Necrosis in Preoperative Cross-Sectional Imaging and Postoperative Histology Is a Diagnostic Marker for Malignancy of Adrenocortical Tumors

Abstract

Necrosis in postoperative histology has been reported as being specific for adrenocortical carcinoma (ACC) compared to adenoma. We therefore retrospectively analyzed the diagnostic accuracy of the finding of necrosis in preoperative cross-sectional imaging and postoperative histology as a marker for ACC in our patient cohort. Among the 411 adrenalectomies in 396 patients performed between 2008 and April 2022, 30 cases of ACC (7.6%) were identified, with one tumor measuring less than 40 mm excluded. All 45 benign adrenocortical tumors of at least 40 mm in diameter, including Cushing, Conn, and hormonally inactive adenomas, served as controls. Preoperative imaging was available for 40 benign and 27 malignant adrenocortical tumors. In total, 10 of 40 (25%) benign adrenocortical tumors and 22 of 27 (81%) ACCs showed signs of possible necrosis in preoperative imaging. Pathologic examination confirmed necrosis in 1 of 40 (2.5%) benign tumors and in 26 out of 27 (96%) malignant tumors. The specificities of possible necrosis in preoperative imaging and necrosis in histology for diagnosing ACC were 75% and 97.5%, respectively, whereas the sensitivities were 81% and 96%, respectively. Signs of possible necrosis in radiologic imaging and tumor necrosis in histology proved to be very good predictive markers for the diagnosis of malignant adrenocortical tumors.

Keywords: adrenalectomy; adrenocortical adenoma; adrenocortical carcinoma; computed tomography; magnetic resonance imaging; tumor necrosis.

Figure 1

(a) A T2-weighted magnetic resonance image of a 59-year-old male patient with a 17-OH-progesterone-producing right-sided ACC (arrow), measuring 85 mm in the largest diameter. Hyperintense lesions correspond with necrosis; (b) contrast-medium-enhanced computed tomography in a 25-year-old patient with a cortisol- and androstendion-producing left-sided ACC measuring 150 mm, showing diffuse areas of necrosis (arrow); (c) contrast-enhanced computed tomography in a 49-year-old male with a cortisol- and 17-OH-progesterone-producing left-sided ACC (arrow), measuring 130 mm in the largest diameter, with inhomogeneous enhancement, calcifications, and hypodense areas suspicious of necrosis; (d) a picture of the excised ACC after formalin fixation in correlation with the preoperative computed tomography scan (Figure 1c). The large tumor shows indistinct borders and a variegated cut surface with central hemorrhage and necrotic areas.

Figure 2

(a) Microscopic image of an adrenocortical adenoma (a 56-year-old female patient with hyperaldosteronism) showing nests of lipid-rich cells (upper right corner, continuous arrow) and compact lipid-poor cells (lower left corner, dotted arrow) with small and uniform nuclei. Necrosis, increased mitotic activity, or nuclear pleomorphism are absent (H&E stain, 100 $\times$ magnification). (b) In contrast, the ACC (a 78-year-old female patient with a hormonally inactive tumor) is composed of solid to diffuse growing tumor cells with large highly atypical nuclei and frequent confluencing necrosis (upper left corner, block arrow; H&E stain, 200 $\times$ magnification).

Figure 3

Flowchart depicting the inclusion/exclusion criteria for adrenocortical tumors.

Figure 4

Receiver operating characteristic (ROC) curve representing sensitivity versus specificity of logistic regression using only the size of adrenocortical tumors as an explanatory variable.

Figure 5

(A) Large, inhomogeneous adrenal tumor with areas suspected of necrosis in CT (arrow) in a 54-year-old male patient. In macro- and microscopic examination, the tumor did not show necrosis. (B) Metastases were detected during the course of the disease. Despite therapy with mitotane, chemotherapy, and radiotherapy, the tumor progressed. (C) On a CT 2 years after the primary diagnosis and 2 months before the patient’s death, a recurrent tumor in the upper abdomen with a compression of the vena portae and vena lienalis (arrow), as well as metastases in the abdominal wall next to the arteria iliaca communis (dotted arrow), were identified.