Journal of Islamabad Medical & Dental College (JIMDC); 2014:3(1):36-38 Case Report

Plasma Cell with Hyperleukocytosis A Rare Presentation

Naghmi Asif1, Aftab Ahmed2 and Khalid Hassan3 1Associate Professor Pathology IMDC/ Consultant Hematologist Islamabad Diagnostic centre, Islamabad 2Consultant Hematologist, Islamabad Diagnostic Centre/Assistant Prof. Pathology Al- Nafees Medical College, Islamabad 3Professor and Head, Department of Pathology, Islamabad Medical & Dental College (IMDC) , Islamabad (1,3Baharia University Islamabad)

Abstract involvement, pallor, petechiae or palpable extramedullary Leukemia is a rare aggressive of soft-tissue . plasma cells. The disease has acute onset, rapid course, Primary presents with high tumor poor prognosis and poor response to therapy. PCL may be burden and poor prognosis. Lytic bone lesions are more primary (arising de –novo) or secondary transformation of common in secondary plasma cell leukemia and rare in . We present a case of 50 years old man primary one. Peripheral blood film shows marked rouleaux who presented with bone pains and weakness and was formation. shows diffuse infiltration by referred to us with suspicion of leukemia. To our surprise plasmablasts. Normal hemopoietic tissues are markedly he had very high leukocyte count with more than 70,000 reduced. These patients thus present with more profound plasma cells in peripheral blood. His ESR was 140mmHg and . The morphological features and Serum electrophoresis showed strong M band. of plasma cells (PCs) can differ depending upon their Based on all these findings he was labelled as a case of maturity. Mature PCs are oval with abundant basophilic plasma cell leukemia. He was started with the treatment but unfortunately it did not work and he died within a cytoplasm. The nucleus is round and eccentrically located month. and the chromatin arranged in pyramidal blocks against the nuclear membrane, giving the characteristic “cartwheel” Key words: Plasma cell leukemia; primary plasma cell appearance. Immature PCs have dispersed nuclear leukemia; secondary plasma cell leukemia chromatin, prominent nucleoli and high nuclear to Introduction cytoplasmic ratio. The findings on bone marrow aspiration and biopsy are similar to those seen in multiple myeloma Plasma cell leukemia (PCL) is a rare and aggressive variant without PCL and demonstrate an increased number of of , characterized by presence of monoclonal PCs. The pattern of infiltration is mostly diffuse circulating plasma cells, acute course, extramedullary 1 in all cases and this infiltration is able to disrupt normal involvement and poor prognosis. The diagnosis of PCL is hematopoiesis. Immunophenotypic characteristics shows based on presence of > 20% plasma cells or absolute 2 CD38 and CD138 expression and are excellent PC number > 2,000 in peripheral blood. The incidence of marker, but these do not differentiate between multiple plasma cell leukemia varies between 2-4% patients with myeloma and plasma cell leukemia. However negative multiple myeloma. Median age at diagnosis is 55 years.3 4 expression of CD56 characteristically expressed on Male to female ratio is 3:2. Plasma cell leukemia may be a myeloma cells is absent from patients with PCL and has primary disease (primary plasma cell leukemia – pPCL) been associated with extramedullary multiple myeloma. which presents as de novo leukemia or secondary leukemic Acquisition of the CD28 antigen on PCs appears to correlate transformation (secondary plasma cell leukemia – sPCL) of with an increased proliferative rate and disease progression.6 pre-existing multiple myeloma.5 The median time to In general, patients are treated with aggressive induction leukemic transformation for patients with MM who evolve therapy followed by HCT (haematopoietic to sPCL is 21 months.4 transplantation) in those who are appropriate candidates for Patients of plasma cell leukemia may present with this approach. alone is the principal option symptoms due to profound anemia, hypercalcemia or for those ineligible for HCT. bleeding diathesis owing to thrombocytopenia. On physical examination, patients may exhibit a higher prevalence of We present a case of 50 years old man who came to us with with involvement of the liver, spleen, lymph suspicion of acute leukemia and was diagnosed as a case of nodes, pulmonary findings associated with pleural effusions, plasma cell leukemia on basis of peripheral blood and bone neurological deficits due to central nervous system marrow examination.

36 Journal of Islamabad Medical & Dental College (JIMDC); 2014:3(1):36-38

Figure 1: Groups of Plasma cells in Peripheral film Figure 2: Binucleate Plasma cell in Peripheral film (Field (Field stain 10X100) stain 10X100)

Figure 3: Plasma cells in Bone marrow aspirate (Field Figure 4: Serum protein electrophoresis showing strong stain 10X 100) M band

Case Report Serum protein electrophoresis showed a strong M band(Figure4), however x-rays skull and chest were A 50 years old man was referred to our centre for peripheral unremarkable (no lytic lesions). On the basis of all these blood examination with suspicion of acute leukemia. He findings the final diagnosis of plasma cell leukemia was gave history of epistaxis (off and on) for the past three made. He was started with treatment and initially improved years, bone pains in arms and legs for the past 6 months, clinically but unfortunately his condition detoriated and he cough for 1 month and pain in right hypochondrium for the died within a month after the diagnosis. last 1 month. Apparently the patient was very toxic and pale looking. Other physical examination was unremarkable Discussion except that his liver was palpable 3 cm below costal margin. His Blood CP showed TLC of 84,800/μl, 7.74 Plasma cell leukemia (PCL) is a rare disorder. Patients may gms/dl and platelet count of 65,700/μl. Peripheral blood either present de novo (PPCL), or PCL may occur during the examination revealed marked rouleaux formation with 91% course of multiple myeloma (secondary PCL). PPCL may plasma cells (absolute count=77,168) (Figure1 &2). ESR account for about 60% and secondary PCL for about 40% of was 140mm/hr and the patient was thus advised for bone cases.7 Patients with PPCL are described to have more marrow biopsy, serum protein electrophoresis, urine protein extramedullary disease, anemia, thrombocytopenia, electrophoresis and skeletal x-rays for lytic lesions. Bone hypercalcemia, renal failure, increased LDH, and β2- marrow biopsy was done; it showed markedly increased 8 microglobulin, as compared to secondary disease. The plasma cells (92% of nucleated cells) with distinct median survival and response to therapy is also poor in suppression of erythroid, myeloid and megakaryocytic series PPCL as compared to SPCL. Amongst the unfavourable cells) ( Figure3). Histological examination of trephine prognostic variables, serum β-2 microglobulin level > 6mg/l biopsy also showed diffuse infiltration by plasma cells. is significant.

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Rarity of PCL can be accessed from the fact that at M.D. References Anderson Cancer Center, 27 patients with PCL were seen in 20 years period whereas at Policlinico San Matteo in Italy, 1. Kraj M, Pogłód K, Szlęzak J and Kruk B et al. Plasma cell 15 cases were seen in 15 years.5,6 Overall, incidence of leukemia: clinical and immunophenotypic characteristics, PCL is less than 1 case per million population.7 This is also treatment and survival. Nowotwory Journal of 2011; 61 (3): 29e–41e the reason for lack of prospective data on treatment regimes 2. Larrea C.F, RA, Durie BGM and Ludwig H et al. Plasma cell and treatment outcome in large trials in this disease. Very leukemia: consensus statement on diagnostic requirements, few cases have been reported from Pakistan. Jameel response criteria and treatment recommendations by the International Myeloma Working Grou Leukemia 2013; 1– reported a case of 51 years old man who presented with 12. weakness and bone pains and had TLC of 21600 with 24% 3. Ramsingh G, Mehan P, Luo J, Vij R, Morgensztern D. plasma cells in peripheral blood and patient died on the 8th Primary plasma cell leukemia: a surveillance, epidemiology, 9 and end results database analysis between 1973 and 2004. day after diagnosis despite treatment. Our case presented Cancer 2009; 115: 5734–5739.61 almost similarly with weakness and bone pains but had very 4. Tiedemann RE, Gonzalez-Paz N, Kyle RA and Santana-Davila high TLC with groups of plasma cells in peripheral blood R et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia. 2008; 22(5):1044–52. and physician suspicion was of acute leukemia rather than 5. International Myeloma Working Group. Criteria for the unexpected plasma cell leukemia. Unfortunately the patient classification of monoclonal gammopathies, multiple could not respond to chemotherapy and died within a month myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haemat 2003; 121:749–757. after diagnosis. Badhe et al presented two cases of plasma 6. Hayman SR, Fonseca R. Plasma cell leukemia. Curr Treat cell leukemia, both had abrupt onset of disease and Options Oncol. 2001;2(3):205-16. presented with fatigability and weakness, organomegaly and 7. Saccaro S, Fonseca R, Veillon DM and Cotelingam J et al. Primary Plasma Cell Leukemia: Report of 17 New Cases radiological and hematological evidence of plasma cell Treated With Autologous or Allogeneic Stem-Ce American leukemia. Both had poor response to therapy and short Journal of 2005; 78:288–294. survival time.10 8. Ojeda J, Esparza MA, Cabral A et al. Intermediate doses of melphalan and dexamethasone are better than vincristine, Fathima J.L et al. presented a case of PCL in 40 years old adriamycin, and dexamethasone (VAD) and 11 polychemotherapy for the treatment of primary plasma cell female who responded well to treatment. Singh et al. leukemia. Ann Hematol 2002; 81:362–367. reported a case of 70 year old male who presented with 9. Jameel A et al. Case Report of a Rare and Aggressive Variant weakness and showed plasma cells and plasmablasts in of Multiple MyelomaAbid Jameel. Plasma Cell Leukemia: 12 Case Report of a Rare and Aggressive Variant of Multiple peripheral blood and bone marrow. Review of local Myeloma J Pak Med Assoc. 2005;55(10):452-453 literature also revealed few cases of plasma cell 10. Badhe BA, Basu D, Toi PCh and Dutta TK et al. Plasma cell leukaemia.13,14 Sajid and Moiz et al reported a case of 55 leukemia--a case report. Indian J Pathol years old female of SPLCL who presented with productive Microbiol. 2003;46(3):484-7 15 11. Fathima J.L. Sitalakshmi S. et al. Primary Plasma Cell cough, shortness of breath and pleural fluid . Leukemia- A Case Report. International Journal of Basic and Our case presented with very high leukocyte count of Applied Medical Sciences 2012; 2 (2): 260-262. 84,800/μl with distinctly high plasma cell count of 77,168. 12. Singh T, Premalatha CS, Sanjeevan KV et al. Ig A Plasma cell leukemia. Journal of Lab Physicians 2009; 1(1): 19-21. Very few cases of plasma cell leukemia presenting with 13. Prabhat D, Bijur SJ, Pathare AV et al. Plasma cell leukaemia-- hyperleukocytosis have been reported. Desai reported a case a report of two cases. Journal of postgraduate medicine. of plasma cell leukemia in a 55 years old male with total 1998; 44:47-9. 16 14. Raj RS, Najeeb S, Aruna R, Pavithran K and Thomas M. leukocyte count of 45,000/μl and 78% plasma cells. Moiz. Primary plasma cell leukemia occuring in the young. Indian et al reported an unusual case of plasma cell leukemia in a journal of cancer 2003; 40:116-7. 35 years old multigravida at 34th week of pregnancy with 15. Raihan Sajid, Bushra Moiz, Nausheen Kamran, Salman 9/ Naseem Adil Pleural fluid plasmacytosis in a patient with unusually high leukocyte count of 259 X 10 l and 90% plasma cell leukemia.. Turk J Hematol 2010; 27: 135-6. plasma cells.17 16. Desai SR, Angarkar NN, Kulkarni AG et al. Primary Plasma Cell Leukemia. JAPI 2004; 52 : 510 Response of PCL to treatment is not good. Median survival 17. Moiz B and Ali S. Plasma cell leukemia in pregnancy. Blood of 2-8 months and with primary plasma cell leukemia and 2012; 120(18):3633. 18. Chokshi M, Baji S and Gandhi A. Plasma Cell Leukemia: A with high tumor burden it is very short. Even intensification Comprehensive Analysis of Clinical & Pathological Features of treatment regimens has not given promising results. of 7 Cases. International Journal of Medical Science and However bone marrow transplant has shown some Public Health 2014;3 (1)6-9. improvement in younger patients.18

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