A 36-year-old man presented with lower back and left lower extremity pain that had been present for 6 months; the pain was increasing in intensity. The patient had no history of trauma or any other significant past medical history. The patient was homosexual and had normal CD4 cell counts; his human immunodeficiency virus status remained unclear. Magnetic resonance imaging of the pelvis showed a large sacral mass that replaced the sacrum and compressed the thecal sac, extending superiorly to the L5 level and anteriorly into the pelvic cavity, occupying a major portion of it. The preoperative impression of this destructive lesion involving the spinal cord was highly suggestive of chordoma.
At surgery, a 15-cm epidural mass was removed. The intraoperative frozen section diagnosis of a poorly differentiated neoplasm was made. The final surgical specimen received in pathology consisted of multiple irregular fragments of white-tan soft tissue, measuring 5 × 4 × 1.3 cm in aggregate, admixed with irregular fragments of bony tissue. On permanent hematoxylin-eosin sections, the tumor was composed of diffuse sheets of pleomorphic malignant cells with a high nuclear-cytoplasmic ratio (Figure 1). The nuclei were pleomorphic with irregular nuclear contours, clumped chromatin, prominent nucleoli, and frequent intranuclear inclusions (Figure 2). An initial panel of immunohistochemical stains revealed the neoplastic cells to be positive for CD45 and CD10 only. They were negative for B- and T-cell markers, S100, cytokeratin AE1/AE3, α-fetoprotein, placental alkaline phosphatase, and myeloperoxidase. Subsequent stainings with CD38 (Figure 3) and cytoplasmic λ light chain (Figure 4) were performed. Staining for cytoplasmic κ light chain was negative. In situ hybridization for Epstein-Barr virus was positive in the neoplastic cells.
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Pathologic Diagnosis: Immature Plasmacytoma
The final diagnosis of this sacral mass was “immature plasmacytoma involving soft tissue and bone.” This diagnosis was based on the findings that the neoplastic cells stained positively for CD38, CD10, and CD45, together with evidence of cytoplasmic λ light chain monoclonality with severe cytologic atypia. The anaplastic morphology, immature phenotype, unusual location of the disease, and presentation at a young age make this case unique.
Solitary plasmacytomas are localized clonal proliferations of plasma cells that are immunophenotypically and cytologically identical to multiple myeloma. Plasmacytomas of bone (osseous plasmacytomas) constitute 5% of plasma cell neoplasms. Although 60% of osseous plasmacytomas arise in the spinal vertebrae, the rate of involvement of sacrum by plasmacytoma or multiple myeloma is 2% to 4%. Solitary osseous plasmacytomas usually have longer survival periods following radiation therapy. Osseous plasmacytomas presenting as presacral or pelvic masses are rare. To our knowledge, only 5 such cases have been reported to date.1 None of these cases were described as immature myeloma with anaplastic morphology.
There are several classifications of myeloma, one of which divides the entity into mature, intermediate, immature, and plasmablastic types, based on cytology. The plasmablastic type is associated with poor survival and aggressiveness.2 Immature-type myeloma is characterized by plasma cells with high nuclear-cytoplasmic ratio and prominent nucleoli, but with obvious plasmacellular differentiation. Larger cells with more cytoplasm, very prominent nucleoli, and condensed chromatin are called immunoblasts. The term anaplastic myeloma is used when pleomorphic immunoblastic cells are present. When anaplastic plasmacytomas occur at extramedullary sites, such as in maxillary sinus, cecum, and pleura,3–5 they can be confused with other malignancies. Immature plasma cells have the following phenotype: CD10+, CD45+, CD56+, interleukin-6+, CD38+, and CD34−. Neoplastic plasma cells can be subdivided phenotypically into 5 subpopulations with a restricted subpopulation expressing CD45. Only immature CD45+ plasma cells proliferate in response to interleukin-6, a growth factor for myeloma cells. Interleukin-6 could induce expression of CD45 on CD45− cells.6 In addition, immature plasma cells can exhibit an increase in serum-soluble interleukin-6 receptor levels and a higher incidence of ras mutation.7 It was also found that expression of vascular endothelial growth factor was elevated in immature plasma cells,8 indicating a direct association of immature morphology with angiogenesis of the tumor. From the view of cytogenetics, complex karyotypes with multiple chromosomal anomalies are present in 20% to 40% of newly diagnosed myeloma cases and in 60% to 70% of patients with progressive disease. Among the aberrations, trisomy 8 and t(11;14)(q13;icq32) are related with anaplastic type.
The median age of onset is 50 years, although solitary osseous plasmacytomas can rarely occur before the age of 30 years. Infection with human immunodeficiency virus and other immunodeficiency conditions have significantly changed the hematopoietic disease profile. The early onset, unexpected locations, and increased incidences of plasmacytoma have been described.9 Epstein-Barr virus coinfection may contribute not only to the alterations described, but also to the development of an anaplastic type of plasmacytoma.10
In summary, immature plasmacytomas with anaplastic morphology can mimic poorly differentiated neoplasms arising from any cell lineage. It is necessary to include this entity in the differential diagnosis, especially when it occurs with unexpected ages and locations.
References
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