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Year : 2017  |  Volume : 60  |  Issue : 1  |  Page : 139-140
Crystalline inclusions in myeloma cells: Need to go beyond morphologic curiosity

1 Department of Pathology, Bharati Vidyapeeth Deemed University Medical College, Sangli, Maharashtra, India
2 The Oncopathology Centre, Mahatma Gandhi Cancer Hospital, Miraj, Maharashtra, India

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Date of Web Publication14-Feb-2017

How to cite this article:
Agashe SR, Pol JN, Kadkol GA, Patil PP. Crystalline inclusions in myeloma cells: Need to go beyond morphologic curiosity. Indian J Pathol Microbiol 2017;60:139-40

How to cite this URL:
Agashe SR, Pol JN, Kadkol GA, Patil PP. Crystalline inclusions in myeloma cells: Need to go beyond morphologic curiosity. Indian J Pathol Microbiol [serial online] 2017 [cited 2022 Oct 3];60:139-40. Available from:


Plasma cell neoplasms are clonal proliferations of plasma cells which in most cases secrete in excess, a complete monoclonal immunoglobulin or its fraction, usually a light chain (LC). Rarely, these are seen as crystalline inclusions within the plasma cells or histiocytes.

We would like to share two interesting cases of plasma cell myeloma (PCM) who had crystalline inclusions in myeloma cells. Extensive literature search revealed only 35 such cases. All are single case reports except that of Gruszecki and Reddy who have reported two cases.[1] From India, only eight single case reports could be traced.

We describe here two such cases of PCM. The first case was a 50 years female who presented with history of gradually increasing backache and paraplegia. Spinal X-ray and magnetic resonance imaging studies revealed multiple lytic lesions in D7, D8 vertebrae, and sacrum. Bone marrow (BM) aspiration smears stained with Leishman stain showed 25% plasma cells. Many plasma cells showed multiple, pink, Auer rod-like crystalline intracytoplasmic inclusions. Scattered extracellular crystals were also noted. Interestingly, these crystals stained with Leishman but not with H and E and looked like hollow spaces [Figure 1]. These crystals were negative for myeloperoxidase and Congo red. Serum protein electrophoresis revealed hypergammaglobulinemia with M band in the gamma region. The second case was a 60 years female who presented with generalized body ache and intermittent per rectal bleeding. Radiological study revealed multiple lytic lesions in flat bones. BM aspiration showed 69% plasma cells and their precursors. Many plasma cells showed multiple, intracytoplasmic rod, or needle-shaped crystalline inclusions [Figure 2]. Similar crystals were also seen extracellularly.
Figure 1: Case 1 - Crystalline inclusions in plasma cells (Leishman, ×100; Inset: Unstained crystals on H and E stain)

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Figure 2: Case 2 - Crystalline inclusions in plasma cells (Leishman, ×100; Inset: Stained and unstained crystals on Leishman stain)

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In both the cases, the crystals were stained positively with kappa antibodies [Figure 3]. The myeloma cells showed positivity for CD138 [Figure 4] and MUM1 with kappa LC restriction. Staining for CD20 and lambda was negative.
Figure 3: Kappa-positive crystalline inclusions (×100)

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Figure 4: CD138-positive plasma cells

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Crystalline deposits of LC in myeloma cells are a rare finding. Roberts et al. reported an incidence of 1.0% of myeloma cases.[2] We have diagnosed thirty cases of PCM in last 7 years. We reviewed all these cases, only to find no additions to the cases presented here, giving a relatively higher incidence of 6.67%.

The crystalline LC deposits can be intra- and extracellular and are predominantly in the form of needle- or rod-shaped crystals which may mimic  Auer rods More Details. Many different shapes and sizes of crystals are on record.

These crystals can be present not only in PCM and some B-cell lymphomas but also in some reactive lymphoplasmacytic lesions. PCM is rarely associated with a “Crystal-storing Histiocytosis” (CSH), a reactive process in which the histiocytes show prominent crystalline inclusions. CSH can involve various organs, and 90% of cases are associated with lymphoproliferative or plasma cell disorders.[3]

Recently, Dogan et al.[3] have classified CSH in two main categories – (1) Localized CSH (L-CSH) defined as involving only one organ or site (2) Generalized CSH (G-CSH) defined as involving two or more organs or distant sites; G-CSH is almost always associated with grave prognosis while L-CSH has a more favorable clinical course.

PCM associated with acquired Fanconi syndrome (FS) shows crystalline LC deposition in renal proximal tubular epithelial cells and has a good prognosis.[3] Crystalline LC deposits in PCM not associated with CSH or FS do not influence the prognosis of the disease.[1]

Almost all cases of PCM associated with CSH or FS show kappa restriction [3] while crystalline LC deposition unassociated with CSH or FS shows either kappa or lambda restriction.

In a very elaborate study, Lebeau et al. examined the molecular configuration of stored kappa LC in a case of CSH and observed several amino acid substitutions. They postulated that conformational alteration induced by the abnormal amino acid sequences was a probable crucial factor in promoting crystallization of the protein or adversely affecting its intralysosomal degradation or both.[4] Amino acid substitutions such as alanine at position 30 in the CDR-L1 loop have been suggested by Messiaen et al.[5] The molecular changes associated with such crystalline deposits have been studied only by few authors.[4],[5] Rather, such finding is considered only a morphologic surprise by most of the pathologists, and hence, it is not given its due importance.

Clarification of certain observations needs to be obtained such as (1) If mutations with amino acid substitutions are considered to be the pathogenetic mechanism, why similar crystal deposition is observed in some cases of reactive plasmacytosis also? (2) Why crystalline deposition of kappa LCs outnumbers lambda LC deposition? (3) Why almost all cases of CSH and FS show kappa restriction, while crystalline LC deposition unassociated with CSH or FS shows either kappa or lambda restriction?

All these questions need to be answered, and for this, more data collection, analysis, and documentation needs to be done regarding these cases which are sparingly reported.


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Conflicts of interest

There are no conflicts of interest.

   References Top

Gruszecki AC, Reddy VV. Plasma cell crystalline inclusions. Arch Pathol Lab Med 2002;126:755.  Back to cited text no. 1
Roberts GT, Khalil SH. Multiple myeloma with bone marrow crystal deposition and marrow fibrosis. Ann Saudi Med 1998;18:432-6.  Back to cited text no. 2
Dogan S, Barnes L, Cruz-Vetrano WP. Crystal-storing histiocytosis: Report of a case, review of the literature (80 cases) and a proposed classification. Head Neck Pathol 2012;6:111-20.  Back to cited text no. 3
Lebeau A, Zeindl-Eberhart E, Müller EC, Müller-Höcker J, Jungblut PR, Emmerich B, et al. Generalized crystal-storing histiocytosis associated with monoclonal gammopathy: Molecular analysis of a disorder with rapid clinical course and review of the literature. Blood 2002;100:1817-27.  Back to cited text no. 4
Messiaen T, Deret S, Mougenot B, Bridoux F, Dequiedt P, Dion JJ, et al. Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients. Medicine (Baltimore) 2000;79:135-54.  Back to cited text no. 5

Correspondence Address:
Dr. Shobhana R Agashe
Department of Pathology, Bharati Vidyapeeth Deemed University Medical College, Sangli, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.200036

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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