Multiple myeloma or lymphoma? The increasing role of flow cytometry and serum-free light chain assay

Nabhajit Mallik; Ram Vasudevan Nampoothiri; Sreejesh Sreedharanunni; Man Updesh Singh Sachdeva; Pankaj Malhotra; Neelam Varma

doi:10.4103/IJPM.IJPM_381_17

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Year : 2018 | Volume : 61 | Issue : 1 | Page : 149-150

Multiple myeloma or lymphoma? The increasing role of flow cytometry and serum-free light chain assay

Nabhajit Mallik, Ram Vasudevan Nampoothiri, Sreejesh Sreedharanunni, Man Updesh Singh Sachdeva, Pankaj Malhotra, Neelam Varma
Department of Hematology and Internal Medicine (Clinical Hematology), Postgraduate Institute of Medical Education and Research, Chandigarh, India

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Date of Web Publication

22-Mar-2018

How to cite this article:
Mallik N, Nampoothiri RV, Sreedharanunni S, Singh Sachdeva MU, Malhotra P, Varma N. Multiple myeloma or lymphoma? The increasing role of flow cytometry and serum-free light chain assay. Indian J Pathol Microbiol 2018;61:149-50

How to cite this URL:
Mallik N, Nampoothiri RV, Sreedharanunni S, Singh Sachdeva MU, Malhotra P, Varma N. Multiple myeloma or lymphoma? The increasing role of flow cytometry and serum-free light chain assay. Indian J Pathol Microbiol [serial online] 2018 [cited 2023 Sep 30];61:149-50. Available from: https://www.ijpmonline.org/text.asp?2018/61/1/149/228171

A 53-year-old gentleman with no previous comorbidities presented with complaints of increased frequency of micturition, low backache, and easy fatiguability of 1-month duration. The clinical examination revealed pallor. His hemogram showed anemia (hemoglobin of 65 g/L, total leukocyte count of 8.8 × 10⁹/L, platelet count of 250 × 10⁹/L, and normal differential leukocyte count) and very high erythrocyte sedimentation rate (96 mm/1^st h). Serum creatinine was raised (67 mg/L). Workup for a possible diagnosis of multiple myeloma (MM) revealed lytic lesions in the skull on roentgenogram. β2 microglobulin (6.8 mg/L) and lactate dehydrogenase (410 IU/L) were raised. However, serum calcium (96 g/L) was normal; serum protein electrophoresis, urine protein electrophoresis as well as immunofixation electrophoresis (IFE) using antibodies against IgG, IgA, IgM heavy chains, and kappa (κ) and lambda (λ) light chains did not reveal monoclonal protein. Bone marrow aspirate and biopsy was hypercellular with 75% cells showing lymphoplasmacytic morphology [Figure 1]a. The morphology favored a lymphoproliferative disorder over MM. However, on six-color flow cytometry (antibodies from BD Biosciences, SanJose, CA), the immunophenotype was consistent with clonal plasma cells (CD38pos, CD138pos, CD19pos, CD20neg, CD45pos, CD56pos, CD81neg, CD27neg, CD28neg, CD117neg, and CD200neg) but with lack of expression of cytoplasmic light chains. Fluorescence in situ hybridization revealed IgH/cyclin D1 translocation [Figure 1]b and absence of TP53 deletion, IgH/FGFR3, and IgH/MAF translocations. A diagnosis of IgH/cyclin D1 positive, revised International Staging System Stage III MM possibly nonsecretory, was considered at this stage. However, serum-free light chain (SFLC) assay (Freelite®) revealed raised κ light chain of 2401 mg/L (normal 3.3–19.4 mg/L), normal λ light chain of 17.8 mg/L (normal 5.7-26.3 mg/L), and altered κ:λ ratio of 134.8 (normal 0.26–1.65) modifying the diagnosis to an oligosecretory MM. Patient was treated with plasmapheresis, along with a 4-drug combination chemotherapy regimen containing cyclophosphamide, dexamethasone, thalidomide, and bortezomib. After 2 cycles, his anemia (hemoglobin 102 g/L) and uremia (serum creatinine – 1.6 mg/dl) improved, and SFLC assay showed >50% reduction in κ light chain. He is planned for maximal disease reduction with 4–6 cycles of chemotherapy followed by autologous hematopoietic stem cell transplant.

Figure 1: (a) Bone marrow aspirate smear showing predominantly cells with lymphocytic or lymphoplasmacytic morphology (May–Grunwald Giemsa ×100) (inset shows cells at ×400); (b) Fluorescence in situ hybridization using dual fusion probe showing IgH/cyclin D1 translocation (white arrow)

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The case exemplifies various difficulties in diagnosing and categorizing MM. The absence of monoclonal protein in serum and urine even on sensitive IFE together with lymphoplasmacytic morphology and IgH/cyclin D1 translocation can lead to an erroneous diagnosis. It has been observed that free κ light chain can be missed on IFE, even when present in quantities above the expected threshold.^[1] The real diagnostic utility of SFLC arises in such cases which help in the distinction of so-called “oligosecretory” or “free light chain (FLC) restricted” MM from true nonsecretory MM.^[2] This distinction is important as the nonsecretory myelomas less frequently lead to renal failure.^[3] The SFLC assay can also be used for disease monitoring in the FLC-restricted cases.^[4] MM with lymphoplasmacytic morphology is rare constituting approximately 3% of all myelomas ^[5] but strongly associated with IgH/cyclin D1 translocation.^[6] These cases pose a diagnostic challenge for the hematopathologist and can be easily mistaken for a lymphomatous infiltration of the bone marrow, especially in the absence of classical clinical and laboratory features. The judicious use of flow cytometry using a proper panel of antibodies proves to be of immense help in reaching a correct diagnosis in such cases. A few studies have also shown that myelomas with lymphoplasmacytic morphology have a low monoclonal protein component.^[5],[6]

In conclusion, the present case highlights the need for clinicians and pathologists to recognize that MM can show atypical clinical and laboratory features masquerading as lymphomas. The judicious use of flow cytometry and SFLC assay in the workup improves the accuracy of diagnosis and categorization of suspected plasma cell neoplasms.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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