—  SPECIALTY CONFERENCE  —

Neuropathology

Case 1 - Multiple Myeloma

Richard A. Prayson
Cleveland Clinic Foundation
Cleveland, OH


Click on each slide thumbnail image for an enlarged view
Clinical History
A 72-year-old male with a history of olfactory neuroblastoma diagnosed five years earlier presented with a three-month history of right parietal headaches, intermittent dizziness, and intermittent right-sided blurred vision and diplopia. The patient had no complaints of memory problems, decreased hearing, arm or leg numbness, or limb incoordination. Physical examination showed decreased vision in the right eye and was otherwise unremarkable. A MRI study of the brain performed at another institution showed evidence of an enhancing skull-based mass which appeared to be centered in the sphenoid sinus but also involved the clivus, right cavernous sinus, and infratemporal fossa. The mass measured approximately 6.7 cm in greatest extent. The patient underwent right frontotemporal craniotomy via a skull-based approach and subtotal resection of the lesion.


Case 1 - Figure 1 - Frozen section appearance of the tumor showing a small cell neoplasm. (Hematoxylin and eosin, original magnification 200x)
Case 1 - Figure 2 - Sheet of small blue cells. No obvious rosette structures are identified. (Hematoxylin and eosin, original magnification 400x)
Case 1 - Figure 3 - A slightly more discohesive area of the tumor. Some of the cells have eccentric nuclei with eosinophilic cytoplasm. (Hematoxylin and eosin, original magnification 400x)



Case 1 - Figure 4 - CD134 immunostain demonstrating diffuse positivity consistent with a plasma cell dyscrasia. (original magnification 400x)
Case 1 - Figure 5 - Lambda immunostain showing positive immunostaining in most of the tumor cells. (original magnification 400x)

Diagnosis: Multiple Myeloma

Plasmacytoma is defined as a clonal proliferation of plasma cells that are identical both cytologically and immunophenotypically to plasma cell myeloma, but in contrast, presents as an osseous or extra-osseous masses [1]. Many patients with apparent plasmacytoma, upon further investigation as was the case in this patient, are diagnosed with a plasma cell myeloma, which is marked by multifocality, serum monoclonal protein, and skeletal destruction with osteolytic lesions, pathologic fractures, bone pain, hypercalcemia, and anemia. The most common sites of origin for plasmacytoma are in bone marrow areas in which active hematopoiesis is occurring, including in decreasing order of frequency, vertebra, ribs, skull, pelvis, femur, clavicle, and scapula. Although approximately 80% of all extramedullary plasmacytomas occur in the head and neck region, skull-based tumors are relatively uncommon (and are primarily extradural in origin [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12] . Rarely, tumors directly extend to involve neural parenchyma. Most of the skull-based lesions have been described in the region of the sphenoid and apex of the petrous bone. Sometimes, the lesions are so extensive at the time of presentation that the exact site of origin is impossible to determine. Serum and urine show no evidence of M-protein and some patients may have low level gammopathies.

In this particular patient, the initial presentation was that of an apparent plasmacytoma. On further investigation and work-up, a diagnosis of plasma cell myeloma was made in this patient, based on the presence of an apparent plasmocytoma on biopsy and marrow plasmocytosis. Plasma cell myeloma represents 15% of all hematological malignancies. The median age at diagnosis is approximately 68-70 years with no obvious gender predilection [13]. Increased risk of developing myeloma has been associated with a variety of exposures to agents such as pesticides, petroleum products, asbestos, rubber, plastic and wood products, and radiation [14, 15] . It has been suggested that the development of myeloma follows the classic "two-hit hypothesis". An antigenic stimulus results in the generation of multiple benign clones. A second "hit" results in a mutagenic event and malignancy.

The morphology of plasma cell myeloma can run the gamut from cells resembling normal plasma cells to anaplastic cells that bear only a rudimentary resemblance to their plasma cell precursor. The classic mature plasma cell has an oval configuration with a round, eccentrically positioned nucleus. The chromatin pattern is often described as "clock-face" or "spoke wheel". Abundant, slightly basophilic staining cytoplasm and perinuclear clearing (hof) are typical. Immature forms with a more dispersed chromatin pattern, prominent nucleoli and less cytoplasm are often present. In the current case, the more typical cytologic features of the plasma cells are best visualized in the areas where the cells are more dispersed.

Plasma cell myeloma cells immunophenotypically express cytoplasmic immunoglobulin and often demonstrate either kappa or lambda immunoreactivity. The current case was lambda positive. Collagen-1 binding proteoglycan, syndecan-1 expression (CD138) is found in most cases of myeloma; syndecan-1, may be involved in the anchoring of cells in the bone marrow [16]. The main differential diagnostic considerations in this case were olfactory neuroblastoma or lymphoma. The immunohistochemical profile of the tumor confirmed the diagnosis.

Table 1 - Immunohistochemical/special Stain Profile of Current Case

Cytokeratin AE1/3 - Alcian blue -
Cytokeratin CAM5.2 - Muramidase -
S-100 protein - CD138 +
CD99 - Kappa -
GFAP - Lambda +
Synaptophysin - Congo red -
Neuron specific enolase -    
CD45RB (CLA) -    

Myeloma is usually incurable; median survival is about 2-3 years [1], with the major causes of mortality often being renal failure and infection [5]. Poorer prognosis has been correlated with higher stage of tumor, poor renal function, plasmoblastic morphology, higher Ki-67 labeling indices, and deletions on chromosomes 13q14 and 17p3 [1, 17, 18, 19, 20, 21] .

References

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