Benign cervical schwannoma with tracheal invasion.

Schwannomas commonly develop in the cervical region, 25% - 45% of cases are diagnosed in this anatomical region. Tracheal neurogenic tumors are exceedingly rare and can be misdiagnosed as invasive thyroid carcinomas or other infiltrating malignancies when present at the level of the thyroid gland. Here, we present a case of synchronous benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma in a patient who was initially hospitalized for COVID-19. The patient presented with dyspnea that was later found to be caused by tracheal extension of a cervical tumor. Surgical excision was performed, and the surgical team proceeded with segmental tracheal resection, removal of the cervical mass, and total thyroidectomy. The specimen was sent for pathological analysis, which revealed synchronous findings of a benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma. The literature on this subject, together with the present case report, suggests that neurogenic tumors should be included in the differential diagnosis of obstructing tracheal cervical masses. Surgical excision is the first-line of treatment for benign cervical schwannomas.

Benign cervical schwannoma with tracheal invasion

ABSTRACT Schwannomas commonly develop in the cervical region, 25% - 45% of cases are diagnosed in this anatomical region. Tracheal neurogenic tumors are exceedingly rare and can be misdiagnosed as invasive thyroid carcinomas or other infiltrating malignancies when present at the level of the thyroid gland. Here, we present a case of synchronous benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma in a patient who was initially hospitalized for COVID-19. The patient presented with dyspnea that was later found to be caused by tracheal extension of a cervical tumor. Surgical excision was performed, and the surgical team proceeded with segmental tracheal resection, removal of the cervical mass, and total thyroidectomy. The specimen was sent for pathological analysis, which revealed synchronous findings of a benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma. The literature on this subject, together with the present case report, suggests that neurogenic tumors should be included in the differential diagnosis of obstructing tracheal cervical masses. Surgical excision is the first-line of treatment for benign cervical schwannomas.

Cytopathology of mesenchymal tumors of the thyroid gland: analysis of 12 cases from multinational institutions with review of the literature.

INTRODUCTION: Mesenchymal tumors of the thyroid gland are extremely rare. We report the cytomorphologic characteristics of 12 mesenchymal tumors occurring in the thyroid gland and highlight the diagnostic difficulties encountered in their cytologic evaluation. MATERIALS AND METHODS: The cytopathology and surgical pathology archives from 5 large institutions were searched for thyroid mesenchymal tumors that had an FNA available for review. Clinicopathologic and cytomorphologic characteristics for each case were evaluated. RESULTS: Twelve cases of mesenchymal tumors occurring in the thyroid were identified in our search. Patient age ranged from 28 to 84 years (median, 60 years). The cases occurred in 7 women and 5 men. The tumor size ranged from 1.4 to 14 cm (median, 3.3 cm). The tumors were as follows: hemangioma (n = 4; 33.3%), angiosarcoma (n = 2; 16.7%), schwannoma (n = 2; 16.7%), solitary fibrous tumor (n = 2, 16.7%), metastatic synovial sarcoma (n = 1, 8.3%) and metastatic pleomorphic rhabdomyosarcoma (n = 1, 8.3%). The cytomorphologic features of the tumors were similar to those of their counterparts occurring in different sites. An accurate diagnosis was achieved in six primary thyroid mesenchymal cases (60%). Five patients (41.7%) underwent total thyroidectomy, and 3 patients received partial thyroidectomy (25%). Three patients (25%) did not receive a thyroidectomy and subsequent surgical information was not available in 1 case (8.3%). CONCLUSIONS: Mesenchymal tumors of the thyroid are extremely uncommon. Cytologic diagnosis of these tumors is often challenging due to the morphologic overlap with diverse epithelial and non-epithelial thyroid lesions. Ancillary studies such as immunohistochemistry and molecular studies are essential for accurate diagnosis.

Rhabdomyosarcoma Associated with Core Myopathy/Malignant Hyperthermia: Combined Effect of Germline Variants in RYR1 and ASPSCR1 May Play a Role.

Rhabdomyosarcomas have been described in association with thyroid disease, dermatomyositis, Duchenne muscular dystrophy, and in muscular dystrophy models but not in patients with ryanodine receptor-1 gene (RYR1) pathogenic variants. We described here an 18-year-old male who reported a cervical nodule. Magnetic resonance images revealed a mass in the ethmoidal sinus corresponding to rhabdomyosarcoma. As his father died from malignant hyperthermia (MH), an in vitro contracture test was conducted and was positive for MH susceptibility. Muscle histopathological analysis in the biopsy showed the presence of cores. Molecular analysis using NGS sequencing identified germline variants in the RYR1 and ASPSCR1 (alveolar soft part sarcoma) genes. This report expands the spectrum of diseases associated with rhabdomyosarcomas and a possible differential diagnosis of soft tissue tumors in patients with RYR1 variants.

Parotidectomy and neck dissection in locally advanced and relapsed cutaneous squamous cell carcinoma of the head and neck region,,

Abstract Objective: To investigate the prognostic factors to developing parotid and neck metastasis in locally advanced and relapsed Cutaneous Squamous Cell Carcinoma (CSCC) of the head and neck region. Methods: Single-center retrospective cohort study enrolling consecutive patients with advanced CSCC from 2009 to 2019. Seventy-four cases were identified. Study variables demographic data, clinical skin tumor stage, neck stage, parotid stage (P stage), surgical treatment features, and parotid, regional, and distant metastases. Survival measures: Overall Survival (OS) and Disease-Specific Survival (DSS). Results: The study group included 72.9% men (median age, 67 years); 67.5% showed T2/T3 tumors, 90.5% comorbidities, 20.2% immunosuppressed, with median follow-up: 35.8 months. The most frequent skin primary were auricular and eyelid regions, 75% underwent primary resection with flap reconstruction. Parotid metastasis was present in 50%, 32.4% showing parotid extracapsular spread, multivariate analysis found OR = 37.6 of positive parotid metastasis evolving into positive neck metastasis, p = 0.001. Occult neck metastasis, neck metastasis, and neck extracapsular spread were observed in 13.5%, 51.3%, and 37.8%, respectively. Kaplan-Meier survival: Clinical T4 versus T1, p = 0.028, P1 stage: 30% and 5% survival at 5 and 10 years, P3 stage: 0%, p = 0.016; OS and DSS showed negative survival for the parotid metastasis group, p = 0.0283. Conclusion: Our outcomes support a surgically aggressive approach for locally advanced and relapsed CSCC, with partial parotidectomy for P0, total parotidectomy for P1-3, selective I-III neck dissection for all patients and adjuvant radiochemotherapy to appropriately treat these patients with advanced CSCC of the head and neck region. Level of evidence: II b - Retrospective Cohort Study - Oxford Centre for Evidence-Based Medicine (OCEBM).

Secretory carcinoma of the salivary gland, a rare entity: An international multi-institutional study.

BACKGROUND: Secretory carcinoma (SC) of the salivary gland is a rare entity with limited published literature on cytomorphology. The authors present the largest cohort to date of SC fine-needle aspiration (FNA) cases. METHODS: FNA cases of histologically confirmed SC were retrospectively retrieved from 12 academic institutions in the United States, Italy, Finland, and Brazil. The collated data included patient demographics, imaging findings, cytopathologic diagnoses according to the Milan System for Reporting Salivary Gland Cytopathology, cytomorphologic characteristics, and immunohistochemical/molecular profiles. RESULTS: In total, 40 SCs were identified (male-to-female ratio, 14:26) in patients with a mean age of 52 years (age range, 13-80 years). Ultrasound imagining revealed a hypoechoic, ovoid, poorly defined, or lobulated mass. The most common primary site was the parotid gland (30 of 40 tumors). Regional lymph node metastasis (9 patients) and distant metastasis (4 patients; brain, liver, lungs, and mediastinum) were noted. Two patients died of disease. FNA smears were cellular and demonstrated mainly large, round cells with intracytoplasmic vacuoles or granules and round-to-oval nuclei with smooth nuclear contour, minimal irregularities, and prominent nucleoli arranged predominantly in clusters, papillary formations, and single cells. The background was variable and contained inflammatory cells, mucin, or proteinaceous material. The diagnoses were malignant (19 of 38 tumors; 50%), suspicious for malignancy (10 of 38 tumors; 26%), salivary gland neoplasm of uncertain malignant potential (7 of 38 tumors; 18%), and atypia of undetermined significance (2 of 38 tumors; 6%) according to the Milan System for Reporting Salivary Gland Cytopathology. Two malignant cases (2 of 40 tumors; 5%) were metastases. The neoplastic cells were immunoreactive for S100 (23 of 24 tumors), mammaglobin (18 of 18 tumors), GATA-3 (13 of 13 tumors), AE1/AE3 (7 of 7 tumors), and vimentin (6 of 6 tumors). ETV6-NTRK3 fusion was detected in 32 of 33 tumors by fluorescence in situ hybridization (n = 32) and next-generation sequencing (n = 1). CONCLUSIONS: Familiarity with cytomorphologic features and the immunohistochemical/molecular profile of SC can enhance diagnostic accuracy.

Parotidectomy and neck dissection in locally advanced and relapsed cutaneous squamous cell carcinoma of the head and neck region.

OBJECTIVE: To investigate the prognostic factors to developing parotid and neck metastasis in locally advanced and relapsed Cutaneous Squamous Cell Carcinoma (CSCC) of the head and neck region. METHODS: Single-center retrospective cohort study enrolling consecutive patients with advanced CSCC from 2009 to 2019. Seventy-four cases were identified. Study variables demographic data, clinical skin tumor stage, neck stage, parotid stage (P stage), surgical treatment features, and parotid, regional, and distant metastases. Survival measures: Overall Survival (OS) and Disease-Specific Survival (DSS). RESULTS: The study group included 72.9% men (median age, 67 years); 67.5% showed T2/T3 tumors, 90.5% comorbidities, 20.2% immunosuppressed, with median follow-up: 35.8 months. The most frequent skin primary were auricular and eyelid regions, 75% underwent primary resection with flap reconstruction. Parotid metastasis was present in 50%, 32.4% showing parotid extracapsular spread, multivariate analysis found OR = 37.6 of positive parotid metastasis evolving into positive neck metastasis, p = 0.001. Occult neck metastasis, neck metastasis, and neck extracapsular spread were observed in 13.5%, 51.3%, and 37.8%, respectively. Kaplan-Meier survival: Clinical T4 versus T1, p = 0.028, P1 stage: 30% and 5% survival at 5 and 10 years, P3 stage: 0%, p = 0.016; OS and DSS showed negative survival for the parotid metastasis group, p = 0.0283. CONCLUSION: Our outcomes support a surgically aggressive approach for locally advanced and relapsed CSCC, with partial parotidectomy for P0, total parotidectomy for P1-3, selective I-III neck dissection for all patients and adjuvant radiochemotherapy to appropriately treat these patients with advanced CSCC of the head and neck region. LEVEL OF EVIDENCE: II b - Retrospective Cohort Study - Oxford Centre for Evidence-Based Medicine (OCEBM).

Application of the Milan System for Reporting Salivary Gland Cytopathology in pediatric patients: An international, multi-institutional study.

BACKGROUND: Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category. METHODS: Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%). CONCLUSIONS: The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.

Perineural Invasion as Worsening Criterion for Salivary Gland Mucoepidermoid Carcinoma.

Mucoepidermoid carcinomas (MECs) are a form of salivary gland malignancy. They are classified according to histological grade and perineural invasion (PNI). In another cancer subtypes, positive-PNI suggests increased poor prognosis; however, the role of isolated positive-PNI salivary gland MEC can still be better investigated as a risk factor. This study investigated whether isolated PNI is independently associated with poor outcomes. Retrospective study, cohort case-series, single-center hospital from 2009 to 2019. Patient demographics, primary tumor, intervention, and survival data are included. Univariate, multivariate, and Kaplan-Meier survival curve analyses were used for comparison.The study group consisted of 32 patients (15 PNI-positive tumors, and 17 PNI-negative tumors), all admitted for surgery. Univariate analysis showed differences in grade (p = 0.038), positive margins (p = 0.034), soft tissue invasion (p < 0.001), pathological stage (p = 0.014), recurrence (p = 0.015), distant metastasis (p = 0.015) and MEC related death (p = 0.015). The risk in PNI-positive patients to develop soft tissue invasion and positive surgical margins was OR = 8.57 and OR = 4.88, respectively. Multivariate analysis found age differences (p = 0.038), with OR = 1.08. The Disease Specific Survival (DSS) was worst in the PNI-positive group (log-rank p-value = 0.0011), where the probability of dying occurred in the 12-24 months period (log-rank p-value = 0.002). PNI-positive salivary gland MEC is an independent prognostic factor, with poor DSS, increased locoregional recurrence, close correlation with a more aggressive pattern of the disease, and should be reviewed as a high grade histological criteria. Our findings may imply changes in the clinical approach with a more aggressive attitude in the overall treatment.

Machine learning algorithm improved automated droplet classification of ddPCR for detection of BRAF V600E in paraffin-embedded samples.

Somatic mutations in cancer driver genes can help diagnosis, prognosis and treatment decisions. Formalin-fixed paraffin-embedded (FFPE) specimen is the main source of DNA for somatic mutation detection. To overcome constraints of DNA isolated from FFPE, we compared pyrosequencing and ddPCR analysis for absolute quantification of BRAF V600E mutation in the DNA extracted from FFPE specimens and compared the results to the qualitative detection information obtained by Sanger Sequencing. Sanger sequencing was able to detect BRAF V600E mutation only when it was present in more than 15% total alleles. Although the sensitivity of ddPCR is higher than that observed for Sanger, it was less consistent than pyrosequencing, likely due to droplet classification bias of FFPE-derived DNA. To address the droplet allocation bias in ddPCR analysis, we have compared different algorithms for automated droplet classification and next correlated these findings with those obtained from pyrosequencing. By examining the addition of non-classifiable droplets (rain) in ddPCR, it was possible to obtain better qualitative classification of droplets and better quantitative classification compared to no rain droplets, when considering pyrosequencing results. Notable, only the Machine learning k-NN algorithm was able to automatically classify the samples, surpassing manual classification based on no-template controls, which shows promise in clinical practice.

Cytologic grading of primary malignant salivary gland tumors: A blinded review by an international panel.

BACKGROUND: Fine needle aspiration (FNA) is commonly used for the preoperative evaluation of salivary gland tumors. Tumor grade is a key factor influencing clinical management of salivary gland carcinomas (SGCs). To assess the ability to grade nonbasaloid SGCs in FNA specimens, an international panel of cytopathologists convened to review and score SGC cases. METHODS: The study cohort included 61 cases of primary SGC from the pathology archives of 3 tertiary medical centers. Cases from 2005 to 2016 were selected, scanned, and digitized. Nineteen cytopathologists blinded to the histologic diagnosis reviewed the digitized cytology slides and graded them as low, high, or indeterminate. The panelists' results were then compared to the tumor grades based on histopathologic examination of the corresponding resection specimens. RESULTS: All but 2 of the 19 (89.5%) expert panelists review more than 20 salivary gland FNAs per year; 16 (84.2%) of the panelists work at academic medical centers, and 13 (68.4%) have more than 10 years' experience. Participants had an overall accuracy of 89.4% in the grading of SGC cases, with 90.2% and 88.3% for low- and high-grade SGC, respectively. Acinic cell carcinoma and mucoepidermoid carcinoma had the highest degree of accuracy, while epithelial-myoepithelial carcinoma and salivary duct carcinoma had the lowest degree of accuracy. As expected, the intermediate-grade SGC cases showed the greatest variability (high-grade, 42.1%; low-grade, 37.5%, indeterminate, 20.4%). CONCLUSION: This study confirms the high accuracy of cytomorphologic grading of primary SGC by FNA as low- or high-grade. However, caution should be exercised when a grade cannot be confidently assigned.

Instant messenger smartphone application for endosonographer/cytopathologist real-time interaction at a distance in EUS-FNA for solid pancreatic lesions.

Background and study aims Telecytopathology (TCP) may allow proper and timely evaluation of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens. The aim of this study was to evaluate the feasibility of TC through a multiplatform instant messenger smartphone application to evaluate specimens of EUS-FNA of pancreatic solid lesions. Patients and methods Twenty-three patients (14 male/9 female; median age: 56 yr.; age range: 33 - 86) with a solid pancreatic lesion were included. Exclusion criteria were as follows: age < 18 yr and predominantly cystic lesions. During each EUS-FNA, after each pass, the aspirated material was spread over a glass slide and was stained by the endoscopist. The glass slide was then reviewed on a microscope with a smartphone fitted in, and the most representative fields were captured and sent to the cytopathologist using WhatsApp Messenger. Results In initial evaluation using TCP rapid on-site evaluation (ROSE), adequate cellularity of the glass slide was detected in 16 of 23 patients (69.6 %). An initial diagnosis of malignancy (positive or suspicious) was possible in 14 of 23 patients (60.8 %). Conclusion The current study demonstrated the feasibility of a low-cost, Internet-based, telecytopathology system using WhatsApp Messenger to provide ROSE of EUS-FNA slides in patients with solid pancreatic lesions.

Application of the Milan System for Reporting Submandibular Gland Cytopathology: An international, multi-institutional study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a 6-tier diagnostic category system with associated risks of malignancy (ROMs) and management recommendations. Submandibular gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a higher relative proportion of malignancy, and this may affect the ROM and subsequent management. This study evaluated the application of the MSRSGC and the ROM for each diagnostic category for 734 submandibular gland FNAs. METHODS: Submandibular gland FNA cytology specimens from 15 international institutions (2013-2017) were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. A correlation with the available histopathologic follow-up was performed, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The case cohort of 734 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 21.4% (0%-50%); nonneoplastic, 24.2% (9.1%-53.6%); AUS, 6.7% (0%-14.3%); benign neoplasm, 18.3% (0%-52.5%); SUMP, 12% (0%-37.7%); SM, 3.5% (0%-12.5%); and malignant, 13.9% (2%-31.3%). The histopathologic follow-up was available for 333 cases (45.4%). The ROMs were as follows: nondiagnostic, 10.6%; nonneoplastic, 7.5%; AUS, 27.6%; benign neoplasm, 3.2%; SUMP, 41.9%; SM, 82.3%; and malignant, 93.6%. CONCLUSIONS: This multi-institutional study shows that the ROM of each MSRSGC category for submandibular gland FNA is similar to that reported for parotid gland FNA, although the reported rates for the different MSRSGC categories were variable across institutions. Thus, the MSRSGC can be reliably applied to submandibular gland FNA.

Correlaçäo interobservadora da graduaçäo de Gleason: avaliaçäo de 50 carcinomas de próstata / Interobserver correspondence of Gleason's grading: evaluation of 50 prostatic carcinomas

O sistema de Gleason tem grande aceitaçäo entre os urologistas devido a boa correlaçäo com o prognóstico dos pacientes portadores de câncer de próstata. Sua reprodutibilidade interobservadora é pouco questionada na literatura e, por este motivo, foram avaliados os resultados de dois patologistas entre 50 casos tratados pelo Serviço Urologia do Hospital A. C. Camargo. A concordância (reprodutibilidade) do Gleason primário e do escore de Gleason foi de 66 e 48 por cento respectivamente. Concluímos que boa reprodutibilidade pode ser alcançada no sistema de Gleason desde que utilizado por patologista experiente e familiarizado com a classificaçäo, caso contrário poderia haver sub ou supragraduaçäo, prejudicando o planejamento terapêutico