Plasma cell neoplasm - kappa light chain restricted
FOLLOW-UP LABORATORY WORKUP
Intra-operative interpretation was challenging and the differential diagnoses included a plasma cell neoplasm, pituitary tumor and a meningioma with plasmacytoid morphology. The prior biopsy report, available on next follow-up, revealed a diagnosis of plasma cell neoplasm of the chest wall. A laboratory workup for multiple myeloma revealed a M-spike on serum protein electrophoresis (SPEP) which was confirmed on immunofixation studies to be a IgA Kappa monoclonal protein. Serum IgA and free kappa levels were increased to 2108 mg/dl (ref: 81 to 463 mg/dl) and 82.6 mg/L (ref: 3.3 to 19.4 mg/L). The kappa:lambda ratio was also markedly increased to 13.1. Other significant laboratory results included Hemoglobin of 11.9 g/dl, total WBC count of 5700/mm3 with no evidence of plasma cells in the peripheral blood, slightly elevated serum calcium (11 mg/dl), and creatinine of 1.1 mg/dl. The patient had no radiological evidence of lytic lesions in other parts of his skeleton. A bone marrow study performed did not reveal increased plasma cells.
Pituitary adenomas comprise the bulk of the cases with intra-sellar masses. Plasma cell neoplasms are uncommon in the brain and tend to occur in the leptomeninges with or without parenchymal involvement. They rarely present as an intra-sellar mass, especially extramedullary forms [1,2,3]. Silverstein et al did not document plasma cell tumor involving the pituitary region in 273 analyzed cases of multiple myeloma with neurological involvement. These tumors often mimic non-functional pituitary adenoma clinically and radiologically [1,2].
A review of 21 plasma cell tumors involving the sella by Yaman et al, average age of presentation was 55.8 years (range 35-70) with slight female predominance. Most frequent clinical symptom was headache followed by diplopia and visual loss. Cranial nerve involvement was seen in 81% patients; abducent (VI), trochlear (IV) and occulomotor (III) being the most frequent victims. Radiologically, all tumors mimicked non-functional pituitary tumors with sellar destruction. Four of 21 patients had anterior pituitary hormonal abnormalities - hyperprolactinemia, increased ACTH, increased thyrotropin releasing hormone and primary hypothyroidism. Five cases were initially misdiagnosed as pituitary adenoma but immunohistochemical and electron microscopic studies established the diagnoses of plasma cell tumor. Post-operatively, 48% patients received radiotherapy and about 24% received chemo and radiotherapy. About 29% patients were known to have multiple myeloma at the time of diagnosis. Of the remainder patients, 38% had non-progressive disease and 33% progressed to multiple myeloma. The demographic and clinical features seen in our patient were similar to that described in literature, although we did not document abnormal hormonal profile in this patient.
Morphological examination of tumors in the sellar region can be challenging at times and differential diagnoses may include pituitary adenoma, meningioma, plasma cell tumor, chordoma, germinoma. Metastatic epithelial tumors and craniopharyngioma [2,5]. It is important to distinguish these causes as therapeutic and prognostic implications vary greatly. Plasmacytoid morphology in addition to plasma cell neoplasms, can be seen in pituitary adenoma, meningioma, plasma cell rich inflammatory process (hypophysitis) and metastatic tumors. Plasma cell tumors are comprised of plasma cells with characteristic cell morphology; eccentrically placed nuclei with "cart-wheel" chromatin, peri-nuclear hoff, and moderate to abundant eosinophilic cytoplasm. These cells can often demonstrate numerous intracytoplasmic vacuoles containing immunoglobulins (Russell bodies, mott cells, flame cells). Plasma cell rich hypophysitis is an important differential diagnoses and often show overwhelming proportion of plasma cells which conceal the native pituitary cells. Meningioma with plasmacytoid morphology, although rare, can be confused with plasma cell neoplasm and other metastatic tumors . These tumors however will show other areas with characteristic meningothelial cells arranged in whorls and psammoma bodies. Pituitary adenomas may show a predominant population of oval cells with eccentric nucleus and acidophilic cytoplasm and these can be mistaken for plasma cell tumor . Metastatic tumor can sometimes demonstrate plasmacytoid morphology. Metastatic lobular breast cancer may show predominance of plasmacytoid appearing cells. Renal cell carcinoma with abundant rhabdoid cell morphology can be confused with a plasma cell tumor.
Immunohistochemical analysis is very helpful in supporting the morphological diagnosis or establishing the diagnosis in morphologically difficult cases. Table 1 shows the commonly used panel of markers for establishing the correct diagnosis of sellar tumors.
Table 1: Immunohistochemical panel for distinction of sellar tumors
In the current case, the intraoperative interpretation was challenging due to the clustering of the plasma cells, although the touch preparation did show the individual cells with characteristic plasma cell morphology. Final diagnosis was substantiated by morphology and immunohistochemical panel. Although rare, it is important to be aware of the possibility of a plasma cell tumor in the sellar region and thoroughly rule out other differential diagnoses due to specific therapeutic implications associated with plasma cell tumors.
Contributed by Somak Roy, MD, Ken Clark, MD, Ronald L. Hamilton, MD.