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In daily routine pathology of the adrenal glands three tumor entities are important: adrenocortical tumors, adrenomedullary tumors and metastases. The differentiation of these three main tumor types can often be difficult structurally but immunostaining enables a definite diagnosis in nearly all cases. Adrenocortical tumors are positive for steroidogenic factor 1 and melan-A and always negative for chromogranin A whereas adrenomedullary tumors express chromogranin A but never keratin. A broad spectrum of antibodies is available for the identification of metastases and even the rare epithelioid angiosarcomas. For adrenocortical tumors, adenomas and carcinomas can be differentiated using three scoring systems and the Ki-67 index in adenomas should not exceed 3%. Using scoring systems and the Ki-67 index approximately 90% of cortical tumors can be differentiated into benign or malignant tumors. For pheochromocytomas two scoring systems are used for differentiating benign and malignant tumors but the results are less dependable.

Background: Somatostatin mediates its action through five receptor subtypes (sst1-5) that are widely distributed in various endocrine tissues and tumours. Because of the inhibitory effects of somatostatin, long-acting analogues have been synthesized. In contrast to their well-established use in neuroendocrine and pituitary tumours, little is known about their potential use in adrenal tumours., Objective: We examined somatostatin receptor protein expression in adrenal tumours of various aetiologies. Immunostaining was performed with specific polyclonal antibodies for sst1-5., Design: Seven benign and eight malignant pheochromocytomas (PHEOs), eight aldosterone-secreting adenomas (APAs), nine cortisol-secreting adenomas (CPAs), seven nonfunctioning adrenal tumours (NFAs) and 25 adrenal carcinomas (CAs) as well as eight normal adrenal glands were investigated., Measurements: Staining pattern, distribution and subcellular localization of the somatostatin receptor subtypes were evaluated., Results: In the majority of normal cortices the expression of sst1-5 was limited to the reticular zone. The medulla was predominantly positive for sst3. Most cortical adenomas were positive for all five subtypes. However, in the majority of these tumours, less than 30% of cells were positively stained. A high expression of sst4 was found in CPAs but only very few cortical carcinomas exhibited sst immunostaining. All benign PHEOs were positive for sst3. The majority presented with more than 60% of tumour cells stained. By contrast, only six out of eight malignant PHEOs were positive for sst3., Conclusions: Somatostatin receptor subtypes are expressed in PHEOs as well as in tumours of the adrenal cortex with tumour-specific distribution patterns. This may offer new diagnostic and therapeutic possibilities.

Ghrelin is a newly characterized, widely distributed peptide thought to be involved in the regulation of appetite. Significant effects on the release of growth hormone (GH) and ACTH have been demonstrated. This study compares the expression of ghrelin and its receptor (GHS-R) in various adrenal tumors and normal adrenal gland. Normal adrenal tissue was obtained after autopsy. Tissue was obtained from 13 pheochromocytomas (PHEOs), 15 cortisol-secreting adenomas (CPAs), 12 aldosterone-secreting adenomas (APAs), and 16 nonfunctional adenomas (NFAs) following laparoscopic surgery. Expression of ghrelin and GHS-R1a was investigated on RNA levels by using real-time reverse transcription polymerase chain reaction (RT-PCR) and on protein levels by using immunohistochemistry. In the seven normal adrenal glands analyzed, ghrelin mRNA levels were 12-fold lower than in stomach. Ghrelin protein expression was confirmed by immunohistochemistry. In all adrenal tumors, relevant levels of ghrelin mRNA were observed, with significantly lower expression in PHEOs and APAs than in normal adrenal gland. Ghrelin protein was detected in 0% of PHEOs, 55% of APAs, 87% of CPAs, and 54% of NFAs. GHS-R1a mRNA expression was detectable in normal adrenal gland, but the receptor protein was absent. In adrenal tumors, detectable levels of receptor mRNA were found in 38% of PHEOs, 13% of CPAs, and 25% of NFAs. GHS-R1a protein was absent in the majority of adrenal tumors. Expression of ghrelin in normal adrenal gland and adrenal tumors may indicate some unknown physiological function. The pathophysiological relevance of ghrelin expression in adrenal tumors remains to be investigated.

This study provides a base for evaluating incidentalomas. The incidence and type of pathological findings in a large group of surgically removed adrenal glands were analyzed: 282 resected adrenals from the years 1995 to 2004 were examined; 242 adrenals were removed for therapy of renal cell carcinomas (in one case both adrenals were removed). Other indications for adrenalectomies were malignant tumors (urothelial carcinoma, squamous cell carcinoma, sarcoma, lymphoma, etc.) and benign findings (oncocytoma, angiomyolipoma, pyelonephritis, etc.). A total of 18 adrenals exhibited a metastasis or diffuse infiltration of the adrenal or para-adrenal tissue by a malignant tumor (17 renal cell carcinomas, 1 non-Hodgkin's lymphoma). Seven adrenals exhibited an adenoma. Eighty-nine adrenal hyperplasias were diagnosed. Eighty-six adrenals included myelolipomatous or lipomatous foci. One hundred and thirteen adrenals (40.1%) did not exhibit any pathological findings. The adrenals exhibited infiltration or metastasis by malignant tumors (6.4%), adrenal adenomas (2.5%), adrenal hyperplasias (31.6%), and other alterations (38.7%).

Decrease in connexin (Cx) expression and loss of gap junctional intercellular communication (GJIC) have been associated with aberrant cell growth and enhanced neoplastic phenotype. We studied the expression of Cx26, Cx32, Cx43, and Cx50 in chromaffin cells of 10 normal human adrenal glands, 10 benign, and 13 malignant pheochromocytomas. Immunohistochemistry showed that Cx50 expression seemed to be the predominant form of Cx expressed in human chromaffin cells, whereas Cx43 immunoreactivity was the most prominent form found in the adrenal cortex. However, Western blotting revealed that nonphosphorylated and singly and doubly phosphorylated forms of Cx43 were present within the malignant adrenomedullary cells at the same time. Cx26 and Cx32 were distributed inhomogeneously with no emphasis of expression in the types of tissues studied. Cx50 expression was diminished in malignant pheochromocytomas. We conclude that there is a differential expression of Cx in human adrenals. Immunohistological testing for Cx expression does not however allow differentiation of benign from malignant pheochromocytomas.

Incidentally detected adrenal tumors are a common finding during abdominal ultrasonography, computed tomography, and magnetic resonance imaging. Although most of these lesions are benign adenomas, adrenocortical carcinomas and metastases constitute 5% to 10% of all tumors. Adrenal biopsy may be helpful, but its diagnostic value is controversial and disputed, and prospective studies have not yet been performed. Therefore, the diagnostic accuracy of adrenal core biopsy was evaluated in a prospective multicenter study involving 8 surgical centers in Germany and Austria. A total of 220 biopsies from surgical specimens of the adrenal gland were punctured in an ex vivo approach and processed for pathohistologic diagnosis using paraffin sections, routine staining, and immunohistochemistry (keratin KL1, vimentin, S100 protein, chromogranin A, synaptophysin, neuron-specific enolase, D11, MiB-1, and p53 protein). The evaluating pathologist was blinded for clinical data from the patients. A total of 89 adrenal adenomas (40.5%), 22 adrenal carcinomas (10.0%), 55 pheochromocytomas (25.0%), 15 metastases (6.8%), 16 adrenal hyperplasias (7.2%), and 23 other tumors (10.5%) were studied. Nine cases were excluded due to incomplete data (n = 2) or insufficient biopsy specimen (n = 7). In the remaining 211 tumors, compared with the final diagnoses of the surgical specimen, bioptic diagnoses were absolutely correct in 76.8% of the cases, nearly correct in 13.2% of the cases, and incorrect in 10% of the cases. Pheochromocytomas were correctly diagnosed in 96% of the cases, cortical adenomas were correctly or nearly correctly reported in 91% of the cases, cortical carcinomas were correctly or nearly correctly reported in 76% of the cases, and metastases were correctly or nearly correctly reported in 77% of the cases. Of the 39 malignant lesions, only 4 were misclassified, 2 as benign and 2 as possibly malignant. This resulted in an overall sensitivity for malignancy of 94.6% and specificity of 95.3%. Our findings suggest that adrenal core biopsy is a useful method for identifying and classifying adrenal tumorous lesions if sufficient biopsy specimens can be obtained. However, in clinical practice it remains to be shown whether the benefits of biopsy outweigh the risks of the procedure., (Copyright 2003, Elsevier Science (USA). All rights reserved.)

The pituitary and adrenal glands are a functional endocrine unit affected by local or organ-limited senile amyloid syndromes. These occur as interstitial (pituitary only) or intracellular (pituitary and adrenal) varieties. The pituitary and right adrenal glands of each of 108 consecutive autopsy cases of individuals aged 85 years and over were investigated for the prevalence, distribution and immunostaining characteristics of local amyloid. Intracellular amyloid was detected in 77 (71%) pituitaries and 73 (68%) adrenals. Interstitial amyloid was found in 86 pituitaries (80%). Immunohistochemical studies, investigating different amyloid fibril proteins, amyloid P component, ubiquitin, intermediate filaments and pituitary hormones, failed to demonstrate any similarities, and a common origin is unlikely. Statistical analyses demonstrated significant correlations between the occurrences of all three local amyloids. The clinical and histopathological significance of local pituitary and adrenal amyloid remains obscure. The results suggested that the pathogenesis of the local senile amyloidoses of the pituitary and adrenals may be influenced by a common, still uncharacterized variable. It is not clear whether this variable also contributes to the pathogenesis of other senile amyloid syndromes, such as those associated with Alzheimers' disease.

In 498 consecutive autopsy cases, the adrenal glands were light microscopically and morphometrically studied. 265 (53.7%) patients showed single or multiples nodules, 25 (5.0%) adenomas. The diameter of nodules was between 0.3 to 8.0 mm and that of adenomas between 3.2 to 28.0 mm. Clinically, 265 (36.5%) patients revealed arterial hypertension. 283 (63.5%) were normotensive. For the diagnosis of adenomas, the architecture and the cell structure were more important than the size of the tumor. Normotensive patients showed more often (55.%) nodules than hypertensive patients (52.8%). Adenomas were more frequently found in hypertensive patients. There was no correlation between age, sex and nodules, but adenomas were more frequently found in females. Normotensive patients exhibited mainly one nodule, whereas multiple nodules were found in hypertensive patients. In patients with nodules arteriosclerosis with intima hyalinosis was present in 184 (56.3%) cases, in patients without nodules in 81 (47.4%) cases. Our study clearly demonstrates that no correlation exists between the occurrence of adrenocortical nodules and age or hypertension. The etiology of adrenal nodules should be considered together with the arteriopathy.

The sudden infant death syndrome (SIDS) is at present based on unknown pathogenetical mechanisms but in industrial nations is the most common cause of death in infancy after the perinatal period. Studies of a large number of adrenal glands in this syndrome have not been reported. Therefore, we evaluated 146 SIDS cases (85 males, 61 females, aged 14-465 days) and 24 control cases (17 males, 7 females, aged 18-623 days) by light microscopy, morphometry and immunocytochemistry (anti-chromogranin A and anti-S100 protein). Our data revealed a normal maturation of the adrenal glands in SIDS cases. Necroses, extensive hemorrhages or inflammation were not found. A focal lipid depletion of the zona fasciculata was seen in 92% of the adrenal glands of the SIDS and control cases. We found a siderosis (in 33% of the SIDS cases and 4% of the control cases) and calcium deposits (13% and 12% respectively) due to hyperemic involution of the fetal zone. The medulla, including the sustentacular cells (S 100 protein-positive cells) and chromaffin cells (chromogranin A-positive cells) was unchanged. Our results indicate that the few morphological alterations of the adrenal glands in SIDS cases are the effect of the underlying disease and not the cause of the sudden death.

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A case of a feminizing adrenocortical tumor associated with Cushing's syndrome in a 29 year old male is presented. The ultrastructural features are compared with adrenal tumors secreting aldosterone, glucocorticoids or androgens. As in adrenal carcinomas, this tumor demonstrates nuclear pleomorphism with enlarged nucleoli and nuclear pseudoinclusions. The cytoplasmic organelles show some parallels between feminizing and androgensecreting adrenal tumors. Different types of mitochondria occur with varying amounts of smooth endoplasmic reticulum. Numerous microbodies are present. Histological and ultrastructural signs indicating probable malignancy are discussed and it is noted that most of the feminizing adrenal tumors are carcinomata. Neither local recurrence nor distant metastases have yet been detected in this case, two years after excision of the tumor. [ABSTRACT FROM AUTHOR]

The pituitary and adrenal glands are a functional endocrine unit affected by local or organ-limited senile amyloid syndromes. These occur as interstitial (pituitary only) or intracellular (pituitary and adrenal) varieties. The pituitary and right adrenal glands of each of 108 consecutive autopsy cases of individuals aged 85 years and over were investigated for the prevalence, distribution and immunostaining characteristics of local amyloid. Intracellular amyloid was detected in 77 (71%) pituitaries and 73 (68%) adrenals. Interstitial amyloid was found in 86 pituitaries (80%). Immunohistochemical studies, investigating different amyloid fibril proteins, amyloid P component, ubiquitin, intermediate filaments and pituitary hormones, failed to demonstrate any similarities, and a common origin is unlikely. Statistical analyses demonstrated significant correlations between the occurrences of all three local amyloids. The clinical and histopathological significance of local pituitary and adrenal amyloid remains obscure. The results suggested that the pathogenesis of the local senile amyloidoses of the pituitary and adrenals may be influenced by a common, still uncharacterized variable. It is not clear whether this variable also contributes to the pathogenesis of other senile amyloid syndromes, such as those associated with Alzheimers' disease. [ABSTRACT FROM AUTHOR]