Mapping of somatostatin receptor types in GH or/and PRL producing pituitary adenomas.

BACKGROUND: Somatostatin is a tetradecapeptide exerting inhibitory action on endocrine and exocrine cell secretion and proliferation. Somatostatin receptors (SST) are widely expressed in various neoplasms including endocrine tumours. Using immunohistochemistry, the expression of SST(1), SST(2A), SST(2B), SST(3), SST(4), and SST(5) was studied in tissue microarrays (TMAs), using a series of 90 human pituitary adenomas producing growth hormone and/or prolactin, including 30 of each somatotroph, lactotroph, and mixed somatotroph/lactotroph adenoma type. METHODS: For immunohistochemistry, the standard avidin biotin complex method enhanced by tyramide was used, using polyclonal antisera for all SST types. A four point scoring system was used to assess the membranous immunopositivity. RESULTS: All SST types were positive in all tumour types, showing varying immunoreactivity scores. SST(5) and SST(2A) were the predominant receptors, showing strong expression in high frequency in all three adenoma types. Strong expression of SST(1) was higher in lactotroph adenomas than in other tumour types. CONCLUSIONS: The immunohistochemical results of SST expression are in agreement with most findings of previous molecular studies. The fact that SST(2A) expression is predominant suggests that pharmaceutical octapeptide somatostatin analogues may act through this receptor, while the role of SST(2B) may be merely synergistic.

Intrasellar chordomas mimicking pituitary adenoma.

OBJECT: Whereas chordomas involving the sellar region are uncommon, largely or entirely intrasellar examples are rare. The goal in this study was to present examples of these rare tumors as a guide to their proper diagnosis and treatment. METHODS: The authors report three cases in which the chordomas filled the pituitary fossa and presented as nonfunctioning pituitary adenomas. All lesions exhibited the typical histological patterns and immunophenotype of chordoma. One tumor, studied ultrastructurally and subjected to DNA analysis, was shown to have a diploid histogram. The authors present a clinicopathological study of these three cases and review the literature on intrasellar chordomas. CONCLUSIONS: Although these tumors are easily misdiagnosed and therefore may not receive optimal treatment, aggressive surgical resection can yield a favorable prognosis in lesions with a limited extent.

Structure-function correlations of growth hormone or/and prolactin-producing pituitary adenomas: an in vitro study with the reverse hemolytic plaque assay.

The purpose of this study was to detect in vitro growth hormone (GH) and prolactin (PRL) secretion from adenomas clinically associated with GH or PRL hypersecretion. The reverse hemolytic plaque assay (RHPA) was applied in order to reveal possible differences among various morphologic adenoma types, and to examine the inhibitory effects of octreotide on GH release as well. The 20 surgically resected pituitary adenomas studied included 15 from acromegalic patients and 5 from patients with hyperprolactinemia. All adenomas were diagnosed by histology, immunocytochemistry and electron microscopy. Among tumors associated with acromegaly, 5 were densely granulated (DG), 5 were sparsely granulated (SG) somatotroph (SM) adenomas, 2 were mammosomatotroph (MSM) and 3 mixed somatotroph-lactotroph cell (mixed SM-LT) adenomas; tumors causing hyperprolactinemia included 4 lactotroph (LT) adenomas and 1 mixed SM-LT adenoma. GH release assessed by the RHPA corresponded to in vivo hormone secretion and to tissue immunoreactivity. Statistical analysis showed significant differences among all morphologic types of SM adenomas, exclusive of SG-SM adenomas compared to mixed SM-LT adenomas. The mean plaque size in DG-SM and MSM adenomas was significantly greater than that of SG-SM and mixed SM-LT adenomas, indicating higher GH secretion by the former two types during the same incubation time. PRL secretion was documented in 2 mixed SM-LT adenomas. Plaques for PRL, but not for GH were formed in all LT adenomas. In all SM and LT adenomas, cells producing large plaques represented a minority of the plaque-forming cell population, however, they accounted for the largest part of the total plaque area, thus the largest part of hormone secretion. Octreotide effects on GH release were studied in 6 adenomas by the RHPA. Octreotide treatment induced a rapid and significant reduction in GH secretion by SM cells in vitro, with a selective effect on high-secreting cells.

Immunocytochemical accumulation of p53 in corticotroph adenomas: relationship with heat shock proteins and apoptosis.

The pathogenesis of corticotroph adenomas is unknown. In a recent study accumulation of p53 protein was detected by immunohistochemistry in a substantial proportion of pituitary corticotroph adenomas, and it has been suggested that it may be causally related to their development. However, other immunohistochemical studies have not confirmed the high incidence of p53 accumulation in this tumor type. Therefore, in the present study, p53 protein accumulation was re-examined in a series of 31 cases of corticotroph adenomas, using different sets of well validated anti-p53 antibodies. Furthermore, in view of the known association of p53 protein with apoptosis, and the known property of p53 to form complexes with heat shock proteins (HSPs), the relationship of p53 accumulation in corticotroph adenomas with apoptosis and HSP-70 was also investigated. Tumor samples from 31 patients with Cushing's disease or Nelson's syndrome were studied. Accumulation of p53 protein was tested by the standard ABC method using two different sets of clone Pab1801 and DO-7 monoclonal antibodies, applied after incubation of sections in a microwave oven. Using the DO-7 antibody, nuclear accumulation of p53 protein was detected in a total of 15 cases, with cytoplasmic staining observed in only 3 tumors. In contrast, using the Pab1801 antibody nuclear staining was observed in only 5 adenomas, with 11 adenomas demonstrating focal cytoplasmic immunoreactivity. Parallel sections of all corticotroph tumors demonstrating cytoplasmic accumulation of p53 protein were tested for the immunohistochemical presence of heat shock protein HSP-70. A striking similar distribution pattern of these two proteins was observed. Apoptosis, identified by the in situ end labeling technique, was detected in a total of 15 out of 28 corticotroph adenomas tested. Calculation of the apoptotic labeling index (ALI) by image analysis showed a significantly lower ALI in those corticotroph adenomas demonstrating nuclear p53 accumulation compared to those with no nuclear p53 immunostaining (p < 0.05). There was no significant difference in the ALI between cytoplasmic p53 positive and negative tumors. It is concluded that depending on the antibody used there is a significant variation of p53 protein detection in corticotroph adenomas. Overall, a significant proportion of corticotroph adenomas studied expressed the p53 protein, which depending on the antibody used, was located either in the nucleus and/or the cytoplasm of tumorous corticotroph cells. Cytoplasmic accumulation of p53, as shown by our colocalization studies with HSP-70, may be due to p53/HSP-70 complex formation. Although such a complex-mediated cytoplasmic exclusion of p53 has no significant effect on apoptosis, nuclear accumulation of p53 protein is associated with a significantly lower apoptotic index indicating a failure of p53 protein to exert its apoptotic action in at least a subset of this tumor type.

Rapid cytological diagnosis of primary skin tumours and tumour-like conditions.

This study presents the results of fine needle aspiration cytology performed on 1,263 skin lesions which were clinically suspicious for neoplasia. The purpose of the study was to investigate the accuracy of fine needle aspiration cytology for the diagnosis of skin tumours and to assess its clinical value. Twenty-one to 27 Gauge needles were used and the specimens were stained by a quick Giemsa stain. The cytological examination reported 826 primary malignant tumours and 437 benign lesions. Five hundred and thirteen of the cytologically malignant cases and 123 of the benign ones had a subsequent histological examination. The correlation between cytology and histology revealed 6 false positive cytological results and one false negative. Persuaded by our results, we believe that fine needle aspiration cytology can give highly reliable information concerning the histological type or primary skin tumours. It can also detect or exclude relapses of previously treated neoplasms. The procedure is non-traumatic, safe, quick, inexpensive and very well tolerated by the patients.

Asynchronous pituitary adenomas with differing morphology.

Recurrent pituitary tumors can sometimes pose a diagnostic and therapeutic challenge. We report a case of a 43-year-old man who presented twice, 13 years apart, with pituitary adenoma marked by headaches, visual impairment, and no signs of endocrinologic abnormality. At initial presentation computed tomographic scan documented a pituitary mass eroding the sellar floor, with suprasellar and parasellar extension. The patient underwent transsphenoidal surgery and the tumor was classified as a silent corticotroph adenoma, subtype 2. Thirteen years later, clinical symptoms of a destructive pituitary mass reappeared. This time, the adenoma revealed typical ultrastructural features of an oncocytoma; it had a different immunocytochemical profile from the first tumor. Given these striking morphologic differences, we consider the two adenomas to represent asynchronous, de novo formations. We conclude that the recurrence of a resected pituitary tumor may also represent a metachronous development of two distinct pituitary adenomas.

Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings.

This report describes the clinicopathological features of 16 patients with lymphocytic hypophysitis and compares the results with the published literature. There were 2 males and 14 females in this series. In 10 of the 14 females (71%), the presentation was associated with pregnancy. Nine patients (56%) presented with symptoms of an expanding pituitary sellar mass, 10 (63%) had anterior pituitary hypofunction, 3 had diabetes insipidus (19%). Progressive undiagnosed hypopituitarism led to the demise of 3 patients (19%). Hyperprolactinemia was encountered in 6 patients (38%), and elevated growth hormone levels (GH) resulted in IGF-1 excess in one patient. Computed tomography (CT) and magnetic resonance (MR) imaging revealed features of a pituitary mass mimicking an adenoma in 10 cases (83%). Four patients (25%) had associated autoimmune thyroiditis. Morphologic examination of the pituitary and immunohistochemistry showed a polyclonal lymphoplasmacytic infiltrate as well as occasional neutrophils, eosinophils, and macrophages; the chronic inflammatory process resulted in focal or diffuse adenohypophysial destruction of variable severity with associated fibrosis. The inflammatory infiltrate involved the neurohypophysis in 2 cases and one of these patients had diabetes insipidus; the posterior lobe of two other patients with diabetes insipidus was not examined morphologically. We conclude that lymphocytic hypophysitis should be considered in the differential diagnosis of females with pituitary enlargement presenting in the peripartum period as well as those patients in whom pituitary hormone deficiency and/or excess is noted in association with a co-existing autoimmune disorder. This clinical suspicion should probably also be extended to include patients presenting with rapidly growing pituitary masses associated with compressive symptoms with or without pituitary hormone dysfunction. Because of the transient endocrine and compressive features of this condition in many instances, conservative treatment on the basis of clinical suspicion alone may obviate the need for aggressive pituitary surgery.