Solitary liver metastasis from adenoid cystic carcinoma of the submandibular gland.

Adenoid cystic carcinoma (ACC) is a rare tumour of the salivary glands characterised by distant metastases, mainly to lungs and bone. Isolated metastasis to the liver is unusual. We present the case of a woman with an ACC of the submandibular gland (pT1N0) who underwent radical submandibular gland excision and selective neck dissection. Preoperative imaging identified a liver lesion with features suggestive of a haemangioma. Two-year postoperatively, a surveillance CT neck/trunk showed an increase in size of the left liver lobe lesion. Subsequent MR liver and US-guided biopsy confirmed the lesion to be metastatic ACC. The patient underwent a successful left lateral liver sectionectomy. She remains disease-free 2.5 years after her liver resection. A literature search revealed only four other similar cases. This report highlights that even early-stage ACCs of the salivary gland may present with synchronous solitary liver metastasis which can be effectively treated with curative surgery.

Leiomyoma of submandibular gland.

Leiomyoma is a benign tumour of smooth muscle origin. Leiomyoma arising in major salivary gland is under-reported. We report a case of a woman in her 40s with a submandibular gland tumour which represented a diagnostic challenge during preoperative assessment. The core needle biopsy of submandibular gland tumour revealed a spindle cell tumour suggestive of an undifferentiated tumour. As a malignancy could not be excluded, the submandibular gland tumour was removed en bloc with surrounding lymph nodes in level Ib of the neck. Leiomyoma may be included in the differential diagnosis of spindle cell salivary gland tumours, particularly when there are no signs of infiltration and preoperative investigations are inconclusive.

Primary Epithelioid Angiosarcoma of the Submandibular Gland-A Case Report with Histology-Cytology Correlation and Comprehensive Molecular Analysis.

BACKGROUND: Angiosarcoma is a sarcoma that occurs in a range of tissue types, and only rarely in the salivary glands, showing a predilection for the parotid glands of older patients. Preoperative diagnosis may be challenging, especially on cytology, with significant morphological overlap with high-grade primary salivary gland carcinomas. The molecular alterations of this rare salivary gland neoplasm are also not well-characterized. METHODS AND RESULTS: We present a case of right submandibular gland swelling in a 73-year-old male. On fine needle aspiration, including immunohistochemical stains on cell block, the tumor was initially diagnosed as poorly differentiated carcinoma. Resection of the submandibular gland revealed epithelioid angiosarcoma. We performed molecular work-up of the tumor, utilizing targeted next-generation sequencing, DNA methylation profiling and fluorescence in-situ hybridization. Histopathologic assessment revealed an infiltrative tumor comprising solid sheets of epithelioid cells. The tumor cells formed haphazardly anastomosing vascular channels with intracytoplasmic lumina containing red blood cells. On immunohistochemistry, the tumor cells were positive for CD31, CD34 and ERG. Approximately 40% of the tumor cells showed nuclear expression of GATA3. A pathogenic TP53 R267W mutation was detected on next-generation sequencing. DNA methylation analysis did not cluster the tumor with any known sarcoma type. Copy number analysis showed possible MYC amplification and CDKN2A losses, although only the latter was confirmed on fluorescence in-situ hybridization. CONCLUSION: Epithelioid angiosarcoma is an important differential diagnosis to high-grade salivary gland carcinoma. In particular, GATA3 expression may be encountered in both angiosarcoma and high-grade salivary gland carcinomas and cause diagnostic confusion. Identification of TP53 mutations and CDKN2A losses suggest shared oncogenic pathways with soft tissue angiosarcomas, and should be further investigated.

Novel decision tree models predict the overall survival of patients with submandibular gland cancer.

BACKGROUND: While the accurate prediction of the overall survival (OS) in patients with submandibular gland cancer (SGC) is paramount for informed therapeutic planning, the development of reliable survival prediction models has been hindered by the rarity of SGC cases. The purpose of this study is to identify key prognostic factors for OS in SGC patients using a large database and construct decision tree models to aid the prediction of survival probabilities in 12, 24, 60 and 120 months. MATERIALS AND METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology and End Result (SEER) program. Demographic and peri-operative predictor variables were identified. The outcome variables overall survival at 12-, 24-, 60, and 120 months. The C5.0 algorithm was utilized to establish the dichotomous decision tree models, with the depth of tree limited within 4 layers. To evaluate the performances of the novel models, the receiver operator characteristic (ROC) curves were generated, and the metrics such as accuracy rate, and area under ROC curve (AUC) were calculated. RESULTS: A total of 1,705, 1,666, 1,543, and 1,413 SGC patients with a follow up of 12, 24, 60 and 120 months and exact survival status were identified from the SEER database. Predictor variables of age, sex, surgery, radiation, chemotherapy, tumor histology, summary stage, metastasis to distant lymph node, and marital status exerted substantial influence on overall survival. Decision tree models were then developed, incorporating these vital prognostic indicators. Favorable consistency was presented between the predicted and actual survival statuses. For the training dataset, the accuracy rates for the 12-, 24-, 60- and 120-month survival models were 0.866, 0.767, 0.737 and 0.797. Correspondingly, the AUC values were 0.841, 0.756, 0.725, and 0.774 for the same time points. CONCLUSIONS: Based on the most important predictor variables identified using the large, SEER database, decision tree models were established that predict OS of SGC patients. The models offer a more exhaustive evaluation of mortality risk and may lead to more personalized treatment strategies.

Imaging of salivary gland cancers derived from a sublingual gland herniated into the submandibular space: a report of three cases.

Sublingual gland herniation into the submandibular space through a mylohyoid muscle defect is a common anatomical variation; however, salivary gland cancers that arise from a herniated sublingual gland have not been described yet. Here, we report three patients with salivary gland cancers originating from a herniated sublingual gland. All tumors were detected as palpable submandibular masses, located anterior to the submandibular gland, medial to the mandible, and lateral to the mylohyoid muscle, with contact with the sublingual gland through a mylohyoid muscle defect. Intraoperative findings confirmed that the masses were derived from herniated sublingual glands. Pathological examination showed one case of mucoepidermoid carcinoma and two cases of adenoid cystic carcinoma. Imaging findings of the tumor location, in addition to the continuity with the sublingual gland through the mylohyoid muscle defect, are crucial for accurately diagnosing the tumor origin, which is essential for determining the appropriate clinical management.

Primary intestinal-type adenocarcinoma: Report of a rare case involving a young patient.

The aim of this report was to describe a rare example of sporadic intestinal-type adenocarcinoma of the major salivary glands and oral cavity. A 23-year-old female patient presented an asymptomatic, progressive-growing mass involving the floor of mouth and the left submandibular gland. Fine-needle aspiration cytology, imaging exams, and surgical specimen findings were consisted with the diagnosis of primary intestinal-type adenocarcinoma, despite its similar immunohistochemical results with colorectal adenocarcinoma. Adjuvant chemotherapy and radiotherapy were performed, but the patient developed multiple metastatic lesions after one year of initial the intervention and deceased following 13 months of follow-up, despite several therapeutic efforts. We verified that sporadic cases of primary intestinal-type adenocarcinoma still lack information regarding etiology and tumorigenesis, especially in young and females. A complete diagnostic workflow is indispensable to rule out the presence of primary colorectal adenocarcinoma.

Recurrence of Submandibular Adenocarcinoma with Intra-cranial Metastasis as the First Symptom.

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Benign submandibular gland tumours: outcomes of gland-preserving excision by endoscopic or conventional approach.

Endoscope-assisted surgery is becoming a preferred technique in salivary gland surgery. However, this technique has not yet been applied in submandibular gland (SMG) preservation surgery. This retrospective study was performed to evaluate the outcomes of endoscope-assisted gland-preserving surgery through a hairline incision in patients with benign SMG tumours. The study included 38 patients with benign SMG tumours who underwent tumour excision with gland preservation: 19 who underwent local excision of the tumour through an endoscope-assisted hairline approach and 19 who received the conventional cervical approach. The feasibility of the surgical procedure, perioperative patient variables, and postoperative appearance and functional outcomes were evaluated. Patients in both groups had their tumours removed successfully with tumour-free margins. The intraoperative blood loss, postoperative amount of drainage, mean length of the incision, and unstimulated saliva flow rate did not differ between the two groups. There was no difference in the stimulated saliva flow rate between the preserved gland and unaffected SMG. The aesthetic result was better in the endoscope-assisted hairline incision group. No tumour recurrence occurred during follow-up (range 12-52 months). Thus, gland-preserving tumour dissection appears to be a safe method for benign SMG tumours, with good functional results. Furthermore, the endoscope-assisted hairline incision is a feasible method with excellent cosmetic results.

The rate of occult nodal metastasis in submandibular gland malignancies: A case series and meta-analysis.

OBJECTIVE: Submandibular gland (SMG) malignancies are exceedingly rare. Lymph node metastasis is one of the most important determinants of outcome in SMG malignancies. The aim of this study was to investigate the overall rate of occult neck nodal metastasis in SMG malignancies. STUDY DESIGN: The study design is a meta-analysis of all studies on patients with a primary SMG malignancy, without evidence of neck nodal metastasis, who underwent an elective neck dissection (END). The search strategy identified 158 papers that appeared in print from January 1980 to July 2020. All eligible patients from the Tel-Aviv Medical Center were analyzed and consolidated into a case series. A total of 12 retrospective studies that included 306 suitable patients met inclusion criteria. RESULTS: The risk for occult metastasis in primary SMG malignancies was 0.0% to 50.0%, with a fixed effect model of 19.52% (95% CI, 14.9%-24.5%). The analyzed studies included a wide range of pathologies. The most common malignancies were adenoid cystic carcinoma and mucoepidermoid carcinoma. CONCLUSIONS: The overall rate of occult neck metastasis in SMG malignancies is relatively high, and an END should be the default intervention in these cases. An END is unwarranted in tumors judged clinically to be low stage and low grade.

Primary desmoplastic small round cell tumor of the submandibular gland: a case report and literature review.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a sporadic, highly malignant tumor with a poor prognosis. The abdomen and pelvis have been reported as the primary localization sites. However, to the best of our knowledge, there are few reports on primary DSRCT in the submandibular gland. CASE PRESENTATION: We report a case of a 26-year-old Chinese man with a mass in the right submandibular gland. Imaging studies showed a hypoechoic mass in the right submandibular region. Intraoperative pathology revealed that the tumor tissue was composed of small round tumor cells and a dense desmoplastic stroma. On immunostaining, the tumor cells showed markers of epithelial, mesenchymal, myogenic, and neural differentiation. The EWSR1 gene rearrangement was detected by fluorescence in situ hybridization. Based on the overall morphological features and immunohistochemical findings, a final diagnosis of DSRCT was made. The patient was treated with comprehensive anti-tumor therapy mainly based on radiotherapy and chemotherapy. CONCLUSIONS: DSRCT is an uncommon malignant neoplasm with rare submandibular gland involvement. In this report, we have described a case of DSRCT in the submandibular gland and reviewed the literature on DSRCT over the past 5 years. Considering the importance of differential diagnosis between DSRCT, especially with rare extra-peritoneal involvement, and small round blue cell tumors, a full recognition of the clinicopathological features will help to better diagnose this neoplasm.

Functional gland-preserving surgery for submandibular gland pleomorphic adenoma.

PURPOSE: Conventional surgery for submandibular gland tumour is total excision of the gland affected by the tumour. Gland-preserving surgery is commonly used for benign tumours arising in the parotid gland but not in the submandibular gland. This study evaluated long-term oncological and functional outcomes after gland-preserving surgery in patients with pleomorphic adenoma of the submandibular gland via the submental approach. METHODS: This longitudinal study included 105 consecutive patients with submandibular gland pleomorphic adenoma who underwent the gland-preserving surgery combined with the en-bloc resection of tumours via the submental approach. Salivary scintigraphy was performed 6 months after surgery, and ultrasonography was regularly followed. Intraoperative findings, postoperative complications, cosmetic and salivary functions, and tumour recurrence were assessed in these patients. RESULTS: Median tumour size and submental incision length were 2.0 and 3.3 cm, respectively. Median operation time and amount of blood loss were 25 min and 18.5 mL, respectively. None had marginal or lingual nerve paralysis and most patients were satisfied with incision scar and facial contour. The salivary function of the affected gland was equal to that of the unaffected gland. One patient (0.9%) had single nodular recurrence 54 months after surgery and others had no recurrence for follow-up of median 96 months. CONCLUSIONS: Pleomorphic adenoma of the submandibular gland can be safely removed by the gland-preserving surgery via the submental approach which has operation time, cosmetic and functional benefits with compromising oncological outcomes.

Hsp27 and Hsp60 in human submandibular salivary gland: Quantitative patterns in healthy and cancerous tissues with potential implications for differential diagnosis and carcinogenesis.

Tumors of the submandibular salivary gland (SMG) are uncommon but sufficiently frequent for the physician to consider them in routine examinations and for the pathologist to be prepared to differentiate them from other tissue abnormalities. However, scarcity of specimens makes training difficult, a situation compounded by the lack of accepted universal diagnostic guidelines. Furthermore, there is little information on the chaperone system (CS) of the gland, despite the increasing evidence of its participation in carcinogenesis as a biomarker for diagnosis and patient follow up, and in the mechanisms by which the tumor cells thrive. We are investigating this aspect of various tumors, and here we describe standardized methods for assessing the tissue levels of two chaperones, Hsp27 and Hsp60, in normal SMG and its tumors. We present illustrative results obtained with immunohistochemistry (IHC) and immunofluorescence-confocal microscopy (IF-CM), which we propose as a platform onto which a data base could be built by adding new information and which would provide material for developing guidelines for tumor identification and monitoring. The initial findings are encouraging in as much as the tumors surveyed showed quantitative patterns of Hsp27 and Hsp60 that distinguished tumoral from normal tissue and certain tumors from the others, and the results from IHC were confirmed by IF-CM.

The role of frozen section biopsy for submandibular gland tumors.

BACKGROUND: Although there have been several reports of the diagnostic accuracy of frozen section biopsy (FSB) for parotid gland tumors, few studies have focused on its diagnostic accuracy for submandibular gland tumors. AIM/OBJECTIVES: This study aimed to investigate the necessity of FSB with regard to its diagnostic accuracy for submandibular gland tumors (SGTs). MATERIALS AND METHODS: About 42 SGT patients underwent both fine-needle aspiration cytology (FNAC) and FSB between 2005 and 2020. The results of FNAC and FSB were analyzed and compared with the final histological diagnoses. RESULTS: The respective sensitivity and specificity in detecting malignant tumors in 38 cases, excluding the four indeterminate FNAC cases, they were 0 and 97% for FNAC, and 100 and 97% for FSB. Considering the four indeterminate FNAC cases to be malignant, the respective sensitivity and specificity in detecting malignant tumors in the 42 cases were 50 and 92% for FNAC, and 100 and 95% for FSB. CONCLUSIONS AND SIGNIFICANCE: FSB may be useful for malignancy detection as a final histological diagnosis in cases that are diagnosed as benign or indeterminate by FNAC in SGTs.

Epithelial-Myoepithelial Carcinoma of the Submandibular Gland: Case Report.

Epithelial-myoepithelial carcinoma (EMC) is a rare malignant salivary gland tumor that occurs mostly in the parotid gland. We report a case of EMC of the submandibular gland in a young man. The patient was aware of a slow-growing mass in the right submandibular gland for 1 year. Clinical examination and ultrasound confirmed a right submandibular mass, 2.5 × 3 cm2 in size. Ultrasound-guided fine-needle aspiration indicated a diagnosis of pleomorphic adenoma, which was also suggested by magnetic resonance imaging. The submandibular gland tumor was excised. Immunohistochemical analysis showed carcinoma ex pleomorphic adenoma with a major epithelial-myoepithelial component. The patient was not treated with radiotherapy after surgery. No recurrence was observed during 24 months of follow-up. Because the morphology of EMC is similar to that of a benign tumor, it is frequently initially misdiagnosed. Surgery is always the most effective diagnostic and therapeutic measure for salivary gland tumors, especially those that grow slowly. Resection with negative margins is the treatment of choice for EMC; use of adjuvant radiotherapy is controversial.

Surgical treatment of liver and kidney metastasis from an adenoid cystic carcinoma of the submandibular gland: case report.

INTRODUCTION: Adenoid cystic carcinomas (ACCs) account for 10% of all malignant salivary tumours. They are slow-growing but locally aggressive. Reports of liver and renal metastases are rare. CASE DESCRIPTION: A 58-year-old woman who had undergone resection of a left submandibular ACC in 1995 was referred to our centre for follow-up in 2018. A computed tomography scan revealed two lesions: one on segment six of the liver and the other on a kidney. A hepatic wedge resection and right nephrectomy were performed. The postoperative course was uneventful. At 2-year follow-up, the patient was alive and well with no evidence of disease. CONCLUSION: Management of ACC is a therapeutic challenge because of its tendency for distant metastases. The literature recommends regular follow-up imaging and radical surgical treatment but specific guidelines for the approach to recurrence are lacking.

Histopathologic and clinical outcomes of Milan System categories "non-diagnostic" and "non-neoplastic" of salivary gland fine needle aspirations.

INTRODUCTION: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) specifies six categories with estimated risks of malignancy (ROM) and suggested management. The estimated ROM is 25% for Non-Diagnostic (ND) category, and 10% for Non-Neoplastic (NN). This study aimed to investigate histopathologic and clinical outcomes of MSRSGC categories ND and NN at the authors' institution. MATERIALS AND METHODS: Cytopathology fine needle aspiration reports from 2008-2020 were searched for the word "salivary", "parotid", and "submandibular". Cases fitting Non-Diagnostic (ND) and Non-Neoplastic (NN) categories were identified. Follow-up cyto-/histopathologic and clinical data were extracted. RESULTS: There were 43 ND and 46 NN cases. The average age was 58.3 years. Neoplastic lesions were found in 13 of 43 (30%) ND and 3 of 46 (6.5%) NN. The rate of malignancy in ND category was 14.0% (6/43) and 0% (0/46) in NN category. Four cases in ND (9.3%) and 6 (13.0%) in NN had no neoplasm and instead had an underlying reactive condition (e.g., chronic sialadenitis) or inflammatory lesion (e.g., lymphoepithelial cyst) on histologic follow-up. There was no follow-up pathology in 46.5% NDs (20/43) and 82.6% NNs (38/46); however, no lesions were apparent clinically with a mean follow-up of 3 years and 1.5 years, respectively. CONCLUSIONS: MSRSGC categories ND and NN are helpful for reporting salivary gland FNA results. With proper clinical and radiologic correlation, ROM of NN is low; however, ROM of ND remains significant. Repeat FNA after correlation for ND cases seems prudent as neoplasms and malignancies may have gone undetected.

Endobronchial sialolipoma. Case report.

BACKGROUND: A 52-year-old woman presented with shortness of breath and cough. An endobronchial sialolipoma was found at the left entrance of the main bronchus. Sialolipoma is an exceedingly rare type of lipoma reported of the minor salivary glands, especially within the bronchus. CASE PRESENTATION: A 52-year-old woman presented with shortness of breath and cough with 6 months´ evolution. Endobronchial endoscopy revealed a tumour at the left entrance of the main bronchus. The entire removal of the tumour was removed using a cryoprobe device. Pathological examination showed a tumour consistent with the diagnosis of sialolipoma due to the presence of mature adipose cells blended with acinar, ductal, basal, and myoepithelial cells. The patient had a favourable outcome. CONCLUSION: The infrequent tracheobronchial presentation of this tumour can be challenging for correct diagnosis.

Solitary fibrous tumour of the submandibular gland: Novel insights from clinical practice on a close mimicker of pleomorphic adenoma and a diagnostic challenge for the cytopathologist.

Spindle cell lesions of the salivary glands are rare and account for less than 3% of the salivary gland aspirates. A definitive classification of salivary gland neoplasms by fine needle aspiration is possible for the most common lesions but remains a challenge for the less common entities. We present a case of a 72-year-old male with a solitary fibrous tumour (SFT) of the submandibular gland mimicking a myoepithelial-rich pleomorphic adenoma (PA). In this article, we discuss novel insights that help differentiate SFT from PA and other spindle cell lesions.