Pharyngeal Mucosal Margin Vessel Counts Predict Pharyngocutaneous Fistula in Salvage Laryngectomy.

OBJECTIVE: We evaluated vessel counts in the pharyngeal mucosal margins of patients who underwent salvage laryngectomy to establish whether mucosal vascularity might predict fistula risk. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary Medical Center. METHODS: Patients who underwent salvage total laryngectomy at our institution between 1999 and 2015 were identified. Pharyngeal mucosal margins from laryngectomy specimens were evaluated histologically for each patient, and vessel counts were performed on 5 ×10 images. The primary outcome measure was fistula within 30 days of surgery and mean vessel counts were assessed as the principle explanatory variable. RESULTS: Seventy patients were included and 40% developed a postoperative fistula. There was a large difference in the mean vessel count in patients who did develop fistula (48.6 vessels/×10 field) compared to those who did not (34.7 vessels/×10 field). A receiver operative characteristic curve found that a cutoff value of 33.9 vessels/×10 field provided a sensitivity of 75% and specificity of 62% to predict the likelihood of fistula occurrence (area under the curve = 0.71, 95% confidence interval [CI]: 0.59-0.83). In a binary logistic regression, patients with vessel counts greater than 33.9 had a 5-fold increased risk of developing fistula (95% CI: 1.8-16.45). Histologically, vessels in the pharyngeal mucosa of patients who developed fistulas were more disorganized. CONCLUSION: After salvage laryngectomy, patients with higher mean mucosal margin vessel counts are at increased risk of fistula. The mechanism is unknown, but the disorganization of the vasculature may contribute to poor wound healing. Vessel counting may allow for fistula risk stratification and guide postoperative care.

Conjunctival Apocrine Hidrocystoma: A Case Report and Review of Literature.

PURPOSE: To describe the clinical features of a conjunctival apocrine hidrocystoma that developed 6 decades after a strabismus surgery and review existing literature on apocrine hidrocystomas of the conjunctiva and caruncle. METHODS: Case report and review of literature on conjunctival apocrine hidrocystomas. RESULTS: A 71-year-old man with a history of strabismus surgery as a child presented with a cystic lesion on the nasal conjunctiva and caruncle for 1 year. Excision of the lesion showed a unilocular cavity lined by a double layer of cells with the hallmark finding of apical decapitations, confirming a diagnosis of apocrine hidrocystoma. Seven additional cases of conjunctival and caruncular apocrine hidrocystomas were reviewed. All cases presented after 50 year of age. Most cases presented nasally or within the caruncle and had a pigmented appearance. No other reported cases had a history of trauma or surgery. All cases were treated with surgical excision without recurrence. CONCLUSIONS: History of strabismus surgery or conjunctival trauma may lead to ectopic deposition of apocrine glands that may contribute to the formation of an apocrine hidrocystoma.

Histologic Features of Mycobacterial Spindle Cell Pseudotumors: A Multi-institutional Clinicopathologic Analysis of 14 Cases.

Mycobacterial spindle cell pseudotumors (MSPs) are a rare and diagnostically challenging manifestation of non-tuberculous mycobacterial (NTM) infections. Proper recognition of these pseudotumors is important because they are treatable and benign. In this study, we evaluated the morphologic patterns of MSPs to improve their pathologic identification. Clinical and morphologic features of 14 MSPs were analyzed. Histologic factors evaluated included the architectural growth pattern of spindled or epithelioid macrophages, granulomas and their location within the lesion, neutrophilic microabscesses, multinucleated giant cells, necrosis, and effacement of background tissue. The composition of inflammatory infiltrates, organism density by acid-fast staining, and stromal changes were also assessed. In addition, 8 of 14 cases underwent molecular microbiology identification by a clinical amplicon-sequencing assay for non-tuberculous mycobacteria. MSP sites included 2 bowel, 10 lymph nodes, 1 liver, and 1 extremity. Cases with available clinical history (n=10) all occurred in immunocompromised patients. All demonstrated effacement of normal structures with spindled cells arranged in a storiform or fascicular architectural pattern. In addition, all cases showed lymphocytic inflammation, with prominent concurrent neutrophilic inflammation in 50% (7/14) of cases. Other morphologic findings included foamy histiocytes (64%, 9/14), peripherally situated granulomas (21%, 3/14), and neutrophilic microabscesses (21%, 3/14). All tested cases were positive for NTM by PCR methods. Mycobacterium avium was the most commonly isolated pathogen (6/8). Mycobacterial spindle cell pseudotumors show predominantly spindled morphology that may be mistaken as a neoplasm. Surgical pathologists who evaluate lymph nodes, soft tissue, and gastrointestinal tissues should be aware of this spindled tumefactive phenomenon in the setting of immunocompromised patients. Recognition of key morphologic features of neutrophilic inflammation, peripheral granulomas, or foamy histiocytes within a spindled lesion can help guide the pathologist to a correct diagnosis of an inflammatory process secondary to infection rather than a spindle cell neoplasm. Accurate diagnosis to facilitate appropriate antimicrobial and/or surgical therapy requires a comprehensive evaluation combining clinical, histopathologic, and microbiological findings.

Upfront Neck Dissection for Treatment Selection and Improvement in Quality of Life as a Novel Treatment Paradigm for Deintensification in HPV+ OPSCC.

PURPOSE: Locoregionally advanced HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has excellent cure rates, although current treatment regimens are accompanied by acute and long-term toxicities. We designed a phase II deescalation trial for patients with HPV+ OPSCC to evaluate the feasibility of an upfront neck dissection to individualize definitive treatment selection to improve the quality of life without compromising survival. PATIENTS AND METHODS: Patients with T1-3, N0-2 HPV+ OPSCC underwent an upfront neck dissection with primary tumor biopsy. Arm A included patients with a single lymph node less than six centimeters, with no extracapsular spread (ECS) and no primary site adverse features underwent transoral surgery. Arm B included patients who had two or more positive lymph nodes with no ECS, or those with primary site adverse features were treated with radiation alone. Arm C included patients who had ECS in any lymph node and were treated with chemoradiation. The primary endpoint was quality of life at 1 year compared with a matched historical control. RESULTS: Thirty-four patients were enrolled and underwent selective neck dissection. On the basis of pathologic characteristics, 14 patients were assigned to arm A, 10 patients to arm B, and 9 to arm C. A significant improvement was observed in Head and Neck Quality of Life (HNQOL) compared with historical controls (-2.6 vs. -11.9, P = 0.034). With a median follow-up of 37 months, the 3-year overall survival was 100% and estimated 3-year estimated progression-free survival was 96% [95% confidence interval (CI), 76%-99%]. CONCLUSIONS: A neck dissection-driven treatment paradigm warrants further research as a deintensification strategy.

A rare entity: Ganglioneuroma of the prostate.

Ganglioneuromas are benign tumors arising from the neural crest. Histologically, they are composed of mature Schwann cells and ganglion cells admixed with fibrous tissue. While they frequently are seen in the abdomen and mediastinum, rare reports have highlighted their occurrences in the genitourinary system. The only prior reported prostatic ganglioneuroma arose in a patient with a history of neurofibromatosis type 1. In this report, we highlight the first reported prostatic ganglioneuroma without a known genetic linkage.

Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols.

BACKGROUND: Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread. METHODS: A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998- 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival. RESULTS: Median overall survival (mOS) improved over time (6.7 months in 1998-2007 to 11.8 months in 2008-2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2-2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4-3.0], disease-free interval (DFI) ≤6 months (HR, 1.4 [1.02-2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1-3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4-4.0]), DFI >6 months (OR, 2.4 [1.5-4.0]), and body mass index ≥30 (OR, 2.3 [1.1-4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24-0.55). CONCLUSION: These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials. PLAIN LANGUAGE SUMMARY: After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body. This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns. Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients. These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.

Sinonasal Neuroendocrine Carcinoma: 15 Years of Experience at a Single Institution.

Objectives Sinonasal neuroendocrine carcinomas (SNECs) are among the rarest paranasal sinus cancers. Consensus guidelines for therapy are difficult to develop due to limited data regarding the natural history and successful treatment of these tumors. This study presents 15 years of experience treating SNEC at a single institution and a review of the literature. Design Retrospective review. Setting Academic medical center in the United States. Participants Patients diagnosed with primary SNEC. Main Outcome Measures Overall survival. Results Thirteen patients were identified and included. Overall estimated survival was 74.6% at 5 years. Ten of 13 (76.9%) patients were diagnosed with high-grade neuroendocrine carcinoma and three (23.1%) with intermediate or low grade. All three patients with low- or intermediate-grade cancer survived more than 10 years from their initial diagnosis (median survival: 11.6 years) and are currently alive. The four patients who died had high-grade carcinoma, and estimated overall 5-year survival for all patients with high-grade carcinomas was 65.6%. Five patients, all with high-grade carcinoma, of seven who completed primary chemoradiation therapy (CRT) required salvage resection, and 60% are alive without disease. Conclusion This cohort has a higher overall rate of survival than many recent case series and reviews. There is consensus that multimodal therapy is preferred over monotherapy, but approaches to treatment vary widely. Our approach of surgical resection as primary therapy for low-grade tumors and primary CRT for high-grade SNEC has been successful, and could indicate hope for improved survival among these patients.

Gastroblastoma of the Pylorus: A Case Report and Review of the Literature.

Gastroblastoma is an extremely rare biphasic tumor that typically occurs in the stomach in patients between the ages of 10 and 30. Only 16 cases have been reported previously. These tumors are important to diagnose and distinguish from more aggressive neoplasms; although numbers are small, prognosis appears excellent overall with complete excision, with only occasional metastasis and/or local recurrence. We report a case of gastroblastoma in a 26-year-old male arising from the pylorus and extending through the first and second portions of the duodenum. This is the first case to be reported from this specific location.

Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma.

Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor CRTC1/3-MAML2 gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma. Bioinformatics analysis was performed on 48 MEC transcriptomes. Subsequent targeted capture DNA sequencing was used to annotate HPV content and integration status in the host genome. HPV of any type was only identified in 1/48 (2%) of the MEC transcriptomes analyzed. Importantly, the one HPV16+ tumor expressed high levels of p16, had high expression of HPV16 oncogenes E6 and E7, and displayed a complex integration pattern that included breakpoints into 13 host genes including PIK3AP1, HIPI, OLFM4,SIRT1, ARAP2, TMEM161B-AS1, and EPS15L1 as well as 9 non-genic regions. In this cohort, HPV is a rare driver of MEC but may have a substantial etiologic role in cases that harbor the virus. Genetic mechanisms of host genome integration are similar to those observed in other head and neck cancers.

Prognostic value of CD103+ tumor-infiltrating lymphocytes and programmed death ligand-1 (PD-L1) combined positive score in recurrent laryngeal squamous cell carcinoma.

OBJECTIVES: In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery. MATERIALS AND METHODS: This was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson's correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests. RESULTS: Only CD103+ TILs showed a statistically significant, weakly-positive correlation with PD-L1 CPS (r2 = 0.264, p < 0.015). No other TIL subsets correlated with PD-L1 CPS in our cohort. The most favorable survival outcomes were seen in patients with pathologic N0 tumors showing high CD103+ TILs and/or high PD-L1 CPS staining. CONCLUSION: Among patients with persistent or recurrent LSCC, CD103+ TILs only modestly correlated with PD-L1 CPS. A combined biomarker score incorporating CD103+ TILs and PD-L1 CPS greatly enhanced survival discrimination. This model may have additional utility in predicting the clinical benefit of immunotherapies in persistent or recurrent LSCC in the future.

Deadly Fungi: Invasive Fungal Rhinosinusitis in the Head and Neck.

Invasive fungal rhinosinusitis (IFRS) is a serious infection that is associated with high morbidity and mortality rates. The incidence of IFRS has been increasing, mainly because of the increased use of antibiotics and immunosuppressive drugs. Rhino-orbital cerebral mucormycosis has recently reemerged among patients affected by COVID-19 and has become a global concern. The detection of extrasinus involvement in its early stage contributes to improved outcomes; therefore, imaging studies are essential in establishing the degree of involvement and managing the treatment properly, especially in immunocompromised patients. The common sites of extrasinus fungal invasion are the intraorbital, cavernous sinus, and intracranial regions. Fungi spread directly to these regions along the blood vessels or nerves, causing devastating complications such as optic nerve ischemia or compression, optic neuritis or perineuritis, orbital cellulitis, cavernous sinus thrombosis, mycotic aneurysm, vasculitis, internal carotid arterial occlusion, cerebral infarction, cerebritis, and brain abscess. IFRS has a broad imaging spectrum, and familiarity with intra- and extrasinonasal imaging features, such as loss of contrast enhancement of the affected region, which indicates tissue ischemia due to angioinvasion of fungi, and the surrounding anatomy is essential for prompt diagnosis and management. The authors summarize the epidemiology, etiology, risk factors, and complications of IFRS and review the anatomy and key diagnostic imaging features of IFRS beyond the sinonasal regions. ©RSNA, 2022.

Extent of Extranodal Extension in Oral Cavity Squamous Cell Carcinoma is Not Independently Associated With Overall or Disease-Free Survival at a 2.0-mm Threshold.

PURPOSE: The presence of extranodal extension (ENE) conveys a poor prognosis in oral cavity squamous cell carcinoma (OSCC); however, there is no consensus regarding whether the histopathologic extent of ENE (e-ENE) may be a more discriminating prognostic indicator. The purpose of this study was to assess the impact of minor ENE (<2.0 mm) versus major ENE (≥ 2.0 mm) on overall survival (OS) and disease-free survival (DFS) in OSCC. MATERIALS AND METHODS: A single-institution, retrospective cohort study was designed using an electronic medical record review. Inclusion criteria included patients with OSCC and cervical node metastasis. All subjects were treated between the years 2009 and 2017 in the Michigan Medicine Department of Oral and Maxillofacial Surgery (Ann Arbor, Michigan). The primary predictor variable was e-ENE, measured as the maximum distance of tumor invasion into extranodal tissue from the outer aspect of the nodal capsule. Primary outcome variables were OS and DFS. Other covariates included demographic data, tumor staging, and histopathologic data. Descriptive statistics were performed. Kaplan-Meier survival plots for OS and DFS were performed. The data were mined for an alternative threshold at which e-ENE may impact survival using Cox proportional hazards models. RESULTS: One hundred sixty eight subjects were included (91 ENE-negative, 48 minor ENE, and 29 major ENE). Most subjects were male (62%) and the mean age was 62.9 years. Mean follow-up time was 2.97 +/- 2.76 years. There was no statistically significant difference in OS or DFS between minor and major ENE. Five-year OS for minor ENE was 30.4% versus 20.7% for major ENE (P = .28). Five-year DFS for minor ENE was 26.7% versus 18.1% for major ENE (P = .30). Five-year OS and DFS was worse for subjects with ENE-positive disease versus ENE-negative disease (OS: 26.9% vs 63.1%, hazard ratio [HR]: 2.70, 95% confidence interval [CI]: [1.77, 4.10], P < .001; DFS: 23.7% vs 59.7%, HR = 2.55, 95% CI [1.71, 3.79], P < .001). At an alternative threshold of 0.9 mm e-ENE, there was greater DFS in subjects with e-ENE 0.1-0.9 mm versus e-ENE > 0.9 (40.6% vs 18.9%, respectively) (HR = 0.49, 95% CI [0.24, 0.99], P = .047). CONCLUSION: There was no independent association between survival and e-ENE at a 2.0-mm threshold.

Relationships between contrast-enhanced computed tomography features of hard palate cancer and pathological depth of invasion.

OBJECTIVE: The study aimed to determine the relationships between contrast-enhanced computed tomography (CECT) features of hard palate cancer (radiological depth of invasion [r-DOI], detectability of the lesion, and tumor invasion into the palatal bone) and the pathological DOI (p-DOI) of the tumors. STUDY DESIGN: In total, 36 lesions were retrospectively evaluated by 2 board-certified radiologists, who examined CECT scans for the radiological features, and 2 board-certified pathologists, who measured the p-DOI on histopathologic sections. Correlation between r-DOI and p-DOI was calculated. The Youden index was used to calculate the optimal p-DOI cutoff values to distinguish between detectable and undetectable lesions and between tumors with and without bony structure invasion. RESULTS: There was excellent agreement between r-DOI and p-DOI (intraclass correlation coefficient = 0.80). The p-DOI of CECT-detectable lesions was significantly greater than that of CECT-undetectable lesions (P < .001), with a p-DOI cutoff value of 4 mm. The p-DOI of lesions that had invaded the palatal bone was significantly larger than that of lesions without invasion (P = .039), with a p-DOI cutoff value of 7 mm. CONCLUSION: Radiological DOI, tumor detectability, and invasion into the palatal bone can be useful in planning surgical treatment strategies for hard palate cancer.

Microsecretory Adenocarcinoma of the Ear Canal: Novel Cutaneous Analog of a Salivary Gland Neoplasm.

ABSTRACT: Microsecretory adenocarcinoma (MSA) of the salivary gland is a new entity recently added to the World Health Organization Classification of Head and Neck Tumors. This tumor is characterized by a recurrent MEF2C-SS18 translocation. We present a nodular tumor confined to the dermis of the ear canal of a 44-year-old patient, which demonstrated classic histopathologic features and molecular alteration of MSA. Specifically, the tumor was composed of numerous tubules and microcysts filled with abundant basophilic mucinous secretion and associated with a fibromyxoid stroma. The tumor cells were diffusely positive for CK7 and SOX10 and variably positive for S100 and p63. Breakapart fluorescence in situ hybridization for SS18 confirmed rearrangement of this gene. Together, these findings support a primary cutaneous MSA, presumably arising from ceruminous glands of the ear canal. Based on current knowledge of its salivary gland counterpart, cutaneous MSA is expected to be locally invasive but unlikely to recur or metastasize on complete excision.

Cytomorphology of nodular histiocytic/mesothelial hyperplasia.

Nodular histiocytic/mesothelial hyperplasia (NHMH) is a pathologic entity that has not been well characterized in the cytopathology literature. This is unfortunate because if unrecognized, NHMH may be misdiagnosed when encountered in cytology specimens. The aim of this communication is to accordingly alert cytologists about NHMH by means of an illustrative case report.

Phosphaturic Mesenchymal Tumors of the Sinonasal Area and Skull Base: Experience at a Single Institution.

OBJECTIVES: Phosphaturic mesenchymal tumor (PMT) is a rare, polymorphous neoplasm with a highly variable presentation and natural history and unpredictable clinical course. The primary objective was to describe our clinical experience with and management of 4 markedly different cases of sinonasal and skull base PMT. METHODS: A retrospective case series with chart review, and relevant literature review, was performed at a tertiary academic medical center between 1998 and 2020. Adult patients treated for PMTs of the sinonasal area and skull base were included. Our main outcome measures included postoperative laboratory findings and radiological evidence of disease remission. RESULTS: Four patients (2 Males, 2 Females; Mean Age: 63.5 years) with PMTs of the skull base have been managed at our institution since 1998. Patient presentations varied, ranging from severe phosphorus wasting and osteoporosis to symptoms secondary to mass effect, including nasal obstruction and rhinorrhea. All 4 patients were eventually found to have elevated levels of fibroblast growth factor 23. Tumors were located in the sinonasal area (right frontal sinus, right ethmoid sinus, and right nasal cavity, respectively) in 3 patients and in the lateral skull base (right jugular foramen) in 1 patient. All 4 patients underwent complete surgical resection of their tumors. PMT tissue pathology was confirmed in all cases. Gross total resection was achieved in all patients. There was no chemical or radiological evidence of disease recurrence in any patients at follow-up. CONCLUSIONS: The presentation of skull base PMT is variable, and it may mimic other mass pathologies of the head and neck. Complete surgical resection with negative margins is potentially curative.