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Year : 2017  |  Volume : 60  |  Issue : 4  |  Page : 618-619
Intracytoplasmic inclusions in plasma cells: A diagnostic adjunct in monoclonal gammopathy of undetermined significance

1 Department of Pathology and Laboratory Medicine, Medanta - The Medicity, Gurgaon, Haryana, India
2 Department of Medical Oncology and Haematology, Medanta - The Medicity, Gurgaon, Haryana, India

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Date of Web Publication12-Jan-2018

How to cite this article:
Gajendra S, Sharma R, Jain S, Sachdev R, Sood N. Intracytoplasmic inclusions in plasma cells: A diagnostic adjunct in monoclonal gammopathy of undetermined significance. Indian J Pathol Microbiol 2017;60:618-9

How to cite this URL:
Gajendra S, Sharma R, Jain S, Sachdev R, Sood N. Intracytoplasmic inclusions in plasma cells: A diagnostic adjunct in monoclonal gammopathy of undetermined significance. Indian J Pathol Microbiol [serial online] 2017 [cited 2022 Oct 3];60:618-9. Available from:

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell (PC) disorder characterized by the presence of monoclonal (M) protein in the blood, less than the myeloma level without any features of end-organ damage (lytic bone lesions, anemia, hypercalcemia, renal insufficiency, and hyperviscosity). Bone marrow (BM) PCs are usually <10% in MGUS. Changes in the cell nucleus as an increase in size, irregular shape, diffuse chromatin pattern, and the presence of nucleoli along with cytoplasmic contour irregularities and anisocytosis in PCs are markers of abnormal PCs and can be used to cytomorphologically differentiate this from reactive plasmacytosis.[1] Auer rod-like/crystalline intracytoplasmic inclusions in PCs are described rarely in multiple myeloma (MM).[2] Other conditions associated with intracytoplasmic inclusions are plasmacytoma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, mucosa-associated lymphoid tissue lymphomas and rarely, high-grade lymphomas.[3] Although very rarely Auer rod-like PC inclusions were described in reactive plasmacytosis in a patient of aplastic anemia [4] and acute myeloid leukemia,[5] its presence surely warrant further evaluation in the direction of PC dyscrasia for prompt diagnosis. We report a case of MGUS having 3% PCs in BM aspirate with the presence of multiple discrete azurophilic intracytoplasmic inclusions.

A 52-year-old-female presented with chest pain. The patient underwent coronary artery angiography (CAG) which revealed non critical disease. Post-CAG serum urea (289 mg/dl: Normal range 10–50 mg/dl) and creatinine (8.5 mg/dl: Normal range 0.8–1.5 mg/dl) along with urine protein (20.3 mg/dl: Normal range 0–15 mg/dl) levels were increased and dialysis was done. Subsequently, the serum creatinine was improved (1.4 mg/dl). Her complete blood count showed a hemoglobin of 118 g/L, white blood cells 7.6 × 109/L and platelets 349 × 109/L. Erythrocyte sedimentation rate was 59 mm/1st h. Peripheral blood smear revealed normocytic normochromic blood picture with mild rouleaux formation. BM aspiration was cellular showing normal marrow components along with 3% PCs. Most of the PCs exhibited intracytoplasmic azurophillic large discrete inclusions which varied in shape and size from amorphous granules to rectangular and Auer rod-like inclusions [Figure 1]. These were Periodic acid–Schiff (PAS) and Perls' stain negative. The BM biopsy was cellular and revealed normal hematopoetic cells along with mild increase in PCs (6%–8% of total cellularity). CD138 (Dako, MI 15) showed scattered and few small aggregates of PCs with Kappa (Biogenix, L1C1) preponderence. CD 20 (Dako, L26) and CD3 (Dako, IS503) showed scattered B and T cells, respectively. There was no evidence of amyloidosis. Serum protein electrophoresis showed the presence of monoclonal M band (0.39 g/dl) which was confirmed as IgG kappa on immunofixation. Serum-free light chain assay revealed increased serum-free light chain ratio (kappa: 97.92 mg/L [normal range: 3.30–19.40 mg/L], lambda: 15.67 mg/L [normal range: 5.71–26.30 mg/L] and Kappa/Lambda Ratio: 6.25 [normal range: 0.26–1.65]). Serum calcium and beta-2 microglobulin levels were normal. On further evaluation, no lytic lesions or other related organ tissue injury was identified. In view of mild increase in PCs with the presence of intracytoplasmic azurophilic inclusions and M band in serum protein electrophoresis with raised serum-free light chain ratio, a diagnosis of PC dyscrasia, possibly MGUS was considered.
Figure 1: Bone marrow aspirate showing plasma cells with intracytoplasmic azurophilic large discrete inclusions of various shape and size ranging from amorphous granules to rectangular and Auer rod-like inclusions

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Intracytoplasmic inclusions in PCs were first described by Russel in 1890 and subsequently termed Russell bodies which are accumulations of mucopolysaccharides and immunoglobulins within the rough endoplasmic reticulum. The needle/Auer rod-like intracytoplasmic inclusions in PCs were first described by Steinmann in 1940. Some authors postulated that these inclusions are related to abnormal synthesis, trafficking, or excretion of the immunoglobulin or immunoglobulin light chains that accumulate in excess within the cytoplasm but immunocytochemical examinations revealed no reaction with antibodies against immunoglobulins, light chains, or amyloid A antibodies inside the inclusions. These inclusions are negative for Peroxidase, Sudan black B, Chloroacetate esterase, PAS. Butyrate esterase, Congo red, Thioflavin, Luxol fast blue, Methyl Green, Oil red O and Alkaline phosphatase. These are also positive for α-naphthyl acetate esterase (sensitive to sodium fluoride treatment) and β-glucuronidase, suggestive of a lysosomal origin.[2] After a thorough review of literature, interestingly Hütter et al. found that these inclusions are exclusively seen in MM with kappa light chain type paraprotein.[2] However, a rare case of nonsecretory MM of lambda light chain type was also described by Kuyama et al.[6] To the best of our knowledge, intracytoplasmic inclusions of PCs in MGUS with <5% PCs in BM is not reported in the literature till date.

As MGUS is asymptomatic and the percentage of PCs is less posing a diagnostic challenge, and there is absence of tissue injury, the presence of these intracytoplasmic granules should raise the suspicion of monoclonal gammopathy, as in our case. Due to its rarity, the prognostic importance of these inclusions is still not clear in patients with PC dyscrasias. The prognostic importance should also be studied in patients with MGUS with respect to progression to MM.

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   References Top

Millá F, Oriol A, Aguilar J, Aventín A, Ayats R, Alonso E, et al. Usefulness and reproducibility of cytomorphologic evaluations to differentiate myeloma from monoclonal gammopathies of unknown significance. Am J Clin Pathol 2001;115:127-35.  Back to cited text no. 1
Hütter G, Nowak D, Blau IW, Thiel E. Auer rod-like intracytoplasmic inclusions in multiple myeloma. A case report and review of the literature. Int J Lab Hematol 2009;31:236-40.  Back to cited text no. 2
Gupta A, Gupta M, Handoo A, Vaid A. Cystalline inclusions in plasma cells. Indian J Pathol Microbiol 2011;54:836-7.  Back to cited text no. 3
[PUBMED]  [Full text]  
Lemez P. Auer-rod-like inclusions in cells of B-lymphocytic lineage. Acta Haematol 1988;80:177-8.  Back to cited text no. 4
Sharma S, Malhan P, Pujani M, Pujani M. Auer rod-like inclusions in reactive plasmacytosis seen with acute myeloid leukemia. J Postgrad Med 2009;55:197.  Back to cited text no. 5
[PUBMED]  [Full text]  
Kuyama J, Kosugi S, Take H, Matsuyama T, Kanayama Y. Non-secretory multiple myeloma with azurophilic granules and vacuoles: An immunological and ultrastructural study. Intern Med 2004;43:590-4.  Back to cited text no. 6

Correspondence Address:
Ritesh Sachdev
Department of Pathology and Laboratory Medicine, Medanta - The Medicity, Sector - 38, Gurgaon - 122 001, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_80_17

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