[Myxoid variant of adrenocortical carcinoma]. / Carcinome corticosurrénalien variante myxoïde : aspects clinico-pathologiques et immunohistochimiques d'une variante rare et agressive.

We report two cases of patients presenting myxoid variant of adrenocortical carcinoma (ACC). This very rare variant is characterized by a tumoral proliferation organized in trabeculae, cords or even pseudo-glands within an acellular myxoid materiel stained by Alcian Blue and negative for PAS. Tumor cells have a small to medium size and have little atypia. Their immunohistochemical profil (positivity of Synaptophysin, SF1, Melan A, Vimentin and Inhibin, with a weak or negative pancytokeratin expression) eliminate the main differential diagnoses (metastasis of a myxoid adenocarcinoma and soft tissue myxoid tumor). Many scoring systems have been proposed in order to evaluate the risk of malignancy of these lesions: the Weiss score seems less efficient to evaluate malignancy in this variant than the reticulinic algorithm or the Helsinki score. Prognosis of myxoid variant of ACC seems worse than classical ACC.

Prognostic Value of Microscopic Tumor Necrosis in Adrenal Cortical Carcinoma.

Adrenal cortical carcinoma (ACC) is an uncommon neoplasm with variable prognosis. Several histologic criteria have been identified as predictors of malignancy in adrenal cortical tumors. The Weiss score is the system most widely employed for diagnostic purposes, but also possesses prognostic value. We aim to determine the relative impact of each Weiss parameter on ACC patient survival. A multicenter retrospective analysis was conducted on a series of 79 conventional ACCs surgically treated at the Florence and Utrecht centers of the European Network for the Study of Adrenal Tumors (ENSAT). Weiss classification was recapitulated using principal component analysis (PCA). The Kaplan-Meier and Cox multivariate regression analyses were applied in order to estimate the prognostic power of Weiss versus other clinical parameters. PCA reduced the nine Weiss parameters to the best fitting 4-component model, each parameter clustering with a single component. Necrosis and venous invasion clustered together with the highest scores, thus establishing the most relevant component (Component 1) to explain Weiss distribution variability. Only Component 1 significantly predicted overall survival (OS, log-rank = 0.008) and disease-free survival (DFS, log-rank < 0.001). When considering the prognostic power of Weiss parameters, necrosis alone could independently assess OS (log-rank = 0.004) and DFS (log-rank < 0.001) at both the Kaplan-Meier and multivariate Cox regression analyses [hazard ratio (HR) = 7.8, 95% confidence interval [CI] = 1.0-63.5, p = 0.05, and HR = 12.2, 95% CI = 1.6-95.0, p = 0.017, respectively]. The presence of necrosis significantly shortened time to survival (TtS) and time to recurrence (TtR), 57.5 [31.5-103.5] vs 34 [12-78] months (p = 0.05) and 57.5 [31.5-103.5] vs 7 [1.0-31.5] months (p < 0.001), respectively. Our study suggests that, of the Weiss parameters, necrosis is the most powerful adverse factor and the best predictor of OS and DFS in ACC patients.

Prognostic value of the Weiss and Wieneke (AFIP) scoring systems in pediatric ACC - a mini review.

Histopathological differentiation in pediatric adrenocortical carcinoma (pACC) is difficult and clinical prediction and stratification scores are not evaluated yet. Therefore, this review aims to summarize current evidence on the value and accuracy of the two commonly used scoring systems (Weiss/Armed Forces Institute of Pathology (AFIP)) pACC. On this base, one might be able to evaluate if patients may benefit from a unique scoring system. For this, we performed a systematic review of the published literature and included 128 patients in our analysis. The majority (72%) of the pACCs had a good clinical course. The follow-up time ranged from 0 to 420 months with a mean age of 5.6 years at diagnosis. Patients with a good clinical course were younger (mean 4.8 years) than patients with a poor outcome (mean 7.6 years). Comparing the two scoring systems, the specificity of the Weiss score was very low (25%), whereas the sensitivity was 100%. According to the AFIP score, specificity (77%) was higher than the Weiss score, whereas the sensitivity of the AFIP score was minimal lower with 92%. Age differences were recognizable as the specificity was lower in infants <4 years (20%) than in older children (32%). In contrast, the specificity of the AFIP score was higher in infants <4 years (82%) than in older age groups (76%). Summarizing our results, we could show that the Weiss score is not a suitable tool for the prediction of malignancy in pACC in comparison with the AFIP score, but further efforts may seek to ensure early and accurate stratification through augmented scoring.

Adrenocortical carcinoma: Pediatric aspects (Review).

Adrenocortical carcinoma (adrenal cortex-derived cancer), an orphan malignancy, is a very aggressive disease that affects both adults and children with an annual incidence of 1-2 adult and 0.2-0.38 pediatric cases/million (in the pediatric population it represents 0.2% of all cancers), with a female predominance. A total of 80-90% of cases have hormonal imbalances such as Cushing syndrome, virilization, and puberty anomalies. Precocious puberty (PP) of iso- or hetero-sexual pattern is independent of gonadotropin-releasing hormone (GnRH) (high testosterone/estrogens and low FSH/LH) but post-operative activation of GnRH may be expected (central PP). PP is accompanied by accelerated growth while Cushing syndrome by reduced growth velocity. Pure androgen-secreting tumors have been exceptionally described. A total of 50-80% of children have different genetic/epigenetic anomalies involving tumor protein p53 (most often, almost half of the cases; with a population cluster in Southern Brazilian children), insulin-like growth factor, multiple endocrine neoplasia type 1 (MEN1), PRKAR1A, dysfunctional alternative lengthening of telomeres. Hereditary syndromes associated to adrenocortical carcinoma include Li-Fraumeni, Beckwith-Wiedemann, MEN1, and Lynch. Recently, mutations in epidermal growth factor receptor have been reported in teenagers, suggesting the future use of tyrosine kinase inhibitors. Adrenalectomy is the first line therapy offering the best prognosis if complete tumor removal is achieved; genetic testing is recommended before surgery. Adjuvant therapies are less standardized in children (mitotane is a key adjuvant drug in addition with different regimes of chemotherapy such as etoposide, Adriamycin and cisplatin). A Ki-67 value of at least 15% is a predictor of poor outcome. Weiss score also serves as a prognostic factor, as well as the tumor size at diagnosis. The prognosis of adrenocortical carcinoma is poor with an overall 5-year survival rate of 55%; a Weiss score of at least 6 is associated with a 2-year survival rate of 35%. At present, pediatric adrenocortical carcinoma still represents a severe condition that requires prompt intervention and a multidisciplinary team. Further development of molecular markers is required for an improved understanding of the disease thus improving the protocols of approach and the prognostic.

Clinical and Histopathological Variables and Prognostic Factors of Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive tumor with a poor prognosis. The literature on prognosis from low-income or low-middle-income countries is limited and scarce. This study aimed to determine the clinical and histopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and the factors affecting ACC's prognosis. This was a retrospective study of patients that presented with ACC to the Shaukat Khanum Memorial Cancer & Research Center, Lahore, Pakistan, between January 2011 and May 2018. Information regarding demographics and clinical and histopathological variables were extracted and analyzed. Of the 25 subjects, 16 (64%) were female. The median age of the sample was 35 years (range; 21 - 72 years). Statistically significant associations were found between RFS and functional status of the tumor (p = 0.014), cortisol overproduction (p = 0.02), androgen excess (testosterone [p = 0.03] and dehydroepiandrosterone sulfate [DHEA SO4] [p = 0.004]), Ki-67 score (p = 0.03), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.01), and composite variable of disease (p = 0.004). The OS was found to have statistical associations with cortisol hypersecretion (p = 0.02), DHEA SO4 excess (p = 0.01), Modified Weis Score (p < 0.001), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.003), and composite variable of disease (p = 0.001). Linear regression (forward-type) analysis suggested that the functional status of the tumor and the disease recurrence index statistically predicted the variance in RFS and OS, respectively. Multiple clinical and histopathological variables appear to affect the prognosis of ACC. However, based on multivariable analysis, it appears that the functional status of the tumor and the composite variable of disease recurrence are predictors of RFS and OS, respectively.

Adrenocortical carcinoma, case report.

The adrenocortical carcinoma is rare and aggressive. It has a bimodal presentation, predominantly female, > 20% of cases will be diagnosed incidentally. 43-year-old male, with colic pain in the left flank, weight loss and intermittent fever. Computed tomography with a tumor on the left adrenal with liver metastases, block resection surgery was performed, pathological report of adrenocortical carcinoma with a 7 points of Weiss score and Ki67 40%. Adrenocortical carcinoma is a rare and aggressive neoplasm; the clinical presentation is variable. Systemic therapy is important even in patients with localized disease and independent of surgical approach.

El carcinoma corticoadrenal es una neoplasia rara, altamente agresiva, de distribución bimodal, con predominio en el sexo femenino, de la cual el 20% de los casos se diagnostican de manera incidental. Se presenta el caso de un varón de 43 años con dolor de tipo cólico en el flanco izquierdo, pérdida de peso y fiebre intermitente. La tomografía computarizada mostró un tumor en la glándula suprarrenal izquierda y metástasis hepática. Se realizó adrenalectomía radical en bloque, con reporte anatomopatológico de carcinoma corticoadrenal, Weiss de 7 puntos y Ki67 40%. El carcinoma corticoadrenal es una neoplasia agresiva y de presentación clínica variable. La terapia sistémica es importante incluso en pacientes con enfermedad localizada e independientemente de la cirugía.

Adrenal cortical carcinoma: pathology, genomics, prognosis, imaging features, and mimics with impact on management.

Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Most tumors are either metastatic or locally invasive at the time of diagnosis. Differentiation between ACC and other adrenal masses depends on clinical, biochemical, and imaging factors. This review will discuss the genetics, pathological, and imaging feature of ACC.

The computed tomography adrenal wash-out analysis properly classifies cortisol secreting adrenocortical adenomas.

PURPOSE: Adrenocortical lesions are characterized through imaging, hormonal and histopathological analysis. Our aim was to compare the radiological features of adrenocortical lesions with their cortisol-secreting status and histopathological Weiss score. METHODS: Seventy five patients operated between 2004 and 2016 in the University Hospital of Nancy for either adrenocortical carcinomas (ACC) or adrenocortical adenomas (ACA) were enrolled in this study. We collected cortisol parameters, Computed Tomography (CT) scans (unenhanced density, wash-out (WO) analysis) and 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) datas. The histopathological Weiss score ultimately differentiates ACA (score ≤ 2) from ACC (score ≥ 3). One-way ANOVA, Fisher's exact and unpaired t tests were used for statistical analysis with significancy reached at p < 0.05. RESULTS: There were 23 ACC and 52 ACA with 40 patients (53%) who had an autonomous secretion of cortisol. On CT scan, ACC were larger compared to ACA (108 vs. 37 mm, p < 0.0001). A roughly similar proportion of cortisol-secreting (22/25) and non-secreting (15/19) ACA were atypical (i.e., unenhanced density value ≥ 10 Hounsfield Units [HU]), however 85% of cortisol-secreting vs. 40% of non-secreting ACA were classified as benigns by the relative WO analysis (p = 0.08). Likewise, there was a trend for a higher 18F-FDG uptake in cortisol-secreting ACA compared to non-secreting ACA (p = 0.053). CONCLUSIONS: The relative adrenal WO analysis consolidates the benign nature of an ACA, especially in case of cortisol oversecretion, a condition known to compromise the diagnostic accuracy of the 10 HU unenhanced CT attenuation threshold.

Helsinki score-a novel model for prediction of metastases in adrenocortical carcinomas.

Histopathologic diagnosis of adrenocortical tumors is based on adverse features that indicate malignant potential. Proliferation index has served as a supplemental tool in assessing the malignant potential of adrenocortical tumors. None of the current histologic classification systems can sufficiently accurately predict tumors' metastatic potential. We studied 177 consecutive adult patients with primary adrenocortical tumors operated on at Helsinki University Central Hospital between 1990 and 2003, all patients with a minimum follow-up of 5 years. We determined for each tumor the Weiss score and the Weiss revisited score by Aubert. Proliferation index was measured by computer-assisted image analysis. Each of the 9 Weiss criteria and the proliferation index were then used to establish a scoring system to predict the metastatic potential of adrenocortical tumors. Use of stepwise regression analysis led us to propose a calculation: 3 × mitotic rate (>5/50 high-power fields) + 5 × presence of necrosis + proliferation index in the most proliferative area of the tumor. Using a cutoff value of 8.5, the new scoring system was able to diagnose metastatic adrenocortical carcinoma with 100% sensitivity (confidence interval [CI], 76.8%-100%) and 99.4% specificity (CI, 96.6%-100%). The corresponding sensitivity of the Weiss system was 100% (CI, 76.8%-100%), and specificity, 90.2% (CI, 84.6%-94.3%), with sensitivity of the Weiss revisited system at 100% (CI, 76.8%-100%) and specificity at 96.9% (CI, 93.0%-99.0%). The new Helsinki score thus was accurate in predicting the metastatic potential of adrenocortical tumors.

Clinical and histopathological features of adrenocortical neoplasms in children: retrospective review from a single specialist center.

BACKGROUND/PURPOSE: Adrenocortical tumors (ACTs) are rare in children and the extent to which histopathological features can predict clinical behavior remains uncertain. The aim of this study was to investigate the relationship between histopathological features (Weiss score), surgical approach, tumor size, underlying genetic predisposition syndrome, and outcome. METHODS: Twenty-nine ACTs treated at our institution between 1987 and 2011 were identified from a histopathology database. The histological features were categorized using the Weiss scoring system. For tumor staging, the UKCCSG staging system was utilized. RESULTS: At a median follow-up of 25 months, 19 patients (65.5%) survived without evidence of disease and 10 patients (35.5%) had died. There was a strong association between high Weiss score and both large tumor size (P<0.01) and adverse outcome (P<0.01). Outcome for stage I and IIA disease was significantly better compared to higher stage disease and/or tumor rupture (P<0.01). CONCLUSION: There is an association between high Weiss score, large tumor size, underlying genetic predisposition syndrome and an adverse outcome for pediatric ACTs. Regardless of histopathological findings, complete surgical resection, without tumor spillage, is optimal for survival. Genetic evaluation is recommended in patients with ACTs, particularly those with a high Weiss score.