BRAF V600E mutation co-existing with oncogenic mutations is associated with aggressive clinicopathologic features and poor prognosis in papillary thyroid carcinoma.

BACKGROUND: The aim of this study was to evaluate the correlation among mutations in cancer-related genes, clinicopathologic features, and clinical outcome in classical papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: A total of 130 patients with classical PTC who underwent curative surgery between April 2012 and June 2023 at Hokuto Hospital were included. Mutations in targeted regions of 160 cancer-related genes were detected by next-generation sequencing (NGS)-based cancer panel testing. RESULTS: The BRAF V600E mutation was detected in 108 (83.1%) of 130 PTC patients. Among the 108 patients with the BRAF V600E mutation, other co-existing oncogenic mutations were found in 12 (9.2%) patients. When we divided into 3 groups of no mutations, BRAF V600E mutation alone, and BRAF V600E and other oncogenic mutations, significant differences were observed in terms of tracheal invasion (P = 0.0024), and bilateral neck lymph node metastasis (P = 0.0047). Kaplan-Meier analysis of overall survival (OS) revealed patients with BRAF V600E and other oncogenic mutations had significantly poorer survival than those with BRAF V600E mutation alone (P = 0.0026). Multivariate cox proportional hazard analysis revealed BRAF V600E and other oncogenic mutations was an independent prognostic factor for OS (HR: 10.559; 95%CI: 1.007-110.656, P = 0.0493). CONCLUSIONS: The BRAF V600E mutation co-existing with other oncogenic mutations but not the BRAF V600E mutation alone was associated with aggressive clinicopathologic features, resulting in poor prognosis in patients with classical PTC. Detection of oncogenic mutations using NGS-based cancer panel testing could enhance understanding of the clinical features of classical PTC.

Renal Cell Carcinoma Metastasizing to the Cricoid Cartilage Presenting With Subglottic Stenosis: A Case Report and Literature Review.

A 72-year-old Japanese man with a 4-month history of hoarseness and 1-week history of difficulty breathing was admitted to our department. He underwent right total nephrectomy for primary clear cell-type renal cell carcinoma (RCC) 6 years ago and left partial nephrectomy for the metastasis 4 years ago. Flexible laryngeal fiberscope examination revealed bilateral subglottic stenosis without obvious mucosal lesions. Enhanced computerized tomography (CT) scan of the neck revealed that the cricoid cartilage had become bilaterally expansive and tumorous lesion exhibiting enhancement. We performed tracheostomy on the appointed day and biopsied the tumor in the cricoid cartilage via the skin incision. Results of histologic and immunohistologic examinations for AE1/AE3, CD10, and vimentin positivity were consistent with clear cell-type RCC. Chest and abdomen CT scans revealed a few tiny metastases in the upper lobe of the left lung but no recurrence in the abdomen. At 2 weeks from the day of tracheostomy, total laryngectomy was performed. Postoperatively, the patient was treated transorally with axitinib (10 mg/day) and as of 12 months he remains alive with unchanging lung metastasis. Next-generation sequencing of targeted regions using a surgical specimen from the tumor revealed a frameshift mutation in the von Hippel-Lindau gene (p.T124Hfs*35) and a missense mutation in the TP53 gene (p.H193R).

Epstein­Barr virus­associated lymphoepithelial carcinoma arising in the parotid gland: A case report and literature review.

A 60-year-old woman presented with a 3-year history of a slow-growing, painless mass in their left parotid gland. Ultrasonography revealed a well-circumscribed, lobulated, hypoechoic mass measuring 19x12x10 mm in the left parotid gland. Computed tomography revealed a well-circumscribed, solid mass with homogeneous enhancement. Fluorodeoxyglucose-positron emission tomography revealed uptake by the tumor but no uptake in other organs, including the nasopharynx. The patient underwent superficial parotidectomy with adequate safety margins and selective neck dissection followed by radiotherapy. No facial paralysis or recurrence of the tumor had been observed as of 20 months post-operation. Histologically, the tumor was composed of sheets of syncytial cancer cells with prominent nucleoli in a dense lymphoplasmacytic background. Epstein-Barr virus (EBV)-encoded RNA in situ hybridization was diffusely positive in the tumor cells. These findings indicated that the tumor was an EBV-associated lymphoepithelial carcinoma. Metastasis, especially from the nasopharynx, was excluded endoscopically and radiologically. Targeted next-generation sequencing of 160 cancer-related genes using the surgical specimen revealed no mutations, including known significant mutations detected in EBV-associated nasopharyngeal carcinoma.

Endoscopic Resection of a Massive Pleomorphic Adenoma of the Nasal Septum.

Pleomorphic adenoma is a benign tumor that commonly arises from the major salivary glands, such as the parotid and submandibular glands. However, they rarely originate from the nasal cavity. Herein, we describe the case of a 49-year-old woman who presented with nasal obstruction. Preoperative evaluation revealed a giant pleomorphic adenoma attached to the nasal septum. Transnasal endoscopic removal was successfully performed using a specimen retrieval bag. We performed an endoscopic complete en-bloc resection of a large pleomorphic adenoma in the nasal cavity, using a specimen retrieval bag. There were no complications seen, no local recurrences after 2 years of follow-up, and the patient satisfaction was high. We therefore recommend that this technique of using specimen retrieval bags can be favorably utilized for endoscopic removal of large nasal tumors like pleomorphic adenoma.

The efficacy of PD-1 inhibitors in patients with salivary gland carcinoma: A retrospective observational study.

Objective: Immune checkpoint inhibitors (ICIs) have been considered as novel therapeutic approaches for various cancers. ICIs were reportedly efficacious against rare cancers, including salivary gland carcinoma (SGC). We aimed to analyze the efficacy and safety of ICIs in patients with SGC. Methods: We retrospectively analyzed the oncologic outcomes and immune-related adverse events (irAEs) in patients with SGC treated with at least one cycle of nivolumab or pembrolizumab. Results: Among 12 patients, there were two with a complete response (CR), two with a partial response, five with stable diseases, and three with progressive diseases. The overall response rate was 33.3%. A CR was achieved in patients with poorly differentiated carcinoma (carcinoma ex pleomorphic adenoma) and salivary duct carcinoma. The progression-free survival ranged between 1 and 18 months (median, 4 months), while the overall survival ranged between 2 and 25 months (median, 13.5 months). An irAE was observed in only one patient who developed grade 3 erythema multiforme, and this patient's condition improved with withdrawal of pembrolizumab alone. Conclusion: Programmed death-1 blockade was an effective therapy for patients with SGC, including aggressive histologic types.

A retrospective study of parotid gland tumors at a single institution.

The aim of the present study was to analyze the clinical characteristics, surgical treatments and clinical outcome of patients with parotid gland tumors and to compare the results with those cited in the literature. A retrospective study was conducted in 140 patients (male, n=77; female, n=63) with parotid gland tumors who underwent parotidectomy at Hokuto Hospital Department of Otolaryngology-Head and Neck Surgery (Obihiro, Japan) between April 2007 and December 2021. Of the 140 patients enrolled, 118 (84.3%) patients had benign tumors, including 63 (45%) patients with pleomorphic adenomas and 43 (30.7%) patients with Warthin tumors, and 22 patients (15.7%) had parotid carcinoma. Comparison of the three groups of patients with parotid gland tumors indicated that pack years as an indicator of smoking status were significantly higher in patients with Warthin tumors than in those with parotid carcinomas (P=0.011) or pleomorphic adenoma (P<0.001). Fine-needle aspiration cytology (FNAC) was non-diagnostic for only 6 (4.3%) of 140 patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC by both conventional smear and liquid-based cytology (LBC) for parotid carcinomas were 70, 99, 93.3, 94.4 and 82.9%, respectively. Among the 22 patients with parotid carcinoma, extended total/total and superficial parotidectomy were performed in 10 (45%) and 11 (50%) cases, respectively. Total and selective neck dissection of the area from level II to I, II and III were performed in 6 (24%) and 7 (32%) patients, respectively. Postoperative radiotherapy (50 Gy) was performed in 15 (68%) patients. The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 51.5 and 76.4%, respectively. Univariate analysis revealed that age >65 years was significantly associated with poorer 5-year OS (P<0.001) and DFS (P<0.001). Multivariate analysis revealed that an age of more than 65 years combined with high-grade histologic malignancy was associated with worse DFS (P=0.02; hazard ratio, 3.628; 95% confidence interval, 1.283-9.514). In conclusion, the clinical characteristics and treatment outcomes of parotid gland tumors were consistent with the results of previous reports. Smoking may be closely related to the pathogenesis of Warthin tumors. LBC potentially provides improved accuracy in FNAC.

A case of primary histiocytic sarcoma arising from a neck lymph node.

Histiocytic sarcoma (HS) is an aggressive and rare hematological malignancy. Its treatment has not been established, and most patients die within 2 years of diagnosis. Resection can provide a favorable prognosis for solitary lesions. We present the case of an 80-year-old Japanese man with HS. He presented a history of a slow-growing painless mass in the lower part of his right jaw. Ultrasonography showed a swollen lymph node in the vicinity of the right submandibular gland. Contrast-enhanced computed tomography revealed a heterogeneous, low-contrast mass on the right of the neck. Magnetic resonance imaging revealed a heterogeneously enhanced mass in gadolinium-enhanced T1-weighted images. The fine needle biopsy showed spindle-shaped cells and HS was suspected. Fluorodeoxyglucose positron emission tomography revealed uptake by the tumor alone. The patient underwent right upper neck dissection and resection of the submandibular salivary glands. No postoperative adjuvant treatment was administered, but 2-year survival was achieved. Histopathological examination showed proliferation of large, pleomorphic atypical cells without differentiation into lymphocytes, which proved their differentiation into histiocytes. A bone marrow biopsy showed no evidence of monocytic leukemia. Thus, a diagnosis of HS was made. With local treatment alone, our patient achieved long-term survival, maintaining his quality of life.

Sclerosing Polycystic Adenosis Arising in the Parotid Gland Without PI3K Pathway Mutations.

A 15-year-old old Japanese male with a 2-month history of swelling of his left subauricular area was admitted to our department. A thumb-sized, hard mass with mild tenderness was palpated on the left parotid gland. Ultrasonography revealed a well-circumscribed, hypoechoic mass exhibiting heterogeneity in the left parotid gland measuring 1.7 × 1.5 × 1.3 cm. Computed tomography scan revealed a well-circumscribed, solid mass exhibiting slight peripheral enhancement in the left parotid gland. Magnetic resonance imaging revealed a hypointense mass in the left parotid gland on both T1- and T2-weighted images. Clinicoradiologic findings suggested a benign or low-grade malignant parotid tumor. The patient underwent left superficial parotidectomy with adequate safety margins. The facial nerve was identified and preserved. Neither facial paralysis nor tumor recurrence was observed as of 1 year postoperatively. Histologically, the nodule consisted of a vaguely nodular arrangement of variably sized ducts and acini in a hyalinized fibrous background with focal myxoid changes. The ductal/acinar component exhibited a bilayered arrangement of cuboidal luminal and flattened abluminal cells exhibiting a variety of epithelial proliferative patterns, including micropapillary and cribriform. Areas of oncocyte-like changes with intracellular coarse eosinophilic granules, apocrine-like feature, foamy/vacuolated changes, and clear cells were noted in the proliferating epithelium. Immunohistologically, the luminal cells were positive for gross cystic disease fluid protein-15. The Ki-67 labeling index was 2-3%. The histologic features and immunohistologic profile were consistent with sclerosing polycystic adenosis. Targeted next-generation sequencing of 160 cancer-related genes using the surgical specimen revealed no mutations, including known significant mutations in PTEN, PIK3CA, or PIK3R1.