Figure: 1 Intraabdominal nodal mass FNA, Papanicolaou and Diff-quik Stains, 200 X; showing cellular smear comprising of plasmacytoid cells
Figure 2. Cell block of FNA sample, 200X showing sheets of plasma/plasmacytoid cells.
Figure 3. Immunohistochemical stains on the cell-block, 200X showing
3a. Plasmacytoid cells are negative for AE1/AE3 (cytoplasmic),
3b. Plamsacytoid cells negative for HMB 45, ruling out melanoma
3c & 3d: Plasma cells are negative for lambda light chain antibody, while positive for cytoplasmic kappa light chain antibody.
3e. Positive CD 138(cytoplasmic) in plasma cells,
3f. Flow-cytometry report from Integrated Oncology revealed a clonal IgG kappa plasma cell population (~28%).
1. The most likely diagnosis is:
b. Neuroendocrine tumor
c. Plasmablastic lymphoma
d. Plasma cell dyscrasias/ plasmacytoma e. lobular carcinoma of the breast
2. On rapid on-site evaluation (ROSE), what would be the next crucial step in appropriately triaging the specimens so that the adequate work up can be performed?
b. Next Generation Sequencing
d. Culture studies
3. What are the characteristic cytomorphological features on the smears?
a. Single plasmacytoid small cells with salt and pepper chromatin, scant cytoplasm and small intracytoplasmic vacuoles.
b. Single plasmactyoid and groups of cells forming papillary groups and large intracytoplasmic vacuoles.
c. Dyscohesive plasmacytoid cells with eccentric nuclei, clumped chromatin, abundant basophilic cytoplasm and binucleated cells.
d. Single plasmacytoid cells with prominent macro-nucleoli, binucleate cells, intranulcear inclusions and vesicular chromatin.
4. What is the required panel of immunohistochemical stains for reaching the diagnosis?
a. CD 20, CD 3, Kappa & Lambda
b. AE1/AE3, Synaptophysin and Chromogranin
c. AE1/AE3, HMB45, Melan A
d. CD 138, Kappa & Lambda e. CD 163, CD 34, Kappa
5. Once the final diagnosis is made, what are the next important steps on the management perspective?
a. Whole body imaging with CT/PET study
c. Bone marrow biopsy with cytogenetic and FISH study
d. All of the above
Extramedullary presentation of multiple myeloma (MM) is a rare presentation, occurring in 10 % – 15 % of patients (2). Five percent of patients with multiple myelomas are diagnosed with extramedullary plasmacytomas, and even less than that are diagnosed as a primary lesion (3). The diagnosis of extramedullary plasmacytoma without the clinical signs or symptoms in an unknown primary is difficult and challenging. This case highlights a first presentation of multiple myeloma diagnosed by EUS-FNA and presented as an unknown primary in the setting of known history of prostate carcinoma; and the diagnosis had a major impact on the treatment and management.
EUS-FNA is a minimally invasive and effective method for sampling of malignant and benign lesions of the pancreas, the biliary system, the gastrointestinal tract wall and of lymph nodes in its vicinity playing a key role in primary diagnosis and in staging of gastrointestinal malignant tumors(6). The diagnosis of extramedullary plasma cell neoplasm by imaging studies is difficult due to lack of typical features on CT, magnetic resonance imaging (MRI) and ultrasound (12).
In current case, the Diff-Quik and Papanicolaou stained slides showed highly cellular smear consisting of numerous, dyscohesive, single, large and small plasmacytoid cells, with clumped chromatin and abundant basophilic cytoplasm. Some cells were binucleated. Based on this morphology, the differential diagnoses included plasmablastic lymphoma, plasmacytoma, melanoma, neuroendocrine tumor and lobular carcinoma of the breast (17, 18). Hence, an aliquot of the sample was submitted for flow-cytometry with a request to add plasma cell markers; and part of the specimen was collected for cell-block for ancillary studies. Flow-cytometry was negative for lymphoma, however showed that ~28% of the cells were CD 38 positive with kappa light chain restriction.On immunohistochemical studies, these plasmacytoid cells were positive for CD79a, CD138 and kappa light chain while lambda light chain was negative establishing its monoclonality. The plasmacytoid cells were negative for pan-cytokeratin, HMB-45 and synaptophysin and chromogranin antibodies. Once the diagnosis of extramedullary plasma cell dyscrasia was made on cytomorphology and immunophenotype; the cytopathologist recommended serum and urine protein electrophoresis, whole body imaging (CT/PET), 24 hour urine protein analysis and bone marrow biopsy with cytogenetic and FISH study in the report. This step is crucial to rule out underlying multiple myeloma. Based on the cytomorphological diagnosis and recommendation, a CT/PET scan was requested, which revealed multiple FDG avid lesions, including extensive bone lesions, markedly elevated kappa free light chain and kappa: lambda ratio. The case was finally diagnosed as light chain restricted multiple myeloma.
Above mentioned steps in clinical management are important to rule out presence of underlying multiple myeloma as multiple myeloma complicated by secondary extramedullary plasmacytoma carries a poor prognosis, like in current case.
In summary, we present herein a rare presentation of multiple myeloma as an extramedullary plasmacytoma of an unknown solitary, intraabdominal mass. We also highlight herein, the importance of EUS-FNA as a minimally invasive, cost effective diagnostic modality with very low rate (1.5 to 2%) of complications and high diagnostic yield (6, 16). This case emphasizes the importance of appropriately triaging the specimen during the rapid on-site evaluation, obtaining the material for ancillary studies to aid to the appropriate diagnosis and, avoiding diagnostic pitfalls. The role of cytopathologist during on-site evaluation remains crucial and pivotal for the successful diagnosis. Awareness of the unusual presentation of this entity and the need for high degree of suspicion is required to avoid delay in diagnosis, and for appropriate treatment.
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Sharvari Dalal M.D., FCAP; FASCP Director Cytopathology & Clinical Chemistry CMC Philadelphia VA Medical Center
Darshana Jhala M.D., B.Mus., FCAP Professor of pathology University of Pennsylvania Perelman School of Medicine Chief, Pathology and Laboratory Medicine CMC Philadelphia VA Medical Center