Mammary analogue secretory carcinoma involving submandibular gland: Diagnostic pitfall with review of literature.

ABSTRACT: Mammary analogue secretory carcinoma (MASC) is a recently defined entity among salivary gland tumors. MASC bores a striking resemblance to secretory carcinoma of breast along with the characteristics of ETV6-NTRK3 translocation. Hence, the entity was designated as MASC and was formally included in the 4th edition of World Health Organization classification of head and neck tumors in 2017. To the best of our knowledge, around 12 cases of MASC have been described in the Indian literature. MASC commonly involves parotid gland (70%). Involvement of submandibular gland is still rarer (7%). Prognosis of MASC is comparable to other low grade salivary gland malignancies; however, aggressive behavior has also been reported in few cases. This case is one of the very few reported cases describing MASC with detailed clinical, cytology, and microscopy findings along with special stains and immunohistochemistry.

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.

A tale of recurrent secretory carcinoma of submandibular gland in an adolescent male: A rare presentation of a rare tumor.

Mammary analogue secretory carcinoma (MASC) is a rare salivary gland tumor which shares its histologic, immunohistochemical, and genetic features with the secretory carcinoma (SC) of breast. In this case report, we describe a case of MASC in a young adolescent male with swelling in the right angle of mandible which is a relatively rare site to present along with its correlation of cytological, histological, and immunohistochemical features. A 16-year-old male came with the complaint of swelling in the right angle of mandible since 2 years. Contrast-enhanced computed tomography (CECT) neck revealed differential diagnosis of nerve sheath tumor, pleomorphic adenoma, and adenoid cystic neoplasm was kept, and subsequently fine-needle aspiration cytology (FNAC) was done. FNAC was done in which differential diagnosis of myoepithelial neoplasm, acinic cell carcinoma, and SC was given. Surgical excision was done followed by histopathological examination. Immunohistochemistry panel was also applied, and final diagnosis of SC was rendered. SC has distinct cytological, histological, and immunohistochemical features which should be recognized by the pathologists for the appropriate management of the patient.

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.

Management of malignant submandibular gland tumors: A 30-year experience from a single center.

OBJECTIVE: Owing to histologic heterogeneity, biological behavior, and rarity, recommendations for the treatment of malignant submandibular gland tumors (MSGT) are inconsistent. The aim of this study was to present a single-center experience in the treatment of MSGT with an emphasis on surgical treatment, including indication on elective neck dissection (END). STUDY DESIGN: Twenty-four MSGT were primary surgically treated (gland excision with neck dissection). Their records were retrospectively collected and analyzed. RESULTS: The most frequent histology was adenoid cystic carcinoma (41.6%), followed by mucoepidermoid carcinoma (25%) and carcinoma ex pleomorphic adenoma (16.7%). There were 18 elective and 6 therapeutic neck dissections. Histopathologic examination confirmed 29% (7/24) of positive neck dissection specimens. The Kaplan-Meier analysis presented rates of disease-specific survival, disease-free survival, and overall survival (OS) of 81%, 78%, and 52% at 5 years, respectively. Patients undergoing postoperative radiotherapy had significantly higher OS rates compared with patients treated with surgery alone (P = .0209). CONCLUSION: Results of this study suggest that END has questionable benefit in early stage MSGT. Elective selective neck dissection levels I-III is recommended in high-grade and advanced stage MSGT without evidence of multilevel lymphadenopathy.

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.

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.

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.

Giant submandibular sialolipoma masquerading as huge goitre: a case report.

BACKGROUND: Sialolipoma is a rare tumour which may arise from both major and minor salivary glands and has recently been described as a variant of salivary gland lipomatous lesions. CASE PRESENTATION: We report a 54-year-old male who presented with a 7-year history of large right anterior neck swelling. He was clinically euthyroid and had no compressive or infiltrative symptoms. He sought medical attention due to the discomfort exerted by the weight of the mass and was keen for excision. The swelling appeared like a goitre but physical examination proved otherwise. Imaging was suggestive of a benign tumour arising from the right parapharyngeal fossa. The mass was surgically excised and was noted to be adherent to part of the submandibular gland. Histopathological examination revealed a new variant of benign adipocytic tumour of salivary gland or sialolipoma arising from the submandibular gland. Besides being the largest sialolipoma to be reported, there are also no reports of giant submandibular sialolipomas masquerading as a huge goitre in appearance. CONCLUSION: Submandibular sialolipomas can present in really large sizes and appear as a giant goitre. It is important to differentiate between benign lipomas from liposarcomas and tailor the management accordingly. Surgical enucleation is the preferred choice of treatment for these benign tumours with low recurrence rates.

Unusual presentation of submandibular lingual nerve sheath tumour as sublingual stone.

A 60-year-old woman was referred to the otolaryngologist for 18 months of left-sided tongue pain and taste changes. Surgeon-performed ultrasound of the submandibular region revealed a hyperechoic mass. Wharton's duct was dilated proximally and the submandibular gland demonstrated normal vascularity. While these findings were highly suspicious for submandibular gland sialolith, an in-office attempt at sialolithotomy suggested an alternate process or mass. After imaging failed to further elucidate an aetiology, surgical exploration revealed a well-circumscribed submandibular mass associated with the lingual nerve. The mass was removed en-bloc and pathology revealed a schwannoma of the lingual nerve.

A case of oncocytic lipoadenoma of the submandibular gland and its diagnostic cytology challenges.

Lipomatous tumors of the salivary gland in general are rare and oncocytic lipoadenomas are even much rarer. Most of the reported cases of oncocytic lipoadenoma were located in the parotid gland and to the best of our knowledge, only four cases reported to arise from the submandibular gland. The preoperative interpretation of the aspirates taken from these lesions can be difficult and challenging. We report a case of a 41 year old gentleman who presented with submandibular gland swelling. CT scan of the neck revealed an oval-shape enhancing mass in the inferior aspect of the right submandibular gland measuring 19 × 12 mm. Fine needle aspiration biopsy (FNAB) showed hypocellular smears with few clusters of epithelial cells having oncocytic appearance. The cytologic findings were interpreted as "oncocytic lesion." Submandibular gland excision was done. Histologically, a final diagnosis of oncocytic lipoadenoma was rendered. We present this rare entity to add to the few cases reported to date and to upsurge awareness during cytologic examination of oncocytic salivary gland lesions.

Schwannoma-Like Pleomorphic Adenoma: Two Cases and a Review of the Literature.

Schwannoma-like pleomorphic adenoma is a rare variant of the common benign salivary neoplasm, pleomorphic adenoma. This entity's cytomorphology closely mimics a schwannoma, potentially making a diagnosis of cytologic preparations or of surgical specimens a challenge. To the best of our knowledge, there are only six previous reports of schwannoma-like pleomorphic adenoma with eight total cases in the English language literature prior to the addition of the two cases detailed in this report. Our report includes what we believe to be the first documented case of this entity occurring in the submandibular gland. One of our cases occurred in the submandibular gland of a 90-year-old woman and the other occurred in the left parotid gland of a 40-year-old woman. We also examine the diagnostic considerations used to differentiate these two entities.

Sialoblastoma of the submandibular gland: a distinct entity?

Sialoblastoma is a rare congenital malignant tumor of the salivary glands. A case of a submandibular sialoblastoma in a 1.5-year-old child is presented. A comparative analysis on 79 pediatric cases reported in the literature suggests a less aggressive behavior for submandibular sialoblastoma in comparison with other sites. Classically, diagnosis is confirmed by open biopsy, but fine-needle aspiration may offer an alternative with reduced morbidity. Expression of AFP and high levels of Ki-67 have been associated with poor prognosis. Whilst early surgical resection with negative margins is widely accepted as first-line treatment, there is no consensus on therapy of recurrence and follow-up. MRI and sonography represent valid tools for the follow-up, which is usually restricted to 3-5 years.Conclusion: Submandibular sialoblastomas may have a different biological profile in comparison with parotid tumors with the absence of metastasis and much lower rate of recurrence. Comprehensive diagnostics should include additional options such as fine-needle aspiration and markers to assess cell proliferation and AFP. Literature suggests that surgery alone is sufficient for the treatment of tumors with low malignancy. Follow-up should be tailored according to the tumor site and might be limited to 3-5 years. What is Known: • Sialoblastoma is a rare congenital malignant tumor with an unpredictable clinical outcome. What is New: • Sialoblastoma of submandibular origin seems to have a less aggressive behavior in comparison with other sites. • Fine-needle aspiration and markers to assess proliferation index (i.e., suggestive of potential more aggressive course/malignancy) should be strongly considered in the diagnostic work-up. • Radical surgery as first-line therapy and a 3-5-year follow-up are acceptable for tumors with a low malignancy.

Synchronous double malignancy of lip and submandibular salivary gland with rare histology.

In the modern era, there is an increase in the incidence of double malignancies owing to the remarkable improvement in cancer diagnostics and patient survival. Double malignancies can be either synchronous or metachronous. Synchronous double malignancy can present either at the same time or within 6 months of diagnosis of the first one. We present a case of double malignancy of lip and submandibular salivary gland, diagnosed in a 55-year-old male, who presented with ulceroproliferative lesion of the upper lip and a hard swelling in the right submandibular gland. The tissue diagnosis was suggestive of squamous cell carcinoma of the lip and mucoepidermoid carcinoma of the submandibular gland. The patient underwent successful wide local excision of the lip and submandibular gland along with prophylactic supraomohyoid neck dissection. This case is reported for the rarity in site and histopathology of double malignancy.