Cases reported "Pituitary Neoplasms"

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1/26. A case of atypical granular cell tumor of the neurohypophysis.

    A case of granular cell tumor (GCT) arising in the neurohypophysis of a 63-year-old woman is reported. The tumor consisted of ovoid, polygonal or spindle-shaped cells in a sheet-like or fascicular arrangement. Its abundant cytoplasm contained granules positive for diastase-resistant periodic acid-schiff reaction. Ultrastructurally, the tumor cells contained numerous polymorphic lysosomes of various densities. Immunohistochemically, the tumor cells were positive for S-100 protein, glial fibrillary acidic protein and Leu7, suggesting that the tumor originated from pituicytes that were thought to be modified astrocytes in the neurohypophysis and its stalk. The granular cells showed nuclear atypia, pleomorphism and increased mitotic activity. Therefore, the present tumor was considered as a histologically atypical GCT. Interestingly, proliferating cell nuclear antigen, Ki-67 and p53 were stained in a few tumor cells of this case. These findings indicate that the present tumor had a malignant potential.
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2/26. The 'hook effect' on serum prolactin estimation in a patient with macroprolactinoma.

    Large quantities of antigen in an immunoassay system impair antigen-antibody binding, resulting in low antigen determination. This is called the 'high dose hook effect'. We report this phenomenon in a patient with a large macroprolactinoma. In this patient, the correct estimate of serum prolactin (PRL) was obtained only after appropriate dilution of serum. We suggest that in order to avoid the high dose hook effect, the serum PRL be estimated in appropriate dilution in all patients with large pituitary tumours. This is particularly important when the clinical suspicion of high PRL is strong, as in women with amenorrhoea-galactorrhoea and men with long standing hypogonadism.
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3/26. Absent p53 immunohistochemical staining in a pituitary carcinoma.

    BACKGROUND: Carcinomatous transformation of pituitary adenomas is uncommon, and is generally accompanied by nuclear accumulation of p53 protein. Pituitary carcinoma lacking accumulation of p53 protein is very rare, only two such cases being previously reported. methods: A patient presented with visual disturbance and cranial nerve palsies and was found to have a suprasellar mass. He underwent both transphenoidal and transfrontal excision of a nonfunctioning pituitary adenoma which recurred several times. The third recurrence was accompanied by multiple dural-based metastases. Despite aggressive surgical management, he continued to develop additional intracranial lesions and died two years after the discovery of metastatic disease. Specimens from 1984, 1995, 1997 and 1998 were available for histological and immunocytochemical analysis. antibodies recognizing the pituitary hormones (ACTH, PRL, GH, FSH, LH and TSH), as well as cytokeratin, epithelial membrane antigen (EMA), glial fibrillary acidic protein (GFAP) and chromogranin a were applied to investigate the lineage of the neoplasm. Antisera specific for Ki-67 (MIB-1) and p53 protein were also applied to further delineate the biology of the tumour. RESULTS: Although cytokeratin and chromogranin a were detected in neoplastic cells. no expression of pituitary hormones was demonstrable, indicative of a nonfunctioning, null-cell pituitary adenoma. Nuclear pleomorphism and mitotic activity increased with subsequent resections. Abnormal accumulation of p53 protein was not observed, neither in early resections nor in the metastatic deposits. CONCLUSIONS: Failure to demonstrate p53 protein accumulation does not ensure a favourable outcome for pituitary adenoma. Accordingly, pituitary carcinoma may occur in the absence of p53 accumulation. The factors which underlie aggressive behaviour of pituitary neoplasms are uncertain but are under investigation.
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4/26. Significant gene expression of insulin-like growth factor ii and proliferating cell nuclear antigen in a rapidly growing recurrent pituitary acth-secreting adenoma.

    BACKGROUND: We quantified the expression of various growth-related factors in an adrenocorticotropic hormone (ACTH)-secreting adenoma that had recurred very rapidly as invasive macroadenoma. methods/RESULTS: A 43-year-old woman underwent successful transsphenoidal surgery for Cushing's disease. Seven years later, she was admitted to our ward for further endocrine examinations. In spite of a very high plasma ACTH level, the serum cortisol level was normal. Discrepancies between ACTH and cortisol levels were detected on the basis of diurnal rhythms, dexamethasone suppression tests, and corticotropin-releasing hormone test. The patient showed no clinical features of Cushing's disease. magnetic resonance imaging of the pituitary showed an almost empty sella, and no microadenoma was found. These results, along with those of Sephadex column gel filtration and high-performance liquid chromatography of plasma-immunoreactive ACTH, suggested that the patient's residual corticotrophs secreted biologically inactive ACTH. Two years later, the patient suddenly developed diplopia and right abducens nerve palsy. She was slightly moonfaced and centrally obese. Her plasma ACTH and serum and urinary free cortisol levels were elevated, although discrepancies between ACTH and cortisol still existed. magnetic resonance imaging revealed a large pituitary mass with suprasellar and cavernous sinus extensions. The tumor was excised, and the proopiomelanocortin gene and the expression of growth-related factors were analyzed. No mutations were found in the ACTH-coding region of the proopiomelanocortin gene. A significant expression of insulin-like growth factor II and proliferating cell nuclear antigen mRNAs was demonstrated. A high MIB-1 antibody labeling index was also detected in the adenoma tissue, suggesting high Ki-67 expression. CONCLUSION: These growth- and proliferation-related factors might be involved in the rapid growth and aggressiveness of this patient's pituitary adenoma.
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5/26. Plasma cell granuloma of the pituitary gland. Case report.

    BACKGROUND: Plasma cell granuloma, one of the subtypes of inflammatory pseudotumor, is non-neoplastic proliferation of plasma cells and occurs extremely rarely in the intracranial space. We encountered a case of plasma cell granuloma in the pituitary gland, which initially presented with left oculomotor palsy. CASE DESCRIPTION: A 34-year-old female presented with left ptosis. Magnetic resonance image (MRI) demonstrated an intrasellar mass extending to the pituitary stalk with dural enhancement. The lesion was subtotally resected by a transsphenoidal approach. Histopathological findings showed that the resected mass consisted of mature plasma cells, and some cells had infiltrated the surrounding normal pituitary tissue. Immunohistochemical study demonstrated that these cells were positive for leukocyte common antigen, kappa and lambda light chains of IgG, indicating polyclonality of these plasma cells. CONCLUSIONS: We propose that, in the case of an intrasellar mass with unusual neurological symptoms including oculomotor palsy, inflammatory disease of the pituitary gland such as plasma cell granuloma should be included in the differential diagnosis.
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6/26. Metastatic adenocarcinoma to a pituitary adenoma.

    Metastatic tumor to a pituitary adenoma has rarely been documented in the literature. We report a case of a 60-year-old man who presented with a history of progressive blurred vision and an incomplete homonymous hemianopsia. magnetic resonance imaging showed a 5 cm heterogeneous mass which focally was contrast enhancing, involving the sella turcica and extending into the right cavernous sinus region. After worsening symptoms, repeat magnetic resonance imaging showed an increase in size of the lesion. Histologically, the mass consisted of a metastatic adenocarcinoma to a nonsecreting pituitary adenoma. The carcinoma stained focally positive with antibodies to carcinoembryonic antigen, cytokeratin 20, and p53 (60% of tumor cells), and did not stain with antibody to cytokeratin 7. The histologic appearance and immunohistochemical profile of the metastasis suggests a colorectal primary.
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7/26. Corticotroph carcinoma of the pituitary: a clinicopathological study. Report of four cases.

    To understand the relationship between pituitary adenoma and carcinoma, four adrenocorticotropic hormone-producing pituitary adenomas and corresponding metastatic carcinomas were studied. All were functional macroadenomas (three cases of nelson syndrome and one of Cushing disease) that initially invaded the sella turcica and occurred in women ranging in age from 17 to 66 years (mean 45 years). Metastases (two craniospinal and two systemic) occurred after latency periods of 6 to 13 years. Histological specimens were immunostained for pituitary hormones, ki-67 antigen (MIB-1), p53 and p27 proteins, D-type cyclins, and glucocorticoid receptor messenger (m)rna. The dna content of the specimens was assessed using Feulgen stain. Reactivities were quantified by digital image analysis. Primary/recurrent lesions and metastatic tumors differed according to their respective mean mitotic indices (1.2/10 hpf compared with 4.3/10 hpf), MIB-1 labeling (1.7% compared with 8%), p53 staining (37.3% compared with 49.9%), and p27 labeling (48% compared with 25%). cyclin d, immunoreactivity provided no prognostically significant information. Glucocorticoid receptor mRNA was detected in all cases. Results of a ploidy analysis were variable and nonprognostic. In keeping with the 2000 world health organization classification of endocrine neoplasms, our findings support the concept that primary tumors that exhibit mitotic activity, an increased (> 3%) MIB-1 labeling index, and/or p53 immunoreactivity should be termed "atypical adenomas" to denote their aggressive potential and the possibility of future malignant transformation.
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8/26. Ectopic pituitary adenoma with malignant transformation.

    We report here a case of ectopic pituitary adenoma with malignant transformation after repeated relapses. First, an ectopic pituitary adenoma producing follicle-stimulating hormone was found in the nasal cavity extending to the frontal cranial fossa. Despite repeated surgical resections of the tumor, it recurred three times in 2 years. The tumor gradually showed cellular atypia, mitosis, and necrosis. Immunohistochemical analyses revealed that the expressions of proliferating cell nuclear antigen and MIB-1 increased progressively. Moreover, the expression of p53 was detected at the second recurrence. Finally, at the third recurrence the tumor showed dissemination to the subarachnoid space and multiple metastases in the brain. The patient died of the tumor 10 months after the last resection. These findings indicate that the ectopic pituitary adenoma became malignant. To our knowledge, this is the first report on malignant transformation of ectopic pituitary adenoma. It is important to know that ectopic pituitary adenomas show malignant transformation and that the above parameters (proliferating cell nuclear antigen, MIB-1, and p53) may be useful indicators of the malignant potential of both ectopic and sellar pituitary tumors.
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9/26. Pituicytomas, a mis-diagnosed benign tumor of the neurohypophysis: report of three cases.

    Pituicytoma is a rare benign primary tumor of the neurohypophysis, occurring in the sellar and suprasellar spaces. We report here three new cases with immunohistochemical and electron microscopic study. Particular attention was paid to the expression of some cell adhesion molecules. These tumors were characterized by bundles of elongated cells strongly immunoreactive to anti-vimentin, S-100 protein, neural cell adhesion molecule and neuron-specific enolase antibodies. glial fibrillary acidic protein (GFAP) was not recorded. It expressed the very late antigen alpha2 (VLAalpha2), but not VLAalpha5, and lacked epithelial markers expression (epithelial membrane antigen, E-cadherin), and specific neuronal markers (synaptophysin, chromogranin, neurofilament). Staining for pituitary hormones was negative. At the ultrastructural level, tumor/blood vessel basal lamina and cytoplasmic intermediate filaments were observed but desmosome or pericellular basal lamina were lacking. In one case few secretory granules were recorded. Differential diagnoses include granular cell tumors, pilocytic astrocytomas and spindle cell tumors such as solitary fibrous tumors, fibroblastic meningiomas and schwannomas. However, the unique pattern of antigenic expression and ultrastructural features of pituicytomas distinguish this rare tumor. As a subpopulation of pituicytes (which are distinctive glial cells of the neurophypophysis), some pituicytomas do not expressed GFAP. This suggests that pituicytomas presumably arise from pituicytes at various stages of their differentiation.
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10/26. "Hook effect" in prolactinomas: case report and review of literature.

    OBJECTIVE: To present a case of the "hook effect" occurring in the prolactin immunoassay in a patient with giant prolactinoma and to review this phenomenon. methods: We describe the clinical, biochemical, radiologic, and pathologic data of a patient with a giant prolactinoma, in which dilution testing of serum prolactin levels confirmed the presence of the hook effect. We discuss the historical and mechanistic aspects of the hook effect and then review its occurrence with the prolactin assay. RESULTS: A 65-year-old man sought medical attention because of headaches, personality changes, and "bulging" eyes. Cranial magnetic resonance imaging disclosed a 10-cm-diameter, lobulated, heterogeneous, locally invasive mass in the anterior skull base and cranial fossa. Initial laboratory testing showed a prolactin level of 164.5 ng/mL (normal range, 1.6 to 18.8). The pathology specimen from his surgical debulking procedure was consistent with prolactinoma. Retesting of the original serum prolactin sample with serial dilutions revealed a prolactin level of 26,000 ng/mL. A postoperative diluted prolactin level was 22,000 ng/mL. Both prolactin samples demonstrated the hook effect. dopamine agonist therapy was initiated, and the prolactin level and size of the tumor decreased substantially. The hook effect most commonly occurs when excess antigen (for example, prolactin) is present during testing. Dilution testing can counteract this assay phenomenon. CONCLUSION: Clinicians should be aware of this laboratory phenomenon when evaluating large pituitary or parasellar masses. When the hook effect is suspected, dilution testing of prolactin samples may prevent incorrect diagnosis and unnecessary surgical intervention in patients with prolactinomas.
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