Composite mantle-cell lymphoma and classical Hodgkin lymphoma in a very old adult.

Abstract

To the Editor: Composite lymphoma (CL) denotes the occurrence of two or more morphologically and immunophenotypically distinct lymphoma clones in a single anatomical site.1, 2 CL is a rare condition, documented in the literature mostly as case reports3 rather than study series.4 No single definite mechanism has been proposed to explain the pathogenesis of the different types of CL because it is likely that the etiology differs according to the type of lymphoma involved. Generally, immunological status is a crucial element that may predispose to composite lymphoma; CL may arise during the course of atypical lymphoproliferative lesions, Castleman disease,5 states of immunosuppression, chemotherapy, or multiple viral infections.6 The different combinations of lymphomas documented in the literature are two different types of non-Hodgkin lymphoma together (even small lymphocytic leukemia),7, 8 B-cell lymphoma with T-cell lymphoma,9 and non-Hodgkin lymphoma with Hodgkin lymphoma.3, 4 Mantle cell lymphoma has been reported in composite form together with follicular lymphoma, small lymphocytic lymphoma, and plasmocytoma.10, 11 The first report of a composite mantle cell and classical Hodgkin lymphoma dates to 2003. Since 2003, only four cases of this CL have been reported.3, 4, 12 We report a case of mantle cell and Hodgkin CL in an 89-year-old woman who presented with pulmonary embolism, involvement of axillary and mediastinal lymph nodes, hepatomegaly, and splenomegaly. The woman was admitted to the emergency department because of an episode of syncope. Chest computed tomography performed because of high D-dimer revealed multiple mediastinal lymph nodes approximately 1.5 cm in diameter, bilateral axillary lymph nodes with a maximal diameter of 3 cm, and signs of distal bilateral pulmonary embolism. The woman was then admitted to the Geriatric Unit. Blood analysis showed hemoglobin 10.5 g/dL, white blood cell count 8,460/μL, and 4,580 lymphocytes/μL. An excisional biopsy of a 3-cm-diameter axillary lymph node was performed. Microscopy showed a diffuse sheet of monomorphic small lymphoid cells containing small nucleoli. Immunohistochemistry analysis was positive for CD20, CD79a, and cyclin D1 and negative for CD5 and CD23, although among these cells were CD15- and CD30-positive and CD20- and cyclin D1–negative Reed-Sternberg cells. Fluorescence in situ hybridization (FISH) was performed to examine interphase cells for the presence of the IgH/CCND1 gene rearrangement due to a translocation between chromosomes 11 and 14, which characterizes mantle cell lymphoma. A t(11;14)(p13;q32) was demonstrated in the small lymphoid but not in the Reed-Sternberg cells. A diagnosis of coexisting mantle cell and Hodgkin lymphoma (CL) was made. Considering the woman's age, therapy was started with prednisone 37.5 mg/d (Figure 1). This is the fifth case of mantle cell and Hodgkin CL and the first one in a very old adult; previous cases occurred in individuals aged 42 to 69. In any case of CL, the question arises as to whether it is a single or two clonally different lymphomas. Some pathogenetic hypotheses have been made. B-cell CL could be due to clonal selection. A clone of malignant B-cells within a tumor may be exposed to additional mutational accumulation and change into a more-aggressive neoplasm, coexisting with the original clone. An example is Richter syndrome of B-cell small lymphocytic lymphoma changing to diffuse large B-cell lymphoma with the persistent coexistence of both clones in the same tissue. Another hypothesis is that immature precursor cells may have a multideviant pathway that results in more than one type of B-cell lymphoma. In the current case, the absence of the translocation in Reed-Sternberg cells revealed using FISH suggests the unrelated clonality of the two type cells, therefore representing “true” CL. This report adds to the available knowledge by demonstrating that CL may occur even in very old adults. Aging is characterized by immune depression and dysregulation,13 which probably puts older adults at risk of CL, but the lack of previous reports of CL in very old adults does not support this hypothesis. Finally, the rising awareness of CL should lead to a more-systematic search for and diagnosis of this seemingly rare condition. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Renato Giua was one of the attending physicians, had the original idea for the case report, and collected all the material used in this report. Davide Fontana was one of the attending physicians and contributed to drafting the manuscript. Giuseppe Deda, Antonella Bianchi, and Carla Rabitti performed and interpreted the histological analysis and reviewed the manuscript for important intellectual content. Raffaele Antonelli Incalzi contributed to drafting the manuscript and reviewed it for important intellectual content. All authors read the final manuscript and approved it for publication. Sponsor's Role: No sponsorship was received for this paper.