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Background: Although perineural invasion (PNI) is recognized as an adverse prognostic factor in oral tongue squamous cell carcinoma (SCC), the patterns of failure are poorly defined., Methods: Patients with oral tongue SCC who received primary surgical treatment were identified. Specimens were reviewed by head and neck pathologists. Disease-specific survival (DSS) and locoregional recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant recurrence-free survival (DRFS) were calculated. The PNI and PNI characteristics were analyzed as predictors of outcome. The utility of grading the extent of PNI was assessed by quantifying the number of PNI foci per slide reviewed, nerve caliber, and percent circumference involved., Results: Patients with PNI had a decreased DSS; however, PNI was not predictive of LRFS or RRFS. Patients with PNI were more likely to develop a distant recurrence and 19.40 (confidence interval [CI] 6.70-56.14; P < .001) times more likely to develop a distant recurrence if PNI foci density was >1., Conclusion: The presence of PNI in oral tongue SCC predicts worse DSS, with distant recurrence as the most common pattern of failure. High PNI foci density is associated with worse DRFS., (© 2018 Wiley Periodicals, Inc.)

Background: In 2016, encapsulated follicular variant of papillary thyroid carcinoma without invasion was renamed "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) in order to reduce overtreatment of this indolent tumor. However, many endocrinologists remain uneasy about managing large (≥4 cm) NIFTP conservatively without radioactive iodine (RAI) therapy. The objectives of this study are to characterize the clinicopathologic characteristics and outcome of large NIFTP in order to assist therapeutic decision making., Methods: The pathology databases of four tertiary hospitals were searched for large (≥4 cm) NIFTP. Cases with separate foci of carcinoma were excluded. Seventy-nine cases fulfilled the inclusion criteria. Among them, 56 (71%) had at least two years of clinical follow-up (FU), and 49 (62%) had four or more years of FU. The clinicopathologic characteristics were reviewed and documented by four endocrine pathologists., Results: The median size of the NIFTP was 4.5 cm (range 4.0-8.0 cm). The entire capsule was sampled in 50 (63%) tumors, while in the remaining 29 (37%) cases, it was submitted representatively, with a median of 2.1 blocks per centimeter of tumor examined. Large NIFTP had a female preponderance with a male:female ratio of 1:1.8, and presented at a median age of 49 years. There were no lymph node metastases at diagnosis in any of the patients, and none of the patients (n = 25) in whom nodal tissue was available for microscopic examination had positive findings. Twenty-six (33%) underwent thyroid lobectomy alone, and 37 (47%) did not receive RAI ablation. No recurrence was observed in the entire cohort, including all 32 patients with two or more years of FU who did not receive RAI therapy (median FU: 6.7 years). Among patients with four or more years of FU, all 25 individuals without RAI therapy did not recur, with a median FU of 11.2 years. Patients with a larger tumor size tended to receive postoperative RAI ablation (p = 0.001)., Conclusions: Similar to their small counterparts, large NIFTP appear to have an extremely low risk of recurrence (zero in this cohort), even when treated conservatively without RAI therapy. Surgical treatment alone, including lobectomy, appears to be adequate for large NIFTP.

Struma ovarii (SO) infrequently harbor carcinomas that are histologically similar to those arising in the eutopic thyroid. We identified 10 such cases in our files. Eight patients presented with pelvic-related symptoms whereas 2 were incidentally discovered during pregnancy, all with disease confined to the ovary. There were 8 papillary thyroid carcinomas (PTCs) (2 classic and 6 follicular variant) and 2 poorly differentiated thyroid carcinomas. Two of the 10 thyroid carcinomas relapsed after an initial diagnosis of "benign" struma. Both occurred in young women with ovarian cysts discovered during pregnancy. The cystectomy from 1 patient showed thyroid follicles with nuclear features of the follicular variant of PTC whereas the cyst from the second patient showed thyroid follicles with subtle nuclear features, suggestive but not diagnostic of PTC. Both patients presented with disseminated PTC 3 and 4 years after the initial diagnosis, involving the pelvis in both cases and also the liver parenchyma in 1 case. The 2 patients received radioactive iodine therapy after thyroidectomy and are both alive with disease 6 years after diagnosis. The criteria separating hyperplastic nodules from well-differentiated follicular variant of PTC in the thyroid gland seem to be applicable to thyroid-type carcinomas arising in SO. The propensity for adverse clinical behavior does not seem to be related to the grade or histologic type of carcinoma in this small series. The hormonal milieu during pregnancy may lead to progression of malignant SO and such patients should be closely followed, particularly if their treatment consists of cystectomy alone.

Purpose: External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer., Methods and Materials: Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT were identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%)., Results: The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%)., Conclusion: The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.

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: Follicular carcinomas of the thyroid gland, including its oncocytic variant (so-called Hurthle cell carcinoma), are subdivided into the indolent encapsulated ("minimally invasive") and the clinically aggressive widely invasive tumors. There are, however, cases of encapsulated follicular carcinoma that recur and metastasize. Identifying these cases at the time of diagnosis is crucial for prognostic and therapeutic considerations. Because to the authors' knowledge most studies do not focus exclusively on the encapsulated Hurthle cell carcinoma (EHC), the current study attempted to identify predictors of recurrence in EHC., Methods: A tumor was defined as EHC if it was encapsulated, macroscopically well defined with microscopic but no macroscopic evidence of vascular or capsular invasion, and composed of > 75% follicular oncocytic cells. Retrospective chart review and microscopic examination identified 50 primary tumors meeting the above criteria at the Memorial Sloan-Kettering Cancer Center between 1967 and 2005. The cases were analyzed for various histologic and clinical parameters. Each parameter was correlated with recurrence-free survival (RFS)., Results: Seven of 50 (14%) patients developed disease recurrence. All patients who developed recurrence were found to have a high number of foci of vascular invasion (> or = 4). In univariate analysis, > or = 4 foci of vascular invasion (P <.0001), tumor size > 4 cm (P = .049), the presence of mitosis (P = .018), and a solid/trabecular growth pattern (P = .009) were found to be correlated with a decreased RFS. Extensive capsular invasion, gender, and age did not confer a statistically higher recurrence rate. The finding of a solid/trabecular growth and mitosis correlated with the presence of numerous foci (> or = 4) of vascular invasion (P = .01 and P = .005, respectively)., Conclusions: A diligent search for vascular invasion is recommended in EHC that display mitosis or a solid/trabecular growth pattern. The presence of > or = 4 foci of vascular invasion should alert the pathologist and the clinician to a significantly higher risk of recurrence in EHC., (2006 American Cancer Society)

Background: We identified factors predictive of outcome for recurrent differentiated thyroid carcinoma (DTC)., Methods: Fifty-seven patients with local (LR), regional (RRec), and/or distant recurrence (DR) of 431 recurrent DTCs were studied. Disease-specific survival (DSS) rate was estimated with the Kaplan-Meier method. Univariate and multivariate comparisons were conducted by log-rank and Cox regression analysis., Results: The median follow-up was 13 years. Distribution of the first relapse was LR only (35%), LR and RRec (23%), LR and DR (30%), and LR, RRec, and DR (12%). Factors predictive of resectability were a long (>or=5-year) disease-free interval (DFI) and subclinical and thyroid remnant recurrence. Only 26% of symptomatic and 45% of thyroid bed LR, and 43% with DFI <5 years, could be resected completely. No isolated thyroid remnant and 75% of thyroid bed LR resulted in tumor-related mortality. Age <45 years, subclinical recurrence, isolated LR, and the ability to render the patient disease free independently predicted DSS. Fifteen-year DSS for LR only; LR and RRec; LR and DR; and LR, RRec, and DR were 49%, 28%, 15%, and 0%, respectively., Conclusions: Isolated thyroid remnant recurrence defines a benign phenotype. Age, method of detection, site and extent of recurrence, and the ability to render the patient disease free predict outcome for recurrent DTC. Multimodality long-term follow-up is warranted to detect recurrence at a subclinical potentially curative stage.