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
 ETIOLOGY
• 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

The WHO Classification of the Lymphoid Neoplasms
III. Precursor T-cell Neoplasms

ALL
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 Monotonous appearance, tumor cells

macrophages  Starry sky appearance 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:

Mast cell various degrees of plasma cell differentiation
 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 γδ 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
 Lymphocyte predo-
V. Hodgkin minant.

Lymphoma
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 I Involvement of a single lymph node region
A/Ba or
IE A single extra lymphatic organ or site
Stage II II Involvement of 2 or more lymph node regions on the same
A/B side of the diaphragm, or
IIE With localized contiguous involvement of an extra
lymphatic organ or site
Stage III III Involvement of lymph node regions of both sites of the
A/B diaphragm
IIIE Or, with localized contiguous involvement of an extra
lymphatic organ or site, or
IIIS With involvement of spleen, or
IIIES both extra lymphatic organ or site and spleen involvement

Stage IV IV Diffuse or disseminated involvement of one or more extra

A/B lymphatic organs with or without associated lymph node
involvement
 References
• Rubin’s Pathology. Clinical Foundations of
Medicine, 2005. Emanuel Rubin cs; Lippincott
Williams & Wilkins.
• Robbin’s Pathologic Bases of Medicine, 2005.
Cotran, Kumar, Collins. Saunders
• Pathology, 2nd 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 The epidermis is involved, mainly with

atypical, cerebriform lymphocytes single cells
in the upper dermis
 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)