RESUMEN
Breast carcinomas often metastasize into various organs, most commonly into the lung and rather infrequently into the pineal gland. There were only 20 cases of the latter recorded until 1950. Currently, the total number of reported cases, including this report, is 74. At Sunnybrook Health Science Centre, between 1984 and 1992, 27 patients died of disseminated breast cancer; 2 patients had metastases to the pineal gland. Five patients had metastatic deposits in the pituitary and J had metastases in both organs. Average survival time from diagnosis of breast tumor to death was nearly 3 years. In contrast, the 2 patients with pineal metastasis lived for 1 and 7 months, respectively, after diagnosis. The significance of pineal metastases with regard to short survival may be related to the fact that destruction of the pineal parenchyma reduced melatonin production, thereby decreasing the nonspecific oncostatic effect normally exerted by pineal gland secretions.
RESUMEN
A dystopic neurohypophysis was noted incidentally at autopsy in a 51 -year-old man with no endocrine abnormality. The dystopic gland was situated in the upper region of the tuber cinereum and macroscopically simulated a neoplasm. The pituitary fossa contained only anterior hypophyseal elements. Review of the literature disclosed 19 such cases discovered at autopsy; 11 occurred in normal individuals with no endocrine abnormality. Radiological study revealed 145 additional cases. Except for the 6 occurrences described in normal individuals, the rest occurred in patients with anterior pituitary dysfunction. No instance of isolated diabetes insipidus has been reported due to dystopia of the neurohypophysis. Dystopia of the neurohypophysis in normal individuals should be distinguished from those occurring in patients with anterior pituitary abnormalities. The former represent a true dystopia and are not associated with perinatal injury, in contrast to the latter, which are acquired dystopias secondary to regeneration of the neurohypophysis and are associated with perinatal injury. Although anterior and posterior pituitary glands are formed by appositional growth, their development and functional status are entirely independent. Finally, the most significant clinical feature of dystopic neurohypophysis is the absence of any related symptoms and this condition should always be considered in the clinical differential diagnosis of hypothalamic lesions. In such patients, a surgical procedure may be avoided because other hypothalamic lesions, such as hamartomas and astrocytomas, are more frequently symptomatic.
RESUMEN
Allergic adenohypophysitis was produced in rats by injection of anterior lobe tissue, Freund's adjuvant, and pertussis vaccine. In addition to the inflammatory changes in the parenchyma, fluid and inflammatory cells were found in the lumen of Rathke's pouch. The cells entered the lumen through small ulcers of the lining of the anterior wall of the pouch. Pituitaries with inflammation were increased in size and weight. The enlargement was caused mostly by dilation of Rathke's pouch with fluid and cells.
RESUMEN
Various categories of ovarian tumors, particularly those of gonadal stromal origin, are capable of producing a variety of hormones that occasionally induce interesting clinical manifestations. The endocrine manifestations associated with gonadal stromal tumors are often due to hormone production by the tumor cells. Sometimes the tumor cells produce only one hormone, while more frequently the hormonal manifestations result from a summation of various hormones including transformation of a variety of prehormones produced by different components of the tumor including its supportive or reactive stroma. The mechanisms involved in the production and transformation of various hormones and prehormones are complex and not thoroughly established at this time. This review will focus on gonadal stromal tumors and discuss evidence available for linkage of the clinical manifestations to hormones produced by the various neoplasms.
RESUMEN
Pheochromocytoma usually shows prominent nuclear atypia, but the presence of such atypical cells is known to be an unreliable predictor of malignancy. DNA ploidy of pheochromocytomas has been analyzed by flow cytometry or photospectrometry on paraffinem-bedded tissue, but the results were controversial. We performed DNA analysis on cytology specimens of 11 pheochromocytomas using an image analysis system. All tumors had a mixed pattern of a large population of diploid cells and a small population of polyploid cells. DNA content correlated with nuclear size, and larger cells had more DNA content. Such larger tumor cells had polyploid nuclei, such as 4 C, 8 C, 16 C, and 32 C, in both malignant and benign pheochromocytomas. The larger polyploid nuclei may result from difficulty of duplication at the mitotic phase of the cell cycle.
RESUMEN
Small tumors producing adrenocorticophic hormone (ACTH) ectopically may be very difficult to locate. We describe a 57-year-old woman who presented with ectopic Cushing's syndrome as diagnosed by bilateral inferior petrosal sinus catheterization with corticotrophin-releasing hormone (CRH) test. Thoracic pentetreotide (a somatostatin analogue) revealed a small "hot spot" in the base of the left lung. This "hot spot" was constant throughout the procedure. A second thoracic CT scan with 3-mm cuts showed a small image in the area under suspicion, similar to vascular images found elsewhere in both lungs. At surgery, an 8-mm tumor was found and excised. Pathological examination revealed a carcinoid tumor immunoreactive for ACTH, beta-endorphin, bombesin, serotonin, and the α-subunit. One month after surgery, the patient was clinically well and had normal adrenal function. An111ln-pentetreotide scintiscan clearly identified a small ACTH-producing neuroendocrine tumor of the lung undetectable by plain chest radiography or CT scan.
RESUMEN
In human reproductive endocrinology and pathology, it is important to localize the sites of steroid hormone production to obtain a better understanding of steroid metabolism. Previous approaches, including morphological and biological studies, could not sufficiently demonstrate which cells produce what steroids in both normal and pathological human ovaries. Recent development of immunohistochemistry and in situ hybridization of the enzymes specifically involved in sex steroid biosynthesis made it possible to detect the expression of steroidogenic enzymes, and subsequently the sites of specific steroid production in diagnostic pathology materials. There are, however, some limitations in the approaches, including correlation of the findings with preoperative systemic hormonal manifestations in the patients with sex cord-stromal tumors of the ovary, and great care should be taken when interpreting results.
RESUMEN
In addition to its structural function, cytokeratin may have other important roles within cells. We have reported that in growth hormone-producing adenomas (GH cell adenomas), two distinct types can be recognized by their cytokeratin distribution patterns (dot-like or perinuclear pattern) and that each type has different clinicopathological and endocrinological properties. To confirm these phenomena in a larger series and to clarify the significance of different cytokeratin distribution patterns, we studied cytokeratin localization in 70 GH cell adenomas from acromegalic patients. Type I adenomas ( 15) almost exclusively (>98%) composed of cells with a prominent, dot-like distribution; type 2 adenomas (36) comprised of cells with perinuclear cytokeratin; and type 3 adenomas (11) comprised of both cell types were separated. The remaining 8 did not exhibit a distinct distribution pattern. By electron microscopic immunocytochemistry for cytokeratin, dot-like distribution corresponded to fibrous bodies, whereas perinuclear distribution represented immune deposition in the perinuclear zone. Immunohistochemistry for GH, prolactin, ß-thyrotropin, and α-subunit of glycoprotein hormones revealed a reduced expression of these hormones in type 1 adenomas, compared with types 2 and 3 adenomas. In normal pituitary glands, almost all GH cells showed a perinuclear cytokeratin distribution, and only a few GH cells exhibited a dot-like pattern. These findings suggest that a dot-like cytokeratin distribution in GH cells may be pathological (a change from physiological perinuclear distribution) and that adenomas with such a distribution may reduce endocrine activities as a result of unknown factors.
RESUMEN
A 60-year-old woman with an 8-year history of Cushing's syndrome was evaluated. Biochemical data were consistent with those of Cushing's disease. Plasma ACTH levels responded paradoxically to GnRH. MRI demonstrated a large tumor occupying the sphenoid sinus, which was enhanced by gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The pituitary gland was normal in shape and was located in the sella turcica without dislocation. The pituitary gland and the sphenoid tumor could be distinguished by the obvious difference in their MRI intensities. Three consecutive partial resections of the sphenoid tumor were performed, but plasma ACTH and cortisol levels remained high just after the third operation. Histological studies revealed a chromophobe adenoma immunohistochemically positive for ACTH. However, adrenal crisis occurred 3 months after the third operation during reserpine administration ( 1.5 mg/day for approximately 2 mo) for the treatment of Cushing's syndrome due to the residual tumor in the sphenoid sinus. Subsequent MRI showed no change in the tumor shadow, and the paradoxical response of plasma ACTH levels to GnRH remained unchanged. The fourth operation reconfirmed the existence of the ACTH-producing adenoma in the sphenoid sinus. There was no anatomical interaction between the sphenoid tumor and the pituitary gland, and, histologically, no tumor cells were present in the pituitary gland. These findings suggest that the tumor is an ACTH-producing ectopic pituitary adenoma arising from the sphenoid sinus. The patient has been in remission for 4 years on glucocorticoid replacement therapy. The factors responsible for the adrenal crisis were not well understood, although reserpine administration might have had some role.
RESUMEN
We report an 86-year-old woman who presented with a 6-month history of a mass in the left side of her neck. MRI and MRI angiography favored a diagnosis of a neural tumor. FNAB showed a large cluster of cohesive, pleomorphic cells with intranuclear inclusion bodies; a diagnosis of adenocarcinoma was favored. At surgery, a 7 x 5 x 2.5 cm, firm, encapsulated mass was excised. Microscopically, the richly vascularized tumor had characteristics of a CBT, with large pleomorphic chief cells and spindle-shaped sustentacular cells in small, poorly formed nests. The chief cells were strongly immunoreactive for neuron-specific enolase and chromogranin, and focally positive for neurofilament, enkephalin, somatostatin, and beta-endorphin. The sustentacular cells were strongly immunoreactive for S-100 protein and glial fibrillary acidic protein and focally positive for vimentin. Ultrastructurally, the chief cells contained abundant neurosecretory granules. We emphasize that CBT must be included in the differential diagnosis of lateral neck masses. The distinction from adenocarcinoma is difficult on FNAB. The marked cytological atypia in an aspirate of a CBT does not indicate malignancy and may lead to an erroneous diagnosis.
RESUMEN
Fifty-three primary non-small-cell lung carcinomas (NSCLC) were immunohistochemically investigated with antibodies against chromogranin A, chromogranin B, and ecretoneurin. All 3 peptides were focally immunolocalized in 3 of 25 adenocarcinomas and in 2 of 6 large-cell anaplastic carcinomas in more than 20% of tumor cells. Two of 15 squamous-cell carcinomas showed chromogranin B reactivity in more than 20% of tumor cells. Neuroendocrine (NE) differentiation was also demonstrated in lymphnode metastases of large-cell anaplastic carcinomas, in 1 adenocarcinoma, and in 1 squamous-cell carcinoma, with NE differentiation of the respective primary tumors. All tumors with NE differentiation exhibited (large cell) anaplastic tumor areas. We conclude that NE differentiation should be immunohistochemically proven or excluded, particularly in NSCLC with anaplastic components. Chromogranin B and secretoneurin are proposed as useful additional neuroendocrine markers for demonstration of NE differentiation in lung carcinomas.
RESUMEN
Seventy-three adrenal glands of 44 patients with acquired immunodeficiency syndrome (AIDS) were examined and graded histologically to reveal cytomegaloviral (CMV) adrenalitis. The number of CMV inclusion bodies (IB) were evaluated and compared with 3 methods in 58 adrenal glands of 40 patients: histological sections, immunocytochemistry for early antigens of CMV, and in situ hybridization with biotinylated probes for CMV DNA All 73 adrenal glands contained foci of lymphocytic infiltrate. Forty (55%) showed CMV adrenalitis and necrosis, which were more extensive in the medulla than in the cortex. The number of CMV IB increased with the severity of necrosis and fibrosis (grades I, 1.0; II, 3.6; III, 27.8 IB/ thousand cells counted in 20 fields). More than 85 percent of both glands were necrotic in0 only I patient (2.3%). For the 3 methods, the means of the number of CMV IB were as follows: in situ hybridization with biotinylated probe, 17.7; immunocytochemistry, 12.9; and H&E, 8.1. However, using multivariant analysis, there was no statistically significant difference. Thirty-three (45%) adrenal glands contained no CMV IB by any of the 3 methods. We conclude that CMV adrenalitis is a common finding in patients with AIDS. Destruction of adrenal tissue is usually not widespread enough to result in adrenocortical insufficiency.
RESUMEN
No current histological or cytological indices can distinguish reliably malignant from benign tumors in neuroendocrine tumors, including pheochromocytomas, pancreatic endocrine tumors, and carcinoid tumors. We investigated immunohistochemically the expression of Ki-67 in 52 neuroendocrine tumors, including 17 pheochromocytomas, 9 pancreatic endocrine tumors, 23 carcinoid tumors, 2 neuroendocrine carcinomas (NEC), and 1 neuroblastoma with liver metastasis. Of the 52 tumors, distant metastasis was observed in 4 pheochromocytomas, 2 pancreatic endocrine tumors, 4 carcinoids, 2 NEC, and 1 neuroblastoma. We classified these tumors into 3 groups; Groups A, B, and C, depending on the number of Ki-67-positive cells counted under a 200 x magnified field. Expression of Ki-67 was extremely high in group A (> 50 labeled nuclei/field), moderately high in group B (20-50 labeled nuclei), and very low in group C (< 10 labeled nuclei). There was a significant correlation between expression of Ki-67 and tumor progression. The tumors in group A progressed rapidly with the worst outcome; the tumors in group B progressed slowly but with a bad outcome; and the tumors in group C had no metastasis and a good prognosis. Ki-67 is an excellent indicator to assess progression of neuroendocrine tumors.
RESUMEN
The neurofibromatosis 1 (NF1) gene encodes a protein neurofibromin, which contains a glutamyl transpeptidase (GTP)-activating protein (GAP)-related domain: NF1 GRD. This domain is able to down-regulate P21ras by stimulating its intrinsic GTPase. Because P2lras has an important role in regulating growth and differentiation, somatic mutations in the NF1 gene may result in mutant neurofibromins that might interfere with the Ras signaling pathway and contribute to the development of tumors. In this study, we used polymerase chain reaction (PCR)-coupled single-stranded conformational polymorphism (SSCP) and DNA sequencing to examine possible mutations in the NF1 GRD in human pituitary tumors. We screened 36 nonfunctioning and 20 growth hormone-secreting adenomas. No mutation was detected in these tumors. Our results indicate that inactivation of neurofibromin may not have a primary role in the formation of pituitary adenomas.
RESUMEN
To assess the proliferative activity of pituitary adenomas, 36 surgically removed adenomas were studied by light microscopical parameters; mitotic count; expression of PCNA, Ki-67, cathepsin D, and EGF; and image cytometry. Three adenomas (9%) showed high, 11 (34%) medium, 17 (53%) moderate, and 1 (3%) low structural differentiation. In 10 adenomas (31%), no mitosis was observed. The average was 2.4 mitoses/100 HPF; the highest count was 7.1 mitoses/100 HPF. Eleven adenomas (33.3%) were PCNA-negative; in 20 adenomas (60.6%), between 0.05 and 3.9, and in 2 adenomas (6.0%), between 10.5 and 16.4 PCNA-positive nuclei were observed. Only a recurrent null-cell adenoma (9%) was Ki-67-negative. Three adenomas (9.1%) were EGF-negative, 28 (84.8%) showed up to 10% positive cells, and 2 (6.1 %) showed between 10 and 30% positive cells; 19 adenomas (68%) were cathepsin D-negative, including all endocrine-inactive adenomas. Half the adenomas had an euploid DMA stem line. Endocrine-inactive adenomas displayed a higher rate of euploid DNA stem lines than endocrine-active adenomas. The S-phase fraction varied between 2.97 and 28%, with a mean value of 14.4%. Half the adenomas showed an S-phase fraction of 11.65% or lower.
RESUMEN
A 76-year-old woman presented with enlargement and weakness of her hands and feet coarsening of facial features, proximal muscle weakness, and worsening of her noninsulindependent diabetes mellitus. Serum growth hormone, somatomedin-C, and prolactin levels were elevated. Thyroid function test results and serum cortisol and adrenocorticotropic hormone levels were within normal limits. Luteinizing and follicle-stimulating hormone levels were both low, suggesting possible partial hypopituitarism. Magnetic resonance imaging of the sella demonstrated a pituitary lesion that measured 2.2 x 1 x 0.5 cm; it partially obliterated the suprasellar cistern and it distorted the optic chiasm. Light microscopic and ultrastructural examination of the trans-sphenoidally resected tissues identified characteristic features of 2 discrete pituitary adenomas that were in close apposition, but they were sharply demarcated. The 2 components were a corticotroph adenoma and a sparsely granulated somatotroph adenoma. Multiple adenomas of the pituitary are not rare; however, the majority are endocrinologically "nonfunctional." We report a patient with clinical features of acromegaly whose tumor was a composite lesion: one area exhibited morphological characteristics of a corticotroph adenoma and another distinct area exhibited features of a somatotroph adenoma. The possible histogenesis is discussed.
RESUMEN
Distribution of basic fibroblast growth factor (bFGF) in non-neoplastic and adenomatous human pituitaries was analyzed by immunohistochemistry, in situ, and Northern hybridization analyses. Basic FGF protein and mRNA were present in most hormone-producing cells of the non-neoplastic pituitary and in all pituitary adenomas examined. Northern hybridization analysis revealed 7.3 kb and 3.7 kb transcripts, which were most abundant in PRL-and ACTH-secreting adenomas. Three null cell and 3 gonadotroph adenomas were cultured for 7 days in the presence of 10-7 mol/L GnRH. There was an increase (range, 0.4-1.8-fold based on mean grain counts after in situ hybridization) in bFGF in most adenomas (5 of 6). Northern analysis showed an increase in the 7.3-kb transcript in a null-cell adenoma. Chromogranin B mRNA was also increased by Northern analysis in the same neoplasm. These results indicate that bFGF protein and mRNA are widely distributed in non-neoplastic and adenomatous human pituitaries and that the mRNA levels of bFGF in null cell and gonadotroph adenomas can be modulated by GnRH, implicating hypothalamic peptides in regulating bFGF in the anterior pituitary.
RESUMEN
A retrospective morphological and immunohistochemical study of 21 cases of dyshormonogenetic goiter was carried out correlating patterns of hyperplasia and the atypias of the glandular tissues with specific defects in hormonal synthesis, including (1) thyroglobulin synthesis defect (Group I, n = 8); (2) defective organification of iodide (Group II, n = 11); and (3) iodide transport defect (Group III, n = 2). Microfollicular, trabecular, papillary, and oxyphilic cell patterns were more frequent in Group II compared with Group I (Group III was excluded because of the small number of cases). The combined microfollicular and trabecular patterns were more frequently seen in patients in Group II. Two cases of thyroglobulin synthesis defect demonstrated certain morphological specificity characterized by an alveolar pattern. Atypias were more frequent and severe in patients in Group II relative to patients in Group I, but features of malignancy were not found in any patients. Immunohistochemical study using thyroglobulin antiserum demonstrated correlation between morphology and positivity of follicular cells. Scarce C cells were verified in these cases by immunohistochemistry. Using two-paired samples, respectively, of 21 endemic and 21 dyshormonogenetic goiters, we distinguished 85.7% of the cases examined, presented in a double-blind fashion. Scarcity of colloid and prominent cellular atypia were highly suggestive of dyshormonogenetic goiter. Considering the relative rarity of dyshormonogenetic goiter, our studies point out the most common patterns of hyperplasia and atypias in this pathology to avoid misdiagnosis, principally when considering the possibility of malignancy.
RESUMEN
A case of ectopic ACTH secretion by primary small-cell carcinoma of the urinary bladder is described. The patient, a 38-year-old woman, presented with Cushing's syndrome. Although immunocytochemistry of the tumor for ACTH and corticotropin-releasing factor yielded negative results, in situ hybridization demonstrated a conclusive signal for proopiomelanocortin messenger RNA. This case report shows the value of in situ hybridization in diagnostic pathology.