Gland Adenocarcinoma Research Articles

Apocrine Gland Anal Sac Adenocarcinoma in Dogs: 22 Cases (2015-2020)

Background: Apocrine gland anal sac adenocarcinoma (AGASACA) is a highly malignant disease mostly invading regional lymph nodes at the time of disease diagnosis.Methods: Twenty- two cases of Apocrine gland anal sac adenocarcinoma (AGASACA) were treated during five years. Contrast radiography with Iohexol and Lipidol were carried out to detect primary anal sac mass and regional lymph node through indirect lymphography technique. For clinical staging, ultrasonography, fine-needle aspiration cytology, histopathology of both primary tumor mass and regional lymph node were performed. Closed anal Sacculectomy was performed as curative therapy for anal sac adenocarcinoma.Result: The median age and weight of dogs at presentation were 8.4 years and 20.9 kg, respectively. Diagnostic radiology, histopathology and biochemical assay confirm twenty-two cases of anal sac adenocarcinoma and medial iliac lymph node to be sentinel lymph node. Carcinoma was of unilateral occurrence in all the dogs. Four (18%) dogs had hypercalcemia and twelve (54%) had metastases to the regional lymph nodes with clinical signs of tenesmus or constipation, polyuria -polydipsia and anorexia. Apocrine gland Adenocarcinoma of anal sac was found to initially metastasize to the medial iliac lymph node. Survival times of dogs treated with the surgical procedure only (8 out of 22 dogs) were appreciably longer than the dogs with therapeutic only. Animals with metastasis to regional lymph nodes or lymphadenopathy had poor prognosis.

SalvGlandDx – a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets

Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the “SalvGlandDx” panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.

A retrospective study (2006-2020) of cytology and biopsy findings in pet rabbits (Oryctolagus cuniculus), ferrets (Mustela putorius furo) and four-toed hedgehogs (Atelerix albiventris) seen at an exotic animal clinic in Tokyo, Japan

ABSTRACT Background: Rabbits, ferrets, and four-toed hedgehogs are popular exotic pets, but comprehensive epidemiological studies in these animals have been rarely conducted. The present study aims to clarify the incidence of neoplastic and non-neoplastic diseases in pet rabbits, ferrets and four-toed hedgehogs in Japan. Methods: We histologically/cytologically investigated 1098 samples from 883 rabbits, 812 samples from 521 ferrets and 561 samples from 468 four-toed hedgehogs that were collected at Miwa Exotic Animal Hospital and submitted to the Laboratory of Veterinary Pathology, The University of Tokyo between 2006 and 2020. The examinations of necropsy samples were not included in the present study. Results: Of the 1098 samples from diseased rabbits, 721 (65.7%) were diagnosed as neoplastic and 377 (34.3%) were as non-neoplastic. Uterine adenocarcinoma (21.1%), cutaneous soft tissue sarcoma (15.1%) and mammary gland adenocarcinoma (8.2%) were the most commonly encountered neoplasms. Endometrial hyperplasia (35.8%), testicular atrophy (4.2%) and uterine adenomyosis (3.7%) were the most common non-neoplastic lesions in rabbits. Of the 812 samples from diseased ferrets, 487 (60.0%) were diagnosed as neoplastic and 325 (40.0%) were as non-neoplastic. Adrenocortical tumor (23.2%), lymphoma (19.3%) and pancreatic islet cell tumor (11.5%) were the most commonly encountered neoplasms. Extramedullary hematopoiesis in the spleen (10.5%), lymph node hyperplasia (7.7%) and cholangiohepatitis (4.6%) were the most common non-neoplastic lesions in ferrets. Of the 561 samples from diseased hedgehogs, 338 (60.2%) were diagnosed as neoplastic and 223 (39.8%) were as non-neoplastic. Endometrial stromal tumor and endometrial mixed tumor (23.7%), oral squamous cell carcinoma (13.0%) and cutaneous soft tissue sarcoma (11.5%) were the most commonly encountered neoplasms. Gingivitis/stomatitis (39.5%), endometrial hyperplasia (18.8%) and dermatitis (6.7%) were the most common non-neoplastic lesions in hedgehogs. Conclusions and clinical relevance: Information obtained from the present study will provide a useful reference for veterinarians working with these exotic animals. Based on the literature search, this is the largest-scale retrospective study on disease incidence in hedgehogs.

Immunohistochemical Expression of BCL-2 in Malignant Salivary Gland Tumors

Background: Malignant salivary gland tumors (MSGTs) consist of a heterogeneous group of neoplasms with complex clinicopathological features and biological behaviors. The purpose of this study was to determine the expression of Bcl-2 antiapoptotic protein in mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ADCC), acinic cell carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) of salivary glands and to find out its association with different grades of these tumors.
 Material and Methods: This descriptive study included 55 cases of MSGTs. Tissue sections were stained with routine hematoxylin and eosin stain as well as Bcl-2 immunostain. MSGTs were graded as low grade (Low grade MEC, ACC, PLGA, and tubular pattern of ADCC), intermediate grade (cribriform pattern of ADCC, and intermediate grade of MEC) and high grade (high grade of MEC and solid pattern of ADCC) tumors on H&E sections. Bcl-2 expression was scored as ‘negative’ (<5% of neoplastic cells), ‘1’ (5-19% of neoplastic cells), ‘2’ (20-49% of neoplastic cells), and ‘3’ (>50% of neoplastic cells), respectively.
 Results: MSGTs most commonly involved the parotid gland (52.7%), while ADCC (40%) and MEC (38.2%) were the most common tumors. Expression of Bcl-2 was strongly positive in 56.4% cases of MSGTs which included ADCC (71%), MEC (19.4%) and ACC (9.7%), respectively. A significant association was found between Bcl-2 staining and types of MSGTs i.e., MEC, ADCC, ACC (P = .001) as well as between Bcl-2 staining and grades of MSGTs (P = .013).
 Conclusions: Bcl-2 protein is expressed in malignant salivary gland tumors. Its expression maybe helpful in grading small biopsies, predicting behavior, and planning targeted therapy of MSGTs.
 

Comparison of dosimetry parameters of three-dimensional conformational radiation therapy and volumetric modulated arc therapy on the example of treatment of a patient with salivary gland adenocarcinoma

An optimal choice of radiation therapy method is the main prerequisite for successful completion of treatment.
 Continuous analysis of radiation therapy methods’ advantages and comparing their parameters and dose load in typical cases will increase the treatment efficacy and reduce the unavoidable load on critical organs.
 The purpose was to check the plans of treatment by volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiation therapy (3D-CRT) methods, make their comparison and identify the advantages using an example of a treatment design for a patient treated at the Daily Radiotherapy Hospital of the Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan).
 Results: The presented illustrations of the process planning and the numerical analysis of the dose load on critical organs show VMAT advantages for radiation therapy of salivary gland cancer: optimal coverage, sparing load on critical organs and healthy tissues, gradient decay at the borders of the neoplasm.
 Conclusion: The variability of radiation therapy methods ensures the most acceptable coverage that keeps the dose load within international standards’ ranges. Mastering these methods will improve the effectiveness of radiation therapy for various cancer cases

Comparison of dosimetry parameters of three-dimensional conformational radiation therapy and volumetric
 modulated arc therapy on the example of treatment of a patient with salivary gland adenocarcinoma

Relevance: An optimal choice of radiation therapy
 method is the main prerequisite for successful completion
 of treatment. Continuous analysis of radiation therapy
 methods’ advantages and comparing their parameters
 and dose load in typical cases will serve to increase the
 treatment efficacy and reduce the unavoidable load on
 critical organs.
 Purpose: To check the plans of treatment by volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiation therapy (3D-CRT) methods, make their comparison, and identify the advantages using an example of a treatment design for a patient treated at the Daily Radiotherapy Hospital of the Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan).
 Results: The presented illustrations of the process
 planning and the numerical analysis of the dose load on
 critical organs show VMAT advantages for radiation therapy of salivary gland cancer: optimal coverage, sparing
 load on critical organs and healthy tissues, gradient decay
 at the borders of the neoplasm.
 Conclusion: The variability of radiation therapy methods ensures the most acceptable coverage that keeps the
 dose load within international standards’ ranges. Mastering these methods will improve the effectiveness of radiation therapy for various cancer cases.

In vitro estrogenic, cytotoxic, and genotoxic profiles of the xenoestrogens 8-prenylnaringenine, genistein and tartrazine

Phytoestrogens have been widely praised for their health-promoting effects, whereas synthetic environmental estrogens are considered a toxicological risk to human health. The aim of this study was therefore to compare in vitro the estrogenic, cytotoxic, and genotoxic profiles of three common estrogen-like endocrine-disrupting chemicals: the phytoestrogens 8-prenylnaringenine (8-PN) and genistein and the synthetic xenoestrogen tartrazine. As assessed by a yeast bioreporter assay and estrogen-dependent proliferative response in human mammary gland adenocarcinoma cell line (MCF-7), 8-PN showed the highest estrogen-like activity of the three compounds, followed by tartrazine and genistein. After 24-h incubation on MCF-7 cells, all three compounds exhibited low cytotoxicity in the lactate dehydrogenase assay and no genotoxicity in the micronucleus assay. These results demonstrate that 8-PN, genistein and tartrazine possess variable estrogenic activity but display little cellular toxicity in short-term tests in vitro. No difference between phytoestrogens and a synthetic xenoestrogen could be established.

SS18 Break-Apart Fluorescence In Situ Hybridization is a Practical and Effective Method for Diagnosing Microsecretory Adenocarcinoma of Salivary Glands.

Molecular analysis has allowed for refinement of salivary gland tumor classification and, in some cases, the recognition of entirely new tumor types. Microsecretory adenocarcinoma (MSA) is a salivary gland tumor described in 2019 characterized by microcystic growth, bland cytomorphology, luminal secretions, fibromyxoid stroma, and S100/p63 positivity with negative p40. Most important, MSA is defined by MEF2C-SS18 fusion. While this fusion has, to this point, been detected by next-generation sequencing, this is a technique that is currently inaccessible in most diagnostic laboratories. On the other hand, SS18 break-apart fluorescence in situ hybridization (FISH) is widely available and frequently used as an adjunct for diagnosing synovial sarcoma. It is not known if SS18 break-apart FISH is positive in tumors with MEF2C-SS18, or if it is entirely specific for MSA.Break apart FISH for SS18 was performed on 4 cases of MSA, as well as 8 tissue microarrays (TMAs) containing 423 various salivary gland carcinomas: 26 acinic cell carcinomas, 35 adenocarcinomas not otherwise specified, 96 adenoid cystic carcinomas, 3 basal cell adenocarcinomas, 20 epithelial-myoepithelial carcinomas, 15 hyalinizing clear cell carcinomas, 3 intraductal carcinomas, 12 myoepithelial carcinomas, 117 mucoepidermoid carcinomas, 30 polymorphous adenocarcinomas, 45 salivary duct carcinomas, 19 secretory carcinomas, and 2 undifferentiated carcinomas. SS18 break-apart FISH was also performed on whole slides of 2 tumors from the TMAs.All MSA cases demonstrated classic split patterns on SS18 break-apart FISH. On the TMAs, 374 cases were evaluable by FISH, and 372 cases were clearly negative for SS18 rearrangement. Two cases, both mucoepidermoid carcinomas, had rare split signals below the positivity threshold of 12% on their TMA cores, so FISH was performed on whole sections. On the whole sections both tumors were unequivocally negative for SS18 rearrangement. Taken together, SS18 break-apart FISH was 100% sensitive and 100% specific for a diagnosis of MSA.SS18 break-apart FISH, a diagnostic tool widely available in pathology laboratories, appears to be a highly accurate method for diagnosing MSA of salivary glands. Accordingly, this new tumor type may be molecularly confirmed without needing to resort to highly specialized techniques like next-generation sequencing.

Diagnostic value of biomarkers of bone metabolism in the gingival fluid in inflammatory-destructive and tumor oral pathology

The aim of the work was to determine the informativeness of the assessment of biochemical markers in the gingival fluid with destructive bone changes in the peri-implantation area, primary tumor lesion of the alveolar processes of the jaws and metastatic destruction of the jaw bone tissue in cancer of the large salivary glands. The study included 51 patients aged 30 to 75 years of both sexes. Depending on the genesis of destruction of the bone tissue of the lower jaw, three groups of patients were identified. Group 1 - 20 patients with peri-implantitis. Group 2 - 22 patients diagnosed with cancer of the oral floor mucosa (ICD C04) with erosion of the cortical bone or dental socket by a primary tumor. Group 3 - 9 patients with adenocarcinoma of the large salivary glands with metastatic lesions of the lower jaw. 15 people were practically healthy persons without periodontal pathology. The test material was gingival fluid or exudate from peri-implantation pockets. The content of cathepsin K, tartrate-resistant acid phosphatase (TAP) was determined by the enzyme immunoassay, and the bone fraction of alkaline phosphatase (BAP) was determined by the kinetic method. As a result, it was found that in group 1 in the exudate of the peri-implantation sulcus, the content of cathepsin K increased in comparison with the control by 2.5 times (p<0.05), TAP by 1.6 times (p<0.05). in groups 1 and 2, there was a moderate increase in the production of activated osteoblasts of KAP. In cancer of the mucous membrane of the floor of the mouth, a tenfold increase in the concentration of cathepsin K and TAP in the gingival fluid was observed. With metastatic lesions of the jaw in patients with adenocarcinoma of the large salivary glands, along with a multiple increase in the concentration of cathepsin K and TAP in the gingival fluid, there was a twenty-fold increase in the bone formation marker BAP, which indicated a mixed type of metastases and was a differential diagnostic criterion for metastatic lesion of bone tissue in comparison with the primary metastatic lesion of bone tissue. Thus, biochemical markers are sensitive indicators of remodeling of bone tissue both in local inflammatory and destructive processes in peri-implantitis and in primary and metastatic tumor lesions of the jaws.

Поширеність пухлинної патології собак в умовах мегаполісу

A statistical analysis of the prevalence of tumor pathology of dogs in the city of Dnipro. 418 cases of registered oncological diseases of dogs were analyzed. It was found that malignant neoplasms are 1.5 times more common than benign. The most common tumors in dogs are tumors of the breast (35,9%), skin (22,0%), genitals (15,3%) and lymphoma(8,4%). Malignant neoplasms of the breast are registered 3.6 times more often than benign and surpass them in morphological varieties. Fibroadenomas and infiltrating and non-infiltrating carcinomas were mainly registered. Approximately the same number of cases of infiltrating and non-infiltrating cancers were noted. Benign skin tumors are more common than malignant. Mastocytosis, melanoma, and squamous and basal cell carcinomas of the skin and sebaceomas were the most commonly reported. In terms of morphological varieties, benign skin neoplasms are superior to malignant ones. Lipomas and papillomas are very common. Genital neoplasms of females and males are also common. Almost half of male genital tumors were malignant seminomas. Among benign neoplasms, serteliomas and leydigomas were more common. In females, the most common are uterine leiomyoma, vaginal fibroma and ovarian carcinoma. Lymphomas (8.4%) are also widespread in dogs in the metropolis. The average age of registration of these neoplasms was 7.5 years. Benign tumors in the oral cavity of dogs were twice as common as malignant, of which fibrosarcomas, squamous keratinized and non-keratinized carcinomas, and salivary gland adenocarcinomas were reported. In females, oral neoplasia occurred 3.2 times more often than in males. Only malignant venereal sarcomas and carcinomas were found in the nasal cavity of dogs. Sexual and pedigree predisposition was not observed here. Among neoplasms of muscles and bones there was only a malignant oncological pathology. Rhabdomyosarcomas, fibrosarcomas, myxoid liposarcomas and other soft tissue sarcomas were diagnosed in different parts of the dog’s body. Bone neoplasms are represented by osteosarcomas. Dogs of large breeds were most often affected and in most cases the hind limbs were affected. The predominant histological subtype was osteoblastic osteosarcoma.

Novel TBP-RET (TATA.binding protein-rearranged during transfection) fusion in a rare case of Skene gland adenocarcinoma: Sequencing unicorns

Novel TBP-RET (TATA.binding protein-rearranged during transfection) fusion in a rare case of Skene gland adenocarcinoma: Sequencing unicorns

MiR-96-5p, miR-134-5p, miR-181b-5p and miR-200b-3p heterogenous expression in sites of prostate cancer versus benign prostate hyperplasia\u2014archival samples study

MicroRNAs are involved in various pathologies including cancer. The aim of the study was to assess the level of expression of miR-96-5p, -134-5p, -181b-5p, -200b-3p in FFPE samples of prostate cancer, adjacent cancer-free tissue, and benign prostatic hyperplasia. Samples of 23 FFPE prostate cancer and 22 benign prostatic hyperplasias were dissected and HE stained. Compartments of tumor tissue and adjacent healthy glandular tissue were isolated from each sample using Laser Capture Microdissection. Total RNA was isolated from dissected tissues. Expression of miR-96-5p, miR-134-5p, 181b-5p, and miR-200b-3p was determined by real-time RT-qPCR method. The expression of miR-200b-3p was significantly higher in cancerous prostate: both in adenocarcinomatous glands and in the adjacent, apparently unaffected glands compared to BPH samples. The expression of miR-181b-5p was lower in in both prostate cancer tissues and adjacent tissue compared to BPH samples. Expression of miR-96-5p and miR-134-5p was lower in prostate cancer tissues compared to BPH. Levels of miR-96-5p, miR-134-5p, and 181b-5p negatively correlated with the Gleason score. Given further studies, miR-96-5p, miR-134-5p and especially miR-200b-3p and miR-181b-5p may differentiate BPH and PC.

Leptin Modulates the Metastasis of Canine Inflammatory Mammary Adenocarcinoma Cells Through Downregulation of Lysosomal Protective Protein Cathepsin A (CTSA).

Canine malignant mammary gland tumors present with a poor prognosis due to metastasis to other organs, such as lung and lymph node metastases. Unlike in human studies where obesity has been shown to increase the risk of breast cancer, this has not been well studied in veterinary science. In our preliminary study, we discovered that leptin downregulated cathepsin A, which is responsible for lysosomal-associated membrane protein 2a (LAMP2a) degradation. LAMP2a is a rate-limiting factor in chaperone-mediated autophagy and is highly active in malignant cancers. Therefore, in this study, alterations in metastatic capacity through cathepsin A by leptin, which are secreted at high levels in the blood of obese patients, were investigated. We used a canine inflammatory mammary gland adenocarcinoma (CHMp) cell line cultured with RPMI-1640 and 10% fetal bovine serum. The samples were then subjected to real-time polymerase chain reaction, Western blot, immunocytochemistry, and lysosome isolation to investigate and visualize the metastasis and chaperone-mediated autophagy-related proteins. Results showed that leptin downregulated cathepsin A expression at both transcript and protein levels, whereas LAMP2a, the rate-limiting factor of chaperone-mediated autophagy, was upregulated by inhibition of LAMP2a degradation. Furthermore, leptin promoted LAMP2a multimerization through the lysosomal mTORC2 (mTOR complex 2)/PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1)/AKT1 (Serine/threonine-protein kinase 1) pathway. These findings suggest that targeting leptin receptors can alleviate mammary gland cancer cell metastasis in dogs.

The Stage-Specific Plasticity of Descending Modulatory Controls in a Rodent Model of Cancer-Induced Bone Pain.

Simple SummaryThe mechanisms that underlie pain resulting from metastatic bone disease remain elusive. This translates to a clinical and socioeconomic burden—targeted therapy is not possible, and patients do not receive adequate analgesic relief. The heterogeneous nature of metastatic bone disease complicates matters. Early stage cancers are molecularly very different to their late stage counterparts and so is the pain associated with early stage and advanced tumours. Thus, analgesic approaches should differ according to disease stage. In this article, we demonstrate that a unique form of brain inhibitory control responsible for the modulation of incoming pain signals at the level of the spinal cord changes with the progression of bone tumours. This corresponds with the degree of damage to the primary afferents innervating the cancerous tissue. Plasticity in the modulation of spinal neuronal activity by descending control pathways reveals a novel opportunity for targeting bone cancer pain in a stage-specific manner.Pain resulting from metastatic bone disease is a major unmet clinical need. Studying spinal processing in rodent models of cancer pain is desirable since the percept of pain is influenced in part by modulation at the level of the transmission system in the dorsal horn of the spinal cord. Here, a rodent model of cancer-induced bone pain (CIBP) was generated following syngeneic rat mammary gland adenocarcinoma cell injection in the tibia of male Sprague Dawley rats. Disease progression was classified as “early” or “late” stage according to bone destruction. Even though wakeful CIBP rats showed progressive mechanical hypersensitivity, subsequent in vivo electrophysiological measurement of mechanically evoked deep dorsal horn spinal neuronal responses revealed no change. Rather, a dynamic reorganization of spinal neuronal modulation by descending controls was observed, and this was maladaptive only in the early stage of CIBP. Interestingly, this latter observation corresponded with the degree of damage to the primary afferents innervating the cancerous tissue. Plasticity in the modulation of spinal neuronal activity by descending control pathways reveals a novel opportunity for targeting CIBP in a stage-specific manner. Finally, the data herein have translational potential since the descending control pathways measured are present also in humans.

Outcomes of carcinoma ex pleomorphic adenoma compared to de novo adenocarcinoma of major salivary glands.

Carcinoma ex pleomorphic adenoma (CXPA) is a rare disease of the major salivary glands that remains poorly characterized. Our objective was to compare the clinical outcomes of patients with CXPA of the major salivary glands to those with de novo adenocarcinomas. Review of the NCDB between 2004 and 2016 to compare cases of CXPA and adenocarcinoma of major salivary glands. Demographics, clinical characteristics, and survival were analyzed. We identified 1181 patients with CXPA and 3326 patients with adenocarcinoma of major salivary glands. Adenocarcinomas presented with higher rates of nodal metastasis (54.7% vs. 30.4%, p < .001). Five-year survival of adenocarcinoma (55.8%) was worse than that of CXPA (68.5%, p < .001). When stratified by nodal status, there was no significant difference in 5-year survival between CXPA and adenocarcinoma node-negative (75.3% vs. 71.6%, respectively) and node-positive (40.4% vs. 36.1%, respectively) patients. CXPAs of the major salivary glands present at an earlier stage with lower rates of regional metastasis compared to adenocarcinomas. After controlling for lymph node metastases, the outcomes are quite similar.

Brunner's Gland Adenocarcinoma in an Aged Western Gorilla (Gorilla gorilla)

A 50-year-old male western gorilla (Gorilla gorilla) presented with severe bradypragia, anorexia and vomiting. Despite continuous administration of antiphlogistic analgesic drugs and supportive care, the animal died and was submitted for post-mortem examination. Macroscopically, a large mass was located in the duodenum. The mucosal surface of the duodenum was irregular and thickened, and the lumen narrowed. The duodenal lesion was identified as a tubular adenocarcinoma and the neoplastic cells were strongly positive for cytokeratin AE1/AE3, cytokeratin 7, cytokeratin 19 and mucin-6 protein. Ultrastructurally, the apical cytoplasm of neoplastic cells had electron dense granules and apical microvilli. This is the first reported case of Brunner's gland adenocarcinoma in a gorilla.

Cancer stem cell markers in adenocarcinoma of the salivary glands - reliable prognostic markers?

PurposeAdenocarcinoma of the salivary glands is of low incidence and a broad range of histopathological subtypes. Cancer stem cell markers (CSC) might serve as novel prognostic parameters. To date, only a few studies examined the expression of CSC in adenocarcinoma of the salivary glands with diverging results. To further investigate the reliability in terms of prognostic value, a histopathological analysis of CSCs on a cohort of patients with adenocarcinomas of the major salivary glands was performed.MethodsTumor samples of 40 consecutive patients with adenocarcinoma of the major salivary gland treated with curative intend at one tertiary center were stained with the CSCs ALDH1, BMI-1, CD44, Nanog, and SOX2. Expression of these markers was correlated with clinicopathological parameters and survival estimates.ResultsCorrelation of high expression of ALDH1 with higher grading (p < 0.001) and high expression of CD44 with the localization of the neoplasm (p = 0.05), larger tumor size (p = 0.006), positive pN-category (p = 0.023), and advanced UICC stage (p = 0.002) was found. Furthermore, high expression of SOX2 correlated with a negative perineural invasion (p = 0.02). No significant correlation of any investigated marker with survival estimates was observed.ConclusionIn conclusion, our study did not find a significant correlation of the investigated CSCs with survival estimates in adenocarcinoma of the major salivary glands. Recapitulating the results of our study in conjunction with data in the literature, the CSCs ALDH1, BMI-1, CD44, Nanog, and SOX2 do not seem to serve as reliable prognostic parameters in the treatment of adenocarcinoma of the salivary glands.

S2920 Oxyntic Gland Adenoma of the Stomach; A Case Study of an Under-Reported Entity

INTRODUCTION: Oxyntic gland adenoma (OGA), also known as gastric adenocarcinoma with chief cell predominance is a rare entity, with incidence and prevalence data unknown. Given its rarity, we present a case of OGA incidentally found on EGD in a patient with complaints of dyspepsia. CASE DESCRIPTION/METHODS: A 58-year-old female with a history of smoking presented to the GI clinic for colorectal cancer screening. On presentation, ROS was only notable for dyspepsia not related to food intake or exercise. Her physical exam was unremarkable. She was scheduled for both colonoscopy for cancer screening and EGD for evaluation of dyspepsia. Colonoscopy was negative for cancer. EGD showed a solitary papule in the gastric fundus (Figure 1). The papule was raised, pale/white in color, 4 mm in diameter, and had a highly vascularized base. The papule was completely excised with cold biopsy forceps. Pathological analysis was notable for a completely resected papule without evidence of intestinal metaplasia. Further analysis revealed that the papule was composed of fundic gland mucosa, with chief cells predominating and low-grade cytologic features consistent with an oxyntic gland adenoma (Figures 2 and 3). DISCUSSION: OGA is characterized as a benign, solitary, polypoid growth, usually located in the fundus and less often in the cardia of the stomach. Prior studies have explored the histological patterns of these polyps and have defined them as either chief cell predominant, or a mixture of chief and parietal cells. The nomenclature is disputed as multiple names have been proposed for a similar histological description including: chief cell hyperplasia, chief cell hamartoma, and oxyntic gland adenocarcinoma with chief cell predominance. The last is a misnomer as these polyps lack atypical features such as mucous gland cells or foveolar epithelium. Additionally, they do not invade through the submucosa, as seen in other carcinomas. As some pathologists and gastroenterologists are still unfamiliar with the clinical and histological presentation of OGA, we highlight this rare finding for further discussion of its proper nomenclature and a better understanding of etiology, incidence, and prevalence in the United States.Figure 1.: Endoscopic View of Polyp (Encompassed in Black Circle).Figure 2.: Full Slice of Polyp revealing Fundic Type Mucosa Containing Oxyntic Gland Adenoma.Figure 3.: 200x Zoomed view of Fundic Mucosa with Oxyntic Gland Adenoma (Black Arrow points to normal Oxyntic gland and White arrows point to Oxyntic gland with Chief cell predominance).

An LCM-based genomic analysis of SPEM, Gastric Cancer and Pyloric Gland Adenoma in an Asian cohort

Spasmolytic polypeptide-expressing metaplasia (SPEM) and pyloric gland adenoma (PGA) in the stomach are metaplastic and neoplastic lesions, respectively, in which gastric body glands are replaced by pyloric glands. The aim of this study was to evaluate the genomic profile of SPEM and compare it with intestinal-type gastric cancer (GC) and PGA. Thirteen gastrectomies showing PGA with or without dysplasia, GC and SPEM were retrospectively selected. MUC5AC, MUC6, gastrin, and TFF2 IHC were performed. Lesions were subjected to laser capture microdissection followed by DNA extraction. Forty-three DNA samples were extracted from PGA without cytological dysplasia, PGA with low-grade and high-grade dysplasia and pyloric gland adenocarcinoma, GC, SPEM, and adjacent normal tissue from the body of the stomach and were subjected to exome sequencing for 49 genes that are commonly dysregulated in GC. Sanger sequencing was performed for confirmation. Twenty nonsynonymous mutations were identified in SPEM, and none of these were frameshifts or indels. PGA with or without cytological dysplasia showed a significantly higher number of mutations compared with SPEM. As cytological dysplasia increased from no dysplasia to dysplasia in PGA, the percentage of frameshift mutations, indels, and missense variations increased. Further missense or frameshift mutations were observed in the KRAS, APC, TP53, and CTNNB1 genes in the PGA group. In GC, mutations were observed in the TP53 gene (p.Arg248Gln). Missense mutations in the MUC5AC, KRAS, BRAF, and EZH2 genes were common between SPEM and GC. SPEM showed fewer genomic variations than GC and PGA, and was genomically distinct from the pyloric epithelium in PGA. Stepwise progression of PGA from PGA without dysplasia to PGA with dysplasia/adenocarcinoma was associated an increase in mutations. SPEM appears to be more genomically similar to GC than PGA.

Primary adenocarcinomas of the vulva and related structures: An enigmatic and diverse group of tumors✰.

Approximately half of adenocarcinomas that involve the vulva are secondary, either through direct extension or metastases from elsewhere. Primary vulvar adenocarcinomas are rare and encompass a diverse array of neoplasms that are nominally classified based on the presumed tissue or organ of origin, the tumoral phenotype, or both. In this review, we summarize the clinicopathologic features of adenocarcinomas that originate from the vulva and related structures, including the terminal urethra. Adenocarcinomas of this region encompass lesions that are defined by their primary site (such as adenocarcinomas of the Bartholin gland, which by definition must be in the region of the Bartholin gland), histomorphology and immunophenotype (such as clear cell carcinoma and adenocarcinoma of intestinal [cloacogenic] type), or both (such as adenocarcinoma of skene gland origin, which is associated with that specific organ but which also displays a distinctive phenotype that is similar to the phenotype of high grade prostatic adenocarcinoma). Other types, such as mammary-type adenocarcinomas, are presumed to originate from the putative mammary-like glands of the vulva and display a spectrum of pathologic features that are similar to their mammary counterparts. Similarly, vulvar carcinomas of sweat gland origin are pathologically similar to their counterparts in the non-vulvar skin and include a variety of cutaneous adnexal-type malignancies such as apocrine adenocarcinoma and eccrine adenocarcinoma. Some tumors, such as adenoid cystic carcinoma, may represent a Bartholin gland adenocarcinoma, a carcinoma of sweat gland origin, or a carcinoma arising from extramammary Paget disease (EMPD), depending on the context. Invasive carcinomas of various types have been reported in 7-12.7% of EMPD, and these are likely the most common primary glandular malignancy of the vulva. Occasional vulvar adenocarcinomas have been reported to be HPV-associated, although this association has not been established for the broader group of vulvar adenocarcinomas. Rare adenocarcinomas are not classifiable by the aforementioned nosologic scheme, and are designated as vulvar adenocarcinoma NOS.