Final Diagnosis -- Pituitary oncocytoma with metastatic malignant melanoma




The pituitary gland is an unusual site of metastatic tumor spread. The incidence of metastases to the normal pituitary gland, was 18 out of 1857 (1%) in autopsy cancer cases, with breast and lung representing the most common primary sites (9). Fewer than 15 cases of pituitary metastatic melanoma have been documented in the literature (10). Pituitary adenoma as recipient tumor for metastases represents an extremely rare condition. Eighteen cases of metastatic cancer to pituitary adenomas have been reported in the literature. The most common primary sites were breast and lung cancers. The other primary sites included stomach, renal, colorectum, carcinoid tumor of anterior mediastinum, pancreas, prostate, and unknown origins (1, 2, 3, 5, 6, 7, 9, 11, 12, 13, 14, 15, 16, 18, 19, 20). To our knowledge, this is the first reported cases of metastatic melanoma to a pituitary oncocytoma.

Most of the patients presented with symptoms similar to that of an ordinary pituitary adenoma. Diabetes insipidus, visual disturbances, cranial nerve palsy and anterior hypopituitarism are major clinical presentations noted in patients with pituitary metastases (8). The current case had visual disturbance, hypothyroidism and partial insufficiency of the adrenocorticotropic hormone. The interruption of the pathway of inhibitory influence of hypothalamus on anterior pituitary prolactin secretion may induce the mild hyperprolactinemia in this case (4). There were 10 cases of metastatic tumor to a nonfunctioning pituitary adenoma, 6 cases of metastases to functional pituitary adenomas ( 2 secreted prolactin, 2 adrenocorticotropic hormone, 2 growth hormone), and 2 cases of metastases to oncocytic adenoma (including ours). The intraoperative findings were unremarkable in this case, although unusual consistency of the tumor found during resection have been reported (1, 19). The prognosis of these patients was poor, since most patients had widespread metastases. Surgical intervention has been reported to be a prognostic factor for survival in cerebral metastatic melanoma (17). However, this patient died one month after operation.

The differential diagnosis of pigmented tumor included melanoma, melanotic schwannoma, and melanotic meningioma. The histologic features of melanoma in this case composed of typical epithelioid cell with pleomorphic nuclei and large nucleoli. Because primary intrasellar melanomas are rare, and the cell type is similar to the operated melanoma on left big toe, metastasis from the previous cutaneous lesion is diagnosed. The presence of typical melanoma infiltrating in pituitary adenomatous cells with disruption of reticular fiber in this specimen was clearly established with reticular stain under microscopic examination. The disruption of reticular fiber network without acinar structure indicated the pituitary adenoma instead of normal pituitary gland.

Immunohistochemical studies are useful in differentiation of metastatic melanoma component to pituitary adenoma component. Melanomas contain S-100 protein and had HMB-45 reactivity. In contrast, the adenomatous cells were negative for S-100 protein and HMB-45. M1B-1 monoclonal antibody is a cell proliferation marker (Ki-67 antigen). Significantly higher M1B-1 labeling index was observed in metastatic adenocarcinoma while low index was noted in the adenomatous component (12). The labeling index in the current case showed high index metastatic melanoma component and low index in pituitary adenomatous component. This indicated that the pituitary metastatic melanoma was a neoplasm with higher proliferation.

The pathogenetic explanation for the development of metastases in pituitary adenoma has not been established yet. Abnormalities of pituitary vasculature and non-portal vessels or neovascularization in adjacent areas of pituitary adenomas have been the most commonly proposed mechanism for metastatic seeding to the pituitary adenoma (8). Metastases to the posterior lobe via direct systemic arterial blood supply with later metastases to the anterior lobe by direct extension from posterior lobe or from the portal vessels may occur in this case.

In conclusion, this report documents metastatic melanoma to a pituitary oncocytoma. Because the clinical presentations and imaging studies of the patient was similar to those of pituitary metastatic tumor, the correct diagnosis was established on the basis of pathological examination with immunostaining and ultrastructure.


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Contributed by Shih-Ming Jung, MD; Yuan-Yu Hsu, MD; Chi-Cheng Chuang, MD; Chen-Nen Chang, MD; Chuen Hsueh, MD; Tseng-tong Kuo, MD, PhD

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