Salivary gland polymorphous adenocarcinoma: Clinicopathological features and gene alterations in 36 Japanese patients.

BACKGROUND: Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma. METHODS: We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations. RESULTS: This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p = 0.0005), the presence of prominent nucleoli (p = 0.0003), and ARID1A split positivity (p = 0.004) were independent risk factors for disease-free survival. CONCLUSION: Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested.

Sarcopenia at the infrahyoid level as a prognostic factor in patients with advanced-stage non-virus-related head and neck carcinoma.

PURPOSE: The purpose of this study was to assess whether the infrahyoid skeletal muscle index (IHSMI) can be used instead of the L3 skeletal muscle index (L3SMI) to define sarcopenia and predict prognosis in patients with locally advanced head and neck squamous cell carcinoma (LHNSCC). METHODS: Patients treated for LHNSCC between January 2009 and April 2018 were assessed. The muscular area at the L3 transverse process and infrahyoid was contoured on absorption-corrected computed tomography prior to treatment. Sarcopenia based on L3SMI (S-L) was defined as values of < 52.4 cm2/m2 for men and < 38.5 cm2/m2 for women. Sarcopenia based on IHSMI (S-I) was determined via receiver operating curve analysis. Overall survival (OS) and cause-specific survival (CSS) curves were constructed using the Kaplan-Meier method. RESULTS: In total, 101 patients were analyzed. The median follow-up period was 19 months (range 3-101 month). S-L and S-I were identified in 74 (73.3%) and 56 patients (55.4%), respectively. The 5-year OS rate did not differ between patients with and without S-L (64.9% vs. 79.2%, p = 0.635), whereas the rate was lower in patients with S-I than without S-I (57.1% vs. 93.0%, p = 0.006). Similarly, the 5-year CSS rate did not differ between patients with and without S-L (77.0% vs. 82.3%, p = 0.523), but the rate was lower in patients with S-I (61.2% vs. 93.0%, p = 0.02). CONCLUSION: Pretreatment S-I, but not S-L, was a good predictor of OS and CSS in patients with LHNSCC.

Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm.

AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.

Retroperitoneal hibernoma resected via laparoscopic surgery.

Hibernomas are extremely rare, benign tumors of brown fat origin with no specific symptoms. Surgery is the only treatment option, and because a definitive preoperative diagnosis is often not obtained, open surgery is usually chosen. In this case, we performed laparoscopic surgery on a 33-year-old woman with retroperitoneal hibernoma. As in most cases, a definitive diagnosis had not been preoperatively made; therefore, we laparoscopically removed the retroperitoneal tumor of unknown pathology as a diagnostic treatment. We chose laparoscopic surgery because of the magnifying effect of the laparoscope and to minimize scarring. The surgery was uneventful, with a procedure time of 280 minutes and a blood loss of 20 mL. The postoperative course was uneventful with no complications or recurrence. We conclude that laparoscopic surgery may be a viable option for hibernomas.

Complete Response to Nivolumab of Resected Adenocarcinoma NOS With Parotid Gland Origin and Lung Metastasis.

BACKGROUND/AIM: Salivary gland adenocarcinoma not otherwise specified (NOS) is classified under the 2017 WHO Classification of Head and Neck Tumors as a malignant neoplasm without the histological features characteristic of other cancer types. Japan's national health insurance program began covering nivolumab in March 2017 for the treatment of patients with recurrent or metastatic head and neck cancer, including salivary gland carcinoma, previously treated with platinum agents. Existing literature does not include cases of patients with salivary gland carcinoma, adenocarcinoma NOS or otherwise, who have achieved complete response to nivolumab. CASE REPORT: Our patient was a 32-year-old woman. Following diagnosis of adenocarcinoma of a right accessory parotid gland, she underwent reconstructive surgery of the parotid gland followed by postoperative adjuvant therapy with radiotherapy and cisplatin. Multiple lung metastases were found 14 months thereafter. Given a history of cisplatin administration, she was treated with nivolumab. Computed tomography (CT) showed partial response after 5 months and complete response after 9 months of nivolumab treatment. Based on CT findings, the lung metastases remained absent 39 months after nivolumab treatment was halted due to the patient's plans for pregnancy. CONCLUSION: Nivolumab may be an effective option for treating high-grade salivary gland carcinomas that recur or metastasize.

A multi-institutional study of salivary gland cytopathology: Application of the Milan System for Reporting Salivary Gland Cytopathology in Japan.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a risk-stratification reporting system that was introduced in 2018. The objective of this multi-institutional study was to evaluate the utility of the MSRSGC in Japan. METHODS: In total, 1608 fine-needle aspiration samples with matching histologic diagnoses were retrieved from 12 large institutions in Japan. The diagnostic categories of the MSRSGC were assigned prospectively or retrospectively, and the results were compared with the histologic diagnoses. RESULTS: The cases were classified as follows: nondiagnostic, 18.1%; non-neoplastic, 4.1%; atypia of undetermined significance, 11.5%; neoplasm-benign, 43.7%; salivary gland neoplasm of uncertain malignant potential, 9.6%; suspicious for malignancy, 3.6%; and malignant, 9.4%. The risk of neoplasm and the risk of malignancy in each MSRSGC category were as follows: nondiagnostic, 72.9% and 13.4%, respectively; non-neoplastic, 15.2% and 9.1%, respectively; atypia of undetermined significance, 77.9% and 24.9%, respectively; neoplasm-benign, 99% and 1.8%, respectively; salivary gland neoplasm of uncertain malignant potential, 94.8% and 37%, respectively; suspicious for malignancy, 100% and 89.7%, respectively; and malignant, 100% and 99.3%, respectively. The accuracy of the MSRSGC for diagnosing neoplasms was 97.8%, and its accuracy for diagnosing malignancy was 97.3%. Institutions that used Romanowsky-stained preparations had lower nondiagnostic rates and lower risks of neoplasm and malignancy in the non-neoplastic category. CONCLUSIONS: The MSRSGC is useful for risk stratification and quality control. Widespread use of the MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care in Japan.

The Diagnostic Utility of RAS Q61R Mutation-specific Immunohistochemistry in Epithelial-Myoepithelial Carcinoma.

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland cancer characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety and overlap of histologic features with other salivary gland tumors, there are broad differential diagnoses. The HRAS Q61R mutation has been reported to be frequent in and specific to EMC. We evaluated the usefulness of RAS Q61R mutant-specific immunohistochemical (IHC) staining for detecting this genetic alteration in EMC. We investigated 83 EMC cases and 66 cases of salivary gland tumors with an EMC-like component, including pleomorphic adenoma, adenoid cystic carcinoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. Sanger sequencing was performed for HRAS, KRAS, and NRAS. The diffuse and membranous/cytoplasmic RAS Q61R IHC expression was observed in 65% of EMC cases, in which all cases harbored the HRAS Q61R mutation. IHC-positive cases were present only in de novo EMCs (54/76 cases, 71%) but not in EMCs ex pleomorphic adenoma. The immunoreactivity was almost always restricted to the myoepithelial cells. Conversely, all EMC cases lacking the HRAS Q61R mutation were negative on IHC. In addition, only 3% of EMC-like tumors showed the abovementioned immunopositivity. None of the cases examined carried KRAS or NRAS mutations. IHC for RAS Q61R is highly sensitive and specific for detecting the HRAS Q61R mutation in EMC. Since significant immunopositivity was almost exclusively identified in nearly two thirds of EMCs but seldom in the histologic mimics, the IHC of RAS Q61R is a useful tool for diagnosing EMC in general pathology laboratories.

Sialadenoma Papilliferum of the Bronchus: An Unrecognized Bronchial Counterpart of the Salivary Gland Tumor With Frequent BRAF V600E Mutations.

Sialadenoma papilliferum (SP) is a rare benign tumor of the salivary glands, and only 3 unequivocal cases of SP arising in the bronchus have been reported. We herein describe the histomorphologic and molecular features of 4 bronchial SP cases and discuss the differential diagnosis of this entity and the relationship with its clinicopathologic mimics, in particular, glandular papilloma and mixed squamous cell and glandular papilloma (GP/MP). We encountered 2 male and 2 female patients with bronchial SP (mean: 66.8 y old). All 4 tumors arose in the central bronchus and were characterized by a combination of surface exophytic endobronchial papillary proliferation and a submucosal multicystic component with complex architecture. The neoplastic epithelium consisted predominantly of nonciliated stratified columnar cells with ciliated, squamous, and mucinous cells present focally. While 2 tumors (50%) harbored a BRAF V600E mutation by molecular and immunohistochemical analysis, similar to GP/MP, no KRAS, HRAS, AKT1, or PIK3CA mutations were detected in any of the cases. Two patients were treated with limited resection, while 2 patients underwent lobectomy based on the diagnosis of adenocarcinoma or possible squamous cell carcinoma in situ in the preoperative biopsy. All survived without recurrence or metastasis for 23 to 122 months after treatment. SP can develop in the central bronchus as the bronchial counterpart of the salivary gland tumor and should be considered in the differential diagnosis of endobronchial tumors. In addition, some histologic resemblance and frequent BRAF V600E mutation raise the possibility of SP and GP/MP being on the same disease spectrum.

Diffusion-weighted imaging might be useful for reactive lymphoid hyperplasia diagnosis of the liver: A case report.

BACKGROUND: Reactive lymphoid hyperplasia (RLH) of the liver is a rare liver lesion. It is considered difficult to differentiate radiologically from hepatocellular carcinoma, metastatic liver tumor and other pathologies. CASE SUMMARY: A 54-year-old woman presented to our hospital with RLH of the liver. The patient had a diagnosis of metastatic carcinoma of the liver from an unknown origin and subsequently underwent partial hepatectomy. However, histopathological analysis revealed RLH. The lesion showed perinodular enhancement in the arterial phase on contrast-enhanced computed tomography and magnetic resonance imaging. On diffusion-weighted imaging (DWI), we encountered linear hyperintensity along the portal tract consecutive to the liver lesion, which is a new characteristic radiologic finding. This finding corresponded to the lymphoid cell infiltration of the portal tract. Furthermore, there was strongly restricted diffusion on the apparent diffusion coefficient map. We used these characteristic radiologic findings to diagnose the lesion as a lymphoproliferative disease. CONCLUSION: The linear hyperintensity consecutive to the liver lesion on DWI provided additional valuable diagnostic information.

Salvage carbon ion radiotherapy for recurrent solitary fibrous tumor: A case report and literature review.

BACKGROUND: Malignant solitary fibrous tumor (MSFT) arising from the spinal cord is extremely rare and poorly understood mesenchymal neoplasms: only a few MSFT in the spinal canal has been described. We describe the clinical course of the patient with MSFT arising from the thoracic spinal cord. CASE REPORT: We describe the clinical course of the patient and the radiological and pathological findings of the tumor. The tumor had been resected by microscopic posterior approach and video-assisted thoracic surgery, but local recurrence was observed by MRI at 1-year follow-up period. No metastatic lesion was confirmed. Then, carbon ion radiotherapy (CIRT) was administered to the recurrent lesion. Local suppression has been observed for 40 months after irradiation. CONCLUSION: Dumbbell-shaped MSFT arising from thoracic spinal cord is a highly unusual presentation. CIRT might be effective for treatment of recurrent tumors.

Diagnostic Significance of HRAS Mutations in Epithelial-Myoepithelial Carcinomas Exhibiting a Broad Histopathologic Spectrum.

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor that is histologically characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety, it is sometimes challenging to make an accurate diagnosis, and useful ancillary tests are essential for this purpose. We investigated 87 cases of EMC arising in the major and minor salivary glands and seromucinous glands in the nasal cavity or bronchus to describe the histologic features and mutation status of selected key oncogenes. Classic EMC accounted for 40.2% of all cases. Other cases showed various growth patterns and cytologic features in addition to the typical histology; cribriform patterns, a basaloid appearance, and sebaceous differentiation were relatively common (17.2% to 18.4%), whereas oncocytic/apocrine, papillary-cystic, double-clear, squamous, psammomatous, Verocay-like, and high-grade transformation were rare. HRAS mutations were found in 82.7% of EMCs and were concentrated in codon 61. There was no significant correlation between the HRAS mutation status and the histology. No EMC ex pleomorphic adenoma cases had HRAS mutations. PIK3CA and/or AKT1 mutations were the second most frequent mutations (20.7%, 6.5%, respectively) and almost always cooccurred with HRAS mutations. It is noteworthy that the HRAS mutation was not identified in any salivary gland tumor entities manifesting EMC-like features, including adenoid cystic carcinoma, pleomorphic adenoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. We conclude that HRAS mutations are a frequent tumorigenic gene alteration in EMC, despite its histologic diversity. This study provides further insight into strategies for diagnosing EMC and discriminating it from its mimics.