The Premetastatic Lymph Node Niche in Gynecologic Cancer.

It has been suggested that a primary tumor can "prepare" the draining of lymph nodes to "better accommodate" future metastatic cells, thus implying the presence of a premetastatic lymph node niche. However, this phenomenon remains unclear in gynecological cancers. The aim of this study was to evaluate lymph-node draining in gynecological cancers for premetastatic niche factors, such as myeloid-derived suppressor cells (MDSCs), immunosuppressive macrophages, cytotoxic T cells, immuno-modulatory molecules, and factors of the extracellular matrix. This is a monocentric retrospective study of patients who underwent lymph-node excision during their gynecological-cancer treatment. In all, 63 non-metastatic pelvic or inguinal lymph nodes, 25 non-metastatic para-aortic lymph nodes, 13 metastatic lymph nodes, and 21 non-cancer-associated lymph nodes (normal controls) were compared for the immunohistochemical presence of CD8 cytotoxic T cells, CD163 M2 macrophages, S100A8/A9 MDSCs, PD-L1+ immune cells, and tenascin-C, which is a matrix remodeling factor. PD-L1-positive immune cells were significantly higher in the control group, in comparison to the regional and distant cancer-draining lymph nodes. Tenascin-C was higher in metastatic lymph nodes than in both non-metastatic nodes and control lymph nodes. Vulvar cancer-draining lymph nodes showed higher PD-L1 values than endometrial cancer and cervical cancer-draining lymph nodes. Endometrial cancer-draining nodes had higher CD163 values and lower CD8 values, compared to vulvar cancer-draining nodes. Regarding regional draining nodes in low- and high-grade endometrial tumors, the former showed lower S100A8/A9 and CD163 values. Gynecological cancer-draining lymph nodes are generally immunocompetent, but vulvar cancer draining nodes, as well as high-grade endometrial cancer draining nodes, are more susceptible to harboring premetastatic niche factors.

Epidemiology and Antimicrobial Resistance Patterns of Urinary Tract Infections: A Cross-Sectional Study from Southwestern Saudi Arabia.

Background: Urinary tract infections (UTIs) are a prevalent form of urinary tract diseases affecting individuals of all ages and genders. In the Kingdom of Saudi Arabia (KSA), UTIs are a significant burden on the healthcare system, comprising 10% of all infections and ranking as the second leading cause of emergency department admissions. Despite this, limited research has been conducted in Saudi Arabia, particularly in Jazan Province, located in the southwestern region. Methods: This retrospective, cross-sectional study encompassed individuals with positive urine cultures who sought care at a tertiary hospital in Jazan between January 2022 and March 2023. A standardized data collection form was utilized to retrieve relevant information from microbiology lab test results and patients' electronic medical records. Variables such as sex, urine sample collection date, bacterial isolates, antibiotic sensitivity, and resistance were collected using the data collection form. Data were analyzed using SPSS software, version 23.0 (IBM Corp., Armonk, NY, USA). Results: A total of 1082 urinary bacterial samples were isolated and identified. Females accounted for more bacterial infections (62.66%) than males (37.34%). Gram-negative bacteria represented 94% of all isolated strains. The most prevalent pathogens associated with UTIs were Escherichia coli (47.97%), Klebsiella pneumoniae (24.58%), and Pseudomonas aeruginosa (11.55%). Antimicrobial resistance patterns indicated the presence of extended-spectrum beta-lactamase (ESBL) (30.13%), carbapenemase-resistant Enterobacter (CRE) (1.94%), methicillin-resistant Staphylococcus aureus (MRSA) (0.74%), and vancomycin-resistant Enterococci (VRE) (0.18%). UTI incidence demonstrated a higher prevalence in September (13%) compared to other months in 2022. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the predominant Gram-negative multidrug-resistant organisms (MDRO), accounting for 34.42%, 13.95%, and 1.63% of the population. Conclusions: The prevalence of UTIs caused by antibiotic-resistant microbes is notable in Jazan. Consistent with findings from other regions, Escherichia coli remains the most common causative pathogen of UTIs, displaying a seasonal pattern that warrants attention. Approximately 35% of reported cases involve MDRO, with ESBLs accounting for 30%. These results should raise concerns among healthcare officials, highlighting the necessity for further investigations into factors contributing to the circulation of MDRO in Jazan.

A Cross-Sectional Study about Knowledge, Attitude, and Practices among Primary Health Care Physicians in Jazan Province, Saudi Arabia, Regarding Rome IV Criteria for Diagnosis of Irritable Bowel Syndrome.

Background and objectives: Most individuals with irritable bowel syndrome (IBS) are diagnosed by primary health care (PHC) physicians. However, a significant percentage of patients remain undiagnosed or misdiagnosed owing to the lack of knowledge or a systematic strategy regarding the use of ROME IV criteria for the diagnosis of IBS. Thus, in this study, we aimed to assess the knowledge, attitude, and practices among primary health care physicians in Jazan Province, Saudi Arabia, regarding ROME IV criteria for the diagnosis of IBS. Methods: A cross-sectional study was conducted using a pretested self-administered questionnaire that determines participants' sociodemographic data and measures knowledge about ROME IV criteria, targeting PHC physicians in Jazan Province, Saudi Arabia. Data were analyzed using the Statistical Package for Social Sciences (SPSS) v.23. Results: We included 200 participants, and the majority of participants in our study (approximately 78%) were aware of the ROME IV diagnostic criteria for IBS; this awareness was associated with age, nationality, specialty, and classification. The participants' mean level of knowledge was 4.30 (out of 6). However, knowledge was higher among Saudi and family medicine doctors in this study, as compared to non-Saudi and doctors of other specialties. More than two-thirds of participants who were aware of ROME IV criteria thought that they are sufficient to diagnose IBS; however, only 47.5% of physicians reported using ROME IV frequently in their daily practice. Conclusions: Most of the participants of this study are aware of ROME IV criteria, and better knowledge was noted among Saudi and family medicine physicians. About 70% thought that ROME IV criteria are effective enough to diagnose IBS, and only about half of the participants use ROME IV criteria in their practice. Therefore, due to its high prevalence in the region, further efforts are required to disseminate basic knowledge and improve attitudes and practices related to ROME IV criteria among PHC physicians of all specialties.

Vascular Involvement: An Uncommon Histologic Finding of Rectal Endometriosis.

Deep infiltrating endometriosis frequently affects the rectosigmoid region. It clinically presents as a chronic painful condition affecting women in their reproductive time. Here, we present a case of a 28-yr-old female patient who had a history of dysmenorrhea, dyspareunia, chronic abdominal and pelvic pain, and constipation secondary to rectal wall endometriosis. Microscopic examination of the resected rectal segment showed endometriosis with vascular and lymph node involvement. Vascular involvement is an uncommon histologic finding that may raise concern for potential malignancy. The aim of this report is to alert pathologists and physicians about this infrequent pitfall that can be mistaken for a neoplastic process and to discuss the underlying pathophysiology of vascular involvement by endometrial tissue in otherwise benign conditions.

FOXA1 in HPV associated carcinomas: Its expression in carcinomas of the head and neck and of the uterine cervix.

BACKGROUND: FOXA1 is a major transcription factor involved in the action of human papilloma virus (HPV). However, it has been never studied in HPV-associated tumors. AIM OF THE STUDY: To investigate its expression in cervical and head and neck tumors. MATERIAL AND METHODS: 63 cervical carcinomas/dysplasias and 152 head and neck squamous cell carcinomas (HNSCC) were immunohistochemically studied for the expression of FOXA1. RESULTS: 63.1% of cervical SCC and 40.7% of endocervical adenocarcinomas strongly expressed FOXA1. Most (90%) pre-invasive lesions (CIN3 and in situ adenocarcinomas) strongly expressed FOXA1 and this difference from invasive lesions was statistically significant (p=0.005). No association with clinicopathological factors was found. 51.3% of HNSCC expressed FOXA1. In these tumors, FOXA1 expression was associated with the non-keratinizing morphology but not with the HPV/p16 status neither other clinicopathological features. Of normal structures, salivary glands, endocervical glands and basal/parabasal cell layer of squamous epithelium of both uterine cervix and head and neck mucosa, all strongly expressed FOXA1. CONCLUSION: FOXA1 is expressed by basal cells of squamous epithelium, pre-invasion lesions of the uterine cervix and the head/neck and almost half invasive cervical and head/neck carcinomas, supporting its possible implication in HPV pathogenesis.

Frozen Sections in Pleural Pathology: A Valuable Tool.

BACKGROUND: Knowledge of pleural malignancy can lead to immediate pleurodesis during thoracoscopy. However, the accuracy of pleural frozen sections is largely unknown. OBJECTIVES: To investigate the accuracy of frozen sections in pleural tumor pathology. METHODS: A total of 156 frozen pleural sections performed with the question of malignancy were retrospectively reviewed. The original frozen sections were compared to the permanent section slides which were considered as the gold standard. The influence of the following parameters on the frozen section response was evaluated: specimen size, clinical information, as well as the processing by a specialized pulmonary pathologist or not. The reasons of discrepancies were categorized as sampling errors or interpretation errors. RESULTS: Frozen sections made up 16.4% of 951 pleural biopsies performed in the same time period. Accurate diagnosis was feasible in 92.3% of the cases. There were 7 (4.5%) deferred (inconclusive) cases and 5 (3.2%) discrepant cases. Sensitivity of the method was 96.26%, specificity 97.87%, the positive predictive value was 99.04%, and the negative predictive value was 92%. There was no association between the responses given during frozen section and specimen size, clinical information, or the evaluation by a specialized pulmonary pathologist. Four of the 12 cases were sampling errors, while 8 cases were interpretation errors mostly made in the absence of fat tissue invasion. Thus, paucicellular lesions without prominent invasion - fat invasion or haphazardly invading cellular proliferation - were those posing most of the difficulties during frozen section. CONCLUSIONS: Frozen sections are a highly accurate tool in pleural pathology. Thus, they can be used when an immediate pleurodesis is requested.

Endocervicosis of the Uterine Cervix.

Endocervicosis is considered a form of Mülleriosis affecting mainly the bladder and is comprised of endocervical-type glands and cysts. It has been rarely described in the uterine cervix where the extensive involvement of cervical and paracervical tissue poses the suspicion of malignancy, mostly minimal-deviation adenocarcinoma. We describe a case of cervical endocervicosis causing long-term symptoms leading to hysterectomy. We provide evidence that this pathology is associated with cesarean section similar with isthmocele. Its differential diagnosis is discussed.

High endothelial venules in the pleura: MECA-79 expression in mesothelioma, pleural metastasis and pleuritis.

INTRODUCTION: High endothelial venules (HEVs) are vessels specialized in the extravasation of lymphocytes from the blood to the tissue implicated in the immune microenvironment of several tumors. Their presence has been never studied in the pleural tissue. MATERIAL AND METHODS: We retrospectively studied 149 surgical pleural biopsies by immunohistochemistry for MECA-79 expression, a marker specifically recognizing HEVs. The tissues included 44 (44 %) inflammatory and 105 (56 %) neoplastic diseases. The latter corresponded to 34 (22.8 %) mesotheliomas and 71 (47.7 %) metastases from lung (n=50) or breast (n=21) primaries. RESULTS: HEVs were present in 102 (68 %) of all pleural specimens with a mean number of foci containing HEVs of 13.33 (±20.64). Neoplastic pleural pathologies harbored HEVs in 73.3 % of the cases compared to the non-neoplastic pathologies which harbored HEVs in 56.8 % of the cases (p=0.048). Their presence did not differ between pulmonary or mammary metastasis (p=0.7). CONCLUSION: We show for the first time that HEVs are present in the pleural cavity probably participating in the immune microenvironment of inflammatory and neoplastic pleural disease.

The detailed histopathological characteristics of ovarian fibroma compared with thecoma, granulosa cell tumor, and sclerosing stromal tumor.

BACKGROUND: Ovarian fibromas are benign tumors that can present peculiar morphological features not studied sufficiently. MATERIAL AND METHODS: In this retrospective study, 75 consecutive cases of ovarian fibroma were morphologically compared with 46 thecomas, 16 granulosa cell tumors, and 5 sclerosing stroma tumors for the following factors: the growth pattern as diffuse or nodular, the presence of hyaline plaques, necrosis, keloid-like sclerosis, calcifications, cystic degeneration, fibrous or edematous stroma, prominent vascularity, lutein cells, cellularity, scant or abundant cytoplasm, prominent cell membranes, nuclear grooves, atypia, and mitotic activity. RESULTS: The tumors differed significantly in terms of hyaline plaques presence, nuclear grooves, growth pattern, stroma type, tumor cellularity, cytoplasm, prominence of cell membranes, atypia, mitotic activity, and prominent vascularity. CONCLUSION: Ovarian fibromas can present some maybe unexpected features rather frequently, such as cystic degeneration, hyaline plaques, prominent vascularity, increased cellularity, and some mitotic activity, thus their presence should not always prompt to an alternative diagnosis.

The immune microenvironment of cancer of the uterine cervix.

While several treatment choices exist for cervical cancer, such as surgical therapy, chemotherapy, and radiotherapy, some patients will still show poor prognosis. HPV infection is a principal factor for cervical cancer development, from early inflammation to proliferation, angiogenesis, and neoplastic growth. While HPV T-cell responses exist, the tumor seems to evade the immune system upon its tolerance. The latter suggests the existence of a confluent tumor microenvironment responsible for the evasion tactics employed by the neoplasm. Therefore, novel biomarkers governing prognosis and treatment planning must be developed, with several studies tackling the significance of the tumor microenvironment in the genesis, development, proliferation, and overall response of cervical cancer during neoplastic processes. This review aims to analyze and contemplate the characteristics of the tumor microenvironment and its role in prognosis, progression, evasion, and invasion, including therapeutic outcome and overall survival.

Immunohistochemical characteristics of uterine lipoleiomyomas.

Lipoleiomyomas are rare variants of uterine leiomyomas rarely studied in the literature. We retrospectively studied 20 cases of uterine lipoleiomyomas showing that these lesions represent 0.7 % of all uterine leiomyomas diagnosed histologically. The patients did not experience any recurrence, and the tumors showed no morphological criteria of malignancy. They did not show significant p16, p53 or MiB1 expression. They showed diffuse and strong expression or estrogen and progesterone receptors by the smooth muscle component but without accompanying expression by the adipocytic component in one third of the cases. Androgen receptors were rarely expressed. They expressed in their majority HMGA2 in both components, while RB1 was usually not found. Fumarate hydratase (FH) is expressed by lipoleiomyomas, while they are negative for HMB45. In conclusion, uterine lipoleiomyomas are rare, benign tumors, characterized by HMGA2 expression, while they show no elements suspicious of malignancy, PEComas or FH deficiency. The role of RB1 in these tumors should be further explored.

Artefacts in Hysterectomies with a Special Focus on Vascular Pseudoinvasion.

BACKGROUND: Since the advent of laparoscopic hysterectomy, several studies have described artefacts, such as vascular pseudoinvasion, constituting potential pitfalls in the histological evaluation of these specimens. The use of an intrauterine manipulator is often suggested as the factor creating these artefacts. OBJECTIVES: To describe possible artefacts, such as vascular pseudoinvasion, myometrial clefts, and tumor cells in the lumen of the cervix, on the serosa, and in the tubal lumen, and to correlate them with clinical and pathological characteristics. MATERIAL AND METHODS: This is a retrospective monocentric study of 60 patients having been treated for benign (n = 27, 45%) or malignant (n = 33, 55%) uterine pathologies. RESULTS: Vascular pseudoinvasion was found in 13 (22%) adenocarcinomas and in one (2%) benign uterine pathology. Clefts within the myometrium were observed in 16 (27%) uteri. Cells in the tubal lumen were observed in six (10%) hysterectomies. True vascular emboli were not correlated with the use of an intrauterine manipulator (p = 0.47) or the type of surgery (p = 0.21). Vascular pseudoinvasion was correlated with the presence of tumor cells in the lumen of the cervix (p = 0.013) and the presence of clefts in the myometrium (p < 0.001), but not with the other factors studied. CONCLUSIONS: Overall, in our series, we did not observe any statistical association between the use of an intrauterine manipulator and the presence of true emboli or vascular pseudoinvasion during hysterectomy in women with malignant or benign uterine pathologies. Vascular pseudoinvasion was also associated with the presence of other artefacts.

Knowledge, Attitudes, and Determinants of Nonalcoholic Fatty Liver Disease Among Adults in Jazan Province: A Cross-Sectional Study.

Background Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally, with its prevalence rising worldwide. This study aimed to evaluate the knowledge, attitudes, and determinants related to NAFLD among adults in Jazan, Saudi Arabia. Methods  A cross-sectional study was conducted using a validated online questionnaire distributed to 540 participants in Jazan Province. Data analysis involved descriptive and comparative statistics to assess knowledge, attitudes, and influencing factors related to NAFLD. Results The majority of participants (244, 45.2%) demonstrated poor knowledge about NAFLD, while 226 (41.9%) had fair knowledge. Notably, individuals aged 40-49, males, healthcare workers, those with obesity and diabetes mellitus, and those with a family history of NAFLD showed significantly higher levels of knowledge (p < 0.05). Regarding attitudes, most participants (64.4%) exhibited a positive attitude toward NAFLD, 28.3% had a satisfactory attitude, and only 7% demonstrated a poor attitude. Conclusion The findings highlight the need for targeted educational interventions and public awareness campaigns to enhance the general public's understanding of NAFLD. Providing accurate and up-to-date information about the disease, its consequences, and preventive measures is crucial for improving awareness and knowledge.

Gastrointestinal Tactile Corpuscle-Like Bodies: Report of Two Cases and Review of the Literature.

Gastrointestinal tactile corpuscle-like bodies are a rare, incidental, entirely benign finding. It is mainly reported in the colorectum and esophagus/gastro-esophageal junction. Rare cases have been documented in the stomach. Here, we present two cases of gastric and colonic tactile corpuscle-like bodies of a 38-year-old female and a 55-year-old male, respectively. Endoscopically, the colonic lesion was resected as an adenomatous polyp, while the gastric biopsies were taken to rule out Helicobacter pylori (H. pylori) gastritis. Microscopically, both specimens revealed the same histopathologic aspects of eosinophilic fibrillary material with round to oval cells and peripherally placed nuclei. Immunohistochemically, these lesions were positive for anti-S100, confirming the diagnosis of tactile corpuscle-like bodies. A thorough literature review is provided.

Crystal-Storing Histiocytosis: The Iceberg of More Serious Conditions.

Crystal-storing histiocytosis is a rare condition that is histologically characterized by intracellular cytoplasmic crystalline inclusions. It usually presents monoclonal immunoglobulins that deposit within histiocytes, which accumulate and affect different organs of the human body and are commonly associated with lymphoproliferative conditions, especially those with plasmacytic differentiation. The prognosis of this condition is variable and related to the underlying clinical disease. In this review article, we aim to describe and discuss the clinical and pathological characteristics of crystal-storing histiocytosis based on the available literature and to provide a thorough differential diagnosis.

Pediatric Gastrointestinal Basidiobolomycosis: A Retrospective Study from Jazan Province, Saudi Arabia.

Introduction: Basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum, and its incidence is poorly understood due to its rarity. Gastrointestinal Basidiobolomycosis (GIB) is an uncommon presentation with limited reports in Saudi Arabia. This retrospective study aims to describe risk factors, clinical findings, diagnosis, and management of GIB in the pediatric population. Methods: We conducted a retrospective analysis of all pediatric patients diagnosed with GIB at a tertiary hospital between 2010 and 2022. Patients were identified based on their diagnosis of GIB. A self-administered questionnaire was distributed to assess risk factors associated with GIB. Results: We analyzed 25 cases of pediatric GIB, with approximately half of the cases (56%) occurring during the COVID-19 pandemic. The mean age of affected patients was 6.6 years, with a male predominance (60%, n=15). About 100% of parents acknowledged gecko existence in their residence, and their children were exposed to insect bites. Poor appetite was reported in all patients, and high counts of eosinophils and erythrocyte sedimentation rate were observed. Thrombocytosis was present in approximately 90% of patients, and 87% had anemia. Abdominal computerized tomography scans and ultrasound-guided biopsies were the most used diagnostic tools, with cases being diagnosed based on histopathological findings and confirmed via fungal culture. Conclusion: Our study provides valuable information on the potential risk factors, clinical features, diagnosis, and management of pediatric GIB in the Jazan region. The observed increase in cases during the COVID-19 pandemic highlights the need for continued surveillance and research to understand better the epidemiology and associated risk factors with this rare fungal infection. These findings emphasize the need for heightened awareness, early detection, and effective prevention strategies to mitigate the impact of pediatric GIB.

Human polyomaviruses JCPyV and MCPyV in urothelial cell carcinoma: a single institution experience.

Objective: Urothelial cell carcinoma (UCC) is the most common type of urinary bladder. JCPyV and BKPyV have been detected in the urine and tissue of urothelial cell carcinomas (UCC) in immunocompetent patients. Here, we investigated the presence of several HPyVs in UCC samples using diverse molecular techniques to study the prevalence of HPyVs in UCC. Methods: A large single-institution database of urine cytology specimens (UCS; n = 22.867 UCS) has previously been searched for decoy cells (n = 30), suggesting polyomavirus infection. The available urine sediments and formalin-fixed paraffin-embedded (FFPE) tissue samples of UCC patients were tested for the presence of JCPyV-LTAg expression by immunohistochemistry (IHC) labeled with SV40-LTAg antibody (clone: PAb416) and subsequent PCR followed by sequencing. In addition, the presence of the oncogenic Merkel cell polyomavirus (MCPyV) and the presence of human polyomavirus 6 (HPyV6) and 7 (HPyV7) DNA were tested with DNA PCR or IHC. Results: Of the 30 patients harboring decoy cells, 14 were diagnosed with UCC of the urinary bladder (14/30; 46.6%) before presenting with decoy cells in the urine. The SV40-LTAg IHC was positive in all 14 UCC urine sediments and negative in the FFPE tissues. JCPyV-DNA was identified in all five available UCS and in three FFPE samples of UCC (three of 14; 21.4%). Two UCC cases were positive for MCPyV-DNA (two of 14; 14.3%), and one of them showed protein expression by IHC (one of 14; 7.1%). All specimens were HPyV6 and HPyV7 negative. Conclusion: Our findings show the presence of JCPyV in the urine and UCC of immunocompetent patients. Moreover, MCPyV was detected in two UCC cases. In total, five UCC cases showed the presence of either JCPyV or MCPyV. The evidence here supports the hypothesis that these viruses might sporadically be associated with UCC. Further studies are needed to confirm the relevance of JCPyV or MCPyV as a possible risk factor for UCC development.

Submucosal Necrotic Nodule of the Colon: An Enigmatic Entity Potentially Related to Anisakis Infection.

CONTEXT.­: Discrete submucosal necrotic nodules may rarely manifest as colon polyps. OBJECTIVE.­: To characterize the clinical and pathologic features of this lesion, which has been under-studied in the literature. DESIGN.­: We conducted an international search to compile a series. For each potential case, photomicrographs were centrally reviewed to confirm the diagnosis. We gathered clinical and pathologic information on each confirmed case. RESULTS.­: The final cohort included 25 patients, with 23 having 1 lesion and 2 having several (31 lesions total). Mean patient age was 62 years; 13 patients (52%) were male. Symptoms were nonspecific, although 4 patients (16%) had blood in stool; 14 patients were asymptomatic. Patient history and medications appeared noncontributory. Most cases were located in the right colon (n = 18; 58%). Mean lesion size was 0.4 cm (range, 0.1-1.7 cm). Histology typically showed a centrally necrotic nodule with peripheral fibrosis, chronic inflammation, and sometimes palisading granulomatous inflammation. Percent necrosis ranged from 5% to 95% (average, 70%), and percent fibrosis ranged from 3% to 70% (average, 25%). In 3 cases, degenerated parasitic structures consistent with Anisakis could be seen on hematoxylin-eosin and trichrome special stain. No patient experienced disease recurrence. CONCLUSIONS.­: Submucosal necrotic nodules can present as colon polyps. Most cases are unifocal, and patients do well on follow-up. At least some examples appear to be caused by Anisakis, implicating patient diet. Patients are often asymptomatic, and many cases show no histologic evidence of the causative agent.