Salivary Gland Adenocarcinoma Research Articles

A rare case of an aggressive polymorphous adenocarcinoma of minor salivary gland in the retro-maxilla

Abstract Polymorphous adenocarcinoma (PAC) is a low-grade malignant tumour of minor salivary glands of the oral cavity, which rarely presents with invasive features. Low metastatic and excellent survival rates are some of its favorable features. A 36-year-old woman reported with swelling, pain, and mobility of teeth in the left upper inner cheek region. Contrast enhanced computed tomography (CECT) revealed a large, lobulated, heterogenous mass in the left retro-maxillary region with a few enlarged left cervical lymph nodes (levels IB and II). After surgery, the final histopathology report gave a definitive diagnosis of PAC with certain invasive characteristics – perineural invasion, infiltration into skeletal muscle, and depth of invasion of 10 mm, which recurred in a different location 1.5 years later. A few predictable features of PAC include incidence in elderly women, asymptomatic presentation, occurrence in the posterior hard of soft palate, very low incidence of nodal or distant metastases, perineural spread, skeletal muscle infiltration, and low rates of recurrence with good survival outcomes. However, in our case, the patient appeared to present with a relatively aggressive form of PAC, considering her young age, symptomatic presentation, uncommon anatomic location in the retro-maxilla, cervical nodal metastasis, perineural and skeletal muscle infiltration, and local recurrence within a short period. Although PAC is a low-grade tumour with excellent prognosis, it may occasionally present with invasive characteristics, and early diagnosis and prompt management with strict adherence to post-operative regimens and follow-up is of prime importance to prevent any untoward outcomes.

First report of primary tonsillar salivary gland adenocarcinoma in a dog

AbstractA 9‐year‐old, female, spayed, mixed breed dog was presented for diagnosis of adenocarcinoma of the minor salivary glands of the right tonsil by histopathology. A whole‐body computed tomography scan showed no detectable abnormalities in the major salivary glands. No pulmonary metastasis or lymphadenopathy was noted. An anaesthetised oropharyngeal examination revealed an erythematous and irregular broad‐base mass in the right tonsil, and an erythematous and slightly irregular nodular area in the contralateral tonsil. Bilateral excisional biopsies of the tonsils via tonsillectomies were performed for definitive diagnosis. Histopathology of the right tonsillar mass was consistent with an incompletely excised adenocarcinoma of the minor salivary gland, and reactive lymphoid hyperplasia of the contralateral tonsil. Based on this case report, it is important to consider salivary adenocarcinoma as a differential diagnosis for primary tonsillar tumour, as there are lobules of salivary glands in normal canine tonsils.

The immunohistochemical expression Ki-67 In Polymorphous Low Grade Adenocarcinoma of the Salivary Glands

Background: Polymorphous Low Grade Adenocarcinoma is a rare malignant tumor of minor salivary glands. It has an unique histopathological, clinical and behavioural features. Most of its incidence has been presented in the palate. It shows a variety of growth patterns within the same one lesion, including cribriform, tubular, and solid areas that may mimic adenoid cystic carcinoma. The tumor cells histologically are characterized by lacking of nuclear atypical and hyperchromatism with rare mitoses. However, the prognosis of this tumor is good because of its low grade, although it has an unpredictable potential to metastasize.
 Objectives: To evaluate the histopathological expression of Ki-67 proliferation antigen in Polymorphous low grade adenocarcinoma and compare the results with the clinicopathological parameters and grading of the tumors.
 Materials and Methods: This study includes 20 cases with Polymorphous Low Grade Adenocarcinoma of minor salivary glands diagnosed histopathologically and treated surgically, were investigated for the immunohistochemical expression of Ki-67 antigen. Immunohistochemical staining was performed using a Labeled Strept- Avidin Biotin method (LSAB) and 0.05 (two-sided) was the level of significance.
 Results: Twenty cases of Polymorphous Low Grade Adenocarcinoma of salivary glands were histologically diagnosed in this retrospective study to evaluate the expression of Ki-67. The mean age for patients with PLGA was nearly (50.6). (12) (60%) cases were males and (8) (40%) cases were females and also male to female ratio was (1.5:1).
 In regarding to site distribution, the most common site was the palate followed by the submandibular gland and floor of the mouth. 
 Conclusions: it was observed that there is a higher rate of cellular proliferation in malignant tumors with high grade, indicating their role in the malignancy and aggressive behavior of these tumors.

BubR1 and cyclin B1 immunoexpression in pleomorphic adenoma and polymorphous adenocarcinoma of minor salivary glands

The immunoexpression of BubR1 and cyclin B1 in pleomorphic adenoma (PA) and polymorphic adenocarcinoma (PAC) in minor salivary glands is poorly studied. Thus, a retrospective and observational study was performed to provide a better understanding of the role and immunopositivity patterns of these proteins in these lesions. Sixteen cases of PA and 16 cases of PAC were selected. Parenchyma cells were submitted to quantitative immunohistochemical analysis through the labeling index. Cytoplasmic immunoexpression of BubR1 was observed in neoplastic cells from all analyzed PA and PAC cases. All PA cases and 93.7% of PAC exhibited nuclear immunoexpression of BubR1. Higher cytoplasmic and nuclear immunoexpression of BubR1 was observed in PAC (p = 0.001 and p = 0.122, respectively). Cytoplasmic immunoexpression of cyclin B1 was observed in all cases of PA and PAC, with a higher labeling index in the latter (p < 0.001). There was a significant positive correlation between nuclear and cytoplasmic BubR1 immunoexpressions (p < 0.001) in PA and a significant negative correlation between BubR1 and cyclin B1 cytoplasmic immunoexpressions (p = 0.014) in PAC. The higher cytoplasmic and nuclear immunoexpression of BubR1 in PACs suggests the continuous maintenance of neoplastic cells in the cell cycle and migration. Higher immunoexpression of cyclin B1 supports this lesion's enhanced proliferative and migration ability.

A comprehensive analysis of GATA3 expression in carcinomas of various origins with emphasis on lung carcinomas.

GATA3 is a transcription factor involved in the embryogenesis of multiple human tissues and organs and in maintaining cell differentiation and tissue homeostasis in the adult organism. GATA3 is also involved in carcinogenesis and is regarded as a sensitive marker for urothelial and breast carcinomas, although its expression in carcinomas of non-breast/urothelial origin has been frequently reported. In this study, we sought to examine the extent and intensity of GATA3 expression in various carcinomas, mainly lung, urothelial, breast, and various other primary sites. Patients with breast carcinoma (n=40), carcinoma of the urinary bladder/renal pelvis (n=40), lung carcinoma (n=110), and various other origins (n=45) were included in the study. 165 patients had a primary tumor diagnosis, and 70 cases had a metastatic tumor diagnosis. Our results showed that GATA3 expression was significantly more common in carcinomas of the breast, urinary bladder, and renal pelvis compared to all other origins. All primary and 93% of metastatic urinary bladder carcinomas and 94% of primary and 80% of metastatic breast carcinomas expressed GATA3. Expression was lower in the non-urothelial histology of urinary primaries and in triple-negative breast carcinomas (TNBC). Focal staining, mostly faint, was seen in 5.6% of the primary lung adenocarcinomas and 35% of the primary lung squamous cell carcinomas. More extensive and intense staining was seen in 3.7% of the primary lung adenocarcinomas and 12% of the primary lung squamous cell carcinomas. Expression, mostly focal, was also seen in 30% of the metastatic lung carcinomas. Finally, high expression was seen in 12.5% of the other tumors (one metastatic pancreatic carcinoma, one metastatic salivary gland adenocarcinoma not otherwise specified, one metastatic squamous cell carcinoma of the skin, one primary uterine cervix serous carcinoma, and one squamous cell carcinoma of the head and neck), and focal expression was present in another 22% of them. No ideal cut-off for positivity for GATA3 staining could be identified, as increasing the cut-off in either the extent or the intensity of staining increased specificity but decreased sensitivity. In conclusion, our study shows that although GATA3 staining is very helpful in everyday practice in determining the breast/urothelial origin of carcinomas, there are two caveats to its use: the first is that nonclassical histologies of urothelial carcinomas and TNBC may be negative for the marker, and secondly, carcinomas of various origins may show (although rarely) intense positivity.

Evaluation of cervical lymph nodes using multispectral optoacoustic tomography: a proof-of-concept study

ObjectivesExamination of lymph nodes is one of the most common indications for imaging in the head and neck region. The purpose of this study is to evaluate whether multispectral optoacoustic tomography can be used to observe chromophore differences between benign and malignant neck lymph nodes.Materials and methodsProof-of-concept ex vivo study of resected cervical lymph nodes from 11 patients. The examination of lymph nodes included imaging with hybrid ultrasound and multispectral tomography system followed by spectral unmixing to separate signals from the endogenous chromophores water, lipid, hemoglobin and oxygenated hemoglobin; calculation of semi-quantitative parameters (total hemoglobin and relative oxygenation of hemoglobin). Comparison of the results from the hybrid measurement with the histopathological results.ResultsMost patients suffered from squamous cell carcinoma (n = 7), also metastasis from salivary gland adenocarcinoma and papillary thyroid carcinoma, were included. The comparison between benign cervical lymph nodes and metastases showed significant differences for the absorbers water, lipid, hemoglobin and oxygenated hemoglobin and total hemoglobin.ConclusionsOur ex vivo study suggests that multispectral optoacoustic tomography can be used to detect differences between reactive lymph nodes and metastases. The measurement of endogenous chromophores can be used for this purpose. The examinations are non-invasively and thus potentially improve diagnostic prediction. However, potential influences from the ex vivo setting must be considered.

Tubarial Salivary Gland – The New Member of Nasopharynx

Tubarial Salivary Gland – The New Member of Nasopharynx

Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification

Organoids are invitro three-dimensional structures that can be grown from patient tissue. Head and neck cancer (HNC) is a collective term used for multiple tumor types including squamous cell carcinomas and salivary gland adenocarcinomas. Organoids were established from HNC patient tumor tissue and characterized using immunohistochemistry and DNA sequencing. Organoids were exposed to chemo- and radiotherapy and a panel of targeted agents. Organoid response was correlated with patient clinical response. CRISPR-Cas9-based gene editing of organoids was applied for biomarker validation. A HNC biobank consisting of 110 models, including 65 tumor models, was generated. Organoids retained DNA alterations found in HNC. Comparison of organoid and patient response to radiotherapy (primary [n= 6] and adjuvant [n= 15]) indicated potential for guiding treatment options in the adjuvant setting. In organoids, the radio-sensitizing potential of cisplatin and carboplatin could be validated. However, cetuximab conveyed radioprotection in most models. HNC-targeted treatments were tested on 31 models, indicating possible novel treatment options with the potential for treatment stratification in the future. Activating PIK3CA mutations did not predict alpelisib response in organoids. Protein arginine methyltransferase 5 (PRMT5) inhibitors were identified as a potential treatment option for cyclin-dependent kinase inhibitor 2A (CDKN2A) null HNC. Organoids hold potential as a diagnostic tool in personalized medicine for HNC. Invitro organoid response to radiotherapy (RT) showed a trend that mimics clinical response, indicating the predictive potential of patient-derived organoids. Moreover, organoids could be used for biomarker discovery and validation. This work was funded by Oncode PoC 2018-P0003.

Immunoexpression of Autophagy-Related Proteins in Salivary Gland Tumors: An Exploratory Study.

Autophagy is a cellular survival mechanism involved in several human diseases, but its participation in the development of salivary gland tumors is not fully understood. This study investigated the immunoexpression of autophagy-related proteins (autophagy-related 7 [Atg7], microtubule-associated protein 1 light chain 3A [LC3A], microtubule-associated protein 1 light chain 3B [LC3B], protein p62 [p62], and phosphorylated mammalian target of rapamycin [p-mTOR]) in pleomorphic adenoma (PA), polymorphous adenocarcinoma (PAC), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) of salivary glands. Twenty PAs, 20 PACs, 20 MECs, and 14 ACCs were selected. The percentages of cytoplasmic and nuclear positivity for autophagy-related proteins in neoplastic cells were assessed and correlated with histopathological parameters. Cytoplasmic immunoexpression of Atg7 was observed in all groups, with high median percentages of positivity. Regarding LC3A and LC3B, cytoplasmic immunoexpression was found in most PACs (95%) and in all cases of PA, MEC and ACC, with the highest percentages of positivity in PACs and PAs (p < 0.005). ACCs exhibited lower cytoplasmic immunoexpression of p-mTOR (p < 0.005) and lower nuclear expression of p62 (p < 0.05) when compared to PAs, PACs and MECs. Low nuclear immunoexpression of Atg7, LC3A and p-mTOR and absence of nuclear staining for LC3B were observed in all groups. Regarding histopathological parameters of PAs, MECs and ACCs, there were no significant differences in the expression of autophagy-related proteins. In all groups, positive correlations were observed between the immunoexpression of some autophagy-related proteins (p < 0.05). The results suggest the participation of autophagy in the pathogenesis of PA, PAC, MEC, and ACC of salivary glands. Upregulation of autophagy and reduced nuclear translocation of p62 may contribute to the aggressive biological behavior of salivary gland ACC.

Cribriform adenocarcinoma of the minor salivary glands: a case report

BackgroundPolymorphous adenocarcinoma is the third most common malignant salivary gland tumor. Within polymorphous adenocarcinoma, cribriform adenocarcinoma of salivary glands is a rare subtype and resembles papillary thyroid carcinoma histopathologically. Diagnostically, cribriform adenocarcinoma of salivary glands is challenging for pathologists and surgeons alike as initial presentation and cytologic nuclear features can be easily confused with papillary thyroid carcinoma arising from a thyroglossal duct remnant or lingual thyroid.Case presentationA healthy 64-year-old Caucasian woman presented to a community otolaryngologist with a 4-year history of progressive postnasal drip, globus sensation, and eventual dysphonia. Flexible fiberoptic laryngoscopy showed a large, smooth, vallecular lesion filling the oropharynx. Computed tomography imaging of the neck showed a rounded heterogeneous mass centered within the right aspect of the oropharynx measuring 4.2 × 4.4 × 4.5 cm. Fine needle aspiration biopsy was suspicious for papillary carcinoma due to microscopic findings of malignant cells, nuclear grooves, and a powdery chromatin pattern. In the operating room, the tumor was resected en bloc using a lateral pharyngotomy approach with partial resection of the right lateral hyoid. A limited cervical lymphadenectomy was performed to facilitate the lateral pharyngotomy approach and two out of three lymph nodes demonstrated regional metastatic disease. Nuclear grooves, nuclear membrane notching, and occasional intranuclear pseudoinclusions were identified, which are overlapping histopathological characteristics of papillary thyroid carcinoma and cribriform adenocarcinoma of salivary glands. It was negative for thyroglobulin and thyroid transcription factor-1, which was in keeping with cribriform adenocarcinoma of salivary glands rather than papillary thyroid carcinoma.ConclusionIt is difficult to distinguish cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma solely by cytology, and the distinct characteristics of regional lymph node metastasis coupled with nuanced histologic differences should be emphasized in the evaluation of patients presenting with neck lymphadenopathy and an unknown primary or tongue mass. If sufficient fine needle aspiration biopsy material is available, thyroid transcription factor-1, thyroglobulin, or molecular testing may prove useful in differentiating cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma. A misdiagnosis of papillary thyroid carcinoma may lead to inappropriate treatment including unnecessary thyroidectomy. Therefore, it is critical for both pathologists and surgeons to be aware of this uncommon entity to avoid misdiagnosis and subsequent mismanagement.

Oropharyngeal cancer diagnosis and treatment in actual clinical practice in the Republic of Bashkortostan: analysis for 2020

Introduction. Th e growing incidence of oropharyngeal cancer is driven by an increase in frequency of HPV-associated oropharyngeal cancer. Th e morbidity pattern of oropharyngeal cancer is area-specific.Aim. To analyze the oropharyngeal cancer diagnosis and treatment in the Republic of Bashkortostan for 2020.Materials and methods. Th e authors carried out a 2020 retrospective analysis of the diagnosis and treatment results of patients with oropharyngeal cancer. 79 patients were identified with this diagnosis. 84.8% (67/79) among them were males and 15.2% females (12/79). Th e mean age of the patients was 59.1 years. Th e site of primary tumor was on the oropharynx lateral wall in 37.8% cases (30/79), in the tongue root area — 24.1% (19/79), in the tonsils area — 17.7% (14/79), on the soft palate — 16.5% (13/79), on the oropharynx posterior wall — 3.8% (3/79).Results. Examination of tumor morphological types revealed squamous cell carcinoma (SCC) with various degrees of differentiation in 92.4% cases (73/79), adenocarcinoma of minor salivary gland — in 6.3% (5/79) and sarcoma in 1.2% (1/79). 57.5% of 73 patients with SCC (42/73) underwent protein (p16) immunohistochemistry, while 42.5% of the patients (31/73) did not. According to a surrogate marker for HPV, the following results were obtained for 42 patients: p16-positive in 23.8% cases (10/42), p16-negative in 76.2% (32/42). Stage distribution according to TNM-7: stage I — 11.4% (9/79), stage II — 17.7% (14/79), stage III — 36.7% (29/79), stage IV — 46.8% (37/79). Stage distribution according to TNM-8 (patients who underwent p16 immunohistochemistry): stage I — 11.9% (5/42), stage II — 23.8% (10/42), stage III — 19% (8/42), stage IV — 45.2% (19/42). In 2020, 72% of patients (57/79) received definitive treatment, 10.1% (8/79) — palliative care, 15.2% (12/79) — supportive care, and 2.5% (2/79) refused medical treatment.Discussion. Th e various types of radiation therapy were used as the main defi nitive treatment for patients with oropharyngeal cancer in 69.2% cases (45/65). Only 18.5% of patients (12/65) underwent surgery, 58.3% of which (7/12) received post-surgery radiation therapy.Conclusion. 57.5% of patients (42/73) were detected with HPV status, 23.8% (10/42) revealed surrogate markers for HPV association. 69.2% of patients (45/65) received radiation therapy as the definitive treatment. 18.5% of patients (12/65) underwent surgery, 58.3% of which (7/12) received postsurgery radiation therapy.

Surgical treatment of cervical neurovascular bundle tumors

To determine the main principles of a patient-oriented individual approach to diagnosis and surgical treatment of cervical neurovascular bundle tumors considering the capabilities of neurosurgical hospital. There were 92 patients with cervical soft tissue tumors affecting neurovascular bundle. Age of patients ranged from 9 to 81 years (mean 47). There were 65.1% women and 34.9% men. We found chemodectoma (47.4%), neurofibroma (15.8%), neurinoma (13.2%), papillary thyroid cancer (5.3%), salivary gland heterotopia (5.3%), salivary gland adenocarcinoma (5.3%), Hodgkin lymphoma (2.6%), hemangioendothelioma (2.6%) and cavernous lymphangioma (2.6%). Diagnostic algorithm included neurological examinations, Doppler ultrasound of supra-aortic arteries, transcranial ultrasound of cerebral vessels, MRI of cervical soft tissues, CT-AG, MR-AG, CT-perfusion, direct selective angiography. A total of 94 surgical interventions were performed. All surgeries were performed using surgical optics and neurophysiological monitoring of cranial nerves IX, X, XII. We chose resection technique depending on localization, histological features and blood supply of tumor. En-bloc resection was performed in 46 cases, removal of fragments - in 23 cases, intracapsular resection of tumor followed by resection of the capsule - in 26 cases. Total and subtotal resection was performed in 68 (72%) and 23 (24%) cases, respectively. Three (4%) patients underwent partial resection of infiltrative tumors for carotid artery decompression and histological analysis. In 76% of cases, baseline symptoms of disease regressed after surgery. Persistent moderate bulbar disorders were observed in 16 patients (17%). Ischemic complications with additional surgical interventions were observed in 2 cases. Patients with cervical soft tissue tumors require individual approach regarding choosing the optimal surgical treatment including possible preoperative embolization of tumor, en-bloc or intracapsular resection and carotid artery repair.

Microsecretory Adenocarcinoma of Salivary Glands.

Salivary gland classification has benefitted immensely from the growing field of molecular diagnostics. Microsecretory adenocarcinoma, a novel salivary gland malignancy recently included in the fifth edition of the World Health Organization Classifications of Head and Neck Tumours, is one such example. This novel entity was discovered among the umbrella category of adenocarcinoma, not otherwise specified, using a combination of careful histologic analysis and advanced molecular techniques. Its strikingly characteristic histologic features including subtle infiltration, flattened tubules, and abundant blue secretions highlight the necessity of meticulous morphologic observation, even in the age of increased molecular testing. It harbors a recurrent novel MEF2C::SS18 gene fusion, which is amenable to fluorescence in situ hybridization analysis. It presents predominantly in the oral cavity with a propensity for the palate and the majority are thus far low grade, clinically indolent tumors. The recent discovery of a cutaneous corollary to this tumor suggests that the spectrum of its presentation has not entirely been delineated. In the context of expanding molecular testing, pathologists are tasked to sift through constantly evolving molecular data to incorporate diagnostically relevant tests into their practice. In salivary gland pathology, the example of microsecretory adenocarcinoma demonstrates that primary histologic assessment, with sensible use of immunohistochemistry, can lead to accurate diagnosis. Molecular testing is beneficial in cases with significant diagnostic challenges.

Adenosquamous Carcinomas and Mucinous Adenocarcinoma of the Minor Salivary Glands: Immunohistochemical and Molecular Insights

There is confusion about the diagnosis, histogenesis and taxonomical efforts regarding adenosquamous carcinomas (ASCs) and mucinous adenocarcinomas (MACs), especially with calls for reconsidering the nature of high-grade mucoepidermoid carcinoma (MEC). This study aims to compare the genetic profiles of ASCs and MACs that have been previously reported in the literature and investigate if either ASC or MAC is closer in genetic mutations to high-grade MEC. Systematic searches in the NCBI, Web of Science, and Scopus databases were performed between January 2000 and August 2022. The retrieved genetic mutations were processed and annotated. Protein–protein network analysis was conducted for each neoplasm. The results were viewed and discussed in terms of molecular oncogenesis of ASCs and MACs at different topographies. Molecular profile mapping was conducted by annotating all the retrieved genes for each neoplasm using genetic network analysis (Cystoscape software program). The genetic profile of each lesion was compared to that of high-grade MEC. To conclude, both genetic profiles do not tend to intersect specifically with high-grade MEC, except for the generic mutations commonly detected in all high-grade head and neck tumors. However, the availability of data on the molecular profile of each lesion limits the generalizability of the findings of this study.

Microcribriform Adenocarcinoma of Salivary Glands: A Unique Tumor Entity Characterized by an SS18::ZBTB7A Fusion.

The landscape of salivary gland carcinomas is ever-changing, with a growing list of new tumors and newly elucidated variants of well-known tumor entities. The routine use of next-generation sequencing has been instrumental in identifying novel fusions and tumor entities, which has helped bring the classification to a more objective and evidenced-based model. However, morphology remains critical in assessing the validity of these novel molecular findings, and most importantly, in assessing which of these findings will have an impact on the prognosis and treatment decisions for patients. The recognition of microsecretory adenocarcinoma (MSA) as a distinct low-grade malignancy of salivary glands, underpinned by MEF2C::SS18 , and a single possibly related case of SS18::ZBTB7A , recently expanded this growing list of distinctive tumors. It was not until now, however, that the morphology of the latter case was known to be unique and reproducible. The authors have now seen 4 of these distinctive tumors that show a combination of distinctive oncocytic cells forming compact glandular growth as well as amphophilic cells forming tubular growth, and suggest the appellation "microcribriform adenocarcinoma" (MCA). So far, these tumors appear to preferentially occur in nonoral sites (2 parotid, 1 submandibular gland, and 1 bronchial seromucous glands). By immunohistochemistry, they express S100 and SOX-10 with focal outer myoepithelial cells marked by circumferential p63, p40, and smooth muscle actin staining around some of the nests and tubules. The tumors show infiltrative growth within a hyalinized and myxoid stroma. Cytologically, they appear generally low grade, similar to MSA. The morphologic and molecular uniformity of these 4 microcribriform adenocarcinoma cases warrants their recognition, and while related to MSA, they are sufficiently different to be classified as a distinct tumor. So far, in limited follow-up, these tumors appear to be relatively indolent.

PRIMARY INTESTINAL-TYPE ADENOCARCINOMA OF THE TONGUE: REPORT OF A RARE CASE

Intestinal-type adenocarcinoma of the salivary glands is an exceedingly rare tumor. A 55-year-old male patient presented with an ulcerated mass in the tongue, measuring approximately 5 cm in diameter, with 2 years of evolution. The patient complained of pain. Histopathologically, the tumor presented proliferation of tall columnar cells, presenting basophilic nuclei and eosinophilic cytoplasm. Neoplastic cells were organized in anastomosing cords, showing patterns of papillary and solid growths, with duct-like structures. Cytologic and architectural features resembled those seen in well-differentiated colonic adenocarcinoma. Areas of comedonecrosis and perineural invasion were also identified. A preliminary diagnosis of adenocarcinoma was made, with 2 possibilities: intestinal-type adenocarcinoma of the salivary gland or metastatic adenocarcinoma of gastrointestinal origin. Both morphologic and immunohistochemical profiles are indistinguishable for these entities. Whole-body examination failed to identify any gastrointestinal primary tumor or that of other origins. Therefore, a gastrointestinal origin was clinically excluded. The patient was referred for cancer treatment. Intestinal-type adenocarcinoma of the salivary glands is an exceedingly rare tumor. A 55-year-old male patient presented with an ulcerated mass in the tongue, measuring approximately 5 cm in diameter, with 2 years of evolution. The patient complained of pain. Histopathologically, the tumor presented proliferation of tall columnar cells, presenting basophilic nuclei and eosinophilic cytoplasm. Neoplastic cells were organized in anastomosing cords, showing patterns of papillary and solid growths, with duct-like structures. Cytologic and architectural features resembled those seen in well-differentiated colonic adenocarcinoma. Areas of comedonecrosis and perineural invasion were also identified. A preliminary diagnosis of adenocarcinoma was made, with 2 possibilities: intestinal-type adenocarcinoma of the salivary gland or metastatic adenocarcinoma of gastrointestinal origin. Both morphologic and immunohistochemical profiles are indistinguishable for these entities. Whole-body examination failed to identify any gastrointestinal primary tumor or that of other origins. Therefore, a gastrointestinal origin was clinically excluded. The patient was referred for cancer treatment.

New entity of microsecretory adenocarcinoma of salivary glands: first case with recurrence and metastases - proof of malignancy.

Microsecretory adenocarcinoma (MSA) of the salivary glands is a recently described entity. Due to lack of reported metastases, in 30 cases described until now, the designation as low-grade cancer was so far solely based on demonstration of local tumor invasion and in a single case with perineural invasion. We herein describe the first documented case with local recurrence and hematogenous metastases.

Circulating tumor DNA profiling and serial analysis in salivary gland carcinomas reveal unique mutational subsets and actionable alterations.

6097 Background: Salivary gland carcinoma is a rare head and neck malignancy without any FDA approved treatment options. ctDNA profiling has been shown to be a valuable tool in identifying novel targets and expanding potential therapeutic options. Here, we report the landscape of ctDNA in a large dataset of salivary gland carcinomas. Methods: Analysis of genomic results from blood samples with a diagnosis of salivary gland carcinoma that were prospectively collected between January 2017 to December 2021 for clinical Guardant360 testing. Histologic subtype was documented by ordering providers as available. Serial tests were defined as having Guardant360 analysis performed on more than one sample collected at more than one timepoint. Results: Among 222 patients tested with Guardant360, 59.5% were male and the median age was 64 years (range 22-93 years). Of reported diagnoses, 137 (61.7%) patients had salivary gland carcinoma NOS. The remaining samples were designated by specific salivary histology: 13 (5.9%) salivary gland mucoepidermoid carcinoma (SGMC), 19 (8.6%) salivary gland adenocarcinoma (SGA), 37 (16.7%) salivary gland adenoid cystic carcinoma (SGACC), and 16 (72%) salivary duct carcinoma (SDC). ctDNA genomic alterations (GAs) were identified in 205 (81.3%) of 252 samples. The median variant allele fraction was 0.6% (range 0.01%-46.4%). TMB was evaluated in 45 samples of which 33 were evaluable and the median and 80th percentile of TMB was 8.44 and 11.81 mut/Mb. MSI-H was not detected in any of the 181 samples tested for MSI. The most commonly altered genes were TP53, PIK3CA, ERBB2, ATM, EGFR and HRAS across all collected salivary samples. Further analysis stratified genetic alterations by tissue subtype. Other than TP53, common mutations by salivary gland carcinoma subtype included: PI3KCA (SGACC/SDC), ERBB2 (SGA), and EGFR (SGMC). In regards to serial analysis, 16 patients had at least 2 serial tests. When comparing the subsequent testing within the same patient, 3 patients had potentially new actionable GAs (including BRAF, KRAS mutations and EGFR amplification) on the subsequent test that were not identified on the original test. Conclusions: Blood-based liquid biopsy can be applied in salivary gland tumors to detect genomic alterations in ctDNA which may provide opportunities for therapeutic intervention in a cancer with limited treatment options. Additionally, ctDNA testing may be used to identify resistant alterations to potential therapy. Finally, longitudinal assessment of ctDNA may shed light on tumor evolution and additional therapeutic targets may be found. Further assessment of serial ctDNA analysis and the potential impact on patient clinical outcomes needs to be elucidated.

Clear Cell Adenocarcinoma of the minor salivary glands: Case Report

BACKGROUND: Clear cell adenocarcinomas of the minor salivary glands are rare epithelial tumors that account for less than 1% of all malignant salivary gland tumors. CASE REPORT: We present the case of a 54-year-old male patient who presented with a painless right retroauricular tumor of progressive growth. Ultrasound reported a heterogeneous retroauricular soft tissue tumor with no local or regional lymphadenopathies. Culture and tumor markers were negative, BAFF was reported as suspicious for malignancy. CLINICAL COURSE: Right retroaurilar tumor was excised, without complications. The pathology report informed a right retroauricular clear cell carcinoma with negative limits. The patient has been under follow up care for one year, with no evidence of disease recurrence. CONCLUSION: Although clear cell carcinoma of the minor salivary glands is a rare tumor, it should be considered as a differential diagnosis in patients with head and neck injuries. Its standardized treatment is surgical; adjuvant treatments have not shown an improvement in the control of recurrence, nor have they improved survival rates.

Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells

Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, triggered apoptosis, modulated the expression and activation of pro-survival signaling transduction pathways proteins activated by ErbB receptors and inhibited proteasome activity in vitro. Intraperitoneal administration of Bortezomib delayed tumor growth of SALTO-5 cells transplanted in BALB-neuT mice, protracted mice survival and adjusted tumor microenvironment by increasing tumor-infiltrating immune cells (CD4+ and CD8+ T cells, B lymphocytes, macrophages, and Natural Killer cells) and by decreasing vessels density. In addition, Bortezomib modified the expression of proteasome structural subunits in transplanted SALTO-5 cells. Our findings further support the use of Bortezomib for the treatment of HNC and reveal its ineffectiveness in counteracting the activation of deregulated specific signaling pathways in HNC cell lines when resistance to proteasome inhibition is developed.