophagocytosis
Hemophagocytic
lymphohistiocytosis
Blood transfusion
Laboratory values - Amebiasis?
Pendekatan pola histopatologi lesi limfoid reaktif

91. • Lesi KGB reaktif dapat menyerupai limfoma, dasar-dasar histopatologi
penting untuk dipelajari.
• Korelasi klinis dan histopatologi sangat penting. Bila perlu duduk Bersama
dengan klinisi ”MDT”
• Pada kasus sulit, pemeriksaan lanjutan sangat diperlukan.
• Sample yang tidak adekuat, tehnik proses jaringan suboptimal, interpretasi
yang salah dari patolog dapat menyebabkan kesalahan diagnosis dan terapi
berlebihan.
Take home messages

92. Terima kasih kepada:
• Prof. dr. Hj. Bethy S Hernowo Sp.PA, Subsp. H.L.E(K),PhD
• dr. Nungki Anggorowati Sp.PA, Subsp. H.L.E(K),PhD

93. Selamat belajar
Semoga bermanfaat