Polymorphous Low-grade Adenocarcinoma Research Articles

MASPIN EXPRESSION IN PLEOMOPHIC ADENOMA, POLYMORPHOUS LOW GRADE ADENOCARCINOMA AND ADENOCYSTIC ADENOCARCINOMA OF SALIVARY GLANDS SEEN AT THE LAGOS UNIVERSITY TEACHING HOSPITAL, LAGOS, NIGERIA

Objectives To immunostain with Maspin antibody, formalin fixed, paraffin embedded tissues of 41 samples of Pleomorphic Salivary Adenoma [PSA], 10 samples of Polymorphous Low-Grade Adenocarcinoma [PLGA] and 34 samples of Adenoid Cystic Carcinoma [AdCC]. To quantitatively assess Maspin expression in each of the three (3) Salivary Gland Tumours (SGTs) by combining immunostaining intensity scores with scores of proportion of positively stained cells (Total mean scores) in each, using the method described by Reiner et al 1990. To analyze data using Chi square, Fisher's Exact tests and analysis of variance to compare total mean scores of maspin expression among the three (3) SGTs, the statistical significance level being set at p Findings PSA had the greatest proportion of Maspin immunopositivity (73.2%), followed by PLGA (40.0%) and AdCC (35.2%). Mean total Maspin score of PSA (3.5±2.4) was statistically significantly higher than that of PLGA (1.2±1.8) [p=0.005]. and that of AdCC (1.0±1.5) [p Conclusion In this study, there was decreasing expression of Maspin from PSA to PLGA to AdCC, which is consistent with established increased order of clinical aggression of these tumors. It is suggested that Maspin expression could be a useful adjunct diagnostic tool to discriminate between PSA, PLGA and AdCC.

Minor salivary gland tumors of the head and neck-Memorial Sloan Kettering experience: Incidence and outcomes by site and histological type.

Minor salivary gland carcinomas of the head and neck are rare cancers with variable clinical behavior. This study explored the incidence, pathology, clinical behavior, and factors predictive of outcomes in a large cohort of patients treated at Memorial Sloan Kettering Cancer Center over a 30-year period (1985-2015). Clinical, pathological, treatment, and outcome data were collected. Unadjusted and adjusted hazard ratios for each variable were calculated with univariate and multivariable Cox regression for survival and recurrence outcomes. Four hundred fifty patients were included: 55% were female, 56% were younger than 60years, and the median follow-up was 74months (range, 1-364months). The most common site was the oral cavity with 305 tumors (68%), which was followed by the oropharynx with 96 (21%), the sinonasal cavity with 38 (8%), the trachea with 7 (2%), and the larynx with 4 (1%). The most common histological types were mucoepidermoid carcinoma (180 tumors [40%]), adenoid cystic carcinoma (141 tumors [31%]), and polymorphous low-grade adenocarcinoma (54 tumors [12%]). The 5-year predicted overall survival rate was 86%, and the disease-specific survival rate was 94% at 5years. Pathology and tumor stage were significant variables on multivariate analysis for overall survival, disease-specific survival, recurrence-free survival, local recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival. American Joint Committee on Cancer stage and pathology were the most predictive variables across all outcomes. Tumor site, postoperative radiotherapy, and margin status were not statistically significant variables after tumor stage and pathology were controlled for in most outcomes.

Polymorphous Low-Grade Adenocarcinoma: A Proposed Reconstruction Protocol Based on Past Surgical Experience.

To propose a reconstructive protocol based on surgical management experience of polymorphous low-grade adenocarcinoma (PLGA) and the location of the primary lesion. Data on the surgical management and the reconstructive technique of 14 histologically conformed patients with PLGA, all treated by the same surgeon, were analyzed and evaluated. Mean follow-up period in our series was 6.2 years. Mean age at diagnosis was 55.5 years and female to male ratio was 2.2:1. The most common presenting sign was a nonpainful lump or mass in an intraoral location. Most patients were managed by wide local excision and reconstruction method varied from primary closure to the use of radial forearm graft. Recurrence appeared in one of the patients in this series, while 2 required further radiation therapy. A protocol for reconstruction of intraoral patients with PLGA is suggested based on our analysis. Surgical management is the gold standard for PLGA treatment. Neck dissection is recommended only in patients with presurgery fine-needle aspiration confirmed lymph node involvement. The reconstruction depends mainly on location and size of the primary lesion.

Polymorphous adenocarcinoma: an overview of immunohistochemical features and insights on molecular pathology.

Polymorphous adenocarcinoma (PAC), represents a common minor salivary gland tumor (SGT) characterized by local growth, low metastatic potential and non-aggressive biologic behavior. Due to the clinical aggressiveness noted in a subset of such tumors, the former term polymorphous low-grade adenocarcinoma (PLGA) was recently revised. PAC's clinical features and histological diversity result in clinical overlap of this entity with several other SGTs including mainly adenoid cystic carcinoma (AdCC). Differential diagnosis among the entities is crucial, in terms of tumor management and patients' prognosis. The aim of the present review is to summarize the histological, cytological, immunohistochemical and molecular features of PAC. Histopathological examination is usually adequate for PAC differential diagnosis from other SGTs, except of AdCC. Several immunohistochemical markers including c-Kit, S-100/ MG, Mcm-2 and Integrin β-1, -3, -4, are reported to be useful diagnostic aids in borderline cases. Limitations in sample numbers and study methodology issues of the immunohistochemical PAC studies complicate the identification and selection of appropriate markers useful in the differential diagnosis. Additionally, molecular analyses of PAC specimens indicate that the PAC spectrum phenotypes result from different genotypes (protein kinase D positive; PRKD(+) and PRKD(-) tumors). PAC pathogenesis remains to be determined in each particular genotype while the convergence issue should be addressed in future studies.

Immunohistochemical evaluation of salivary gland tumors differentiation and proliferation by using calponin and telomerase

BackgroundSalivary gland tumors are a heterogeneous group of lesions with diverse histological features. Hence they are considered as a diagnostic challenge for the pathologist. Myoepithelial cells are considered as a key in the morphogenetic process, with diverse differentiation in various salivary gland tumors. Calponin is an actin filament- associated protein that represents a sensitive marker of myoepithelial cells. Telomerase is a ribonucleoprotein that adds telomere repeats at the end of chromosomes in order to prevent replicative senescence. It has a key role in cellular immortality and tumorgenesis of various tumors. This study evaluates the immunohistochemical expression of calponin and telomerase in various salivary gland tumors. MethodsThis retrospective study involved 30 formalin fixed paraffin embedded blocks of salivary gland tumors. The immunohistochemical staining and evaluation of subcellular localization, pattern, intensity, and distribution for calponin and immune scoring for telomerase were done. The statistical analyses of data were conducted by Chi-square and ANOVA-test, a P-value of <0.05 was considered significant. ResultsCalponin showed expression at the periphery of acini and intercalated ducts in the normal salivary gland. It revealed cytoplasmic expression in 83.3% of benign tumors. The pleomorphic adenoma showed a diffuse pattern of staining (85.7%), strong intensity (64.3%), and mixed distributions (57.1%). The diffuse pattern of calponin was seen in all cases of mucoepidermoid, polymorphous low-grade adenocarcinoma and epithelial-myoepithelial carcinoma (100%). Telomerase revealed negative expression in the normal salivary gland. Pleomorphic adenoma illustrated high telomerase expression in score 2 and score 3 (93.3%). Telomerase immune scoring is significantly related to the benign tumors as P value was 0.03. Both polymorphous low grade and epithelial-myoepithelial carcinoma were detected only in score 3. Finally, the mean level of telomerase activity was slightly higher in malignant tumors than benign ones with non-significant relation as P value was 0.6. ConclusionsCalponin showed high diffuse staining with altered distribution in salivary gland tumors, which might give an additional role for this marker in the identification of luminal immuno-modified neoplastic cells. Telomerase is considered as a useful marker in identifying proliferation capacity of salivary gland tumors and is remarkably more detected in malignant salivary gland tumors.

Polymorphous Low-Grade Adenocarcinoma: Multifocal Clinical Presentation

A 53-year-old woman presented with two asymptomatic nodules measuring 35 mm and 10 mm in diameter on the buccal mucosa and upper lip, respectively. Diagnostic hypotheses included salivary gland lesions, and incisional and excisional biopsies were performed in the buccal mucosa and lip. The histopathologic examination revealed malignant neoplasm of the salivary glands with a deceptively uniform appearance, characterized by rounded and polygonal cells with indefinite borders and pale cytoplasm, presenting nuclei of varied morphology. The cells had different growth patterns, predominantly arranged in cords and nests. Both lesions were positive for S-100 and CK7 and negative for SMA. The final diagnosis was polymorphous low-grade adenocarcinoma. The patient underwent surgical resection and radiation therapy. No evidence of recurrence was found at follow-up.

Polymorphous Low-Grade Adenocarcinoma of the Palate: A Case Report

A 64-year-old female patient was referred by a dental surgeon, approximately 2 years ago, with complaints of “a hard little red ball in the roof of the mouth that does not hurt.” She reported to have controlled hypertension and to be under treatment with antibiotics, during anamnesis. In an intraoral physical examination, a total superior prosthesis was used, and in the region of transition between the hard and soft palates, a nodule measuring approximately 2 cm was observed on the left side, dark pink in color, with smooth surface and rubbery consistency. No abnormalities were observed on panoramic radiography. The diagnostic hypothesis was salivary gland neoplasia. Biopsy was performed, and the material was sent to the laboratory of anatomopathology, and the results were conclusive for polymorphous low-grade adenocarcinoma. The patient was referred to the head and neck surgeon.

Abstract 1556: Does surgical treatment affect serum levels of vascular endothelial growth factor (VEGF) in orofacial tumors

Abstract Introduction: Angiogenesis, the generation of new vessels, is regulated by several growth factors. The most important of them is vascular endothelial growth factor (VEGF), which is closely related to tumor progression and prognosis. To my knowledge no study in sub-Saharan Africa has evaluated the level of VEGF following surgery in African patients. This study therefore aims to evaluate the pattern and clinical implication of VEGF expression in benign and malignant neoplasms and determine the effect of surgical intervention on the levels of circulating VEGF. Methods: This case-control study was carried out at the University of Benin Teaching Hospital (UBTH), Benin City, Nigeria, between October 2015 and February 2017. Cases were drawn from among histologically confirmed orofacial tumors, while controls were from consecutive, ambulatory dental patients, matched for age and sex. Calculated sample size for minimum effect was 77 for both cases and controls. Blood samples were taken from cases and controls, pre- and 1-month post-surgery, allowed to clot and serum aliquots were stored at -600 C till analyses. Post-surgery tissue was processed and stained with anti-VEGF antibody for immunohistochemical analysis. Serum VEGF was analyzed using Sandwich ELISA, and mean levels as well as median were measured. Spearman correlation was estimated, t-test measured significance (at p ≤ 0.05), and one-way ANOVA measured between group differences. Results: Following 12% attrition, 81 subjects were retained in the study (55 cases [20 malignant, 35 benign] and 26 controls). The most common malignant neoplasms were head and neck squamous cell carcinoma (35%) and polymorphous low-grade adenocarcinoma (20%), while the benign tumors were mostly unicystic ameloblastoma (42.9%) and solid multicystic ameloblastoma (31.4%). Before surgical treatment, there were significantly different serum levels of VEGF in benign (48.11 ± 25.19 pg/ml) vs. malignant cases (1065.00 ± 412.14 pg/ml), and compared with controls (45.42 ± 29.83 pg/ml), p &amp;lt;0.001. Also, the level of circulating VEGF correlated strongly and positively with tumor tissue expression in malignant cases (r = 0.674, p &amp;lt;0.001). After definitive surgical intervention, there was a significant reduction in the level of serum VEGF in both benign (45.50 ± 24.71 pg/mL) and malignant cases (51.22 ± 16.84 pg/mL), p &amp;lt;0.001. One-way ANOVA revealed no significant differences between cases and controls post-surgery. Conclusion: There were elevated levels of serum VEGF in benign and malignant orofacial neoplasia, which correlate positively with the expression of VEGF in tumor tissue. Surgery caused a significant reduction of circulating VEGF to normal levels irrespective of age, gender, previous medical history, perceived duration of the lesion and lymph node involvement. Citation Format: Aimuamwosa Obarisiagbon, Peter Egbor, Ozoemene Ndubuisi Obuekwe, Osagie Akpata, Akin Ojo, Nosayaba Osazuwa-Peters. Does surgical treatment affect serum levels of vascular endothelial growth factor (VEGF) in orofacial tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1556.

Radiotherapy for Polymorphous Low-grade Adenocarcinoma of the Head and Neck

Radiotherapy for Polymorphous Low-grade Adenocarcinoma of the Head and Neck

Polymorphous adenocarcinoma of the salivary glands: reappraisal and update.

Although relatively rare, polymorphous adenocarcinoma (PAC) is likely the second most common malignancyof the minor salivary glands (MiSG). The diagnosis is mainly based on an incisional biopsy. The optimal treatment comprises wide surgical excision, often with adjuvant radiotherapy. In general, PAC has a good prognosis. Previously, PAC was referred to as polymorphous low-grade adenocarcinoma (PLGA), but the new WHO classification of salivary gland tumourshas also included under the PAC subheading, the so-called cribriform adenocarcinoma of minor salivary glands (CAMSG). This approach raised controversy,predominantlybecauseof possible differences in clinical behaviour. For example, PLGA (PAC, classical variant) only rarely metastasizes, whereas CAMSG often shows metastases to the neck lymph nodes. Given the controversy, this review reappraises the definition, epidemiology, clinical presentation, diagnostic work-up, genetics, treatment modalities, and prognosis of PAC of the salivary glands with a particular focus on contrasting differences with CAMSG.

The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas.

Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.

Immunohistochemical study of salivary gland tumors in a tertiary institution in South-South Region of Nigeria

Aim:The aim of this study was to see the usefulness of immunohistochemistry in diagnosing salivary gland tumors found in a tertiary health institution.Materials and Methods:Twenty-six formalin-fixed paraffin embedded salivary gland tumors were accessioned, and 2 μm were sectioned and processed using Streptavidin-Biotin immunoperoxidase method.Results:Adenoid cystic carcinoma (ADCC) was positive to alpha-smooth muscle actin (α-SMA) while mucoepidermoid carcinoma (MEC), polymorphous low-grade adenocarcinoma (PLGA), squamous cell carcinoma (SCC) and oncocytic carcinoma (OCC) were all negative to it. MEC, PLGA, ADCC and the only pleomorphic adenoma (PA) were positive to Ki-67 while both SCC and OCC were negative to it. All the tumors except PA were positive to p63.Conclusion:It appears that α-SMA may be used to distinguish ADCC from MEC and PLGA, but Ki-67 cannot be used for this purpose. Furthermore, p63 cannot help in the diagnosis of ADCC, MEC or PLGA. It was concluded that immunochemistry can be used as adjunct to routine H and E stain in the diagnosis of the various salivary gland tumors.

Expression of α-smooth muscle actin in benign and malignant salivary gland tumors: An immunohistochemical study.

Myoepithelial cells (ME) are known to contribute in the patterning of salivary gland neoplasms (SGN) and possess cytoplasmic smooth muscle actin (SMA) revealed by alpha SMA (α-SMA). The present study aimed to assess the expression of α-SMA in selected benign and malignant SGN (pleomorphic adenoma [PA], mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ACC), and polymorphous low-grade adenocarcinoma (PLGA). The intensity and pattern of expression of α-SMA were studied in 25 cases of SGN's ACC (n = 7), MEC (n = 8), PA (n = 8), and PLGA (n = 2), and correlated with the histological patterns. Maximum expression of α-SMA in the epithelial compartment was seen in ACC, followed by PA, whereas MEC and PLGA showed completely negative staining. The connective tissue expression was mild in ACC and MEC. The myxoid stroma of PA with "melting" pattern was weakly positive for α-SMA. The stroma in PLGA showed complete negativity. In ACC, α-SMA-positive cells were lining the cribriform spaces, small islands, and dispersed within large islands. Small nests showed complete positivity for α-SMA. In ACC, α-SMA expression supports the involvement of ME in epithelial organization explaining the histological patterns seen. In PA, the expression correlates with the predominantly secretory nature of ME. The absence of epithelial positivity in MEC and PLGA suggest that ME has less role to play in their histogenesis. The weak stromal positivity observed in MEC and ACC may be attributed to the positive immunoreactivity of myofibroblasts playing a role in modulating the course of SGN's.

Canalicular adenoma: A rare case report

Canalicular adenomas (CAs) are uncommon benign salivary gland neoplasms of the oral cavity. They are typically located on the upper lip, buccal mucosa, and infrequently found on the palate and derived from minor salivary glands. Due to benign character of the tumor, CAs rarely present with bone erosion. Histologically, trabecular type of basal cell adenoma, pleomorphic adenoma, and polymorphous low-grade adenocarcinoma should be discriminated from CAs. A-36-year-old female patient with CA was presented. The lesion was managed surgically under local anesthesia, and 2 months follow-up was uneventful.

A demographic study of salivary gland tumors

Background: Salivary gland lesions, especially the neoplastic lesions constitute a highly heterogeneous histopathologic group. Several studies have reported a significant difference in the global distribution of salivary gland tumors, but no formal study has been carried out in this part of the globe. Objectives: The objectives were: (1) retrieval of salivary gland tumors from the files of Department of Oral Pathology and Microbiology, Government Dental College and Hospital (GDC and H), Nagpur, to analyze the relative frequency of individual salivary gland tumors and (2) to correlate the various salivary gland tumors according to age, sex, location, and duration and compare the findings of this study with studies conducted in other countries. Materials and Methods: This is a retrospective study of all salivary gland tumors retrieved from the files of Department of Oral Pathology and Microbiology, GDC and H, Nagpur. Data thus collected archives were analyzed. Results: Out of total 75 cases, 29 pleomorphic adenoma, 8 basal cell adenoma, 16 mucoepidermoid carcinoma, 5 adenoid cystic carcinoma, 4 acinic cell carcinoma, 4 adenocarcinoma, 2 polymorphous low-grade adenocarcinoma, and single case each of cyst-adenoma, basal cell adenocarcinoma, epimyoepithelial carcinoma, salivary duct carcinoma, carcinoma in ex-pleomorphic adenoma, malignant myoepithelioma, and mucinous adenocarcinomas were reported. These cases were analyzed considering the parameters such as age, sex, location, duration, radiographic findings, and histopathological appearances. These were compared with studies conducted in other parts of the world. Conclusion: In conclusion, the data and results presented herein were similar to previously published reports in other countries and other areas of India and globe. However, some differences were observed, these differences can be attributed to racial factors, the pathology centers of sample collection and the duration of the studies.

Polymorphous low-grade adenocarcinoma of parotid gland – A case report and review

Polymorphous low-grade adenocarcinoma of parotid gland – A case report and review

The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA.

Polymorphous adenocarcinoma (PAC) of the palatal minor salivary glands, previously known as polymorphous low-grade adenocarcinoma, is the second most common intraoral malignant salivary gland carcinoma after adenoid cystic carcinoma (ACC) and carries an excellent prognosis. Unfortunately, PAC demonstrates cytological overlap with 2 other salivary gland tumors frequently encountered in the same location, namely ACC and pleomorphic adenoma (PA). Recently, the protein kinase D1 (PRKD1) hotspot mutation E710D was demonstrated to be specific for PAC and to be present in the majority of cases. The objective of the current study was to investigate the value of PRKD1 hotspot sequencing in identifying PAC in paired fine-needle aspiration (FNA) and surgical specimens from cases of PAC, ACC, and PA. Paired May-Grunwald-Giemsa-stained FNA and corresponding surgical specimens were collected from 18 PAC cases, 25 ACC cases, and 21 PA cases. Both sets of specimens were subjected to dideoxynucleotide sequencing of PRKD1 exon 15, including the PRKD1 E710D hotspot. Of the PAC cases, approximately 50% demonstrated identical PRKD1 E710D hotspot mutations on the FNA specimen and corresponding surgical specimen. Two ACC specimens had point mutations within the sequenced region in the FNA specimen as well as the surgical specimen, but none were located in the hotspot region. None of the PA cases demonstrated PRKD1 mutations. The specificity of the PRKD1 hotspot mutation for identifying PAC among ACC and PA cases was 100% whereas the sensitivity was 50%. The PRKD1 E710D hotspot mutation is highly specific for identifying PAC on FNA among cases of ACC and PA, whereas the sensitivity is only modest. Alternative PRKD1 mutations exclude PAC, and are more suggestive of ACC. Cancer Cytopathol 2018;126:275-81. © 2017 American Cancer Society.

1047PD - Mammary analogue secretory carcinoma (MASC): clinical characteristics in 28 ETV6-NTRK3 fusion gene confirmed patients

Background: Recently, a new subtype of salivary gland cancer (SGC), mammary analogue secretory carcinoma (MASC), has been defined, which is characterized by the presence of ETV6-NTRK3 fusion gene. Previously, MASC was mixed up with acinic cell carcinoma (AciCC), polymorphous low grade adenocarcinoma and (cyst)adenocarcinoma. At present the clinical features and outcome of MASC patients are not well known. We aimed to describe the clinical presentation and outcome of MASC. Methods: Firstly, we re-evaluated the pathological diagnosis of salivary gland cancers with a morphological resemblance to MASC, diagnosed in 4 of the 8 head and neck centres in the Netherlands, for their presence of ETV6-NTRK3 and also included genetically confirmed prospectively diagnosed cases. The ETV6-NTRK3 fusion gene was analyzed using RT-PCR. Secondly, the clinical characteristics were retrieved from the patient files. Results: Twenty-eight patients with ETV6-NTRK3 fusion gene positive MASC were included (10 prospectively and 18 retrospectively). Of these 18 retrospective patients 13 patients were previously diagnosed as AciCC, the other 5 patients as (low-grade) adenocarcinoma. The median age at diagnosis was 49 years (range 19 – 83 years), 15 patients (54%) were male. The duration of symptoms varied from 6 weeks until 20 years with a median of 14 months. In 18 patients (64%) the tumour was located in the parotid gland; the other patients had tumours of the minor salivary glands (2), submandibular gland (1), oral mucosa/lip (5) or palate (2). All patients had a T1-2 tumour. One patient had lymph node metastasis at diagnosis. All patients underwent surgery of which 4 patients needed re-resection and 12 patients (43%) underwent postoperative radiotherapy. One patient had a local recurrence 50 months after primary surgery, but was cured after second resection. None of the patients had regional recurrences or distant metastases. The median follow-up was 49 months and both the 5- and 10-year overall survival rate were 94%. Conclusions: MASC is a recently acknowledged new entity of SGC characterized by the ETV6-NTRK3 fusion gene. The clinical course seems to be favourable with a very low rate of recurrences and an excellent survival. Legal entity responsible for the study: Radboudumc Funding: None Disclosure: All authors have declared no conflicts of interest.

Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies

BackgroundRelapsed/metastatic salivary gland carcinomas (SGCs) have a wide diversity of histologic subtypes associated with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling could define the tumor subtypes and uncover clinically relevant genomic alterations, revealing new routes to targeted therapies for patients with relapsed and metastatic disease.Patients and methodsFrom a series of 85 686 clinical cases, DNA was extracted from 40 µm of formalin-fixed paraffin embedded (FFPE) sections for 623 consecutive SGC. CGP was carried out on hybridization-captured, adaptor ligation-based libraries (mean coverage depth, >500×) for up to 315 cancer-related genes. Tumor mutational burden was determined on 1.1 Mb of sequenced DNA. All classes of alterations, base substitutions, short insertions/deletions, copy number changes, and rearrangements/fusions were determined simultaneously.ResultsThe clinically more indolent SGC including adenoid cystic carcinoma, acinic cell carcinoma, polymorphous low-grade adenocarcinoma, mammary analog secretory carcinoma, and epithelial–myoepithelial carcinomas have significantly fewer genomic alterations, TP53 mutations, and lower tumor mutational burden than the typically more aggressive SGCs including mucoepidermoid carcinoma, salivary duct carcinoma, adenocarcinoma, not otherwise specified, carcinoma NOS, and carcinoma ex pleomorphic adenoma. The more aggressive SGCs are commonly driven by ERBB2 PI3K pathway genomic alterations. Additional targetable GAs are frequently seen.ConclusionsGenomic profiling of SGCs demonstrates important differences between traditionally indolent and aggressive cancers. These differences may provide therapeutic options in the future.

Newly Described Entities in Salivary Gland Pathology.

Salivary glands may give rise to a wide spectrum of different tumors. This review concentrates on 4 salivary gland tumors that have been accepted in the recent literature as new neoplastic entities: mammary analog secretory carcinoma, cribriform adenocarcinoma of minor salivary glands (CASG), sclerosing polycystic adenosis/adenoma (SPA), and the mucinous/secretory variant of myoepithelioma. Mammary analog secretory carcinoma is a distinctive low-grade malignant salivary cancer that harbors a characteristic chromosomal translocation, t(12;15) (p13;q25), resulting in an ETV6-NTRK3 fusion. Cribriform adenocarcinoma (CASG) is a distinct tumor entity that differs from polymorphous low-grade adenocarcinoma by location (ie, most often arising on the tongue), by prominent nuclear clearing, differing alterations of the PRKD gene family, and clinical behavior with frequent metastases at the time of presentation of the primary tumor. Early nodal metastatic disease is seen in most cases of CASG; yet, they are still associated with indolent clinical behavior, making it a unique neoplasm among all low-grade salivary gland tumors. SPA is a rare sclerosing tumor of the salivary glands characterized by the combination of cystic ductal structures with variable cell lining including vacuolated, apocrine, mucinous, squamous, and foamy cells, by prominent large acinar cells with coarse eosinophilic cytoplasmic zymogen-like granules, and by closely packed ductal structures, surrounded by a peripheral myoepithelial layer and stromal fibrosis with focal inflammatory infiltrates. SPA frequently harbors intraductal epithelial dysplastic proliferations ranging from mild dysplasia to severe dysplasia/carcinoma in situ. Moreover, SPA has been proven to be a clonal process by HUMARA assay and is associated with considerable risk of recurrence. Therefore, on the basis of all these newly recognized findings, we believe that SPA is likely a neoplasm, and we suggest the name "sclerosing polycystic adenoma." The mucinous variant of myoepithelioma is a myoepithelial tumor with foci of prominent cytoplasmic clearing frequently containing intracellular mucin material and having signet-ring morphology.