Solitary bone plasmacytoma: An interesting case report with unusual clinico-cytological features.

Solitary bone plasmacytoma (SBP) is a rare entity characterized by localized proliferation of monoclonal plasma cells primarily occurring in the axial skeleton without systemic involvement. Involvement of the distal extremity is unusual. In the absence of typical clinical presentation, diagnosis may not be suspected clinico-radiologically; hence, fine-needle aspiration cytology may help in early and definitive diagnosis, hastening meticulous diagnostic workup and appropriate management of these patients. Intracytoplasmic crystalline inclusions (CI) have been reported in multiple myeloma and lymphoproliferative disorders. The present case highlights unusual clinico-cytological features of SBP with primary involvement of humerus, progression to tibia, and presence of extracellular and intracytoplasmic CI in plasma cells, a morphologic finding not reported in SBP earlier.

Introduction

Plasma cell dyscrasias are neoplastic proliferation of B-cells, and classified as multiple myeloma (MM, generalized medullary type) and plasmacytoma (localized extramedullary type). When the plasmacytoma occurs only in bone, it is known as solitary bone plasmacytoma (SBP) and when involving the soft tissue, it is named as extramedullary plasmacytoma (EMP); however, both the lesions are characterized by absence of systemic involvement attributing to myeloma.[1] SBP arises from plasma cells of bone marrow (BM), whereas EMP arises from those in the mucosal surfaces. SBP is infrequent, representing 3-7% of all plasmacytoma.[2] The median age for SBP is 55 years and involves bones of the axial skeleton (vertebra, skull); involvement of the distal appendicular skeleton below elbow and knee is rare. SBP has a significantly high risk of progression to MM (65-84% in 10 years).[3]

The present case of SBP is being reported for its unusual clinical and morphological findings and the role of fine-needle aspiration cytology (FNAC) in its early diagnosis.

Case Report

A 40-year-old male presented with fractures left arm and left leg following a trivial trauma. He had progressively increasing and painful swellings at both the sites; in the arm since 2½ years and the leg since 1-year. Clinically, the swelling measured 7 cm × 6 cm in size in left lower arm and 3 cm × 2 cm in size in left leg below the knee [Figure 1]. Radiographs revealed osteolytic lesions in left distal humerus and proximal tibia, suggestive of pathological fracture at both sites [Figure 1].

Figure 1

(a) Clinical photograph showing swelling in the lower arm; Radiographs showing osteolytic lesions, pathological fractures in diaphysis of left humerus (b and c) and left tibia (d and e)

Fine-needle aspiration cytology was performed from both the swellings as per the standard technique. Giemsa-stained smears showed similar morphology from both sites. Smears showed predominantly dispersed mature and immature plasma cells including many binucleate, multinucleate forms, and few “Russell bodies.” These plasma cells had eccentric nuclei, abundant cytoplasm, a peri-nuclear “hof,” prominent nucleoli, and frequent mitoses [Figure 2]. Interestingly, fair number of plasma cells showed needle-shaped, single to multiple intracytoplasmic crystalline inclusions (CI); similar inclusions were seen extracellularly in the background also [Figure 2]. Periodic acid-Schiff was negative in the crystals, and they were nonpolarizing on polarized microscopy. However, on immunocytochemistry crystals were positive for lambda and negative for kappa and the plasma cells also showed lambda restriction [Figure 2]. Due to these features, no other differential diagnosis could be considered and thus on cytology, a provisional diagnosis of plasmacytoma was made. A complete clinical, hematological, biochemical, and radiological work-up was advised to exclude MM.

Figure 2

(a) FNA smear from humerus showing sheets of plasma cells with binucleate forms and frequent mitoses (Giemsa, ×250). (b) FNA from leg swelling showing similar plasma cells with prominent intracytoplasmic inclusions (Giemsa, ×600). (c) Immunocytochemistry on FNA smear showing reactivity for kappa (IHC, ×250)

There was no history of headache, decreased vision, bladder or bowel complaints, hemoptysis, dysphagia, dyspnea; and no hepatosplenomegaly or lymphadenopathy. Biochemical investigations for total protein, serum creatinine, blood urea, calcium, serum protein electrophoresis were within normal limits. Urine for myeloma protein was negative. Complete hemogram revealed hemoglobin of 12 g/dL with normal leukocyte count and mild eosinophilia. BM aspirate and biopsy were cellular and showed a mild increase in eosinophilic precursors, plasma cells constituted 1-2% of the marrow nucleated cells. A whole body magnetic resonance imaging was done and did not show bony lesion at any other sites in the body.

Based on the above findings, a diagnosis of primary SBP of the distal humerus with progression to the proximal tibia was made. The patient was given one sitting of radiotherapy (RT) and two cycles of chemotherapy (CT). Subsequently, the leg mass disappeared, and the size of the arm lesion decreased considerably; a repeat FNAC showed a few plasma cells with degenerative changes and disappearance of CI. Since the size of the lesions decreased significantly postchemotherapy, so the biopsy could not be performed. Moreover, on treatment, serum calcium levels remained within normal limits and showed no change in levels.

Discussion

Solitary bone plasmacytoma is a rare immunoproliferative monoclonal disease with localized proliferation of plasma cells. It occurs more commonly in men than in women (M:F-2:1) and presents a decade younger than MM.[4] It mostly involves the axial skeleton, that is, vertebra and skull; involvement of the bones of extremities is rare.[4] EMP generally involves the head and neck region with most common sites being nasal cavity and nasopharynx. In contrast to MM, both SBP and EMP show absence of CRAB (increased serum calcium, renal insufficiency, anemia, and multiple bone lesions). The diagnostic criteria for SBP includes a solitary bone lesion confirmed by skeletal survey, biopsy proven clonal plasma cell infiltration, lack of myeloma-related organ damage, plasma cell constituting <10% of BM nucleated cells and absence of urine/serum “M” protein.[34] EMP, on the other hand, will be characterized by absence of any osteolytic bone lesion with monoclonal plasma cells on tissue biopsy. Durie and Salmon[5] have graded SBP as stage-I myeloma.

Histopathological analyses alone are not sufficient for making a diagnosis; all the above investigations are mandatory to exclude MM. FNAC often helps in early provisional diagnosis, as in the present case. An interesting morphological feature in the present case was the presence of extracellular and intracytoplasmic CI in plasma cells. These are composed of monoclonal immunoglobulins and have been reported in MM and lymphoproliferative disorders.[6] Similar inclusions have been rarely defined in EMP of the parotid gland.[27] To the best of our search, there is no report in the published literature describing CI in SBP of the appendicular skeleton. CI are stained with anti-light or anti-heavy chains of globulin. The relationship of this finding to tumor progression, prognosis and disease recurrence remains uncertain.

Radiograph of plasmacytomas shows a well-defined punched out lytic lesion with destruction of bone cortex and peripheral ridging. A complete skeletal survey is beneficial in detecting an osteoblastic response to bone destruction; however, recent advancements have improved the precision of diagnosis. Flow cytometry and molecular detection of heavy and light chain rearrangements may reveal monoclonality of plasma cells.[8]

Higher risk of progression has been detected in lesion >5 cm of size, age ≥40 years, spine lesions, high ‘M’ protein levels and persistence of ‘M’ protein after treatment.[39] Bataille and Sany[10] reported new solitary lesions in 15% of their patients, of which 75% converted to MM. Whether this development is a harbinger of the ultimate conversion to MM is still unclear.[10] Our case had poor prognostic features and some interesting and unusual features; it was of large size, showed progression of the lesion from humerus to the proximal tibia and did not show the presence of M band.

Treatment for SBP is RT to eradicate the local lesion. In some cases, surgical intervention is required for stabilizing fractured ends or for nerve decompression. RT alone is curative in many cases; however, adjuvant CT is recommended for tumor with poor prognostic factors.[3] Since our patient also had a tumor with poor prognostic factors in terms of significantly large swelling and progression to another bone, combined RT and CT were given. SBP has a benign clinical behavior but has a poor prognosis in comparison to EMP. Local control is achieved by RT in most cases, but up two-thirds of patients eventually evolve to generalized myeloma or additional solitary or multiple plasmacytomas.[11] In spite of curative treatment, the median time of progression to MM is 2-3 years and the rate is 65-84% in 10 years.[3]

To conclude, SBP of the appendicular skeleton is very rare in a young adult. Not only does this case illustrate the unusual site of affliction, it is also probably the first case showing presence of intracytoplasmic and extracellular CI in plasma cells from SBP. Thus, FNAC helps in the early and provisional diagnosis in a case clinico-radiologically unsuspected of SBP.