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Year : 2012  |  Volume : 55  |  Issue : 1  |  Page : 130-132
Seemingly insignificant, but crucial morphological leads in the diagnosis of non-secretory multiple myeloma in an adolescent

1 Unit of Laboratory Oncology, Institute Rotary Cancer Hospital, All-India Institute of Medical Sciences, New Delhi, India
2 Department of Medical Oncology, Institute Rotary Cancer Hospital, All-India Institute of Medical Sciences, New Delhi, India

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Date of Web Publication11-Apr-2012

How to cite this article:
Mishra J, Chopra A, Gogia A, Kumar R. Seemingly insignificant, but crucial morphological leads in the diagnosis of non-secretory multiple myeloma in an adolescent. Indian J Pathol Microbiol 2012;55:130-2

How to cite this URL:
Mishra J, Chopra A, Gogia A, Kumar R. Seemingly insignificant, but crucial morphological leads in the diagnosis of non-secretory multiple myeloma in an adolescent. Indian J Pathol Microbiol [serial online] 2012 [cited 2023 Mar 20];55:130-2. Available from:


Clinical and laboratory features of multiple myeloma are well known and make diagnosis possible even in atypical settings. We report a case of multiple myeloma, where a correct appreciation of the atypical morphology made the diagnosis possible in an adolescent in the rare clinical setting of normal serum protein electrophoresis.

A 17-year-old boy presented with a two months history of generalized bone pain, fever, loss of appetite, pallor, and weight loss of 25 kg. Relevant lab parameters included hemoglobin of 6.5 g/dl, reduced serum albumin, elevated serum calcium, raised lactate dehydrogenase, and negativity for HIV. There were widespread multiple punched-out lytic lesions in the skeleton. Multiple myeloma (MM), Langerhans cell histiocytosis, leukemia/lymphoma, metastatic neuroblastoma, or Ewing's sarcoma were considered as possible diagnoses. High resolution electrophoresis of serum and urine was normal. Based on the presence of nucleolated bare nuclei on bone marrow (BM) biopsy imprint, the patient had been diagnosed of acute leukemia in the referring hospital. Flow cytometry using acute leukemia panel had been non-contributory. The patient did not respond to therapy and succumbed after a brief hospital stay.

Peripheral blood smear (leukopenic) and BM touch imprint made in our laboratory showed essentially bare nuclei - abnormal cells with prominently nucleolated nuclei and no or a very small amount of frayed cytoplasm [Figure 1]a-c. They were interpreted as immature plasma cells and confirmed to be so by flow cytometry - CD38 + , CD138 + and CD19-, and intracytoplasmic κ+ and λ- [Figure 2]. The corresponding BM biopsy showed replacement by prominently nucleolated cells of appearance characteristic of immature abnormal plasma cells [Figure 1]d. Serum free light chain assay (SFLC) values and ratio (35.5; normal: 0.26-1.65) were abnormal. Immunohistochemistry (IHC) on BM biopsy showed tumor cells negative for leukocyte common antigen (LCA), cytokeratin, chromogranin, myeloperoxidase, vimentin, and MIC-2; and positive for epithelial membrane antigen (EMA). Positive EMA and negative LCA indicate myeloma, but are also seen in plasmablastic lymphoma. Presence of c-myc translocations and positivity for EBV that have been reported in association with plasmablastic lymphoma [1] were not looked into. Even so, the possibility of plasmablastic lymphoma seemed remote, as unlike in our case, this disease occurs predominantly in the setting of immunodeficiency, most commonly HIV, organ transplant and autoimmune diseases, [2] and has predilection for oral cavity and other extranodal sites. The possibility of ALK + large B-cell lymphoma with plasmablastic differentiation was excluded, as ALK was negative.
Figure 1: Photomicrographs of malignant plasma cells (a, b and c) Fields of peripheral blood smears showing immature plasma cells with very small amount of frayed cytoplasm and prominent nucleoli (Jenner Giemsa, ×100); (d) BM biopsy showing infiltration by prominently nucleolated plasma cells. Mitotic Figures are evident (H and E, ×100)

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Figure 2: Flow cytometric plot of bone marrow aspirate. (a) Malignant plasma cells co-expressing intense CD138 and CD38. (b) Malignant plasma cells are negative and normal B cells are positive for CD19

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With the identity of the tumor cells established, plasma cells, rather than leukemic blast cells, we considered the best diagnostic label for the patient to be multiple myeloma. Non-secretory myeloma at 17 years of age and running a clinical course of unrelenting aggression are both rare. [3] The diagnostic difficulty was compounded in our patient by the presence of degenerated blast-like cells in the peripheral blood and BM.

We regard peripheral blood/BM imprint cells present essentially as bare nuclei, having frayed remnants of cytoplasm and very prominent nucleolus of a rather distinct kind, [Figure 1]a-c and the prominently nucleolated cells in the BM biopsy, as so as highly suggestive of plasma cells, that even if the clinical history seems at variance, we opt to investigate myeloma. This is what led us to the correct line of investigation. This kind of morphology seen in BM imprint is clearly evident in publications, [4] and if not, adequately emphasized in the context of a diagnostic dilemma, at least well described and illustrated in texts. [5] Blasts of acute leukemia, in our experience, generally have a different appearance.

From the perspective of diagnostic hematopathology, this case teaches us two things. First, initial assessment of peripheral blood and BM morphology unbiased by the clinical history should precede correlation with the clinical picture. This also means that in relevant situations, as in our case, pursuing possibilities that seem plausible from morphology alone, may be rewarding. Second, it pays to thoroughly familiarize oneself with the appearance of even degenerated cells, as many cells in a degenerated state have a characteristic recognizable appearance. Plasma cells, in our experience, particularly malignant ones, come in this category. Our case also shows that as the panel for flow cytometry is generally decided after looking at the morphology, correct morphological interpretation is vital in planning the panel.

   Acknowledgment Top

Thanks are due to Mr. Zubair Abdullah for his help in typing the manuscript.

   References Top

1.Taddesse-Heath L, Meloni Ehrig A, Scheerle J, Kelly JC, Jaffe ES. Plasmablastic lymphoma with MYC translocation: Evidence for a common pathway in the generation of plasmablastic features . Mod Pathol 2010;23:991-9.   Back to cited text no. 1
2. Jaffe ES, Harris NL, Vardiman JW, Campo E, Daniel AA. Diffuse large B-cell lymphomas. In: Alexander CL, John KC, editors. Hematopathology. 1 st ed. Philadelphia, PA: 2010. p. 378.   Back to cited text no. 2
3. Blade J, Kyle RA. Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia. Hematol Oncol Clin North Am 1999;13:1259-72.  Back to cited text no. 3
4.Chopra A, Anand M, Kumar R, Kalita D, Raina V. Unusual sighting: Amyloid deposits in bone marrow aspirate in multiple myeloma. Indian J Pathol Microbiol 2008;51:562-3.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
5.Brunning RD, McKenna RW. Tumors of the Bone Marrow. In Washington DC: Armed Forces Institute of Pathology; 1993. p. 323-67.  Back to cited text no. 5

Correspondence Address:
Anita Chopra
Unit of Laboratory Oncology, Institute Rotary Cancer Hospital, All India of Institute of Medical Sciences, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.94898

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