Lymphoma Discussion

8/2/2019 Lymphoma Discussion

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Your Answer is CORRECT presented byEdward G. Weir, M.D.

You answered:Marginal zone lymphoma

The correct diagnosis is:Marginal zone lymphoma

Review the Slides

Histology: Lymph node histology is notable for an atypical nodular lymphoidproliferation and a paracortex that is largely replaced by fibrosis andadipocytes. Patent and occasionally distended lymph node sinuses can beappreciated. Some of the lymphoid nodules demonstrate germinal centers.Cytologically, the nodules are composed of a monomorphous population ofsmall, slightly irregular lymphocytes with mature chromatin. In addition, thelymphocytes have moderately abundant clear cytoplasm, rendering them amonocytoid appearance. There is no evidence of plasmacytoiddifferentiation. The germinal centers comprise a polymorphous populationof centrocytes, centroblasts and tingible body macrophages.

By immunohistochemistry, the monomorphous lymphocytes are positive forCD20 and negative for both CD5 and CD10. The stain for CD5 highlightsonly the few paracortical T cells present, and the stain for CD10 highlightsonly the germinal center cells. Also, an immunostain for bcl-2 (not shown) ispositive on the monomorphous population of lymphocytes and is negative

in the germinal centers.

Discussion: The monocytoid morphology of the malignant cells is a classic histologicmanifestation of a low-grade marginal zone B cell lymphoma. The nodulargrowth pattern and apparent follicular colonization of the lymphomaunderscores the marginal zone origin of the infiltrate. Furthermore, the lackof a prominent interfollicular expansion suggests an early stage oflymphoma development.

The immunohistochemical studies clearly confirm that the lymphoma is ofmarginal zone and not mantle or follicular derivation. The lack of aberrantCD5 expression essentially excludes a diagnosis of mantle cell lymphomaas well as small lymphocytic lymphoma. A follicular lymphoma of low-grade

histology should be positive for CD10 and should show germinal centerreactivity for bcl-2.

Most patients present with localized or generalized peripherallymphadenopathy and a good performance status. Occasional bonemarrow involvement is observed. The clinical course of nodal marginalzone lymphomas has not been well studied. Recent series suggest thatpatients respond to chemotherapy, but show a high early relapse rate.Nonetheless, the relatively long median survival in these patients is
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consistent with an indolent biology.

Next Case

Case prepared by: Bahram R. Oliai, M.D.

[email protected]


You answered:Small lymphocytic lymphoma The correct diagnosis is:Small lymphocytic lymphoma

Review the Slides

Histology: The nodal architecture is diffusely effaced by an abnormal lymphoidinfiltrate. Lymph node sinuses are inapparent and cortical follicles areessentially absent. Numerous pale zones render the infiltrate a vaguenodular appearance on low power examination. Cytologically, theinfiltrate is predominantly comprised of a monomorphous population ofsmall, mature lymphocytes. The pale zones are comprised of slightlylarger lymphocytes with moderately abundant cytoplasm andprominent central nucleoli. Mitoses are few and there is no evidence of

necrosis. By immunohistochemistry, the infiltrate is positive for CD20and CD5, and negative for CD3 and CD10.

Discussion: Small lymphocytic lymphoma (SLL) is generally a disease of theelderly, and is the lymph node manifestation of chronic lymphocyticleukemia. Though occasional patients present with aleukemic nodalinvolvement at diagnosis, most patients will ultimately develop bonemarrow and peripheral blood infiltration. Moreover, generalizedlymphadenopathy and hepatosplenomegaly are not uncommon clinicalmanifestations. Furthermore, advanced stages of the disease aretypically characterized by hypogammaglobulinemia and autoimmunephenomenon, often resulting in infectious complications, hemolyticanemia and thrombocytopenia. Like most indolent lymphomas, SLL is

not considered to be curable with currently available therapy. However,treatment with alkylating agents, prednisone, and more recently, purineanalogs has been found to be remarkably effective in producing long-term remissions. The extent of the disease at the time of diagnosis isthe best predictor of survival. Lymph nodes involved by SLL usuallydemonstrate diffuse architectural effacement by a monomorphousproliferation of small, mature lymphocytes with sparse cytoplasm. Thelymphocyte nuclei typically are round and have a condensed chromatinpattern. A very specific histomorphologic feature of SLL is the
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presence of pseudofollicular growth centers, which renders the infiltratea vaguely nodular appearance on low power examination. Unlike the Bcell follicles of follicular hyperplasia and follicular lymphoma, growthcenters have ill-defined margins and are cytologically comprised ofpredominantly prolymphocytes. Prolymphocytes are characterized aslarger lymphoid cells with more abundant, slightly basophilic cytoplasm

and a prominent central nucleolus. Immunophenotypically, the tumorcells demonstrate expression of B cell markers (CD20 and CD79a) andaberrant expression of the T-related markers, CD5 and CD43. Theyare negative for the T cell marker CD3 and the follicle center cellmarker CD10. Among CD5-positive B cell lymphomas, the presence ofCD23 reactivity distinguishes SLL from mantle cell lymphoma. Mantlecell lymphoma, which is not characterized by growth centers, isnegative for CD23 but positive for the PRAD1 oncogene proteinproduct CyclinD1. SLL is a low-grade lymphoma with few mitoses anda low proliferation index. Alternatively, Burkitts lymphoma is a veryaggressive tumor characterized by numerous mitoses, macrophagesengulfing apoptotic bodies, and necrosis.

Next Case

Case prepared by:Carol Allan, M.D.

[email protected]

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You answered:T cell-rich B cell lymphoma

The correct diagnosis is:T cell-rich B cell lymphoma

Review the Slides

Histology: Histologic sections of the lymph node demonstrate complete architecturaleffacement by a diffuse lymphoid infiltrate. Both lymph node sinuses andcortical follicles are absent. The infiltrate is comprised of numerous large,atypical cells surrounded by a background population of small, maturelymphocytes. Few plasma cells and granulocytes are identified. The atypicalcells have abundant cytoplasm and complex nuclei; some cells appear to bebinucleated. Many of the atypical cells are mitotically active. Byimmunohistochemistry, the large cells are positive for CD20, and negative forCD3, CD15 and CD30. Moreover, several of these large cells demonstratekappa Ig light chain expression and none of them demonstrate lambda lightchain expression. The vast majority of small lymphocytes in the backgroundare positive for CD3, and negative for CD20 and CD57.

Discussion: Diffuse effacement of lymph node architecture by a dual population of largeatypical cells and small mature lymphocytes is characteristic of manylymphoma types, including those listed above. Though these lymphomas mayhave unique but often subtle morphologic features, immunophenotypicstudies are frequently necessary to establish a definitive diagnosis. A T cell-rich large B cell lymphoma (TCRBCL) is cytologically notable for numerouslarge, atypical cells that typically have an unequivocally malignantappearance. These cells are very polymorphous, may have bizarrely-shapednuclei, and are mitotically active. The small cells in the background, whichusually predominate in number, are round and regular and represent hostreactive T cells. This pattern is in contrast to a peripheral T cell lymphoma,which characteristically demonstrates a spectrum of atypicality from small-to-

intermediate-to-large lymphocytes. Also, unlike both mixed cellularityHodgkins lymphoma and peripheral T cell lymphoma, there is a generalpaucity of plasma cells and granulocytes. Moreover, the large atypical cells inTCRBCL are immunophenotypically positive for the B cell marker CD20, andnegative for the T cell marker CD3 and the Hodgkins markers CD15 andCD30. In addition, the lack of reactivity for CD30 differentiates TCRBCL fromanaplastic large cell lymphoma, often referred to as Ki-1(CD30) lymphoma. Itshould be noted that TCRBCL may be difficult to distinguish from a diffusevariant of lymphocyte predominant Hodgkin lymphoma (LPHL), bothmorphologically and immunophenotypically. Like TCRBCL, LPHL isconsidered to be a B cell neoplasm. However, the malignant cells of TCRBCLlack the popcorn cytology of the L&H cells of LPHL. Furthermore, animmunostain for CD57 may be helpful since increased numbers of CD57-positive T cells are commonly found in LPHL and are usually distributed inrings around the L&H cells. TCRBCL is considered to be a morphologicvariant of diffuse large B cell lymphoma. It is an aggressive lymphoma but isamenable to cure with multiagent chemotherapy.

Next Case

Case prepared by: Carol Allan, M.D.
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Your Answer is CORRECT presented byRisa Mann, M.D.

You answered:Burkitts lymphoma

The correct diagnosis is:Burkitts lymphoma

Review the Slides

Histology: A large abdominal mass is composed of a monotonous cellular

proliferation infiltrating diffusely through adipose tissue. The neoplasticcells have a high mitotic rate and this is associated with the so-calledstarry sky pattern, which is due to the presence of benign appearinghistiocytes scattered throughout the tumor mass. The neoplastic cellshave relatively round nuclei with multiple medium sized nucleoli. Thetumor has an extremely high proliferation rate with many mitoticfigures. The nuclei of the tumor cells are approximately the same sizeas the nuclei of the benign starry sky histiocytes. The neoplastic cellshave a small amount of basophilic cytoplasm. Although not visible onH&E stained slides, a touch prep of these tumor cells woulddemonstrate deep basophilic cytoplasm with numerous cytoplasmiclipid vacuoles.

Discussion: The dense infiltrate in the abdominal adipose tissue is easilyrecognized as a neoplastic lymphomatous process. The differentialdiagnosis involves the subclassification of this lymphoma. The starrysky pattern which is characteristic of any lymphoma with a highproliferation rate is commonly seen in Burkitt lymphoma but it may alsobe seen in other high grade lymphomas such as lymphoblasticlymphoma as well as large cell lymphomas. The size of the nuclei ishelpful in further subclassifying this tumor. In Burkitt lymphoma theneoplastic cells have nuclei, which are about the same size of thenuclei of starry sky histiocytes. In contrast, the nuclei of lymphoblasticlymphoma cells are usually smaller than the nuclei of the benignhistiocytes and the nuclei of large cell lymphomas are usually largerthan the nuclei of the starry sky histiocytes. Lastly, most helpful in this

differential diagnosis is the immunophenotype. The neoplastic cells ofBurkitt lymphoma usually demonstrate membranous IgM with lightchain restriction and B cell associated antigens such as CD19, CD20,CD22, CD10 and BCL6. The cells are negative for CD23, CD5 andTdT. Burkitt lymphoma has one of the highest proliferation rates of alllymphomas and nearly 100% of the cells are positive for Ki-67 staining.

The tumor cells show clonal rearrangement of the immunoglobulinheavy and light chains and most cases have a translocation of MYC


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from chromosome 8 to the IgG heavy chain region on chromosome 14or less commonly to the light chain loci on chromosomes 11 or 22.Epstein Barr Virus (EBV) is identified in the majority of the neoplasticcells in endemic cases, however, the frequency of EBV association insporadic Burkitt lymphoma is low. Sporadic Burkitt lymphoma occursmainly in children and young adults but it can occur at any age.

Patients usually present with bulky disease often presenting inextranodal sites.

Next Case

Case prepared by:Bahram R. Oliai, M.D.

[email protected]




You answered:Follicular lymphoma

The correct diagnosis is:Follicular lymphoma

Review the Slides

Histology: Histologic sections of lymph node demonstrate significant fattyreplacement and an abnormal nodular proliferation of lymphocytes.

The lymphoid nodules, which are round, discrete and fairlyhomogeneous in size, resemble B cell follicles. However, unlike normalB cell follicles, they lack well-defined mantle zones and polarizedgerminal centers. Furthermore, the abnormal lymphoid nodules arelargely comprised of a monomorphous population of small, mature,cleaved lymphocytes and are notable for a conspicuous absence oftingible body macrophages. By immunohistochemistry, theselymphocytes are positive for CD20, CD10 and Bcl-2, and are negativefor CD3, CD43 and CD5. The Ki-67 proliferation marker demonstrates
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a low level of expression.

Discussion: Follicular lymphoma is morphologically defined as a tumor comprisedof follicle center cells, usually a mixture of small, cleaved centrocytesand larger, noncleaved centroblasts. Low-grade follicular lymphomastypically demonstrate a nodular growth pattern and a predominance of

centrocytes, whereas more aggressive follicular lymphomas tend to bearchitecturally diffuse and show a greater proportion of centroblasts.Molecularly, follicular lymphomas are characterized by thet(14;18)(q32;q21) chromosomal translocation that has been identifiedin approximately 80% of cases using routine karyotyping methods. Thet(14;18) is a reciprocal translocation that juxtaposes the bcl-2oncogene on chromosome 18q21 with the IgH gene on 14q32. As aresult, transcription of the bcl-2 gene is brought under the control of theIgH gene regulatory elements, most likely an enhancer region, leadingto constitutive overexpression of the bcl-2 gene. The bcl-2 protein,which is localized to subcellular membranes such as the outermitochondrial membrane, endoplasmic reticulum and nuclearenvelope, plays a prominent role in protecting the cell from apoptotic

death. Cells, which overexpress the bcl-2 protein, have a prolongedhalf-life, rendering these cells more susceptible to secondary geneticevents that may result in transformation to a more aggressivephenotype. By immunohistochemistry, the neoplastic follicular cells arepositive for the B cell markers CD20 and CD79a, as well as thegerminal center cell marker CD10. Other low-grade B cell lymphomaslack CD10 expression. Also, unlike small lymphocytic lymphoma andmantle cell lymphoma, follicular lymphoma cells lack expression ofCD5 and CD43. Lastly, the immunohistochemical expression of thebcl-2 protein is useful in distinguishing follicular lymphoma fromfollicular hyperplasia, since bcl-2 is absent from reactive processes.

Next Case

Case prepared by:Carol Allan, M.D.

[email protected]


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Your Answer is CORRECT presented byRisa Mann, M.D.

You answered:Follicular lymphoma, mixed smallcleaved and large cell type (WHOgrade 2)

The correct diagnosis is:Follicular lymphoma, mixed smallcleaved and large cell type (WHOgrade 2)

Review the Slides

Histology: This lymph node shows replacement of the normal nodal architectureby prominent nodular proliferation of lymphoid cells. The normalsinuses have been obliterated by this process. The germinal center-likestructures proliferate within the lymph node in a back-to-back patternwith little intervening paracortical areas. The germinal center-like

structures lack tingible body macrophages and lack obvious areas ofpolarization. At high power, the cellular proliferation within the germinalcenters demonstrates a mixed cell population comprised predominantlyof small cleaved lymphocytes admixed with larger centroblasts whichdemonstrate more cytoplasm and prominent nucleoli, sometimesopposed to the nuclear membrane.

Discussion: The major differential diagnosis in this case is between that of a floridreactive follicular hyperplasia and follicular lymphoma. A mantle celllymphoma may grow in a vaguely nodular pattern, but rarelydemonstrates this prominent follicular growth pattern. The germinalcenters in this case proliferate in a back-to-back pattern within thelymph nodes, leaving very little intervening paracortical areas. This

pattern is more typical of a neoplastic rather than a reactive process.Other features that morphologically favor a neoplastic follicular processinclude the lack of tingible body macrophages and the lack ofpolarization within the germinal centers. On closer examination theneoplastic proliferation within the germinal centers is composedpredominantly of small cleaved lymphocytes admixed with largeratypical lymphocytes (centroblasts). The number of large cells seen athigh power within the nodules is within the range accepted for a mixedsmall cleaved and follicular lymphoma (greater than 5 and less than 15large cells per high powered field).

Although the morphologic features described above are helpful inarriving at a diagnosis of follicular lymphoma, flow cytometry and/or

immunoperoxidase stains may be helpful in further documenting thediagnosis. Flow cytometry in this case showed the phenotype typical offollicular lymphoma. The cells are CD10 positive B cells, whichdemonstrated light chain restriction. In addition, BCL2 stains could beperformed on the paraffin embedded tissue, documenting the BCL2positivity of the proliferating B cells within the neoplastic nodules. Thisobservation correlates with the characteristic 14/18 translocationassociated with follicular lymphomas.


9/23

Next Case

Case prepared by:Greg Seidel, M.D.

[email protected]



Your Answer is CORRECT presented byMichael Borowitz, M.D., Ph.D.

You answered:Small lymphocytic lymphoma/chroniclymphocytic leukemia transforming todiffuse large B cell lymphoma(Richter syndrome)

The correct diagnosis is:Small lymphocytic lymphoma/chroniclymphocytic leukemia transforming todiffuse large B cell lymphoma(Richter syndrome)

Review the Slides

Histology: Much of the node shows characteristic changes of SLL/CLL, witharchitecture effacement by a pseudofollicular proliferation. Cells are roundand outside the pseudofollicles the cells are mostly small. Cells in thepseudofollicles have more abundant cytoplasm and include manyprolymphocytes and paraimmunoblasts with larger nuclei and moreprominent nucleoli. Other parts of the node, however, show a very differentpattern, with diffuse architectural effacement by a more monotonouspopulation of large cells. Immunophentoypically these two areas are alsodifferent; both express CD20,
mailto:[email protected]:[email protected]:[email protected]://pathology2.jhu.edu/sp/mailform.cfmhttp://pathology2.jhu.edu/sp/mailform.cfmhttp://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pathology.jhu.edu/http://pathology.jhu.edu/http://pathology.jhu.edu/http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology.jhu.edu/researchbrochure/division.cfm?id=9Borowitzhttp://pathology.jhu.edu/researchbrochure/division.cfm?id=9Borowitzhttp://pathology.jhu.edu/researchbrochure/division.cfm?id=9Borowitzhttp://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology.jhu.edu/researchbrochure/division.cfm?id=9Borowitzhttp://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology.jhu.edu/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pathology2.jhu.edu/sp/mailform.cfmmailto:[email protected]


10/23

but there is loss of CD23 on the larger cells,


11/23

and a much higher expression of the proliferation marker Ki-67.


12/23

Flow cytometry plots also show this; while all cells are CD5+ B cells withclonal expression of kappa light chain, there is a distinct population of largercells with much brighter CD20, FMC7, and loss of CD23.


13/23

Discussion: The number of large cells can vary greatly in SLL/CLL, and their numberalone is not sufficient to establish a diagnosis of transformation. It isparticularly important not to over-interpret cases with unusually prominentpseudofollicles, some of which can even coalesce. True Richtertransformation is invariably associated with a distinctly different architecturalappearance from the background SLL/CLL.


14/23

Next Case

Case prepared by:Amy Duffield, M.D., Ph.D.

[email protected]

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Your Answer is CORRECT presented byAndrea Subhawong, M.D.

You answered:Anaplastic large cell lymphoma

The correct diagnosis is:Anaplastic large cell lymphoma

Review the Slides

Histology: The biopsy is notable for large lymphoid cells which infiltrate in a cohesivepattern with a predilection for the nodal sinuses. Cytologically the nuclei areenlarged, often multinucleated, and have prominent nucleoli, which tend tobe smaller and less eosinophilic than those observe in Hodgkin lymphoma.Some cells have nuclei which are eccentric and indented by a cytoplasmiclight zone (hoff), and are thus defined as hallmark cells

Discussion: The morphologic findings are highly suggestive of ALCL.Immunohistochemical confirmation is made by intense and diffusemembranous and golgi staining with CD30 in the absence of B-cell markers.
mailto:[email protected]:[email protected]:[email protected]://pathology2.jhu.edu/sp/mailform.cfmhttp://pathology2.jhu.edu/sp/mailform.cfmhttp://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pathology.jhu.edu/http://pathology.jhu.edu/http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology.jhu.edu/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pathology2.jhu.edu/sp/mailform.cfmmailto:[email protected]


15/23

In this context, ALK positivity confirms the diagnosis but is not positive in allcases and in fact becomes less frequent as a function of patient age.

In ALK negative cases, staining with CD4, CD2 and/or TIA-1 can beconfirmatory in conjunction with appropriate morphology, however thereappears to be no uniform criteria for separating ALK negative ALCL fromperipheral T-cell lymphoma, NOS. The distinction is prognostically relevantas the survival decreases from ALCL ALK+ (best), ALCL ALK-(intermediate), to PTCL NOS (worst). Isolated cutaneous ALCL has the best


16/23

prognosis of all.

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Your Answer is CORRECT presented byAndrea Subhawong, M.D.

You answered:

T cell/ histiocyte rich large B-celllymphoma

The correct diagnosis is:

T cell/ histiocyte rich large B-celllymphoma

Review the Slides

Histology: The architecture is effaced by a diffuse lymphoid infiltrate. Most of theinfiltrate is composed of small lymphocytes and histiocytes, but thereare scattered large, atypical cells with abundant cytoplasm andcomplex nuclei; some cells appear to be binucleated. Byimmunohistochemistry, the large cells are positive for CD20, andnegative for CD3, CD15 and CD30 (not shown). There is no residualnodularity in the background of the node.

Discussion: TCRBCL may be difficult to distinguish from a diffuse variant of nodularlymphocyte predominant Hodgkin lymphoma (NLPHL), bothmorphologically and immunophenotypically. Like TCRBCL, NLPHL isconsidered to be a B cell neoplasm. However, the malignant cells ofTCRBCL lack the popcorn cytology of the atypical cells of NLPHL.Furthermore, an immunostain for CD57 may be helpful since increasednumbers of CD57-positive T cells are commonly found in NLPHL andare usually distributed in rings around the popcorn cells. TCRBCL is
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considered to be a morphologic variant of diffuse large B celllymphoma. It is an aggressive lymphoma but is amenable to cure withmulti-agent chemotherapy.

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incorporated into any information retrievel system, electronic or mechanical, without the written permission of JHU.


Copyright 2000-2006 The Johns Hopkins UniversityAll rights reserved. No part of this website may be reproduced in any form or by any

means or

incorporated into any information retrievel system, electronic or mechanical, without the

written permission of JHU. Discussion:

MALT lymphoma is characterized by a dense, monotonous

population of centrocyte-like cells, lymphoepithelial lesions

(infiltration of glandular epithelium by lymphocytes) and

frequent follicular colonization. The tumor cells may also

have plasmacytoid differentiation. Tumor cells are

immunoreactive for B cell markers, including CD19, CD20,

and CD79a, as well as bcl-10, with variable CD43 staining.

They exhibit monoclonal light chain staining. This case

demonstrated monoclonal heavy chain rearrangement by

molecular studies.
http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/mailform.cfmhttp://pathology2.jhu.edu/sp/mailform.cfmhttp://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pathology.jhu.edu/http://pathology.jhu.edu/http://pathology2.jhu.edu/sp/mailform.cfmhttp://pathology2.jhu.edu/sp/mailform.cfmhttp://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pathology.jhu.edu/http://pathology.jhu.edu/http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/result.cfm?CFID=6417107&CFTOKEN=32851047http://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047http://pathology.jhu.edu/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pathology2.jhu.edu/sp/mailform.cfmhttp://pathology.jhu.edu/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pds17.pathology.jhmi.edu/N/n.web?EP=N&URL=/MCGI/DICLKUP%5EWEBDICT%28304,1%29/http://pathology2.jhu.edu/sp/mailform.cfmhttp://pathology2.jhu.edu/sp/continue.cfm?grp=0&CFID=6417107&CFTOKEN=32851047


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Gastric MALT lymphomas are closely linked to Helicobacter

pyloriinfection, and H. pylorieradication therapy produces

a long term favorable outcome (Tohoku J Exp Med

2008;214:79)

Celiac disease, or gluten-sensitive enteropathy, is a T-cell

mediated disease of genetically susceptible individuals,

induced by ingesting proteins in wheat (gliadins), barley

(hordeins) or rye (secalinin). Symptoms include episodic

diarrhea, abdominal pain and distention and weight loss

(Clin Med Res 2004;2:71), with clinical and microscopic

improvement after dietary withdrawal. Microscopic changes

include an increase in intraepithelial lymphocytes of 40+lymphocytes/100 surface or upper crypt enterocytes, or early

clustering of 12+ lymphocytes at the tip of villi and extending

evenly down the sides of the villus (Mod Path

2003;16:342). There is also diffuse enteritis with marked

atrophy or total loss of villi and elongated crypts. Definitive

diagnosis requires these histologic findings plus positive

serology and favorable clinical and serologic responses after

dietary change. The differential diagnosis includes duodenal

intraepithelial lymphocytosis with normal villous architecture,

associated with H. pyloriinfection, but without any other

features of celiac disease (Mod Path 2005;18:1134).

In this case, the presence of celiac sprue appears to be

incidental. Celiac sprue is associated with an increased risk

of malignant intestinal disease, but this is usually T cell

intestinal lymphoma of the small bowel, not MALT lymphoma

of the stomach. Celiac sprue does not appear to be

associated with H. pylorigastritis (Am J Gastroenterol

2006;101:1880).

Additional references: PathologyOutlines.com chapters

-small bowel,Lymphoma: B cell,Stomach
http://www.ncbi.nlm.nih.gov/pubmed/18212490http://www.ncbi.nlm.nih.gov/pubmed/18212490http://www.ncbi.nlm.nih.gov/pubmed/18212490http://www.ncbi.nlm.nih.gov/pubmed/18212490http://www.ncbi.nlm.nih.gov/pubmed/15931338http://www.ncbi.nlm.nih.gov/pubmed/15931338http://www.ncbi.nlm.nih.gov/pubmed/15931338http://www.ncbi.nlm.nih.gov/pubmed/12692199http://www.ncbi.nlm.nih.gov/pubmed/12692199http://www.ncbi.nlm.nih.gov/pubmed/12692199http://www.ncbi.nlm.nih.gov/pubmed/12692199http://www.ncbi.nlm.nih.gov/pubmed/15803187http://www.ncbi.nlm.nih.gov/pubmed/15803187http://www.ncbi.nlm.nih.gov/pubmed/15803187http://www.ncbi.nlm.nih.gov/pubmed/16780559http://www.ncbi.nlm.nih.gov/pubmed/16780559http://www.ncbi.nlm.nih.gov/pubmed/16780559http://www.ncbi.nlm.nih.gov/pubmed/16780559http://www.pathologyoutlines.com/smallbowel.html#celiacspruehttp://www.pathologyoutlines.com/smallbowel.html#celiacspruehttp://www.pathologyoutlines.com/smallbowel.html#celiacspruehttp://www.pathologyoutlines.com/lymphoma.html#MALThttp://www.pathologyoutlines.com/lymphoma.html#MALThttp://www.pathologyoutlines.com/lymphoma.html#MALThttp://pathologyoutlines.com/stomach.html#MALThttp://pathologyoutlines.com/stomach.html#MALThttp://pathologyoutlines.com/stomach.html#MALThttp://pathologyoutlines.com/stomach.html#MALThttp://www.pathologyoutlines.com/lymphoma.html#MALThttp://www.pathologyoutlines.com/smallbowel.html#celiacspruehttp://www.ncbi.nlm.nih.gov/pubmed/16780559http://www.ncbi.nlm.nih.gov/pubmed/16780559http://www.ncbi.nlm.nih.gov/pubmed/15803187http://www.ncbi.nlm.nih.gov/pubmed/12692199http://www.ncbi.nlm.nih.gov/pubmed/12692199http://www.ncbi.nlm.nih.gov/pubmed/15931338http://www.ncbi.nlm.nih.gov/pubmed/18212490http://www.ncbi.nlm.nih.gov/pubmed/18212490


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20/23

Grossly, most central lymphomas are solid, grey, ill-defined,

and usually deep-seated. Some travel along white matter

tracts and transcend the corpus callosum, like infiltrating

gliomas. Histologically, they are widely infiltrating with aperivascular predilection. Most are discohesive, but may

occur in a glial meshwork within the CNS. Primary brain

lymphomas have scant cytoplasm, high grade nuclei and

multiple nucleoli, but less pleomorphism than other high

grade CNS tumors. Most primary CNS lymphomas are

diffuse large B cell subtype, and are immunoreactive for

CD20, CD79a and CD22, but negative for CD3. However,

nearly all tumors have a background of reactive T cells that

may lead to an erroneous diagnosis of T cell lymphoma.

The mitotic index is often > 50%.

Smears show single cells with discrete cell borders,

vesicular nuclei, prominent nucleoli and frequent apoptosis.

Treatment includes high-dose methotrexate therapy with or

without radiation. Chemotherapy has extended median

survival in immunocompetent patients to 44 months

(eMedicine). Although tumors can be classified by

immunohistochemistry into germinal center and non-

germinal center phenotypes, this does not appear to

influence prognosis (Neuropathology 2009 Nov 18 [Epub

ahead of print],J Ne

Discussion

Intravascular lymphoma is a rare subtype of diffuse large B

cell lymphoma, with intravascular growth in the skin, CNS,

and other sites. The presenting signs and symptoms are

often complex, and include mental status changes, as in this

case, and rapidly progressive dementia. Patients may

present with a mass lesion (Pathol Int 2004;54:231), a skin
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rash or fever of unknown origin.

Patients are typically elderly, with a median age of 71 years.

Although chemotherapy may be effective (Ann Oncol

2004;15:1215), these tumors are often not diagnosed until

autopsy, which typically shows involvement of most organs.

In this case, the patient was 72 years old, and expired two

weeks after the brain biopsy. A post-mortem examination

revealed widespread disease, with involvement of the heart,

lung, kidneys, adrenals, stomach, pancreas and spleen. No

skin lesions were found.

Histologically, the tumor is composed of large centroblast-

like lymphoid cells with prominent nucleoli within small

vessel lumina, often capillaries. Mitotic figures are frequent,

and there are often fibrin thrombi. Immunohistochemistry

results are similar to diffuse large B cell lymphoma, with

immunoreactivity for CD19, CD20, CD22 and CD79a.

Tumors are usually bcl2 positive. Rarely, these tumors are T

cell lymphomas with corresponding immunoreactivity.

Discussion

The initial flow cytometry showed CD20 and CD5 co-

expression without CD23 expression, generating a

differential diagnosis of atypical CLL (atypical since CD23

was not expressed), prolymphocytic leukemia (either de

novo or secondary to CLL) and mantle cell lymphoma. A

diagnosis of atypical CLL was favored based on the lack of

organomegaly / lymphadenopathy, only moderately

increased and stable WBC counts, prolymphocytes < 55%

and lack of t(11;14). The subsequent lymph node biopsyhad the characteristic CLL/SLL immunophenotype of CD5+,

CD23+ B cells.

The paraimmunoblastic variant of SLL/CLL is a rare

morphologic variant characterized by a diffuse to nodular
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proliferation of paraimmunoblasts, the cells usually seen in

pseudoproliferation centers of SLL. In classic SLL, the

predominant population is small lymphocytes with scant

cytoplasm, coarsely clumped chromatin and inconspicuous

nucleoli. In the paraimmunoblastic variant, the predominant

cells are slightly larger, with moderately abundant cytoplasm,more open/vesicular chromatin and a single prominent,

central nucleolus. The paraimmunoblasts have the same

staining pattern as classic CLL/SLL (i.e. expression of CD19,

CD20, CD5 and CD23, negative for CD10 and FMC7). It is

considered the tissue counterpart of a prolymphocytic

transformation of CLL.

The paraimmunoblastic variant was first described by Pugh

as an aggressive variant that presents with generalizedlymphadenopathy, and occasionally splenomegaly (Am J

Surg Pathol 1988;12:907). The term paraimmunoblast

was first used by Lennert (Malignant Lymphomas other than

Hodgkins disease. Berlin/Heidelberg: Springer-Verlag,

1978:111-36) to describe a mitotically active, medium-sized

cell with weakly staining eosinophilic cytoplasm, irregular

nuclear borders, vesicular chromatin and a single,

prominent, central nucleolus. In contrast, immunoblasts are

larger cells with moderate basophilic cytoplasm, large round

nuclei and a similar prominent, central nucleolus.

Centroblasts are larger cells with multiple basophilic,

peripherally-placed nucleoli.

The differential diagnosis in this case includes a Richters

transformation and blastoid variant of mantle cell lymphoma.

Richters transformation of CLL/SLL usually presents with a

single area of marked nodal growth, unlike the diffuse,

symmetrical lymphadenopathy in this and other

paraimmunoblast variant cases. The Richters node may

show complete or partial involvement by sheets of

centroblasts or immunoblasts with a proliferation fraction in

transformed areas greater than 40% (Cancer J

2005;11:161).

Blastoid variant of mantle cell lymphoma also has a vaguely
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nodular architecture and slightly larger cells with less

clumped chromatin. However, cyclin D1 is overexpressed

and t(11;14) is detected by FISH analysis.

The original flow cytometric examination demonstrated

several features associated with a poor prognosis, including

CD38 expression, a complex karyotype and p53 mutation

(Jaffe: WHO Classification of Tumors, Pathology and

Genetics of Tumours of the Haematopoietic and

Lymphoid System,Blood 1998;91:4342, Blood

2001;98:181). In addition, patients with the

paraimmunoblastic variant of CLL/SLL have an aggressive

clinical course (Hum Path 2002;33:1145).

Nat Pernick, M.D., President

PathologyOutlines.com, Inc.30100 Telegraph Road, Suite 404Bingham Farms, Michigan (USA) 48025Telephone: 248/646-0325

Fax: 248/646-1736
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