Overview of the 2022 WHO Classification of Adrenal Cortical Tumors

Abstract

The new WHO classification of adrenal cortical proliferations reflects translational advances in the fields of endocrine pathology, oncology and molecular biology. By adopting a question–answer framework, this review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the adrenal cortex pathologies that are now reflected in the 2022 WHO classification. The pathological correlates of adrenal cortical proliferations include diffuse adrenal cortical hyperplasia, adrenal cortical nodular disease, adrenal cortical adenomas and adrenal cortical carcinomas. Understanding germline susceptibility and the clonal-neoplastic nature of individual adrenal cortical nodules in primary bilateral macronodular adrenal cortical disease, and recognition of the clonal-neoplastic nature of incidentally discovered non-functional subcentimeter benign adrenal cortical nodules has led to redefining the spectrum of adrenal cortical nodular disease. As a consequence, the most significant nomenclature change in the field of adrenal cortical pathology involves the refined classification of adrenal cortical nodular disease which now includes (a) sporadic nodular adrenocortical disease, (b) bilateral micronodular adrenal cortical disease, and (c) bilateral macronodular adrenal cortical disease (formerly known primary bilateral macronodular adrenal cortical hyperplasia). This group of clinicopathological entities are reflected in functional adrenal cortical pathologies. Aldosterone producing cortical lesions can be unifocal or multifocal, and may be bilateral with no imaging-detected nodule(s). Furthermore, not all grossly or radiologically identified adrenal cortical lesions may be the source of aldosterone excess. For this reason, the new WHO classification endorses the nomenclature of the HISTALDO classification which uses CYP11B2 immunohistochemistry to identify functional sites of aldosterone production to help predict the risk of bilateral disease in primary aldosteronism. Adrenal cortical carcinomas are subtyped based on their morphological features to include conventional, oncocytic, myxoid, and sarcomatoid subtypes. Although the classic histopathologic criteria for diagnosing adrenal cortical carcinomas have not changed, the 2022 WHO classification underscores the diagnostic and prognostic impact of angioinvasion (vascular invasion) in these tumors. Microscopic angioinvasion is defined as tumor cells invading through a vessel wall and forming a thrombus/fibrin-tumor complex or intravascular tumor cells admixed with platelet thrombus/fibrin. In addition to well-established Weiss and modified Weiss scoring systems, the new WHO classification also expands on the use of other multiparameter diagnostic algorithms (reticulin algorithm, Lin–Weiss–Bisceglia system, and Helsinki scoring system) to assist the workup of adrenal cortical neoplasms in adults. Accordingly, conventional carcinomas can be assessed using all multiparameter diagnostic scheme...

Bilateral adrenal uptake of 123I MIBG scintigraphy with mild catecholamine elevation, the diagnostic dilemma, and its characteristics

“…Since FGFR4 -G388R variant has been shown to be a possible initiator of adrenocortical adenoma within pheochromocytoma 19 , we investigated the association between this variant and these adrenocortical adenomas besides AMH rather than mutations in protein kinase A (PKA) pathway, well-known genetic abnormalities in cortisol-producing adenomas 20 . We detected a somatic homozygous FGFR4- G388R variant from the adrenocortical adenoma specimens of Case 3, a heterozygous variant from Case 1, and wild-type FGFR4 - G388R from Case 2.…”

Prognostic Factors in Advanced Adrenocortical Carcinoma: Summary of a National Referral Center’s 20 years of Experience

“…The multivariate analysis is detailed in Table 3 . Of note, the cohort included 1 case of oncocytic ACC, which was evaluated by the Lin–Weiss–Bisceglia system [ 13 ] and was included in the high-risk grading group due to a mitotic rate of 27 per 10 mm 2 and a Ki 67 proliferation index of 70.…”

“…Data collected included age of diagnosis; gender; ethnic origin; tumor side, TNM, capsular invasion, ENSAT at initial diagnosis, mENSAT and involved organs at diagnosis with locoregional or metastatic disease; R status; histological grade (according to mitotic rate as per novel 2022 WHO classification) [ 13 ]; Ki 67 proliferation index determined by manual immunohistochemistry using the same antibody (Cell Mark Ki 67; SPS, rabbit monoclonal antibody: RRID:AB 2892217); Weiss histopathological score; Lin–Weiss–Bisceglia for oncocytic subtype; symptoms at diagnosis; treatment type; maximal mitotane levels reached; treatment tolerability and adverse events; response to treatment and duration of response; time from diagnosis until death or last follow-up.…”

Sex-specific Association of Primary Aldosteronism With Visceral Adiposity

“…Then, unilateral APA was diagnosed for those whose pathological result was concordant with a classical histology (ie, aldosterone-producing adrenal cortical adenoma or aldosterone-producing nodule), but not with a nonclassical histology (ie, suspected multiple aldosterone-producing nodule/micronodule nor aldosterone-producing diffuse hyperplasia) [ 29 ]. Classical histopathology represents a solitary neoplasm or nodule composed of clear cells, compact eosinophilic cells, or a mixture of both by hematoxylin-eosin staining [ 29 ]. The bilateral PA subtype or IHA was diagnosed when the lateralized ratio was < 2 and the contralateral ratio was ≥ 1 [ 25 , 27 , 28 ].…”