Received: January 23, 2017
Accepted: April 1, 2017
Mediterr J Hematol Infect Dis 2017, 9(1): e2017033 DOI 10.4084/MJHID.2017.033
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report a case of hairy cell leukemia (HCL) initially misdiagnosed as
plasma cell dyscrasia due to various clinical, morphological and
On the assessment at our center, he was asymptomatic. He did not complain of bone pains. Physical examination was not contributory. His pancytopenia recovered (Hb-112 g/L, TLC-3.2 x109/L, ANC-1.4 x109/L, platelets-522 x109/L). A repeat bone marrow examination was performed to evaluate suspected plasma cell dyscrasia. Bone marrow aspirate (BMA) revealed 5% plasma cells; however showed 36% larger lymphoid cells with clumped chromatin and a moderate amount of pale basophilic cytoplasm. A few cells had grooved/reniform nucleus or cytoplasmic projections (Figure 1A). An increase in mast cells was also noted. Trephine biopsy showed an interstitial infiltrate, typical of hairy cell leukemia (Figure 1B, C) along with an increase in mast cells confirmed by mast cell tryptase immunohistochemistry (Figure 1D). No significant clusters of mast cells were highlighted. Repeat SPEP and immunofixation study, done at our center, revealed polyclonal hypergammaglobulinemia.
Multiparametric flow cytometry (Figure 2) was performed on the BMA using four/six color antibody panels by lyse-wash-stain method (antibodies from BD Biosciences, San Jose, CA). One tube containing unstained leukocytes was used as negative control. A minimum of one lakh events was acquired on dual laser BD FACS Canto II and analyzed using BD FACS Diva software. Bright CD19positive low side scatter events (5.3% of viable gated leucocytes) were gated which were positive for CD10, CD20, CD22, CD79b, surface Igκ, CD25, CD11c, CD103, and CD123. Serendipitously, we found a large subclone of cells (15% of viable gated leucocytes) expressing exactly the same immunophenotype markers except for CD19, indicating its loss of expression from hairy cells. The fluorochrome related technical issues were ruled out as the cells showed similar profile using both anti-CD19PECy7 and anti-CD19APC-H7 (clone SJ25C1, BD Biosciences). The CD19 negative cells had an immune profile exactly similar to CD19+ve cells and revealed expression of hairy cell markers along with CD20, CD22, CD79b, CD45, and CD10. The plasma cells (CD38pos/CD138pos/CD19pos/CD81pos/CD56neg and no light chain restriction – Figure 2) and mast cells (CD117pos/CD33pos/CD2neg/CD25neg) showed normal immunophenotype indicating reactive plasmacytosis and mast cell hyperplasia. A diagnosis of hairy cell leukemia with atypical features (CD19 negative subclone, CD10 positivity, reactive plasmacytosis and mast cell hyperplasia) was made which was subsequently confirmed by amplification-refractory mutation system polymerase-chain-reaction (ARMS-PCR) for BRAF V600E mutation (Figure 1E).
The patient remained asymptomatic, and his laboratory parameters remained normal; not warranting purine analogue therapy. He has been keeping under close medical observation.
Splenomegaly is an important feature seen in up to 90% of patients with HCL. However, its absence should not exclude a diagnosis of HCL. And more importantly, a changing trend has been observed in the symptomatology of HCL over the past 30 years. Number of cases are being diagnosed at an early stage with a less marked splenomegaly.
A co-existence of plasma cell myeloma with HCL as well as the development of myeloma in patients with HCL has been reported in the literature. At times, plasma cell myeloma/leukemia may mimic HCL also.[6-7] Clonal plasma cells were excluded by flow cytometry and SPEP studies. The initial report of small monoclonal band in SPEP from outside our institute might represent a transient monoclonal gammopathy, as has been reported previously with several infections.[8-9] However, a wrong interpretation could not be conclusively resolved in the absence of immunofixation studies. The association of mast cell hyperplasia with HCL has been well characterized by Macon et al. This has been attributed to the angiogenesis and further progression of the disease, confirmed by a latter study. There has also been a case report of systemic mastocytosis associated with a clonal hematopoietic non-mastcell lineage disease (SM-AHNMD) where the coexisting neoplasms were of both lymphoid and myeloid origin. Our case shows a striking mast cell hyperplasia, however, a systemic mastocytosis has been ruled out based on immunophenotype studies.
Immunophenotype aberrancies have been well described in HCL, like negativity for CD103 or CD25; and positivity for CD10 or CD23. In our case, the cells showed positivity for CD10, and there was a subclone with absence of CD19 expression. While CD10 expression is relatively common (5-26% of cases) and explained by alternate origin of leukemic cells from germinal center, the absence of CD19 expression in HCL has not been previously reported in the literature. CD19 plays an important role in B-cell growth and differentiation and its expression increases as a B-cell matures. This characteristic is often the basis of using it in flow cytometry as a gating marker for the diagnosis and for minimal residual disease (MRD) testing in various B-cell malignancies. In fact, of all the B-NHLs, HCL cases show the maximum level of expression of CD19. The abnormal immunophenotypic pattern should be borne in mind while performing the MRD analysis during follow-up. An alternate marker (CD20) should also be considered for gating leukemic cells in these patients.
AcknowledgementThe authors are thankful to Mrs. Jasbir Kaur Hira and Mrs Praveen Bose for the technical help in performing molecular and immunophenotypic studies respectively.
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