A, The arrowhead highlights the area of ischemic necrosis (original magnification ×10). B, Interphase between viable tumor cells and the area of ischemic necrosis (original magnification ×40). C, The arrowhead highlights the area of ischemic necrosis (original magnification ×10). The inset shows high magnification (×40) of necrosis. D, The arrowhead highlights a mitotic figure next to the area of ischemic necrosis (original magnification ×40).
A, The arrowhead highlights an area of ischemic necrosis on an axial slice. B, The arrowhead highlights another area of ischemic necrosis on a coronal slice.
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Pearlstein SS, Conroy PC, Menut KC, et al. Evaluation of Necrosis as a Diagnostic and Prognostic Indicator in Adrenocortical Carcinoma. JAMA Surg. 2021;156(12):1173–1174. doi:10.1001/jamasurg.2021.3646
Adrenocortical carcinoma (ACC) is rare and has a poor prognosis. In part because of its rarity, the pathological diagnosis of ACC is based on unstandardized criteria that are difficult to apply. Histologic variants further complicate the differentiation of benign and malignant disease in the adrenal gland.1 Scoring systems and algorithms for the pathological diagnosis of ACC have been proposed. For example, the widely used Weiss scoring system evaluates 9 histologic parameters, but it is difficult for nonexpert pathologists to apply, is not reproducible for morphologic variants, is not universally recognized or reported, and fails to predict adverse outcomes for patients with low-grade disease.2,3 Attempts to simplify the Weiss scoring system include the modified Weiss criteria and the Helsinki score.4 In 2020, Walz et al5 proposed a simplified system to evaluate necrosis exclusively and differentiate benign from malignant adrenocortical neoplasms (ACNs). We used our adrenal tissue biorepository to evaluate this system’s potential and review the presence of necrosis in ACC as a diagnostic and prognostic indicator.
We established an adrenal tissue biorepository at the University of California in 2000. A blinded pathologist (R.R.-C.) reviewed the tissue histology samples independently, determined macro- and micronecrosis for each sample, and confirmed the diagnosis. Other pathological data, including Weiss score components and reported diagnoses, were also reviewed. Patient demographic characteristics and long-term clinical data to determine disease-free survival, recurrence, and mortality were collected. The University of California, San Francisco Institutional Review Board approved this project (18-26671) and granted a waiver of informed consent because the research involved no more than minimal risk.
Through an adrenal tissue biorepository search, we identified 570 adrenal glands from 558 unique patients. We excluded pheochromocytomas, Cushing disease–related specimens, tissues obtained from bilateral resections, ACNs with a Weiss score of 0, and samples from patients undergoing resection for a nonadrenal indication. We identified 38 patients with ACNs meeting the criteria. More than half of patients were men with left-sided ACNs (52.6%), and the median patient age was 53.5 years (interquartile range [IQR], 44.2-63.7). The median length of follow-up was 31 months (IQR, 9-32.5) and 47 months (IQR, 5-74) for malignant and benign lesions, respectively. Necrosis was more frequent in ACCs (93.3%; 14 of 15) compared with benign ACNs (8.7%; 2 of 23), with a risk ratio of 10.7 (95% CI, 2.8-40.6; P < .001), corresponding to 93.3% sensitivity and 91.3% specificity.
No benign ACNs had evidence of recurrence. Of 2 benign ACNs with necrosis, 1 was a right-sided, 3.7-cm, well-encapsulated tumor with a high nuclear grade. Necrosis was the only feature suggestive of ACN. The tumor was resected laparoscopically, with no recurrence at 2 years. The second benign ACN with necrosis was a 15-cm, low-grade, p53-negative, oncocytic cortical neoplasm with necrosis as the only positive Weiss score point. There was no evidence of recurrence at 1 year of follow-up.
The 1 ACC without necrosis was an 8-cm, virilizing, right adrenal mass with inferior vena cava invasion. The ACC was diagnosed as malignant, given the high nuclear grade, clear cells comprising less than 25% of the tumor, and the presence of venous invasion. There was no recurrence or metastasis at 4 years.
Figure 1 demonstrates micronecrosis found with histologic hematoxylin-eosin staining. Figure 2 shows macronecrosis found with preoperative cross-sectional computed tomography.
Although necrosis is not exclusive to ACC, may be an indicator of malignancy and should be a key component of diagnostic ACC scoring systems. However, the results of this case series show that the simplified system to evaluate necrosis exclusively had 93.3% isolated sensitivity and 91.3% specificity, making it inferior to scoring systems that include necrosis as a key, but not the sole, component.
Accepted for Publication: June 12, 2021.
Published Online: September 8, 2021. doi:10.1001/jamasurg.2021.3646
Corresponding Author: Quan-Yang Duh, MD, Section of Endocrine Surgery, Department of Surgery, University of California, UCSF Medical Center at Mount Zion, 1600 Divisadero St, San Francisco, CA 94115 (email@example.com).
Author Contributions: Dr Pearlstein had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Pearlstein, Kim, Graves, Duh.
Acquisition, analysis, or interpretation of data: Pearlstein, Conroy, Chomsky Menut, Kim, Ruiz-Cordero.
Drafting of the manuscript: Pearlstein, Ruiz-Cordero, Duh.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Pearlstein.
Administrative, technical, or material support: Pearlstein, Chomsky Menut, Kim, Duh.
Supervision: Ruiz-Cordero, Duh.
Conflict of Interest Disclosures: Dr Chomsky Menut reported receiving consulting fees from Prescient Surgical. No other disclosures were reported.