Letters
RESEARCH LETTER
PACIFIC COAST SURGICAL ASSOCIATION
Evaluation of Necrosis as a Diagnostic and Prognostic Indicator in Adrenocortical Carcinoma
Adrenocortical carcinoma (ACC) is rare and has a poor progno- sis. In part because of its rarity, the pathological diagnosis of ACC is based on unstandardized criteria that are difficult to apply. His- tologic 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 pro- posed. For example, the widely used Weiss scoring system evalu- ates 9 histologic parameters, but it is difficult for nonexpert pa- thologists to apply, is not reproducible for morphologic variants, is not universally recognized or reported, and fails to predict ad- verse 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 differen- tiate 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 diag- nostic and prognostic indicator.
Methods | 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, de- termined macro- and micronecrosis for each sample, and con- firmed the diagnosis. Other pathological data, including Weiss score components and reported diagnoses, were also re- viewed. Patient demographic characteristics and long-term clinical data to determine disease-free survival, recurrence, and mortality were collected. The University of California, San Fran- cisco Institutional Review Board approved this project (18- 26671) and granted a waiver of informed consent because the research involved no more than minimal risk.
Results | Through an adrenal tissue biorepository search, we identified 570 adrenal glands from 558 unique patients. We ex- cluded pheochromocytomas, Cushing disease-related speci- mens, tissues obtained from bilateral resections, ACNs with a Weiss score of 0, and samples from patients undergoing re-
A Ischemic necrosis
B Interphase
C Ischemic necrosis
D Mitotic figure
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 (x40) of necrosis. D, The arrowhead highlights a mitotic figure next to the area of ischemic necrosis (original magnification x40).
A ☒ Axial slice
B
Coronal slice
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.
section 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 me- dian length of follow-up was 31 months (IQR, 9-32.5) and 47 months (IQR, 5-74) for malignant and benign lesions, respec- tively. 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-en- capsulated tumor with a high nuclear grade. Necrosis was the only feature suggestive of ACN. The tumor was resected lapa- roscopically, 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 recur- rence 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 histo- logic hematoxylin-eosin staining. Figure 2 shows macro- necrosis found with preoperative cross-sectional computed tomography.
Discussion | 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 necro- sis exclusively had 93.3% isolated sensitivity and 91.3% speci- ficity, making it inferior to scoring systems that include ne- crosis as a key, but not the sole, component.
Sarah S. Pearlstein, MD Patricia C. Conroy, MD Kathryn Chomsky Menut, MD
Jina Kim, MD Claire E. Graves, MD Robert Ruiz-Cordero, MD Quan-Yang Duh, MD
Author Affiliations: Department of Surgery, University of California, San Francisco (Pearlstein, Conroy, Menut); Inova Schar Cancer Institute, Fairfax, Virginia (Kim); Department of Surgery, University of California, Davis (Graves); Department of Pathology, University of California, San Francisco (Ruiz-Cordero); Section of Endocrine Surgery, Department of Surgery, University of California, San Francisco (Duh).
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 (quan-yang.duh@ucsf.edu).
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.
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