Clinical Features. Follicular lymphoma mainly occurs in adults older than 50 years of age and affects males and females equally. It usually manifests as painless, generalized lymphadenopathy. The bone marrow is involved at diagnosis in approximately 80% of cases. Although the natural history is prolonged (overall median survival, approximately 10 years), follicular lymphoma is not curable, an unfortunate feature shared with most other relatively indolent lymphoid malignancies. As a result, therapy with cytotoxic drugs and rituximab (anti-CD20 antibody) is reserved for those with bulky, symptomatic disease. BTK and BCL2 inhibitors are also active in this disease and are being evaluated in clinical trials. In about 30% to 40% of patients, follicular lymphoma progresses to diffuse large B cell lymphoma. This transformation is an ominous event, as tumors arising from such conversions are much less curable than de novo diffuse large B cell lymphomas, described later.
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Fig. 12.16 Follicularlymphoma—lymphnode.(A)Nodularaggregatesoflymphomacellsarepresentthroughout.(B)Athighmagnification,smalllymphoidcellswithcondensedchromatinandirregularorcleavednuclearoutlines(centrocytes)aremixedwithapopulationoflargercellswithnucleoli(centroblasts).(A,Courtesy of Dr. Robert W. McKenna,Department of Pathology,University of Texas Southwestern Medical School,Dallas,Texas.)
Mantle cell lymphoma is composed of cells resembling the naive B cells found in the mantle zones of normal lymphoid follicles. It constitutes approximately 6% of all NHLs and occurs mainly in men older than 50 years of age.
Almost all tumors have an (11;14) translocation that fuses the cyclin D1 gene to the IgH locus. This translocation leads to overexpression of cyclin D1, which you will recall stimulates growth by promoting the progression of cells from the G1 phase to the S phase of the cell cycle (Chapter 6).
MORPHOLOGYMantlecelllymphomamayinvolvelymphnodesinadiffuseorvaguelynodularpattern.Proliferationcentersareabsent,afeaturethathelpstodistinguishmantlecelllymphomafromCLL/SLL.Thetumorcellsusuallyareslightlylargerthannormallymphocytesandhaveanirregularnucleus,inconspicuousnucleoli,andscantcytoplasm.Lesscommonly,thecellsarelargerandmorphologicallyresemblelymphoblasts.Thebonemarrowisinvolvedinmostcasesandtheperipheralbloodinabout20%ofcases.Thetumorsometimesarisesinthegastrointestinaltract,oftenmanifestingasmultifocalsubmucosalnodulesthatgrosslyresemblepolyps(lymphomatoidpolyposis).
Immunophenotype. The tumor cells express surface IgM and IgD, the B cell antigen CD20, and CD5, and they contain high levels of cyclin D1 protein.
Clinical Features. Most patients present with fatigue and lymphadenopathy and are found to have generalized disease involving the bone marrow, spleen, liver, and (often) the gastrointestinal tract. These tumors are moderately aggressive and incurable. The median survival is 4 to 6 years. Like CLL/SLL cells, mantle cell lymphoma cells depend on signals generated through BTK for survival, and it is hoped that newly available BTK inhibitors will improve clinical outcomes.
This indolent B cell tumor arises most commonly in epithelial tissues such as the stomach, salivary glands, small and large bowel, lungs, orbit, and breast.