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Laryngectomy margin assessment is an important part of patient care and can affect outcomes. There is no standard approach to grossing laryngectomy specimens, with variations in the published guidelines. A uniform approach to margin assessment may be helpful to improve patient care and future research. At the very least, sampling of all mucosal margins (arytenoid area, hypopharyngeal, and anterior epiglottis) and tracheal margin should be performed. Sampling of soft tissue margins may be delegated to the pathologist, and contingent on the tumor extent into soft tissue. If a tracheostomy is present, skin and soft tissue margins should be sampled from the stoma. This review provides a template for laryngectomy margin assessment and can be used as a guideline as to which margins should be assessed., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: KRAS mutation is a common occurrence in Pancreatic Ductal Adenocarcinoma (PDA) and is a driver mutation for disease development and progression. KRAS wild-type PDA may constitute a distinct molecular and clinical subtype. We used the Foundation one data to analyze the difference in Genomic Alterations (GAs) that occur in KRAS mutated and wild-type PDA., Methods: Comprehensive genomic profiling (CGP) data, tumor mutational burden (TMB), microsatellite instability (MSI) and PD-L1 by Immunohistochemistry (IHC) were analyzed., Results and Discussion: Our cohort had 9444 cases of advanced PDA. 8723 (92.37%) patients had KRAS mutation. 721 (7.63%) patients were KRAS wild-type. Among potentially targetable mutations, GAs more common in KRAS wild-type included ERBB2 (mutated vs wild-type: 1.7% vs 6.8%, p <0.0001), BRAF (mutated vs wild-type: 0.5% vs 17.9%, p <0.0001), PIK3CA (mutated vs wild-type: 2.3% vs 6.5%, p <0.001), FGFR2 (mutated vs wild-type: 0.1% vs 4.4%, p <0.0001), ATM (mutated vs wild-type: 3.6% vs 6.8%, p <0.0001). On analyzing untargetable GAs, the KRAS mutated group had a significantly higher percentage of TP53 (mutated vs wild-type: 80.2% vs 47.6%, p <0.0001), CDKN2A (mutated vs wild-type: 56.2% vs 34.4%, p <0.0001), CDKN2B (mutated vs wild-type: 28.9% vs 23%, p =0.007), SMAD4 (mutated vs wild-type: 26.8% vs 15.7%, p <0.0001) and MTAP (mutated vs wild-type: 21.7% vs 18%, p =0.02). ARID1A (mutated vs wild-type: 7.7% vs 13.6%, p <0.0001 and RB1(mutated vs wild-type: 2% vs 4%, p =0.01) were more prevalent in the wild-type subgroup. Mean TMB was higher in the KRAS wild-type subgroup (mutated vs wild-type: 2.3 vs 3.6, p <0.0001). High TMB, defined as TMB > 10 mut/mB (mutated vs wild-type: 1% vs 6.3%, p <0.0001) and very-high TMB, defined as TMB >20 mut/mB (mutated vs wild-type: 0.5% vs 2.4%, p <0.0001) favored the wild-type. PD-L1 high expression was similar between the 2 groups (mutated vs wild-type: 5.7% vs 6%,). GA associated with immune checkpoint inhibitors (ICPIs) response including PBRM1 (mutated vs wild-type: 0.7% vs 3.2%, p <0.0001) and MDM2 (mutated vs wild-type: 1.3% vs 4.4%, p <0.0001) were more likely to be seen in KRAS wild-type PDA., Competing Interests: All Foundation Medicine co-authors disclose that they are employees of Foundation Medicine and own shares in Roche Holdings. Authors affiliated with Upstate have no conflict of interest to disclose., (Copyright © 2023 Ashok Kumar, Serinelli, Zaccarini, Huang, Danziger, Janovitz, Basnet, Sivapiragasam, Graziano and Ross.)

Background: Barium sulfate is utilized for imaging of the gastrointestinal tract and is usually not deposited within the wall of the intestine. It is thought that mucosal injury may allow barium sulfate to traverse the mucosa, and allow deposition to occur uncommonly. Most pathology textbooks describe the typical barium sulfate deposition pattern as small granular accumulation in macrophages, and do not describe the presence of larger rhomboid crystals. This review will summarize the clinical background, radiographic, gross, and microscopic features of barium sulfate deposition in the gastrointestinal tract. A review of the PubMed database was performed to identify all published cases of barium sulfate deposition in the gastrointestinal tract that have been confirmed by pathologic examination., Conclusions: A review of the literature shows that the most common barium sulfate deposition pattern in the gastrointestinal tract is finely granular deposition (30 previously described cases), and less commonly large rhomboid crystals are seen (19 cases) with or without finely granular deposition. The fine granules are typically located in macrophages, while rhomboid crystals are usually extracellular. There are various methods to support that the foreign material is indeed barium sulfate, however, only a minority of studies perform ancillary testing. Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDS) can be useful for definitive confirmation. This review emphasizes the importance of recognizing both patterns of barium sulfate deposition, and the histologic differential diagnosis., (© 2022. The Author(s).)

Low-grade fibromyxoid sarcoma is an uncommon soft tissue malignant neoplasm with deceptively bland histologic appearance, and a tendency for late recurrence and metastasis. Cases with significant heterotopic ossification are exceedingly rare. In the literature, only 9 cases of low-grade fibromyxoid sarcoma with bone formation proven by histopathology have been described in detail in the literature. We report the case of a 42-year-old male presenting with a 20-year history of a painless tumor in his left upper thigh. Computed tomography images showed coarse punctate central and peripheral calcifications, and the mass was resected. The tumor cells were immunohistochemically positive for MUC4, and also positive for FUS (16p11.2) gene rearrangement by fluorescence in situ hybridization. Besides, immunohistochemistry showed focal weak to moderate staining for TLE-1. At histology, heterotopic ossification was also observed. A diagnosis of low-grade fibromyxoid sarcoma (grade 1, stage T4) was rendered, and prior reports of these tumors with bone formation have not concomitantly described TLE-1 staining. This paper aims to characterize the radiologic, pathologic, and clinical features of low-grade fibromyxoid sarcoma showing heterotopic ossification reported in the literature, and further review the morphologic spectrum of this malignant neoplasm., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Oncocytic histologic features can be seen in a variety of salivary gland carcinomas. We performed a comprehensive molecular profiling of 15 salivary gland malignancies with oncocytic features (diagnosed as oncocytic carcinoma, carcinoma NOS with oncocytic features, or salivary duct carcinoma with oncocytic features). We reveal multiple novel molecular alterations that have not been previously described in other salivary gland malignancies, including, but not limited to, KEL amplification (13.3%, 2/15), PARP1 amplification (13.3%, 2/15), and EPHB4 amplification (13.3%, 2/15). Alterations in KMT2C (13.3%, 2/15), ERBB3 (13.3%, 2/15), CTNNA1 (13.3%, 2/15), and SMAD4 (20%, 3/15) were also found in this series and have been reported in other salivary gland malignancies. Alterations that have been reported in salivary duct carcinoma were also identified, including TP53 (40%, 6/15) , ERBB2 mutations (13.3%, 2/15) , ERBB2 amplification (13.3%, 2/15), PIK3CA (26.7%, 4/15) , PTEN (20%, 3/15), BRCA2 (20%, 3/15), BRAF (20%, 3/15), CDKN2A/B (20%, 3/15), CDH1 (13.3%, 2/15), and HRAS (13.3%, 2/15). Oncocytic salivary gland malignancies are a molecularly heterogenous group of tumors with partial overlap with salivary duct carcinoma subtypes., Competing Interests: E.S., R.S.P.H., D.C.P., T.J., J.S.R. are employees of Foundation Medicine, Inc., which is a wholly owned subsidiary of Roche and hold equity in Roche Holdings. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess the effect of tobacco use on oral mucosal tissue harvested for urethroplasty., Materials and Methods: Retrospective histologic and immunohistochemical (IHC) evaluation of available buccal mucosa tissue samples from patients that underwent buccal mucosa graft urethroplasty from 2018 to 2020. Patients were asked about tobacco use during pre-operative workup. Patients were counseled on and provided resources to aid in cessation of tobacco use, but surgical cases were not canceled or delayed if patients are unable cease all tobacco use. Patients that ceased use 3 months prior to surgery were considered former users. A single pathologist blinded to the smoking status evaluated the buccal mucosa specimens for histologic changes. Quantitative IHC for p75 and Sox2 were obtained. These investigative markers were selected due to their clear and direct involvement in oral mucosa's regenerative mechanism. Current tobacco users, former users and control patients were compared using ANOVA and Chi-square analyses., Results: Study cohort was 16 current users, 16 former users, 32 controls. Demographics did not differ across the groups. Blinded histologic analysis between all groups found no differences. Pair-wise statistical analysis found greater collagen density in the control group compared to current users (P = .01). No differences were found between former and current users or former users and controls. IHC analysis did not demonstrate any difference in the amount or localization of epithelial stem cell markers., Conclusion: Our study of buccal mucosa did not find clear or clinically significant histologic or IHC differences between patients with or without a history of tobacco use., (Published by Elsevier Inc.)

Transcription factor E3 (TFE3) represents a useful target for immunohistochemistry assays in routine surgical pathology practice. This protein has shown nuclear expression in a variety of normal tissues; however, this expression is usually at very low levels, while strong nuclear immunoreactivity of TFE3 has been seen almost exclusively in tumors. We present the case of a 30-year-old female on oral contraceptive pill (drospirenone/ethinylestradiol) and with complaints of dysmenorrhea and menorrhagia. She was found to have a cervical mass on pelvic ultrasound, and the biopsy showed fragments of benign squamous epithelium and polypoid endometrial tissue with stromal pseudodecidualization and abundant mixed inflammation. The pseudodecidualized stromal component showed moderate to strong nuclear staining in ~85% of stromal cells for TFE3. We discuss the intracellular role of TFE3 during inflammatory states and hypothesize that TFE3 expression can be associated with ongoing inflammation. Our case shed light upon the possibility that non-neoplastic environments with an inflammatory background could lead to increased nuclear expression of TFE3. Pathologists should be aware of the possibility of strong nuclear expression of TFE3 in non-neoplastic endometrium to avoid potential misdiagnosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Frozen section evaluation of head and neck squamous cell carcinoma (SCC) is critical for margin status and subsequent patient therapy. In this study, we retrospectively reviewed the rate of frozen-permanent section discrepancies in blocks with two frozen section levels compared to ≥ three levels in oral cavity and oropharyngeal SCCs. A search of the cases with both intraoperative frozen sections and corresponding permanent sections for SCCs in the oral cavity and oropharynx was performed. Frozen sections and permanent slides were compared. The nature of discrepancies was assigned to one of the following: change in diagnosis, margin status, or distance of the tumor from the margin. The cause of the discrepancy was designated as one of the following: block sampling, gross sampling, interpretation, or technical error. The pathologist experience, frozen section technical experience, and intraoperative impact of each discrepancy were also evaluated. A total of 654 frozen and corresponding permanent blocks were assessed. For 532 of the frozen section blocks, two levels were cut, while 122 frozen section blocks had ≥ three levels. Thirty-five frozen-permanent section discrepancies were observed (5.4% of all blocks). Among these, 2.5% had a possible or definitive intraoperative impact. The percentage of discrepancies in the ≥ three levels group (5.7%) was slightly higher than the two-level group (5.3%), and this difference was not statistically significant. For the two-level group, the overall block sampling error rate was 4.5%. This was not significantly different from the 4.1% block sampling error rate seen in the ≥ three levels group. The rate of block sampling discrepancy did not show significant differences based on attending or frozen section technical experience. A change in margin distance (closer margin detected on permanent) occurred in 4% of the blocks and involved 16% of the patients. This review of oral cavity and oropharynx SCCs frozen/permanent section discrepancies shows that the error rate is not significantly different depending on the number of levels cut. The results suggest that always performing more than two frozen section levels may not yield a decreased discrepancy rate. A change in margin distance occurred quite frequently, but only in rare cases it had a definitive impact on the intraoperative management. Given the importance of correct intraoperative diagnosis in patient management, additional levels may be warranted depending on the clinical scenario., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To determine the prevalence of patients who require vaginal cavity remnant excision and obliteration during neourethral stricture repair and to characterize the histological composition of the excised tissue., Methods: A retrospective review was performed of all transgender men who underwent neourethral stricture repair. Preoperative imaging and operative reports were reviewed to determine the presence of a vaginal cavity remnant that was excised and obliterated during neourethral reconstruction. Pathology slides were reviewed by 2 pathologists to determine if there was presence of stratified squamous epithelium consistent with vaginal tissue within the vaginal cavity remnant., Results: A total of 47 consecutive transgender men underwent neourethral stricture repair between January 2014 and December 2020. Of these, 18 patients (38%) with a mean age of 37 years (23-59) underwent excision and obliteration of a vaginal cavity remnant. Seventy eight percent (14/18) had a prior phalloplasty and 22% (4/18) had a prior metoidioplasty. Primary vaginectomy type was not associated with whether or not a patient had a vaginal cavity remnant (P = .12). Histological evaluation demonstrated the presence of vaginal epithelium in all vaginal cavity remnant specimens., Conclusion: A high percentage of transgender men with neourethral strictures present with vaginal cavity remnants despite prior vaginectomy. Pathological evaluation confirms that all vaginal cavity remnant specimens contain vaginal epithelium that was either incompletely excised or regenerated. While the implications of this residual vaginal epithelium require further investigation, total removal of vaginal tissue primarily or during reconstruction is important given the risk of associated symptoms., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma resembling breast ductal carcinoma. It accounts for ~10% of malignant tumors of the salivary glands. Most cases show expression of CK7 and androgen receptor. PAX-8 is a transcription factor, with expression reported in renal, Müllerian, and thyroid carcinomas. Previous studies have described an absence of PAX-8 immunostaining in most primary salivary gland neoplasms, including SDCs. However, PAX-8 expression is frequently found in neoplasms that can metastasize to salivary glands, suggesting the possibility that this protein can be used to differentiate SDC from secondary neoplastic involvement of the salivary gland. We evaluated the expression of PAX-8 in 14 cases of SDC from our institution. One case showed diffuse moderate to strong PAX-8 positivity, while 2 tumors showed focal weak staining. Therefore, we conclude that although the majority of SDC are negative for PAX-8, rare diffuse positivity can be seen in these primary salivary gland tumors. This could potentially pose difficulty in ruling out metastatic disease from another PAX-8-positive primary neoplasm., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Synovial sarcomas are infrequent malignant tumors occurring mostly in adolescents and young adults. The occurrence of synovial sarcoma in the hand-wrist area is rare (4 to 8.5% of all synovial sarcomas in different studies)., Case Presentation: This report documents an uncommon case of synovial sarcoma occurring in the hand-wrist of a 69-year-old Caucasian woman. She was subsequently treated with surgical excision and radiotherapy without recurrence after follow up., Conclusions: This paper aims to characterize the demographic, pathologic, and clinical features with a literature review. The present literature review confirms that hand-wrist synovial sarcomas are more frequent among males and subjects 10 to 40 years old. Most cases in this location are usually not larger than 5 cm in size. The five-year survival rate is higher than that reported in a previous review on hand synovial sarcomas, and this suggests an improved survival in recent decades.

Warthin tumor is the second most common benign parotid neoplasm. Its association with non-salivary gland neoplasms has been sporadically reported. We reviewed clinical records of Warthin tumor diagnosed on aspiration cytology and surgical pathology to determine if there is any association with other extra-salivary gland malignant neoplasms. Computer search was made for all cases of Warthin tumor diagnosed in the parotid gland by aspiration cytology and surgical pathology at our institution between January 2007 and August 2016. Clinical records of all cases were reviewed for any associated malignant neoplasms and any surgical follow up. All available cytology and histologic material was reviewed. Seventy-three patients (mean 66.9, M:F 1.1:1, age range 43 to 87 years) with Warthin tumor were identified. 45 (62%) were diagnosed on aspiration cytology only, 19 (26%) had cytologic diagnosis as well as concordant surgical follow up, and 9 (12%) were diagnosed based on surgical pathology only. Average age for patients with and without secondary malignancy was 70.5-years, and 63.4-years, respectively (p < 0.05). Average pack years for patients with and without secondary malignancy was 45.4, and 39.8, respectively (p > 0.05). Twenty-seven (37.0%) patients harbored a malignant neoplasm. Association of extra salivary gland malignant neoplasms in 37.0% of our cases suggest that the prevalence of secondary non-salivary neoplasms in patients harboring Warthin tumor might have been underestimated. Squamous cell carcinoma was the most commonly associated non-salivary malignant neoplasm. The association of Warthin tumor with smoking plays an important role in this increased rate of malignancy, and this is supported by the fact that smoking is highly associated with head and neck and lung cancers.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor most commonly seen in young adults and children. We report a case with morphology and immunohistochemistry supporting the diagnosis of synovial sarcoma. On core biopsy, the tumor had spindle cell and epithelioid morphology with a myxoid background. Staining for transducin-like enhancer of split 1 and CD99 were positive; however, subsequent fluorescence in situ hybridization for SYT (SS18, nBAF chromatin remodeling complex subunit) break apart returned negative. Further study showed fluorescence in situ hybridization for EWSR1 (EWS RNA binding protein 1) gene rearrangement, supporting the diagnosis of AFH. The resected specimen showed a predominant spindle cell proliferation along with histiocytoid areas supporting a diagnosis of AFH. This case report highlights the fact that synovial sarcoma and AFH can overlap morphologically and immunohistochemically. When approaching a biopsy specimen with spindle cell morphology, and transducin-like enhancer of split 1, CD99, and epithelial membrane antigen positivity it is important to include AFH in the differential diagnosis.

The characteristic immunoprofile for the diagnosis of synovial sarcoma, a neoplasm of unclear tissue origin, is expression of transducer-like enhancer of split 1 (TLE-1), CD99, partial expression of cytokeratin, and epithelial membrane antigen by immunohistochemistry (IHC). Diagnostic dilemma or misdiagnosis can occur due to overlap in IHC and morphology with carcinomas, and particularly poorly differentiated and metastatic tumors. The frequency of TLE-1 and CD99 expression in carcinomas by IHC has not been previously assessed. We evaluated TLE-1 and CD99 expression in various carcinomas and evaluated the expression of the SS18 (SYT) gene rearrangement (a characteristic biomarker for synovial sarcoma) in tumors with TLE-1 and/or CD99 expression. Immunostains of TLE-1 and CD99 were performed in 100 various carcinomas. Seven of the 98 cases (7%) of carcinomas showed TLE-1 expression, including 1 each of prostate adenocarcinoma (ADCA), esophageal ADCA, basal cell carcinoma, adrenocortical carcinoma, endometrial ADCA, ovarian serous carcinoma, and small cell carcinoma. Twenty-one of the 100 cases (21%) of carcinomas demonstrated CD99 expression, including 6 prostate ADCA, 3 esophageal ADCA, 5 squamous cell carcinomas, 2 hepatocellular carcinomas, 1 each for endometrial ADCA, renal cell carcinoma, urothelial cell carcinoma, neuroendocrine carcinoma, and mucoepidermoid carcinoma. An esophageal ADCA was positive for both TLE-1 and CD99. None of the carcinomas with positive TLE-1 (n=7) or CD99 (n=21) by IHC showed SS18 gene rearrangement by fluorescent in situ hybridization. TLE-1 and CD99 expression were identified in 7% and 21% of carcinomas, respectively. This is a potential pitfall in the IHC interpretation for diagnosis of synovial sarcoma. SS18 gene rearrangement by fluorescent in situ hybridization is helpful for the diagnostically challenging cases, either for confirmation or exclusion of synovial sarcoma.

Objective: Anal cytology is being increasingly used as part of anal cancer screening in patients at high risk for anal neoplasia. Most studies in anal cytology have focused on correlating the abnormal anal Pap smear with histopathologic outcomes. The aim of this study was to document histopathologic or repeat anal cytology outcomes in patients with unsatisfactory cytology., Materials and Methods: Unsatisfactory anal Pap tests in high risk male patients were correlated with follow-up histopathologic diagnoses or cytology., Results: 1205 anal tests were performed during the study period and 214 (17.8%) were unsatisfactory. Adequate follow-up cytology was available in 75 cases and revealed epithelial cell abnormality (ECA) in 40% [30/75] (atypical squamous cells of undetermined significance (ASCUS) [20%] and low-grade squamous intraepithelial lesions (LGSIL) [20%]) and was negative for intraepithelial lesion or malignancy (NILM) in 60% [45/75] of cases. 28.7% of unsatisfactory Pap smears had unsatisfactory repeat cytology. Histopathological follow-up on these unsatisfactory Pap smears revealed anal intraepithelial neoplasia (AIN) 1 and AIN 2/3 or 2/3+ in 39% and 18% of the total number of biopsy cases, respectively., Conclusions: High risk male patients with unsatisfactory Pap smears are at significant risk of epithelial cell abnormality and histopathologically verifiable anal intraepithelial lesions.