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.     

Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms

We analyzed a series of adrenocortical neoplasms to compare the clinicopathologic features and the expression of insulin-like growth factor-2 (IGF-2) in adrenocortical adenomas and carcinomas. IGF-2 is a growth factor commonly expressed in many tumors including adrenal cortical and medullary neoplasms. Formalin-fixed paraffin-embedded tissues from 64 adrenocortical adenomas and 67 adrenocortical carcinomas were analyzed. The carcinomas were histologically graded from 1 to 4 based on mitotic activity and necrosis. Tumor weight, size, and follow-up information were obtained by chart review. Expression of IGF-2 was detected by immunohistochemistry with the avidin-biotin-peroxidase complex method and a monoclonal antibody against IGF-2. Adrenocortical carcinomas were larger (mean: 13.1 cm, 787 g) than adenomas (mean: 4.2 cm, 52 g) (p<0.001). In patients with adrenocortical carcinomas, high tumor grade (3 or 4) (p=0.01) was associated with decreased survival. Expression of IGF-2 was higher in adrenocortical carcinomas than in adenomas (p<0.001). These results show that tumor size and weight along with expression of IGF-2 protein are useful features to assist in distinguishing between adrenocortical adenomas and carcinomas, and that high tumor grade is a predictor of survival in adrenocortical carcinomas. However, single immunohistochemical markers such as IGF-2 or single histopathologic features cannot by themselves separate adrenocortical adenomas from carcinomas, and a combination of clinical, gross, and microscopic features are needed to establish the diagnosis in difficult cases.     

Myxoid adrenal cortical neoplasms

Myxoid adrenal cortical neoplasms are rare, and to our knowledge, only about 23 cases have been reported in the literature, including 13 carcinomas and 10 adenomas. We recently experienced 4 cases of myxoid adrenal cortical neoplasms (3 benign and 1 borderline malignancy) and studied the clinical, histopathological, and immunohistochemical features of these neoplasms. There were 2 male and 2 female patients (age range, 37-61 years, mean, 48 years). All but 1 patient had hormone-related symptoms. The tumors weighed from 24.1 to 94 g (size, 4.1-9.8 cm). They were variably encapsulated with areas of hemorrhage. Histologically, the tumor cells were arranged in delicate arborizing cords or trabecula with myxoid areas varying from 30% to 70%. Three tumors were benign and 1 was of borderline morphology with mitoses of 3/10 high-power fields and mild to moderate nuclear pleomorphism. Two cases contained areas of myelolipomatous component. The tumor cells were positive for vimentin, synaptophysin, and inhibin but negative for cytokeratin. All patients are alive with no recurrence of their tumors or evidence of metastasis (follow-up of 14-20 months). Myxoid changes in adrenal cortical neoplasms are rare but can be seen in both an adenoma and a tumor of uncertain malignant potential. Because of prominent myxoid changes, other myxoid tumors occurring in the retroperitoneum should be excluded. The usual clinical and histological features can be applied to classify the lesions as benign, borderline tumor, or malignant. In our series, there was no case with frank malignant tumor.     

A103 immunostaining in the diagnosis of adrenal cortical tumors: an immunohistochemical study of 316 cases

CONTEXT: The monoclonal antibody A103 recognizes an antigen on melanoma cells known as Melan-A or MART-1. Recent studies have shown that A103 also reacts with adrenal cortical cells and may be useful in the diagnosis of adrenal cortical tumors. However, only small numbers of some of the tumors in the differential diagnosis of adrenal cortical neoplasms have been studied. OBJECTIVE: To study the specificity of A103 immunohistochemistry in a large number of tumors in the differential diagnosis of adrenal cortical neoplasms. DESIGN: Formalin-fixed, paraffin-embedded tissue from 21 adrenal cortical tumors, 16 cases of metastatic carcinoma to the adrenal, 10 pheochromocytomas, and 269 extra-adrenal carcinomas was evaluated for A103 immunoreactivity using a commercially available antibody (Novocastra, Newcastle, UK). RESULTS: Positive staining was seen in all of the adrenal cortical tumors but in none of the adrenal metastases or pheochromocytomas. In the 269 extra-adrenal carcinomas, A103 immunoreactivity was limited to a single ovarian serous carcinoma. CONCLUSION: A103 immunostaining is useful in distinguishing adrenal cortical neoplasms from other carcinomas and pheochromocytoma.     

Symptomatic Intraspinal Oncocytic Adrenocortical Adenoma

Most intraspinal neoplasms of epithelial origin are metastases from primary carcinomas. Benign epithelial tumors are rarely found at this site. We here present the case of a 44-year-old woman with a lesion in the cauda equina that fulfilled the radiologic criteria of schwannoma and caused clinical symptoms for 3 years. The excised tumor was composed of nests of large polygonal cells with eosinophilic partial granular cytoplasm. Significant atypia, necrosis, and mitosis were absent from this lesion. The tumor showed diffuse positivity for melan-A, synaptophysin, and alpha-inhibin. Steroidogenic factor 1 and cytokeratins 8 and 18 were focally seen in the absence of S-100 and chromogranin. This immunoprofile indicated adrenocortical origin. Ultrastructural examination showed abundant mitochondria, suggesting an oncocytic tumor. The diagnosis of an oncocytic adrenal cortical adenoma was made. These extraadrenal tumors are thought to arise from heterotopic adrenocortical tissue in the spinal cavity. Oncocytic tumors are rare neoplasms and they comprise non-functioning variants of adrenal cortical adenomas. To date, only five such intraspinal tumors have been observed. Immunohistochemistry excluded oncocytic paraganglioma, oncocytic meningioma, renal cell carcinoma, alveolar soft part sarcoma, and granular cell tumor. A view of the literature of these rare but probably underdiagnosed intraspinal tumors is given.     

Adrenal cortical neoplasia: from histology to molecular biology

Characterization of adrenal cortical proliferations requires integration of dynamic endocrine tests with imaging and histopathological characteristics. While pathologists are more frequently exposed to adrenalectomy specimens from patients with presumed adrenal cortical neoplasms, pre-operative biopsy specimens from non-functional adrenal lesions have also expanded the clinical tasks of pathologists. Confirmation of the adrenal cortical origin and distinction of benign cortical proliferations from adrenal cortical carcinomas are well-defined clinical responsibilities of pathologists. However, application of immunohistochemical and/or molecular biomarkers in adrenal cortical neoplasia and careful correlation of morphological features with laboratory findings and disease pathogenesis have evolved the impact of pathologist's role in the multidisciplinary team of endocrine disorders. This review provides an overview of what surgical pathologists need to know about the clinical, morphological, immunohistochemical and molecular features of various forms of adrenal cortical neoplasms (ACNs) in order to advance the clinical care.     

Adrenocortical carcinomas: a 12-year clinicopathologic study of 15 cases

Adrenal cortical carcinomas are rare neoplasms and the definitive diagnostic criteria are distant metastasis and / or local invasion. Due to advances in imaging techniques, adrenal cortical neoplasms are discovered earlier and are smaller, increasing the need for more accurate diagnosis and pathologic indicators of prognosis. A twelve year retrospective clinicopathologic analysis of 15 histopathologically proven cases of adrenocortical carcinomas was done. Clinical details including radiologic findings, endocrine manifestations and gross finding were analysed. Hematoxylin and eosin stained slides were reviewed. Emphasis was on application of Weiss criteria. All fifteen tumors fulfilled Weiss criteria of malignancy, ie. all 15 possessed 3 or more of these criteria of malignancy. Functional tumors showed a greater representation of mixed cell type. It was concluded that Weiss criteria is easy to apply and that a combined evaluation of clinical features, size, weight and microscopic appearance seems necessary for the diagnosis of adrenocortical carcinomas.     

Follicular thyroid neoplasm: clinicopathologic features suggesting malignancy

Thyroid follicular neoplasms are the most common tumors of the thyroid. The criterion for their malignancy is evidence of capsular or vascular invasion, which makes preoperative diagnosis difficult. The poorly differentiated thyroid carcinoma entity was introduced by World Health Organization in its 2004 classification with an incidence still poorly known. We found 356 follicular neoplasms treated between 1990 and 2006. Among these tumor patients, adenomas were more common in women than in men (3.6:1), but carcinomas differed little with respect to gender (1.2:1). All follicular carcinomas (n=39), atypical adenomas (n=6), and oxyphilic adenomas (n=15) were included in the study, as well as 30 consecutive conventional follicular adenomas. Five tumors were reclassified as poorly differentiated follicular thyroid carcinomas, representing 13% of carcinomas in this unselected material. Predictors of malignancy were high proliferation index (PI) by MIB-1 (p<0.001), large tumor size (p<0.001), and old age (p=0.006). High PI was also a marker of worse prognosis in malignant tumors. Oxyphilic tumor cells were more frequent in carcinomas than in adenomas; however, among carcinomas, they were non-prognostic. Probability for malignancy is thus greater in a male patient with a large oxyphilic follicular neoplasm. The PI requires evaluation in all follicular thyroid carcinomas to identify poorly differentiated tumors with worse prognosis.     

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.     

Aldosterone-Secreting Adrenal Cortical Carcinoma. A Case Report and Review of the Literature

Adrenal cortical carcinomas (ACC) are rare, typically aggressive malignant neoplasms with a reported incidence of 1–2 cases per 1 million population and account for 0.05–0.2 % of all malignancies. The majority of these tumors are functional with approximately 60 % of patients experiencing endocrine symptomatology typically characterized by Cushing’s syndrome (40 %) or a mixed hormonal picture of Cushing syndrome seen in association with virilization. Rarely, patients present with a pure hormonal syndrome of feminization or hyperaldosteronism, 6 and 2.5 %, respectively. We report a case of a 76-year-old woman presenting with recently diagnosed hypertension secondary to primary hyperaldosteronism. The patient underwent laparoscopic converted to an open adrenalectomy and a diagnosis of adrenocortical carcinoma (aldosteronoma clinical) was rendered. This case and review of the literature highlight that while rare, aldosterone-secreting adrenal cortical carcinomas may occur. In this case report, we discuss the clinical presentation, pathologic findings, and review the literature for adrenal cortical carcinomas and aldosterone-secreting adrenal cortical carcinomas.     

N-cadherin expression in adrenal tumors: upregulation in malignant pheochromocytoma and downregulation in adrenocortical carcinoma

Cell adhesion molecules (CAMs) are important regulators of tumor growth. The aim of the present study was to evaluate the expression pattern of CAMs in adrenal tumors regarding origin (cortex vs medulla) and biologic behavior (benign vs malignant). Eighty-seven adrenal tumors were investigated by immunocytochemistry (ICC) using monoclonal antibodies against N-cadherin (NCAD), E-cadherin (ECAD), neural cell adhesion molecule (NCAM), and CD44. Western blotting was performed on 30 tumors using the same antibodies. Markers for proliferation (Ki-67) and catecholamine synthesis (tyrosine hydroxylase) were also analyzed in tumors by ICC. NCAD was expressed in 12/27 benign pheochromocytomas (BPCs) (12 familial cases), 8/8 malignant pheochromocytomas (MPCs), 28/30 adrenocortical adenomas, and 9/22 adrenocortical carcinomas. ECAD was expressed in 0/27 BPCs, 0/8 MPCs, 0/30 adrenocortical adenomas, and 2/22 adrenocortical carcinomas. NCAM was expressed in 26/27 BPCs, 7/8 MPCs, 21/30 adrenocrotical adenomas, and 17/22 adrenocortical carcinomas. CD44 was expressed in 23/27 BPCs, 6/8 MPCs, 7/30 adrenocortical adenomas, and 4/22 adrenocortical carcinomas. Both cortical and medullary adrenal tumors expressed NCAD, NCAM, and CD44 but were devoid of ECAD. The expression of CD44 and NCAM did not correlate with the malignant potential of tumors. NCAD was upregulated in MPCs, but downregulated in adrenocortical carcinoma. Thus, NCAD appears to be involved in the development of both cortical and medullary adrenal tumors.     

High diagnostic accuracy of adrenal core biopsy: results of the German and Austrian adrenal network multicenter trial in 220 consecutive patients

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.     

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.     

Primary epithelial neoplasms and other epithelial lesions of the appendix (excluding carcinoid tumors)

Epithelial tumors of the appendix range from low-grade mucosal-based tumors which, when confined to the appendix, have an excellent prognosis but, once outside the appendix, have a fair prognosis and often a prolonged disease course, to high grade invasive carcinomas that are rapidly fatal. Low grade mucinous neoplasms may rupture and spread to the peritoneum as pseudomyxoma peritonei, and the nomenclature of these tumors has been the subject of considerable disagreement among pathologists; the designation "low grade appendiceal mucinous neoplasm" has recently been proposed for reasons discussed herein. Demonstrating rupture of these neoplasms may require particularly diligent gross and microscopic evaluation as the rupture site often heals over leaving only subtle evidence of its presence. Invasive adenocarcinomas are often mucinous and may also spread to the peritoneum. Against this backdrop, the clinical and pathologic features of low grade appendiceal mucinous neoplasms and mucinous adenocarcinomas, as well as other types such as typical colorectal type and signet-ring cell type, are reviewed. In addition, emerging entities, serrated polyps and serrated adenomas, whose significance is only beginning to be understood, are considered. Retention cysts, hyperplastic polyps, and diffuse mucosal hyperplasia, although not necessarily neoplastic, are reviewed here as they may enter into the differential diagnosis of appendiceal mucinous neoplasms.     

Renal tumors exhibiting granular cytoplasm.

Renal epithelial neoplasms consist of a group of distinct genetic and clinical entities that occasionally have overlapping morphological features. Pronounced cytoplasmic granularity or eosinophilia may be seen in a number of tumor types, including conventional (clear-cell) carcinomas, papillary carcinomas, chromphobe carcinoma, collecting duct carcinomas, and oncocytomas. Mesenchymal neoplasms such as angiomyolipomas as well as metastatic lesions such as malignant melanoma may have marked epithelial features and cytoplasmic granularity, thus mimicking a renal epithelial tumor. The same can be said for adrenal cortical neoplasms, which sometimes may be confused clinically, radiographically, and pathologically with a renal neoplasm. Close attention to morphological and cytologic detail will solve the differential diagnosis in the majority of cases, although some will require ancillary studies such as histochemistry, immunohistochemistry, and election microscopy. In a small percentage of cases molecular genetic studies are required to properly classify the tumor.     

Frequent chromosomal DNA unbalance in thyroid oncocytic (Hürthle cell) neoplasms detected by comparative genomic hybridization.

Thyroid oncocytic (Hürthle cell) neoplasms represent a distinct subset of follicular thyroid tumors characterized by abnormal accumulation of mitochondria, whose chromosomal abnormalities have never been systematically analyzed. We have used comparative genomic hybridization to investigate chromosomal DNA alterations in 11 thyroid oncocytic tumors (7 adenomas and 4 carcinomas). Unbalanced chromosomal DNA profiles were detected in 6 of 7 adenomas and 3 of 4 carcinomas, numerical chromosomal aberrations being the dominant feature. Comparative genomic hybridization findings are compatible with two separate groups of tumors with karyotypic abnormalities, one characterized by multiple chromosomal gains with polysomy of chromosomes 5 and 7, the other by loss of chromosome 2. Pathologic and clinical features were similar in the two groups with no difference observed between adenomas and carcinomas. Activating H-, K-, or N-Ras mutations are commonly detected in follicular adenomas and carcinomas of the thyroid gland. However, Ras mutational analysis demonstrated that only one of the tumors in this series, an oncocytic carcinoma with a balanced karyotype, had activating Ras mutations (at codon 13 of K-Ras). The lack of Ras mutations in the 9 oncocytic neoplasms exhibiting chromosomal aneuploidy indicates that numerical chromosomal abnormalities are independent of activating Ras mutations in oncocytic tumors.     

结直肠癌、结直肠腺瘤微卫星不稳定性检测及其临床意义

目的 探讨微卫星不稳定性（ＭＳＩ）在结直肠癌发生中的意义及其与结直肠癌细胞增殖活性和预后的关系,方法 采用聚合酶链反应－简单序列长度多态性（ＰＣＲ－ＳＳＬＰ）及免疫组化ＳＰ方法,对５６例结直肠癌,９例腺瘤及６例腺瘤癌变的ＭＳＩ和增殖细胞核抗原（ＰＣＮＡ）表达进行了检测。结果 显示结直肠癌ＭＳＩ总阳性率为４４．６４％（２５／５６例）,共中遗传性非息肉病性结直肠癌３／４例阳性,散发性结直肠癌２２／５２     

Immunodetection of Insulin-Like Growth Factor I (IGF-l) in Normal and Pathological Adrenocortical Tissue

IGF-I is one of the peptides that participates in normal adrenocortical cell growth and, possibly, in the genesis and/or maintenance of tumors and hyperplasias of the adrenal cortex. An immunohistochemical technique was used for the analysis of IGF-I expression in eight control and four hyperplastic adrenals, 11 adrenal cortical adenomas, and 18 adrenal corticalcarcinomas. A large number of IGF-I positive cells with granular cytoplasmic (GC) staining pattern was found in the reticularis layer of control adrenal tissues. Fifty percent of the hyperplasias had the GC pattern and the other 50% a mixed pattern; in 64% of the tumors, the adenomas showed a LM (linear membrane) pattern, while adenocarcinomas usually showed a GC pattern (94%). Approximately 75% of the hyperplasias had between 10 and 50% of IGF-I positive cells, while adenomas and carcinomas had over 50% of IGF-I positive cells in 64% and 83% of the samples, respectively. The size of the tumors with 50% positive cells, compared with those with less than 50%, was, on average, greater, but no statistical differences between cell positivity and corresponding clinical syndrome were observed. Thus, detection of IGF-I in control and pathological adrenal tissue suggests participation of this growth factor in cell function and/or growth and proliferation.     

Immunocytochemical differential diagnosis of adrenocortical neoplasms using the monoclonal antibody D11

Summary The monoclonal antibody D11 is a valuable aid in the accurate typing of adrenal tumours as, in formalin-fixed, paraffin-embedding material, strong nuclear D11 positivity was observed only in adrenocortical cells in 190 neoplasms (including 100 adrenal tumours). This pattern was demonstrated for all zona glomerulosa cells in 27 normal adrenals and for the neoplastic cells of 15 adrenocortical adenomas derived from that zone, as judged from clinically evident hyperaldosteronism. Normal cells of zona fasciculata and reticularis also showed strong diffuse D11 immunostaining and the same nuclear plus cytoplasmic D11 reactivity was evident in 15 benign and malignant adrenocortical neoplasms derived from these zones, documented by hypercortisolism. Cytoplasmic and/or nuclear D11 staining made topohistogenetic typing possible in 15 non-functioning cortical tumours. D11 immunostaining gave negative results in 50 specimens containing normal, hyperplastic and neoplastic adrenomedullary cells. In addition, absence of D11 reactivity was recorded in 4 adrenal metastases of extra-adrenal carcinomas, 5 paragangliomas, 25 primary renal carcinomas and 59 of 60 primary thyroid carcinomas. D11 immunocytochemistry allows the accurate typing of benign and malignant adrenocortical neoplasms, irrespective of histology and function. With this method, primary adrenocortical tumours can be separated from carcinomas metastatic to the adrenal gland, including secondary tumours of similar phenotype (such as renal carcinomas). By exclusion, D11 negativity provides evidence of the medullary origin of primary adrenal tumours even in the absence of clinical, structural, histochemical and conventional immunohistochemical indicators of phaeochromocytoma. Dedicated to Prof. Dr. Dr. h.c. mult. Wilhelm Doerr on the occasion of his 75th birthday. This study has been sponsored by the Deutsche Forschungsgemeinschaft and the Hamburger Krebsgesellschaft and was presented in part at the 80th Annual Meeting of the American Association for Cancer Research, San Francisco, California, 24–27 May 1989 (Schr?der et al. 1989)