Zarka, Matthew A.

Objective: To report a single institutional series of high-grade neuroendocrine carcinoma of the larynx (NCL), a very rare yet aggressive tumor. To review the management of NCL, including discussion of clinical behavior, treatment outcome, and prognosis. Method: A retrospective chart review of high-grade laryngeal neuroendocrine carcinomas at a single institution, including small- and large-cell neuroendocrine carcinomas. A total of 8 patients with high-grade NCL treated at our institution from 1992 to 2014 were identified. Results: The median age at diagnosis was 65.5 years (range, 43-80). Five patients were male. Two patients had a known smoking history. Primary tumor location was supraglottic in 7 patients and glottic in 1 patient. Primary treatment consisted of surgery alone (3 patients), radiotherapy alone (1 patient), combination of chemotherapy and radiotherapy (1 patient), and surgery followed by postoperative chemoradiotherapy (3 patients). Locoregional recurrence followed by distant metastasis occurred in 6 patients. Median overall survival was 44.0 months (95% CI, 3-62.0). Conclusion: High-grade NCL is a rare diagnosis. Compared to well- and moderately differentiated NCL, high-grade NCL has a far more aggressive clinical course and associated with a worse prognosis. To our knowledge, this is the largest series of patients with high-grade NCL treated at a single institution. Prompt diagnosis and multimodality therapy including elective neck dissection may improve survival.

Aims We wanted to improve the quality of histopathology addenda and amendments by introducing standardised nomenclature and procedures. Methods We standardised amendment and addenda definitions, implemented a pathologist visual work tool, and evaluated and quantitated all amendments and addenda for 3 months prior to implementation and 17 months after. Results In the 3-month pre-intervention period, 32 of 979 addenda (3.3%) were misused and 18 of 98 amendments (18.4%) were incorrectly classified. In the 17-month post-intervention period, 57 of 5906 addenda (1.0%) were misused and 54 of 752 amendments (7.2%) were incorrectly classified. These differences were statistically significant (p<0.0001). Conclusions The introduction of standardised nomenclature and a visual work tool significantly improved the quality of histopathology addenda and amendments.

The 2001 Bethesda system recommends further classifying atypical glandular cells (AGCs) as either endocervical or endometrial origin. Numerous studies have investigated the clinical significance of AGC. In this study, we investigated the incidence of clinically significant lesions among women with liquid-based Papanicolaou cervicovaginal (Pap) interpretations of atypical endometrial cells (AEMs) or AGC favor endometrial origin (AGC-EM). More importantly, we correlated patients of AEM or AGC-EM with their clinical presentations to determine if AEM/AGC-EM combined with abnormal vaginal bleeding is associated with a higher incidence of significant endometrial pathology. All liquid-based Pap tests with an interpretation of AEM and AGC-EM from July, 2004 through June, 2009 were retrieved from the database. Women with an interpretation of atypical endocervical cells, AGC, favor endocervical origin or AGC, favor neoplastic were not included in the study. The most severe subsequent histologic diagnoses were recorded for each patient. During this 5-year period, we accessioned 332,470 Pap tests of which 169 (0.05%) were interpreted as either AEM or AGC-EM. Of the 169 patients, 133 had histologic follow-up within the health care system. The patients ranged in age from 21 to 71 years old (mean 49.7). On follow-up histology, 27 (20.3%) had neoplastic/preneoplastic uterine lesions. Among them, 20 patients were diagnosed with adenocarcinoma (18 endometrial, 1 endocervical, and 1 metastatic colorectal), 3 with atypical endometrial hyperplasia, and 4 with endometrial hyperplasia without atypia. All patients with significant endometrial pathology, except one, were over 40 years old, and 22 of 25 patients reported abnormal vaginal bleeding at the time of endometrial biopsy or curettage. This study represents a large series of women with liquid-based Pap test interpretations of AEM and AGC-EM with clinical follow-up. Significant preneoplastic or neoplastic endometrial lesions were identified in 20.3% of patients. Patients with Pap test interpretations of AEM or AGC-EM and the clinical presentation of abnormal vaginal bleeding should be followed closely.

ABSTRACT Genital human papillomavirus (HPV) is the etiologic agent of more than 99% of all cervical cancers worldwide, with 14 genotypes being considered oncogenic or “high risk” because of their association with severe dysplasia and cervical carcinoma. Among these 14 high-risk types, HPV-16 and -18 account for approximately 70% of cervical cancers. The aim of this study was to evaluate three FDA-approved HPV nucleic acid-based tests for the ability to predict high-grade cervical intraepithelial neoplasias (CIN2 or worse) in corresponding tissue biopsy specimens. Residual specimens (total n = 793, cervical n = 743, vaginal n = 50) collected in ThinPrep PreservCyt medium with a cytologic result of ≥atypical squamous cells of undetermined significance were tested by the Hybrid Capture 2 (HC2) assay (Qiagen, Gaithersburg, MD), the cobas HPV test (Roche Diagnostics, Indianapolis, IN), and the APTIMA HPV assay (Hologic, San Diego, CA). Genotyping for HPV-16 and HPV-18 was simultaneously performed by the cobas HPV test. Results were compared to cervical or vaginal biopsy findings, when they were available ( n = 350). Among the 350 patients with corresponding biopsy results, 81 (23.1%) showed ≥CIN2 by histopathology. The ≥CIN2 detection sensitivity was 91.4% by the cobas and APTIMA assays and 97.5% by HC2 assay. The specificities of the cobas, APTIMA, and HC2 assays were 31.2, 42.0, and 27.1%, respectively. When considering only positive HPV-16 and/or HPV-18 genotype results, the cobas test showed a sensitivity and a specificity of 51.9 and 86.6%, respectively. While the HC2, cobas, and APTIMA assays showed similar sensitivities for the detection of ≥CIN2 lesions, the specificities of the three tests varied, with the greatest specificity (86.6%) observed when the HPV-16 and/or HPV-18 genotypes were detected.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound guided fine‐needle aspiration biopsy, techniques of the endoscopic retrograde cholangiopancreatography, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and postbiopsy management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings over an 18‐month period and synthesis of online comments of the draft document on the Papanicolaou Society of Cytopathology website [www.papsociety.org]. This document presents the results of these discussions regarding the use of ancillary testing in the cytological diagnosis of biliary and pancreatic lesions. This document summarizes the current state of the art for techniques in acquiring cytology specimens from the biliary tree as well as solid and cystic lesions of the pancreas. Diagn. Cytopathol. 2014;42:333–337. © 2014 Wiley Periodicals, Inc.

AbstractBackgroundHibernomas are rare, benign tumors of brown adipose tissue uncommonly found in the head and neck.MethodsA review of the English‐language literature was conducted for this study. We present a series of 2 laryngeal hibernomas treated with transoral laser microsurgical resection at a tertiary referral center over a period of 18 years.ResultsOnly 2 cases of laryngeal hibernoma have been previously described in the literature. Two additional cases were encountered at our institution. Preoperative imaging demonstrated a well‐circumscribed neoplasm with fat density compatible with lipoma, but internal heterogeneity and vascularity seen in the context of liposarcoma. Transoral laser microsurgical resection was successfully performed in each case.ConclusionDespite unique radiographic features, hibernomas are difficult to distinguish from well‐differentiated liposarcoma and lipoma variants without pathologic correlation. Complete surgical resection is indicated. In our experience, transoral laser microsurgical excision of laryngeal hibernomas is a safe, effective treatment modality with little associated morbidity. © 2013 Wiley Periodicals, Inc. Head Neck 36: E39–E43, 2014

BackgroundThe purpose of this study was to report the treatment outcomes of patients with advanced oropharyngeal cancer treated with transoral laser microsurgery (TLM) followed by radiation therapy (RT) at Mayo Clinic in Arizona.MethodsA retrospective study of 80 patients treated from January 1, 2000 to November 7, 2011 was performed. All patients had stage III/IV oropharyngeal tumors and underwent TLM with neck dissection. Adjuvant RT was then given. Thirty‐seven patients received concurrent adjuvant chemotherapy. The primary outcome was locoregional control.ResultsMedian follow‐up was 47.3 months (range, 9.7–139.2 months). The 3‐year locoregional control, recurrence‐free survival, and overall survival rates were 98.6% (95% confidence interval [CI], 91% to 100%), 91.1% (95% CI, 81% to 96%), and 93.7% (95% CI, 84% to 98%), respectively. There were a total of 5 treatment failures, 1 regional and 4 distant. Twenty‐six patients underwent neck only RT with exclusion of the primary site.ConclusionTLM followed by RT for advanced oropharyngeal cancer results in excellent locoregional control rates. © 2013 Wiley Periodicals, Inc. Head Neck 36: 220–225, 2014

Objectives/HypothesisTo evaluate the results of patients treated by transoral laser microsurgery and margin mapping with attention to deep margin dimensions in the lateral pharyngeal wall.Study DesignA microscopic margin analysis of multiblock surgical specimens applied to a prospectively accrued case series of squamous cell carcinoma of the palatine tonsils.MethodsThere were 128 tonsil cancers analyzed that were removed transorally, using microscopic margin mapping by surgeon and pathologist. The closest deep and peripheral margins were assessed. The results were then related to a study of the normal dimensions of the lateral pharyngeal wall in 20 healthy patients using magnetic resonance imaging. Outcome measures included number of positive margins, narrowest margin, local control, and disease‐free and overall survival.ResultsThe average closest margin was 1.98 mm (range, 0.30–6.50 mm) deep and 2.82 mm (range, 1.00–5.00 mm) peripheral. There was one positive margin encountered in the previously untreated group (1%), and one local recurrence ultimately developed. Radiographic measures revealed a mean minimal thickness of the lateral pharyngeal wall musculature of 2.4 mm. With mean follow‐up of 4.3 years (range, 2–14 years), the 5‐year estimate for local control is 99%, disease‐free survival is 94.5%, and overall survival is 76%.ConclusionsMargin mapping achieves a low rate of positive margins and is associated with good local control. Based on lateral pharyngeal wall anatomy, wide margins are often unobtainable and may be unnecessary so long as the final inked margin is clear.Level of Evidence4.

AbstractTo determine cytologic features of epithelioid hemangioendothelioma (EHE) that would enable accurate diagnosis, we evaluated fine-needle aspiration biopsy (FNAB) smears from 11 histologically confirmed EHEs. The variably cellular smears comprised dispersed single cells and occasional cell aggregates. Dense stromal fragments were present in association with some tissue fragments. The cells were epithelioid, containing moderate or large amounts of dense cytoplasm. Nuclei exhibited mild pleomorphism, and nuclear grooves were identified in all cases. At least occasional intranuclear pseudoinclusions (INPIs) and intracytoplasmic lumina (ICLs) were present in all cases and in 9 cases (82%), respectively, and rare erythrocytes were seen within ICLs in 5 cases (45%). Mitotic figures were identified in 4 cases (36%). The background was bloody in 6 cases (55%) and contained hemosiderin and/or hemosiderin-laden macrophages in 5 cases (45%). The combination of the following features in FNAB samples should raise strong suspicion for EHE: predominantly dispersed single cells with occasional cohesive cell clusters; epithelioid cytomorphology; dense cytoplasm with well-defined cytoplasmic borders; ICLs (with or without erythrocytes), INPIs, and nuclear grooves. The presence of these features should prompt correlation with clinical, radiologic, and histologic features and immunohistochemical evaluation using vascular markers.