Primary Adrenocortical Carcinoma Research Articles

Differential diagnosis of incidentally detected adrenal masses revealed on routine abdominal CT

Purpose The aim of this study was to compare CT findings of adrenal incidentalomas with a definitive histological diagnosis in order to establish CT features characteristic for individual types of lesions. Patients and methods The retrospective study comprised of patients with adrenal lesions detected on abdominal CT. The patients with these incidental findings subsequently underwent adrenalectomy. The adrenalectomy was followed by a histological assessment of the expansion process. The study consisted of 62 adrenal expansions found in 55 patients (in seven patients bilateral lesions were found). According to the definitive histological diagnosis after adrenalectomy, the lesions were divided into the following six groups: primary adrenocortical carcinoma ( n = 4), metastasis ( n = 7), adrenocortical adenoma ( n = 37), pheochromocytoma ( n = 9), myelolipoma ( n = 2), and others ( n = 3). CT observations were categorized as follows: size, shape, margins, density, side of the expansion, homogeneous or heterogeneous density before and after contrast application, presence of central hypodensity, presence of central calcifications and fat deposits. Statistical analysis was carried out using the χ 2-test, Kruskal–Wallis test and Mann–Whitney test. To estimate the differences between the subgroups, the t-test was used. For the evaluation of the mutual relations of maximum size, mean size, and volume, regression analysis (coefficient of determination R 2) was used. Results The correlation and regression analysis suggest that there will be no statistically significant error if the maximum size measurements are used instead of the mean size or volume measurements of the lesion. Sensitivity, specificity, accuracy, positive predictive value, negative predictive value for distinguishing adenomas and non-adenomas using a cut-off diameter of 41.5 mm were 81.1%, 70.0%, 77.2%, 83.3%, 66.7%, respectively; using the non-contrast density threshold of 23 HU, they were 89.2%, 100%, 93%, 100%, 83.3%, respectively; using the post-contrast density threshold of 47.5 HU, they were 80.6%, 100%, 88.2%, 100%, 76.9%, respectively; using the increase of density threshold of 34.5 HU, they were 74.2%, 70.0%, 72.5%, 79.3%, 63.6%, respectively. A study of receiver operating characteristics (ROC) analyses resulted in the following conclusions: (a) the most accurate parameter for distinguishing adenomas from non-adenomas is the value of non-contrast density, (b) the second most accurate parameter is the post-contrast density, (c) the least suitable parameters are the size of the lesion and increase of density, (d) therefore, in practice, the value of non-contrast density parameter should be used. Conclusion Standard CT of the abdomen (not specifically aimed at adrenal glands) is a suitable method for distinguishing adrenal lesions which need to be operated on from those which are probably benign but need to be monitored.

Bilateral Primary Adrenal Non-Hodgkin's Lymphoma and Primary Adrenocortical Carcinoma - Review of the Literature Preoperative Differentiation of Adrenal Tumors

Most of the adrenal tumors that are incidentally detected are benign adenomas. The incidence of malignant adrenal tumors including adrenocortical carcinoma (ACC) and primary adrenal lymphoma (PAL) is rather low. As many patients with ACC and PAL are diagnosed at an advanced stage of disease, the overall survival time of both entities remains poor. The therapeutic strategies for both entities differ. Thus an early differentiation between ACC and PAL is necessary. Unfortunately hitherto preoperative diagnosis of potentially malignant adrenal masses is still a main problem in the treatment of adrenal tumors. We present the case of a 57-year-old male patient with ACC and the case of an 87-year-old male patient with PAL and provide a systematic comparison of the clinical and pathological features of both entities. In both cases clinical and radiological features resulted in an initially false diagnosis. Primary surgical therapy was performed in both patients. The patient with PAL died five months after initial surgery. The patient with ACC showed tumor progression with local and systemic recurrence despite adjuvant therapy with mitotane and additional surgical therapy. Prognosis of patients with ACC and PAL seems to be dependant on the ability to start accurate treatment without any time delay. We propose some guidelines for diagnosis and surgical management of adrenal tumors.

Current management of adrenal tumors

Adrenal tumors evoke considerable interest and diagnostic challenges. This rare group of tumors includes functional tumors with a gamut of clinical presentations, as well as adrenocortical carcinoma, with its advanced disease at presentation and dismal prognosis posing additional challenge. Increasing detection of incidentalomas adds further interest with the concomitant diagnostic and management dilemmas. Significant advances have been made in diagnostic imaging modalities for identifying malignancy risk in adrenal incidentalomas. Considerable progress has occurred in understanding adrenocortical carcinoma pathogenesis from the study of genetics at the germline level in familial carcinomas, as well as at the somatic level by analyzing molecular alterations in sporadic tumors; this research supplies opportunities to develop novel therapeutic agents against a tumor with poor prognosis. Laparoscopic adrenalectomy has emerged as standard of care in the treatment of functional benign adenomas and nonfunctional tumors larger than 4 cm when adrenocortical carcinoma is not suspected. Open adrenalectomy with en-bloc excision has been the mainstay for primary and recurrent adrenocortical carcinoma due to the lack of effective adjuvant therapy. International consensus conferences have attempted to standardize diagnostic and treatment approaches in the management of adrenal tumors; further research is necessary.

Primary adrenocortical sarcomatoid carcinoma: case report and review of literature

Adrenocortical carcinoma (AC) mixed with a sarcoma or sarcoma-like component is exceptional, and only six cases have been detailed in the literature, three including osteo-, chondro-, or rhabdomyosarcoma components, and three others only showing a malignant spindle cell component. These histological subtypes, respectively called adrenal carcinosarcomas and sarcomatoid AC, represent poorly differentiated and extremely aggressive forms of carcinoma, with locoregional recurrence and metastases rapidly arising from the sarcomatous or sarcomatoid component, and death occurring in a few months. We report a case of AC in a 31-year-old man presenting as a nonfunctional tumor, with a histological biphasic pattern combining few areas of differentiated AC and extensive areas of sarcomatoid spindle cell proliferation. The patient died 3 months of locoregional and distant recurrences after surgery despite apparently total tumor resection and VP16-cisplatinum chemotherapy. This case underlines the necessity to identify and isolate these carcinoma's subtypes with worse prognosis and the difficulties to distinguish them from metastatic carcinomas and retroperitoneal sarcomas, in relation to the particular adrenal cortex immunoprofile. According to the World Health Organization principles of terminology, we suggest these tumors be collectively classified as "adrenal sarcomatoid carcinomas," a designation that tends to unify all carcinomas with "pleomorphic, sarcomatoid, or sarcomatous elements."

Spontaneous rupture of adrenocortical carcinoma

Massive hemorrhage from an adrenocortical carcinoma seldom occurs in the retroperitoneal or abdominal cavity. We report a case of spontaneous rupture of primary adrenocortical carcinoma occurring in an adolescent. A right adrenalectomy with complete removal of the tumor was performed successfully.

Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

Purpose To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1–4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9–48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival.

CT findings of primary adrenocortical carcinoma

目的 分析原发性肾上腺皮质腺癌(ACC)的CT表现及其动态增强特征,以提高其诊断准确性.方法 回顾性分析经手术病理证实的ACC11例,术前均经CT平扫、动脉期(30 s)和门静脉期(70～80 s)扫描,复习CT扫描表现并和手术病理作对照.结果 11例ACC中,右侧5例,左侧6例.直径4.1～16.0 cm,其中,＜5.0 cm者2例,5.0～10.0 cm者4例,＞10.0 cm 5例;肿瘤境界清楚3例,邻近脂肪间隙见条索状异常密度影3例,邻近实质脏器受侵犯5例.肿瘤实质成分平扫、动脉期和门静脉期CT值分别为21.9～46.7 HU(平均35.3 HU)、30.5～65.8 HU(平均47.1 HU)和52.6～97.0 HU(平均74.2 HU).肿瘤中央坏死形成假囊肿4例,网络状改变6例,实质为主伴小囊变1例;6例网络状改变者动脉期可见显著强化的不规则肿瘤血管.结论 ACC具有较明显的形态学和血液动力学特征,动态增强扫描尤其是动脉期扫描有明显的诊断价值。

Rare syndromes

Dermatologists may also encounter patients presenting with skin lesions that reflect an underlying endocrine disorder not commonly seen in daily practice. Some of these endocrine disorders include glucagonoma, neurofibromatosis type 1, McCune-Albright syndrome, multiple endocrine neoplasia, the Carney complex, carcinoid tumors, and mastocytosis. The clinical syndrome classically associated with glucagonoma includes necrolytic migratory erythema, weight loss, diabetes mellitus, anemia, cheilitis, venous thrombosis, and neuropsychiatric symptoms. The hallmarks of neurofibromatosis type 1 are the multiple café-au-lait spots and associated cutaneous neurofibromas. Other presenting features include freckling, peripheral neurofibromas, Lisch nodules, bone abnormalities, tumors, neurologic abnormalities and hypertension. McCune-Albright syndrome is characterized by café-au-lait spots, polyostotic fibrous dysplasia, sexual precocity, and hyperfunction of multiple endocrine glands. Multiple endocrine neoplasia type 2A is characterized by medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia. In some patients with multiple endocrine neoplasia type 2A, cutaneous lichen amyloidosis may also be present. Multiple endocrine neoplasia type 2B is characterized by medullary thyroid cancer and pheochromocytoma but not hyperparathyroidism. The syndrome also includes mucosal neuromas, typically involving the lips and tongue, intestinal ganglioneuromas and a marfanoid habitus. Multiple endocrine neoplasia type 1 is an autosomal dominant predisposition to tumors of the parathyroid glands (four-gland hyperplasia), anterior pituitary, and pancreatic islet cells; hence, the mnemonic device of the “3 Ps”; multiple cutaneous lesions (angiofibromas and collagenomas) are frequent in patients with multiple endocrine neoplasia type 1. Carney complex may be viewed as a form of multiple endocrine neoplasia because affected patients often have tumors of two or more endocrine glands, including primary pigmented nodular adrenocortical disease (some with Cushing's syndrome), pituitary adenoma, testicular neoplasms, thyroid adenoma or carcinoma, and ovarian cysts. Additional unusual manifestations include psammomatous melanotic schwannoma, breast ductal adenoma, and a rare bone tumor, osteochondromyxoma. Carcinoid syndrome is the term applied to a constellation of symptoms mediated by various humoral factors elaborated by some carcinoid tumors; the major manifestations are diarrhea, flushing, bronchospasm, and cardiac valvular lesions. Mast cell diseases include all disorders of mast cell proliferation. These diseases can be limited to the skin, referred to as “cutaneous mastocytosis,” or involve extracutaneous tissues, called “systemic mastocytosis.” Patients present with urticaria pigmentosa, mastocytoma, or diffuse cutaneous mastocytosis. Systemic involvement may be gastronintestinal, hematologic, neurologic, and skeletal.

Primary adrenocortical carcinoma: A retrospective review of The Cleveland Clinic Foundation experience between 1995 to 2002

18614 Background: Primary adrenocortical carcinoma (PAC) is a rare disease with a incidence of 1 per million. PAC’s are highly malignant tumors with guarded prognosis. Radical surgery is the treatment of choice. Methods: The pathology database and medical charts of these patients were retrospectively reviewed. Results: There were 14 females, 8 males, and 95% were caucasion. The mean age was 49.2 ± 11.8 years (females 51.6 years, males 45 years). The mean size of the tumor was 12.6 ± 5.1 cm (range of 3.6 to 25 cm). Thirteen patients (59.1%) presented with left and nine (40.9%) with right sided PAC. Seventy- two percent of the patients had abdominal, back, and/or flank pain. Forty five percent of patients had symptoms related to hypercortisolism and/or hyperandrogenism. Twelve patients (55%) had functional tumors (hypercortisolism 67%, hyperandrogenism 42%, and DHEA-S hypersecretion 42%) and ten were non-functional. Five percent of the tumors were classified as stage I, 33% were stage II, 38% were stage III, and 24% were stage IV. Twelve patients (55%) had distant metastases (liver 75%, lung 67%, retroperitoneum 33%, kidney 17%, contra-lateral adrenal gland 17%). All 22 patients had adrenalectomies (open 91%; laparoscopic 9%). The microscopic margin of resection were negative in 14 and positive in 6 patients. The information for 18 patients were evaluable for treatment. Eight patients received post-op therapy. Four patients received Mitotane (o,p’-DDD) alone (three died at 2, 29, and 213 months; and one is alive at 38 months after diagnosis). Three patients received both Mitotane and chemotherapy (two died at 3 and 43 months, one is alive at 140 months). One patient received only chemotherapy and died at 8 months. Ten patients received no post-op therapy. The estimated 5-year survival for the entire group was 48% (Kaplan-Meier survival estimate, 95% confidence interval). The estimated 5-year survival for stage III was 33%, and for stage IV was 30%. There were no deaths in patients with stage II group. The estimated 5-year survival for the treated group (8 patients) was 33% and 58% for the untreated group (10 patients). Conclusions: In PACs, surgery remains the main method of therapy. In our experience, Mitotane with or without chemotherapy did not improve survival. No significant financial relationships to disclose.

A Case of Non-Functioning Huge Adrenocortical Carcinoma Extending Into Inferior Vena Cava and Right Atrium

Primary adrenocortical carcinoma (ACC) is a rare tumor and its usual sites of metastasis are the lung (71%), lymph node (68%), liver (42%), and bone (26%). However, intracaval invasion extending into the right atrium is very rare and spontaneous regression of tumor burden in adrenal carcinoma is also rare. We report a case of ACC with direct invasion of the inferior vena cava and right atrium. A 34-yr-old male patient presented with progressive dyspnea, weight loss, and poor oral intake over 3 months. Non-functioning ACC with direct invasion of the inferior vena cava and right atrium was confirmed by imaging, pathologic, and hormonal study. Chemo-radio-therapy was attempted. However, tumor burden was not changed, but rather toxic hepatitis and thrombocytopenia were developed. His subjective symptoms and general conditions were improved after 1 month of conservative management and the patient was discharged. During clinical follow-up, this tumor showed spontaneous regression.

Radiofrequency ablation: other abdominal organs

Primary adrenal malignancy is uncommon and usually presents at an advanced stage. With the exception of pheochromocytoma, adrenal cancers rarely secrete hormones. Advanced adrenal tumors often invade several anatomic compartments, and even radical surgery is usually palliative. For tumors confined to the adrenal gland, laparoscopic surgery provides a minimally invasive approach. A 5-year survival rate of 40% has been reported after complete surgical resection of primary adrenocortical carcinoma, with a 70% 5-year rate survival for stages I and II [1–4]. There are only a few reports of RF ablation of pheochromocytomas being performed under aand bblockade. It is difficult to identify any clinical grounds for radiofrequency ablation (RFA) of primary adrenal cancer except unfitness for surgery [5]. Adrenal metastases are common and usually indicate widespread systemic disease; however, in non–small cell lung cancer and colorectal cancer isolated adrenal metastases that merit treatment can occur. The surgical literature contains many studies that have indicated reasonable outcomes after resection of selected adrenal metastases. However, laparoscopic adrenal resection is time consuming and costly, and the ideal case for the laparoscopic approach could also be easily ablated with RFA [6–9]. RFA of the adrenal gland

Squamous cell carcinoma–related oncogene is highly expressed in developing, normal, and adenomatous adrenal tissue but not in aggressive adrenocortical carcinomas

Our previous work has demonstrated squamous cell carcinoma-related oncogene (SCCRO) expression in adult murine adrenocortical tissue. The aim of this study was to assess patterns of SCCRO expression in the embryonic murine adrenal gland, and in normal and neoplastic human adrenocortical tissues in order to determine its role as a marker of differentiation in adrenocortical development and neoplastic progression. Murine embryos were procured at developmental stages E8 to E18. A tissue microarray was constructed containing 38 normal, 39 adenomatous, and 87 carcinomatous human adrenocortical specimens. Immunohistochemistry for SCCRO was performed and its expression was graded in suitable tissues. SCCRO expression was detected in the murine adrenal cortex as early as E15 and persisted into the postnatal period. High-level SCCRO expression was identified in 94% of normal (32/34) and adenomatous (29/31) adrenocortical specimens but in only 63% (45/72) of adrenocortical carcinoma (ACC) specimens ( P = .001). Loss of SCCRO expression in primary ACC (13/34 (34%)) correlated with advanced stage ( P = .06), presence of M1 disease at presentation ( P = .03), and worse overall survival ( P = .006). SCCRO appears to be a marker of adrenocortical differentiation in both murine and human systems. SCCRO expression may be useful in distinguishing adrenocortical adenomas from ACC. Moreover, loss of SCCRO expression in primary ACC is associated with worse outcome and may be a marker of progressive dedifferentiation in these tumors.

Clinical and molecular aspects of adrenocortical tumourigenesis.

Adrenal masses are a common problem affecting 3-7% of the population. The majority turn out to be benign adrenocortical adenomas, which may be functional or non-functional. Much more rarely, these masses represent a primary adrenal carcinoma. It is becoming increasingly recognized that of the benign functioning adenomas or hyperplasias, the majority will hypersecrete aldosterone and this will be more frequently detected when hypertensive populations are screened for this disease. In contrast, the incidence of primary adrenocortical carcinoma has remained steady and for this disease, surgery represents the mainstay of treatment. The advent of laparoscopic adrenal surgery has lowered the threshold size for recommending surgery for asymptomatic adrenal masses and as such, an increased proportion of adrenocortical cancers are being resected and detected at an earlier stage. Recent progress has been made in our understanding of the key genetic changes which underpin the biology of this disease. Progression from adrenal adenoma to carcinoma involves a monoclonal proliferation of cells which, among other defects, have undergone chromosomal duplication at the 11p15.5 locus leading to overexpression of the IGF2 gene and abrogation of expression of the CDKN1C and H19 genes. TP53 is involved in progression to carcinoma in a subset of patients and the frequency of ACTH receptor deletion needs to be more fully explored. Other key oncogenes and tumour suppressor genes remain to be identified although the chromosomal loci in which they lie can be identified at 17p, 1p, 2p16 and 11q13 for tumour suppressor genes and chromosomes 4, 5 and 12 for oncogenes.

Adrenocortical Carcinoma: Clinical, Morphologic, and Molecular Characterization

PURPOSE: To define multimolecular phenotypes of adrenocortical carcinoma (ACC) and to correlate outcome with morphologic and molecular parameters. PATIENTS AND METHODS: Clinical data were analyzed for 124 patients, histopathologic slides for 67 primary tumors, and tissue specimens for 74 patients (38 primary and 36 metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular expression profiles were investigated by immunohistochemistry. The prognostic significance of 12 gross and histologic parameters in 67 primary ACCs was evaluated. Morphologic and protein expression patterns were correlated with disease-specific survival (DSS). Univariate influence of prognostic factors on DSS was analyzed by log-rank test and multivariate analysis by Cox regression. RESULTS: The median follow-up period was 4.7 years. Significant predictors of DSS included distant metastasis at time of initial presentation; venous, capsular, and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic parameters was as follows: one to two, 84%; three to four, 37%; more than four, 9% (P = .005).The phenotype Ki-67(−)p53(−)mdm-2(+)cyclinD1(−)Bcl-2(−)p21(−)p27(+) was observed in 83% of normal and 3% of malignant adrenal tissue (P = .01). Molecular phenotypic expression was more heterogeneous in malignant than in normal (10 v five phenotypes) adrenal tissue. CONCLUSION: Meticulous morphologic evaluation, mitotic count, and tumor stage are essential in determining prognosis for patients with ACC. Multimolecular phenotyping demonstrates that the molecular complexity and heterogeneity of these neoplasms are such that targeted therapy needs to be patient specific.

Adrenocortical carcinoma: clinical, morphologic, and molecular characterization.

To define multimolecular phenotypes of adrenocortical carcinoma (ACC) and to correlate outcome with morphologic and molecular parameters. Clinical data were analyzed for 124 patients, histopathologic slides for 67 primary tumors, and tissue specimens for 74 patients (38 primary and 36 metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular expression profiles were investigated by immunohistochemistry. The prognostic significance of 12 gross and histologic parameters in 67 primary ACCs was evaluated. Morphologic and protein expression patterns were correlated with disease-specific survival (DSS). Univariate influence of prognostic factors on DSS was analyzed by log-rank test and multivariate analysis by Cox regression. The median follow-up period was 4.7 years. Significant predictors of DSS included distant metastasis at time of initial presentation; venous, capsular, and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic parameters was as follows: one to two, 84%; three to four, 37%; more than four, 9% (P =.005). The phenotype Ki-67(-)p53(-)mdm-2(+)cyclinD1(-)Bcl-2(-)p21(-)p27(+) was observed in 83% of normal and 3% of malignant adrenal tissue (P =.01). Molecular phenotypic expression was more heterogeneous in malignant than in normal (10 v five phenotypes) adrenal tissue. Meticulous morphologic evaluation, mitotic count, and tumor stage are essential in determining prognosis for patients with ACC. Multimolecular phenotyping demonstrates that the molecular complexity and heterogeneity of these neoplasms are such that targeted therapy needs to be patient specific.

RUPTURE OF ADRENAL CARCINOMA AFTER BIOPSY

No AccessJournal of UrologyCLINICAL UROLOGY: Case Reports1 Sep 2001RUPTURE OF ADRENAL CARCINOMA AFTER BIOPSY ABDUL HAFEEZ KARDAR ABDUL HAFEEZ KARDARABDUL HAFEEZ KARDAR More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)65881-8AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "RUPTURE OF ADRENAL CARCINOMA AFTER BIOPSY." The Journal of Urology, 166(3), p. 984 References 1 : The incidentally recovered adrenal mass. Ann Intern Med1983; 98: 940. Google Scholar 2 : Complications of percutaneous abdominal fine-needle biopsy. Review. Radiology1991; 178: 253. Crossref, Medline, Google Scholar 3 : Implantation metastasis of carcinoma after percutaneous fine-needle aspiration biopsy. Chest1992; 102: 313. Google Scholar From the Department of Urology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia© 2001 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byLIGUORI G, TROMBETTA C, KNEZ R, BUCCI S, BUSSANI R and BELGRANO E (2018) Spontaneous Rupture of Adrenal Carcinoma During the Puerperal PeriodJournal of Urology, VOL. 170, NO. 5, (1941-1941), Online publication date: 1-Nov-2003.O’KANE H, DUGGAN B, LENNON G and RUSSELL C (2018) Spontaneous Rupture of Adrenocortical CarcinomaJournal of Urology, VOL. 168, NO. 6, (2530-2530), Online publication date: 1-Dec-2002. Volume 166Issue 3September 2001Page: 984 Advertisement Copyright & Permissions© 2001 by American Urological Association, Inc.Keywordsbiopsyadrenal glandscarcinoma, adrenal corticalMetricsAuthor Information ABDUL HAFEEZ KARDAR More articles by this author Expand All Advertisement PDF downloadLoading ...

Molecular adrenocortical tumourigenesis.

Adrenocortical neoplasms are the most frequent abnormality of the adrenal cortex. Most of these lesions are clinically silent and are detected incidentally by ultrasound or computed tomography. The prevalence of these so-called 'incidentalomas' in the general population is around 1%, increasing with age and reaching 6% among those in the age range 60-70 years. In contrast, primary adrenocortical carcinoma, a highly malignant tumour, is rare, having an incidence of one case per million per year. Recent progress has been achieved in the understanding of adrenocortical tumourigenesis by mapping and identification of genes responsible for hereditary tumours that involve the adrenal gland. Investigation of the clonal composition of adrenal tumours demonstrates that adrenal carcinomas are monoclonal, whereas adrenal adenoma may be polyclonal in approximately 25-40% of cases. Oncogenes and tumour-suppressor genes involved in adrenal carcinomas include mutations in the p53 tumour-suppressor gene and rearrangements of the chromosomal locus 11p15.5 associated with IGF II hyperexpression. Constitutive activation of the ACTH receptor-G protein-cAMP signal cascade does not play a role in adrenal tumour formation. Conversely, deletions of the ACTH receptor gene have recently been found in undifferentiated adenomas and in aggressive adrenocortical carcinomas, and, more recently, confirmed in a larger series of tumours. The available literature indicates that the signalling pathways of adrenocortical tumours are different from those of other endocrine neoplasms, such as pituitary and thyroid adenomas.

Anti-?-inhibin

Anti-alpha-inhibin, an antibody directed against a peptide hormone, has been shown to be a useful diagnostic aid in surgical pathology material for the identification of sex cord-stromal neoplasms and recently has been described in adrenocortical carcinoma (ACC). The diagnosis of ACC versus renal cell carcinoma (RCC) may be difficult morphologically, particularly in fine-needle aspiration (FNA) material. To date, the immunohistochemical distinction of ACC from RCC is based on a panel of antibodies that include vimentin, cytokeratins, and epithelial membrane antigen. However, the reliability of this panel is weakened by inconsistent staining patterns. Archival formalin fixed, paraffin embedded cell block sections from 45 FNAs of known primary and metastatic ACC and RCC as well as benign adrenocortical nodules were stained with anti-alpha-inhibin using an avidin-biotin procedure. All samples were microwave pretreated and a biotin block was performed to reduce the background stain due to the high endogenous biotin often present in these types of samples. All cases of ACC (n = 7; 100%) and benign adrenocortical cells (n = 15; 100%) were immunoreactive with the a-inhibin antibody, showing a diffuse cytoplasmic and granular staining pattern. The staining intensity and number of immunoreactive cells varied within each sample, with the cases of ACC having the greatest proportion of immunoreactive cells and the strongest intensity. None of the cases of RCC (n = 23; 0%) were immunoreactive with anti-alpha-inhibin. The morphologic distinction of ACC versus RCC in FNA material from renal, adrenal, and metastatic neoplasms is not always feasible based on cytology alone. However, due to the advent of the alpha-inhibin antibody, the reliable distinction of these entities now may be possible. The intense and specific immunostaining pattern for cells of adrenal origin, even in paucicellular samples, suggests potential for the widespread clinical utility of this marker by cytopathologists.

Mutations in adrenocortical tumors.

Silent and incidentally detected adrenocortical neoplasms are the most frequent abnormality of the adrenal cortex. The prevalence of these lesions in the general population is around 1%, increases with age and reaches 6% in the seventh decade of life. Primary adrenocortical carcinoma, on the other hand, a highly malignant tumor, is rare with an incidence of 1.7 cases per million per year. Recent progress has been achieved in the understanding of adrenocortical tumorigenesis by mapping and identification of genes responsible for hereditary tumor syndromes like the Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex and the Multiple Endocrine Neoplasia Type I. Investigation of the clonal composition of adrenal tumors demonstrates that adrenal carcinomas are generally monoclonal, whereas adrenal adenoma may be polyclonal in approximately 25% of cases. These adenomas may have a multicellular origin under the putative action of extra-adrenal and local growth factors. Oncogenes and tumor suppressor genes involved in adrenal carcinomas include mutations in the p53 tumor suppressor gene and rearrangements of the chromosomal locus 11 p15.5 associated with IGF II hyperexpression. Constitutive activation of the ACTH receptor-G protein-cAMP signal cascade does not play a role in adrenal tumor formation. Conversely, deletions of the ACTH receptor gene have been recently found in undifferentiated adenomas and in aggressive adrenocortical carcinomas. This indicates that the signaling pathways responsible for adrenocortical tumor formation are different from that of other endocrine neoplasms like pituitary and thyroid adenomas.

Fortuitous Imaging of a Primary Adrenocortical Carcinoma With Tc-99m HDP

The importance of evaluating nonfunctional adrenal masses in the right clinical setting is discussed. A 60-year-old man was initially diagnosed of having a localized lung carcinoma. Metastatic work-up showed an adrenal mass that was not deemed to be related to the lung primary. Although biochemical testing revealed that the adrenal mass was nonfunctional, adrenal scintigraphy was not performed. On resection, the lung neoplasm was shown to be a poorly differentiated adenocarcinoma. Radiologic follow-up of the adrenal finding was recommended. A year later, the patient presented with an abdominal mass that was visualized by bone scintigraphy and, on resection, proved to be adrenocortical carcinoma. In retrospect, the lung mass was a metastasis of an adrenocortical carcinoma.