Colleen M. Kiernan

Pheochromocytoma and Paraganglioma: Diagnosis, Genetics, and Treatment.

This article highlights the epidemiology and pathophysiology of pheochromocytomas and paragangliomas. The current management of pheochromocytoma and paragangliomas, including utilization and interpretation of biochemical testing, preoperative imaging, and genetic screening are discussed. Furthermore, perioperative surgical management, outcomes, and recommended follow-up are reviewed.

Curative surgical resection of adrenocortical carcinoma: Determining long-term outcome based on conditional disease-free probability

Objective: To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC). Background: ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery. Methods: CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at “x” year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x). Results: One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%–88%, &Dgr;60% vs no capsular invasion: 51%–87%, &Dgr;36%). Conclusions: DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.

Actual 10-year survivors following resection of adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited therapeutic options beyond surgical resection. The characteristics of actual long‐term survivors following surgical resection for ACC have not been previously reported.

Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma

IMPORTANCE Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. OBJECTIVES To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction. DESIGN, SETTING, AND PARTICIPANTS Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015. MAIN OUTCOMES AND MEASURES The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47-15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95-3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27-4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02-3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00-3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05-16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51-5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS). CONCLUSIONS AND RELEVANCE Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.

Neutrophil‐lymphocyte and platelet‐lymphocyte ratio as predictors of disease specific survival after resection of adrenocortical carcinoma

The systemic inflammatory response may be associated with tumor progression. We sought to analyze the impact of neutrophil‐lymphocyte ratio (NLR) and platelet‐lymphocyte ratio (PLR) on recurrence‐free survival (RFS) and disease‐specific survival (DSS) among patients who underwent surgery for adrenocortical carcinoma (ACC).

New terminology—noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) and its effect on the rate of malignancy at a single institution

Background. The cytologic qualities of noninvasive follicular neoplasm with papillary‐like nuclear features mimic papillary thyroid carcinoma (PTC) on fine‐needle aspiration, leading to difficulty in distinguishing the 2 preoperatively. The aim of this study was to determine the impact of reclassification of noninvasive follicular neoplasm with papillary‐like nuclear features at our practice. Methods. We searched 1,046 patient charts for those cases with preoperative cytology and subsequent follicular‐variant papillary thyroid carcinoma diagnosis on resection. Endocrine pathologists reviewed the cases to determine the reclassification of noninvasive follicular neoplasm with papillary‐like nuclear features. Results. Sixty (6%) follicular‐variant papillary thyroid carcinomas were identified, 4% (44) in the index nodule. Of the 44 patients, 84% (37) met the criteria for evaluation. Of these, 46% (17) were noninvasive follicular neoplasm with papillary‐like nuclear features. After reclassification of noninvasive follicular‐variant papillary thyroid carcinoma to noninvasive follicular neoplasm with papillary‐like nuclear features, the overall cancer rate changed from 31% to 29%. Malignancy rates across Bethesda cytologic categories changed as follows: benign (n = 419) from 3.5% to 3.3%; atypia of undetermined significance/follicular lesion of undetermined significance (n = 240) from 17% to 15%; suspicious for follicular neoplasm (n = 104) from 23% to 21%; suspicious for malignancy (n = 85) from 68% to 60%, and malignant (n = 198) from 93% to 92%. Conclusion. Reclassification of noninvasive follicular neoplasm with papillary‐like nuclear features led to a small decrease in the overall malignancy rate. The most affected Bethesda category was suspicious for malignancy. Because the majority of noninvasive follicular neoplasm with papillary‐like nuclear features will be indeterminate lesions by cytology/molecular testing, thyroidectomy will remain a common treatment modality. Noninvasive follicular neoplasm with papillary‐like nuclear features classification will primarily affect decision making to avoid excessive treatment/monitoring.

Use of Radioiodine after Thyroid Lobectomy in Patients with Differentiated Thyroid Cancer: Does It Change Outcomes?

BACKGROUND Radioiodine (RAI) lobe ablation in lieu of completion thyroidectomy is not recommended. This study describes RAI use patterns and outcomes in patients with well-differentiated thyroid cancer (DTC) after thyroid lobectomy (TL). STUDY DESIGN A total of 170,330 patients diagnosed with DTC between 1998 and 2011 were identified using the National Cancer Database. Demographic, tumor, and treatment variables were analyzed using both univariate and multivariate regression. RESULTS A total of 32,119 patients (20%) underwent TL as the definitive procedure. Mean age at diagnosis was 48 years, median tumor size was 1 cm, 4% had extrathyroidal extension, 4% had positive lymph nodes, and <1% distant metastases. Radioiodine was administered to 24% of patients in the TL cohort and represented 10% of the overall RAI use. In multivariate analysis, RAI use was associated with age younger than 45 years (odds ratio [OR] = 1.51), community facilities (OR = 1.26), ≥ 1 cm tumors (OR = 5.67), stage II (OR = 1.54) or III (OR = 2.05), positive lymph nodes (OR = 1.78), and extrathyroidal extension (OR = 1.36). On both univariate and multivariate analysis, RAI after TL was associated with improved survival at both 5 and 10 years follow-up (97% vs 95% and 91% vs 89%, respectively; hazard ratio = 0.53; 95% CI, 0.38-0.72; p < 0.001) CONCLUSIONS: Nearly one quarter of TL patients received RAI. The strongest predictors of RAI use were larger cancers and advanced stage. Use of RAI in these patients was associated with improved overall survival. Future studies and guidelines will need to more clearly address this practice and educate providers about the appropriate use of RAI in TL patients.

Influence of adrenal pathology on perioperative outcomes: a multi-institutional analysis

BACKGROUND Endoscopic or open adrenalectomies are performed for variable pathologies. We investigated if adrenal pathology affects perioperative outcomes independent of operative approach. METHODS A multi-institutional retrospective review of 345 adrenalectomies was performed. A multivariate analysis was utilized. RESULTS Pathology groups included benign non-pheochromocytoma tumors (50.4%), pheochromocytomas (41%), adrenocortical carcinomas (5.2%), and metastatic tumors (3.4%). Controlling for age, body mass index, tumor size, procedure type, and pathology, pheochromocytomas exhibited greater blood loss (92 mL more, P = .007) and operative times (33 min more, P < .001) than benign non-pheochromocytoma tumors. Metastatic tumors demonstrated longer operative times (53 min more, P = .013). Open adrenalectomy was associated with greater blood loss (396 mL more, P = .001), transfusion requirement (P = .021), operative times (79 min more, P < .001), hospital stay (6.6 days more, P < .001) and complications (P < .001) when compared with endoscopic adrenalectomy. CONCLUSIONS The type of adrenal pathology appears to influence blood loss and operative time but not complications in patients undergoing adrenalectomy. Open adrenalectomy remains a major driver of adverse perioperative outcomes.

Fine-needle aspiration–based grading of pancreatic neuroendocrine neoplasms using Ki-67: is accurate WHO grading possible on cytologic material?

Introduction The World Health Organization (WHO) has provided grading guidelines for pancreatic neuroendocrine neoplasms (PanNENs) based on mitotic count and Ki-67 proliferation index. Due to the desire to provide earlier tumor grading for clinical management decisions, some groups have proposed grading PanNENs at the time of fine needle aspiration (FNA) using Ki-67 proliferation rates. While a Ki-67 can be performed on FNA cell blocks, there are potential sampling limitations with this technique that may affect the reliability of the Ki-67 result. Materials and Methods Forty-nine PanNENs with FNA cell blocks and corresponding resection material were evaluated by immunohistochemistry for expression of Ki-67. Ki-67 proliferation rate was calculated based on cell counts of >500 cells in the highest staining areas. Ki-67 scores from FNA cell blocks were correlated with Ki-67 scores from resection specimens. Results The FNA Ki-67 proliferation rates overall did not correlate well with the resection specimen. A linear regression analysis of the correlation between FNA %Ki-67 and resection %Ki-67 showed a slope of 3.2 and an R2=0.58. The average difference in Ki-67 proliferation rate between FNA and resection was 5.9%. Thirty-nine percent (19/49 cases) of PanNENs showed discordant grading between the FNA cell block and resection specimen. Almost all (18/19) discordant cases demonstrated a lower FNA-based grade as compared to the resection grade. Conclusions FNA cell block grading using Ki-67 frequently led to under-grading of the tumor. This finding is consistent with concerns that FNA may not provide accurate grading due to the limited sampling of the tumor.

ASO Author Reflections: Additional Organ Resection in Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with a poor prognosis. Extra-adrenal organs often are removed en bloc during index adrenalectomy for ACC. In the past, some have advocated compulsory ipsilateral nephrectomy due to the close association of the adrenal gland and the kidney and their lack of separation by a complete fascial layer, suggesting concurrent nephrectomy may improve outcomes. However, no data exist to support this approach. The anatomic and intraoperative factors that lead to resection of the extraadrenal organs, the most common organs removed, and the benefits and risks of these additional organ resections have yet to be described in detail. The current study attempted to examine the anatomic and intraoperative factors associated with en bloc resection and to determine whether such resections are associated with differences in outcome.