Pendekatan Pola Histopatologi

Dalam Diagnosis
Limfadenopati Reaktif

Ridholia
Departemen/KSM Patologi Anatomik
FK Universitas Airlangga / RSUD Dr. Soetomo
 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
 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

 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
 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)
Folikel primer dan sekunder

Bcl 2 Bcl 6

Diagnostic lymphoid pathology, 2011

 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
 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
 Sinus

• Makrofag
• Beberapa limfosit

Histology for pathologist, 4th edition, 2021

Historical clues Suggested diagnoses Initial testing

Fever, night sweats, weight loss, node
located in supraclavicular, popliteal, ilian,
bruishing, splenomegaly
Fever, chills, malaise, sore throat, nausea,
vomiting, diarrhea, no other red flag
symptoms
High risk sexual behavior
Cats
Leukemia, lymphoma, solid tumor
metastasis
Bacterial or viral pharyngitis, hepatitis,
influenza, mononucleosis, tuberculosis,
rubella
Chancroid, HIV infection, lymphogranuloma
venereum, syphillis
Cat scratch disease, toxoplasmosis
CBC, nodal biopsy or bone marrow biopsy,
imaging USG or CT
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
HIV1/HIV2 immunoassay, rapid plasma
reagen, culture of lesions, nucleic acid
amplification for chlamydia, migration
inhibitory factor test
Serology, PCR

Rabbits, or sheep or cattle wool, hair, or Anthrax, brucellosis, tularemia Serology, PCR
hides
Undercooked meat Anthrax, brucellosis, toxoplasmosis Serology, PCR

Recent travel, insect bites
Arthralgias, rash, joint stiffness, fever, chills,
muscle weakness
Diagnoses based on endemic region
Rheumatoid arthritis, Sjogren syndrome,
dermatomyositis, SLE
Gaddey and Riegel, 2016
Serology and test indicated by suspected
exposure
ANA, ESR, CBC, rheumatoid factor,
creatine kinase, electromyography, muscle
biopsy
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 - Infections of hands
- Bilateral - Viral diseases in children; sarcoidosis, tularemia
Inguinal: - Unilateral - Lymphogranuloma venereum; syphilis
- Bilateral - Gonococcal, Herpetic veneral infections; mycoplasmal infection; urethritis
Progressively enlarged without infection Lymphoma; metastatic carcinoma
Pulmonary hilar : Unilateral - Metastatic lung carcinoma
Bilateral - Sarcoidosis; TB; histoplasmosis; coccidioidomycosis
Mediastinal, asymmetric Hodgkin lymphoma, nodular sclerosis; NHL
Intra-abdominal and retroperitoneal, palpable or displacing Lymphoma; metastatic carcinoma; TB in mesenteric lymph node
viscera
Regional involvement in systemic infections Infectious mononucleosis; viral hepatitis;CMV; rubella; influenza
Generalized lymphadenopathy Sarcoidosis; hyperthyroidism; autoimmune hemolytic anemia; lymphoma
 Pola Histopatologi Dalam Diagnosis Limfadenopati Reaktif
Follicular/Nodular Interfollicular/Para- Diffuse Sinus Mixed/other
cortical
Reactive follicular Immunoblastic Immunoblastic Sinus hyperplasia Mixed hyperplasia
hyperplasia proliferations proliferations
Rosai Dorfman Dermatopathic
Explosive follicular Viral lymphadenitis Viral lymphadenitis disease lymphadenopathy
hyperplasia (HIV) (EBV, CMV, herpes) (EBV, CMV, herpes)
Lymphangiogram Toxoplasmosis
PTGC Post vaccination Post vaccination effect
lymphadenitis lymphadenitis Cat scratch disease
Castleman disease Whipple disease
Drug sensitivity (eg. Drug sensitivity (eg. SLE
Rheumatoid Diphenylhydantoin Diphenylhydantoin Vascular
lymphadenopathy (Dilantin) (Dilantin) transformation of Kawasaki disease
sinuses
Luetic lymphadenitis Kikuchi
Hemophagocytic lymphadenitis
Kimura disease syndrome
Granulomatous
lymphadenitis

Inflammatory
pseudotumor
Rosai and Ackerman’s Surgical Pathology, 11th ed, 2018
Histology for pathologist, 4th edition, 2021
Pola Histopatologi Dalam Diagnosis Limfadenopati Reaktif

Follicular/ Interfollicular/
Nodular Mixed/Others
paracortical

Diffuse Sinus
Pola Follicular/nodular
 Kasus 1. Diagnosis ?
Reactive follicular hyperplasia Follicular lymphoma

RSUD Dr. Soetomo

Reactive follicular hyperplasia (Unspecified)

Tingible body macrophages (starry sky)

RSUD Dr. Soetomo
Follicular Lymphoma vs Reactive Follicular Hyperplasia
 Kasus 2. Diagnosis?

Castleman disease hyaline-vascular type Castleman disease plasma cell type

Castleman Disease

Dr Amos Tay, 2023

 Castleman Disease
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)
• 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
 NEOPLASTIC COUNTERPART
Reactive Follicular Hyperplasia
Clinical >> Children and young adults
Morphology Normal mantle zone
Immunohistochemistry Cyclin D1-, SOX11-.
No clonal Ig gene rearrangement
Mantle cell lymphoma mantle zone
growth pattern
Median age 60 yo
Expanded mantle zone with uniform
moderately atypical population
(centrocyte-like)
Cyclin D1+, SOX11+
Clonal Ig gene rearrangement
(translocation Ig gene and CCND1)
Yuan et al, 2019
 V6 R16+G51 6::+j <NOE 5GXqG<X<j E 5O; 5j } <X6j :15V V 5XNGJ 75} AI GN+O; } NOX5<O<OI Y5G<’
Xq6 b57NG5XNGJ :<O; <OI j <O} 1+; 6 } <G}+15X<OI 5716 O+V 76Gj N: G65} X<Y6 1JV RqN} JX6j E
<OI <V V +O6 } NV R16W6j E } N1; 5I I 1+X<O<Oj q<j X<N} JX6j E R15j V 5 } 611j E 5O; 6Nj <ON’
OX<’ F<Xq q56V N1JX<} 5O56V <5E RNj <X<Y6 Gq6+’ Rq<1j / q6 } 611+15G; 6Oj <XJ Y5G<6j E5O; <O
O<:J
Y6;
NEOPLASTIC COUNTERPART
511J
1; 6G
AITL CD AITL (pattern 1 &2)
Clinical Good Very ill, advanced stage
DCk

b1
<N’
<Xq Follicular + + (pattern 1)
ON.
JV ’ hiperplasia
<N’ Atrophic follicles + + (pattern 2)
5j
GN’ Pattern 1
6j ’
Y<’ Inflammatory +(sel + (a range of reactive
;6 cells plasma cell types including
V5
domi- eosinophiles,histiocy-
nan) tes)
6G1J
<O Cluster of - +
N: atypical TFH
N:
NO. DES4 4 5 1 {HO6}6J{Sx }/ xOO
FVKH 6:x KJ{ 6{
≥≥M K6+ }xHO
{S, pSF}} }%≥ /z6≥ xT f4, 3- r7 g xV}%{K;6};F≥ FKO+ %f4, 3 cells (CD10+,
vM
Szx
x
Vx
HH6S{
SO
x
FV{
OFG U{
OPattern
XFG +
z/
%+
FV{
x
:
VFl z%/
6}}{SM }x
FV/
V6Vx O2%/{Sx}}%≥ /z6{GSF}}H T/xOOFVKy-rC wxHFU{OzGF/
}xHO{S: 6}}{
S}FH U{Oz/ xVxS6VO{
Sx } F>/ xKH{6K x
Pattern
KG ≥ x
}FO
V5FG ;x
FG xOV6/z{
HSM
S:
3 K{HSFKO BCL6+,PD1+,
}x
6}}{
V/ V6}{
:
FVx
S}FH VF≥ {
O
{
6K
oyE 6:wx HO}F≥ xKG{HFx HFx KG ≥ xV5FG / FV{:
6}}{
SM}xVF>/ xKH{6K6:S}Fx VSF}}H T/xOO
FVK - r8 w}x HH{S ≥ 6V/z6}6J%U{ Oz
F::
x SF≥ FKO6:K6V≥ x }x VSz{O
FSOMVFx KG ≥ xV5FG ;x HSM}xV/ V6}{
:FVxO{6Kx HH6S{xOFG U{O
zx JJVFJx O
FH 6:x O%/{
Sx }}%≥ /
z6{G ICOS+,
SF}}H T
/x OO
FVKm-r Swerdlow et al., 2016 CXCL13)
 Castleman Disease
PLASMA CELL VARIANT Lyapichev K, et al. 2020

Morfologi
• Hiperplasia folikel limfoid
dengan germinal center reaktif
• Sebukan sel plasma pada
interfolikuler
• Sinus patent

IOACHIM’S Lymph Node Pathology, 5th edition, 2022

 NEOPLASTIC COUNTERPART
Castleman Disease B-cell lymphoma with Plasmacytoma dan Autoimmune
plasma cell variant plasmacytic differentiation plasma cell myeloma lymphadenopathy (RA,
(Lymphoplasmacytic SLE)
Lymphoma, Marginal zone
Lymphomas)

Arsitektur normal Arsitektur terganggu Arsitektur terganggu • Arsitektur normal

• Gejala klinis,
physical findings?
• Waldenstorm • Lymphoplasmacytic • End organ Lab: Rheumatoid
macroglobulinemia Lymphoma: Waldenstorm damage (CRAB?) factor?, ANA test?
– macroglobulinemia; • Dutcher bodies+;
• Dutcher bodies - Dutcher bodies+; Russell Russell bodies +
Russell bodies - bodies + • Regio interfolikuler
• Regio interfolikuler • Regio interfolikuler tidak tidak kaya
kaya vaskuler kaya vaskuler vaskuler
• Sel plasma: • Sel plasma: Monoclonal • Sel plasma atipik,
Polyclonal monoclonal
Kasus 3.
Laki-laki,
20 th.
Lokasi
dorsum
nasi.
Diagnosis?
Benign
lymphoproliferative
lesion dapat dijumpai
pada Kimura disease
RSUD Dr. Soetomo
Case Report
Iranian Journal of Otorhinolaryngology, Vol.28(3), Serial No.86, May 2016

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
 Kimura Disease
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

 Sebukan luas
eosinofil di
regio
paracortex /
interfollicular

Hiperplasia folikel

Warthin-finkeldey type
polykaryoyte (arrow),
eosinofil dan proliferasi
kapiler IOACHIM’S Lymph Node Pathology, 5th edition, 2022
DIAGNOSIS BANDING

Buder et al., 2013

Angiolymphoid Lymphoid Hyperplasia With Eosinophilia (ALHE)
 DIAGNOSIS BANDING
Diagnosis Kimura Disease Drug reactions Parasitic infection

History - Riwayat -
penggunaan
obat2an

Morfologi Eosinofilia Eosinofilia Eosinofilia

Folikel Hiperplasia Folikel hiperplastik

hiperplastik folikular dan disertai granuloma,
dengan GC parakortikal terdeteksi sisa parasit
reaktif

ResearchGate
 NEOPLASTIC COUNTERPART
Kimura disease Classical Hodgkin Lymphoma Mixed Cellularity
Type
Age >> young adults Bimodal age distribution

location >> head and neck region (infra or >> Nodal

retroauriculer)

Clinical features No B symptoms, peripheral blood B symptoms, no peripheral blood eosinophilia and
eosinophilia and elevated IgE elevated IgE

atlasgeneticsoncology.org
 Langerhans Cell Histiocytosis (histiocytosis x)
Kimura disease Langerhans Cell Histiocytosis

Age >> young adults & male (3-4th decade of life), Any age, mainly in children 1-4 yo
Asians
location >> head and neck region (infra or >> bone and soft tissue, any site
retroauriculer)

Clinical features Involving subcutanous tissue or lymph nodes, Localized LCH: simplex rash, bone damage, lymph nodes
peripheral blood eosinophilia and elevated involvement; disseminated LCH: internal organs were
IgE involved, w/wo dysfunction of lung, liver or hemopoietic
Diabetes insipidus - system
Diabetes insipidus +/-

Lian et al., 2016

 Pola
parakortikal/interfolikular
dan diffuse
 Paracortical Hyperplasia

The admixture of different cell

Partial architecture effacement. types. Lymphocytes, histiocytes, Increase vascularities w/
Expansion of the paracortical plasma cells, eosinophils, prominent high endothelial
area venules
immunoblasts
 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

 Kasus 4. laki-laki, 12 th. Limfadenopati leher posterior.
Riwayat klinis px: tonsillopharyngitis. Diagnosis?
Infectious Mononucleosis lymphadenitis

Proliferasi sel immunoblast tersusun dalam Sel immunoblast dengan inti basophilic dan terdapat
lembaran. Sel limfosit dengan ukuran bervariasi paranuclear hof (RS?)

IOACHIM’S Lymph Node Pathology, 5th edition, 2022

 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)
 Infectious Mononucleosis lymphadenitis

Populasi sel heterogen di paracortex. Mottled Sel immunoblast CD20+ Sel immunoblast CD30+
appearance. 2 sinus yang masih intak (panah)

IOACHIM’S Lymph Node Pathology, 5th edition, 2022

Viral lymphadenitis
 NEOPLASTIC COUNTERPART
Infectious Mononucleosis
Arsitektur KGB terganggu
sebagian (masih tampak
folikel intak)
Sinus + dilatasi, proliferasi
vaskuler +
Populasi sel
heterogen; spektrum sel
limfosit dari kecil ke besar;
Sel immunoblast dengan
inti basophilic dan
terdapat paranuclear hof
(RS-like cells)
EBV +
Classical Hodgkin DLBCL ALCL
Lymphoma
Arsitektur KGB terganggu Arsitektur KGB terganggu Sel neoplastik menginvasi
sebagian (masih tampak sinus dan menggantikan
folikel intak) +/- arsitektur normal
Sinus -/+, proliferasi Sinus -, proliferasi Sinus diinvasi oleh sel
vaskuler - vaskuler - neoplastik, proliferasi
vaskuler -
Sel HRS diantara sel Populasi homogen sel Sel neoplastik tersu-
inflamasi immunoblast sun padat, sinusoidal
- Hallmark cells:
seperti ginjal
Sel HRS: CD30+, CD15+, 5% DLBCL EBV+, usually Marker sel T +/-, CD30+
CD45-, marker sel B-/+, in elderly person strong, compact
sel T-, EBV+/- CD20+, CD30+ ALK+/-, EMA+, EBV-
Kasus 5. Second opinion
Ny. s/36 tahun
Dx. klinis : tumor colli kanan
Dx. PA luar: kesan Hodgkin
Lymphoma. Diagnosis?

RSUD Dr. Soetomo

 Diagnosis?

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

Area padat sel CD3 40x CD3 400x

RSUD Dr. Soetomo

 Diagnosis?

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

RSUD Dr. Soetomo

 Diagnosis?
Kikuchi-fujimoto disease (histiocytic necrotizing
lymphadenitis)

PAX5. 400x ZN negatif. 1000x

RSUD Dr. Soetomo

 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
 Kikuchi-fujimoto disease (histiocytic
Morfologi
necrotizing lymphadenitis)
• 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 Clue:Fokus pucat yang terdiri dari kumpulan histiosit,
• Tidak ada neutrofil dan eosinofil lokasi di antara GC kiri dan kanan. Deaver, et al., 2014
Kikuchi-fujimoto disease (histiocytic necrotizing
lymphadenitis)

Nonphagocytic histiocytes dengan crescent-shaped nuclei, debris inti

Deaver, et al., 2014
DIAGNOSIS BANDING

SLE
 DIAGNOSIS BANDING
SLE Necrotizing Syphilis Infectious Herpes simplex Lymphoma
lymphadenitis granulomatous mononucleo lymphadenitis
lymphadenitis (TB, -sis
histoplasmosis,
Cat-scratch
Disease (CSD))

Sel CSD, fungal: Banyak sel EBV+ Cowdry type A Distribusi patchy
plasma, Neutrofil, plasma intranuclear viral parakorteks - ;
hemato- granuloma, giant mengelilingi inclusion single-cell
xylin cells. pembuluh apoptosis luas -
bodies; darah,
vasculitis TB: nekrosis terutama di Jika perlu:
dengan kaseosa+/-, kapsul pemeriksaan
deposit langhans giant cell lanjutan (IHK),
DNA Spirochetes+ molekuler
pada Special stain: PAS, (warthin-
dinding GMS,ZN, Warthin- starry silver
P.D(Azzo starry stained);
pardi) IHK,PCR
Pola Sinus
 Diagnosis? Sinus Histiocytosis

Expansion of sinuses due to the increased number of histiocytes. Non

spesific reaction of lymph nodes to infections and neoplasia. Tzankov
and Dirnhofer, 2017
Kasus 6. Laki-laki, usia 35 th. Limfadenopati
leher, bilateral, ukuran > 10 cm

Reddy, et al. 2014 Tzankov and Dirnhofer, 2017

 Diagnosis?
Rosai Dorfman Disease
 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

 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
NEOPLASTIC COUNTERPART
 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+
Pola Kombinasi
toxoplasmosis
Kasus 7. Diagnosis?

RSUD Dr. Soetomo

 Diagnosis?
Limfadenitis Tuberculosis

ZN+
RSUD Dr. Soetomo
 Limfadenitis Tuberculosis

Area nekrosis (kanan atas), kumpulan sel Pulasan Ziehl-Nielsen. Single, slender, acid-fast
epitheloid dengan multinucleated giant cells (kiri bacillus
bawah)
IOACHIM’S Lymph Node Pathology, 5th edition, 2022
Kasus 8.
wanita, 25
th.
Limfadeno-
pati leher
posterior.
Diagnosis?

Diagnostic lymphoid pathology, 2011

Limfadenitis
Granulomatous
dapat dijumpai
pada
limfadenitis
toxoplasmosis.
Saran ?

Diagnostic lymphoid pathology, 2011

 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

 DIAGNOSIS BANDING
Limfadenitis Toxoplasmosis Sarcoidosis

Tzankov and Dirnhofer, 2017

A. poorly-formed granuloma located at the

periphery hyperplastic follicle; B. monocytoid B-
cell hyperplasia Rosai and Ackerman’s Surgical Pathology, 11th ed, 2018
Kasus 9.
Diagnosis?

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

UGM
 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
 Dermatopathic Lymphadenopathy (lipomelanotic reticulosis)

Multiple nodul berwarna pucat di regio paracortex . IDCs, sel Langerhans: membran inti pucat, inti
bengkok/berlipat, linear groove, sitoplasma luas,
Tampak pula hyperplasia folikel melanophages

IOACHIM’S Lymph Node Pathology, 5th edition, 2022

 NEOPLASTIC
COUNTERPART

Dermatopathic
Langerhans
lymphadenopat
cell
hy
histiocytosis

Garces et al., 2019

Kasus 10. Laki-laki, 40 th. Limfadenopati inguinal. Dx: Suspect Hodgkin Lymphoma
Diagnosis? Cat-Scratch Disease

RSUD Dr. Soetomo

CD30 Ki67
 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
 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)
 Apoptotic bodies, neutrofil (kanan atas). Sel
plasma dan limfosit (kiri bawah)

Warthin-starry stain
IOACHIM’S Lymph Node Pathology, 5th edition, 2022
Cat-scratch disease

IOACHIM’S Lymph Node Pathology, 5th edition, 2022

 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. Nevus cells inclusion. Blue nevus involving
Inklusi ini juga dapat ditemukan pada lymph node capsule.
KGB mediastinum laki-laki dan axilla
wanita
Rosai and Ackerman’s Surgical Pathology, 11th ed, 2018
 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
 Pendekatan pola histopatologi lesi limfoid reaktif
Pattern Descriptive differential Differential Ancillary Neoplastic Notes
diagnosis diagnosis techniques counterpart

1. Pola Follicular Hyperplasia Unspecific FH, IHC, serology, p24 Follicular -

Folikular HIV-LA type A, staining, rheumatoid lymphoma, Mantle
Autoimmune LA (RA), factor, Warthin- cell lymphoma with
Luetic LA, Starry staining, mantle zone
IgG4-LA type II IgG/IgG4 staining 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- IHC, serology, p24 Mantle cell Look for kaposi
associated LA type C staining, IgG/IgG4 lymphoma with sarcoma
staining mantle zone
pattern,
Angioimmunoblasti
c T-cell lymphoma
(AITL)
 Pendekatan pola histopatologi lesi limfoid reaktif
Pattern Descriptive Differential Ancillary Neoplastic Notes
differential diagnosis diagnosis techniques counterpart

Kimura disease Parasitic disorder, IgE staining ALHE -

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

3. Pola Granulomatous-LA - -
kombinasi

Non necrotizing Toxoplasmosis Sabin-feldman dye

granulomatous LA test,
IgG & IgM anti
Toxoplasma
Sarcoidosis, whipple PAS Masked malignant -
disease tumors (carcinomas,
germ cell tumors,
lymphomas)

Necrotizing Mycobacteriosis Ziehl-Neelsen, - -

granulomatous LA (Tuberculosis), fungal grocott
infection (e.g. methenamin sliver,
histoplasmosis) PAS stain
 Pendekatan pola histopatologi lesi limfoid reaktif
Pattern Descriptive Differential Ancillary Neoplastic Notes
differential diagnosis techniques counterpart
diagnosis

Microabscess or cat-scratch Warthin-starry, Hodgkin -

supurative disease, ZN, the nitro Lymphoma with
granulomatous chronic(septic) blue tetrazolium stellate necrosis
LA granulomatous test (CSG), frei
disease (CSG), test (LV)
Lymphogranulo
ma Venereum,
tularemia,
yerseniosis,
Mycobacteriosis

Histiocytic Kikuchi- IHC; ANA/DS- High grade

necrotizing LA Fujimoto DNA test lymphoma
Disease, SLE
 Pendekatan pola histopatologi lesi limfoid reaktif
Pattern Descriptive Differential Ancillary Neoplastic Notes
differential diagnosis diagnosis techniques counterpart

4. Pola sinus Sinus Histiocytosis - - Metastatic -

carcinomas

Histiocytic reactions Draining of Histochemistry, - -

with foamy histiocytes prostheses polarized light
examination
Hereditary storage Histochemistry, - -
disease genetics,
biochemistry
Sinus histiocytosis with Rosai Dorfman IHC LCH -
massive LA disease

Histiocytic increase Hemophagocytic Laboratory values - Amebiasis?

with lymphohistiocytosis
hemophagocytosis Blood transfusion
 Take home messages
• 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.
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
 Selamat belajar
Semoga bermanfaat