Sinonasal Hamartomas: From Nasal Chondromesenchymal Hamartoma to Respiratory Epithelial Adenomatoid Hamartoma. Report of six Cases and Review of the Literature

Sinonasal hamartomas are uncommon lesions of nasal and sinus cavities. Based on indigenous cellular components and characteristic histologic features, they are further classified into four entities: respiratory epithelial adenomatoid hamartoma (REAH), seromucinous hamartoma (SH), chondro-osseous and respiratory epithelial hamartoma (CORE), and nasal chondromesenchymal hamartoma (NCH). REAH, SH, and CORE are seen in adult patients, while NCH predominantly occurs in newborns and infants. Morphologically REAH and SH are composed of respiratory epithelium and seromucinous glands, CORE is related to REAH but with additional feature of chondroid and/or osseous tissue, and NCH is composed of chondroid and stromal elements but devoid of epithelial component. All four lesions can present as sinonasal mass lesions and with associated obstructive symptoms. Given the rarity of these lesions, diagnosis can be challenging, especially in unusual clinical scenario. In this study, we report six cases of sinonasal hamartoma, including one case of NCH, one case of CORE, two cases of SH, and two cases of REAH. All cases were from adult patients including four men and two women. We also review the literature of the clinical and pathologic features of these rare lesions.

Oral Epithelial Dysplasia Grading Systems: A Systematic Review & Meta-Analysis

This systematic review and meta-analysis aims to provide a robust qualitative and quantitative analysis of the different systems used to assess the grade of oral epithelial dysplasia (OED). This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyzes (PRISMA) statement. Six electronic databases were searched for primary research published over the past four decades. Overall quality and level of evidence were based on the Johns Hopkins Research Evidence Appraisal Tool, while evidence of heterogeneity was determined by the Q-statistic and I^2 statistic. Evidence of publication bias was determined using Egger's regression and the Rank correlation tests. A total of 170 records were identified. Only 9 primary research articles were included in the qualitative systematic review. Four studies (4/9) were included in the final quantitative meta-analysis. The grading systems analyzed included the WHO, binary, Ljubljana, Smith and Pindborg, Brothwell, and the oral intraepithelial neoplasia. The results demonstrate the binary system to be superior to the WHO system in grading OED, by providing better inter-observer agreement, however, the substantial error among the inter-observer κ values analyzed indicates the significance of this finding to be of minimal impact. Lack of reliable reproducibility of the grading systems and lack of common effect size (heterogeneity analysis) were noted.

Genetic Study of BRAF V600E and SMO L412F Mutations in Japanese Patients with Ameloblastoma

Background and aim: Ameloblastoma is a benign, intraosseous, progressively growing, epithelial, odontogenic neoplasm. BRAF and SMO mutations have been reported in ameloblastoma. In this study, we evaluated BRAF V600E and SMO L412F mutations; and assessed the relationship between BRAF V600E mutant expression and the clinicopathological features in Japanese patients with ameloblastoma. Methods: We examined 24 formalin-fixed paraffin-embedded samples. All specimens were from patients with mandibular ameloblastoma: 20 were conventional ameloblastoma and 4 were unicystic ameloblastoma. The BRAF V600E mutation was assessed by Sanger sequencing and immunohistochemistry, and the SMO L412F mutation was assessed only by Sanger sequencing. Results: Twenty of the 24 (83%) ameloblastoma samples carried the BRAF V600E mutation; 22 of the 24 (92%) samples were immunohistochemically positive for BRAF V600E. However, the SMO L412F mutation was not detected in any of them. The BRAF V600E mutation status did not correlate with the clinicopathological features, such as age, sex, location, method, recurrence, and subtype. Conclusion: BRAF inhibitors could be a potential treatment option for Japanese patients with ameloblastoma, harboring the BRAF V600E mutation.

Role of the Immunohistochemical ZEB1 Expression in Uterine Mesenchymal Neoplasms

The distinction of mesenchymal tumors of the uterus is a frequent diagnostic challenge in gynecologic pathology. Especially, distinguishing low-grade endometrial stromal sarcoma (ESS) from leiomyoma or distinguishing low-grade ESS from high-grade ESS can be difficult. Epithelial-mesenchymal transition (EMT) is a physiological and pathological process in which epithelial cells lose their morphological features, become elongated and acquire mesenchymal traits. The signaling pathway of Zinc finger E-box binding homeobox 1 (ZEB1) is one of the most significant pathways involved in the EMT process and it has a crucial role in cancer progression, metastasis, and therapy resistance. We studied a series of 69 uterine mesenchymal neoplasms including 18 endometrial stromal sarcomas (10 cases of low grade and 8 cases of high grade endometrial stromal sarcomas), 26 leiomyosarcomas (8 cases of grade 1 and 19 cases of grade 2-3 leiomyosarcomas), 15 leiomyomas, and 10 rhabdomyosarcomas, using an antibody ZEB1. We graded the leiomyosarcomas depending on the FNCLCC grading system. It was observed that leiomyosarcoma was more intensely stained with ZEB1 than leiomyoma (P < 0.001) and high-grade ESS was significantly more intensely stained with ZEB1 protein than low-grade ESS (P < 0.004). It also was observed that high-grade leiomyosarcoma was significantly more intensely stained with ZEB1 protein than low-grade leiomyosarcoma (P < 0.000). Our data suggest that Zeb1 can be used to differentiate high-grade sarcomas from their low-grade counterparts as well as benign and malignant smooth muscle tumors of the uterus.

Yolk Sac Tumor in a Recurrence of Colonic Adenocarcinoma With Shared Mutations in APC and TP53 Genes: A Case Report

Only four cases of colorectal adenocarcinoma with a yolk sac tumor (YST) component have been reported in the English literature. No genetic investigation has been performed in these cases. We report a case of colorectal adenocarcinoma in which the recurrent tumor had a YST component. A 49-year-old woman presented with a pelvic tumor three years after endoscopic mucosal resection of sigmoid colon adenocarcinoma. The pelvic tumor consisted of an undifferentiated carcinoma component and a YST component. The serum alpha-fetoprotein level was elevated to 42 ng/mL. Treatment as conventional colorectal carcinoma produced some anticancer effects, but the patient died 14 months after the recurrence and 49 months after the EMR. With the help of the next-generation sequencing results of the recurrent tumor, APC c.835 − 8A > G and TP53 c.524G > A (p.R175H) mutations were identified by direct sequencing in both the primary and the recurrent tumors, confirming the relationship between the two metachronous tumors.

Malignant Transformation of Metaplastic Thymoma into High-Grade Sarcomatoid Carcinoma: A Case Report

The correlation of histogenesis between metaplastic thymoma and thymic sarcomatoid carcinoma is unclear. We report a case of metaplastic thymoma transformed into high-grade sarcomatoid carcinoma. A 64 × 54 × 32 mm anterior mediastinal mass in a 61-year-old woman microscopically consisted mainly of classic metaplastic thymoma, with the center dominated by high-grade sarcomatoid carcinoma. In some areas, both epithelial and spindle cell components of the metaplastic thymoma showed increased cellular atypia, mitotic activity, and focal necrosis and gradually transformed into the polygonal/pleomorphic and spindle cell components of sarcomatoid carcinoma. Immunohistochemically, the characteristics of the polygonal/pleomorphic sarcomatoid cells were similar to those of the epithelial component of metaplastic thymoma, while the spindle sarcomatoid cells were more similar to the spindle cells component of metaplastic thymoma. The Ki-67 index was less than 5% in the metaplastic thymoma areas but up to 70% in the sarcomatoid carcinoma area. Radical operation and postoperative radiotherapy were performed. Multifocal relapses at the pleura occurred 13 months after surgery.

Cryptococcal Prostatitis Forming Caseous and Suppurative Granulomas Diagnosed by Needle Biopsy: A Case Report

Cryptococcal granulomatous prostatitis is extremely rare, and there have been few reports of its diagnosis by prostate needle biopsy. The patient, an 81–year–old man, was receiving immunosuppressive treatment for rheumatoid arthritis. He had an oropharyngeal ulcer, and it was diagnosed alongside a methotrexate-related diffuse large B-cell lymphoma. A systemic imaging examination revealed a prostatic tumor-like mass clinically suspected to be prostatic cancer, and a needle biopsy was performed. The biopsy specimen showed various types of inflammatory cell infiltration, and suppurative granuloma and caseous granuloma were observed. Both granulomas showed multiple round and oval organisms that were revealed with Grocott methenamine silver staining. Acid–fast bacilli were not detected by Ziehl–Neelsen staining. We histologically diagnosed granulomatous prostatitis caused by Cryptococcus infection. Caseous granulomas often develop in the prostate after bacillus Calmette–Guerin immunotherapy for bladder cancer, although the possibility of cryptococcal granulomatous prostatitis should also be considered.

Myopericytoma of the Parotid and Molecular Profiling: Report of a Rare Case and Review of the Literature

Myopericytomas are uncommon tumors defined by their round to spindle shaped cells often arranged in a concentric pattern of perivascular growth. They are typically well-circumscribed, nodular, slow-growing lesions that occur in the soft tissue of the extremities. Here, we present a 30-year-old female with a 2.4 cm myopericytoma occurring in the deep lobe of the parotid gland. The diagnosis was made with detailed histopathologic and immunohistochemical findings and positive identification of the specific mutation for PDGFRβ p.Asp666Lys by next generation sequencing (NGS). This is the first case report of a parotid myopericytoma with a genetic testing that shows a particular mutation that has been linked to myopericytomatosis.

Somatic Mutation of BAP1 Can Lead to Expression Loss in Non-Small Cell Lung Carcinoma: Next Generation Sequencing and IHC Analysis in A Large Single Institute Cohort

Introduction. As a tumor suppressor, germline and somatic inactivation of BRCA1 associated protein 1 gene ( BAP1) is a common finding in mesothelioma, melanocytic tumors, clear cell renal cell carcinoma and several other epithelial, mesenchymal and neural tumors. Incidence of BAP1 genetic alterations and subsequent expression loss has not been well established in non-small cell lung carcinoma (NSCLC) by large-scale studies. Design. After IRB approval, a total of 356 NSCLC cases of our institution between July 2016 and June 2020 were reviewed. The study cohort consisted of 214 (60%) adenocarcinomas, 89 (25%) squamous cell carcinomas, and 53 (15%) diagnosed as “non-small cell lung carcinoma” without specified subtype. All tumors underwent comprehensive target cancer gene next generation sequencing (Oncomine Assay). The protein expression status of BAP1 was subsequently evaluated by immunohistochemistry. Results. BAP1 somatic mutations were detected in 8 NSCLC tumors (incidence: 2.2%). Tumors harboring BAP1 mutations were all diagnosed at advanced stage and carried at least one additional genetic alteration. Immunohistochemically, four tumors showed complete loss of BAP1 protein expression, including two adenocarcinomas which harbored different missense BAP1 mutations and another two with bioinformatically predicated deleterious frameshifting mutations. Conclusion. Compared with known BAP1 loss associated other malignancies, such as mesothelioma, inactivation of BAP1 by somatic mutation is a rare occurrence in NSCLC. BAP1 mutations and loss of expression in NSCLC are accompanied by other complex genetic alternations, suggesting BAP1 mutation maybe a late event NSCLC carcinogenesis.