Glandular Component Research Articles

The significance of the immunohistochemical method in diagnosing atypical endometrial polyps as manifestations of localized hyperplasia

The article explores the role of immunohistochemical methods in diagnosing atypical endometrial polyps as manifestations of localized hyperplasia. Endometrial polyps are a widespread pathology among women of reproductive age, frequently accompanied by hyperplastic tissue changes. The aim of the work was to investigate the expression of diagnostic markers in endometrial polyps, which may be manifestations of local endometrial hyperplasia, with the aim of improving differential diagnosis in their atypia.. The research material consisted of histological samples from 37 patients aged 38 to 52 with abnormal uterine bleeding, treated at a clinical hospital in Dnipro. The methods included histological tissue analysis, immunohistochemical studies using a panel of antibodies, and statistical data analysis. Antibodies targeting markers such as ER, PR, PAX-2, PAX-8, PTEN, Ki-67, p16, and p53 were used to evaluate proliferative activity and the degree of tissue atypia. The results showed that polyps associated with atypical hyperplasia are characterized by complex morphological changes, including abnormal glandular architecture, stromal atypia, and increased mitotic activity in both glandular and stromal components. Epithelial differentiation of tubal, mucinous, or mixed types was frequently observed. More than half of the cases exhibited partial atypical changes, while diffuse atypia was noted in fewer instances. The control group of glandular-fibrous polyps with hyperplasia without atypia demonstrated low mitotic activity and no cellular atypia. Immunohistochemical studies confirmed the high sensitivity of markers in identifying pathological chan­ges, particularly in diagnostically challenging cases. The conclusions emphasize that immunohistochemistry is an effec­tive tool for detecting endometrial atypia, and the diagnosis of atypical polyps should be based on a comprehensive analysis of morphological and molecular changes. Polyps associated with hyperplasia and atypia require further observation due to the risk of recurrence and potential malignant transformation. Utilizing markers such as PAX-2, PTEN, and Ki-67 enhances diagnostic accuracy. Additional studies are needed to develop more reliable risk stratification models.

Deep rectal endometriosis mimicking colorectal cancer – Case report

Introduction: Deep infiltrating endometriosis(DIE) can be diagnosed if endometrial-like tissueinvades visceral organs deeper than 5 mm. DIE ismostly found in the rectum and can bemisdiagnosed with colorectal cancer.Case presentation: A 43-year-old woman came toour clinic with suspected colorectal cancer,complaining about alternating diarrhea andconstipation, tenesmus, and abdominal bloating.Colonoscopy and imaging test revealed around 3cm lesion, and histopathology of the biopsyrevealed low-grade dysplasia. Partial resection of the intestine with lesion was performed and thefinal diagnosis confirmed deep rectalendometriosis.Conclusion: Histopathological diagnosis can bedifficult because of the possible coexistence ofendometriosis and atypical glandular components inthe intestines. DIE should be taken intoconsideration as one of the probable diagnoses inpatients with a mass in the rectum.

Perianal Paget Disease With an Enteric Phenotype and Associated In-Situ/Dysplastic Glandular Component: Report of a Potentially Novel Entity and Review of the Literature.

Extramammary Paget disease is an uncommon cutaneous malignancy that primarily affects areas rich in apocrine glands. Here, we aim to present an 84-year-old woman with a distinctive perianal neoplastic process comprised of conventional Paget disease with an intertwined in-situ glandular component. Rare foci of glands embedded in pools of mucin were also identified in the most recent excision, consistent with mucinous adenocarcinoma. Immunohistochemical staining demonstrated an enteric phenotype of the tumor cells, with expression of keratin 20, caudal type homeobox transcription factor 2 (CDX2), and special AT-rich sequence binding protein 2 (SATB2) (patchy, weak); keratin 7 and BerEP4 staining were also noted. Molecular analysis via next generation sequencing revealed pathogenic variants in ERBB2, TP53, and SF3B1. Given the unique histomorphology and immunohistochemical staining pattern, suspicion for a colorectal primary tumor was high, however; extensive workup including imaging, testing for tumor markers, and colonoscopic evaluation has not identified any other lesion thus far. Multiple biopsies and excisions in the area demonstrated recurrent disease over a 4-year span; with no evidence of deep invasion or metastasis. This tumor appears to be exceptional among reports in the literature given its extensive in-situ glandular component; and we are not aware of any documented SF3B1 mutation to date. Disease recurrence in this patient highlights the need for clinical vigilance. Defining the molecular profile in these lesions can also be useful, particularly when assessing potential treatment options for advanced disease.

Comprehensive Clinicopathological and Immunohistochemical Analysis of Human Papillomavirus-independent Squamous Cell Carcinoma and Adenosquamous Carcinoma of the Uterine Cervix.

Human papillomavirus-independent (HPVI) squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the uterine cervix are extremely rare. The aim of this study was to comprehensively describe the clinicopathological features, patient outcomes, and immunophenotypes of HPVI SCC and ASC. We found four and two patients with HPVI SCC and ASC, respectively, and reviewed their electronic medical records and pathology slides. We also performed immunostaining for p16 and p53. All except one patient underwent surgery. Two, one, and one patients with HPVI SCC were diagnosed as having IIIC1, IVA, and IVB diseases, respectively. Two patients with HPVI SCC experienced recurrences, and died of disease within nine months after treatment initiation. Both patients with HPVI ASC developed lung metastasis at four months post-operatively. HPVI SCCs and the squamous component of HPVI ASCs showed keratinizing, condylomatous, or poorly differentiated morphology. The glandular component of HPVI ASCs was gastric-type endocervical adenocarcinoma. None of the six tumors exhibited block positivity for p16. Two HPVI SCCs and one HPVI ASC displayed aberrant p53 expression. HPVI SCC is a rare and aggressive cervical malignancy that presents initially as advanced-stage disease with poor prognosis. Although the patients with initial stage I and II HPVI ASC were treated with curative intent, distant metastases appeared in the lungs during the early course of treatment. Further investigations are necessary to clarify the association between histological features and clinical behavior of HPVI ASC.

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis.

The Mangshan pit viper, Protobothrops mangshanensis, is a rare, highly endangered snake native to the mountainous regions of Hunan Province in China. Snakes possess abdominal scent glands, which have been chemically studied in several species. These glands can contain various lipids and peptides, but very often also complex mixtures of carboxylic acids. We report here the occurrence of novel methyl-branched unsaturated acids found in the secretions of six captive individuals living in a zoo. The structures of these compounds, 4.6-dimethylalk-5-enoates in a homologous series from C11-C16, were characterized by GC-MS and GC-IR analysis and various microderivatization reactions including hydrogenation and esterification leading to methyl and pyridylmethyl esters. In addition, dimethyloxazoline formation helped to localize the double bond. The synthesis of methyl 4,6-dimethyldodec-5-enoate allowed the correct assignment of structures and showed the (E)-configuration of the double bond for the major naturally occurring diastereomers. These acids occur in small amounts compared to the major glandular components, cholesterol, and 1-O-hexadecylglycerol, as well as other common long-chain alcohols and amides. Although a general defensive function has been proposed for snake abdominal scent glands, the specific chemistry and moderate amounts of acids reported here may suggest a function in chemical signaling for the Mangshan pit viper. In addition, proline-containing diketopiperazines were identified for the first time in snake scent glands, although an artificial formation from amino acids likely present in the secretion cannot be excluded.

Primary Malignant Peripheral Nerve Sheath Tumor in the Liver with Glandular Differentiation

Abstract Introduction/Objective Malignant peripheral nerve sheath tumors (MPNST) most commonly affect the proximal extremities and paraspinal region. Primary hepatic MPNST is extremely rare. Here we report a primary hepatic MPNST with heterologous glandular differentiation in a patient with Neurofibromatosis type 1 (NF1). Methods/Case Report Review of the clinical features and histopathological findings of the resected specimen. A review of all the published cases of primary liver MPNST. Results (if a Case Study enter NA) A 69-year-old male patient with a history of NF1, Gastrointestinal Stromal Tumor and treated hepatitis C without pre-existed neurofibroma presented with jaundice. Imaging revealed an ill-defied hypodense mass in the left hepatic lobe. A segmentectomy of the liver revealed an infiltrating 10 cm heterogenous yellow-white-pink slightly firm tumor with 5% necrosis. The tumor showed biphasic histology composed of predominantly spindle cells and clusters of glandular components. The spindle cells showed fascicular growth pattern with vaguely marbled appearance. Focal osteoclast-like multinucleated cells were seen. The glands were well defined, mostly appeared to be low grade, and lined by cuboidal to columnar cells, with a bile-duct and intestinal-like appearance. However, focal malignant glands with hepatic differentiation were also noted. Immunohistochemistry showed patchy loss of H3K27me3 in the spindle cells. The glandular cells were positive for AE1/AE3, CK7 and CK20. The tumor cells showed rare reactivity to TLE1 and were negative for S-100, SOX10, CD34, CD117 and DOG1. These findings supported the diagnosis of MPNST with glandular differentiation. 13 cases of primary MPNST of liver have been reported, and only one case described epithelioid differentiation. Conclusion The differential diagnoses of a primary hepatic biphasic tumor include sarcomatoid carcinoma, carcinosarcoma, biphasic synovial sarcoma and MPNST. Our case illustrates a rare biphasic hepatic MPNST. The morphology and loss of H3K27me3 expression by immunohistochemistry in a patient with NF1 support this challenging diagnosis.

STUDY OF THE ENDOMETRIAL GLANDULAR COMPONENT IN WOMEN WITH FERTILITY AND POST-COVID SYNDROME IN ANAMNESIS

The aim. To increase the effectiveness of the endometrial endometrial glandular component study in women with infertility and post-COVID syndrome. Materials and methods. A study was conducted at the State institution "Carpathian Human Reproduction Centre" of the Ministry of Health of Ukraine in the period from 2022 to the end of the first half-year of 2024. There were included 80 women in the experimental group and 40 women in the control group. The selection criterion for the study group was the presence of documented post-COVID syndrome (COVID-19 symptoms lasted longer than 12 weeks). The selection criterion for the control group was the absence of confirmed SARS-CoV-2 virus in the anamnesis. The following characteristics were common for both groups: diagnosed infertility, age – 25-42 years, written informed consent of the patient to participate in the study. The criteria for exclusion from the study for patients of both groups were: detection of human immunodeficiency virus, viral hepatitis, other sexually transmitted infections, tuberculosis of the genitourinary system, malignant diseases, mental disorders that make communication with person impossible or the awareness of written consent is questioned. General clinical and laboratory examinations and transvaginal sonographic examination of the pelvic organs were performed in the middle stage of proliferation and the middle stage of secretion according to the calendar calculation the menstrual cycle. A visually guided diagnostic office hysteroscopy was performed with the collection of biological material from the most changed areas (biopsies were collected in the middle stage of proliferation and the middle stage of secretion in different menstrual cycles). A routine staining of samples with hematoxylin-eosin, morphometry of the endometrial glandular component, optical determination of the number of glands and measurement of the diameter of the lumen of the studied glands, considering the possible measurement error, glandular-stromal ratio, functional activity of the glands, were performed. A histochemical PAS-reaction to identify the glycoproteins of gland secretions and immunohistochemical staining of the glandular epithelium to express the receptivity of the glands to estrogen and progesterone were carried out. The results. After conducting the PAS-reaction, a higher secretion was noted in the glands than in the stroma of the endometrium during the period of the implantation window in both cohorts. No statistically significant difference between the groups in the amount of glycogen of the middle proliferative phase in the glands (p=0.315) or stroma (p=0.486). Glycogen in this phase was visualized of very small granules and coarse granules, without their formation in clusters. A decrease in secretion was established in 16 (40%) patients of the control group and 49 (61.3%) women of the experimental group in the middle secretory phase, which was statistically significant (p=0.028). A decrease in the expression level of the progesterone receptor in the middle secretory phase was found to be significantly more pronounced in the experimental group than in the control group (р=0.044). Conclusions. In the middle secretory phase, a decrease in the secretion of glycogen by the endometrial glands and a decrease in the level of expression of the progesterone receptor in endometrial biopsies were detected by the routine histological, histochemical techniques and immunohistochemical stude in women with infertility and a history of post-COVID syndrome.

Stress-induced phosphoprotein 1 expression in the endometrium and myometrium of patients with adenomyosis

BACKGROUND: The study of stress-induced phosphoprotein 1 in the pathogenesis of adenomyosis is not only of theoretical interest, but this protein may be also considered as a potential biomarker of the disease. AIM: The aim of this study was to evaluate stress-induced phosphoprotein 1 expression in the endometrium and heterotopic foci in women with isolated adenomyosis and in combination with benign hyperproliferative diseases of the reproductive organs. MATERIALS AND METHODS: This study enrolled 66 women aged 21 to 47 years (34.9 ± 6.7 years), including 49 patients with adenomyosis and 17 women in the control group. The main group was divided into subgroups depending on the concomitant hyperproliferative disease such as isolated adenomyosis (n = 36), adenomyosis combined with uterine fibroids (n = 8), and adenomyosis combined with endometriosis (n = 5). The patients underwent endometrial biopsy and multifocal myometrial biopsy. Histological and immunohistochemical studies were performed to assess stress-induced phosphoprotein 1 expression in the glandular and stromal components of the endometrium and ectopic endometrial tissue within the uterine myometrium. RESULTS: We found increased stress-induced phosphoprotein 1 expression in the adenomyosis lesion compared to that in the myometrium of the control group, regardless of the phase of the menstrual cycle (p 0.001). When studying stress-induced phosphoprotein 1 expression in the endometrium of the main group in the proliferative phase of the menstrual cycle, an increase was found, but the differences were not significant. Stress-induced phosphoprotein 1 expression in the secretory phase of the menstrual cycle was higher in the glandular component of the endometrium of patients with adenomyosis compared to the levels in women in the control group (p 0.05). CONCLUSIONS: The increased expression of stress-induced phosphoprotein 1 in the glandular component of the adenomyosis lesion indicates a potential role of the protein in the pathogenesis of the disease. However, further research is needed to determine its practical significance.

Abstract C070: Keratin 17 and GATA6 correlate with diffusely infiltrative versus gland-forming components of PDAC: Uncovering the transitional state in pancreatic ductal adenocarcinoma

Abstract Purpose: Optimization of pancreatic ductal adenocarcinoma (PDAC) patient survival will depend on advancing our understanding of the mechanisms governing tumor cell plasticity and effectively mitigating their invasive and metastatic capabilities. This study aims to investigate the correlation of cancer biomarkers crucial to these processes by integrating molecular signatures with histopathological characteristics using single-cell RNA sequencing (scRNA-seq) and multiplexed IHC/IF. Methods: Single-cell RNA sequencing (scRNA-seq) data from a comprehensive dataset of over 53,000 PDAC cells and validation of lead targets through 14-plex immunofluorescence, using a customized MICS platform (Miltenyi Biotec) and dual color IHC were employed to assess protein expression of defining biomarkers of basal and classical subtypes of PDAC including Keratin 17 (K17) and GATA6. Results: scRNAseq analysis revealed distinct patterns of K17 and GATA6 expression, highlighting intratumoral heterogeneity among PDAC tumors. Specifically, populations of cells expressing K17+/GATA6+ and K17+/GATA6- exhibited significant enrichment in pathways associated with invasion and cell migration, including PI3K/Akt/mTOR, TGF-β, and epithelial-mesenchymal transition (EMT) signaling. Conversely, GATA6-/K17- cells demonstrated enrichment in biosynthetic and metabolic pathways that govern cell cycle regulation. Additionally, mIF data assessment revealed correlations between histomorphological patterns and dynamic shifts in K17 and GATA6 expression within PDAC tumors. Diffusely infiltrative tumor cells (DITCs) uniformly expressed K17, contrasting with the gland-forming components (GFCs) of PDAC, which showed enrichment in GATA6 and sporadic expression of K17. E-cadherin, a key adhesion marker, exhibited the highest expression levels in the glandular and solid components of PDAC, underscoring their epithelial characteristics. Conversely, vimentin, a marker typically associated with epithelial-to-mesenchymal transition (EMT), was significantly expressed in DITCs, suggesting a mesenchymal-like phenotype in these infiltrative cells. Dual color IHC further validated these findings, reinforcing the correlation between morphologic plasticity and the expression patterns of K17 and GATA6, emphasizing their potential to distinguish distinct tumor cell populations within PDAC. Conclusions: These insights suggest that the interaction between these markers may indicate a distinct biological state characterized by altered cellular metabolism and potentially different therapeutic vulnerabilities. The robust association between K17 expression and diffusely infiltrative tumor cells underscores its potential as a marker for the most aggressive forms of this disease. Our results highlight the heterogeneous nature of PDAC and emphasize the critical importance of understanding these molecular distinctions in histopathological contexts to develop targeted therapies aimed at improving patient survival. Citation Format: Lyanne A Delgado- Coka, Brian Nelson, Michael Horowitz, Shayan Sarkar, Natalia Marchenko, Scott Powers, Luisa F Escobar-Hoyos, Kenneth Shroyer. Keratin 17 and GATA6 correlate with diffusely infiltrative versus gland-forming components of PDAC: Uncovering the transitional state in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C070.

A Case of FIBROADENOMA Cured with Individualized Homoeopathic Medicine- Evidence Based Homoeopathy

Introduction: Fibro-adenomas are the most common benign tumor of female breast having distinct clinical and Histopathological findings. This case report of fibroadenoma highlights clinical presentation along with proper investigation reports like ultrasound, individualized homoeopathic treatment provided and ongoing follow-up. Palpable mass, nodular swelling, pain, redness and changes in the breast appearance along with fibrous and glandular tissue components are emphasized for proper diagnosis. Homoeopathic literature shows that case of fibro-adenoma had been successfully treated with individualized homoeopathic medicine. Individualized homoeopathic approach to breast fibro-adenoma ensures improved outcomes in mental, emotional as well as physical wellbeing. Case summary: The case report presented here wasa 23 year old female patient, from Repertory OPD, Homoeopathy Hospital, North Eastern Institute of Ayurveda and Homoeopathy, Shillong. The patient was treated with individualized homoeopathic medicine (Phosphorous30, 200) for one year, with significant improvement and progressively decreases in size of tumor.

Application and Evaluation of the Antifungal Activities of Glandular Trichome Secretions from Air/Sun-Cured Tobacco Germplasms against Botrytis cinerea.

The secretions of the glandular trichomes of tobacco leaves and flowers contain abundant secondary metabolites of different compounds, such as cebradanes, labdanes, and saccharide esters. These secondary metabolites have shown interesting biological properties, such as antimicrobial, insecticidal, and antioxidant activity. In this study, 81 air/sun-cured tobacco germplasms were used as experimental materials. Quantitative and qualitative analyses of the glandular secretion components were conducted using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF MS) and gas chromatography-mass spectrometry (GC-MS). The ethanol extracts of glandular trichomes from tobacco leaves and flowers were evaluated for antifungal activity against the fungus Botrytis cinerea using the mycelial growth rate method. Orthogonal Partial Least Squares (OPLS) analysis was then performed to determine the relationship between the trichome secretion components and their anti-fungal activity. The results showed significant differences among the antifungal activities of the tested ethanol extracts of tobacco glandular trichomes. The inhibition rates of the upper leaves and flower extracts against B. cinerea were significantly higher than those of the middle and lower leaves, and 59 germplasms (73.75% of the tested resources) showed antifungal rates higher than 50%, with four germplasms achieving a 95% antifungal rate at the same fresh weight concentration (10 mg/mL). The OPLS analysis revealed that the antifungal activity was primarily associated with alpha-cembratriene-diol (α-CBT-diol (Peak7)) and beta-cembratriene-diol (β-CBT-diol (Peak8)), followed by sucrose esters III (SE(III)) and cembratriene-diol oxide. These findings help identify excellent tobacco germplasms for the development and utilization of botanical pesticides against fungi and provide a theoretical reference for the multipurpose utilization of tobacco germplasms.

Rare Histologic Imitator Central Mucoepidermoid Carcinoma Arising from Glandular Odontogenic Cyst of the Mandible: Case Report with Updated Review of Literature.

Central mucoepidermoid carcinoma is a relatively rare salivary gland tumour of the jawbone. Glandular odontogenic cyst is another unique odontogenic developmental cyst characterised by glandular differentiation. Both entities share several histological characteristics, and a pre-existing Glandular odontogenic cyst can evolve into Central mucoepidermoid carcinoma. Case 1: A 56-year-old male presented with chief complaint of swelling in lower left facial region since 1 year. Histopathology revealed multicystic compartments resembling mucoepidermoid carcinoma, but strong positive expression of Cytokeratin 13 upon immunohistochemistry helped us in rendering the final diagnosis as Glandular odontogenic cyst Case 2: A 34-year-old female presented with a lesion on right side of face. Histologically, the biopsy specimen revealed both typical findings of a Glandular odontogenic cyst component and a recognizable component of Mucoepidermoid carcinoma. The results from cytokeratin profiling demonstrated that, while both Mucoepidermoid carcinoma and Glandular odontogenic cyst expressed Cyokeratins 7, 18, and 19. Cytokeratin 13 was interestingly exclusively expressed in Glandular odontogenic cyst. Present case findings showed that central mucoepidermoid carcinoma and Glandular odontogenic cyst may be part of the same disease spectrum. However, because the expression profile of Cytokeratin13 in mucoepidermoid carcinoma and Glandular odontogenic cyst was so diverse, it can be used to differentiate both.

Mixed adenoma-neuroendocrine tumor of the stomach: analysis of nine cases with literature review.

Mixed adenoma-neuroendocrine tumor (MANET) comprises adenoma and well-differentiated neuroendocrine tumor (NET) components. Given the limited information on this due to its rarity, we aimed to clarify the clinicopathologic features and optimal management of gastric MANETs in a case series and literature review. Nine patients with gastric MANETs, including eight male and one female patient (mean age, 72years), were identified from the institutional pathology archive. Endoscopically, the tumors appeared as flat elevated lesions with sizes ranging from 0.8 to 4.4cm. One patient had familial adenomatous polyposis, and no patient had autoimmune gastritis. All MANETs developed in the gastric body mucosa exhibiting chronic metaplastic atrophic gastritis. The glandular components were intestinal-type low-grade adenoma, and focal high-grade dysplasia was also recognized in three cases. The NET component was in middle/deep lamina propria in six cases and confined to deep lamina propria in the remaining three cases. Minimal cytologic atypia was found in the NET component, with no recognizable mitosis and a Ki-67 labeling index of < 2%. The NET component mostly showed diffuse positivity for serotonin and CDX2, suggesting that it consists of enterochromaffin cells. Diffuse p53 immunostaining was observed only in the high-grade adenomatous component of one case. No recurrence was observed during the follow-up period of 2-94months. Correct distinction between the NET and poorly differentiated carcinoma components is crucial to prevent overtreatment of gastric MANETs. Considering its indolent nature, endoscopic resection is the primary recommendation for gastric MANETs as well as for pure adenomas.

Endometrial Tumors with “Shadow Cells” Intimate a Neoplastic Potential for Morules or Their Progenitors in β-Catenin Mutated Endometrial Adenocarcinomas.

Background : Several features are shared by endometrial morules and pilomatrixoma-like endometrial carcinomas including CDX-2 and β-catenin nuclear staining, absence of p63 and p40 nuclear staining, and a unique form of endepithelial differentiation that produces so-called shadow cells. Both endometrial morules and pilomatrixoma-like endometrial carcinomas may be associated with low-grade endometrioid adenocarcinoma. Methods : We present 11 fully staged endometrioid endometrial adenocarcinomas that showed extrauterine metastases (Stages III and IV), morules, shadow cell differentiation, and nuclear β-catenin positive immunohistochemical staining (both in morules and in adjacent malignant glandular cells). Results : All intrauterine adenocarcinomas had at least focal components of grade 1 endometrial adenocarcinoma and morules and showed nuclear β-catenin immunostaining in morules and in adjacent malignant glandular cells. 10 cases were stages III and IV endometrial cancers, and one, initially diagnosed as grade 1 stage II endometrioid endometrial adenocarcinoma, rapidly recurred in the retroperitoneum as a nuclear β-catenin positive pilomatrixoma-like tumor without an obvious glandular component. Two positive lymph node dissections showed metastatic adenocarcinoma with malignant glands, morules and shadow cells. Five cases showed at least focal components of morphologically divergent high-grade tumor with foci resembling malignant pilomatrixoma. Extrauterine “shadow cell granulomas” were detected in 8 cases. Conclusion : Metastatic nuclear β-catenin positive endometrial adenocarcinomas with morules can metastasize and show pilomatrixoma-like tumor foci. This highlights the ability of these cancers to evolve into “other-than-glandular” carcinomas. Furthermore, because of their shadow cell features, we speculate that endometrial morules are not simply inert “epitumoral” elements; but that either they or the population of progenitor cells from which they eventuate harbors an abnormal β-catenin gene that may endow endometrial adenocarcinomas with morules the capacity for progressive, divergent differentiation into a higher-grade matrix-producing tumor.

Efficacy of platinum chemotherapy agents in adenosquamous carcinoma of the pancreas.

e16317 Background: Adenosquamous carcinoma of the pancreas (ASCP) is an aggressive, infrequent subtype of pancreatic cancer that combines a glandular and squamous component and is associated with poor survival. Data regarding adjuvant therapy remain controversial. Methods: Patients with advanced PASC from 2005 to 2021 were consecutively included in this retrospective study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Results: Eighteen PASC patients treated surgically were included (median age, 69.3 years; males, 58.2%). All patients received adjuvant chemotherapy. Ten patients (55%) received newer platinum based regimen combination (FOLFIRINOX) and eight patients (45%) received gemcitabine-based regimens. Platinum based regimen as compared to gemcitabine regimen showed an improvement of overall response rate (42.5% and 12.3 %, p=0.001), PFS (median,10.4 versus 3.1 months, p=0.03) and OS (median, 15.8 vs 6.9 months, p=0.21).Multivariate analysis revealed that, among all patients (n=18), the following factors were independently predictive of poor survival: margin-positive resection (HR =3,15; 95% CI, 1.5-5.9; P&lt;0.001), lymph node involvement (HR =2.9; 95% CI, 1.7 -7.5; P=0.003), and lack of inclusion of a platinum agent in the adjuvant regimen (HR =2.6; 95% CI, 1.5 -4.9; P=0.035). Conclusions: Given the rarity of ASC, optimal management remains poorly defined, particularly in the postoperative period. Therapies based on platinum chemotherapeutics may be preferable to all other chemotherapy regimens.

Giant fibroepithelial breast polyp

Introduction: Fibroepithelial polyps are common benign skin lesionsrarely noted in the female nipple. In this location, they have the potentialto ulcerate and cause bloody discharge.Case history: A 55-year-old female patient presented to a breast clinicwith a left nipple lesion present since childhood. The patient self-reportedthat the lesion had increased in size. Clinical examination revealed a 9 ×7 cm lesion with a soft and pliable stem extending from the left nipple.Mammography from 2017 revealed this previously measured 6 × 6 cm.An excision biopsy under general anaesthetic preserving the nippleanatomy was undertaken on 18/8/23. There were no immediate or subsequentcomplications. The final histology demonstrated the excised specimenweighed 131 g and measured 90 × 70 × 60 mm with an 8 mm base.The specimen was processed and microscopically found to be a giantfibroepithelial polyp (FEP). The central core of the lesion was formed byexcessive collagen deposition. Normal dermal structures including bloodvessels were still present with no glandular component and there was noevidence of atypia or malignancy.Discussion: FEPs are benign dermal mesenchymal tumours also knownas acrochordons. They are noted most commonly on the neck, axilla,perineum, and thighs but have also been found in the vagina, vulva, orcervix and present in &lt; 2% of cases in the nipple area.FEPs rarely grow larger than 5 cm, with larger lesions rarely reportedin medical literature worldwide. It is possible to excise these lesions andpreserve the nipple anatomy with careful surgical planning.

Preliminary study of standardized semiquantitative method for ultrasonographic breast composition assessment

PurposeTo develop a classification tree via semiquantitative analysis for ultrasonographic breast composition assessment using routine breast ultrasonography examination images.MethodsThis study retrospectively enrolled 100 consecutive normal women who underwent screening mammography and supplemental ultrasonography. Based on sonographic breast composition, the patients’ breasts were classified as nondense or dense, which were correlated with mammographic breast composition. Ultrasonographic breast composition was classified based on the fibroglandular tissue (FGT) thickness-to-subcutaneous fat and retromammary fat (FAT) thickness ratio. In addition, the presence of a high glandular tissue component (GTC) in FGT or the presence of evident fat lobules in FGT was investigated. The cutoff point between the nondense and dense breasts was calculated from the area under the curve (AUC).ResultsAll cases with a high GTC were dense breasts, and all cases with evident fat lobules in the FGT were nondense breasts. The AUC of the FGT thickness-to-FAT ratio of all cases, the group without a high GTC, the group without evident fat lobules in the FGT, and the group without a high GTC or evident fat lobules in the FGT were 0.93, 0.94, 0.99, and 1, respectively.ConclusionThe presence of a high GTC indicated dense breasts, and the presence of evident fat lobules in the FGT represented nondense breasts. For the remaining cases, the cutoff point of the FGT thickness-to-FAT thickness ratio was 0.93 for ultrasonographic two-grade scale breast composition assessment with 100% accuracy.

Экспрессия ARID1a в эндометрии женщин репродуктивного возраста с аномальными маточными кровотечениями и ожирением

Objective. The aim of the study was to evaluate the expression of the proliferative marker ARID1a in endometrial biopsies of patients with abnormal uterine bleeding (AUB) and obesity and its role in the pathogenesis of endometrial dysfunction. Materials and methods. The study included 40 endometrial samples from patients of reproductive age with AUB-E: 20 from patients with AUB-E and obesity (group 1) and 20 from patients with normal body mass index (BMI) and AUB (group 2). 10 endometrial samples were obtained from healthy women of reproductive age, taken on the 2nd-3rd day of the menstrual cycle. All patients underwent histological examination according to the standard procedure. At the second stage, an immunohistochemical study of the ARID1a proliferation marker was performed using polyclonal rabbit antibodies to Anti-ARID1a (clone EPR13501-73) in standard dilution (1:500) according to the protocol of the manufacturer Abcam (Great Britain). The IBM SPSS Statistics v.26 program (IBM Corporation, USA) was used for statistical data analysis. To determine statistically significant differences between quantitative parameters with a normal distribution, one-factor analysis of variance (ANOVA) was used with the calculation of a 95% confidence interval followed by the post-hoc Games-Howell test for multiple comparisons. The differences were considered significant at p&lt;0.05. Results. ARID1a expression was evaluated in the glandular and stromal compartments of the endometrium. In the endometrial glands, the expression of ARID1a was statistically significantly higher in the first group of obese patients compared with the normal and control groups. In the endometrial stroma, the expression of the proliferative marker was higher in the main group compared with the control group. However, when comparing between groups within the main group, statistical significance in the level of expression was not achieved. Conclusion. The results obtained demonstrate the possible pathological effect of obesity on the structural and functional properties of the endometrium, which leads to delayed regeneration of the endometrium due to the glandular component and, consequently, to AUB-E.

PD-L1 expression in pancreaticobiliary adenosquamous carcinoma: a single-institution case series.

The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is a potent negative regulator of T-cell-mediated immune response that is upregulated in many neoplasms. Pancreaticobiliary adenosquamous carcinoma (PB-ASC) is an aggressive cancer that carries a poorer prognosis compared with pure pancreaticobiliary adenocarcinoma (PB-AC). To date, there is little published information regarding PD-L1 expression in PB-ASC. The aim of the study was to examine the relationship between PD-L1 expression and tumor-infiltrating lymphocytes in PB-ASC and PB-AC. We evaluated 15 PB-ASCs (10 pancreatic, 5 gallbladder) and 34 control PB-ACs (22 pancreatic ductal, and 12 gallbladder) for tumor expression of PD-L1 using anti-PD-L1 (E1L3N) antibody. All tumors were classified into three immune phenotypes: immune inflamed (II), immune excluded (IE), and immune desert (ID) according to the distribution of tumor-infiltrating lymphocytes in tumor tissues. The frequency of PD-L1 expression was significantly higher in PB-ASC (10/15; 66.7%) than in PB-AC (3/34; 8.8%). In PB-ASC, PD-L1 expression occurred exclusively in the squamous component in six cases, exclusively in the glandular component in one case, and in both the squamous and the glandular components in three cases. PD-L1 expression in PB-ASC was irrespective of the tumor immune status, whereas its expression in PB-AC was observed only in tumors with the II or IE phenotype. The ID phenotype was relatively rare (4/15; 26.7%) in PB-ASC compared with PB-AC (22/34; 65%; P=0.02). PB-ASCs are notably enriched in inflammatory response and showed significantly higher PD-L1 expression than PB-AC (P<0.001), suggesting a potential therapeutic role for immune checkpoint inhibitors in managing patients with PB-ASC.

A new model using deep learning to predict recurrence after surgical resection of lung adenocarcinoma

This study aimed to develop a deep learning (DL) model for predicting the recurrence risk of lung adenocarcinoma (LUAD) based on its histopathological features. Clinicopathological data and whole slide images from 164 LUAD cases were collected and used to train DL models with an ImageNet pre-trained efficientnet-b2 architecture, densenet201, and resnet152. The models were trained to classify each image patch into high-risk or low-risk groups, and the case-level result was determined by multiple instance learning with final FC layer’s features from a model from all patches. Analysis of the clinicopathological and genetic characteristics of the model-based risk group was performed. For predicting recurrence, the model had an area under the curve score of 0.763 with 0.750, 0.633 and 0.680 of sensitivity, specificity, and accuracy in the test set, respectively. High-risk cases for recurrence predicted by the model (HR group) were significantly associated with shorter recurrence-free survival and a higher stage (both, p < 0.001). The HR group was associated with specific histopathological features such as poorly differentiated components, complex glandular pattern components, tumor spread through air spaces, and a higher grade. In the HR group, pleural invasion, necrosis, and lymphatic invasion were more frequent, and the size of the invasion was larger (all, p < 0.001). Several genetic mutations, including TP53 (p = 0.007) mutations, were more frequently found in the HR group. The results of stages I-II were similar to those of the general cohort. DL-based model can predict the recurrence risk of LUAD and identify the presence of the TP53 gene mutation by analyzing histopathologic features.