Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly.

Background: Somatotroph adenomas (SAs) exhibit a variable responsiveness to somatostatin analogue (SS-a) treatment, a process that is not well understood. We investigated established and novel histological markers as predictors of SS-a responsiveness. Methods: We retrospectively investigated pathology samples from 36 acromegalic patients that underwent transsphenoidal surgery. Clinical, hormonal, and imaging data were available in 24/36 patients, before and after SS-a treatment. Specimens were semiquantitatively analyzed with immunocytochemistry for Ki-67, KER, SSTR-2, SSTR-5, ZAC-1, E-cadherin, and AIP. Results: Collectively, 18 (50%) adenomas were each classified as densely/sparsely granulated somatotroph adenomas (DGSAs/SGSAs), respectively. Patients that received preoperative SS-a had lower expression of SSTR-2 compared to those that did not (2.0 (1.0, 3.0) vs. 3.0 (3.0, 3.0), p = 0.042). Compared with DGSAs, SGSAs had higher Ki-67 labeling index (LI) (1.0 (0.5, 1.0) vs. 2.0 (1.0, 3.5), p = 0.013), and a higher proportion of high MR T2 signal (1 (6%) vs. 6 (33%), p = 0.035), and tended to express less ZAC-1 (p = 0.061) and E-cadherin (p = 0.067). In linear regression corrected for baseline growth hormone (GH), ZAC-1 immunostaining was significantly associated with a decrease in GH levels after SS-a treatment (beta (95% confidence interval): -1.53 (-2.80, -0.26), p = 0.021). No markers were associated with changes in circulating insulin-like growth factor-I (IGF-I) after treatment with SS-a. Conclusion: The novel marker ZAC-1 was associated with GH response to medical treatment with SS-a. The SGSA cases were characterized by higher Ki-67 values and MR T2 signals indicative of an inferior response to SS-a. These findings improve our understanding of the mechanisms underlying SA response to medical treatment.

Case report: Primary pituitary non-Hodgkin's lymphoma developed following surgery and radiation of a pituitary macroadenoma.

OBJECTIVE: Primary central nervous system (CNS) non-Hodgkin's lymphoma is a rarely encountered clinical entity. Here we present a case of a primary CNS diffuse large B-cell non-Hodgkin's lymphoma developed on a previously operated and irradiated pituitary macroadenoma. DESIGN-RESULTS: A 60-year-old woman presented with muscle weakness and eye lid ptosis. Thirty years ago, she was diagnosed with a non-functioning pituitary macroadenoma requiring repeated incomplete operations and conventional radiotherapy and accompanied by partial anterior pituitary deficiency. On admission, the magnetic resonance imaging (MRI) identified a pituitary sellar mass extending into the suprasellar region, compressing the optic chiasm and invading the left cavernous sinus. Following transsphenoidal surgery, the histological investigation revealed the presence of a diffuse large B-cell non-Hodgkin's lymphoma without other loci from the systemic staging. Following chemotherapy and despite a marked resolution of the neoplastic pituitary mass in the post-chemotherapy MRI scan, the patient's course was complicated with consciousness deterioration attributed to epileptic seizures and she died of a hospital acquired infection. CONCLUSIONS: Clinicians should include primary CNS lymphoma in the differential diagnosis of an isolated invasive sellar mass. The possible association of primary CNS lymphoma development with the history of operated and irradiated pituitary adenoma is herein discussed.

Ganglion cell containing pituitary adenomas: signs of neuronal differentiation in adenoma cells.

Ganglion cell containing pituitary adenomas are rare. They represent tumors originating in the sella turcica which are composed of adenomatous and neuronal components. Recently accumulated information suggests a common origin for their neuronal and pituitary constituents. The objective of this study was to report the clinical and morphologic findings of pituitary gangliocytomas and study their immunoprofile using neuronal markers. Seven cases of pituitary gangliocytomas retrieved from 1,322 sellar lesions were studied. All tumors were removed from patients with mild acromegaly. Histologically they were biphasic composed of pituitary adenoma and clusters of ganglion cells embedded in a variably dense neuropil substrate. All adenomas belonged to the category of sparsely granulated somatotroph adenoma and were positive for growth hormone, whereas in five tumors, a few adenoma cells were also positive for prolactin. Ganglion cells were immunoreactive for NSE, synaptophysin and neurofilament protein (NFP). NFP-reactive fibrils were observed in the neuropil substrate and varied in number among the cases. Interestingly, all tumors contained varying numbers of adenoma cells with NFP-positive, dot-like areas of cytoplasmic reactivity, mostly tiny paranuclear, a finding not previously reported in human pituitary gangliocytomas. The presence of NFP in pituitary adenomas indicates neuronal differentiation in adenoma cells, suggesting a common origin for neuronal and pituitary adenoma cell elements in gangliocytomas.

Immunohistochemical localization of interleukin-6 in peripheral human endocrine glands.

Interleukin-6 (IL-6) is a pleiotropic cytokine with differentiation and growth-promoting effects. Extensive studies in experimental animals denote that IL-6 is produced in various endocrine organs and participates in the local control of endocrine cell function. The expression of this cytokine in human endocrine glands, however, has only been examined in a limited number of studies. We investigated the immunohistochemical expression and localization of IL-6 in a variety of peripheral human endocrine glands. In the adrenals, IL-6 immunoreactivity was detected in all three zones of the cortex. The reticularis and glomerulosa zones were more heavily stained as compared with the slight immunoreactivity of the fasciculata zone. In the adrenal medulla, chromaffin and sustentacular cells were variably positive. A substantial number of follicular thyroid cells were strongly immunoreactive for IL-6 in all normal and hyperplastic thyroids examined. Parafollicular cells were negative. Parathyroid chief cells were mildly positive; selective and more intense staining was observed in acidophilic cells. Pancreatic islet cells were variably positive. In the testis positive staining was selectively observed in both Leydig and Sertoli cells. In conclusion, IL-6 immunoreactivity is present in almost all the human endocrine glands and it expressed in a cell-specific manner. These observations provide further support for the existence of local immune-endocrine interactions.