Adrenocortical Oncocytic Tumors: Report of 10 Cases and Review of the Literature

Abstract

Ten additional adrenocortical oncocytic tumors are presented: 2 benign oncocytomas, 4 borderline oncocytomas of uncertain malignant potential, and 4 oncocytic carcinomas. Histologically all tumors were entirely or predominantly composed of oncocytes. Immunohistochemically all tumors were immunoreactive for mitochondrial antigen mES-13. Electron microscopy was performed in 8 cases and was confirmatory of the oncocytic cell change. The morphologic parameters of the Weiss system, considered to be predictive of the biologic behavior of conventional (nononcocytic) adrenocortical tumors, are reviewed in the context of their possible application to the oncocytic tumor variant. Proposed major criteria (high mitotic rate, atypical mitoses, venous invasion) and minor criteria (large size and huge weight, necrosis, capsular invasion, sinusoidal invasion) in distinguishing malignant tumors are discussed, and definitional criteria (predominantly cells with eosinophilic and granular cytoplasm, high nuclear grade, diffuse architectural pattern) in common with all types of oncocytic tumors are outlined. The authors' proposed working rules for diagnostic categorization of oncocytic adrenocortical tumors are defined, with the presence of 1 major criterion indicating malignancy, 1 to 4 minor criteria indicating uncertain malignant potential (borderline), and the absence of all major and minor criteria indicative of benignancy. Using these criteria, the diagnosis of malignancy was straightforward in 3 of the 4 cases designated as oncocytic carcinoma (presence of at least 2 major criteria and all the minor criteria), while in 1 case the original diagnosis of benign oncocytoma was reversed to malignant following critical review of the original pathologic material after local tumor recurrence. Tumor recurrence occurred in 2 carcinomas at 8 and 20 months, respectively, and was followed in 1 case by the patient's death. The third patient expired at 6 months from unrelated causes, and the fourth patient is free of disease at the relatively short follow-up interval of 6 months. Regarding the 4 patients with borderline tumors, all are alive with no evidence of disease, with follow-up ranging from 10 to 61 months (mean 38.7 months). The 2 benign tumors have a follow-up of 25 and 30 months, respectively. Diagnostic difficulties are delineated and a complete review of the literature on this topic has also been performed.

Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma

“…Malignancy in the eight oncocytic tumors was also confirmed by using the more accurate Bisceglia scheme. 6 The majority of these patients were treated at our Institution, which serves as a referral center for adrenocortical carcinoma in Italy. The clinical and pathological features of all cases belonging to this data set (summarized in Table 1) have already been reported 3,53-55 and were updated.…”

“…Phospho-histone H3 immunostaining allowed a rapid count of mitotic figures and is also useful for the recognition of atypical mitotic figures, a second relevant parameter included in the Weiss Score (Figure 1). The 'atypical mitotic figure' parameter is relevant also in diagnostic schemes specifically designed for pure oncocytic tumors, 6 an adrenocortical tumor variant often associated to a very low proliferative potential, which could therefore take the maximal advantage from phospho-histone H3 immunostaining.…”

“…This is even more true in those adrenocortical carcinomas with few or borderline features of malignancy, in which the accurate identification of a single parameter can be crucial to reach the threshold of malignancy (for example, in the Weiss Score for classical adrenocortical carcinoma or the Lin-Weiss-Bisceglia scheme for oncocytic tumors. 6 ) Moreover, among all parameters included in the Weiss Score, mitotic rate is the unique criterion strongly associated with patient prognosis. For this reason, a mitotic countbased grading of adrenocortical carcinoma has been also proposed recently, with a cutoff of 20 mitotic figures per 50/high-power fields to separate low from high-grade adrenocortical carcinomas.…”

Cracking the diagnostic puzzle of tumours of adrenal cortex: a histopathological study

“…8 If the oncocytic tumour shows one or more major criteria of 1) a mitotic figure of more than 5 mitoses per 50 high-power fields, 2) any atypical mitosis, or 3) any venous invasion), it is reported as AOC. If one or more minor criteria of 1) large size >10 cm and/or >200 g, 2) confluent necrosis, or 3) capsular invasion or 4) sinusoidal invasion), it is categorized as AONUMP.…”

“…17 However, these schemes may be difficult to apply in case of adrenocortical tumors occurring in childhood, oncocytic variants and tumours with myxoid features. 8,18,19 Wienke JA proposed an alternative scheme for adrenocortical tumours in paedeatric age group. 18 The presence of four or more criteria of tumour weight >400g, tumour size >10.5cm, extension of tumour into periadrenal soft tissue/adjacent organs, invasion into vena cava, venous invasion, capsular invasion, presence of tumour necrosis, >15mitoses/20HPF, and presence of atypical mitotic figures is associated with malignancy.…”