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Mimics of Lymphoma in Routine Biopsies

Patrick Treseler, MD, PhDProfessor of Pathology

University of California San Francisco

I have nothing to disclose regarding the

information to be reported in this talk.

• Follicular hyperplasia (B-cells)• Paracortical hyperplasia (T-cells)

(interfollicular immunoblastic hyperplasia)

• Mixed hyperplasia

Types of Lymphoid Hyperplasia

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Mixed follicular and paracortical

hyperplasia

Pure Reactive Follicular Hyperplasia

Reactive Follicular Hyperplasia and Paracortical Hyperplasia

CD3

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CD20

CD20

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The “Panel o’ Three”(for assessment of lymphoid infiltrates)

CD20CD3CD21

CD20 CD20

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CD21

CD20 CD20

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CD20

CD20

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CD3

CD21 Small B-Cell Lymphomas

Basic Immunophenotypes

CD20 CD5  CD43    CD23     BCL1 BCL6 CD10

CLL/SLL + + + + ‐ ‐ ‐

Mantle cell + + + ‐ + ‐ ‐

Follicular + ‐ ‐ ‐/+ ‐ + +/‐

Marginal + ‐ ‐/+  ‐ ‐ ‐ ‐

Proportion of cases positive: + >90%, +/‐ 50‐90%, ‐/+ 10‐50%, ‐ <10%

Cyclin D1

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The “Panel o’ Nine”(for diagnosis of small B-cell lymphomas)

CD20 CD3 CD5 CD43 CD10 CD21 CD23 BCL-1 (cyclin D1) BCL-6

Paracortical hyperplasia

• Drug reaction• Other hypersensitivity reaction• Viral infection• Post-vaccination• No clear etiology

Paracortical hyperplasia Differential diagnosis

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CD3

CD20

• Diffuse large B-cell lymphoma, NOS• Classical Hodgkin lymphoma• T-cell/histiocyte-rich large B-cell

lymphoma• EBV+ diffuse large B-cell lymphoma

of the elderly• Peripheral T-cell lymphoma

Florid paracortical hyperplasia (e.g., infectious mononucleosis) can mimic:

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Infectious Mono Infectious Mono

Infectious Mono Infectious Mono

CD20

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“One should think twice and thrice before rendering a diagnosis of DLBCL in a patient younger than 20 years. Infectious mononucleosis in particular has to be suspected when … there are many admixed large T-cells and Waldeyer’s ring is involved.”

ACL Chan & JKC Chan, 2011 Diffuse large B-cell lymphoma, in Hematopathology (Saunders/Elsevier)

CD3

Infectious Mono

EBV-ISHSlide courtesy of Dr. Dan Arber, Stanford Univ.

Infectious Mono

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Infectious Mono

CD30

Infectious Mono

CD20

CD20 (CHL) Classical Hodgkin lymphomaHRS Cell Immunophenotype

CD30 + >90% CD15 +/- ~80% CD20 -/+ ~20% (focal, weak)* Oct2 - ~60% (focal, weak)* Pax-5 + >90% (often focal, weak)* CD3 - <10%

Proportion of cases positive: + >90%, +/- 50-90%, -/+ 10-50%, - <10%*Based on data from García-Cosío et al. Mod Pathol 17: 1531; 2004

(Basic Panel for Dx of CHL)

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T-cell/histiocyte-rich large BCL

CD20

• Large B-cells (may resemble immunoblasts, LP cells, or HRS cells) present only as dispersed cells (<10% cells), no aggregates or sheets

• Background cells are small lymphocytes and histiocytes, no eos or plasma cells

• Background small lymphs “nearly all” T-cells• No nodules typical of NLPHL• Most patients present with high-stage disease,

B-symptoms

T-cell/histiocyte-rich large BCLDiagnostic criteria (WHO 2008)

Ratio of small to large B-cells

TCHRLBCL 0.7:1 (range 0.3 – 1.5)

DLPHL 6:1

NLPHL 20-50:1

T-cell/histiocyte-rich large BCLBoudová et al. (Blood 102: 3753; 2003)

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CD30

CD20 Pax-5

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Oct-2 CD20

“There are aggressive B-cell lymphomas, rich in reactive T-cells, in which the neoplastic cells are sparse, and are EBV-positive. In such cases, the neoplastic cells may exhibit a Hodgkin-like morphology. Such cases should not be classified as THRLBCL, and should be considered within the spectrum of EBV-positive DLBCL.”

WHO Classification (2008), p. 238 EBV-ISH

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EBV+ DLBCL of the Elderly

Why not infectious mono?EBV uniformly present in large cells, absent or virtually absent in small cells

CD20

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Peripheral T-cell lymphoma, NOS?

CD3 Clues that a dense T-cell infiltrate might be a T-cell lymphoma…

• Characteristic morphologic features• Aberrant immunophenotype, e.g.,

• CD56+ EBV+ (NK/T-cell lymphoma)• Loss of pan T-cell antigen other than CD7

• Overtly destructive tissue infiltration (difficult to assess in small)

• Nothing (in some cases)

Follicular hyperplasia

Follicular hyperplasia Follicular lymphoma

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Follicular lymphoma grade 3A

CD20 BCL-2

Follicular hyperplasia Follicular lymphoma

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Grade Cases Positive

Grade 1 97%

Grade 2 96%

Grade 3A 80%

Grade 3B 71%

Total 91%

BCL-2 Expression in Follicular LymphomaGuo et al. (Leukemia 19:1058; 2005)

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Densely aggregated poorly formed B-cell follicles

• Follicular lymphoma• Follicular pattern mantle cell lymphoma• Nodular lymphocyte predominant Hodgkin

lymphoma• Nodular lymphocyte-rich classical Hodgkin

lymphoma

Differential Diagnosis

References• Weiss LM. Lymph nodes. New York: Cambridge University Press, 2008.• Ioachim HL, Medeiros LJ. Ioachim’s Lymph Node Pathology, 4th ed.

Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkens, 2009.• Jaffe ES et al. (eds). Hematopathology. Philadelphia: Saunders/Elsevier,

2011.• Swerdlow SH et al (eds). WHO Classification of Tumours of

Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer, 2008.

• Boudová L et al. Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma. Blood. 2003 Nov 15;102(10):3753-8.

• Guo Y et al. Low-grade follicular lymphoma with t(14;18) presents a homogeneous disease entity otherwise the rest comprises minor groups of heterogeneous disease entities with Bcl2 amplification, Bcl6 translocation or other gene aberrances. Leukemia. 2005 Jun;19(6):1058-63.