Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inactivating germline mutations of the novel putative tumor-suppressor gene LKB1/STK11 at 19p13.3 have been shown to cause Peutz-Jeghers syndrome (PJS), an autosomal dominantly inherited disease characterized by a predisposition to mucocutaneous pigmentations, as well as various benign and malignant neoplasms. To elucidate the role of LKB1/STK11 in the carcinogenesis of primary and secondary human brain tumors, a total of 309 tumors were analyzed for loss of heterozygosity (LOH) at microsatellite loci D19S886, DI9S878, and D19S565. Low LOH rates were observed for glioma (17.3%, n = 139), meningioma (5.3%, n = 57), schwannoma (0%, n = 21), pituitary adenoma (18.8%, n = 16), primary CNS lymphoma, neuroblastoma, plasmocytoma, medulloblastoma, germinoma, and papilloma of the choroid plexus (6.6%, n = 15). In contrast, brain metastases exhibited a mean LOH frequency of 42.6% (n = 61), with breast (56.3%) and lung cancer metastases (58.3%) being most frequently affected. Genomic DNA sequencing of the complete coding region of LKB1/STK11 was performed in all brain metastases exhibiting LOH (n = 26); no mutation was revealed, but we did find a germline mutation in a PJS patient. Despite high LOH fiequencies at the 19p13.3 locus in carcinoma metastases to the brain and occasional mutations reported for certain primary carcinomas, there are no mutations in LKB1/STK11. This fact suggests that alterations of LKB1/STK11 occur relatively early in tumorigenesis and are rarely involved in the development of carcinoma metastases. Based on these findings, the genes adjacent to LKB1/STK11 may be relevant for the development of metastases to the brain from certain carcinomas.
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PMID:Frequent loss of heterozygosity at the 19p13.3 locus without LKB1/STK11 mutations in human carcinoma metastases to the brain. 1121 97

Metastatic parotid tumours in the skull are very rare. An interesting case of a mucoepidermoid parotid tumour metastasizing to the skull vault is described in a patient who had previously been operated for a pituitary adenoma 20 years back with no post operative radiotherapy; however, she required hormonal supplementation therapy. She underwent an operation for a parotid tumour 7 years ago and received postoperative radiotherapy for the parotid tumour away from the site of the skull metastases. No local recurrence of the parotid tumour was noted. The initial diagnosis was that of a solitary intradiploic meningioma. Interesting clinico-radiological findings are presented.
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PMID:Solitary skull metastasis from mucoepidermoid mimicking a parotid tumour. 1144 46

Pituitary carcinomas are very rare. Defined as adenohypophysial tumors that undergo craniospinal and/or systemic metastasis, most are PRL- or ACTH-producing. Their ultrastructural features, particularly relative to benign adenomas of similar functional type, have not been sufficiently explored. Eleven cases of immunohistochemically characterized pituitary carcinoma with documented cerebrospinal and/or systemic metastases were collected from various institutions and studied by transmission electron microscopy. The tumors were surgically removed from 7 women and 4 men ranging in age between 28 and 74 years (mean, 50 years). All were endocrinologically functioning. Six tumors secreted PRL; three were ACTH-producing; one each was GH/PRL- and TSH-producing. The patients with the ACTH-producing tumors had all presented with Cushing's disease and two of them had undergone adrenalectomy (Nelson syndrome). In most cases significant cellular atypia and mitotic activity were observed. In terms of morphologic features of functional differentiation, electron microscopy revealed that in 9 cases the tumor cells maintained at least some ultrastructural markers of their basic phenotype. A unique feature in 2 ACTH carcinomas was the variable admixture of smooth endoplasmic reticulum with intermediate (cytokeratin) filaments. In 2 cases, both PRL-producing carcinomas, the cell type comprising the tumor could not be identified on an ultrastructural basis alone. Ultrastructural investigation of pituitary carcinomas confirms their endocrine nature and, in most but not all cases, reveals their functional differentiation. Despite the diagnostic utility of electron microscopy in the assessment of these rare tumors, the distinction of pituitary carcinoma from pituitary adenoma cannot be firmly made on ultrastructural grounds alone.
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PMID:Pituitary carcinoma: an ultrastructural study of eleven cases. 1146 79

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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PMID:Corticotroph carcinoma of the pituitary: a clinicopathological study. Report of four cases. 1183 11

The sella turcica and the surrounding area contain several different tissues varying in morphology and cytogenesis. Thus, it is not surprising that a large number of diverse lesions may arise in the sellar region. The most frequent abnormalities are the pituitary adenomas, which based on histology, immunocytochemistry, and transmission electron microscopy can be classified into several distinct entities. Pituitary adenomas originate in and consist of adenohypophyseal cells. They are usually slowly growing benign epithelial tumors, which may be associated with increased hormone secretion or may be endocrinologically nonfunctioning. Pituitary carcinomas also arise in adenohypophyseal cells. They are rare and can be diagnosed only when cerebrospinal and/or systemic metastases are documented. To illustrate the diversity, practical importance, and diagnostic difficulties, four cases were selected for presentation: lymphocytic hypophysitis, thyrotroph hyperplasia, growth hormone-producing pituitary adenoma with neuronal transformation, and composite tumor consisting of adenomatous periodic acid Schiff-positive as well as adrenocorticotropic hormone-immunoreactive adenohypophyseal cells and adrenocortical cells. The first two cases are important from a practical point of view because the proper diagnosis can easily be missed, and appropriate interpretation of the findings is essential to prognosis and treatment. The latter two cases are odd, unusual entities; their histogenesis is unresolved. Study of these and many other cases convinced us that careful and detailed morphologic investigation of lesions involving the sella turcica is of fundamental significance. Histology, immunocytochemistry, transmission electron microscopy, and, in some cases, molecular methods are essential to reach a correct diagnosis and to draw conclusions on histogenesis, growth potential, biologic behavior, prognosis, and therapeutic responsiveness.
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PMID:The differential diagnosis of lesions involving the sella turcica. 1191 72

In 1992 a 54-year-old man underwent transsphenoidal adenomectomy to remove a clinically nonfunctioning pituitary adenoma during which there was a transient cerebrospinal fluid (CSF) leak. He received radiotherapy to a small residual remnant. Follow-up magnetic resonance imaging (MRI) scan in 1997 showed an increase in the tumour in the pituitary stalk region and an additional intradural lesion at C1 level. In the absence of neurological symptoms and signs, an observational policy was followed. By 1999 the cervical dural lesion had enlarged and laminectomy was performed, during which three intradural lesions were removed. Histology and immunohistochemistry of the metastases were identical to those of the initial pituitary adenoma. Follow-up MRI scan showed extension of the pituitary remnant above the chiasma, requiring transfrontal surgery. Operation was complicated by secondary brain haemorrhage from which the patient died. Autopsy revealed a small amount of residual tumour at the top of the stalk and several small intradural tumour nodules at the level of the foramen magnum. Genetic analysis of the initial pituitary tumour identified significant allelic losses in keeping with its invasive nature, while that of the metastases indicated a separate clone as shown by retention of alleles lost in the primary tumour. The regrown pituitary tumour also appeared to be of a different clone to the initial tumour and the same as two of three of the first metastases (C1 level). The foramen magnum metastasis showed the same loss of heterozygosity (LOH) pattern as one of the original C1 metastases and the pituitary tumour tissue obtained at autopsy. We speculate that at the initial pituitary surgery, cells seeded into the CSF and grew in the dura. These cells were from a different clone, implying that the original pituitary tumour contained at least two clones, possibly three, providing evidence for the contemporaneous oligoclonality of the original pituitary tumour.
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PMID:Pituitary tumours are multiclonal from the outset: evidence from a case with dural metastases. 1207 54

A 48-yr-old woman was evaluated 21 yr after receiving treatment for an ACTH-secreting metastatic pituitary carcinoma. She had been diagnosed with Cushing's disease 35 yr earlier at the age of 14 yr and had undergone bilateral adrenalectomy. Six years later she developed Nelson's syndrome, which was treated with resection of a pituitary adenoma followed by radiotherapy to the sella turcica. Eight years later she was found to have craniospinal metastases with three remote intracerebral lesions. Two of these lesions were surgically resected and stained positive for ACTH by immunofluorescence. She subsequently received whole-brain radiotherapy and is doing well 21 yr later with no lesions seen on magnetic resonance imaging and no evidence of recurrent metastatic disease. We present this case in detail along with a literature review of ACTH-secreting pituitary carcinoma.
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PMID:Long-term survival with ACTH-secreting carcinoma of the pituitary: a case report and review of the literature. 1210 5

Pituitary carcinomas are only defined by their metastatic growth, which may be intracranial or systemic. To establish further morphological and immunohistochemical differences between pituitary carcinomas and adenomas, 19 ACTH-secreting adenomas (10 non invasive and 9 invasive) and 2 ACTH-secreting carcinomas with their metastases were studied for expression of the intermediate filaments keratin and vimentin and the tumor-associated antigens Ki67, proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF), cathepsin D, p53, and carcinoembryonic antigen (CEA). Immunohistochemistry was performed using avidin-biotin techniques on formalin-fixed, paraffin-embedded tissue. With the exception of one noninvasive pituitary adenoma, one carcinoma, and the metastases, all tumors contained keratin; none contained vimentin. All tumors stained negative for CEA and p53. Eleven (58.5%) adenomas and both pituitary carcinomas contained Ki67-positive nuclei; 14 (74%) adenomas and one carcinoma revealed PCNA. No correlation was found between the two markers. Seven (38%) adenomas showed a labeling index <1 % for cathepsin D, whereas none of the carcinomas or metastases did so. EGF was found in 7 (38%) adenomas and in both carcinomas. A tendency to a higher rate of EGF positivity in the invasive adenomas was observed. The metastases showed a higher labeling index, and far more intense staining results for Ki67, PCNA, and EGF than the primary tumor. The metastases also had a higher proliferation rate and growth factor content than the carcinoma itself.
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PMID:Proliferation Markers and EGF in ACTH-Secreting Adenomas and Carcinomas of the Pituitary. 1211 89

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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PMID:Ectopic pituitary adenoma with malignant transformation. 1217 97

Renal cell carcinoma has a complex and variable natural history. We report a case underlining this who presented concomitant renal cell carcinoma metastasis with pituitary and adrenocortical adenomas. A 62-year-old woman presented with visual loss. Imaging revealed a large sellar mass with suprasellar extension. Four years before, nephrectomy and adrenalectomy had been performed for a renal cell carcinoma with metastasis in a coexistent adrenocortical adenoma. Faced with progressive visual loss and the questionable pituitary pathology, the patient underwent trans-sphenoidal surgery. Due to profuse tumor bleeding, only a biopsy was possible. In a second operation, the patient underwent craniotomy with subtotal resection of the tumor. Histological examination of the specimen revealed a metastasis of the renal cell carcinoma and a pituitary adenoma. The case presented here and a review of the reports suggest that there are some differences between the clinical features and outcomes of metastases of renal cell carcinoma and those of pituitary gland metastases from other primary sites.
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PMID:Concomitant renal cell carcinoma with pituitary adenoma. 1263 20


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