BCL-2 expression and inhibin-A in adrenal neoplasms: a comparative study

Differential diagnosis between adrenal cortical and adrenal medullary lesions may be difficult in many cases. Different immunohistochemical, histochemical tools as well as ultrastructural diagnostic techniques have been employed to aid in differentiating between these lesions. Recently, both inhibin-A and BCL-2 have been shown to stain selectively adrenal cortical tissue and its derived neoplasms but not adrenal medulla or pheochromocytomas. In this study we compared the staining reactions of inhibin-A and BCL-2 in cases of adrenal cortical adenomas and carcinomas as well as pheochromocytomas. We found that both inhibin-A and BCL-2 stained cortical derived tissues, but not medullary derived tissues. Staining intensity for inhibin-A was significantly weaker than for BCL-2. We found that fixation techniques may influence the staining reactivity, as some cases did not immunoreact with any of the antibodies. We conclude that both inhibin-A, and, preferentially, BCL-2 are useful additions to a staining protocol to help in the differential diagnosis of cortical and medullary neoplasms.     

应用组织芯片技术研究A103和inhibin α在肾上腺皮质肿瘤中的诊断价值

目的 研究肾上腺皮质肿瘤的免疫组织化学和临床病理特点及A103与inhibin α在其中的诊断价值并探讨组织芯片技术的可行性。方法 制备肾上腺皮质腺瘤(ACA)、肾上腺皮质癌(ACC)及嗜铬细胞瘤组织芯片各1个。肾上腺皮脂腺瘤芯片(79例),其中正常肾上腺皮质3例,胎儿肾上腺皮质2例,肾上腺皮质结节状增生2例,ACA72例;肾上腺皮质癌芯片(56例),其中ACC39例,肾上腺转移肿瘤17例(恶性黑色素瘤4例,转移癌13例);嗜铬细胞瘤芯片(44例)中含肾上腺髓质3例,嗜铬细胞瘤41例;20例正常成人肾上腺的常规石蜡组织作对照。用免疫组织化学EnVision法检测A103、inhibin α、calretinin、Ki-67等的表达情况。结果 A103阳性表达情况分别为正常肾上腺皮质100％(23／23),胎儿肾上腺皮质2／2,皮质增生2／2,ACA90．9％(60／66),ACC94．6％(3,5／37),肾上腺髓质及嗜铬细胞瘤阴性,转移肿瘤中除恶性黑色素瘤3／3阳性外其余均为阴性;inhibin α在正常肾上腺皮质、胎儿肾上腺皮质及皮质增生中100％表达,阳性部位主要在网状带与束状带内层,ACA阳性率75．8％(50／66),ACC75．7％(28／37),肾上腺髓质、嗜铬细胞瘤及转移肿瘤均为阴性。结论 组织芯片技术为快速原位检测提供了强有力的手段。应用组织芯片技术大规模高效检测组织样本是可行的。A103及inhibin α的联合应用对于明确肾上腺皮质肿瘤的诊断与鉴别诊断有较高价值。     

The role of calretinin, inhibin, melan-A, BCL-2, and C-kit in differentiating adrenal cortical and medullary tumors: an immunohistochemical study.

Morphologic distinction between adrenal cortical and medullary tumors can be difficult. Previous studies have shown inhibin, melan-A, and BCL-2 to be useful markers for adrenal cortical tumors. We have recently observed a high level of calretinin expression in normal adrenal cortex but not the medulla and therefore evaluated its diagnostic application for adrenal tumors in comparison with inhibin, melan-A, and BCL-2. C-kit is a transmembrane tyrosine kinase receptor. Immunodetection of c-kit expression has been recently used for tumor diagnosis, and c-kit-positive tumors can potentially benefit from kit kinase inhibitor treatment. Although c-kit expression was reported in adrenal medulla and pheochromocytoma, it has not been evaluated in adrenal cortical tumors. In this study, 28 adrenal cortical tumors (12 carcinomas, 16 adenomas), 20 pheochromocytomas, and 20 extraadrenal paragangliomas were evaluated for calretinin, inhibin, melan-A, BCL-2, and c-kit expression by standard immunohistochemical assays on paraffin sections. The percentage of immunoreactivity in adrenal cortical tumors was as follows: calretinin, 96%; melan-A, 89%; inhibin, 92%; BCL-2, 20%; and c-kit, 5%. Normal adrenal medulla did not stain for c-kit but was positive for BCL-2. Eighty-six percent of pheochromocytomas stained for BCL-2 and none for calretinin, with the exception of the ganglioneuromatous areas in composite pheochromocytomas (n = 5). Extraadrenal paragangliomas showed reactivity with calretinin in 25%, melan-A in 5%, inhibin in 16%, BCL-2 in 38%, and c-kit in 8% of the cases. Our results indicate that calretinin is the most sensitive among all the adrenal markers tested. Like melan-A and inhibin, calretinin is also a very specific marker in differentiating cortical from medullary adrenal tumors. In addition, calretinin can be used to confirm a composite pheochromocytoma. BCL-2 does not appear to be useful in differentiating adrenal cortical from medullary tumors. C-kit is not useful in the diagnosis of adrenal tumors, and kit kinase inhibitor might have a limited role in the treatment of adrenal tumors and paraganglioma because of the low frequency of c-kit expression in these tumors.     

DLK is a novel immunohistochemical marker for adrenal gland tumors

Delta-like protein (DLK) is expressed in fetal and adult adrenal glands. We have investigated if this expression is maintained in adrenal gland-derived tumors. All the studied 37 cortical tumors, including five carcinomas, stained positively as well as the 13 examined pheochromocytomas. Thus, DLK is a very sensitive marker for adrenal tumors of cortical and medullary origin. Renal cell carcinomas, presenting the major differential diagnostic problem for cortical tumors, were all negative, as well as melanomas, which are similar to high portion of adrenocortical tumors that react with melan-A. However, all paragangliomas, some carcinoids, and thyroid medullary carcinomas were also positive for DLK. Therefore, this novel immunohistochemical marker seems useful for the identification of adrenocortical tumors while it has limited value for the distinction of pheochromocytomas from diagnostically related neuroendocrine tumors.     

Immunofluorescence microscopic evaluation of the intermediate filament expression of the adrenal cortex and medulla and their tumors.

Normal adrenal glands (10 specimens) and adrenal gland tumors (58 cases) were immunohistochemically evaluated for different types of intermediate filament (IF) proteins. Some of the normal cortical cells showed cytokeratin positivity, and no positivity was seen for epidermal keratin or other types of IF. In the adrenal medulla, neurofilament positivity was seen in nerve axons, some ganglion cells, and chromaffin cells; and cytokeratin-positive cells could not be detected. Only the vascular and connective tissue elements showed vimentin positivity in both cortical and medullary areas. In half of the cortical carcinomas (13/25), cytokeratin-positive tumor cells were found. Furthermore, vimentin-positive tumor cells were present in 10 of 25 cases, in some of them together with cytokeratin-positive cells. Thus, the results show heterogeneity among the adrenal cortical carcinomas. Interestingly, many benign adrenal cortical tissues and some carcinomas lacked immunoreactivity for all types of IF, suggesting a poorly developed IF system in these tissues. In contrast to adrenal cortical tumors, pheochromocytomas contained neurofilamentlike immunoreactivity. These results reflect the different cellular nature of adrenal cortical and medullary tumors, which apparently can be distinguished from each other with antibodies to intermediate filament proteins.     

Galanin immunoreactivity in neuroendocrine tumors.

We investigated immunoreactivity for galanin, a 29-amino acid peptide, in formalin-fixed, paraffin-embedded sections of 123 neuroendocrine tumors. Galanin-immunoreactive cells were found in one of 12 hypothalamic gangliocytomas, nine of 18 adrenal pheochromocytomas, nine of 14 pituitary corticotroph adenomas, and one of two thymic endocrine tumors. In pheochromocytomas, galanin-immunoreactive cells were seen either singly or in clusters. In corticotroph adenomas, many tumor cells were positive for galanin, indicating colocalization of corticotropin and galanin in the same tumor cells. No galanin-immunoreactive cells were noted in four extra-adrenal paragangliomas; 10 medullary carcinomas of the thyroid; 35 endocrine tumors arising in the lung, pancreas, and gastrointestinal tract; and 28 pituitary adenomas composed of cells other than corticotrophs. In nontumorous counterparts of these neuroendocrine tumors, galanin immunoreactivity was observed in nerve cells of the hypothalamus, nerve fibers of the duodenum, and adenohypophyseal cells corresponding to corticotrophs. These findings indicate that galanin expression in neuroendocrine tumors is uncommon and restricted to some tumor types.     

Diagnostic utility of the monoclonal antibody A103 in fine-needle aspiration biopsies of the adrenal

Fine-needle aspiration (FNA) of the adrenal is a useful modality for the evaluation of primary and metastatic neoplasms. Until now, however, few reliable markers existed for the positive identification of adrenal cortical cells. Originally studied as a melanoma marker, Melan-A, as detected by the murine monoclonal antibody, A103, has gained recent attention as a marker for steroid-producing cells. Formalin-fixed, paraffin-embedded cell blocks from 24 adrenal FNA specimens were stained for cytokeratins (AE1/AE3) and Melan-A (A103). Seven of 8 cases containing normal, hyperplastic, and neoplastic adrenal cortical cells were positive for A103. Among 16 cases of metastatic carcinoma, tumor cells in 14 samples were positive for cytokeratins but negative for A103. The A103 monoclonal antibody is a sensitive marker for the identification of normal, hyperplastic, and neoplastic adrenal cortical cells in cell blocks of adrenal FNA specimens. With the exception of melanoma, A103 reactivity is restricted to adrenal cortical and other steroid-producing cells. A103 should be used routinely for the evaluation of FNA specimens of adrenal mass lesions.     

Immunohistochemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin.

AIMS: To investigate the immunohisto-chemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin. Also, to determine whether immunostaining with this antibody is useful in differentiating between adrenal cortical neoplasms and other tumours involving the adrenal gland that might mimic them. METHODS: Normal adrenal tissue (n = 20) and specimens from cases of adrenal hyperplasia (n = 13), adrenal cortical adenoma (n = 15), adrenal cortical carcinoma (n = 4), phaeochromocytoma (n = 8), and adrenal metastatic tumour (n = 7) were stained with a monoclonal antibody against the alpha subunit of human inhibin. RESULTS: Positive staining with the anti-alpha inhibin monoclonal antibody was seen in all normal adrenal glands. Immunoreactivity was largely confined to the inner cell layers of the adrenal cortex, with no staining of the adrenal medulla. All hyperplastic adrenal glands and adrenal cortical adenomas and carcinomas were also immunoreactive. The other tumours studied were negative. CONCLUSIONS: There is consistent immunoreactivity with the anti-alpha inhibin monoclonal antibody in normal adrenal cortex and in hyperplastic and neoplastic adrenal cortical lesions. In the normal adrenal cortex, positive staining is mainly confined to the zona reticularis. Other neoplasms involving the adrenal gland are negative. Immunohistochemical staining with anti-alpha inhibin monoclonal antibody, performed as part of a panel, may prove to be of value in the distinction between adrenal cortical carcinoma and phaeochromocytoma or metastatic tumour.     

Alpha-inhibin immunoreactivity in soft-tissue neoplasia.

Antibodies directed against alpha-inhibin have been previously reported as staining both sex cord-stromal neoplasms as well as adrenal cortical tumors. This relatively restricted immunoreactivity pattern is useful in the assessment of retroperitoneal masses, especially in a setting of limited tissue (e.g., needle biopsy). However, no study to date has evaluated alpha-inhibin immunoreactivity in soft-tissue neoplasms, which frequently enter the differential diagnosis of retroperitoneal masses. We investigate the incidence of alpha-inhibin staining in a variety of soft-tissue neoplasms by using formalin-fixed, paraffin-embedded tissue sections from 282 previously classified soft-tissue neoplasms with anti-alpha-inhibin (Serotec, 1:75). A modified avidin-biotin complex method was used after heat-induced epitope retrieval. Cytoplasmic granular staining was considered positive. Of the 282 tumors studied, a total of 8 (2.8%) demonstrated positive staining with anti-alpha-inhibin antibody. These included 4 of 25 liposarcomas (16%), 2 of 18 angiosarcomas (11%), 1 of 48 lipomas (2.1%), and 1 of 1 rhabdomyoma (100%). Negative staining was noted among hemangiomas (0/28), schwannomas (0/32), leiomyomas (0/16), fibrosarcomas (0/2), fibromas (0/11), dermatofibromas (0/9), neurofibromas (0/6), synovial sarcomas (0/15), rhabdomyosarcomas (0/10), Triton tumors (0/2), and malignant fibrous histiocytomas (0/59). We conclude that rare soft-tissue tumors, especially those exhibiting either lipomatous or vascular differentiation, demonstrate alpha-inhibin immunoreactivity. These findings re-emphasize the need for a well-construed antibody panel when immunohistochemical methods are employed in the evaluation of retroperitoneal neoplasms. However, the rarity of alpha-inhibin expression by soft-tissue neoplasms provides further support for its overall specificity as a marker of adrenal cortical differentiation in the biopsy evaluation of a retroperitoneal mass.     

Immunohistochemical demonstration of lacto-N-fucopentose III in lung carcinomas with monoclonal antibody 624A12

Bronchopulmonary carcinomas were analyzed immunohistochemically using monoclonal antibody 624A12. The antibody was raised against a human "small cell carcinoma" cell line NCI-H69. It recognizes a particular sugar sequence in lacto-N-fucopentose III, which is preserved in formalin fixed and paraffin embedded tissue. Various bronchopulmonary carcinomas revealed characteristic patterns of immunoreactivity. Forty nine/50 adenocarcinomas were immunoreactive either diffusely or focally. The immunostaining was usually limited to the cell membranes with occasional intracytoplasmic immunostaining in large cells. The only negative case had been irradiated before surgical resection. Twenty seven/38 squamous cells carcinomas did not immunostain while the remaining 11 displayed focal immunoreactivity in areas of "loose cellular apposition" associated with necrosis and, rarely, in squamous pearls. All of six adenosquamous carcinomas showed immunoreactivity focally. Eleven/30 large cell carcinomas and 10/11 bronchiolo-alveolar carcinomas were either diffusely or focally immunoreactive. Seven/26 intermediate cell neuroendocrine carcinomas were focally immunoreactive while none of 33 typical small cell neuroendocrine carcinomas, 21 carcinoids, and 10 well differentiated neuroendocrine carcinomas was immunoreactive. An adenoid cystic carcinoma was diffusely immunoreactive, and a mucoepidermoid carcinoma was focally immunoreactive. We conclude that various bronchopulmonary neoplasms have characteristic patterns of distribution of this antigen, and that monoclonal antibody 624A12 may be useful for the differential diagnose among bronchopulmonary carcinomas, and their differential diagnosis from pleural mesotheliomas.     

Histidine decarboxylase expression in pancreatic endocrine cells and related tumors

Histidine decarboxylase (HDC) is an enzyme for decarboxylating l-histidine to histamine and is expressed in various types of cells including neuroendocrine tumors. Recent findings have demonstrated a high percentage of HDC immunoreactivity in many neuroendocrine tumors, including carcinoid tumors, small cell carcinomas of the lung, pheochromocytomas, and medullary carcinomas of the thyroid. HDC immunostaining was applied to pancreatic islet cells and related tumors to explore possible expression of HDC as a wide spectrum marker for neuroendocrine differentiation. A total of 24 cases (22 pancreatic endocrine neoplasms, one small cell carcinoma of the pancreas, and one mixed exocrine-endocrine carcinoma) along with normal pancreatic tissue were immunostained with the anti-HDC antibody. In a normal pancreas, a double immunostaining revealed possible colocalization of HDC with glucagon- or insulin-positive cells in the islets. Seventeen of 22 pancreatic endocrine neoplasms (77%) were found to be positive for HDC, and no distinct relation to hormonal activity was observed. One small cell carcinoma was strongly positive to HDC. One non-functional tumor with mixed exocrine and endocrine components showed a diffuse positive immunostaining for HDC, and some neoplastic glucagon- or somatostatin (SRIF)-positive cells coexpressed HDC. In conclusion, we demonstrated that the majority of pancreatic endocrine tumors expressed HDC, and we suggest that HDC is a wider new marker for neuroendocrine differentiation.     

Vesicular monoamine transporter 2 as a marker of gastric enterochromaffin-like cell tumors

The vesicular monoamine transporter 2 (VMAT2) facilitates the ATP-dependent accumulation of biogenic amine inside the secretory granules of endocrine cells and neurons and was demonstrated in the histamine-producing enterochromaffin-like (ECL) cells of the stomach. In the present investigation, VMAT2 immunohistochemistry was tested in 85 endocrine tumors, of which 60 were well differentiated gastrointestinal and pancreatic growths, 5 poorly differentiated (neuro)endocrine carcinomas (PDEC) and 1 mixed PDEC/ECL cell carcinoma of the stomach, 12 pheochromocytomas/paragangliomas, 3 adrenocortical lesions, 2 parathyroid and 2 lung neuroendocrine tumors. Extensive and intense VMAT2 immunoreactivity was observed in 16 of 16 gastric ECL cell tumors, 6 of 6 adrenal pheochromocytomas, 2 of 2 chromaffin paragangliomas and in 3 of the 4 carotid body paragangliomas investigated. Rare VMAT2-positive cells were observed in 12 of 21 intestinal enterochromaffin (EC) cell tumors, in 9 of 11 pancreatic neuroendocrine tumors, and in the mixed PDEC/ ECL cell carcinoma of the stomach (differentiated cells only). No VMAT2 immunoreactivity was observed in five gastrin, four somatostatin and three enteroglucagon/peptideYY tumors of the gastrointestinal tract, in six gastric PDECs, in three adrenocortical growths, and two parathyroid and two lung neuroendocrine tumors. These data support VMAT2 immunohistochemistry as being a useful tool for the diagnosis of gastric ECL cell tumors, separating them from all other endocrine tumors arising in the gastroduodenal area i.e., gastrin, somatostatin, EC cell and PDEC tumors, all of which proved essentially negative. Received: 28 June 1999 / Accepted: 20 October 1999     

New developments in the pathologic diagnosis of adrenal cortical neoplasms. A review.

In the past decade, our knowledge of neoplasms arising in the adrenal cortex has been expanded greatly. Histologic criteria for distinguishing benign from malignant adrenal cortical neoplasms have been developed. In this review, three systems useful in making this distinction are reviewed and compared. Pathologic indicators of prognosis for adrenal cortical carcinomas have been proposed and these include mitotic rate, stage, surgical resectability, nuclear grade, and tumor size. Of these, mitotic rate appears to be the best indicator. Adrenal cortical carcinomas with a high mitotic rate behave most aggressively. The role of immunohistochemical and DNA content analysis in the diagnosis of adrenal cortical neoplasms is limited. Neoplastic adrenal cortical cells contain a low density of keratins that is often destroyed by routine fixation and paraffin embedding. Thus, the absence of keratins in adrenal cortical neoplasms, particularly carcinomas, in routinely processed tissue should not dissuade the pathologist from making the diagnosis of an epithelial neoplasm. DNA content analysis has revealed an imperfect correlation between DNA ploidy and histologic diagnosis. Some adrenal cortical adenomas contain aneuploid stem cell lines, whereas some adrenal cortical carcinomas have diploid DNA content. Molecular genetic analyses suggest that one or more tumor suppressor genes may be involved in the pathogenesis of adrenal cortical neoplasms.     

Three cases of adrenocortical tumors mistaken for hepatocellular carcinomas/diagnostic pitfalls and differential diagnosis

Adrenocortical adenomas and carcinomas in other parenchyma are extremely rare, with few cases reported and because of the rarity of these tumors, they occasionally cause problems during diagnosis. Adrenal cortical neoplasms in liver parenchyma can be present in 3 forms, including direct invasion or adhesion to liver parenchyma, tumors arising in adrenohepatic fusion tissue or in ectopic adrenal gland tissue. We report 3 cases of adrenal cortical tumors that were misdiagnosed as hepatocellular carcinoma in the preoperative state. The first case involved an adrenocortical adenoma arising in adrenohepatic fusion tissue. The remaining 2 cases involved an adrenocortical carcinoma and an adrenocortical oncocytoma arising in ectopic adrenal tissue in the liver. We describe the clinical presentations, gross, microscopic findings, immunohistochemical findings with respect to each case, with emphasis on differential diagnosis from hepatocellular carcinoma.     

An immunohistochemical study of pheochromocytomas

Twenty -six adrenal pheochromocytomas and four normal adrenal medullae were studied immunohistochemically. These included four malignant tumors with proven metastases, six tumors in patients with neurofibromatosis, nine tumors in patients with multiple endocrine neoplasia type 2, and seven sporadic nonfamilial pheochromocytomas. Immunohistochemical localization of neuron-specific enolase (NSE) was seen in all tumors and in the four normal adrenals. Methionine enkephalin-like immunoreactivity was present in tumors from all four groups and in the normal adrenals. Corticotropinlike immunoreactivity was found focally in two normal adrenal medullae and in four benign pheochromocytomas. Our results indicated that NSE was present in all four major groups of pheochromocytomas, including benign and malignant tumors. This marker aided in distinguishing between adrenal cortical and medullary tumors in unusually difficult cases, since all normal adrenal cortex and adrenal cortical tumors had negative test results for NSE.     

Update on adrenal cortical neoplasia

The adrenal cortex gives rise to a biologically heterogenous group of neoplasms, each with a distinct morphology, antigen expression and molecular profile. Adrenal cortical adenomas have excellent prognosis and are usually cured by surgical resection alone, while adrenal cortical carcinomas are very aggressive tumors with a poor prognosis regardless of therapy. These tumors are rare and often challenging for a pathologist to diagnose, as significant overlap exists between benign and malignant lesions in some cases. In this review, we attempt to summarize most important histologic and clinical features of adrenal cortical adenomas and carcinomas, clarify the use of different grading systems, the use of special stains and the differential diagnosis for practicing pathologists. Most relevant hereditary syndromes associated with adrenal cortical tumors are listed. Updates in molecular alterations in adrenal cortical neoplasms and hyperplastic diseases as well as their clinical significance and potential therapeutic implications are also discussed.     

Ultrastructure of Adrenal Cortical Carcinoma

The ultrastructural features of 30 adrenal cortical carcinomas have been reviewed and compared with those seen in adrenal cortical adenomas, adrenal cortical hyperplasia, and the normal cortex. A broad range of ultrastructural appearances was found among the carcinomas, but the differences were mainly in the amount of cytoplasmic lipid, number of lysosomes, and quantity and architecture of the mitochondria and endoplasmic reticulum. Structural variants among the carcinomas included lipid-rich, oncocytic, and glycogen-rich cells. Electron microscopy can be extremely useful in differential diagnoses that include adrenal cortical carcinoma.     

Ret protein expression in adrenal medullary hyperplasia and pheochromocytoma

Ret is a developmentally regulated tyrosine kinase involved in formation and maintenance of the nervous system. Ret mutations predisposing to pheochromocytomas and medullary thyroid carcinomas occur in multiple endocrine neoplasia (MEN) syndromes 2A and 2B. Biochemical studies have demonstrated overexpression of Ret mRNA and protein in pheochromocytomas compared to normal adrenal medulla. However, the cellular distribution of Ret in the normal human adrenal and in hyperplastic lesions that antecede pheochromocytomas are unclear. The present investigation was undertaken to resolve the histological distribution of Ret in the normal human adrenal, in pheochromocytomas evolving from adrenal medullary hyperplasia in MEN2A and in sporadic pheochromocytomas. Ret expression was studied by immunohistochemistry using both a polyclonal and a monoclonal antibody, with confirmation by immunoblotting of representative cases. Only occasional cells stained for Ret in the normal adrenal, consistent with the distribution in adult adrenals of other species. Heterogeneous, progressively increased Ret expression was observed during the evolution of pheochromocytomas. In both normal and neoplastic adrenal, the most intense immunoreactivity was observed in cells with neuron-like features. Our finding that Ret is not expressed at high levels in the early stages of disease suggests that elucidation of mechanisms that regulate Ret expression is required for understanding the pathobiology of MEN2A. The association of high-level Ret expression with neuronal morphology suggests that the variable overexpression of Ret in pheochromocytomas might in part be an epiphenomenon, reflecting the known phenotypic plasticity of these tumors.     

Immunoreactivity and receptor expression of insulinlike growth factor I and insulin in human adrenal tumors. An immunohistochemical study of 94 cases.

Using immunoperoxidase methods, 94 human adrenal tumors were examined for evidence of immunoreactivity and receptor expression of insulinlike growth factor I (IGF-I) and insulin. The frequency of IGF-I in adrenocortical carcinomas was significantly higher than that in adenomas of the adrenal glands. The adrenocortical carcinomas showed strong intensity of staining for IGF-I, IGF-I receptors, and insulin receptors. A significant correlation between immunoreactivity and receptor expression of both IGF-I and insulin was found only in the adrenocortical carcinomas. The adrenocortical adenomas with Cushing's syndrome and pheochromocytomas, more than adrenocortical adenomas with Conn's syndrome, also stained strongly for insulin receptors. Thus the IGF-I and insulin probably play a role in the growth of adrenocortical carcinoma tissues, possibly through autocrine mechanisms. The expression of insulin receptors in adrenocortical adenomas in the presence of Cushing's syndrome and pheochromocytomas may be associated with functions.     

肾上腺髓质内、外嗜铬细胞瘤181例与多发性内分泌肿瘤的临床病理资料分析

目的 分析肾上腺髓质内、外嗜铬细胞瘤与多发性内分泌肿瘤2型( MEN2)的发病变化,探讨它们在临床症状、体征、病理变化方面的异同点和相互关系.方法 运用游程检验、方差分析、t检验、x2检验,对天津医科大学总医院病理科1993-2008年181例肾上腺髓质内、外嗜铬细胞瘤(根据世界卫生组织《内分泌器官肿瘤病理学和遗传学2004年版》分别将其分为良性、恶性倾向、恶性病变3组)及伴MEN2的检出率、构成比、平均诊断年龄、性别比例及临床表现、病理变化进行统计学分析.结果 16年外检总数167 702例,肾上腺疾病、肾上腺髓质内、外嗜铬细胞瘤的例数(外检率)分别是910例(0.54％)、139例(0.08％)、42例(0.03％),其中嗜铬细胞瘤的良性、恶性倾向、恶性3组的例数(构成比)在肾上腺髓质内分别是102例(73.4％)、29例(20.9％)、8例(5.7％),102例良性病变中伴MEN2者共8例(7.8％);在肾上腺髓质外分别是18例(42.8％)、12例(28.6％)、12例(28.6％).16年间肾上腺疾病、肾上腺髓质内、外嗜铬细胞瘤及良性病变伴MEN2的检出率和构成比及嗜铬细胞瘤的良性、恶性倾向、恶性3组的构成比均无变化趋势(P＞0.05),并随病变恶性度的增加逐渐由女性多见转变为男性多见的发病规律.嗜铬细胞瘤患者总平均诊断年龄在髓质内良性组、恶性倾向组分别为42.7和40.1岁,均低于恶性组患者的51.6岁.髓质外良性组、恶性倾向组分别为43.1和45.2岁,均高于恶性组的37.8岁(P＜0.05).恶性病变患者中,髓质内的发病年龄(51.6岁)明显高于髓质外(37.8岁,P＜0.05);伴MEN2患者只见于患肾上腺髓质内良性嗜铬细胞瘤的女性,其平均诊断年龄(38.9岁)低于良性病变(42.7岁),而且甲状腺髓样癌的发生均早于肾上腺髓质内嗜铬细胞瘤.肾上腺髓质内、外嗜铬细胞瘤患者均显示恶性病变伴有高血压症状者的比例较良性、恶性倾向者明显下降(P＜0.05).仅肾上腺髓质内嗜铬细胞瘤发生双侧病变,其中恶性病变( 2/8)的发生率明显高于良性(15.7％)、恶性倾向(6.9％).复发病变在肾上腺髓质内、外嗜铬细胞瘤的比例均随良性(11.8％,0)、恶性倾向(13.8％,25％)、恶性(33.3％,37.5％)的病变恶性度的上升而逐渐增加.肾上腺髓质内、外嗜铬细胞瘤体积平均直径亦随良性(4.2、4.0 cm)、恶性倾向(5.3、5.6 cm)、恶性病变(7.3、6.9 cm)的恶性度上升而逐渐增大(P＜0.05).结论 肾上腺髓质内、外嗜铬细胞瘤良性、恶性倾向、恶性病变3组的临床表现与病理变化密切相关,确切的病变类型和肿瘤性质仍要由病理学检查确定.