رد: سرطان خلية بالزما الدم األويل تقرير حالة ومراجعة األدبيات Re: Primary Plasma Cell Leukaemia Case report and review of the literature Dear Editor, I read with interest the recent case report by Singh et al. published in the August 2018 issue of SQUMJ, in which the authors describe a 69-year-old male patient with rectal bleeding associated with pallor, dyspnoea and chest pain.1 Laboratory tests showed microcytic hypochromic anaemia, leukocytosis, low platelets and a high erythrocyte sedim- entation rate. Elevated levels of urea, creatinine, uric acid, immunoglobulin D, kappa light chains and β2-micro- globulins were also detected, while abdominal, thoracic and skeletal imaging did not show any abnormalities.1 A bone marrow aspirate revealed 61% atypical plasma cells. Subsequently, a diagnosis of primary plasma cell leukaemia (PCL) was confirmed and bortezomib-based chemotherapy was administered, resulting in a good response.1 Myeloma cells can travel to the peripheral blood if expression of the cell adhesion molecule cluster of differ- entiation (CD)56 decreases.2,3 Along with CD19, CD20 and CD23 positivity, this phenomenon is often observed among patients with primary PCL, while the positive expression of CD28 and interleukin-6 are considered imp- ortant in secondary cases.2,3 Leukocytosis, high levels of lactate dehydrogenase and β2-microglobulins and the presence of bone lesions can help to differentiate primary PCL from myeloma.4 Singh et al. therefore highlighted the need for consensus guidelines in primary healthcare for the purposes of early diagnosis and prompt and adequate treatment.1 Other case reports have also emphasised the diagnostic pitfalls associated with unsuspected cases of myeloma, rib plasmacytoma, multiple myeloma and secondary PCL.4–6 These cases may help to enhance suspicion of plasma cell malignant disorders among primary healthcare workers. Dos Santos et al. reported a 53-year-old female patient with multiple myeloma and secondary PCL; the patient had 25% plasma cells in a bone marrow aspirate and positive expressions of lambda light chains, CD56 and CD20 as well as 23% circulating peripheral blood plasma cells.4 She had high levels of urea and creatinine and was hyperc- alcaemic and anaemic. An X-ray showed radiolucent speckled areas in the humeral diaphysis with no evidence of organomegaly or lymphadenopathy.4 A diagnosis of leukaemia was made, based on the presence of >2,000/mm3 circulating plasma cells, some of which were dysplastic. Subsequently, the patient demonstrated significant clinical improvement following treatment with dexamethasone, cyclophosphamide, thalidomide, cisplatin, doxorubicin and etoposide.4 Another case report described a 65-year-old female patient who was diagnosed with rib plasmacytoma, overt immunoglobulin (Ig)-A-producing multiple myeloma and hyperviscosity syndrome.5 She had a history of dyspnoea and a mental disorder and subsequently developed chronic renal failure, respiratory disturbance and heart failure. Bio-chemistry tests showed elevated urea, creatinine and calcium levels and β2-microglobulins; in addition, she was anaemic and her IgA and kappa light chain levels were 8,917 mg/dL (normal range: 153–359 mg/dL) and 2,990 mg/dL (normal range: 625–1,668 mg/dL), respectively.5 The presence of >50% plasma cells with basophilic cytoplasm, eccentric nuclei and large nucleoli in a bone marrow biopsy established the diagnosis of multiple myeloma. The patient was treated with dexamethasone and underwent plasmapheresis without improvement.5 Finally, dos Santos et al. reported a 64-year-old male patient who presented with dizziness, fatigue, dyspnoea, lumbar pain and high levels of calcium, urea and creatinine.6 Multiple osteolytic lesions were detected in the cranium and lumbar spine, in addition to a monoclonal peak in the gamma region and high levels of IgG. A bone marrow aspirate revealed >40% plasma cells.6 The patient was eventually diagnosed with multiple myeloma at a late stage, due partly to a history of activities resulting in overload on the axial skeleton because of his profession as a construction foreman, as well as nonsteroidal anti-inflammatory drug abuse. He underwent chemotherapy which resulted in an unsatisfactory response.6 Vitorino M. dos Santos1,2 1Department of Internal Medicine, Armed Forces Hospital, Cruzeiro Novo, Brazil; 2Medical Division, Catholic University of Brasilia, Cruzeiro Novo, Brazil E-mail: vitorinomodesto@gmail.com letter to the editor Sultan Qaboos University Med J, November 2018, Vol. 18, Iss. 4, pp. e563–564, Epub. 28 Mar 19 Submitted 14 Jan 19 Accepted 7 Feb 19 doi: 10.18295/squmj.2018.18.04.026 Re: Primary Plasma Cell Leukaemia Case report and review of the literature e564 | SQU Medical Journal, November 2018, Volume 18, Issue 4 References 1. Singh S, Rath A, Yadav S. Primary plasma cell leukaemia: Case report and review of the literature. Sultan Qaboos Univ Med J 2018; 18:e397–401. https://doi.org/10.18295/squmj.2018.18.03.024. 2. Fernández de Larrea C, Kyle RA, Durie BG, Ludwig H, Usmani S, Vesole DH, et al. Plasma cell leukemia: Consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group. Leukemia 2013; 27:780–91. https://doi.org/10.1038/leu.2012.336. 3. Pellat-Deceunynck C, Barillé S, Jego G, Puthier D, Robillard N, Pineau D, et al. The absence of CD56 (NCAM) on malignant plasma cells is a hallmark of plasma cell leukemia and of a special subset of multiple myeloma. Leukemia 1998; 12:1977–82. 4. Dos Santos VM, Melim SP, de Faria PS, Passini VV, Duarte ML, Casasanta RA. Multiple myeloma and secondary plasma cell leukemia. Rom J Morphol Embryol 2016; 57:837–9. 5. Santos VM, Brito EF, Paz BC, Leal CT. Rib plasmacytoma and IgA multiple myeloma with hyperviscosity syndrome. Arch Iran Med 2012; 15:517–19. https://doi.org/012158/AIM.0015. 6. dos Santos VM, de Castro RA, Marques HV Jr, de Paula FH. Unsuspected multiple myeloma: A growing challenge. Braz Med 2007; 44:138–41. Response from the Authors Dear Reader, Thank you for your letter highlighting similar cases of unsuspected multiple myeloma and primary or secondary plasma cell leukaemia (PCL).1–3 There are certain points upon which we wish to elaborate. Firstly, as mentioned in the original publication by Singh et al., a decrease in the expression of cluster of differentiation (CD)56 is a reliable marker of PCL.4 However, in the 40–50% of cases wherein CD56 is not expressed, diagnostic difficulties ensue.5 Secondly, flow cytometry has proven to be a valuable adjunct in diagnosing myeloma and/or PCL.6 This method should therefore be paired with bone marrow and peripheral blood flow cytometry for the detection of circulating plasma cells by using CD markers such as CD27, CD28, CD117, CD200, CD229 and CD81. Specifically, the expression of MYC, cyclin D1 and p53 in bone marrow biopsies can differentiate between different types of PCL, as cyclin D1 is exclusive to primary PCL, while the other two markers are seen in both forms.7 Thirdly, we wish to caution against the interchangeable usage of the terms dysplastic and anaplastic.2 *Sarika Singh, Ashutosh Rath, Surekha Yadav Department of Pathology, Maulana Azad Medical College, New Delhi, India E-mail: sarikasingh97b@gmail.com References 1. Dos Santos VM, Melim SP, de Faria PS, Passini VV, Duarte ML, Casasanta RA. Multiple myeloma and secondary plasma cell leukemia. Rom J Morphol Embryol 2016; 57:837–9. 2. Santos VM, Brito EF, Paz BC, Leal CT. Rib plasmacytoma and IgA multiple myeloma with hyperviscosity syndrome. Arch Iran Med 2012; 15:517–19. https://doi.org/012158/AIM.0015. 3. dos Santos VM, de Castro RA, Marques HV Jr, de Paula FH. Unsuspected multiple myeloma: A growing challenge. Braz Med 2007; 44:138–41. 4. Singh S, Rath A, Yadav S. Primary plasma cell leukaemia: Case report and review of the literature. Sultan Qaboos Univ Med J 2018; 18:e397–401. https://doi.org/10.18295/squmj.2018.18.03.024. 5. McKenna RW, Kyle RA, Kuehl WM, Grogan TM, Harris NL, Coupland RW. Plasma cell neoplasms. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., Eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon, France: International Agency for Research on Cancer, 2008. Pp. 200–13. 6. Tembhare PR, Ghogale S, Tauro W, Badrinath Y, Deshpande N, Kedia S, et al. Evaluation of CD229 as a new alternative plasma cell gating marker in the flow cytometric immunophenotyping of monoclonal gammopathies. Cytometry B Clin Cytom 2018; 94:509–19. https://doi. org/10.1002/cyto.b.21619. 7. Jelinek T, Kryukov F, Rihova L, Hajek R. Plasma cell leukemia: From biology to treatment. Eur J Haematol 2015; 95:16–26. https://doi. org/10.1111/ejh.12533.