Clinically inapparent adrenal masses are incidentally detected after imaging studies conducted for reasons other than the evaluation of the adrenal glands. They have frequently been referred to as adrenal incidentalomas. In preparation for a National Institutes of Health State-of-the-Science Conference on this topic, extensive literature research, including Medline, BIOSIS, and Embase between 1966 and July 2002, as well as references of published metaanalyses and selected review articles identified more than 5400 citations. Based on 699 articles that were retrieved for further examination, we provide a comprehensive update of the diagnostic and therapeutic approaches focusing on endocrine and radiological features as well as surgical options. In addition, we present recent developments in the discovery of tumor markers, endocrine testing for subclinical disease including autonomous glucocorticoid hypersecretion and silent pheochromocytoma, novel imaging techniques, and minimally invasive surgery. Based on the statements of the conference, the available literature, and ongoing studies, our aim is to provide practical recommendations for the management of this common entity and to highlight areas for future studies and research.

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The Clinically Inapparent Adrenal Mass: Update in Diagnosis and Management

Background. Adrenal cortical carcinoma is rare; the authors have treated only eight patients with the disease at Good Samaritan Regional Medical Center since 1974. No exhaustive collection of cases of this cancer has been done since 1952.



Methods. The authors retrospectively reviewed the medical records of their eight patients with adrenal cortical carcinoma. They also searched the English literature from 1952 to 1992 for reports of patients with the disease. They treated each report as a series if two or more previously unreported patients were reported. They paid special attention to patients for whom stage of disease was noted at diagnosis, treatment with mitotane (o,p'-DDD) was used, and the outcome was reported.



Results. Five were male and three were female patients. Five had nonfunctional tumors. None were pediatric. The authors found 1891 cases in the English literature. Adrenal cortical carcinomas are more common in women (58.6%) than in men (41.4%). The age distribution of tumors is bimodal, with peaks in the first and fifth decades. Tumors in children are more commonly functional (83.5% in female patients, 85.6% in male patients), although nonfunctional tumors are more common in older patients (84.7%). Most (68%) of these tumors are diagnosed late in disease when surgery is no longer curative. Only 35% of patients treated with mitotane had a clinical response.



Conclusions. Adrenal cortical carcinomas are diagnosed most often in children because of functionality and older men because of mass effect. Most tumors are discovered too late for curative resection. Treatment of metastatic disease with mitotane has limited success.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819931201%2972%3A11%3C3145%3A%3AAID-CNCR2820721105%3E3.0.CO%3B2-N

Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature

Solid-pseudopapillary tumor of the pancreas (SPT) has distinctive morphologic and biologic features but an unclear origin. It is classified among the pancreatic epithelial tumors, though many are reported to be negative for cytokeratin. Also unclear are its neuroendocrine differentiation, its capability to express alpha-1-antitrypsin (AAT) and, in view of the tumor's striking prevalence in women, its relationship with the female genital tract. To clarify these issues, the immunoprofiles of 59 SPTs were defined by applying a battery of antibodies against cytokeratin, vimentin, neuron-specific enolase (NSE), synaptophysin, chromogranin A, tyrosine hydroxylase (TH), AAT, LeuM1, Ki-M1P, smooth-muscle actin, CD34, alpha-inhibin, calretinin, placental alkaline phosphatase (PLAP), and progesterone and estrogen receptors. The most consistent markers with the strongest immunoreactivity were vimentin, AAT, NSE, and the progesterone receptor, which were each found in more than 90% of the tumors. Using immunocytochemical methods involving antigen retrieval, cytokeratin was demonstrated in almost 70% of the cases. Synaptophysin was found in 22% of the tumors, while chromogranin was absent and tyrosine hydroxylase was only present in a few tumors. None of the other markers tested were expressed by SPTs. This staining pattern fails to reveal a clear phenotypic relationship with any of the defined cell lineages of the pancreas. In view of the striking female preponderance of SPTs and the known close approximation of the genital ridges to the pancreatic anlage during embryogenesis, it is, however, hypothesized that SPTs might derive from genital ridge/ovarian anlage-related cells, which were attached to the pancreatic tissue during early embryogenesis.

Solid-pseudopapillary tumor of the pancreas: its origin revisited.

Background. Adrenocortical carcinoma is a rare tumor with a poor prognosis. This work was aimed at analyzing the clinical outlook and treatment results of 52 patients with this disease. Methods. This study included patients with adrenocortical carcinoma referred to the Department of Endocrinology at the Center of Postgraduate Medical Education (Warsaw, Poland) during the last 30 years. In 11 patients, the adrenal tumor was found incidentally by ultrasonographic scan. Hormonal examinations made it possible to define the endocrine activity of the tumors, whereas imaging techniques helped to determine their staging. Forty-eight patients underwent surgery, and 36 of them received mitotane. This drug was administered to 26 patients for a range of 10 months to 10 years ; 13 patients received mitotane immediately after the operation, and 13 others after a delay. The patients with severe hypercorticism were pretreated before surgery with aminoglutethimide and mitotane. Results. The study comprised 10 men and 42 women ; hormonally active tumors were diagnosed in 39 of them. Cushing's syndrome was the most frequent entity. At diagnosis, 17 cases were classified as localized disease,15 as regional disease, and 20 as distant disease. Pretreatment with the inhibitors of steroidogenesis improved the survival perspectives in the early postoperative period. As of this writing, there were 12 survivors in the group of 26 patients treated by surgery and long term mitotane therapy and only 2 survivors of 7 patients treated with surgery only. Conclusions. Surgery with immediate adjuvant long term mitotane administration was the most effective form of therapy for patients with adrenocortical carcinoma. Cancer 1995 ;75 :2587-91.

Adrenocortical carcinoma. A clinical study and treatment results of 52 patients.

Background. Adrenocortical carcinoma is a rare and aggressive disease with a poor prognosis. Adjuvant mitotane administration has been suggested as a strategy that might improve the outcome of patients with localized disease.



Methods. The authors analyzed the clinical outcome of patients with localized or regional adrenocortical cancer. The study included 19 patients who were registered at M. D. Anderson Cancer Center during a 3-year period and who had localized or regional disease at the time of surgery. Of these, eight patients received mitotane postoperatively and continued the drug until their last contact or recurrence (Group A, adjuvant); five patients began taking mitotane after surgery but discontinued it after 2–12 months for reasons unrelated to the disease (Group P, postoperative); and six patients did not receive mitotane (Group N, no mitotane). All patients have been followed for at least 12 months.



Results. The treatment groups differed significantly in their time to recurrence; the disease-free interval was shortest in Group A (P = 0.0055, by log-rank test). There was no statistical difference in survival among the groups, but the profile remained unfavorable for Group A. The 2-year survival rate was 100% for Groups N and P but only 43% for Group A. Of the potentially confounding factors, gender, age, steroid hypersecretion, and tumor size, none had any influence on recurrence or survival rates.



Conclusions. These findings do not support the conclusion that adjuvant mitotane is beneficial in patients with localized or regional adrenocortical cancer. Neither the disease-free interval nor survival was improved by the drug. The authors suggest that alternative therapeutic strategies be explored for the management of these patients.

M Miettinen

Papers

Neuroendocrine differentiation in adrenocortical carcinoma. New immunohistochemical findings supported by electron microscopy.