Adenocarcinoma Not Otherwise Specified Research Articles

Liquid-based Cytological Features of Adenocarcinoma Not Otherwise Specified, Extrauterine Adenocarcinoma, and Other Malignant Neoplasms of The Uterine Cervix: A 5-year Single-institutional Experience With 30 Consecutive Patients.

The adenocarcinoma (ADC) and other malignant neoplasm (OMN) terminologies of The Bethesda System represent various histological types of uterine and extrauterine malignancies. This study aimed to clarify the incidences of ADC not otherwise specified (ADC-NOS), ADC extrauterine (ADC-EXT), and OMN in our institution and describe their characteristic cytomorphological features. We searched the database to identify all patients diagnosed with carcinoma, including those diagnosed through cervical liquid-based cytology (LBC), between January 2019 and December 2023. The electronic medical records and all available slides were reviewed. Overall, 30 of the 149,197 (0.02%) patients were diagnosed with ADC-NOS, ADC-EXT, and OMN. All three groups included various histological types of both gynecological and non-gynecological origin. More than two-thirds (23/30; 76.7%) were of uterine origin, but seven patients had metastatic carcinoma of extrauterine organ origin, including the ovary, lung, stomach, breast, colon, urethra, and pancreas. In all patients, the cytological features were concordant with the histological features. In LBC, ADC-NOS does not only encompass uterine cervical tumors, but also various types of extrauterine malignancies. ADC-EXT and OMN also represent both extrauterine and uterine tumors. Awareness of the morphological features observed in LBC samples of non-gynecological malignancies may be helpful in obtaining the correct diagnosis.

Phase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A.

National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) was a multicohort phase 2 trial that assigned patients with advanced pretreated cancers to molecularly targeted therapies on the basis of tumor genomic testing. NCI-MATCH Arm A evaluated afatinib, an EGFR tyrosine kinase inhibitor (TKI) approved for advanced non-small cell lung cancer, in patients with tumors other than lung cancer harboring EGFR mutations. Patients with advanced pretreated cancers other than lung cancer found to have selected actionable EGFR mutations were offered participation in Arm A. Previous therapy with an EGFR TKI was not allowed. Patients received afatinib 40 mg once daily continuously until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Seventeen patients received protocol therapy. Tumor types included glioblastoma multiforme (GBM) (13), gliosarcoma (1), adenocarcinoma not otherwise specified (NOS) (2), and adenosquamous carcinoma of the breast (1). Fifty-nine percent of patients received ≥2 lines of previous therapy. The ORR was 11.8% (90% CI, 2.1 to 32.6), with one complete response lasting 16.4 months (GBM harboring a rare exon 18 EGFR-SEPT14 fusion) and one partial response lasting 12.8 months (adenocarcinoma NOS with the classic EGFR mutation, p.Glu746_Ala750del). Three patients had stable disease. The 6-month PFS was 15% (90% CI, 0 to 30.7); the median OS was 9 months (90% CI, 4.6 to 14.0). Rash and diarrhea were the most common toxicities. Afatinib had modest activity in a cohort of patients with heavily pretreated cancer with advanced nonlung, EGFR-mutated tumors, but the trial's primary end point was not met. Further evaluation of afatinib in GBM with EGFR exon 18 fusions may be of interest.

The extent of androgen receptor and HER2 expression allows for targeted therapy in most cases of salivary duct carcinoma: analysis of clinical and histopathological data in a tertiary care center

PurposeThe incidence of salivary duct carcinoma (SDC) seems to be underestimated due to inaccurate classification. Further, the frequency of SDC patients with targeted therapy options according to current guidelines is unclear. Therefore, this study aimed at (a) describing the proportion of SDC among salivary gland carcinoma (SGC) before and after reclassification of cases initially classified as adenocarcinoma, not otherwise specified (ANOS); and (b) quantifying the frequency of SDC patients with targeted therapy options.MethodsAll patients with SDC or ANOS treated in a tertiary care center between 1996 and 2023 were identified. Histopathological diagnosis was verified for patients primarily diagnosed with SDC and reviewed for patients initially diagnosed with ANOS. Clinical data for SDC patients were retrieved from clinical charts. Immunohistochemical (IHC) androgen receptor (AR) and HER2 staining was performed.ResultsAmong 46 SDC, 34 were primarily diagnosed as SDC and 12 had initially been classified as ANOS. The proportion of SDC among SGC was 12.1% and was rising when comparing the time periods 2000–2015 (7.1–11.5%) versus 2016–2023 (15.4–18.1%). Nuclear AR staining in > 70% of tumor cells was found in 56.8% and HER2 positivity (IHC 3 +) in 36.4% of cases. 70.5% of patients showed AR staining in > 70% of tumor cells and/or HER2 positivity and therefore at least one molecular target. 5-year overall and disease-free survival (DFS) were 62.8% and 41.0%. Multivariate Cox regression revealed positive resection margins (HR = 4.0, p = 0.03) as independent negative predictor for DFS.ConclusionsThe results suggest a rising SDC incidence and show that the extent of the AR and HER2 expression allows for targeted therapy in most SDC cases.

Evaluation 172 patients of submandibular gland swelling with a case of adenocarcinoma, not otherwise specified: a needle in a haystack

Background: Aim of the study was to assess the patients of submandibular gland pathology and to describe a case of adenocarcinoma, not otherwise specified (ANOS) of the submandibular gland in terms of clinical presentation, diagnosis, line of management and prognosis. Methods: The study was conducted as a retrospective review of all the patients who underwent submandibular gland excision in the last 6 years at the department of otorhinolaryngology, M.D.M. hospital, Dr. S.N. Medical college, Jodhpur. The records were assessed and statistically evaluated. Results: Out of 172 cases of submandibular gland excision, only 1 case of ANOS was seen. The rest included 134 cases were of chronic non-inflammatory process, 24 cases of sialolithiasis, 10 cases of metastasis from oral cavity cancer and 3 cases of primary squamous cell carcinoma. Fine needle aspiration cytology (FNAC) was not diagnostic in ANOS. Excision of the gland with primary closure was done. Adjuvant radiotherapy was given. Conclusions: ANOS has a rare occurrence in submandibular gland swelling and it is also very tricky to diagnose it. The nature of this malignancy is invasive and nodal metastasis is present. Surgical excision and post-op evaluation can be life-saving.

Clinicopathological Profile of Colorectal Adenocarcinoma in the Anatomical Pathology Laboratory of Dr. Soedarso Hospital Pontianak

Background: Colorectal adenocarcinoma is ranked third globally in the category of the most commonly diagnosed cancers, as reported by the Global Burden of Cancer (GLOBOCAN) survey in 2020. This condition ranks as the second leading cause of death from cancer with a mortality of 9.40%. Therefore, this study aimed to discover the clinicopathological profile of colorectal adenocarcinoma in the Anatomical Pathology Laboratory of Dr. Soedarso Hospital Pontianak in 2017–2020. Methods: This descriptive study used secondary data from the histopathology reports of the Anatomical Pathology Laboratory obtained by total sampling, which were processed using Microsoft Excel. Results: The total number of colorectal adenocarcinoma patients was 148, and the majority were in the category of 53–61 years, accounting for 30.41%, and 51.35% were female. The majority of the anatomical sites of tumors were in the “Rectum Not Otherwise Specified (NOS)”, with a percentage of 35.14%. The most frequent histopathological subtype was adenocarcinoma NOS, accounting for 85.81%, while the majority of differentiation grade was well differentiated, with a percentage of 90.54%. The most TNM (Tumor, Node, Metastatic) staging system of the American Joint Committee on Cancer (AJCC) was IIA (33.78%). Based on the classification using the Dukes staging system, the most stage suffered by patients was C2 with a percentage of 39.86%. Conclusions: In conclusion, the incidence of diagnosed colorectal adenocarcinoma cases increased yearly in the Anatomical Pathology Laboratory of Dr. Soedarso Hospital Pontianak. Further study of the clinical characteristics and analysis of risk factors in colorectal adenocarcinoma patients were important to support the development of effective preventive strategies.

Surgical Treatment of Carcinomas of the Oral Minor Salivary Glands-Oncological Outcome in Dependence of Tumor Entity and Therapeutic Strategies.

The aim of this study was to analyze the clinical outcomes of three types of minor salivary gland carcinomas (adenoid-cystic carcinomas (ACC), adeno carcinomas not otherwise specified (AC-NOS), and mucoepidermoid carcinomas (MEC)) after primary surgical therapy. A retrospective cohort study was designed and patients with cancer of the minor oral salivary glands treated in our department in the years 2011 to 2022 were included. Clinicopathological data were evaluated to compare overall survival and progression-free survival between the entities. Eighty-one patients were included. The rates of cervical metastases were 38.9% for ACC, 25% for MEC, and 9.1% for AC-NOS. ACC exhibited significantly higher rates of local and systemic disease recurrence (p = 0.02), and the presence of neck node metastases was confirmed as an independent prognostic factor for progression-free survival (p = 0.014). Treatment success in terms of oncological outcome varied significantly between the different entities and implies different treatment regimens for each tumor entity.

Epidemiological, Clinical, and Histopathological Features of Salivary Gland Tumors among 150 Sudanese Patients: 10 Years' Experience.

Salivary gland tumors (SGTs) are serious challenges to pathologists. Herein, we aimed to assess epidemiological and histopathological characteristics of SGTs among Sudanese patients. This retrospective descriptive study was undertaken at The pathology department in Khartoum State between 2008 and 2018. Patient records, histopathological reports, and slides were retrieved; and re-examined by two histopathologists. Diagnoses were reclassified according to the 2017 WHO classification of SGTs. Overall, 150 cases of Sudanese patients with SGT were included (90 [60%] males and 60 [40%] females). Among these, 105 were benign (70%) and 45 were malignant (30%). The parotid glands were the most common site for both benign and malignant tumors (77/150; 51%: 59 benign (76.6%) and 18 malignant [23.4%]). The next common site was the submandibular gland (54 [36%]: 38 benign [70.3%] and 16 malignant [29.7%]), followed by minor salivary glands (19 [12.7%]: 8 benign and 11 malignant [57.9%]). Benign gland entities included pleomorphic adenoma (88/105; 83.7%), oncocytoma (5/105; 4.8%), myoepithelioma (4/105; 3.8%), Whartin tumors (3/105; 2.9%), basal cell adenoma (3/105; 2.9%), and sialolipoma (2/105; 1.9%). Malignant gland entities included adenoid cystic carcinoma (12; 26.7%), mucoepidermoid carcinoma (10; 22,2%), acinic cell carcinoma (6; 13.3%), poorly differentiated carcinoma (4; 8.9%), adenocarcinoma NOS (not otherwise specified) (4; 8.9%), basal cell adenocarcinoma (3; 6.7%), carcinoma ex pleomorphic adenoma (3; 6.7%), polymorphous adenocarcinoma (2; 4.4%), salivary duct carcinoma (1; 2.2%), and epithelial-myoepithelial carcinoma (2.2%). SGTs shared several epidemiological and histopathological features, exhibiting high incidence in the parotid and submandibular glands, lower prevalence in minor glands, and greater male predominance.

Rare Diagnoses and Diagnostic Pitfalls in Female Genital Tract Neoplasms: A Case Series

There is a wide spectrum of disorders that may originate from different parts of the female genital tract. They are often unique and rare, posing a diagnostic challenge for reporting pathologists. Their uniqueness lies in the rare histomorphologic picture and challenging clinical scenarios, accentuated by a paucity of available literature. Sometimes, histomorphology alone may not be sufficient for diagnosis, and ancillary studies like Immunohistochemistry (IHC) may help arrive at a definitive diagnosis. Present article represents a series of six unique cases. The first case presented with virilising features and menstrual irregularities. Gross examination of the adnexal neoplasm showed solid yellowish-orange areas, which were diagnosed as Steroid Cell Tumour (SCT), Not Otherwise Specified (NOS) based on histomorphology. This diagnosis was further substantiated by diffuse and strong Inhibin positivity on IHC. The second case presented with huge abdominal distention and markedly raised CA-125 levels. It was diagnosed as mucinous carcinoma with a focus of Benign Brenner Tumour. The third case presented with postmenopausal bleeding and underwent radical hysterectomy. Gross examination revealed simultaneous involvement of the unilateral adnexa, and it was finally diagnosed as endometrioid carcinoma with adnexal metastasis, International Federation of Gynaecology and Obstetrics (FIGO) stage IIIA. The fourth case was a cervical carcinoma with histomorphology suggestive of high-grade, but it did not fit into any of the known subtypes of adenocarcinoma. Therefore, it was reported as Adenocarcinoma NOS with focal mucinous differentiation. The fifth case was a rare cervical Adenosquamous Carcinoma (ASCC) with both malignant squamous and glandular components. The sixth case was of mesenchymal origin in the vulva, namely Aggressive Angiomyxoma (AA). All these cases highlight the fact that pathologists should be well aware of these entities to make an appropriate diagnosis.

Abstract 6143: Tumor immune microenvironment in salivary gland cancer

Abstract Purpose/Objectives: Salivary gland cancer (SGC) is a rare malignancy with various pathological types. Although immune checkpoint inhibitors for SGC have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) in SGC remain unclear. The aim of this study was to elucidate the TIME of SGC. Materials/Methods: We selected five typical pathological types of SGC, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEC low/high). We investigated the TIME as well as the tumor mutation burden (TMB) of each pathological type in surgical archival tissues obtained from 1999 to 2017 (7 patients in each type, stage III/IVA/IVB [UICC 8th]). TIME was evaluated by multiplexed immunofluorescent staining, including CD3, CD4, CD8, Foxp3, CD204, PD-1, PD-L1, and PD-L2. Tumors with > 1% tumor cells expressing PD-L1 were considered positive for PD-L1. TMB was measured by the Oncomine Tumor Mutation Load Assay, and a high TMB was defined by 10 or more mutations/Mb. Correlation analyses were performed using Pearson’s product moment correlation coefficient. Results: Multiplexed immunofluorescent staining was performed in all 35 archival tissues. ACC showed the lowest infiltration of immune effector cells (ICeff) and suppressor cells (ICsup) in both the tumor and stroma, and a low proportion of cases was positive for PD-L1 (14%). Compared with ACC, MEC high showed higher infiltration of ICeff and ICsup in both the tumor and stroma, and a higher proportion of cases was positive for PD-L1 (71%). Although ANOS, SDC, and MEC low showed modest infiltration of ICeff in the tumor, these subtypes showed higher infiltration of ICeff in the stroma than ACC. TMB was measured in 29 samples; the proportion of TMB high was lower in ACC (33%) and MEC low (0%) than in the other pathological types (ANOS/SDC/MEC high: 60/67/57%). Regarding multiplexed immunofluorescent staining, correlation analysis showed a positive correlation between TMB and CD3+CD8+ T cells in the tumor (r=0.647, P<0.0001). In addition, CD3+CD8+ T cells in the tumor showed a positive correlation with PD-L1 expression in tumor cells (r=0.513, P=0.002) and with CD3+CD4+Foxp3+ T cells in the tumor (r=0.399, P=0.018). However, no correlation was seen between CD3+CD8+ T cells and CD204+ cells in the tumor (r=-0.049, P=0.779). Conclusion: ACC showed less PD-L1 expression in tumor cells and the lowest infiltration of immune cells in both the tumor and stroma compared with other pathological types. These results suggest that the TIME of ACC is the so-called immune desert type, which may in turn explain the mechanisms of the poor response to immune check point inhibitors seen in clinical trials. Citation Format: Yoshiaki Nagatani, Naomi Kiyota, Yoshinori Imamura, Taiji Koyama, Yohei Funakoshi, Masato Komatsu, Masanori Teshima, Ken-Ichi Nibu, Kazuko Sakai, Kazuto Nishio, Manami Shimomura, Tetsuya Nakatsura, Daiki Ikarashi, Takayuki Nakayama, Shigehisa Kitano, Hironobu Minami. Tumor immune microenvironment in salivary gland cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6143.

An Analysis of Clinicopathological Outcomes and the Utility of Preoperative MRI for Patients Undergoing Resection of Mucinous and Non-Mucinous Colorectal Cancer Liver Metastases

Background and AimsMucinous colorectal cancer has traditionally been associated with high rates of recurrence and poor long-term survival. There is limited published data on outcomes for patients undergoing liver resection for metastatic mucinous colorectal cancer. The aim of this study was to compare the clinicopathological outcomes for patients with mucinous colorectal cancer liver metastases (CRCLM) undergoing liver resection to a matched group of patients with adenocarcinoma not otherwise specified (NOS) and to evaluate the accurary of preoperative magnetic resonance imaging (MRI) at detecting the presence of mucin in liver metastases.Materials and MethodsPatients with mucinous CRCLM undergoing liver resection were matched 1:3 to patients with adenocarcinoma NOS CRCLM. Clinicopathological data from the primary tumour and metastatic lesion were collected and compared between the groups. Hepatic recurrence-free, disease-free and overall survival were compared between the groups. The ability of preoperative MRI to detect mucin in CRCLM was also evaluated.ResultsA total of 25 patients with mucinous CRCLM underwent surgery over the 12-year period and were matched to 75 patients with adenocarcinoma NOS. Clinicopathological findings were similar between the groups. Resection of mucinous CRCLM was feasible and safe with similar levels of morbidity to adenocarcinoma NOS. There were no differences identified in hepatic recurrence-free (p=0.85), disease-free (p=0.25) and overall survival (p=0.98) between the groups. MRI had a sensitivity of 31.3% in detecting the presence of mucin in CRCLM.ConclusionPatients with mucinous CRCLM in this study had similar outcomes to patients with adenocarcinoma NOS. Based on our findings, histological subtype should not be taken into account when deciding on resectability of CRCLM.

Elective neck dissection in salivary gland malignancies: Systematic review and meta-analysis.

We defined the occult nodal metastasis (ONM) rate of clinical node-negative salivary gland malignancies and examined the role of elective neck dissection (END). Meta-analysis querying four databases, from inception of databases to March 25th, 2020. Fifty-one studies with 11 698 patients were included. ONM rates were 64% for salivary ductal carcinoma (SDC), 51% for undifferentiated carcinoma, 34% for carcinoma ex-pleomorphic adenoma (CXPA), 32% for adenocarcinoma not otherwise specified (ANOS), 31% for lymphoepithelial carcinoma (LE), 20% for mucoepidermoid carcinoma, 17% for acinic cell carcinoma, and 17% for adenoid cystic carcinoma. T3/T4 tumors had a 2.3 times increased risk of ONM than T1/T2 tumors. High-grade tumors had a 3.8 times increased risk of ONM than low/intermediate-grade tumors. ONM rates were exceedingly high for T3/T4, high-grade, and undifferentiated, SDC, ANOS, CXPA, and LE tumors, indicating the potential role of END.

Bridging the Species Gap: Morphological and Molecular Comparison of Feline and Human Intestinal Carcinomas.

Simple SummaryColorectal cancer (CRC) is the second leading cause of cancer deaths in humans (2020) but modeling late-stage human CRC, including high tumor budding and metastatic activity, experimentally in mouse models is a major challenge. In the present study, histopathological, immunohistochemical and molecular features of spontaneous intestinal carcinomas in cats were evaluated with a special focus on their potential applicability as a valuable model for human CRC. Feline intestinal tumors display aggressive growth patterns and adequately model invasive late-stage human CRC. They exhibit the same histological subtypes and display strikingly high tumor budding activity, both of which are highly significant prognostic factors in human CRC. Moreover, human and feline colorectal tumors harbor the same mutations of the CTNNB1 gene, encoding β-catenin. Our data indicate that feline intestinal carcinomas constitute a valuable and promising in vivo model for human CRC. Further comparative oncological research, and especially investigation of the molecular landscape of feline intestinal neoplasms, is imperative.Limited availability of in vivo experimental models for invasive colorectal cancer (CRC) including metastasis and high tumor budding activity is a major problem in colorectal cancer research. In order to compare feline and human intestinal carcinomas, tumors of 49 cats were histologically subtyped, graded and further characterized according to the human WHO classification. Subsequently, feline tumors were compared to a cohort of 1004 human CRC cases. Feline intestinal tumors closely resembled the human phenotype on a histomorphological level. In both species, adenocarcinoma not otherwise specified (ANOS) was the most common WHO subtype. In cats, the second most common subtype of the colon (36.4%), serrated adenocarcinoma (SAC), was overrepresented compared to human CRC (8.7%). Mucinous adenocarcinoma (MAC) was the second most common subtype of the small intestine (12.5%). Intriguingly, feline carcinomas, particularly small intestinal, were generally of high tumor budding (Bd) status (Bd3), which is designated an independent prognostic key factor in human CRC. We also investigated the relevance of feline CTNNB1 exon 2 alterations by Sanger sequencing. In four cases of feline colonic malignancies (3 ANOS, 1 SAC), somatic missense mutations of feline CTNNB1 (p.D32G, p.D32N, p.G34R, and p.S37F) were detected, indicating that mutational alterations of the WNT/β-catenin signaling pathway potentially play an essential role in feline intestinal tumorigenesis comparable to humans and dogs. These results indicate that spontaneous intestinal tumors of cats constitute a useful but so far underutilized model for human CRC. Our study provides a solid foundation for advanced comparative oncology studies and emphasizes the need for further (molecular) characterization of feline intestinal carcinomas.

Adenocarcinoma NOS arising from accessory lacrimal glands: A case report and a review of the literature

Primary malignant epithelial tumours arising from accessory lacrimal glands (ALGs) are extremely rare, with only few cases reported in literature. They generally appear as gradually increasing masses of the upper or the lower eyelid. Only one case of primary adenocarcinoma or adenocarcinoma not otherwise specified (ACNOS) from ALGs has been reported in literature. Herein, we describe a case of ACNOS arising from ALGs with an atypical clinical presentation and review prior cases of ALGs epithelial malignancies reported in the literature. A 78-year-old man referred to our Ocular Oncology Unit for adjuvant therapy after the excision of a conjunctival tumour of the left eye with a histological diagnosis of squamous cell carcinoma. He underwent topical chemotherapy with MMC and during follow up he presented a multinodular iris mass in his left eye. The MRI of the orbit showed an ocular mass infiltrating orbital soft tissues of the inferior palpebral region with an involvement of the corresponding zygomatic cutis. We performed orbital exenteration and histological studies revealed an epithelial neoplasm with a solido-glandular growth pattern with lumens containing an eosinophilic material positive for PAS and PAS-D. The immunohistochemical findings confirmed the diagnosis of adenocarcinoma NOS from ALGs. Although ALGs epithelial malignancies are extremely uncommon, they should be considered in the differential diagnosis of ocular tumours. A vigilant approach towards these entities is required, since they can be clinically insidious and locally aggressive.

When Should Elective Neck Dissection Be Performed for Parotid Gland Malignancy?

When Should Elective Neck Dissection Be Performed for Parotid Gland Malignancy?

Tumor microenvironment in salivary gland carcinomas: Consequences for new therapeutic concepts

Salivary gland carcinomas (SGCs) are rare tumors which represent achallenge for diagnosis and therapy due to their histological diversity and the different disease courses depending on the respective subtype. Little is known about the composition of the tumor microenvironment in SGCs. Amore comprehensive understanding of the relevant molecular changes and immunological processes of the tumor and surrounding stroma could help to improve therapeutic efficiency, for example by adjuvant immunomodulation. This manuscript highlights recent studies analyzing the composition of the tumor microenvironment in salivary gland carcinomas. The tumor microenvironment displays asignificant diversity in the composition of immune cells among different tumor entities. In one third of the SGCs, an expression of cell surface molecule LAG3 on tumor infiltrating lymphocytes could be observed. LAG3-similar to CTLA‑4 and PD-1-inhibits cellular proliferation, activation, and homeostasis of antitumor-effective Tcells. Especially, prognostically less favorable entities such as salivary duct carcinomas and adenocarcinomas NOS (not otherwise specified) yielded higher expressions. LAG3 is particularly detectable in aggressive entities and advanced tumors. Hence, LAG3 inhibition poses apotential targeted therapy for advanced and metastatic SGCs.

Management of the Neck in High-Grade Parotid Malignancies: A National Cancer Database Study of 1,541 Patients

Parotidectomy remains the standard of care and is recommended as the initial treatment for primary parotid gland malignancies, however, management of the neck remains controversial and studies are lacking that provide definitive evidence regarding the treatment of regional lymph nodes. Many studies have concluded that regional lymph nodes should be treated with either radiation therapy(RT) or neck dissection(ND) in high grade parotid cancers. To examine the overall survival of patients with high-grade parotid malignancies who received parotidectomy with neck dissection or both neck dissection and radiotherapy. A total of 1541 patients with high-grade primary parotid gland carcinoma were identified from the National Cancer Database (1998-2014). Cancer histologies included mucoepidermoid cancer (MEC) (42.6%), adenocarcinoma not otherwise specified (ANOS) (33.7%), adenoid cystic carcinoma (Ad Cy CA) (11.8%), and acinar cell carcinoma (AC CA) (11.8%). Treatment groups were composed parotidectomy + neck dissection (Group 1), and parotidectomy + ND + RT (Group 2). Regardless of histology, Group 2 had a higher survival than Group 1 in all histologies except Ad Cy CA, although not statistically significant. However, this relationship was not found when breaking down patients into clinically negative and positive disease. Group 1 had higher survival in cN0 MEC and Ad Cy CA patients whereas Group 2 had a higher survival in cN0 ANOS and AC CA patients. For cN+ patients, Group 2 had a higher survival in ANOS, but Group 1 had a higher survival in MEC and AC CA. Patients with high-grade parotid cancer appear to benefit from adjuvant RT to the neck. The pathologic findings found after neck dissection also appear to portend a worse prognosis. This study did not provide conclusive evidence to support either ND alone or RT alone to cervical lymph nodes although variations by histology and stage were evident.

ADENOCARCINOMA NOT OTHERWISE SPECIFIED: CONDUCT AND TREATMENT IN DENTAL FIELD AND SPEECH THERAPY

Adenocarcinoma not otherwise specified (NOS) is a group of salivary carcinomas with glandular and ductal differentiation. This article presents a narrative review that aims to determine the conduct and treatment of adenocarcinoma NOS by the optics of the dental surgeon and speech therapist. To identify the study object, articles published between 1998 and 2019, listed in the Scientific Electronic Library Online (SciELO) and PUBMED, indexed with the following descriptors: adenocarcinomas, not otherwise specified adenocarcinomas, and salivary gland adenocarcinomas were chosen. The adenocarcinoma NOS is a neoplasm of high degree of malignancy, with histologic aspect of ductal differentiation and presence of infiltrate in the margins of the tumor. The diagnosis is given by excluding groups of known lesions. The tumor staging is defined as follows: stage I and II are considered initial stages and the stages III and IV are advanced. The ideal treatment is through complete surgical excision of the lesion and contiguous lymph nodes, neoadjuvant radiotherapy, and speech therapy in the rehabilitation of altered voice and swallowing functions, which are the sequelae of the adopted treatment. In view of this, the interdisciplinary action between odontology and speech therapy is indispensable in the therapy of head and neck cancer.

Retrospective Study of Buccal Mucosal Salivary Neoplasms.

Salivary gland neoplasms of the buccal mucosa are relatively rare and often present with an unusual histopathologic profile when compared with other intraoral locations. We present a series of minor salivary gland neoplasms of the buccal mucosa and discuss demographics, clinical presentation, and histologic findings. An IRB approved retrospective search of University of Florida Oral Pathology Biopsy Service archive from 1994 to 2018 for all salivary gland neoplasms of the buccal mucosa was undertaken. Data related to age, gender, clinical presentation, diagnosis, and category of neoplasm recorded. Review for consensus of diagnosis and immunohistochemical (IHC) testing on current diagnostic standards was performed and diagnoses updated based on results. Of 66 cases identified majority were females (72.7%) and age mean was 63 years. Benign tumors were 56.06% and 43.94% malignant, with Mucoepidermoid carcinoma (MEC) being commonest (26/66, 39.4%), followed by canalicular adenoma (CLA) (14/66, 21.2%), ductal papilloma (DP) (10/66, 15.2%), cystadenoma (CA) (8/66, 12.1%), basal cell adenoma (BCA) (4/66, 6.1%), and 1(1.5%) each for pleomorphic adenoma (PA), secretory carcinoma (SC), adenoid cystic carcinoma (ACC) and adenocarcinoma not otherwise specified (ACNOS). This study with respect to demographics and percentage of benign and malignant buccal mucosal salivary gland neoplasms is in conformity with the literature. It underscores the fact that both benign and malignant salivary gland neoplasms should be included in the differential diagnosis of submucosal buccal masses. Future larger multicenter studies with detailed treatment and outcomes data may aid and assist in further understanding the behavior, diverse histomorphology and prognosis of these neoplasms.

1169P - Development and characterization of salivary gland cancer organoid cultures

BackgroundRecently 3D organoid cell cultures have been established for a variety of human cancers. Salivary gland cancer (SGC) is a rare cancer with 22 different subtypes and few treatment options. Our aim is to generate a large repertoire of patient-derived SGC organoids with different phenotypes, which will facilitate pre-clinical and pharmacological studies. MethodsFresh tissues of resected primary tumours and/or metastases of SGC patients were collected. Tissues were minced and digested with collagenase type 2 and TrypLE to generate single cells. After washing, the cells were seeded in growth factor reduced Matrigel. Organoid medium, containing Rho kinase inhibitor Y27632, was refreshed twice a week. Viable organoids were characterized by immunohistochemistry and by DNA/RNA sequencing. Moreover, the organoids were used to evaluate various treatments that are or may be relevant for the treatment of SGC. ResultsBetween 2016 and 2018 we obtained tissue of 17 SGC patients, of which 16 contained sufficient material for processing: 10 salivary duct carcinoma (SDC), 3 adenoid cystic carcinoma (ACC), 2 muco-epidermoid carcinoma (MEC) and 1 parotid adenocarcinoma not otherwise specified (NOS). For 5 tumors (2 SDC, 2 ACC, 1 adenocarcinoma NOS) viable organoids were established, which could be passaged at least three times. Organoids cultures derived from the other tumours stopped growing after the first passage. Viable organoids showed resemblance with the original primary tumour, based on morphology, protein expression, and growth pattern. Various drugs were tested at a single dose, and showed reduced organoid cell growth compared to untreated controls. Moreover, a dose-response relationship was established for an ALK-positive MEC organoid that was treated with crizotinib. Finally, epithelial-mesenchymal transition was shown in SDC organoids of a primary tumour and a lymph node metastasis of the same patient. ConclusionsWe are the first that have successfully developed and characterized long-term organoid cultures for ACC and SDC. These organoid cell lines will facilitate pre-clinical and pharmacological studies. Other SGC organoid cultures do not grow infinitely, but do provide an in vitro model to study different treatments during initial growth. Legal entity responsible for the studyRadboud University Medical Center. FundingDutch Salivary Gland Cancer Patient Platform. DisclosureAll authors have declared no conflicts of interest.

High levels of ANXA2 are characteristic of malignant salivary gland tumors.

Malignant salivary gland tumors (MSGTs) present different phenotypic characteristics and various clinical outcomes, which proved to be a diagnostic challenge. Considering the heterogeneity of MSGT, this study aims to identify molecule related to the nature of MSGT. For screening, proteomic analysis comparing MSGT with pleomorphic adenoma (PA) and salivary gland was performed. The MSGT-associated protein which presented in the higher number in the Gene Expression Omnibus (GEO) database was selected. To validate the data, immunohistochemistry (IHC) was performed in 14 patients with PA, 22 patients with MSGT, and 14 controls. 16 proteins were associated with MSGT. ANXA2 was the primary protein, according to GEO database analyses. ANXA2 was most expressed in the cell membrane. However, some ANXA2 staining was also observed in the cytoplasm and nucleus. ANXA2 was highly expressed in MSGT in comparison with control. Also, ANXA2 has a higher expression in adenocarcinoma not otherwise specified (ANOS) and myoepithelial carcinoma (MC) in comparison with PA. In conclusion, this study demonstrated that MSGT presented higher levels of ANXA2 in comparison with normal salivary glands. Also, ANXA2 might be interesting as a molecular marker of ANOS and MS.