Journal of Hematopathology (2019) 12:27–30 https://doi.org/10.1007/s12308-018-0338-y CASE REPORT CD38 negative anaplastic plasma cell myeloma with (14;16) translocation: a diagnostic dilemma for highly aggressive neoplasm: case report Mansour S. Aljabry1 Received: 10 October 2018 /Accepted: 18 December 2018 /Published online: 2 January 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Anaplastic plasma cell myeloma (PCM) is an aggressive morphological variant of myeloma characterized by involvement of extramedullary sites and extremely poor prognosis. Moreover, anaplastic PCM is frequently associated with high frequency of 17p(p53) deletions, 1q21(CKS1B) amplifications and immunoglobulin A (IgA) isotype. It usually manifests as an adverse pro- gression of previously treated conventional plasma cell myeloma. However, the anaplastic morphology can be encountered in newly diagnosed cases and might pose a major diagnostic challenge. Herein, we present a rare case of anaplastic plasma cell myeloma with (14;16) translocation which was diagnosed initially as a non-hematopoietic malignancies due to its unusual clinicopathological profile comprising acute presentation, extremely anaplastic morphology, and negative staining of CD38 immunohistochemical marker. In view of lack of clinical suspicion of plasma cell myeloma, no serological investigations for myeloma had been requested initially. In fact, high index of suspicion of myeloma arose only when results of MRI and CT scan came out revealing bony lytic lesions and collapsed vertebrae. Subsequently, bone marrow biopsy was repeated and revealed an extensive infiltration with sheets of neoplastic plasma cells which were strongly positive for CD138, KAPPA, and CD56 IHC markers. Keywords Anaplastic myeloma . CD38 IHC markers . t(14;16) Introduction Case report Anaplastic cell myeloma is a rare and therapy-resistant sub- A 62-year-old female presented to the emergency de- type of plasma cell myeloma with poor prognosis. It usually partment with fever, persistent headache, and easy bruis- manifests as an adverse progression of previously treated con- ing for 1 week duration. The patient also complained of ventional plasma cell myeloma. However, the anaplastic mor- progressive lower limb weakness and shortness of phology can be encountered in newly diagnosed cases and breath for the last 1 month. She was also suffering from might pose a diagnostic challenge. diabetes mellitus and osteoarthritis. Her family history Herein, we present a rare case of anaplastic plasma cell revealed that her older sister died of breast cancer myeloma with (14;16) translocation that was initially diag- 10 years ago. On physical examination; she was pale, nosed as a non-hematopoietic malignancy due to unusual had few large bruises on the left flank and her body clinic-pathological profile comprised of acute presentation, temperature was 37.8 °C. There was no extremely anaplastic morphology and for being negative for hepatosplenomegaly or lymphadenopathy. CD38 marker. Methods and materials The laboratory findings revealed a hemoglobin of 82 g/L * Mansour S. Aljabry – 12 [email protected]; [email protected] (120 160 g/L), red blood cell (RBC) count was 3.15 × 10 / L(4.2–5.5 × 1012/L), leukocyte count was 1.9 × 109/L (4.5– 9 1 Hematopathology, King Khalid University Hospital–King Saud 11 × 10 /L) with myelocytes 3%, neutrophils 21%, monocytes University, P.O Box 2925, Riyadh 11461, Kingdom of Saudi Arabia 9%, and lymphocytes 67%. Platelet count was 12 × 109/L 28 J Hematopathol (2019) 12:27–30 (140–450 × 109/L). Biochemical markers revealed high levels However, they were all found to be negative. The conclusion of LDH: 780 U/L (100–190 U/L), uric acid: 509 μmol/L of bone marrow report was undifferentiated neoplasm in favor (155–357 μmol/L) and serum calcium level: 2.78 mmol/L of non-hematopoietic malignancies for further work-up. (2–2.55 mmol/L) while serum albumin was 39 mg/dL (30– Abdominal and pelvic ultrasound examination revealed 50 mg/dL). Renal and liver function tests were within normal mild hepatosplenomegaly with no focal lesion was detected. limits. Peripheral blood smear showed leukoerythroblastic Mutli-sequentail MRI for whole spine showed collapsed L5 blood picture with few large atypical cells (blast-looking vertebral body, anterior wedging of L1 and mild thickening of cells) representing about 1%. Severe thrombocytopenia was prevertebral soft tissue from D7 down to D10 (Fig. 1B). CT confirmed. scan of chest, abdomen, and pelvis revealed presence of a lytic Patient was admitted with a provisional diagnosis of acute bone lesion involving L5 with compression fractures. No leukemia for further investigations. Bone marrow aspirate was lymphadenopathy or organomegaly was noticed. The final a dry tap and showed only few erythroid and myeloid precur- impression of the radiology team was highly suggestive of sors without any abnormal cells. Touch imprint for bone mar- plasma cell myeloma for further investigation. row biopsy was cellular and showed large atypical cells with A monoclonal band of IgG Kappa was detected using se- polymorphic nuclear pattern, inconspicuous nucleoli and rum protein electrophoresis. The Kappa to Lambda ratio (K/L abundant amount of cytoplasm. Some cells were multinucle- ratio) was 19.47 (0.26–1.65) indicating very high level of ated with deeply bluish and vacuolated cytoplasm (Fig. 1A). Kappa light chain. Serum β2 macroglobulin was 5.1 g/dL Flow cytometric immunophenotyping of both peripheral (1–2.5 mg/L). Serological assays for human immunodeficien- blood and bone marrow aspirate did not yield any conclusive cy virus (HIV), Epstein-Barr virus (EBV), and hepatitis B and results. Bone marrow biopsy was markedly hypercellular C were negative. (100% cellularity) with diffuse infiltration by sheets of large A repeat bone marrow examination was performed for def- polymorphic neoplastic cells which were completely replac- inite diagnosis. Bone marrow aspirate showed 10% large atyp- ing the normal hematopoiesis. The initial panel of immuno- ical plasmacytoid cells with polymorphism, multinucleation, histochemistry (IHC) stains was negative for LCA (CD45), and immature morphology. Bone marrow biopsy was exten- cytokeratin and CD38 markers. An extended panel of IHC sively infiltrated with sheets of neoplastic plasma cells that was performed including CD3, CD4, CD5, CD8, CD10, were strongly positive for CD138, KAPPA, and CD56 where- CD20, CD30, CD34, CD61, CD79a, CD99, myeloperoxidase as CD5, CD10, CD20, CD38, CD79a, Lambda, BCL-6, and (MPO), terminal deoxynucleotidyl transferase (TDT), PAX-5, MUM were negative (Fig. 1C–F obtained from the second desmin, neuron-specific enolase (NSE), and S100 markers. bone marrow). Fig. 1 Pathological and radiological features: A: Large atypical marrow biopsy with sheets of large polymorphic neoplastic cells polymorphic plasma cells (megakaryocyte- like) in touch imprint of bone [H&E,100]. D and E: Plasma cells show strongly positivity for CD138 marrow biopsy. B: MRI of spine showed collapsed L5 vertebral body IHC marker (D), whereas CD38 is completely negative (E). F:Kappa with anterior wedging of L1 vertebra. C: Diffuse infiltration of bone light chain revealed strong positivity in almost all plasma cells JHematopathol(2019)12:27–30 29 Flow cytometric immunophenotyping was performed on association poses a major diagnostic challenge that may delay bone marrow biopsy but did not encounter enough plasma the diagnosis and hence, the proper management. cells and hence, IHC stains for CD38, CD56, C138, Kappa, The mechanism underlying the loss of CD38 molecules on and Lambda were carried out on the first bone marrow biopsy the surface of myeloma cells remains obscure. Mikiko et al. and were consistent with the second bone marrow reported spontaneous loss of CD38 phenotype in two relapsed immunophenotyping. Cytogenetic analysis and FISH studies plasma cell myeloma cases and postulated some genetic or demonstrated a t(14;16) (q32;q23)-IGH/MAF translocation in epigenetic modifications occurring within CD38 epitope- 85% of the cells. The final diagnosis was released as CD38 coding regions [11]. However, no conclusive evidence can negative anaplastic plasma cell myeloma. be drawn from such limited data. The patient was admitted in the intensive care unit due to On the other hand, level of expression of CD138 in plasma septicemia and severe thrombocytopenia. She was started on cell myeloma is variable among cells but the overall expres- antibiotics and supportive therapy with pulses of dexametha- sion is usually higher and more consistent than CD38 marker. sone. The plan was to treat her with bortezomib- Interestingly, low level expression of CD138 was associated dexamethasone regimen followed by autologous stem cell with more immature phenotype and poor response to transplantation once recovered from septicemia. lenalidomide [12]. Unfortunately she deteriorated and died with overwhelming According to Mayo Clinic stratification of myeloma and pulmonary infection after 1 week. risk-adapted therapy, t(14;16) is associated with high risk and poor prognosis [13]. However, the data about its clinical im- pact on prognosis of plasma cell myeloma is conflicting. On Discussion multivariate analysis of 32 myeloma patients, it was conclud- ed that t(14;16) is not prognostic. [14] While in the contrary, in Anaplastic plasma cell myeloma is an aggressive morpholog- some other studies, it was associated with worse clinical out- ical variant of myeloma that is usually associated with insid- come [15]. The incidence of this genetic abnormality among ious onset, involvement of extramedullary sites and extremely plasma cell myeloma patients is very low representing only poor prognosis [1–3]. It has been reported as initial presenta- about 3.2% [16]. Ammannagari et al. reported an anaplastic tion of plasma cell myeloma (PCM) or as adverse progression plasma cell myeloma patient with complex karyotype involv- of previously treated conventional plasma cell myeloma [4]. ing 13q deletion, t(14;16), and hyperdiploidy who died shortly The mean age at presentation is 53 years and the survival rate after commencement of novel chemotherapy for myeloma.