Lymphatic endothelial cancerization in papillary thyroid carcinoma: hidden evidence of lymphatic invasion.

We hypothesize that cystic structures in metastatic papillary thyroid carcinoma (PTC) develop along the framework of lymphatic channels. To investigate this phenomenon, different categories of PTC were immunostained for D2-40 and TTF1. In this study, reactivity for D2-40 was considered as positive when there is membranous staining as often seen in lymphatic endothelial cells. Thirty cases of PTC with lymph node metastasis or with potential for lymphatic invasion and 20 cases metastatic PTC in lymph nodes were reviewed and found to show double/mosaic immunoreactivity for TTF1/D2-40 in 40-100% of cases. PTC metastasis in lymph nodes with cysts and some branching lymphatic-like channels lined by follicular cells with or without nuclear features of PTC were diffusely reactive to TTF1, and focally to D2-40. For primary and metastatic PTC, focal membranous D2-40 reactivity was also demonstrated in cysts or cleft linings. For25 thyroid neoplasms with no known potential for lymphatic invasion, there was no such immunoreactivity. The mosaic or double immunoreactivity for TTF1/D2-40 suggests lymphatic cancerization and possible endothelial mimicry of follicular cells. Mosaic/double immunoreactivity is helpful to detect the hidden pattern of lymphatic invasion masquerading as 'benign-appearing' follicles and supports our hypothesis of malignant cells developing along the lymphatic framework.

Paraganglioma with unusual presentation in parotid gland: A diagnostic dilemma in fine needle aspiration.

Paragangliomas (PGLs) are uncommon tumors. Although PGLs are known to occur in the head and neck region, especially the carotid body, middle ear, and larynx, involvement of the parotid glands has not been reported. In this article, we report the fine needle aspiration features of tumor in an unusual location, presenting as a parotid gland mass, submitted to pathology for initial diagnosis. The clinical presentation, cytomorphology, and the immunohistochemical features for the diagnosis are described. To our knowledge, this is the first case of paraganglioma of the parotid gland reported in the literature.

Adenoid cystic carcinoma of the airway: a 30-year review at one institution.

PURPOSE: The purpose of the study was to evaluate the treatment results of adenoid cystic carcinoma (ACC) of the airway at a single institution during a 30-year period. MATERIALS AND METHODS: All cases of ACC of the airway over a 30-year period at one tertiary care institution were reviewed retrospectively. The demographics, treatment modalities, pathologic characteristics, and outcomes were evaluated. RESULTS: Eleven patients were treated for ACC of the airway with an age range of 25 to 72 years (median, 48 years). Six patients presented with ACC in the larynx, and 5 patients had ACC of the trachea. All patients underwent surgical excision and radiation; 9 of 11 patients had postoperative external beam radiation, 1 patient had preoperative external beam radiation, and the remaining patient had postoperative neutron beam therapy. Four patients with tracheal ACC and none with laryngeal ACC had microscopic or grossly positive margins after surgery (P = .048). Eighty percent of patients had perineural invasion on pathology. Two patients with tracheal ACC had local recurrence of disease, which occurred at 1 and 10 months postoperatively. One patient with laryngeal ACC died of distant metastatic disease at 16 months. Follow-up varied from 4 to 168 months (median, 31 months). CONCLUSIONS: We report high disease-free survival rates for ACC of the airway in patients who underwent definitive surgical resection followed by postoperative radiation. There is a higher risk for local recurrence and positive surgical margins with distal tracheal location. Distant disease ultimately determines survival.

A novel classification system for perineural invasion in noncutaneous head and neck squamous cell carcinoma: histologic subcategories and patient outcomes.

OBJECTIVE: The aims of this study were to define a novel classification system of tumor perineural invasion (PNI) with respect to tumor/nerve involvement such as intratumoral (IT), peripheral, or extratumoral (ET) and to determine the prognostic significance of each of these histologic subcategories in patients with noncutaneous head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: This study is a retrospective chart review and histologic analysis of patients with HNSCC in the setting of a tertiary care medical center. METHODS: A clinical chart review of 142 patients with HNSCC who underwent primary surgical treatment from January 2004 through December 2007 was performed. Clinical information collected included patient age, sex, alcohol and tobacco use, tumor location, TNM stage, postoperative adjuvant chemotherapy and/or radiation treatment, and patient outcome. For each case, PNI density, the distance of each PNI focus to the tumor edge, and size of the largest nerve involved were measured. Furthermore, PNI was subcategorized as IT, peripheral, or ET. A Cox regression analysis was performed to determine if PNI was related to regional disease recurrence. Kaplan-Meier survival analysis was also performed. RESULTS: Among the 142 patients, 37 (26%) had disease progression. The maximum extent of PNI was significantly correlated with disease-free survival on multivariate analysis (P = .019) and was also significantly related to disease-free survival when T stage (P = .017), N stage (P = .021), and T and N stages (P = .02) were added to the Cox regression model. Kaplan-Meier analysis demonstrated a trend toward increased disease-free survival of PNI negative and IT/peripheral PNI compared with ET PNI. CONCLUSION: Perineural invasion is correlated with nodal status and T stage and is related to disease-free survival. It can be subcategorized as IT, peripheral, or ET. This novel classification system has important implications with regard to clinical outcome and may help define a cohort of patients that may require more aggressive management.

Snail as a novel marker for regional metastasis in head and neck squamous cell carcinoma.

OBJECTIVE: Previous studies have shown Snail expression integral to the epithelial-mesenchymal transition during tumor progression. However, its behavior in clinical head and neck squamous cell carcinomas (HNSCCs) is yet undefined. We therefore sought to (1) investigate clinical and histopathologic characteristics of Snail-positive HNSCC and (2) understand the link between Snail and other commonly used HNSCC tumor markers. STUDY DESIGN: A retrospective case-control study was conducted. SETTING: This study was conducted in a large-scale academic center. STUDY SUBJECTS: Of 51 consecutive HNSCC, 42 surgical resections were included. METHODS: Two separate pathologists performed standard histopathologic reviews along with immunohistochemistries (Snail, E-cadherin, p16, epidermal growth factor receptor [EGFR]) and in situ hybridization (human papilloma virus [HPV]). Medical review for all cases was performed. RESULTS: Twenty-two (52%) of 42 cases stained 4+ Snail (>75% staining). The remaining 20 cases were considered negative. Snail was strongly inversely related to E-cadherin expression (ρ = -0.69, P < .001), but statistically independent from HPV, p16, or EGFR expression. Snail(+) tumors were equally represented from each anatomic subsite. Snail(+) tumors were strongly associated with poor differentiation (P < .001) and basaloid classification (P = .004). Snail(+) tumors were also strongly associated with lymphovascular invasion (P = .02), but not perineural invasion. Ultimately, 11 (50%) of 22 of Snail(+) tumors demonstrated positive nodal metastasis and 11 (79%) of 14 node-positive cases were Snail(+) (P = .02). CONCLUSION: This pilot study provides promising evidence of Snail' role as a molecular prognostic marker for HNSCC. Snail positivity is significantly predictive of poorly differentiated, lymphovascular invasive, as well as regionally metastatic tumors. Because Snail positivity appears independent of HPV, p16, and EGFR expression, Snail may prove to improve upon these markers' predictive limitations.

Lymphohistiocytic Myocarditis Possibly Due to Moderna mRNA-1273 Vaccine.

OBJECTIVES: Despite the clear benefits of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in mitigating the impact of the coronavirus disease 2019 pandemic, there are emerging reports of postvaccination myocarditis, the majority of which are diagnosed based on the clinical and radiologic findings without biopsy confirmation. We report a case of biopsy-confirmed lymphohistiocytic myocarditis after Moderna mRNA-1273 vaccination. METHODS: We describe a case of a previously healthy 45-year-old woman who had palpitations, exercise intolerance, and syncope 1 week after her first mRNA-1273 vaccine dose. Laboratory tests and cardiac imaging were compatible with myocarditis. Given her unusual clinical presentation, an endomyocardial biopsy was performed to exclude other potential etiologies. RESULTS: The endomyocardial biopsy specimen showed patchy endocardial and intramyocardial lymphohistiocytic infiltrates with scattered eosinophils and focal myocyte injury. CD3 and CD68 immunostains confirmed the lymphocytic and histiocytic nature of the infiltrate, respectively. A focal histiocytic collection suggestive of an ill-defined granuloma was present. The histologic and immunohistochemical findings of a lymphohistiocytic myocarditis were highly suggestive of a postvaccination hypersensitivity reaction. CONCLUSIONS: Myocarditis following SARS-CoV-2 vaccination is a rare adverse event. The findings of a lymphohistiocytic myocarditis with scattered eosinophils and a possible ill-defined granuloma are highly suggestive of a hypersensitivity reaction. The mechanism by which this inflammation occurs remains uncertain. Despite our findings, the benefits of SARS-CoV-2 vaccination far outweigh the risks.

Sebaceous adenoma of the parotid gland: a case report with fine needle aspiration findings and histologic correlation.

BACKGROUND: Sebaceous adenoma of the salivary gland is an extremely rare, benign neoplasm that predominantly involves the major salivary glands. The major problem in dealing with sebaceous adenoma is the recognition of this entity to avoid confusion with other more aggressive neoplasms, such as mucoepidenmoid carcinoma. In particular, recognition of this entity in cytologic specimens is important to avoid radical surgery. CASE: A 29-year-old woman presented with an enlarging parotid mass. Fine needle aspiration (FNA) biopsy showed cellular smears composed of sheets and aggregates of cuboidal to low columnar cells with slightly irregular nuclear contours, prominent nucleoli and a moderate amount of cytoplasm that appeared squamoid and finely vacuolated. The FNA was misinterpreted as possible low grade mucoepidermoid carcinoma. CONCLUSION: We report a case ofa rare and unusual tumor of the salivary glands. The major problem in dealing with sebaceous adenoma is the recognition ofthis entity in cytologic specimens to avoid confusion with other more aggressive neoplasms such as low grade mucoepidermoid carcinoma and potentially to avoid radical surgery. In this paper, the clinical presentation, pathological findings on the fine needle aspirate and surgical resection specimen, and review of the literature will be discussed.

Benign vascular tumors and tumor-like proliferations.

Appropriate nomenclature of benign vascular tumors and tumor-like conditions is problematic due to overlapping histologic features, limited understanding of the pathogenesis, and controversy regarding classification. Benign vascular anomalies are categorized into malformations, neoplasms, reactive proliferations, or ectasias based on their clinical behavior, currently accepted etiologies, and histopathology. We address controversies in the classification of some entities and also discuss recent immunohistochemical developments that have raised questions regarding the origin of certain vascular tumors. This comprehensive review focuses on the clinical presentation, behavior, associated conditions, histopathological findings, and differential diagnoses of benign vascular tumors and tumor-like conditions.

Cholesterol embolization in renal allografts: a clinicopathologic study of 12 cases.

Cholesterol embolization (CE) in renal allografts is a rare occurrence, the natural history and prognostic significance of which is poorly characterized. We studied the clinicopathologic features and outcome of the largest known series of CE in renal allografts and combined our cases with those in the literature. We identified renal allograft biopsies with CE from 1997 to September 2004 at University of Pittsburgh Medical Center (UPMC). All pathology material related to such biopsies were examined and correlated with clinical information to determine the most probable CE source. Among 5435 RAB, 19 from 12 cadaveric transplant recipients comprising 7 males and 5 females (median age=63 y) had CE. Donors consisted of 9 males and 2 females (median age=47 y). One donor's age and sex was unknown. The most probable CE source was recipient in 9 cases and donor in 3 cases. Five had acute renal failure without acute cellular rejection and 2 had CE-specific failed allografts. Of 19 RAB, the most frequent coexisting diagnosis was chronic allograft nephropathy (63%). The median follow-up time was 661 days. Combining UPMC and non-UPMC cases (n=37) revealed a statistically significant loss of grafts with donor-derived (P value=0.00459) and early CE (P value=0.00938). In renal allografts, CE most often correlated with recipient and donor atherosclerosis. It may present with acute renal failure, but usually not acute graft loss. Graft failure is significantly associated with donor-derived and early CE. Although its prognosis may be poor in the setting of primary nonfunction, prolonged graft survival may be seen.

Mucinous adenocarcinomas of the thymus: report of 2 cases and review of the literature.

BACKGROUND: Most adenocarcinomas of the mediastinum are metastatic lesions. Primary thymic adenocarcinomas are extremely rare neoplasms. We could find only 12 cases reported in the literature; of these 12, only 4 were of the mucinous subtype. DESIGN: We report 2 additional cases of the mucinous subtype, including a previously unreported mucinous variant with numerous psammoma bodies. RESULTS: The first case in a 61-year-old woman resembled a mucinous (colloid) carcinoma of other organs such as the breast and colon. It consisted of islands and strips of tumor cells floating in large pools of extracellular mucin. A unique feature of this tumor was the presence of numerous psammoma bodies. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7 and negative for CD5. The second case in an 82-year-old woman was a mucinous adenocarcinoma arising from a thymic cyst with areas of transition from benign to dysplastic epithelium. The tumor cells formed dilated glands, cords, and small nests that infiltrated the thymic cyst wall and exhibited evidence of mucin production. Immunohistochemically, the tumor cells were positive for CK 7 and focally positive for both CD5 and CK 5/6. CONCLUSIONS: Mucinous adenocarcinoma, with or without, psammoma bodies, may be of primary thymic origin and should be considered in the differential diagnosis of malignant mediastinal tumors. These 2 cases provide further documentation of the rare occurrence of primary mucinous adenocarcinomas of the thymic gland.

Irreversible intrapulmonary vascular changes after pulmonary vein stenosis complicating catheter ablation for atrial fibrillation.

BACKGROUND: Pulmonary vein stenosis is a recognized complication of catheter ablation of arrhythmias emanating from the pulmonary vein; however, there is little information on secondary effects of pulmonary vein stenosis on lung tissue. METHODS AND RESULTS: A 55-year-old man with a history of paroxysmal atrial fibrillation refractory to antiarrhythmic medication had radiofrequency ablation in April 2003 and July 2003. Although these procedures were successful in resolving the patient's arrhythmia, they were complicated by the development of pulmonary vein stenosis of all four veins and pulmonary hypertension requiring patch annuloplasty of the pulmonary veins in October 2003. The patient was referred to our center for pulmonary vein stent placement in December 2003, June 2004, and August 2004, each time for recurrent hemoptysis. Due to persistent hemoptysis over the next several months, the patient underwent left lower lung lobectomy in September 2005. Microscopic examination of the lung showed marked medial thickening and intimal hyperplasia of large and small pulmonary veins and arteries, as well as focal organizing thrombi in the small arteries. The lung tissue showed extensive hemosiderin deposition indicative of prior hemorrhage. CONCLUSION: Chronic pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation results in irreversible venous and arterial morphologic changes throughout the lung, including areas both close to, and remote from, the site of catheter ablation. Because there are persistent pathological changes remote from the ablation site causing the pulmonary hypertension, stenting the site of ablation to reopen large pulmonary veins may not be effective in treating the pulmonary hypertension.

Distinctive Head and Neck Bone and Soft Tissue Neoplasms.

Benign and malignant primary bone and soft tissue lesions of the head and neck are rare. The uncommon nature of these tumors, combined with the complex anatomy of the head and neck, pose diagnostic challenges to pathologists. This article describes the pertinent clinical, radiographic, and pathologic features of selected bone and soft tissue tumors involving the head and neck region, including angiofibroma, glomangiopericytoma, rhabdomyosarcoma, biphenotypic sinonasal sarcoma, chordoma, chondrosarcoma, and osteosarcoma. Emphasis is placed on key diagnostic pitfalls, differential diagnosis, and the importance of correlating clinical and radiographic information, particularly for tumors involving bone.

Phosphaturic Mesenchymal Tumor Involving the Head and Neck: A Report of Five Cases with FGFR1 Fluorescence In Situ Hybridization Analysis.

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm; however, it is the most common cause of tumor-induced osteomalacia (TIO), a paraneoplastic syndrome characterized by renal phosphate wasting and hypophosphatemia. A subset of PMTs harbours an FGFR1 translocation although this alteration has not been demonstrated in PMT involving a head and neck site. We present a series of five PMTs involving the head and neck and demonstrate the diagnostic utility of fluorescence in situ hybridization (FISH) for detecting FGFR1 translocations. Patients' age and sex, tumor location, original diagnosis, the duration of symptoms, the presence of TIO, biochemical results, and medical management were reviewed. The median age at presentation was 45 (range, 24-58 years) and TIO was present in three cases. Four tumors involved soft tissue and one involved bone. Four out of the five tumors in our series were initially misdiagnosed. Three tumors were ultimately categorized as malignant PMT (two patients developed metastatic disease). FGFR1 translocation was present in two out of four cases and remained unknown in one case. In summary, we report on five cases of PMTs arising in the head and neck and confirm utility of FGFR1 FISH in the diagnosis of a subset of PMT.

Histopathogenesis of non-HPV-related differentiated oral squamous intraepithelial neoplasia.

INTRODUCTION: A study of immunohistopathologic and cytohistopathologic changes of the parabasal/basal layers in the differentiated squamous intraepithelial neoplasia (DSIN) may elucidate the histopathogenesis and reveal changes aiding early diagnosis and grading of the lesion. MATERIALS AND METHODS: A total of 55 consecutive resection specimens of nonbasaloid squamous cell carcinoma of the anterior oral cavity and 8 biopsies before resections displaying DSIN in the overlying squamous epithelium were examined. RESULTS: Squamous epithelium that is continuous/immediately adjacent to invasive squamous cell carcinoma (type 1) and the more peripheral (type 2) epithelium of resection specimens displayed consistent changes in the parabasal/basal layers: (A) cytologic atypia with proliferation of parabasal cells with downward expansion causing reactive proliferation of the basal cell layer in the early stage, invading the basal layer in the late stage; (B) disordered nuclear/cytoplasmic arrangement; (C) "Cobblestone" appearance. Immunoreactivity for TP53 and Ki67 was helpful in the diagnosis. The epithelial spectrum of changes decreased as one moved from type 1 to type 2 lesions. Five out of 8 biopsies showed type 1 lesions (followed by resection in a period of 11±6 mo) and 3 showed type 2 lesions (followed by resection in a period of 55±20 mo). In addition, resections were margin positive for type 2 lesions in 5 cases associated with recurrence at the site of resection during a period of 69±9 months. CONCLUSIONS: DSIN is characterized by a proliferation of neoplastic parabasal cells with dyskeratosis, downward expansion/pushing of the basal layer with elongation of rete ridges. We proposed grading of DSIN based on the changes of the parabasal/basal layers.

Carcinoma ex-pleomorphic adenoma of the parotid gland consisting of high-grade salivary duct carcinoma and keratinizing squamous cell carcinoma.

Carcinoma ex-pleomorphic adenoma (CXPA) is a rare salivary gland malignancy that presents diagnostic difficulties partly because of its wide range of histologic presentations. We report a case of a 77-year-old man, who presented with a 6-year history of a parotid mass that had undergone rapid growth within weeks. Magnetic resonance imaging revealed an infiltrative mass in the parotid gland, and the fine-needle aspiration (FNA) biopsy result was highly suspicious for carcinoma. Subsequent excision of the tumor demonstrated a poorly differentiated epithelial neoplasm consisting of keratinizing squamous cell carcinoma (SCC) and adenocarcinoma with regions of both ductal carcinoma in situ and invasive salivary duct carcinoma (SDC). Only focal areas exhibited a benign pleomorphic adenoma component. To our knowledge, this is the first case of a CXPA that consists of both a high-grade SDC and a keratinizing SCC in the parotid gland.

Adenoid Cystic Carcinoma of the Lacrimal Gland: A Case Report with a Review of the Literature.

Adenoid cystic carcinomas, the most common malignancies of the lacrimal gland, are rare overall. We describe a patient who presented with right periorbital swelling developing over 5 months and magnetic resonance imaging findings of a soft tissue mass in the lacrimal fossa with invasion of the adjacent bone. The patient underwent right lateral orbitotomy with tumor debulking. Pathologic analysis showed neoplastic cells in a predominantly cribriform pattern, and the patient was diagnosed with an adenoid cystic carcinoma of the lacrimal gland. We review the clinical, radiographic, and histopathologic features of these rare, aggressive malignancies as well as treatment options with reference to the current literature.

A unique case of sclerosing polycystic adenosis of the sinonasal tract.

Sclerosing polycystic adenosis is an extremely uncommon, recently described, sclerosing lesion of the salivary glands that appears histologically similar to fibrocystic changes of the breast. The key histopathologic features of sclerosing polycystic adenosis include lobular proliferation of ductal and acinar elements, cystically dilated ducts exhibiting frequent apocrine and sebaceous metaplasia, eosinophilic intracytoplasmic granules within some acinar-type cells, intraductal epithelial hyperplasia, and dense fibrosis. Most described cases have occurred in the major salivary glands, particularly the parotid gland. Although most authorities consider sclerosing polycystic adenosis to be a pseudoneoplastic process, the occurrence of dysplasia and carcinoma in situ of ductal epithelium reported recurrence rates of up to 30%, and recent evidence of clonality suggests a possible neoplastic etiology. However, there have been no cases of metastasis. Herein, we report the first case of sclerosing polycystic adenosis of the sinonasal tract in a 79-year-old woman presenting with a sinonasal mass.

Glucagon like peptide-1 receptor expression in the human thyroid gland.

BACKGROUND: Glucagon like peptide-1 (GLP-1) mimetic therapy induces medullary thyroid neoplasia in rodents. We sought to establish whether C cells in human medullary thyroid carcinoma, C cell hyperplasia, and normal human thyroid express the GLP-1 receptor. METHODS: Thyroid tissue samples with medullary thyroid carcinoma (n = 12), C cell hyperplasia (n = 9), papillary thyroid carcinoma (n = 17), and normal human thyroid (n = 15) were evaluated by immunofluorescence for expression of calcitonin and GLP-1 receptors. RESULTS: Coincident immunoreactivity for calcitonin and GLP-1 receptor was consistently observed in both medullary thyroid carcinoma and C cell hyperplasia. GLP-1 receptor immunoreactivity was also detected in 18% of papillary thyroid carcinoma (three of 17 cases). Within normal human thyroid tissue, GLP-1 receptor immunoreactivity was found in five of 15 of the examined cases in about 35% of the total C cells assessed. CONCLUSIONS: In humans, neoplastic and hyperplastic lesions of thyroid C cells express the GLP-1 receptor. GLP-1 receptor expression is detected in 18% papillary thyroid carcinomas and in C cells in 33% of control thyroid lobes. The consequence of long-term pharmacologically increased GLP-1 signaling on these GLP-1 receptor-expressing cells in the thyroid gland in humans remains unknown, but appropriately powered prospective studies to exclude an increase in medullary or papillary carcinomas of the thyroid are warranted.

Poorly differentiated adenocarcinoma arising from a cervical bronchial cyst.

Bronchogenic cysts with malignant change are rarely reported. We describe a case of poorly differentiated adenocarcinoma arising from a cervical bronchial cyst in a patient presenting with a thyroid mass, cervical lymphadenopathy, and initial biopsy suggestive of papillary thyroid carcinoma. The clinical presentation, intraoperative findings, radiographic images, and pathology slides are presented. To our knowledge, this is the first report of a poorly differentiated adenocarcinoma arising from a bronchial cyst in the cervical region.