325 ALK Positive Plasmablastic Neoplasm

Introduction/Objective The classification systems for hematolymphoid neoplasms recognize ALK-Positive Large B-cell Lymphoma (ALK+ LBCL) as having plasmablastic morphology and a rearrangement of the ALK gene, resulting in ligand independent activation of ALK kinase. We report an ALK-positive plasmablastic neoplasm by immunohistochemistry (IHC) which did not show an ALK rearrangement by break-apart fluorescent in-situ hybridization (FISH). The neoplastic cells showed increased mitotic activity, morphology ranging from plasmablastic to bizarre, and IHC positivity for CD138 (partial), MUM1, ALK(D5F3), kappa, and CD79a(partial). They were negative for PAX5, CD20, CD19, CD30, lambda, EBER, and HHV8. The case was later clinically matched more closely to a plasma cell myeloma with plasmablastic morphology, and treated as such. We learned that there is evidence supporting that the ALK clone we use in our laboratory (D5F3) is more sensitive but less specific than ALK1 (the other commonly used clone). This discrepancy should be noted when making diagnoses of plasmablastic neoplasms, especially in extramedullary sites. In our particular case, there was also an unusual clinical presentation given the patient’s young age for myeloma, extramedullary involvement, concurrent lymphadenopathy, low level of paraprotein in serum, and lack of other common clinical manifestations of myeloma (i.e. renal deficiency, anemia, hypercalcemia (CRAB)). Methods/Case Report Our patient is a 46 year-old previously healthy male who developed progressive pain and edema in the right knee and tibia. MRI revealed a 10cm osteolytic mass involving bone and soft tissue, which was biopsied. At the time of diagnosis, complete blood count (CBC) was normal and serum protein electrophoresis (SPEP) showed an IgA kappa monoclonal band at 0.6 g/dL. He also had mild inguinal lymphadenopathy (21mm max dimension). A bone marrow biopsy showed involvement by a plasmacytic neoplasm expressing ALK by IHC, albeit not as strongly as in the tissue biopsy. After the FISH was negative for ALK rearrangement, the clinical decision to treat the patient with a myeloma regiment was made (daratumumab, lenalidomide, dexamethasone, and bortezomib, (Dara-VRD)). Additionally the patient received 2500cGy of radiation to the right tibial mass. After 5 cycles of treatment, the patient’s SPEP is no longer detectable and the mass in the right tibia decreased in size considerably. However, the patient developed massive edema in the lower extremities bilaterally. He also developed osseus lesions in the spine which were presumed to be residual/relapsed disease. He has not yet achieved complete remission. Results N/A Conclusion There is a histologic and clinical overlap between the different plasmablastic neoplasms. Relying solely on ancillary testing for classification can lead to misdiagnoses. Multiple myeloma is commonly a disease of older patients with CRAB symptoms which can have plasmablastic morphology. Instead, our patient was relatively young, with normal CBC and calcium levels, and normal renal function who’s presenting symptoms were related to a large tibial/soft tissue mass. In addition the patient’s imaging showed mild lymphadenopathy (in retrospect most likely reactive). ALK+ LBCL is a rare disease with a median age of 38 and aggressive clinical course. It involves lymph nodes and extramedullary sites and is defined by the rearrangement in ALK, which we did not have. However, the ALK expression by IHC could have led us to a misdiagnosis. Other entities with plasmablastic morphology and immunophenotype include plasmablastic lymphoma, seen in HIV/immunodeficient patients and often EBER positive (unlike our case), and HHV8-associated neoplasms (negative in our case). We conclude that IHC, especially the D5F3 ALK clone, is insufficient for diagnosing ALK+ LBCL since it is not specific and since the plasmablastic neoplasms share many clinicopathologic features. FISH and concordance with the clinical data are necessary for definitive evaluation.