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IMPORTANCE: The optimal approach for treatment deescalation in human papillomavirus (HPV)–related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. OBJECTIVE: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16–positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. INTERVENTIONS: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). MAIN OUTCOMES AND MEASURES: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. RESULTS: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03210103

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

New therapies are being developed for breast cancer and in this process some “old” biomarkers are re-utilized and given a new purpose. It is not always recognized that, by changing a biomarker’s intended use, a new biomarker assay is created. The Ki-67 biomarker is typically assessed by immunohistochemistry (IHC) to provide a proliferative index in breast cancer. Canadian laboratories assessed the analytical performance and diagnostic accuracy of their Ki-67 IHC laboratory developed tests (LDTs), of relevance for the LDTs’ clinical utility.

Background: Spindle cell lipomas (SCLs) are benign tumors that are characteristically present on the upper back and neck, but in rare cases present throughout the respiratory mucosa, causing hoarseness, stridor, dyspnea, and obstruction.Objective: To highlight the importance of considering SCL in the diagnosis of benign respiratory tract tumors, a literature review identified all published cases of respiratory tract SCLs, including 2 from our institution: one case in the nasopharynx and 1 in the nasal valve.Methods: All case reports, series and literature reviews from the English literature from 1975 through March 2018 were systematically identified for review in the MEDLINE, EMBASE, and Scopus databases. Two additional cases from our institution were described.Results: In total, 24 cases of SCL in the respiratory tract were identified for review. Two cases from our institution are described here, bringing the total of reported cases to 26. Extensive analyses of oral cavity SCLs already exist, so we excluded this site from our review and focused on sites where SCLs may present with respiratory symptoms. Excluding the oral cavity and oropharynx, the most common location described is the larynx. All 26 cases were treated with excision. One tumor required a second surgery, but there were no other complications nor recurrences.Conclusion: Although rare, SCLs may arise from throughout the respiratory tract and cause dyspnea, hoarseness and stridor. Spindle cell lipoma should be considered in the differential diagnosis of a respiratory tract mass. This diagnosis confers a good prognosis and patients may be reassured that surgery is almost always curative.

Supplemental Digital Content is available in the text.Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1gene rearrangement. Following identification of an RREB1-MKL2fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2fusion product was identified in 19 tumors (90%), a single tumor (5%) had an EWSR1-CREMfusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.

OBJECTIVE Osteocutaneous facial retaining ligaments play an important role in the aging face. We sought to better characterize the biophysical properties of these ligaments and, in doing so, provide an empirical basis for the natural descent seen in facial aging. METHODS Five fresh frozen cadaver heads yielding 10 hemifaces were dissected to expose the orbital, zygomatic, buccomaxillary, and mandibular osteocutaneous ligaments. Each ligament was assessed and subjected to biomechanical testing. The main outcome measures included ligament dimensions, stiffness, percentage of elongation, and force to initial and ultimate failure. RESULTS Initial and ultimate failure testing revealed the zygomatic ligament to be strongest, followed by the orbital, mandibular, and maxillary ligaments. The zygomatic ligament was also stiffest, followed by the orbital, maxillary, and mandibular ligaments. The percentage of elongation acted as a surrogate marker of elasticity, with the greatest elasticity maintained by the mandibular ligament, followed by the orbital, zygomatic, and buccomaxillary ligaments. Ligament dimensions and biophysical properties did not vary relative to cadaveric hemiface, age, or sex. CONCLUSIONS To our knowledge, this is the first investigation to quantify the biomechanical properties of the facial retaining ligaments. Inherent ligament properties seem to be related to the changes observed in facial aging, although further study is required.

Velopharyngeal insufficiency is frequently managed surgically via the superiorly based pharyngeal flap procedure. The flap used in this procedure traditionally consists of both mucosa and muscle. Although muscle is included to potentially increase survival and tissue bulk, its inclusion may result in postoperative dysfunction of pharyngeal sidewall motion. Although the benefits of pharyngeal flap surgery are established, the denervated muscular portion of the flap appears to atrophy. The purpose of this study was to evaluate whether a flap consisting entirely of mucosa provides the same tissue bulk as a conventional pharyngeal flap 12 weeks postoperatively.

Cell survival may be enhanced in tumors by the inhibition of apoptosis, which allows tumor promoters to exert their effects. The bcl-2 related genes have been shown to contribute to either the inhibition or induction of apoptosis in a variety of neoplasms; therefore, it was hypothesized that the expression of these genes might contribute to malignant transformation in ovarian surface epithelial tumors. The expression of bcl-2 family proteins was investigated in 28 ovarian surface epithelial tumors, including serous and mucinous benign, borderline, and malignant tumors by immunohistochemical staining with antibodies to bcl-2, bax, bcl-X, and mcl-1 proteins. Staining intensity was scored on a 1+ to 3+ scale and the benign, borderline, and malignant tumors were compared. Significantly less immunoreactive bcl-2 and bcl-X proteins were present in malignant serous tumors compared to their benign counterparts. No difference was seen in immunostaining for bax or mcl-1 when benign, borderline, or malignant serous tumors were compared. In the mucinous tumors, no differences were seen in immunostaining for any of the bcl-2 family proteins between tumor types. The loss of expression of the antiapoptotic proto-oncogenes bcl-2 or bcl-X in serous carcinomas compared to benign serous tumors, together with previous demonstrations that the presence of bcl-2 in ovarian surface epithelial cancers is a favorable prognostic indicator, suggests that bcl-2 and bcl-X have biological functions in the ovary other than inducing apoptosis, acting instead as tumor suppressor proteins.

Rapidly destructive coxarthrosis (RDC) is a rare syndrome that involves aggressive hip joint destruction within 6–12 months of symptom onset with no single diagnostic laboratory, pathological, or radiographic finding. We report an original case of RDC as an initial presentation of seronegative rheumatoid arthritis (RA) in a 57-year-old Caucasian woman presenting with 6 months of progressive right groin pain and no preceding trauma or chronic steroid use. Over 5 months, she was unable to ambulate and plain films showed complete resorption of the right femoral head and erosion of the acetabulum. There were inflammatory features seen on computed tomography (CT) and magnetic resonance imaging (MRI). She required a right total hip arthroplasty, but arthritis in other joints showed improvement with triple disease modifying antirheumatic drugs (DMARD) therapy and almost complete remission with the addition of adalimumab. We contrast our case of RDC as an initial presentation of RA to 8 RDC case reports of patients with established RA. Furthermore, this case highlights the importance of obtaining serial imaging to evaluate a patient with persistent hip symptoms and rapid functional deterioration.

We describe the presentation, management, and clinical outcome of a massive acinic cell carcinoma of the parotid gland. The primary tumor and blood underwent exome sequencing which revealed deletions in CDKN2A as well as PPP1R13B, which induces p53. A damaging nonsynonymous mutation was noted in EP300, a histone acetylase which plays a role in cellular proliferation. This study provides the first insights into the genetic underpinnings of this cancer. Future large-scale efforts will be necessary to define the mutational landscape of salivary gland malignancies to identify therapeutic targets and biomarkers of treatment failure.