Development of a Novel Molecular Test for Determining HPV Integration Status in HPV-Positive Oropharynx Cancers.

This diagnostic study describes the development of an assay for human papillomavirus­driven cancers of the oropharynx and the role viral integration could play in the process.

Nasopharyngeal Hyalinizing Clear Cell Carcinoma: A Case Report and Review of the Literature.

BACKGROUND: Hyalinizing clear cell carcinomas (HCCCs) are rare, low-grade, malignant tumors which most often arise from the minor salivary glands primarily in palate and tongue but can arise in any location with minor salivary glands including the nasopharynx. METHODS: A case report of primary nasopharyngeal HCCC is presented. Because of the rarity of this tumor and location, a literature search was conducted to determine the most common presenting symptoms, treatment strategies, and outcomes. RESULTS: A 48-year-old man underwent biopsy of a 4.5 cm mass of the right nasopharynx with pathology suggesting an intermediate grade mucoepidermoid carcinoma. After discussing management with the patient, an endoscopic resection was performed. Final pathology revealed an HCCC which was confirmed after negative Mastermind-like 2 (MAML2) and positive Ewing sarcoma breakpoint region 1 (ESWR1) gene rearrangements on fluorescence in situ hybridization (FISH) studies. Literature review of other nasopharyngeal HCCC cases shows diverse presentation and overall excellent prognosis through surgical and radiation therapy. CONCLUSION: HCCCs are rare, low-grade malignant tumors of the minor salivary glands and can present as a nasopharyngeal mass. Presenting symptoms are diverse but frequently involve otologic and sinonasal disturbances. HCCC is an indolent tumor with an excellent prognostic outcome when treated appropriately with surgical resection and adjuvant radiotherapy.

The utility of adaptive eLearning in cervical cytopathology education.

BACKGROUND: Adaptive eLearning allows students to experience a self-paced, individualized curriculum based on prior knowledge and learning ability. METHODS: The authors investigated the effectiveness of adaptive online modules in teaching cervical cytopathology. eLearning modules were created that covered basic concepts in cervical cytopathology, including artifacts and infections, squamous lesions (SL), and glandular lesions (GL). The modules used student responses to individualize the educational curriculum and provide real-time feedback. Pathology trainees and faculty from the authors' institution were randomized into 2 groups (SL or GL), and identical pre-tests and post-tests were used to compare the efficacy of eLearning modules versus traditional study methods (textbooks and slide sets). User experience was assessed with a Likert scale and free-text responses. RESULTS: Sixteen of 17 participants completed the SL module, and 19 of 19 completed the GL module. Participants in both groups had improved post-test scores for content in the adaptive eLearning module. Users indicated that the module was effective in presenting content and concepts (Likert scale [from 1 to 5], 4.3 of 5.0), was an efficient and convenient way to review the material (Likert scale, 4.4 of 5.0), and was more engaging than lectures and texts (Likert scale, 4.6 of 5.0). Users favored the immediate feedback and interactivity of the module. Limitations included the inability to review prior content and slow upload time for images. Learners demonstrated improvement in their knowledge after the use of adaptive eLearning modules compared with traditional methods. CONCLUSIONS: Overall, the modules were viewed positively by participants. Adaptive eLearning modules can provide an engaging and effective adjunct to traditional teaching methods in cervical cytopathology. Cancer Cytopathol 2018;126:129-35. © 2017 American Cancer Society.

Adaptive eLearning modules for cytopathology education: A review and approach.

Clinical training imposes time and resource constraints on educators and learners, making it difficult to provide and absorb meaningful instruction. Additionally, innovative and personalized education has become an expectation of adult learners. Fortunately, the development of web-based educational tools provides a possible solution to these challenges. Within this review, we introduce the utility of adaptive eLearning platforms in pathology education. In addition to a review of the current literature, we provide the reader with a suggested approach for module creation, as well as a critical assessment of an available platform, based on our experience in creating adaptive eLearning modules for teaching basic concepts in gynecologic cytopathology. Diagn. Cytopathol. 2016;44:944-951. © 2016 Wiley Periodicals, Inc.

Usage trends and performance characteristics of a "gene expression classifier" in the management of thyroid nodules: An institutional experience.

BACKGROUND: The gene expression classifier (GEC; Afirma-Veracyte) has proven to be an effective triage modality in the management of thyroid nodules. We evaluate our institutional experience with GEC, specifically examining performance as a first line testing strategy versus in conjunction with repeat fine needle aspiration (FNA), usage trends based on clinical setting, and performance related to diagnostic categories of The Bethesda System for Reporting Thyroid Cytology (TBSRTC). METHODS: All nodules undergoing GEC analysis from 1/2011 to 12/2015 at the Hospital of the University of Pennsylvania were identified using electronic database search methods. Corresponding cytologic diagnoses, GEC results, origin of the sample (in-house vs. satellite site), number and diagnosis of prior FNA's, and clinical and histologic follow-up were collected. RESULTS: The cohort included 294 nodules. Of these, 145 (49%) were classified as benign, 136 (46%) as suspicious, and 13 (5%) as quantity insufficient by GEC. Surgical resection was performed in 130 (130/294-44%) cases (107, 82% "suspicious" by GEC); final histopathologic diagnosis was benign in 85 (65%) and malignant in 45 (35%) cases. Three false negative diagnoses were identified in the setting of GEC analysis as a first line testing strategy. Most cases with GEC as a first line testing strategy came from satellite clinical sites (112, 66%). CONCLUSIONS: The GEC showed improved performance characteristics when coupled with a repeat FNA. It continues to be of low specificity and positive predictive value in oncocytic follicular lesions. Diagn. Cytopathol. 2016;44:867-873. © 2016 Wiley Periodicals, Inc.

The reliability of thyroid nodule ultrasound features and size to predict malignancy in fine needle aspiration specimens: Practical utility for the evaluating pathologist.

BACKGROUND: The prognostic impact of ultrasound features of thyroid nodules is debated. We explore the correlation between nodule size, echogenicity on US, and malignancy. METHODS: We performed a retrospective review of thyroid nodules undergoing ultrasound guided FNA (US-FNA) at our institution between 01/2008-05/2013. RESULTS: In all, 2,403 nodules from 2,293 patients (age range 14-91, mean 54, median 56, M: F-1:3.2) underwent US-FNA. 766 nodules were resected, 337 were malignant (size range 0.4-8.7 cm, median 2 cm, mean 2.37 cm,) and 429 were benign (size range 0.5-9.7 cm, median 2.5 cm, mean 2.79 cm). The malignant diagnoses included: classical variant of PTC 77 (size range 0.5-5.5 cm, mean 1.5 cm), follicular variant of PTC 209 (size range 0.14-7.5 cm, mean 2.1 cm), tall cell variant of PTC 7 (size range 0.5-2.4 cm, mean1.4 cm), poorly differentiated carcinoma 5 (size range 5-8.7 cm, mean 6.42 cm), follicular carcinoma 27 (size range 0.5-7 cm, mean 3.03 cm), and oncocytic follicular carcinoma 9 cases (size range 1.4-7.2 cm, mean 3.2 cm). Of the malignant nodules with echogenicity reported on US, 93 were hypoechoic, 26 hyperechoic, 20 isoechoic, and 76 heteroechoic; increased vascularity on US was seen in 69/337 (20%). On US, 105 benign nodules were reported as hypoechoic, 35 hyperechoic, 43 isoechoic, and 100 as heterogeneous; increased vascularity on US was seen in 88/429 (20%). CONCLUSIONS: A malignant diagnosis was more common in thyroid nodules ≤1.0 cm. No differences were noted in the US-features of benign and malignant thyroid nodules.

The cytopathologic features of mammary analog secretory carcinoma and its mimics.

Mammary Analogue Secretory Carcinoma (MASC) is a newly recognized neoplasm of the salivary gland, first described in 2010. This tumor harbors a unique translocation, t(12;15)(p13;q25) that results in the fusion of ETV6 with NTRK3 which produces a transformative chimeric tyrosine kinase. To date, few cases of MASC sampled by fine needle aspiration have been reported. Cytologically, MASC can be confused with other oncocytic salivary gland tumors, including Warthin-tumor, acinic cell carcinoma (AciCC) and mucoepidermoid carcinoma. It is characterized by a monomorphic population of lesional cells with round nuclei, prominent nucleoli and abundant, eosinophilic foamy cytoplasm; forming papillary groups with transgressing vessels. Though, based on cytomorphology alone, the definite diagnosis can be challenging, in conjunction with available clinical clues (i.e. male patient, extra-parotid site) MASC should be included in the differential diagnosis of FNA specimens diagnosed as oncocytic salivary gland neoplasms or suspicious for AciCC. Here we present a case of MASC with FNA sampling at our institution.

The variable pathologic presentations of medullary and micro-medullary thyroid carcinoma: an institutional experience.

Medullary thyroid carcinoma (MTC) is a rare tumor; its pathologic diagnosis can be difficult due to variability in its clinical presentation, size, morphology, and follow-up. We report our institutional experience with 45 cases of MTC diagnosed at University of Pennsylvania Medical Center between 2000 and 2007. The collected data points included patient's age, sex, family history, tumor size, method of diagnosis, calcitonin and CEA levels, presence of concomitant follicular derived thyroid carcinoma (FDTC), lymph node (LN) status, and clinical follow-up. The cohort included 17 males and 28 females (average age 53 years); 6 had a history of multiple endocrine neoplasia II (MENII). Pre-operative FNA was performed in 33/45 cases (33%); 23/33 were diagnosed as MTC or suspicious for MTC. Of 45 cases 20 were micro-MTC; 15 occurred with other thyroid malignancies. LN metastases were present at primary resection in 18/45 cases. Calcitonin levels rose or remained elevated postoperatively in 4 cases; of these, 2 had regional LN recurrence and 1 developed distant metastases and subsequently died of disease. MTC is a heterogeneous disease. Sporadic micro-MTC carcinoma is an indolent tumor and can occur with other malignant tumors of the thyroid gland.

Bone marrow B cell precursor number after allogeneic stem cell transplantation and GVHD development.

Patients without chronic graft-versus-host disease (cGVHD) have robust B cell reconstitution and are able to maintain B cell homeostasis after allogeneic hematopoietic stem cell transplantation (HSCT). To determine whether B lymphopoiesis differs before cGVHD develops, we examined bone marrow (BM) biopsies for terminal deoxynucleotidyl transferase (TdT) and PAX5 immunostaining early post-HSCT at day 30 when all patients have been shown to have high B cell activating factor (BAFF) levels. We found significantly greater numbers of BM B cell precursors in patients who did not develop cGVHD compared with those who developed cGVHD (median = 44 vs 2 cells/high powered field [hpf]; respectively; P < .001). Importantly, a significant increase in precursor B cells was maintained when patients receiving high-dose steroid therapy were excluded (median = 49 vs 20 cells/hpf; P = .017). Thus, we demonstrate the association of BM B cell production capacity in human GVHD development. Increased BM precursor B cell number may serve to predict good clinical outcome after HSCT.