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Lymphoma
From Libre Pathology

Lymphoma is almost a specialty for itself. It can be subclassified a number of ways.

This article is an introduction to lymphoma. An introduction to lymph nodes and lymph node pathology that is not
lymphoma are in the articles lymph node and lymph node pathology.

A general introduction to haematopathology is in the haematopathology article.

Contents Lymphoma at cut-up.

(WC/Emmanuelm)
1 General
1.1 B symptoms
2 Lymphoma classification
2.1 Leukemia as a med student
2.2 Histologic classification
2.2.1 "Size"
2.2.2 Histologic terms
2.3 IHC
2.3.1 General
2.3.2 T cell markers
2.3.3 B cell markers
2.3.4 Plasma cell
2.3.5 Follicular dendritic cells
2.3.6 Hodgkin's lymphoma
2.3.6.1 Classic
2.3.6.2 NLPHL
2.3.7 Others
2.4 Molecular pathology
2.4.1 Chromosomal translocations
3 Hodgkin's lymphoma
3.1 General
3.2 Microscopic
3.2.1 Classical HL
3.2.1.1 Subtypes
3.2.2 Nodular lymphocyte-predominant HL
4 Small cell lymphomas
5 Diffuse large B-cell lymphoma
5.1 General
5.2 Microscopic
6 Intravascular lymphoma
7 Burkitt's lymphoma
7.1 General
7.2 Microscopic
8 Plasma cell neoplasms
9 Acute myeloid leukemia
9.1 General
9.2 Complications
9.3 Classification
9.4 Histology
10 Enteropathy-associated T-cell lymphoma
11 Angioimmunoblastic T-cell lymphoma
11.1 General
11.2 Microscopic
11.3 IHC
12 Primary mediastinal B-cell lymphoma
13 Anaplastic large cell lymphoma
14 Cutaneous T cell lymphoma
14.1 General
14.2 Microscopic
15 T-cell large granular lymphocytic leukemia
15.1 General
15.2 Microscopic
15.3 IHC
16 Lymphoplasmacytic lymphoma
16.1 General
16.1.1 Clinical
16.2 Microscopic
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16.3 IHC
17 Adult T-cell leukemia/lymphoma
17.1 General
17.2 Microscopic
17.3 IHC
18 Hepatosplenic T-cell lymphoma
19 Extranodal NK/T-cell lymphoma, nasal type
20 Table of lymphoma
20.1 B cell lymphomas
20.2 T cell lymphomas
21 See also
22 References

General
The presentations are variable and similar to that of other malignancies. They may include:

Mass effect.
Weight loss.
Fever.
Night sweats.
Infection.
Incidental:
Routine blood work for something unrelated.
Life insurance work-up.

B symptoms

May be seen in Hodgkin lymphoma and non-Hodgkin lymphoma.

Presence correlates with higher stage.
Predictor of poor prognosis independent of stage.

All of 'em are required to call "B symptoms"[1] - mnemonic These Bothersome features cause Wednesday Night Fever:[2]

Weight loss - >10% in 6 months.

Night sweats.
Fever - 38 degree C that is unexplained.

Note:

A symptoms do not exist. The term comes from the staging system. In the "A" of the staging system the above symptoms are absent.

Lymphoma classification
Lymphomas can be divided into:

Hodgkin's lymphoma.
Non-Hodgkin's lymphoma (NHL).

Other categorizations:

T cell lymphomas (rare).

B cell lymphomas (more common).

Two most common NHLs:

Follicular lymphoma (FL).

Diffuse large B-cell lymphoma (DLBCL).

Leukemia as a med student

Acute lymphoid leukemia (ALL) - predominantly in smALL people, i.e. children.
Acute myeloid leukemia (AML).
Chronic myeloid leukemia (CML).
Chronic lymphocytic leukemia (CLL) - relatively good prognosis.

Histologic classification

1. "Size".
2. Nodularity.

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"Size"

The single most important factor for classifying lymphomas.

Not really based on size.

"Large" "Small" Utility

Nucleoli present absent most discriminative
Size >2x RBC dia. <2x RBC dia. moderate
Chromatin pattern "open" (pale) "closed" moderate/minimal
mold-minimal
Cytoplasm scant cytoplasm minimal
basophilic cytoplasm

Histologic terms

Lymphomas = cells look discohesive, may be difficult to differentiate from poor differentiated carcinoma.
Auer rods = acute myeloid leukemia.
Granular cytoplasmic rod (0.5-1 x4-6 micrometres).
Not pathognomonic.
Reed-Sternberg cells = Hodgkin's lymphoma.
Large cell - very large nucleus.
Classically binucleated.
Russell bodies = plasmacytoma (+others).
Eosinophilic, large, homogenous immunoglobulin-containing inclusions.[3]
Mott cell is a cell that contains Russell bodies.[3]
Effacement of nodal architecture.
Loss of proliferation centers.

IHC

General

CD45.
AKA common lymphocyte antigen.
Useful to differentiate from carcinomas (e.g. small cell carcinoma).

Others:

AE1/AE3 -ve -- to r/o carcinoma.

T cell markers

CD2 -- T cell marker (all T cells).

CD3 -- T cell marker (all T cells).
CD4 -- subset of T cells.
CD8 -- subset of T cells.
CD7 -- often lost first in T cell lymphomas.
CD5 -- +ve in CLL & mantle cell lymphoma.
CD43 -- +ve in mantle cell lymphoma

ALK1[4] - prognostic in anaplastic large cell lymphoma (ALCL).[5]

TIA1 - cytotoxic T-cell.[6]
Granzyme B.

B cell markers

CD20 -- B cell marker.

CD19 -- B cell marker - used for flow cytometry.
PAX5 -- nuclear staining.[7]
Image: PAX5 in Hodgkin's lymphoma (http://www.pathologypics.com/PictView.aspx?ID=529).
CD79a.

CD10 -- follicle center.

BCL6 -- follicle center.
BCL2 -- normally negative in germinal centers (GCs), marks T cell; +ve in small B cell lymphomas.
MUM1 -- -ve in follicular lymphoma, +ve in DLBCL that did not arise from follicular lymphoma.

Plasma cell

Kappa -- usu. slightly stronger than lambda.

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Lambda.
CD56[8] -- also +ve in NK/T cell lymphomas.
CD57 -- +ve in T-cell large granular lymphocytic leukemia.[9].
CD138.

Follicular dendritic cells

CD23 -- follicular dendritic cells.

CD21 -- follicular dendritic cells, considered more sensitive than CD23.[10]

Hodgkin's lymphoma

Classic

CD30 +ve -- Hodgkin's lymphoma (most sensitive).

CD15 +ve.
PAX5 +ve.
EMA -ve.
EBER +ve/-ve.

Others:

CD20, CD45: weak +ve or -ve.

NLPHL

CD20 +ve.
CD30 -ve, CD15 -ve.
EMA +ve/-ve.
EBER -ve.

Others

Myeloperoxidase - in PMNs.
Glycophorin C.
CD61 -- megakaryocytes.
TdT.
CD34.

Molecular pathology
Main article: Molecular pathology
Main article: Molecular pathology tests

T cell clonality study.

B cell clonality study.

Chromosomal translocations

Main article: Chromosomal_translocations#Lymphoma

Hodgkin's lymphoma
Main article: Hodgkin's lymphoma

General
Abbreviated HL.

Microscopic

By definition, HL has Reed-Sternberg cells (RSCs).

Classical HL

Features (classic HL):

Reed-Sternberg cell.
Large binucleated cell.

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May be multinucleated.
May have a horseshoe-like shape.
Macronucleolus - approximately the size of a RBC (~8 micrometers).
Well-defined cell border.

Notes:

Large mononuclear cells are common (so called "mononuclear RSCs") but not diagnostic.

Images (classic HL):

HL mixed cellularity - cytology (WC) (http://commons.wikimedia.org/wiki/File:Hodgkin_lymphoma_cytology_large.jpg).

HL mixed cellularity - cytology (WC) (http://commons.wikimedia.org/wiki/File:Hodgkin_lymphoma_cytology_small.jpg).
HL mixed cellularity (WC) (http://en.wikipedia.org/wiki/File:Hodgkin_lymphoma_%281%29_mixed_cellulary_type.jpg).

Subtypes

There are four CHL subtypes:[11]

1. Nodular sclerosis CHL - ~70% of CHL.

Mixed cellular background - T cell, plasma cells, eosinophils, neutrophils and histiocytes.
Nodular sclerosing fibrosis - thick strands fibrosis.
2. Mixed cellularity CHL - ~20-25% of CHL.
Like nodular sclerosis - but no fibrosis.
May be associated with HIV infection.[12]
3. Lymphocyte-rich CHL - rare.
T lymphocytes only (no mix of cells).
4. Lymphocyte-depleted CHL - rare.
May be associated with HIV infection.[12]

Memory device:

The subtypes prevalence is in reverse alphabetical order.

Nodular lymphocyte-predominant HL

Features (nodular lymphocyte-predominant Hodgkin's lymphoma):

Popcorn cell (previously known as Lymphocytic & histiocytic cell (L&H cell)[13]) - variant of RSC:
Cells (relatively) small (compared to classic RSCs).
Lobulated nucleus - key feature.
Small nucleoli.
Subtle nodularity at low power (2.5x or 5x objective).

Images (NLPHL):

Popcorn cell (webpathology.com) (http://webpathology.com/image.asp?case=388&n=16).

Popcorn cell (WC) (http://commons.wikimedia.org/wiki/File:Popcorn_cell_in_nodular_lymphocyte_predominant_Hodgkin_lymphoma_-_very_high_
mag_cropped.jpg).

Small cell lymphomas

Main article: Small cell lymphomas

This grouping includes:

Follicular lymphoma.
Marginal zone lymphoma.
Nodal marginal zone lymphoma.
Extranodal marginal zone lymphoma (MALT lymphoma).
Splenic marginal zone lymphoma.
Mantle zone lymphoma.
Small lymphocytic lymphoma (SLL) / chronic lymphocytic leukemia (CLL).
Hairy cell leukemia.

Diffuse large B-cell lymphoma

Main article: Diffuse large B cell lymphoma

General

Abbreviated DLBCL.

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Microscopic

Features:[14]

Large cells -- 4-5 times the diameter of a small lymphocytes.

Typically have marked cell-to-cell variation in size and shape.
Cytoplasm usu. basophilic and moderate in abundance.
+/-Prominent nucleoli, may be peripheral and/or multiple.

Notes:

Large bizarre cells can occasionally mimic Reed-Sternberg cells, seen in Hodgkin lymphoma.

Intravascular lymphoma
AKA angiotropic lymphoma, intravascular malignant lymphomatosis, malignant angioendotheliomatosis
Rare.
Usually B-cell lineage (see intravascular large B-cell lymphoma).
May be T-cell lineage.[15]

Burkitt's lymphoma
Main article: Burkitt lymphoma

General

Abbreviated BL.
Subtyped by etiology.

Microscopic

Features:

"Starry-sky pattern":
The stars in the pattern are: tingible-body macrophages.
Tingible-body macrophages = macrophages containing apoptotic tumour cells.
The tumour cells are the sky.
Tumour cells:[16]
Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- key feature.
Round nucleus.
Small nucleoli.
Relatively abundant cytoplasm.
Brisk mitotic rate.

Image: Starry-sky pattern - Ed Uthman (WC) (http://en.wikipedia.org/wiki/File:Burkitt_lymphoma,_H%26E.jpg).

Plasma cell neoplasms

Main article: Plasma cell neoplasms

These arise from plasma cells.

AKA plasma cell myeloma, plasmacytoma.
Multiple myeloma (a clinical diagnosis) fits into this category.

Acute myeloid leukemia

General

May afflicits young adult.

Males>females.

Complications

Chloroma - soft tissue mass.

Leukostasis.
Occurs - lungs and brain.[17]
Hyperviscosity syndrome.
Spontaneous bleeding with low platelet counts.

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Classification

There are two classifications:

1. FAB (French-American-British) - based on histologic appearance/maturation.

2. WHO classification.

Histology

Auer rods - not required to diagnose.[18]

Cytoplasmic granular rods in blast cells.
Dimensions: approx. 0.5-1 x 4-6 micrometres.
Images: Auer rods (WP) (http://en.wikipedia.org/wiki/File:Auer_rods.PNG), Auer rods (virginia.edu) (http://www.healthsystem.virginia.edu/inter
net/hematology/HessImages/Acute-myelogenous-leukemia-M4-100x-Auer-rods-website-arrow.jpg).

Enteropathy-associated T-cell lymphoma

Abbreviated EATL.
AKA enteropathy-type T-cell lymphoma (ETTL).

Main article: Enteropathy-associated T-cell lymphoma

Angioimmunoblastic T-cell lymphoma

Abbreviated AITL.

General
Rare.
Common among T-cell lymphomas.
Middle age or elderly.

Microscopic

Features:

Intermediate size cells with:

+/-Vesicular nuclei.
Clear, moderate cytoplasm.
"Empty" sinus; subcapsular sinuses "open".

Images:

AITL (ijpmonline.org) (http://www.ijpmonline.org/viewimage.asp?img=IndianJPatholMicrobiol_2010_53_4_640_72010_f4.jpg).[19]

AITL - several images (upmc.edu) (http://path.upmc.edu/cases/case650.html)

IHC

Features - positives:[19]

CD3 +ve.
CD5 +ve.
CD43 +ve.

Others:

CD4 +ve and CD8 +ve with CD4>CD8.

CD20 +ve/-ve!
CD10 +ve/-ve!
CD21 +ve -- prominent FDC meshworks;[20] tumour cell not +ve.

Negatives:

CD30 -ve.[19]
CD15 -ve.[19]
CD7 -ve.
TIA-1 -ve.

Primary mediastinal B-cell lymphoma

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Abbreviated PMBL.
AKA primary mediastinal large B-cell lymphoma.

Main article: Primary mediastinal B-cell lymphoma

Anaplastic large cell lymphoma

Abbreviated ALCL.

Main article: Anaplastic large cell lymphoma

Cutaneous T cell lymphoma

See Dermatologic neoplasms.

General

Abbreviated as CTCL.
Sézary syndrome is a subset of CTCL.

Microscopic

Features:[21]

Cerebriform nucleus (Sézary cell):[22]

Hyperchromatic.
"Convoluted" = twisted, coiled.[23]

Images:

Sézary cell (flickr.com) (http://www.flickr.com/photos/32549645@N02/3040759595/).

Sézary cell (wadsworth.org) (http://www.wadsworth.org/chemheme/heme/glass/cytopix/slide015_sezary2.jpg).

T-cell large granular lymphocytic leukemia

General

May be seen in the context of Felty syndrome.

Microscopic

Features:

Large cell lymphoma.

Images:

T-cell large granular lymphocytic leukemia (upmc.edu) (http://path.upmc.edu/cases/case695.html).

IHC

CD57 +ve -- important.

CD3 +ve.
CD5 +ve.
CD45 +ve.

Lymphoplasmacytic lymphoma
Waldenström macroglobulinemia redirects here.

General

Features:[24]

B cell neoplasm.
Secretes monoclonal IgM.

Note:

Waldenström macroglobulinemia is a type of lymphoplasmacytic lymphoma[25] - it is characterized by:

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Hyperviscosity syndrome.
Bony destruction (seen in multiple myeloma) is absent.[24]

Clinical

Features:[24]

Symptoms of blood hyperviscosity - these include:

Visual impairment.
Neurologic impairment.
Bleeding.
Cryoglobulinemia - may have Raynaud phenomenon.
Hemolysis.
Bence-Jones proteinuria - seen in over half of patients.[26]

Treatment:

Watchful waiting or chemotherapy.

Hyperviscosity syndrome: plasmapheresis.

Microscopic

Features:[24]

Plasmacytoid lymphocytes.
Mixed inflammatory infiltrate with mast cells, plasma cells, lymphocytes.

DDx:

Plasma cell neoplasm.

IHC

Features:[27]

PAX5 +ve.
CD20 +ve.
CD38 +ve.
CD138 +ve.

Others:[27]

CD5 -ve.
CD10 -ve.
CD23 -ve.
CyclinD1 -ve.
CD3 -ve.
CD7 -ve.

Adult T-cell leukemia/lymphoma

General

Etiology: Human T-cell Lymphoma Virus 1 (HTLV-1).[28]

Poor prognosis ~ 1 year survival with treatment.

Microscopic

Features:[29]

Cloverleaf nuclei.
Nuclei with multiple lobulations.

Image:

Cloverleaf nucleus (pathpedia.com) (http://www.pathpedia.com/education/eatlas/histopathology/blood_cells/adult_t-cell_leukemia_htlv1-positive_acut

e_form/adult-t-cell-leukemia-htlv1-%5B2-bl095-2%5D.jpeg?Width=600&Height=450&Format=4).[30]

IHC

Features:[31]

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CD3 +ve.
CD5 +ve.
CD25 +ve.
CD45 +ve.
HTLV-1 +ve.

Others:[31]

CD7 -ve.
CD20 -ve.
CD79a -ve.

Hepatosplenic T-cell lymphoma

Main article: Hepatosplenic T-cell lymphoma

Extranodal NK/T-cell lymphoma, nasal type

Abbreviated as ENKL or ENKTCL.
AKA extranodal natural kill lymphoma
AKA angiocentric lymphoma.

Main article: Extranodal NK/T-cell lymphoma, nasal type

Table of lymphoma
B cell lymphomas

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Size of
Name Site Histomorphology IHC Translocations Clinical Prevalence DDx
cells
abundant atypical
follicles (lack GC
lymph node, polarity, lack polar CD10+, usually indolent,
Follicular small DLBCL, other small
germinal mantle zone), t(14,18) may transform to very common
lymphoma (centrocytes) bcl-6+[32] cell lymphomas
center effaced sinuses, DLBCL
scattered large cells
(centroblasts)
monomorphic CD5+,
lymphoid, abundant CD23-, other small cell
Mantle cell small, lymph node, mitoses. +/-scattered t(11;14) lymphomas, PTGC,
CD43+, indolent ??? uncommon
lymphoma monomorphic mantle zone epithelioid cyclin (q13;q32)[33] Castleman disease,
histiocytes, sclerosed Burkitt's lymphoma
blood vessels D1+[32]

mucosa-
Extranodal CD21+,
associated other small cell
marginal zone +/- lymphepithelial CD11c+,
lymphoid lymphomas,
lymphoma small lesion (cluster of 3+ CD5-, ??? indolent ??? common
tissue, GI neuroendocrine
(MALT cells in epithelium) [32]
tract + CD23- tumours
lymphoma)
elsewhere
nuclei slightly large
than resting
Precursor B-
lymph lymphocytes, scant CD10+,
cell basophilic CD5-,
node ???,
lymphoblastic small
bone cytoplasm, irregular TdT+, +/-t(12;21)[35] aggressive ??? uncommon small cell lymphomas
lymphoma/
leukemia
marrow nuclear membrane, CD99+[32]
no nucleoli, stippled
chromatin[34]
splenomegaly, no
bone
perinuclear clearing, CD25+, lymphadenopathy, small cell
Hairy cell marrow, CD103+,
small clear cytoplasm, translocations ? pancytopenia, uncommon leukemias/lymphomas
leukemia peripheral
central nucleus CD5-[36] good prognosis (e.g. SMZL)
blood
with Tx
tingible-body
macrophages ("starry rapid growth,
lymph node, CD10+,
Burkitt's medium, sky" appearance), may be associated DLBCL, mantle cell
germinal BCL6+, t(8;14) (q24;q32) uncommon
lymphoma monomorphic round nucleus, small with EBV, lymphoma
center (???) BCL2-
nucleoli, mitoses HIV/AIDS
+++
none / like
large cells lymph node sheets of large follicular
Diffuse large Burkitt lymphoma,
(>2x RBC, usually, discohesive cells; if MIB1 lymphoma
B cell poor prognosis very common ALCL, Hodgkin
often larger), germinal only nodular = >40% t(14,18) / c-MYC
lymphoma lymphoma
variable size center follicular lymphoma (like Burkitt
lymphoma)
Primary large (>2x predominantly
mediastinal RBC, often young adults,
mediastinum histomorphology ? IHC ? translocations ? uncommon DLBCL
B-cell larger), better prognosis
lymphoma variable size than DLBCL
B cell small
lymphocytic CD5+, trisomy 12;
lymphoma / lymph node CD23+, deletions of 11q, good prognosis / other small cell
small proliferation centres common
chronic (???) CD43+, [37] indolent course lymphomas
lymphocytic cyclin D1- 13q, 17p
leukemia

T cell lymphomas

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Size
Name of Site Histomorphology IHC Translocations Clinical Prevalence DDx
cells
Angioimmunoblastic size of
site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
lymphoma cells ?
Enteropathy-type T size of
site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
cell lymphoma cells ?
Precursor
lymphoblastic size of
site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
lymphoma / cells ?
leukemia
poor
Adult T-cell prognosis ~ 1
size of cloverleaf nuclei
lymphoma / site ? IHC ? translocations ? year survival prevalence ? DDx ?
cells ? (multilobular nuclei)
leukemia w/ Tx; d/t
HTLV-1
Peripheral T cell size of
site ? histomorphology ? TIA-1+ translocations ? clinical ? prevalence ? DDx ?
lymphoma (NOS) cells ?
deep & eosinophilic cytoplasm,
Anaplastic large cell subcapsular nucleoli, often cohesive, CD30+/-, Alk+/-, t(2,5)
large clinical ? uncommon carcinoma
lymphoma sinuses of wreath cell (C-shaped CD4+, CD3- (p23;q35)[38]
LN nucleus)
EBER+, CD16+,
Extranodal NK/T
CD56+, CD57-, common in
cell lymphoma nasal large ??? nasal ??? histomorphology ? translocations ? uncommon DDx ?
TIA-1+, East Asia
type
Granzyme B+
Blastic NK cell size of
site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
lymphoma cells ?

See also
Haematopathology - introduction.

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