Patologi Sistem

Retikulo-Endhotelial
Kuliah FK. UMS Surakarta

oleh : dr. Oyong, SpPA.

meliputi ;
- sel darah putih (leukopenia,
neutropenia), leukemia,
- inflamasi sel darah putih &
kel.getah bening,
- neopl. sel darah putih& LM,
- leukemia (oleh PK),
- mieloma multiple,
- histiositosis sel Langerhans,
splenomegali.

Enlargement of Lymph Nodes

Anatomy & Topography

Lnn. :
1. tdk teraba/sangat kecil,
2. teraba: reaktif,
infeksi(spesifik/tdk), neoplasma
primer, neoplasma sekunder.

Physical Characteristics of enlarged nodes

Nodes with metastatic Ca : Stony hard, nontender, welllocalized, bound to surrounding tissue, nonmovable.
Acute infection : firm, tender, asymetric, matted, overlying
skin might be red & edematous.
Chronic infection : nontender, nonedematous.
Acute leukemia : tender.
Nodes in lymphoma : large,symetric, rubbery, firm, movable,
discrete, nontender.

Location of enlarged nodes

Generalized adenopathy ( > 2 separate nodes)
- Non-Hodgkin Lymphoma
- Chronic Lymphocytic leukemia
- immunoblastic lymphadenopathy
Generalized adenopathy.
- Uncommon in adult with infection, except
- mononucleosis, TBC, hepatitis, secondary syphilis,
toxoplasmosis, histoplasmosis.

Specific Location
Post auricular adenopathy : Rubella
Unilateral anterior auricular adenopathy : Trachoma,
conjunctivitis, TBC, syphilis.
Bilateral cervical adenopathy : TBC, mononucleosis,
toxoplasmosis, lymphoma, leukemia.
Unilateral cervical mass : Metastatic from NPC.
Palpable supraclavicular nodes : Neoplastic in
abdomen/chest.
Axillary nodes : drain part of breast.

Specific location.
Inguinal adenopathy : Lymphogranuloma venereum,
chancroid,syphilis.
Enlarged mediastinal/hilar nodes (X-ray) maybe asymptomatic
or tracheobronchial compression.
Bilateral mediastinal adenopathy : common in NHL.
Hilar adenopathy : TBC (unilateral), coccidioidmycosis &
sarcoidosis (bilateral).
Abdominal nodes might enlarge in any disorderwith cause
general adenopathy.
Retroperitoneal adenopathy : Neoplastic, especially
lymphomatus.

Lymph Node

Lymph Node

1. AFF LYMPH. VES.

2. CAPSULE
3. PERI PHER SINUS
4. PARA FOLICULAR
CORTEX/ T CELL
ZONE
5. LYMPHOID FOLICLE/
B CELL ZONE
6. EFF LYMPH VES
7. ARTERI & VEIN
8. MEDULLA
9. MEDULLARY
SINUSES

LYMPH NODE
ARCHITECTURE
Cortex
Paracortex
Medulla
Capsule and fibrous trabeculae
Sinuses

The cortex: B-zone of lymph

node
Primary lymphoid follicle

Virgin B cells and mature B cells

Follicular dendritic cells

CD21

Organization of
secondary lymphoid follicle
Marginal zone cells (IgM)

Mantle zone cells (IgM+D)

Follicle center cells (IgM,

IgG, IgA or IgE, not IgD)

CD2

REACTIVE VS LYMPHOMA

KAPPA

LAMBDA

BCL2

0905657, CHILD, 1 YRS, ABDOMINAL MASS + MULTIPLE LYMPHADENOPATHY

ENSRH-PAFKUI

ACUTE NON SP LYMPHADENITIS

REACTIVE
CHANGES :
Micro organism
Cell debris
Foreign material
cervical
axillaries
inguinal

Macros : Enlarged,
swollen, grey-red,
pain.
Micros : Lymphoid foll
prominent, large
germinal
center,histiosit,
neutrophil.

massa papabel, colli :

limfonodi membesar :
radang dan neoplasma maligna
(primer, sekuder)
sitologi/sitopatologi ; diagnostik
pendahuluan, bkn final

THE TECHNIQUES OF FNA

Needle moved back
and forth within
target tissue

Negative pressure
released while
needle remains in
target tissue

Acute Non specific Lymp-itis

Reactive changes
Cervical, axillaries, inguinal, mesenteric
Morphology : enlarged, swollen, grey-red,
distended caps tender.
Histopathology
: Lymph. Follicles >>,
Large germ C with mitotic activity,
neutrophil infiltration. Sinuses cell hyper
trophi / plasia.

Chronic Non Specific Lymp.itis

Inguinal, axillaries, not tender.
Histopathology:
follicular hyperplasia-B cell
dark zone, light zone, plasma cell,
histiosit, PMN, Eosinophyl.
Follicular Lymphoma :
1. Archi. Inter foll. T & Sinus
2. Variation shape & size nod
3. Dark-Light, Phagocytic-mac.

Chronic Non Specific

Lymphadenitis
I.

Follicular hyperplasia
activated B cell, larged, round germinal center.

II.

Paracortical lymphoid hyperplasia

Reactive chages T cell
Viral Infection.

III.

Sinus histiocytosis.
Distention-prominent sinusoid
Lymph node draining cancer

LIMFADENITIS KRONIS
NON SPESIFIK
1. Gambaran jaringan kelenjar limfe dengan
sentrum germinativum membesar dan
aktif mengandung limfosit-limfosit muda
yang menunjukkan mitosis atau proliferasi
sel-sel retikulum yang sering mengandung
kuman atau debris seluler yang telah
difagositosis.
2. Penambahan sel retikulum dan limfosit
dalam sinus disebut sinus catarrh.
3. Fibrosis diantara jaringan limfoid.
4. Kapsul dari nodus limfatikus bisa
mengalami periadenitis akan tampak tebal
dengan infiltrasi sel-sel radang kronis

LIMFADENITIS KRONIS
NON SPESIFIK

Chronic specific Lymphadenitis

TUBERCULOSA
MACROS
:
bergerombol, packed, central caseous.
MICROS
:
tubercle, cheese, necrotic, langhans cell,epitheloid cell.

Chronic specific Lymphadenitis

Morphology : besar, multiple,

bergerombol, tdk nyeri, livide, fistel
Histopatology :tuberc, epiteloid, caseosa,
langhans.
Lokasi : Leher, Supraclav, axilla
LYMPHOID NEOPLASMA

Limfoma - Leukemia

HD

NHL

LIMFADENITIS KRONIS SPESIFIK

(TBC)
1. Tampak struktur jaringan limfoid dengan
sarang-sarang tuberkel yang khas, berupa
nekrosis perkejuan di tengah dikelilingi oleh
sel-sel yang tersusun epiteloid dan tampak
beberapa sel datya Langhans
2. Fibrosis disekitarnya dengan infiltrasi
limfosit yang padat.

Introduction
Lymphoproliferative malignancies originating from the Bcell (B-NHL) or the T-cell lineage (TNHL).
Depending on the clinical course, classification as high-grade
(aggressive) or low-grade lymphoma is justified.
There is a worldwide epidemic of NHLs with more than 60,000
cases diagnosed in the United States each year.
Distribution : Male > Female.
ICD-10 : C82-C88, C91.1

Introduction
Lymphoma refers to a clonal tumor arising
from the malignant transformation of
mature or immature lymphocytes (B cells,
T cells, or NK cells)

No
1
2
3
3
5
6
7
8
9
10
11
12

Solid Tumor in
2011*
Malignancy

Frequency

Lymphoma
Gastrointestinal
Gynecology
Breast
Urinary tract
Head and neck
Thyroid
Skin Ca
Lung Ca
Osteosarcoma
CNS
Soft tissue tumor
Total

47 (20%)
44 (19%)
42 (18%)
27 (12%)
24 (10%)
18 (7.7%)
10 (4.3%)
7(3%)
6 (2.5%)
4 (1.7%)
2 (0.8%)
1 (0.4%)
232

* Data Pathology anatomy Depart RSMH

Palembang

Solid Tumor in 2012*

No

Malignancy

Frequency

1
2
3
4
5
6
7
8
9
10
11

Gynecology
Breast
Lymphoma
Head and neck Ca
Gastrointestinal
Soft tissue tumor
Urinary tract
Skin Ca
Osteosarcoma
Lung Ca
CNS
Total

130 (22%)
114 (19%)
86 (15%)
74 (13%)
65(11%)
36 (6%)
25 (4%)
21 (3%)
14(2%)
11(1.8%)
4 (0.7%)
584

* Data from Pathology Anatomy Dept RSMH Palembang

Characteristic*
Age (y)

Male

Female

Total

<20
20 29
30 39
40 49
50 59
60 69
70

4
6
10
7
11
3
2

4
4
6
4
1
-

4 (6%)
10 (16%)
14 (22%)
13 (20%)
15 (24%)
4 (6%)
2 (3%)

43

25

62

* Population : HD and NHL pts at Internal Med Depart, in 2011 - 2012

Clinical Features
Subjectives :
Chief complain

Frequency

Masses or nodal enlargement in cervical

32

Masses or nodal enlargement in abdomen

Dysphagia or dyspnea

Masses or nodal enlargement in cervical,

supra clavicula, axilla and inguinal

Masses in shoulder

Masses in Arm

Clinical Features (cont.)

Wide variety of presentations

B symptoms (fevers, night sweats, wt loss)
Painless adenopathy, mostly in cervical region
Intraabdominal masses
Dysphagia
Dyspnea
Obstipation

Etiological & Risk Factors

Immune deficiency syndromes

REAL Classification of
non-Hodgkin lymphomas
Precursor lymphoblastic lymphoma/leukemia
(B or T cell type)
Peripheral B-cell neoplasms

Peripheral T-cell & postulated NK-cell lymphomas

Introduction (cont)
Non-Hodgkins lymphoma (NHL) :
is a heterogeneous group of lymphoproliferative
malignancies.
NHL results from clonal expansion of tumor cells
derived from B, T, or natural killer (NK) cells.
Most NHLs, about 85% to 90% in the United States,
are derived from B cells.
NHLs are characterized by variable natural histories
and therapeutic responses.
The clinical courses : vary greatly, ranging from
indolent to rapidly fatal.
NHL is a disease predominantly of the elderly

PERIPHERAL B CELL
NEOPLASMS

B-cell SLL/CLL/PLL
Lymphoplasmacytoid
lymphoma
Mantle cell lymphoma
Follicle center
lymphoma
Marginal zone B cell
lymphoma

Extranodal (MALT)
Nodal*
* Provisional entities

Splenic marginal zone

B cell lymphoma*
Hairy cell leukemia
Plasmacytoma
Diffuse large B cell
lymphoma
Burkitt lymphoma
High grade B cell
lymphoma, Burkittlike*

Pendahuluan (1)
Morfologi LM sel T : tidak jelas
Morfologi LM sel B : sebagian bisa dikenal
Sel T di korteks thymus : Tdt, CD1a, CD3,
CD5, CD6
Sel T mature : CD4 atau CD8
Sel NK : KIR (Killer Inhibitory Receptor)
49

PERIPHERAL T CELL &

POSTULATED NK CELL
NEOPLASMS
T-cell CLL/PLL
Large granular
lymphocyte leukemia

T cell or NK cell type

Mycosis fungoides
Peripheral T cell
lymphoma unspecified
Angioimmunoblastic T
cell lymphoma

Angiocentric lymphoma
Intestinal T cell
lymphoma
Adult T cell lymphomaleukemia, HTLV1+
Anaplastic large cell
lymphoma, T & null-cell
Anaplastic large cell
lymphoma, Hodgkin-like*

Limfoma sel T mature (2)

Extranodal NK / T cell lymphoma nasal
type
Enteropathy associated T-cell lymphoma
Hepatosplenic T-cell lymphoma
Subcutaneous penniculitis like T-cell
lymphoma
Mycosis fungoides
Sezary syndrome
51

Limfoma sel T mature (3)

Primary cutaneous peripheral T-cell
lymphoma
Peripheral T-cell lymphoma NOS
Angio immunoblastic T-cell lymphoma
Anaplastic large cell lymphoma, ALK
positive
Anaplastic large cell lymphoma, ALK
negative
52

Limfoma sel T mature (3)

Primary cutaneous peripheral T-cell
lymphoma
Peripheral T-cell lymphoma NOS
Angio immunoblastic T-cell lymphoma
Anaplastic large cell lymphoma, ALK
positive
Anaplastic large cell lymphoma, ALK
negative
53

Extranodal NK/T-cell
lymphoma
1.Clinical finding
2.Morphology
3.Immunophenotyping
4.Genetic alteration
5.Treatment

Extranodal NK/T-cell
lymphoma

1.Clinical finding
Location :
2.Morphology
Prototype : Nose
3.Immunophenotyping-----ENKTCL, nasal type
Lethal midline granuloma
palate, paranasal sinus
4.Prognosis
nasopharynx
5.Treatment
Extra-nasal :

----- skin, soft tissue, G

testis

Extranodal NK/T-cell
lymphoma

1.Majority : polymorphous
* small, medium, large atypical lymphocytes
* inflammatory cells : lymphocytes, plasma cells,
macrophages, neutrophils polymorphic reticulosis
malignant histiocytosis
malignant reticulosis
Steward granuloma

Morphology :

2.

Prominent necrosis

3.Angiocentricity

lethal midline granuloma

angiocentric T-cell lymphoma

TAKE HOME
MESSAGE (1)NK/T-cell
Extranodal

lymphoma

1.Majority : polymorphous
Morphology
* small,
medium, large: atypical lymphocytes
* lymphocytes, plasma cells, macrophages,
neutrophils -----be careful of nasal

predilection!!
2. Prominent necrosis -----search for atypical
cells !!
3.Angiocentricity

17 yo female, mass in nasal cavity

540H12

540H12

Other extra nodal lymphoma

Extranodal NK/T-cell lymphoma nasal
type
Enteropathy associated T-cell
lymphoma
Hepatosplenic T-cell lymphoma

61

Introduction (cont)
Hodgkins Disease :
Characterized by Reed-Sternberg Cells
Tends to occur in young adults
Mediastinal disease common
Spreads to contiguous nodes
Common to have a localized
presentation
Highly curable with current treatments

Hodgkin Disease
Chain nodes-spread characteristic
Giant cells, Reed-Stenberg cell induced
RX lymph, histiocyt, granulocyt.
Nodular sclerosis
mixed cellularity
lymph predominant
lymphocyte-depleted

Reed-Sternberg cells and variants

Cytopathologic diversity of H-RS cells
Diagnostic Reed-Sternberg cells
Mononuclear Hodgkin cell
Lacunar cell
L&H cell
Mummified cell (apoptosis cells)
Pleomorphic Reed-Sternberg cell

N-LPHL
L&H cell

NS-HL
Lacunar cell

MC-HL
Diagnostic RS cell

Appropriate cellular environment

Depending on the specific subtype of Hodgkin
lymphoma, presence or absence of the following:

Small lymphocytes, with few or no immunoblasts

Histiocytes
Plasma cells
Eosinophils and neutrophils
Fibroblasts

Hodgkin lymphoma:
If the term of Hodgkin be replaced out,
Nodular lymphocyte predominant Hodgkin lymphoma
Nodular lymphocyte predominant large B-cell
lymphoma
Nodular sclerosis classical Hodgkin lymphoma
Lacunar cell lymphoma with sclerosis
Mixed cellularity classical Hodgkin lymphoma
EBV-associated polymorphous large-cell
lymphoproliferative disorder

Sel Doroty Reed-Carl Stenberg

Hodgkin Disease

Hodgkin disease
100% kel limfe
Tunggal menyebar
20-40 th(30-35 th)
Jenis

Nodular scler.
: 65%
Mixed cellularity
: 25%
Limfositik predominan
10%
Limfositik depletion

RYE CLASSIFICATION

WHO CLASSIFICATION

Lymphocyte predominance

Nodular lymphocyte predominant

Mixed cellularity

Classical Hodgkin lymphoma

Lymphocyte-rich

Nodular sclerosis

Mixed cellularity
Nodular sclerosis

Lymphocyte depletion

Lymphocyte depletion

Clinical staging of HD

HD & NHL
HD

NHL

Local lymph .CERME.ST-P.A

CONTIQUITY

MULTIPHERIPHERAL

EXTRA NODAL
UNCOMMON
WALDEYER &
MESENTERIC
INVOLVED RARE

COMMON

NO

COMMON

NODULAR SCLEROSIS

MOST COMMON 65-75%, , YOUNG

PROGNOSA BAIK, LEHER

SUPRACLAVICULA, MEDIASTINUM.

NODULAR, VARIANT R.S., Lacunar cell,

collagen band, divide lymphositis-nodule.

Reed-Stenberg cell
Microskopis :
Reed-stenberg cell:
besar, binukleus,
berhadap-kaca,
kadang-kadang multi
nuc, single lob,
sekitar halo area
Lacunar cell :
nodular sel

Non Hodgkin Lymphomas

MULTIPLE MYELOMA
PLASMA CELL bone, skin LN.
> , Ig > , prot Bence Jones, Midle age (50).
Clinic :
Multiple bone destruct
Vert, Ribs, Skull, pelvis, femur, R bulat oval,
batas fract. Patol.
Micros : plasma cell >> pleo morphic, exentric nucleus
plasma blast
spleen, liver, kidney, lungs

Folicular lymphoma
NHL : paling sering(45%)
; dewasa
Micros : nodular struktur, small cell irreg.
inti bigger cell chrom >>, nucleoli >
Clinical : Painless limfadenopati general
extra nodul rare, median survival 7-9 th
Tx : Chemoteraphy, radiasi, palliativ Tx

Diffus Large B-cell Lymphoma

20% NHL
<, 60 th
Mic :
Diffus patern

Large cell : 4-5x limf kecil

Nuclei : bulat-oval, cleaved-lobulasi

Anak inti : 2-3 atau 1 di tengah

Clin :
pembesaran kel. limf., kadang-kadang extra nodal : Git, bone,
brain, skin.
Px : Jelek
Tx : Intensive mix chemo Txcomplete remission 60-80%, 50% for
several years.

B-cell lymphoma
Chronic lymphocitic lymphoma
Folicular lymphoma
Diffus large B cell lymphoma
Burkitt lymphoma
Plasma cell neoplasm, etc.

T cell lymphoma & natural killer cell N

1.
2.
3.
4.

Peri T cell L UNSP

Adult T cell Lymphoma
Mycosis fungoides
Hodgkin disease

Precursor B Cell & T cell N

Acut Lymphoblastic L

Klasifikasi bervariasi
mnrt : Asal :sel B,sel T.
Struktur : FOL,DIF.
Vol.sel : LARGE,SM.
DIFERENSIASI : WORKING FROM.,REAL
CLAS.,RAPPAPORT.

ACUT LIMFOBLASTIC LIMFOMA/LEUKEMIA

di AS : 2500 KASUS BARU/TH
< 15 th, kulit putih 2X
> atau = , balita, < 15 th.
Mic : Str Norm kel lif rusak, sel limfoblas dominan : Besar.
Inti Lobulated, Mitosis >>
Clinn : Anemia, Lemah, Panas acut. Infeksi, Bone pain,
Spleen & liver enlargement, General limfadenopati, dll

Chronic lymphocitic / small cell limfoma

Sering pada dewasa
Small B cell pd sirkulasi (leukemia)
Micros : str NL rusak, Small limfosit predominan,
inti kecil, kombinasi dgan sel > besar
(prolimfositic)
Clin :

> 50 tahun
< atau = , sering asimptom, BB, lemah, anoreksi,
Lekosit >>, Limfadenopatia, spleen+ Liver

Burkitt limfoma
Endemic-sporadic-agresif (Afrika).
Mic : invasi intermed size sel limfosit, inti
oval-bulat, nucleoli>1 kromatin kasar,
mitosis>> starry sky
patern( macrophages, ingest nuc debris)
Clin :

extra nodal manifes, mandibula, organ intra

Abdomen.
Children, muda.

SPLEEN

SPLEEN
150 GR : 12 x 7 X 3 CM
MACROS : KAPSUL TIPIS, ABU-ABU
TRABEKULA PD. PARENKIM MERAH
DGN BERCAK PUTIH-WHITE PULP. RED
PULP. SINUSSOID DGN KAPILER DD
TIPIS

FUNGSI
1. Pembentukan sel darah (diluar sumsum
tulang).
2. Proses hemolisis
3. Reservoir darah, mobilisasi bila perlu
4. Reaksi pertahanan-kekebalan tubuh,
produksi limfosit dan zat anti

Neoplasia
Myeloproliferative and myelodysplastic
disorders, leukemia,
and lymphoma
Hemolytic anemias
Hereditary spherocytosis, elliptocytosis
Thalassemias, sickle cell anemia
Autoimmune disorders
Autoimmune hemolytic anemia
Thrombocytopenia, essential neutropenia
Systemic lupus erythematosus
Rheumatoid arthritis
Sarcoidosis
Infections
Infectious mononucleosis, brucellosis, etc.
Malaria, toxoplasmosis, etc.
Sepsis
Congestion
Cirrhosis of the liver
Budd-Chiari syndrome
Chronic congestive heart disease
Storage diseases
Gaucher disease, Niemann-Pick disease
Amyloidosis
66417308

Gangguan sirkulasi
1.
2.
3.

Bendungan akut
Bendungan menahun
Sindroma banti : splenomegali kongestif
>>, lekopeni, anemi.
4. Infark : Obstr. Emboli cor single/ multipleBaji.
Gamna-Gandy bodies : bercak abu2-coklat
(fibrosis+ endapan pigmen) pd Banti
sindrom

Splenomegali
1.
2.
3.
4.
5.
6.

Infeksi : Typ. TBC, Mal syph

Congestiv : Cirh, decomp, portalthrom
Limfo-hematogen dis.
Immunogenic
Storage dis : gaucher, niemann-Pick
Lain : amyloid, neopl

Neoplasm : Jarang
Benign : Hemangioma, Limfangioma, fibroma

histiositosis sel Langerhans

(histiositosis X) ;
- prol. sel LC, normal di
epidermis,
- bervakuola, sitoplasma
banyak, inti vesikular, lonjong
atau berlekuk,

3 klinikopatologik ;
- histiositosis LC akut tersebar
(sindr. Letterer-Siwe),
- histiositosis LC unifokal (gra.
eosinofilik),
- multifokal (peny. Handschuller
Christian)

Dendritic (antigen presenting)

cells
Langerhans cell (skin)
Follicular dendritic cell
Interdigitating dendritic
cell (T-zone)
Indeterminate cell (skin)
Veiled cell (lymphatic)

Follicular dendritic cell

(B cell follicle)
Fibroblastic dendritic
cell (?)