Early relapse after complete remission of primary plasma cell leukaemia manifesting clonal evolution: A case report.

INTRODUCTION: Plasma cell leukaemia (PCL) is a rare variant of multiple myeloma. We report a case of PCL to demonstrate the clonal evolution, resulting in disease relapse after achieving complete remission, and its aggressive nature of the disease, leading to poor clinical outcome. CASE REPORT: A 69-year-old man presented with a three-day-history of worsening generalized body weakness, poor oral intake, nausea, significant loss of weight and lower back pain. He was diagnosed as primary PCL, based on hypercalcaemia, renal insufficiency, anaemia, thrombocytopenia, lytic bone lesions, 24% abnormal plasma cells in peripheral blood, immunophenotype of clonal plasma cells which were positive for CD38, CD138 and CD56 markers with kappa light chain restriction, 49% abnormal plasma cells in bone marrow, monoclonal paraprotein (IgG kappa) in serum and urine, and positive IGH rearrangement (Fluorescence in-situ hybridisation, FISH). He achieved complete remission after four cycles of Bortezomib-based therapy. There was a plan for high-dose therapy plus autologous haematopoietic cell transplantation. A month later, the disease relapsed, as evidenced by 94% abnormal plasma cells in his bone marrow aspirate, complex karyotype and abnormal FISH results. He passed away a few days later, from severe septicaemia. Time-to-progression of disease was 1 month and overall survival was 5 months. DISCUSSION: This case report illustrates the clonal evolution and aggressive nature of primary PCL with older age at presentation, leading to a shorter duration of remission and overall survival.

Extensively drug-resistant tuberculosis in Myanmar: burden and mutations causing second-line drug resistance.

SETTING: Two tuberculosis (TB) reference laboratories in Myanmar. OBJECTIVES: To determine the proportion of extensively drug-resistant TB (XDR-TB) cases among multidrug-resistant TB (MDR-TB) cases and the mutations that cause resistance to second-line drugs in Myanmar. DESIGN: This was a cross-sectional, retrospective study. Multidrug-resistant Mycobacterium tuberculosis isolates were collected during 2015-2016. Phenotypic drug susceptibility testing (DST) was performed and drug-resistant mutations identified by sequencing. Genotypes were determined to explain relationships between drug resistance patterns and genotypes. RESULTS: Of 89 MDR-TB isolates, 12 were XDR-TB and 24 were pre-XDR-TB, with 21 resistant to fluoroquinolones (FQs) and 3 to second-line injectable agents (SLIDs). High rates of cross-resistance among second-line drugs were observed. Correlations between phenotypic and molecular DST against FQs and SLIDs were 91% in both cases. The most frequent mutation in FQ-resistant isolates was D94G (8/21) in gyrA and A1401G (11/15) in rrs in those resistant to SLIDs. The dominant genotype was the Beijing type (76/89). CONCLUSION: There were high proportions of XDR-TB and pre-XDR-TB among MDR-TB cases; cross-resistance among second-line drugs was high, with various types of genetic mutations. These data suggest that resistance to second-line anti-tuberculosis drugs should be monitored intensively, and molecular DST should be employed.

POEMS syndrome.

POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the 2-day-history of inability to walk, 4-month-history of progressive worsening of muscle weakness of both lower limbs and 1-year-history of progressive worsening of bilateral numbness of lower limbs. Nerve conduction study revealed generalized sensorimotor demyelinating polyneuropathy. She was initially treated as chronic inflammatory demyelinating polyradiculoneuropathy with intravenous immunoglobulin (IVIG) and high-dose prednisolone. However, she had no significant neurological improvement despite getting standard therapy. In addition to peripheral neuropathy, the presence of hepatosplenomegaly, skin changes, polycythaemia and thrombocytosis prompted for further investigations. She was diagnosed as POEMS syndrome based on the presence of two mandatory major criteria [polyneuropathy, monoclonal plasma cell proliferative disorder (lambda)], one major criterion (sclerotic bone lesions) and three minor criteria (organomegaly, skin changes and thrombocytosis/polycythaemia). She received treatment with melphalan and prednisolone. She achieved clinical improvement and partial response (haematologic and radiological) after six cycles of therapy. We highlight the awareness of this rare syndrome, for patients presenting with peripheral neuropathy and not responding to its standard therapy, by recognizing other associated clinical manifestations and proceeding further diagnostic work-up.

Diffuse large B cell lymphoma with chronic granulomatous inflammation.

Non-necrotic epithelioid granulomas have been reported in association with neoplasms including Hodgkin and non-Hodgkin lymphoma. We report a case of diffuse large B cell lymphoma with chronic granulomatous inflammation to highlight awareness of obscure tumour cells within the granuloma, to avoid delay in diagnosis and management of lymphoma. A 39-year-old Malay lady with no past medical history, presented with a 2-month history of progressive worsening of difficulty in breathing, cough, low-grade fever, loss of weight and loss of appetite. Chest X-ray showed an anterior mediastinal mass and computed tomography (CT)-guided biopsy was reported as chronic granulomatous inflammation suggestive of tuberculosis. After 2 months of anti-TB treatment, her symptoms were not relieved. The patient underwent another CT-guided biopsy of the anterior mediastinal mass in another hospital and the histopathology revealed diffuse large B cell lymphoma. The patient was referred for treatment. On histopathological review, the first sample showed noncaseating granulomas engulfing tumour cells and large abnormal lymphoid cells which were CD20 positive and with high Ki-67 proliferative index. The patient was diagnosed with diffuse large B cell lymphoma stage IV B IPSS score 3. She underwent chemotherapy (R-EPOCH) and responded well to treatment.