neoplasms of the

Lymphoid System
T. Utoro
Department of Pathology GMUSM

Structure of Normal Lymphnode
Lymphoid Neoplasms
Certain relevant principles must be
emphasized
Can be suspected from the clinical features, but
histological examination of lymph nodes and
other involved tissue is required for diagnosis

The vast majority of lymphoid neoplasm (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
close to immune regulatory system
Lymphoid neoplasm 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 neoplasm, particularly these associated
with EBV infection
Lymphoid Neoplasms
All lymphoid neoplasms are derived from single
transformed cell monoclonal

Divided into 2 big groups: NHLs and HLs

NHLs often 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 systemic therapy are curative

HLs are often presents at a single site spreads
methodically to contiguous lymph nodes 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: naive 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
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
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
Malignant lymph follicles are marked by Bcl-2 positive
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
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) a subset of aggressive
lymphoma occuring in individual with HIV infection
Responds well to short-term, high dose chemotherapy
(children & young adults)
Clinical feature
Both endemic & non-endemic are found largely in
children and young adults (30%)
Most tumor manifests at extra-nodal sites

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
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 features fall
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-yrs
They may be nodal or extra nodal
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
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
Hodgkin lymphoma:
nodular sclerosis type
Well-defined bands of pink, acellular collagen that subdivided
the tumor cells and associated reactive infiltrate into nodules
Hodgkin lymphoma:
mixed cellularity type
Numerous mature-looking lymphocytes surround scattered,
large pale-staining L&H variants (popcorn cells)
Hodgkin lymphoma
lymphocytic predominance type
Reed-Sternberg cells is surrounded by reactive cells, including eosinophils
Ann Arbor Staging System
Stage I
A/B
a
I

IE
Involvement of a single lymph node region
or
A single extra lymphatic organ or site
Stage II
A/B

II

IIE
Involvement of 2 or more lymph node regions on the same
side of the diaphragm, or
With localized contiguous involvement of an extra
lymphatic organ or site
Stage III
A/B

III

IIIE

IIIS
IIIES
Involvement of lymph node regions of both sites of the
diaphragm
Or, with localized contiguous involvement of an extra
lymphatic organ or site, or
With involvement of spleen, or
both extra lymphatic organ or site and spleen involvement
Stage IV
A/B

IV Diffuse or disseminated involvement of one or more extra
lymphatic organs with or without associated lymph node
involvement
References
Rubins Pathology. Clinical Foundations of
Medicine, 2005. Emanuel Rubin cs; Lippincott
Williams & Wilkins.
Robbins Pathologic Bases of Medicine, 2005.
Cotran, Kumar, Collins. Saunders
Pathology, 2
nd
ed. 2002. Arthur S. Schneider,
Philip A. Szanto; Lippinctt Williams & Wilkins
Mycosis Fungoides

Mycosis
Fungoides
A mature T-cell lymphoma presenting
in the skin with patches/plaques, and
characterized by epidermal and
dermal infiltration of small to medium
T-cells with cerebriform nuclei.
Mycosis Fungoides
Plaques lesion with infiltrates of
atypical, cerebriform lymphocytes
in the upper dermis
The epidermis is involved, mainly with
single cells
Mycosis Fungoides
Neoplastic cells with cerebriform nuclei form Pautrier microabscess within epidermis.
Mycosis
Fungoides
Tumor lesion with more massive
infiltrates involving both the
upper and deep dermis
Mycosis Fungoides
B. In the epidermis Pautrier abscess can be seen. C. The neoplastic cells show an
aberrant phenotype with expression of CD3, but no reaction for either CD4 (D) or
CD8 (E)