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Diagnosis & Discussion


Primary cutaneous marginal zone lymphoma (PCMZL), conventional variant. 


Primary cutaneous B-cell lymphomas (PCBCLs) represent a group of lymphomas whose primary site is the skin. The skin can also be the site of secondary involvement by extracutaneous (usually nodal) B-cell lymphomas. Overall, B-cell lymphomas represent 22.5% of all cutaneous lymphomas. Primary cutaneous B-cell lymphomas (PCBCLs) are classified into 3 main categories: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (DLBCLLT). It is important to add that cutaneous cases have a better prognosis compared to other variants of marginal zone lymphoma and the 5-year survival rate is reported to be 98%. The etiology of PCMZL is felt to be similar to other MALT lymphomas and results from longstanding antigenic stimulation from chronic infections or autoimmune diseases. 

There are five main histopathologic presentations of PCMZL: conventional, lymphoplasmacytic (formerly cutaneous immunocytoma), plasmacytic (formerly cutaneous plasmacytoma), blastoid variant and cutaneous amyloidoma. The conventional variant (as in our case) is the most common and comprises approximately 82% of all PCMZL cases. It occurs mostly in younger adults with a male predominance. Clinically these patients present with recurrent pink-violet to red-brown papules, plaques, and nodules that favor the extremities (upper > lower) or trunk.  

Histologically, the conventional variant of PCMZL demonstrates a dermal cellular infiltrate that may extend into the subcutis but spares the epidermis. The infiltrate may have a nodular or diffuse pattern characterized by lymphoid follicles (often with germinal centers) surrounded by pale-staining peri- and interfollicular small to medium-sized cells with indented nuclei, inconspicuous nucleoli and abundant pale cytoplasm (malignant marginal zone cells). In addition, plasma cells (at the margin of the infiltrate or beneath the epidermis), lymphoplasmacytoid cells, small lymphocytes and occasional large blasts are observed. In the interfollicular areas, there are occasional large blasts as well as variable numbers of histiocytes and eosinophils. The neoplastic population includes marginal zone cells, lymphoplasmacytoid lymphocytes and plasma cells. Where there is a more diffuse pattern, the mantles of follicles may be obliterated by the neoplastic component (follicular colonization). In some patients, there may be a granulomatous reaction with epithelioid and giant cells.  

Marginal zone cells stain positively with CD20, CD79a, Fc receptor-like 4 (FCRL4/IRTA1)27a, and Bcl-2; they are negative for CD5, CD10, and Bcl-6. Neoplastic plasma cells are highlighted with CD38 and CD138. The scattered large blastic cells can be CD30 positive. BCL-6 and to a lesser degree CD10 are particularly useful in differentiating PCMZL (negative) from cutaneous follicle center lymphoma (positive). Here one should keep in mind that follicular B lymphocytes in reactive germinal centers are BCL-6 positive, which are a common finding in PCMZL. Plasma cells and lymphoplasmacytoid cells commonly show cytoplasmic immunoglobulin light chain restriction (kappa or lambda). If clonality is still questionable, in situ hybridization for the immunoglobulin (Ig) light chains is a more sensitive method than immunohistochemistry.  

A monoclonal rearrangement of the Ig genes can be observed in approximately 50-60% of cases. A proportion of cases exhibit trisomy 3, the t(14;18)(9q32;q21) translocation, or the t(3;14)(p14.1;q32) translocation. These two translocations involve the IGH and MALT1 genes and the IGH and FOXP1 genes, respectively.  

The main entities in the histologic differential diagnosis are reactive lymphoid infiltrates and other cutaneous lymphomas. Confirmation of malignancy can be routinely achieved by identifying kappa or lambda restriction in tissues or by gene rearrangement studies. In general, the combination of morphologic and immunohistochemical findings allows distinction from other cutaneous lymphomas.  

PCMZL and all low-grade PCBCLs can be managed conservatively with a watchful-waiting strategy. Those with solitary or only a few lesions are treated with local radiotherapy, simple surgical excision, or surgical excision followed by radiotherapy. Antibiotic therapy may be suitable for those with identifiable infectious agent. Cases with multiple lesions are treated with subcutaneous or intralesional interferon and/or anti-CD20 monoclonal antibody (rituximab).


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