TUMOR JAR.

RETIKULOENDOTELIAL
neoplasms of the
Lymphoid System
T. Utoro
Department of Pathology
Gadjah Mada University School of Medicine
THE LYMPHNODE
Structure of Normal Lymphnode
THE LYMPHNODE
LYMPHOID TISSUE
Lymphoid Neoplasms
Certain relevant principles must be
emphasized

Can be suspected from the clinical features, but
histologic examination of lymph nodes and other
involved tissue is required for diagnosis

The vast majority of lymphoid neoplasms (80% -
85%) are of B-cell origin; most of the remainder
being T-cell tumors; only rarely are tumors of NK
origin encountered

Two basic forms of B-cell lymphoma: follicular &
diffuse type
Lymphoid Neoplasms
Lymphoid neoplams are tumors of the immune
system disrupt normal immune regulatory
mechanisms (evidences: susceptibility to
infection, autoimmune diseases)
><
Patients with inherited or acquired immunodefi-
ciency are at high risk of developing certain
lymphoid neoplasms, particularly thse associated
with EBV infection
Lymphoid Neoplasms
All lymphoid neoplasms are derived from single
transformed cell monoclonal

NHLs often present present as involvement of a
particular tissue site, but sensitive molecular
assay usually show that the tumor is widely
disseminated at the time of diagnosis only
systemictherapy are curative

HLs are often often presents at a single site
spreads methodically to contiguous lymphnodes
group early course tumors may be cured with
local therapy alone
Lymphoid Neoplasms
HL spreads in orderly fashion, and as a result
staging is of importance in determining therapy
In contrast, the spread of NHL is less predictable
most patients are assumed to have systemic
disease at the time of diagnosis staging in
particular NHL provides useful prognosis
information, but generally not important in guiding
therapy
E T I O L O G Y
Chromosomal translocation: CML, Burkitt lymphoma
Inherited genetic factors: Bloom syndrome, Fanconi
anemia, ataxia telangiectasia, Down syndrome
Viruses: HTLV-1, EBV, KSHV, HHV-8
Environmental agents: Helicobacter pylorii (gastric B-cell
lymphoma), gluten-sensitive enteropathy (T-cell lymphoma),
HIV (B-cell lymphoma)
Iatrogenic factors: radiotherapy & chemotherapy
mutagenic effect
The WHO Classification of the
Lymphoid Neoplasms
I. Precursor B-cell Neoplasms: neoplasms of
immature B-cells
II. Peripheral B-cell Neoplasms: neoplasms of
mature B-cells
III. Precursor T-cell Neoplasms: neoplasms of
immature T-cells
IV. Peripheral T-cell and NK-cell Neoplasms:
neoplasms of mature T-cell and NK-cell
V. Hodgkin Lymphoma: neoplasms of Reed-
Sternberg cells and variants
Origin of Lymphoid Neoplasms
CLP: common lymphoid precursor; BLB: pre-B lymphoblast; NBC: naif B-cell;
MC: mantle B-cell; GC: germinal center B-cell; MZ: marginal zone B-cell;
DN: CD4/CD8 double negative pre-T cell; DP: CD4/CD8 double positive
pre-T cell; PTC: peripheral T-cell
The WHO Classification of the Lymphoid Neoplasms
I. Precursor B-cell Neoplasms
ALL

The WHO Classification of the Lymphoid Neoplasms
III. Precursor T-cell Neoplasms
Acute lymphoblastic leukemia / lymphoma
-Originate from B-cell or T-cell, mostly from T-cell
-Can be differed by B-cell marker CD22
-The nuclear chromatin is delicate and finely stippled,
and nucleoli are either absent or inconspicuous
CML: bone marrow
CML: lymph nodes
(chloracetate esterase) x 25
CLL: liver
CLL: liver
(EvG) x 25
CLL: bone marrow
(chloracetate esterase) x 100
CLL: periaortic lymph nodes
The WHO Classification of the Lymphoid Neoplasms
II. Peripheral B-cell Neoplasms
CLL / small lymphocytic lymphoma
B-cell prolymphocytic leukemia
Lymphoplasmacytic lymphoma
Splenic and nodal marginal zone lymphoma
Extranodal marginal zone lymphoma
Mantel cell lymphoma
Follicular lymphoma
Marginal zone lymphoma
Hairy cell leukemia
Plasmacytoma / plasma cell myeloma
Diffuse large B-cell lymphoma
Burkitt lymphoma
Morphologic clues to diagnosis
Small cells, round:
CLL/SLL
Small / intermediate cells with atypia:
Mantle cell lymphoma (irregular),
MALT lymphoma (monocytoid)
Intermediate cells:
follicular lymphoma (cleaved),
Burkitt lymphoma (non-cleaved, prominent nucleoli),
lymphoblastic lymphoma (fine chromatin)
Large cells:
diffuse large B cell lymphoma,
mycosis fungoides or Sezary syndrome (cerebriform),
anaplastic large cell lymphoma (pleomorphic)
II. Peripheral B-cell Neoplasms
Small Lymphocytic Leukemia
Small Lymphocytic Lymphoma
The two indistinguishable disorders: morphologically,
phenotypically, and genotypically; differing only in the
degree of peripheral blood lymphocytosis
Proliferation center: loose aggregates of pro-lymphocyte
pathognomonic
Tumor cells usually infiltrate the splenic white and red
pulp, and the hepatic portal tract, although the extent of
involvement varies widely.
II. Peripheral B-cell Neoplasms
Small Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Diffuse effacement of nodal architecture
The majority of the tumor cells are
small round lymphocytes.
Arrow: pro-lymphocyte
II. Peripheral B-cell Neoplasms
Follicular Lymphoma
The most common form of NHL in the USA
(45% of adult lymphomas)
Usually present in the middle age and afflicts
males and females equally
Less common in Europe, and rare in Asian
population
The tumor cells closely resemble normal
germinal center B-cells
II. Peripheral B-cell Neoplasms
Follicular Lymphoma
In most cases, at low magnification, a predominantly
nodular or nodular and diffuse growth pattern is
observed
Two principle cells are observed in varying proportion:
(1) small cell with irregular or cleaved nuclear contour
and scant cytoplasm centrocyte
(2) larger cells with open nuclear chromatin, several
nucleoli, and modest amount of cytoplasm centroblast
Involvement: bone marrow (85%), spleen, liver
Te overall median survival is 7 to 9 years, is not
improved by aggressive therapy
Follicular Lymphoma (spleen)
Prominent nodules represent white pulp follicles expanded by
follicular lymphoma cells
Follicular
Lymphoma
The neoplastic
nodules bulge
onto the surface
follicular lymphoma VS follicular hyperplasia
Even distribution of neoplastic
follicles in follicular lymphoma
Predominantly cortical distribution of
follicles typical of follicular hyperplasia
Follicular Lymphoma
Malignant lymph follicles are marked by Bcl-2 positive
Follicular lymphoma, grade I
(silver stain) x 25
Follicular lymphoma, grade I
(IH; CD20) x 25
Follicular lymphoma, grade III
(Giemsa stain) x 200
Follicular Lymphoma
Small lymphoid cells with condensed chromatin and irregular or cleaved nuclear
outline (centrocyte), mixed with a population of larger cells with nucleoli (centroblast)
Mantle cell lymphoma
Neoplastic lymphoid cells surround a small, atrophic germinal center
exhibiting mantle zone pattern of growth
Homogenous population of small lymphoid cells with somewhat irregular
nuclear outlines, condensed chromatin, and scant cytoplasm.
II. Peripheral B-cell Neoplasms
Diffuse large B-cell lymphoma
(DLBCL)
Slight male predominance
Age about 60 years
5% of childhood lymphoma
Clinically present with a rapidly enlarging,
often symptomatic, mass at a single nodal
or extranodal site
Diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma
Spleen: typical isolated large mass
Diffuse large B-cell Lymphoma
Tumor cells show prominent nucleoli
Diffuse large B-cell lymphoma
Tumor cells with large nuclei, open chromatin, and prominent nucleoli
II. Peripheral B-cell Neoplasms
Burkitt lymphoma
Categories: (1) African (endemic) Burkitt
lymphoma, (2) sporadic (non-endemic), (3)
subset of aggressive lymphoma --- HIV
Clinical feature
Both endemic & non-endemic are found largely
in children and young adults (30%)
Most tumor manifests at extra-nodal sites

Burkitt lymphoma
Burkitt lymphoma
Low power: many tingible body
macrophages Starry sky appearance
Monotonous appearance, tumor cells
with multiple small nucleoli and high
mitotic index (typical)
Burkitt Lymphoma
Several starry sky macrophages was shown (arrows)
II. Peripheral B-cell Neoplasms
Multiple myeloma of the skull
The sharply punched-out bone lesions are most obvious in the calvarium
Plasmacytoma
(punched-out bone lesions in calvaria)
Multiple myeloma (plasmacytoma)
(Giemsa stain) x 200
Multiple myeloma (plasmacytoma)
(IH; lamda chains) x 200
Plasmacytoma: kidney
EvG 100 x
Multiple myeloma (bone aspirate)
Normal marrow cells are replaced by plasma cells
Lymphoplasmacytic lymphoma
Bone marrow biopsy:
various degrees of plasma cell differentiation
Mast cell
The WHO Classification of the Lymphoid Neoplasms
IV. Peripheral T&NK-cell Neoplasms
T-cell prolymhocytic leukemia
Large granular lymhocytic leukemia
Mycosis fungoides / Sezary syndrome
Peripheral T-cell lymphoma, unspecified
Anaplastic large cell lymphoma
Angioimmunoblastic T-cell lymphoma
Enteropathy-associated T-cell lymphoma
Panniculitis-like T-cell lymphoma
Hepatosplenic T-cell lymphoma
Adult T-cell leukemia/Lymphoma
NK/T-cell lymphoma, nasal type
NK-cell leukemia
Peripheral T&NK-cell Lymphoma
Peripheral T-cell lymphoma
T-cell lymphoma without specific defining
featuresfall collectively into the category of
unspecified
Account for approximately half of all T-cell
lymphoma in the western world
As a group they are aggressive malignant with
low 5-ysr
They may be nodal or extranodal
variable expression most nodal expressing
CD4+
They may be associated with eosinophilia
Peripheral T&NK-cell Lymphoma
Peripheral T-cell lymphoma
A spectrum of small, intermediate, and large lymphoid cells,
many with irregular nuclear contours.
Peripheral T&NK-cell Lymphoma
Anaplastic large cell lymphoma
mitosis
Anaplastic large cell lymphoma
Hallmark cells with horseshoe-like or embryo like nuclei
and abundant cytoplasma lie near the center of the field.
IHC: ALK protein
The WHO Classification of the Lymphoid Neoplasms
V. Hodgkin Lymphoma
Classical subtype
Nodular sclerosis
Mixed cellularity
Lymphocyte-rich
Lymphocyte depletion
Lymphocyte pre-dominance
Hodgkins disease, spleen
V. Hodgkin
Lymphoma
Lymphocyte predo-
minant.
Mixed cellularity
Lymphocyte rich
Lymphocyte depleted
Nodular sclerosis
V. Hodgkin Lymphoma
Reed-Sternberg cell, positive for CD30
V. Hodgkin Lymphoma
Reed-Sternberg cell
Mirror-image nuclei contain large eosinophilic nucleoli
Reed-Sternberg cells and variants
A. Diagnostic RS-cells with 2 nuclear lobes, large inclusion-
like nucleoli, and abundant cytoplasm
B. Mononuclear variant.
C. Lacunar variant, characteristic of the nodular sclerosis
subtype. It has a folded or multilobated nucleus lying
within a clear space created by disruption of its
cytoplasm during processing
D. Lymphohistiocytic (L&H) variant, complex nuclear
irregularities, small nucleoli, fine chromatin, and abundant
pale cytoplasm.
Hodgkin lymphoma
(Reed-Sternberg cells and variants)
A B
C D
Lacunar cells
(Giemsa stain) x 300
Reed-Sternberg cell
HE
CD30
Hodgkin lymphoma:
nodular sclerosis type
Well-defined bands of pink, acellular collagen that subdivided
the tumor cells and associated reactive infiltrate into nodules
Hodgkins disease,
nodular sclerosis type (HE) x 25
Hodgkin lymphoma:
mixed cellularity type
Numerous mature-looking lymphocytes surround scattered,
large pale-staining L&H variants (popcorn cells)
Hodgkins disease,
mixed cellularity type (HE) x 200
Hodgkin lymphoma
lymphocytic predominance type
Reed-Sternberg cells is surrounded by reactive cells, including eosinophils
Myelodysplastic Syndromes
Myelodysplastic Syndromes ???
Myelodysplastic syndromes are a group of diseases in
which the bone marrow does not make enough healthy
blood cells.
There are several types of myelodysplastic syndromes.
Age and past treatment with chemotherapy or radiation
therapy affect the risk of developing a myelodysplastic
syndrome.
Possible signs of myelodysplastic syndrome include
feeling tired and shortness of breath.
Tests that examine the blood and bone marrow are used
to detect (find) and diagnose myelodysplastic
syndromes.
Myelodysplastic syndromes are diagnosed based on
certain changes in the blood cells and bone marrow.
Certain factors affect prognosis (chance of recovery) and
treatment options

Image ????
Langerhans cell histiocytosis
Also called
Eosinophilic granuloma;
Pulmonary histiocytosis X;
Nonlipid reticuloendotheliosis;
Pulmonary Langerhans cell
granulomatosis;
Hand-Schuller-Christian disease;
Letterer-Siwe disease;
Langerhans cell histiocytosis
Langerhans cell granulomatosis
Rare disorder of Langerhans cells
Variable clinical picture with single or multiple
lesions or disseminated disease
Nodal involvement may be sole manifestation of
disease or associated with systemic disease
May also have nodal involvement by lymphoma
Rarely have frankly malignant cells (Langerhans
cell sarcoma) associated with more aggressive
clinical behavior
Langerhans cell histiocytosis
Hand-Schuller-Christians disease: term used
previously for more indolent disease of children and
young adults
Hashitmoto-Pritzkers disease: congenital, self limited
form
Letterer-Siwes disease: systemic disease in infants
Langerhans cells capture antigens and present them to
lymphocytes; are considered an immune system
accessory cell
Langerhans cells are normally present as a few cells in
thymus, lymph nodes and skin

Langerhans cell histiocytosis
Eosinophilic granuloma
X-ray of the skull
Femoral langerhans histiocytosis
Langerhans cell histiocytosis
Langerhans cell histiocytosis
Langerhans cell histiocytosis
EM Image : BIRBECK GRANULE

QUIZ
Miniquiz 1
3 y.o. male with destructive process of proximal
humerus with associated soft tissue mass;
Clinical DD. : - Ewings sarcoma
- Osteomyelitis

Tomografi & FNAB cytology Images are .
Miniquiz 1
cytology
Miniquiz 1
cytology
Miniquiz
cytology
Histopathology post operative
Images are .
Miniquiz 1
histology
Miniquiz 1
histology
QUESTION :
What is the diagnosis of this
case ?
QUESTION
Answer:
Langerhans Cell Histiocytosis