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Background: The tall cell variant of papillary thyroid carcinoma has traditionally been treated more aggressively than classic papillary thyroid carcinoma. However, this may not be justified in patients with T1/T2 tall cell variant node-negative tumors., Methods: We evaluated well-differentiated thyroid cancers treated surgically between 1985 and 2015 at our institution. We compared patients undergoing lobectomy for node-negative T1/T2 tall cell variant tumors with the same cohort with classic papillary thyroid carcinoma. Patients who underwent early planned completion thyroidectomy were excluded. Tall cell variant tumors were defined as those with ≥30% tall cells. Survival and recurrence outcomes were determined by the Kaplan-Meier method and groups compared using the log-rank test., Results: Thyroid lobectomy was performed for T1/T2 N0X disease in 70 (15%) tall cell cases and 429 (23%) classic papillary thyroid carcinoma cases. There was no significant difference in 10-year overall survival (P = .56) or locoregional recurrence-free probability (P = .52). Disease-specific survival and local or central nodal recurrence-free probability were 100% in both groups. In 9 papillary thyroid carcinoma cases, subsequent contralateral lobe tumors developed, and in 5, lateral neck metastases developed. No recurrences were seen in the tall cell group., Conclusion: T1 node-negative tumors with tall cell histology can be satisfactorily managed with thyroid lobectomy, with equivalent oncological outcomes to classic papillary thyroid carcinoma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The ThyroSeq v2 next-generation sequencing assay estimates the probability of malignancy in indeterminate thyroid nodules. Its diagnostic accuracy in different practice settings and patient populations is not well understood., Methods: We analyzed 273 Bethesda III/IV indeterminate thyroid nodules evaluated with ThyroSeq at 4 institutions: 2 comprehensive cancer centers (n = 98 and 102), a multicenter health care system (n = 60), and an academic medical center (n = 13). The positive and negative predictive values of ThyroSeq and distribution of final pathologic diagnoses were analyzed and compared with values predicted by Bayes theorem., Results: Across 4 institutions, the positive predictive value was 35% (22%-43%) and negative predictive value was 93% (88%-100%). Predictive values correlated closely with Bayes theorem estimates (r 2  = 0.84), although positive predictive values were lower than expected. RAS mutations were the most common molecular alteration. Among 84 RAS-mutated nodules, malignancy risk was variable (25%, range 10%-37%) and distribution of benign diagnoses differed across institutions (adenoma/hyperplasia 12%-85%, noninvasive follicular thyroid neoplasm with papillary-like nuclear features 5%-46%)., Conclusion: In a multi-institutional analysis, ThyroSeq positive predictive values were variable and lower than expected. This is attributable to differences in the prevalence of malignancy and variability in pathologist interpretations of noninvasive tumors. It is important that clinicians understand ThyroSeq performance in their practice setting when evaluating these results., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Background: The impact of large vessel extension (LVE) as a prognostic factor for adrenocortical carcinoma (ACC) is not fully understood. This study aimed to assess outcome of ACC in the presence and absence of LVE., Methods: A retrospective review of 57 patients undergoing curative intent resection for ACC over 10 years is presented comparing those with and without LVE. LVE was defined as vascular wall invasion or intraluminal extension of the neoplasm into the inferior vena cava or renal vein. Preoperative diagnostics, operative details, pathology, overall survival (OS), and recurrence-free survival (RFS) were analyzed., Results: Multivariable regression analysis showed a significant association for decreased survival with Stage III and IV disease and LVE. Patients with LVE had more functional neoplasms, greater preoperative serum hormone levels, and more positive margins than those without LVE. Median OS was 6 years and RFS 3 years. Kaplan-Meier analysis demonstrated a significant decrease in OS and RFS with LVE. Median OS with and without LVE was 18 vs 111 months and median RFS was 11 vs 64 months. Three-year OS with and without LVE were 29% vs 93% and 3 year RFS was 15% vs 67%., Conclusion: In addition to systemic and lymph node metastases, LVE is associated with poorer OS and RFS., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: Pheochromocytomas are malignant in approximately 10% of patients. The histologic differentiation between benign and malignant tumors is difficult, the latter diagnosed by the presence of metastatic disease or recurrence., Aim: To determine if postoperative histologic evaluation using the previously proposed Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and cell cycle/apoptosis markers can predict patients at risk for recurrence., Methods: Using the Memorial Sloan-Kettering Cancer Center adrenal database, we identified 48 patients with 51 resected pheochromocytomas (1987-2006). A senior endocrine pathologist, blinded to clinical outcome, reviewed the histopathologic characteristics of all cases using the PASS system. This pheochromocytoma scoring system is based on the presence of 12 different histologic parameters, including tumor necrosis, mitotic rate, tumor cell spindling, and the presence of large cell nests. In addition, we constructed a tissue microarray of all 5 malignant tumors and 41 of the benign tumors. By immunostaining of the tissue microarray, we assessed the expression of 7 different cell cycle/apoptosis-related genes (p53, Ki-67, Bcl-2, mdm-2, cyclin D1, p21, and p27)., Results: Forty-three patients had a benign clinical course while 5 patients harbored a clinically malignant pheochromocytoma. Tumor necrosis (focal or confluent) was a particularly powerful indicator of malignancy present in 4 of 5 patients (80%) with malignant tumors, but only in 3 of 42 cases (7%) with benign neoplasms (P = .0009). The presence of a high mitotic rate (>3/10 high power fields) and tumor cell spindling significantly correlated with malignancy (P = .026 and .041, respectively). High cellularity was more often present in the malignant lesions (P = .050). There was a highly significant difference in PASS scores between benign and malignant cases (P = .0003). All malignant pheochromocytomas had a PASS score >/=6, well above the previously proposed >/=4 cutoff value. Two of the 4 patients testing positive for Ki-67 (>2% nuclear staining) had a clinically malignant course while only 3 (7%) of the 41 cases with lower Ki-67 positivity rate behaved in a malignant fashion (P = .055). Ki-67-positive tumor had a significantly higher chance of harboring tumor necrosis than Ki-67-negative neoplasms (P < .01). There was no difference in staining between benign and malignant pheochromocytomas using p53, Bcl-2, mdm-2, cyclin D1, p21, and p27., Conclusions: (1) A PASS score of <4 predicted benign pheochromocytomas. (2) All malignant pheochromocytomas had a PASS score >/=6, which was significantly higher compared with the benign lesions. Patients with a PASS score >/=4 should be followed closely for recurrence. (3) p53, Bcl-2, mdm-2, cyclin D1, p21, and p27 appear to have no role in predicting the behavior of pheochromocytomas. Ki-67 may help identify those neoplasms at risk for recurrence by prompting the pathologist to look aggressively for adverse histologic features.

Background: Our previous work has demonstrated squamous cell carcinoma-related oncogene (SCCRO) expression in adult murine adrenocortical tissue. The aim of this study was to assess patterns of SCCRO expression in the embryonic murine adrenal gland, and in normal and neoplastic human adrenocortical tissues in order to determine its role as a marker of differentiation in adrenocortical development and neoplastic progression., Methods: Murine embryos were procured at developmental stages E8 to E18. A tissue microarray was constructed containing 38 normal, 39 adenomatous, and 87 carcinomatous human adrenocortical specimens. Immunohistochemistry for SCCRO was performed and its expression was graded in suitable tissues., Results: SCCRO expression was detected in the murine adrenal cortex as early as E15 and persisted into the postnatal period. High-level SCCRO expression was identified in 94% of normal (32/34) and adenomatous (29/31) adrenocortical specimens but in only 63% (45/72) of adrenocortical carcinoma (ACC) specimens ( P = .001). Loss of SCCRO expression in primary ACC (13/34 (34%)) correlated with advanced stage ( P = .06), presence of M1 disease at presentation ( P = .03), and worse overall survival ( P = .006)., Conclusions: SCCRO appears to be a marker of adrenocortical differentiation in both murine and human systems. SCCRO expression may be useful in distinguishing adrenocortical adenomas from ACC. Moreover, loss of SCCRO expression in primary ACC is associated with worse outcome and may be a marker of progressive dedifferentiation in these tumors.

Background: The role of operations for distantly metastatic well-differentiated thyroid carcinoma (DTC) is poorly defined. We review the indications for operation for metastatic DTC., Methods: This study consists of 260 patients treated between 1941 and 2000 for metastatic DTC, of which 59 (23%) underwent operations. Median follow-up was 7 years (range, 1 to 49 years). Metastases were identified clinically in 157 (60%) and radiologically in 103 (40%) patients. The disease-specific survival was estimated with the Kaplan-Meier method., Results: Twenty-four patients (9%) were disease-free with resection. Palliative resection was indicated for painful bone metastasis, pathologic fracture, or symptomatic spinal cord involvement (35/260, 14%). Patients who could undergo complete metastasectomy survived longer than those having incomplete/palliative resection or nonoperative treatment for metastatic DTC (5-year disease-specific survival, 78% vs 43% vs 46%, P =.03)., Conclusions: Solitary distant metastasis of DTC amenable to complete resection is infrequent. Complete metastasectomy may be associated with improved survival for localized distant disease. Palliative resection is indicated to improve quality of life for symptomatic distant metastasis.