Feasibility of accelerated image-guided high-dose-rate interstitial brachytherapy with inverse planning simulated annealing (IPSA-HDRBT) for post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue.

PURPOSE: Inverse planning simulated annealing (IPSA) produces highly conformal dose distributions and quick optimizations for high-dose-rate interstitial brachytherapy (HDRBT). We report our dosimetry and overall outcomes using this approach for the accelerated post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue (OTSCC) with high risk of local recurrence. METHODS: Patients with newly diagnosed pN0 OTSCC treated with partial glossectomy, neck dissection, and post-operative HDRBT alone from 2007 to 2021 were retrospectively reviewed. Patients received 30 Gy in 5 fractions over 2.5 days. Target volume and mandible dosimetry are reported. Actuarial rates of local control, regional control, disease-specific survival, and overall survival were estimated using the Kaplan-Meier method. Toxicity was categorized using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: 19 consecutive patients were reviewed. Median follow-up was 3.2 years (IQR 1.4-8.2 years) with a 3-year estimated local control rate of 81%. Target volumes were generally small, as the median volume was 12.66 cc. Median V150% and V200% were 52% and 24%, respectively. D1cc and D2cc to the mandible were 17.31 Gy and 14.42 Gy, respectively. CONCLUSIONS: IPSA-HDRBT is feasible and highly efficient for post-operative treatment of the primary tumor bed in patients with pathologically node-negative squamous cell carcinomas of the oral tongue. Further technical optimization and prospective clinical evaluation in a larger patient cohort are planned.

The utility of high-risk human papillomavirus in situ hybridization in cytology cell block material from cystic head and neck lesions.

BACKGROUND: Human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV-OPSCC) presents frequently as metastasis in a neck lymph node that may be cystic or necrotic. Fine-needle aspiration (FNA) biopsies are often first-line diagnostic procedures. p16 immunohistochemistry (IHC) is a surrogate marker for high-risk HPV (hrHPV) infection but can be challenging to interpret. This study evaluated the use of hrHPV in situ hybridization (ISH) in cytology cell blocks of cystic neck lesions. METHODS: Twenty-four FNA cases with cell blocks and surgical correlates were evaluated. p16 IHC and hrHPV ISH were assessed on cell blocks (C-p16 and C-hrHPV ISH), and hrHPV ISH on surgical samples (S-hrHPV ISH). All results were classified as negative, positive, or equivocal. RESULTS: Two cases were excluded because of insufficient tissue on recut. On the basis of C-hrHPV ISH cases, 12 were positive, 5 were negative, and 5 were equivocal. All 12 positive C-hrHPV ISH cases had concordant S-hrHPV ISH with no false positives. Of the 5 negative C-hrHPV ISH cases, 4 had concordant S-hrHPV ISH, and 1 had a discordant S-hrHPV ISH. Of the 5 equivocal C-hrHPV ISH cases, S-hrHPV ISH were both positive and negative. Fourteen cases were equivocal by C-p16; 9 cases were reliably classified by C-hrHPV ISH (5 positive, 4 negative; 64%). CONCLUSIONS: C-hrHPV ISH can be reliably used, especially when positive. A negative or equivocal interpretation of C-hrHPV ISH may warrant repeat testing. Compared to C-p16, C-hrHPV ISH is more frequently diagnostic and could be helpful for HPV-OSCC diagnosis and management.

Leveraging Technology for Remote Learning in the Era of COVID-19 and Social Distancing.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has rapidly disrupted traditional modes of operation in health care and education. In March 2020, institutions in the United States began to implement a range of policies to discourage direct contact and encourage social distancing. These measures have placed us in an unprecedented position where education can no longer occur at close quarters-most notably, around a multiheaded microscope-but must instead continue at a distance. This guide is intended to be a resource for pathologists and pathologists-in-training who wish to leverage technology to continue collaboration, teaching, and education in this era. The article is focused mainly on anatomic pathology; however, the technologies easily lend themselves to clinical pathology education as well. Our aim is to provide curated lists of various online resources that can be used for virtual learning in pathology, provide tips and tricks, and share our personal experience with these technologies. The lists include videoconferencing platforms; pathology Web sites; free online educational resources, including social media; and whole slide imaging collections. We are currently living through a unique situation without a precedent or guidebook, and we hope that this guide will enable the community of pathology educators worldwide to embrace the opportunities that 21st century technology provides.

The diagnostic utility of next-generation sequencing on FNA biopsies of melanocytic uveal lesions.

BACKGROUND: Uveal melanoma is highly aggressive, and overall prognosis depends on mutation status. Fine-needle aspiration biopsies (FNABs) play an important role in obtaining fresh tissue for cytologic diagnosis and molecular studies. It has been suggested that, although FNAB usually provides high diagnostic accuracy, there may be limited cellularity, which may compromise diagnostic potential for molecular studies. FNABs of uveal melanocytic lesions were evaluated to assess sample adequacy for both cytologic evaluation and next-generation sequencing (NGS). METHODS: The authors retrospectively evaluated 36 cases of melanocytic uveal lesions from 2015 to 2018. Samples were obtained by ophthalmologist-performed FNAB and aliquoted for cytology and NGS. Various combinations of direct smears, liquid-based cytology slides, cell blocks, and immunohistochemical stains for melanocytic markers were performed. All samples were tested for molecular alterations using hybrid-capture-based NGS. RESULTS: There was sufficient material for cytologic diagnosis in 33 of 36 cases (92%), for NGS testing in 30 of 36 cases (83%), and for both cytologic diagnosis and NGS testing in 28 of 36 cases (78%). Of 7 cases that were cytologically categorized as indeterminate or diagnosed as "atypical" or "nondiagnostic," NGS testing was sufficient and diagnostic for melanoma in 5 cases. Of the cases diagnosed as melanoma on pathology, 20 cases (87%) had concordant NGS testing results, 2 lacked molecular alterations, and 1 was insufficient for testing. CONCLUSIONS: FNA sampling of melanocytic uveal lesions is adequate for both cytologic diagnosis and NGS testing. In a subset of cases in which pathologic findings were indeterminate, NGS testing results were clarifying for diagnosis. In addition, specific molecular alterations identified can aid in evaluating prognosis and guide further management.

Xanthogranuloma in the heavily irradiated low neck in a patient with head and neck cancer.

BACKGROUND: Head and neck cancer is often managed with a combination of surgery, radiation therapy, and chemotherapy, and skin toxicity is not uncommon. Xanthogranuloma is a pathological finding resulting from an inflammatory reaction that has not been previously reported following head and neck radiation therapy. CASE PRESENTATION: A patient with squamous cell carcinoma of the oropharynx, treated with definitive chemoradiation and hyperthermia, presented at eight-month follow-up with an in-field cutaneous lesion in the low neck, initially concerning for recurrent tumor. Biopsy showed xanthogranuloma and the patient underwent complete resection with congruent surgical pathology. The patient remained free of malignancy but continued to experience wound healing difficulties at the resection site which resolved with specialized wound care and hyperbaric oxygen. CONCLUSIONS: Skin toxicity is not uncommon in patients with head and neck cancer treated with radiation therapy. Awareness of unusual pathologic sequelae, such as xanthogranuloma, is needed to provide patient counseling while continuing appropriate surveillance for recurrent malignancy.

A case series of patients with HER2-overexpressed primary metastatic gastroesophageal adenocarcinoma.

BACKGROUND: Overexpression of the human epidermal growth factor 2 (HER2) is associated with an aggressive metastatic phenotype in patients with breast cancer but its prognostic impact is not well-characterized in gastroesophageal adenocarcinoma. PATIENTS AND METHODS: This is a retrospective series of three cases of HER2-positive gastroesophageal cancer. RESULTS: In this case series, we describe three patients presenting with widespread metastatic disease prior to development of symptoms from the primary tumor. Two patients presented with brain metastases, while one demonstrated lymphangitic spread to lungs. CONCLUSION: Pooled analyses of outcomes among sub-populations of contemporary trials are needed to better understand the natural history and prognostic impact of HER2 over-expression in patients with gastroesophageal cancers.

Association of tumor morphology with mismatch-repair protein status in older endometrial cancer patients: implications for universal versus selective screening strategies for Lynch syndrome.

Although there is consensus on the cost-effectiveness of a universal approach of screening all colorectal cancer patients for Lynch syndrome (LS) using mismatch-repair (MMR) protein immunohistochemistry (IHC) and/or microsatellite instability (MSI) testing, the question of universal versus selective screening of endometrial cancer patients remains to be resolved. We have prospectively implemented a selective screening algorithm for newly diagnosed endometrial cancer patients, triggered by patient age 50 years or younger, personal/family cancer pedigree that meets Bethesda guideline criteria, and/or presence of MMR-associated tumor morphology. Four-protein MMR IHC and MSI testing were performed if any of the criteria were met. This algorithm excluded screening of older patients without a cancer pedigree and whose tumors lacked MMR morphology. The aim of this study was to retrospectively determine whether these exclusion criteria missed any tumors with abnormal MMR. Among 273 consecutive patients with newly diagnosed endometrial cancers, 181 (66%) lacked criteria for screening. Retrospective MMR IHC confirmed intact MMR in 177 (97.8%) of these 181 unscreened patients, loss of MSH6 in 1 patient (0.5%), and loss of MSH1/PMS2 due to MLH1 promoter hypermethylation in 3 patients (1.7%). In comparison, 41% of patients fulfilling 1 or more criteria for screening had abnormal MMR IHC/MSI, mostly consisting of loss of MLH1/PMS2. MMR morphology contributed to detection of 92% of the abnormal MMR cases while cancer pedigree contributed to detection of the remainder. All of the abnormalities due to MSH2 and PMS2 were detected by the screening algorithm, but 1 of the 4 MSH6 cases was not. The latter finding is consistent with the literature that MSH6 endometrial cancers exhibit a phenotype different than those of the other MMR genes. We conclude that a genotype-specific approach to screening endometrial cancer for LS could consist of universal testing by MSH6 IHC and selective testing by MLH1, PMS2, and MSH2 IHC on the basis of age, cancer pedigree, and MMR morphology. Cost-effectiveness of this hybrid selective strategy deserves further study, particularly in comparison with a universal strategy. Further work to identify phenotypic features of endometrial cancers with methylated MLH1 that would allow them to be excluded from LS screening would also contribute to cost-effectiveness.