Glandular Involvement Research Articles

The role of HIV as an independent risk factor to cervical HSIL recurrence.

To evaluate the role of being human immunodeficiency virus (HIV) positive for predicting the risk of recurrence in women with a cervical high grade squamous intraepithelial lesion (HSIL) diagnosis. Retrospective observational case-control study, comprising HIV positive (case) and HIV negative (control) women in a 1:4 ratio. Women assisted by the Erasto Gaertner Hospital, between 2009-2018, with cervical HSIL diagnosis, submitted to treatment by Loop electrosurgical excision procedure (LEEP), and with a minimum follow-up of 18 months, were included. The immunological status, number and time to recurrence were analyzed, with p<0.05 considered significant. In a second analysis, only patients with free margins were evaluated. The sample consisted of 320 women (64 cases and 256 controls). Presence of HIV, CD4 levels <200 and detectable viral load (CV) were associated with high risk of recurrence, with odds ratio (OR) of 5.4 (p<0.001/95CI:2.8-10); 3.6 (p<0.001 /IC95:0.6-21.1) and 1.8 (p=0.039 /IC95:0.3-9.3), respectively. In the sample with free margins (n=271), this risk was also higher among seropositive patients, with OR 4.18 (p=0.001/95CI:1.8-9.2). HIV is an independent risk factor for cervical HSIL recurrence and reduced disease-free survival time. Glandular involvement, compromised margins, undetectable CV and CD4<200 also increase the risk of relapse.

A Unique Case of Unilateral Pseudogynecomastia.

Gynecomastia is a common condition characterized by the benign enlargement of male breast tissue, often resulting from hormonal imbalances. A rare variant, unilateral pseudogynecomastia, involves enlargement due to adipose tissue accumulation without glandular proliferation and can be associated with occupational factors. We report the case of a 45-year-old male mechanic presenting with unilateral enlargement of the left breast. The patient reported daily microtrauma on his left axilla and chest wall. The clinical evaluation and imaging revealed lipomatosis with pronounced fibrous tissue and no glandular tissue involvement. The hormonal assays were within the normal limits. The patient underwent surgical excision of excess adipose tissue using the Kornstein technique, preserving the nipple-areola complex. The histopathological examination confirmed the absence of malignancy. The postoperative recovery was uneventful, and the follow-up examination at 12 months demonstrated a symmetrical breast appearance with no recurrence. This case underscores the importance of differentiating pseudogynecomastia from true gynecomastia and recognizing potential occupational risks. Surgical management using techniques that preserve the nipple-areola complex can achieve excellent cosmetic outcomes.

Submandibular Gland Preservation in Oral Cavity Squamous Cell Carcinomas: Our Analysis at A Tertiary Care Hospital.

Surgical excision forms the principal treatment of oral cavity squamous cell carcinomas. The comprehensive surgical management consists of Wide Local Excision of the tumor and Neck Dissection with removal ofSubmandibular gland. The submandibular gland accounts for 70-90 % of unstimulated salivary volume. Its excision as a part of neck dissection has been found to cause high Incidence (21% vs 7%) of postoperative xerostomia. Recent studies have highlighted that the preservation of the SMG is possible and oncologically safe in early-grade OCSCC with N0 neck as the involvement of SMG in such cases is low and its preservation decreases the chances of xerostomia. 80 subjects were included in the study to estimate the prevalence of metastatic submandibular gland involvement in oral cavity squamous cell carcinomas. The presence of metastasis into the salivary gland was studied and the mechanism/route of involvement was analysed. The comparison was made between the early and advanced tumors for SMG metastasis irrespective of the primary subsite involvement. In the current study low prevalence (6.2 %) of metastasis to SMG was seen. It was seen in high-grade tumors only. None of the early-grade tumors showed any evidence of SMG metastasis. The most common pattern (80%) of glandular involvement was a direct extension from the primary tumor. Our study concludes that SMG preservation neck dissections can be carried out in early-grade OCSCC irrespective of primary tumor site involvement. The advantages of preserving the SMG are multiple. Furthermore, the morbidity is markedly decreased with its preservation without any compromise on oncological safety.

Whole phenotype of patients with systemic sclerosis and sicca manifestations: Comparison with sicca manifestations from other causes

Introduction & objectivesThis study aimed to characterize the whole phenotype of Systemic sclerosis (SSc) patients with sicca symptoms, using major salivary glands Ultrasound (SGUS) parameters, minor salivary glands biopsies (mSGB) and clinical findings, and to compare these characteristics with those from patients with Sjogren's Disease (SjD), and patients with sicca manifestations from other causes. MethodsSixty SSc patients fulfilling the 2013 ACR/EULAR classification criteria and with subjective self-declared sicca symptoms were consecutively recruited and had SGUS and mSGB. Fifteen SSc patients without subjective sicca symptoms and 65 patients with sicca symptoms from other causes (including 37 SjD with no SSc). ResultsSSc patients with subjective sicca symptoms had frequent objective clinical (up to 83 %), histological (44 % of Focus score≥1/ mm2) and US anomalies (63 % of OMERACT ≥2). 53 % patients without subjective clinical complaint also had abnormal objective tests, suggesting the existence of a sub clinical involvement of salivary glands in SSc. SjD-SSc patients had more severe glandular involvement as compared to patients with isolated SjD and isolated Sicca-SSc patients (70%, 48,6 % and 38% of patients with OMERACT ≥2 respectively) suggesting additive impact of both diseases on glandular physiology and structure. ConclusionSjD-SSc overlap have more severe sicca features as compared to isolated sicca-SSc and isolated SjD, suggesting a specific impact of SSc on salivary gland physiology. Further translational studies are needed to identify the underlying pathways that could serve as therapeutic targets.

Association of focus score and extraglandular involvement in Sjögren's syndrome: A study on antinuclear antibodies and minor salivary gland pathology.

This study aimed to investigate the relationship between patients with and without extraglandular involvement in Sjögren's syndrome (SS) by analyzing ANA (antinuclear antibody) and ENA (extractable nuclear antigen) results and minor salivary gland pathology findings. A total of 265 (245 females; 20 males; mean age: 50.4±12.4; range, 19 to 79 years) patients diagnosed with SS were included in the retrospective cohort study between March 1, 2011, and December 1, 2021. Detailed documentation was performed, capturing demographic characteristics, clinical information, laboratory findings, medication usage, and manifestations of the syndrome. The patients were divided into two groups, with (78 females; 8 males; mean age: 52.7±11.5; range, 22 to 78 years or without (167 females; 12 males; mean age: 49.3±12.8; range, 19 to 79 years extraglandular involvement. The mean follow-up duration was 63.1±31.9 months. Extraganular involvement, including joint involvement, lung involvement, central nervous system involvement, hematological involvement, hepatitis, and lymphoma, was observed in 32.5% of the patients. Patients with extraglandular involvement required multiple medications, while those with only glandular involvement predominantly used hydroxychloroquine. The mean duration from SS diagnosis to extraglandular involvement was 15.2±27.8 months. The comparison between patients with and without extraglandular involvement revealed a significant association between higher focus scores (FS) and extraglandular manifestations. However, no significant differences were observed in terms of ANA positivity, ANA titers, or ENA positivity. Regression analysis indicated that age and FS were linked to systemic involvement. This study highlights the importance of FS as a predictive indicator for extraglandular manifestations in SS. Advanced age was found to be associated with an increased likelihood of extraglandular involvement. Assessing FS and age can aid in predicting extraglandular manifestations.

Risk factors for residual lesions after total hysterectomy in patients with high-grade cervical intraepithelial neoplasia

BackgroundThe purpose of this study was to predict the risk factors for residual lesions in patients with high-grade cervical intraepithelial neoplasia who underwent total hysterectomy.MethodsThis retrospective study included 212 patients with histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2-3) who underwent hysterectomy within 6 months after loop electrosurgical excision procedure (LEEP). Clinical data (e.g., age, menopausal status, HPV type, and Liquid-based cytology test(LCT) type), as well as pathological data affiliated with endocervical curettage (ECC), colposcopy, LEEP and hysterectomy, were retrieved from medical records. A logistic regression model was applied to estimate the relationship between the variables and risk of residual lesions after hysterectomy.ResultsOverall, 75 (35.4%) patients had residual lesions after hysterectomy. Univariate analyses revealed that positive margin (p = 0.003), glandular involvement (p = 0.017), positive ECC (p < 0.01), HPV16/18 infection (p = 0.032) and vaginal intraepithelial neoplasia (VaIN) I-III (p = 0.014) were factors related to the presence of residual lesions after hysterectomy. Conversely, postmenopausal status, age ≥ 50 years, ≤ 30 days from LEEP to hysterectomy, and LCT type were not risk factors for residual lesions. A positive margin (p = 0.025) and positive ECC (HSIL) (p < 0.001) were identified as independent risk factors for residual lesions in multivariate analysis.ConclusionsOur study revealed that positive incisal margins and ECC (≥ CIN2) were risk factors for residual lesions, while glandular involvement and VaIN were protective factors. In later clinical work, colposcopic pathology revealed that glandular involvement was associated with a reduced risk of residual uterine lesions. 60% of the patients with residual uterine lesions were menopausal patients, and all patients with carcinoma in situ in this study were menopausal patients. Therefore, total hysterectomy may be a better choice for treating CIN in menopausal patients with positive margins and positive ECC.

Development of a machine learning-based model for predicting positive margins in high-grade squamous intraepithelial lesion (HSIL) treatment by Cold Knife Conization(CKC): a single-center retrospective study

ObjectivesThis study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model.MethodWe conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model.ResultsThe overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345–2.189), transformation zone III (OR = 2.838, 95% CI: 2.258–3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247–3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537–2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584–4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593–4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826.ConclusionIndependent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.

Radiological Imaging of the Lacrimal Gland in Sjogren’s Syndrome: A Systematic Review and Meta-Analysis

Purpose To critically appraise the evidence on the ability of the lacrimal gland ultrasonography (USG) or magnetic resonance imaging (MRI) to differentiate between Sjogren’s syndrome and non-Sjogren’s syndrome/healthy controls. Methods A systematic review and meta-analysis (based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines) of online literature search was performed using PubMed, Scopus, and Cochrane databases. Cohort studies comparing the imaging features of the lacrimal glands of Sjogren’s syndrome with a control group were included. Quantitative synthesis was performed using the RevMan (Version 5.4.1). Results Six studies used USG as an imaging technique, and three used MRI for the lacrimal gland imaging. The lacrimal gland affected with Sjogren’s syndrome shows glandular heterogeneity on USG and MRI. Heterogeneity on USG had 6.18 times higher odds of the lacrimal gland being involved with Sjogren’s syndrome (95% CI, 3.31–11.55). Gland hyperechogenicity cannot reliably differentiate the glandular involvement in Sjogren’s syndrome. There is insufficient data for analysis on the gland size, hypoechoic areas, fibrous bands, and increased lacrimal artery resistance in Sjogren’s syndrome patients. Of the three MRI-based studies, reduced apparent diffusion coefficient and heterogeneity were the characteristics of Sjogren’s syndrome. Clinical parameters such as dry eye symptomatology and Schirmer values had variable associations with USG or MRI parameters. Ultrasonography parameters were no different between dry eye versus no dry eye in Sjogren’s syndrome patients, whereas small-sized glands had low Schirmer on MRI-based studies. Conclusion Glandular heterogeneity on USG is significantly associated with lacrimal gland involvement in Sjogren’s syndrome patients. However, the role of radiology in predicting lacrimal gland involvement is unclear as the evidence is insufficient and heterogeneous.

Clinical analysis of 314 patients with high-grade squamous intraepithelial lesion who underwent total hysterectomy directly: a multi-center, retrospective cohort study

ObjectiveTo identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL.MethodThe clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading.Result1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2–59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244–12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78–23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947–14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892–11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good.ConclusionThere is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

Inflammatory Markers in Prior Loop Electrosurgical Excision Procedure (LEEP) as a Prognosis Factor in the Recurrence of Cervical Intraepithelial Neoplasia.

To investigate the relationship between preoperative inflammatory markers and recurrence of CIN after loop electrosurgical excision procedure (LEEP). A retrospective historical cohort study was conducted at gynecologic oncology unit, Bhumibol Adulyadej Hospital, Royal Thai Air Force, Thailand. Data was collected from medical records of CIN cases from year 2016 to 2021. Inclusion criteria were subjects who were diagnosed of CIN and underwent LEEP with pathologic confirmation and followed up for two years (at 6 months, 1 year, and 2 years). Preoperative complete blood count (CBC) was obtained within one month for calculation as systemic inflammatory values. One hundred and ten cases of CIN were enrolled. Mean age of participants was 48.1 years old. Three-fourths (83/110) of the participants had histological confirmation as CIN2/3. Sixteen (18/110) and twenty (22/110) percentage of cases had recurrence of disease at 1 and 2 years, respectively. Monocytes /lymphocytes ratio (MLR) and systemic inflammation response index (SIRI) could predict recurrence of CIN within 2 years. MLR more than 0.16 and SIRI more than 0.57 gave the sensitivity and negative predictive value (NPV) at percentage of 77.3/ 81.8 and 91.8/ 90.2, respectively. Combination of MLR and SIRI had sensitivity and NPV at 90.5 and 95.4 percent, respectively. MLR and SIRI could not predict marginal involvement, glandular involvement, and LEEP confirmed CIN 2/3. Pretreatment MLR and SIRI were statistically significant in predicting the recurrence in CIN after post LEEP procedure within 2 years follow up.

Anti-centromere antibody positivity is an independent variable associated with salivary gland ultrasonography score in Sjögren’s syndrome

Sjögren’s syndrome (SS) is an autoimmune disease characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands. SS also exhibits extra-glandular manifestations and specific autoantibodies. Salivary gland ultrasonography (SGUS) is a common procedure used to assess the severity of glandular involvement. However, the association between SGUS and extra-glandular lesions remains poorly understood. This study aimed to identify clinical indices, including disease activity, associated with glandular involvement using SGUS in patients with SS. We included 115 patients with SS and 90 without SS. Patients with SS had significantly higher ultrasonography (US) score than patients without SS. Multivariate analysis revealed focus score, Saxon test positivity, and anti-centromere antibody (ACA) positivity as independent variables associated with the US score in patients with SS. In addition, these results were similar to those obtained in patients with primary SS. Patients with SS and ACA positivity had higher US score and an increased prevalence of hyperechoic bands in the parotid glands and submandibular glands. In conclusion, this study indicated that ACA positivity is associated with the US score in patients with SS. These results suggest that US findings in patients with ACA positivity might show specific changes in the salivary glands, especially fibrosis.

Machine Learning Prediction of Residual and Recurrent High-Grade CIN Post-LEEP.

This study aims to develop a machine learning (ML) model to predict the risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN) after loop electrosurgical excision procedure (LEEP), addressing a critical gap in personalized follow-up care. A retrospective analysis of 532 patients who underwent LEEP for high-grade CIN at Cangzhou Central Hospital (2016-2020) was conducted. In the final analysis, 99 women (18.6%) were found to have residual or recurrent high-grade CIN (CIN2 or worse) within five years of follow-up. Four feature selection methods identified significant predictors of residual or recurrent CIN. Eight ML algorithms were evaluated using performance metrics such as AUROC, accuracy, sensitivity, specificity, PPV, NPV, F1 score, calibration curve, and decision curve analysis. Fivefold cross-validation optimized and validated the model, and SHAP analysis assessed feature importance. The XGBoost algorithm demonstrated the highest predictive performance with the best AUROC. The optimized model included six key predictors: age, ThinPrep cytologic test (TCT) results, HPV classification, CIN severity, glandular involvement, and margin status. SHAP analysis identified CIN severity and margin status as the most influential predictors. An online prediction tool was developed for real-time risk assessment. This ML-based predictive model for post-LEEP high-grade CIN provides a significant advancement in gynecologic oncology, enhancing personalized patient care and facilitating early intervention and informed clinical decision-making.

Sjögren's syndrome: one year in review 2023.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterised by the T-cell-mediated hyperactivation of B-cells and cytokine production. The condition may evolve from an asymptomatic, indolent course, with glandular involvement, to extra-glandular systemic manifestations up to lymphoma development. On tissue level, the typical feature is the lymphocytic infiltration of the salivary gland by B-, T- and antigen presenting cells, as mirrored by the diagnostic cornerstone role of minor salivary gland (MSG) biopsy. Recently, increasing research focused on the investigation of mechanisms underlying the complex pathogenesis of the disease and highlighted the multi-factorial nature of SS consisting of concomitant involvement of environmental, genetic, neuroendocrine and immune factors. In particular, many aspects have been investigated regarding genetic and epigenetics, the role of specific B- and T-cell phenotypes and the investigation of disease-specific biomarkers as predictors of disease development, activity, and lymphomagenesis. Surely, a deeper understanding of these multiple mechanisms may facilitate earlier diagnosis, enable subphenotyping of patients and open novel therapeutic possibilities to address the unmet needs of the disease in the upcoming years.In this review, following the others of this series, we will summarise the most recent literature on pSS pathogenesis and clinical features focusing in particular on new insights into pSS molecular stratification and therapeutic advances in the era of precision medicine.

Risk factors predicting pathological degradation after cervical excision in cervical intraepithelial neoplasia grade II P16-positive patients over 25 years old: a cross-sectional study.

Cervical intraepithelial neoplasia (CIN) is a collective term for pre-cancerous lesions associated with cervical invasive carcinoma. Treatment options depend on the development and progression of the disease. Especially for patients with CINII grade who are aged 25 years and older and have fertility requirements, it is a clinical challenge to determine whether to proceed with conservative or excisional treatment. Excisional treatment increases the risk of overtreatment outcomes, such as cervical insufficiency, preterm labor, miscarriage, and premature rupture of membranes, in young women with childbearing potential. P16 immunohistochemical staining has greatly improved the consistency of CINII patient's diagnosis. The aim of this study was to analyze the risk factors predicting pathological degradation after cervical excision in cervical intraepithelial neoplasia grade II P16-positive patients over 25 years old, and to provide information to help optimize clinical treatments patients with CINII disease. Single-factor and logistic regression models were used to analyze the risk factors for pathological downgrading in the CINII/P16-positive (+) group. The predicted probability of pathological downgrading in the CINII/P16(+) group of patients was calculated according to the logistic regression model to generate a new variable multi-indicator association for receiver operating characteristic (ROC) curve plotting to determine the predictive ability. A total of 248 women who met the inclusion and exclusion criteria were included. Statistical analysis showed that the CINII/P16(+) group had a higher pathological downgrading rate compared with the CINIII group after cold knife conization (CKC) (χ2=6.26, P=0.012). Univariate factors showed that the differences were statistically significant when comparing age, number of biopsy-involved quadrants, menopausal status, and involvement of glands, respectively (P<0.05). In contrast, the differences were not statistically significant when comparing cytological findings, type of transformation zone, high-risk human papilloma virus (HR-HPV) testing, abortion status, pregnancy frequency, time from diagnosis to CKC and Ki67 percentage between the two groups. Multifactorial logistic regression showed that the extent of biopsy CINII involvement [odds ratio (OR), 1.589], menopausal status (OR, 4.031), and glandular involvement (OR, 5.549) were all independent risk factors for pathological downgrading in the CINII/P16(+) patient group (P<0.05). The order of significance of the areas under the ROC curve (AUCs) was as follows: combined multiple indicators (AUC 0.716) > gland involvement (AUC 0.625) > biopsy CINII involvement extent (AUC 0.614) > menopausal status (AUC 0.565). A higher rate of pathological downgrading after CKC was found in CINII/P16-positive patients who were aged over 25 years. Overtreatment exists in patients with CINII/P16-positive diagnosis. Independent factors for pathological downgrading were identified by the factors including if the lesion involved the gland, the extent of CINII involvement on biopsy, and menopausal status.

Gastric Glandular Siderosis but not Lamina Propria Siderosis is Associated With High Serum Ferritin Levels.

Three histologic patterns of gastric siderosis (GS) are described: pattern A (predominantly in lamina propria stromal cells-gastric lamina propria siderosis [GLPS]), pattern B (mostly extracellular crystalline iron) and pattern C (predominantly in glandular epithelium-gastric glandular siderosis [GGS]). This study aimed to analyze the association of GGS with clinicopathologic features using 3 cohorts. Cohort #1 consisted of 76 gastric siderosis cases. Upon classifying the cases into 3 groups by percentage of glandular involvement (negative, 1% to 5%, ≥5% GGS), the degree of GGS was positively associated with serum ferritin levels ( P =0.002), transferrin saturation ( P =0.003), and history of blood transfusion ( P =0.009). After excluding cases with coarse extracellular crystalline iron, cohort #1 was reclassified into 3 groups by degree of GLPS (no, rare [discernible at ×20 or ×40], overt [readily visible at low power]). The degree of GLPS was positively correlated with oral iron pill use ( P =0.01), but not serum ferritin levels or transferrin saturation. Cohort #2 contained 31 gastric samples from patients with hereditary hemochromatosis, most received phlebotomy treatment. GGS was identified in 2 (6.4%) patients; both had high ferritin levels. Cohort #3 included 38 gastric samples from patients with cirrhosis. Three (8%) cases showed GGS; serum ferritin level was available for 1 case and was elevated. These results indicate that GGS is associated with systemic iron overload, while GLPS is correlated with oral iron pill use. The identification of GGS, especially when it's ≥5%, should trigger further workup for potential systemic iron overload and underlying etiologies.

#4323 A RARE CASE OF MEMBRANOUS NEPHROPATHY AS THE INITIAL PRESENTATION OF SJöGREN SYNDROME

Abstract Introduction Primary Sjögren's syndrome (pSS) is an autoimmune disorder characterized by lymphocytic infiltrates in exocrine glands, most commonly manifesting as dry eyes and mouth. Even though extra glandular involvement can occur in Sjögren, renal involvement is rare. It affects less than 10% of the patient population, with tubulointerstitial nephritis being the usual presentation. Glomerular involvement and, in particular, membranous nephropathy are not commonly encountered. We describe a rare case of membranous nephropathy as the initial presentation of Primary Sjögren's syndrome. Case history A 21-year-old female with a history of sickle cell trait presented to our emergency department with one week history of anasarca. Vital signs were unremarkable, and the physical exam was significant for a 2+ pitting edema of bilateral upper and lower extremities. Initial investigation revealed acute kidney injury (Creatinine 2.9 mg/dl from normal baseline), nephrotic range proteinuria of 6 grams on 24-hour urine collection, and hypoalbuminemia (serum albumin 1.5 mg/dl). Immunological workup showed positive ANA (speckled), strongly positive anti-SSA, borderline elevated anti-SSB, negative anti-PLA2R, negative cryoglobulins, negative anti-dsDNA, and negative anti-Smith antibody (Figure 1). Renal biopsy (Figure 2) revealed membranous nephropathy with acute tubular necrosis (ATN). PLA2R staining was negative. We attributed acute kidney injury to ATN and proteinuria to membranous nephropathy. Negative serologies and renal biopsy findings ruled out systemic Lupus. The patient was therefore diagnosed with membranous nephropathy secondary to pSS. The patient was started on Mycophenolate mofetil and steroid taper with an improvement of proteinuria and anasarca and currently follows at our clinic. Discussion Glomerular involvement is rare, and when involved, it is membranoproliferative glomerulonephritis (MPGN) associated with B-cell activation and positive cryoglobulins. Membranous nephropathy is rare with primary Sjögren syndrome. In our patient, a negative anti-PLA2R goes against primary membranous nephropathy. A negative anti-dsDNA and anti-Smith and biopsy findings essentially rule out Lupus nephritis, leaving Sjögren induced secondary membranous nephropathy as the most likely diagnosis. A literature search revealed few described cases of membranous nephropathy as the presenting feature of pSS with later development of sicca symptoms and progression of renal disease to MPGN. Interestingly, our patient had no sicca symptoms at the presentation time. Occult salivary gland involvement has been described in some of these patients; however, our patient deferred salivary gland biopsy. The management of renal disease in pSS has yet to be well described because of its rarity. Rituximab has shown the most benefit in patients with pSS who have positive cryoglobulins and associated MPGN. Steroids and mycophenolate mofetil (MMF) are other possible agents that can be tried. Given that experience, we started on steroids and MMF with an excellent response to treatment indicated by improvement in proteinuria. Conclusion This case adds to the limited available literature on membranous nephropathy as the initial manifestation of pSS. Although the European Alliance of Associations for Rheumatology (EULAR) criteria strongly emphasizes sicca symptoms and glandular involvement in pSS, the possibility of a small subset of pSS patients who present with early renal involvement with latent glandular findings needs to be recognized.

Interobserver Agreement on the Interpretation of Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Among Gynecologic Pathologists.

The anti-programmed cell death (PD-1) checkpoint inhibitor pembrolizumab is approved for the treatment of cervical carcinoma with a programmed cell death-ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1. We assessed interobserver agreement in cervical carcinoma PD-L1 CPS to identify whether it may affect patient selection for immunotherapeutic candidacy. Twenty-nine cervical carcinomas were stained for PD-L1 (Dako 22C3), and slides were interpreted by 5 subspecialty-trained gynecologic pathologists with experience reading PD-L1 immunohistochemistry. Expression was scored using CPS and read out as positive (≥1) or negative (<1); in positive cases, a final score was assigned (1 to 100). There was consensus agreement across all 5 pathologists for 90% (26/29) (Fleiss Kappa value for interobserver agreement: 0.799). The 3 cases with disagreement were composed of 2 squamous cell carcinomas and 1 small cell carcinoma. Of the 26 with unanimous agreement, 88% (23/26) were positive and 12% (3/26) were negative. All (16/16) pure squamous cell carcinomas with full consensus were interpreted as positive, whereas tumors with glandular components were commonly consensus negative (33%, 3/9); this difference was significant ( P =0.037). Disagreements were attributable to low CPS versus negative reads (2 cases) and difficulty discerning glandular involvement from pushing invasion (1 case). In summary, experienced gynecologic pathologists showed substantial interobserver agreement in the interpretation of PD-L1 CPS at the Food and Drug Administration-approved treatment threshold, with the majority of tumors being classified as positive. Pure squamous histology was strongly associated with a consensus-positive read, whereas a subset of tumors with glandular differentiation was negative by all readers. Disagreements occurred in tumors with low versus negative CPS values and in the setting of limited invasion.

Análisis de factores predictores de lesión residual dependientes de la paciente después de conización cervical

Introduction: in the care of women with precursor lesions of cervical cancer, preventing possible progression to invasive cancer without over-treating the high chances of regression is extremely important. Over time, different treatments and protocols have been tested in order to obtain the best results in the control of this condition with conservative techniques. Objective: to identify predictors of residual disease depending on the intrinsic characteristics of the patients with conization, due to high-grade epithelial lesions or with microinvasion. Methods: A prospective descriptive study was conducted to determine the relationship between the diagnosis of residual disease and clinical- epidemiological variables dependent on the patient, in 1090 patients with high-grade cervical epithelial lesions who were treated at the "Héroes del Baire" General Teaching Hospital on the Isle of Youth (Cuba) during the period 2014-2019. Result: a linear trend of the association of age and residual disease was observed, as well as an association with glandular disease, histological severity and infection by oncogenic serotypes of the human papillomavirus. HPV infection (OR=11.3), history of previous lesion (OR=9.8), persistence of viral infection (OR=4.9) and glandular involvement (OR=3.1) were the factors that showed the greatest association with residual disease. Conclusion: the severity and size of the lesion, the glandular extension and the persistent infection by the human papilloma virus were the predictive factors that contribute to the existence of residual lesion.

A cross-sectional study on activity impairment in primary Sjogren's syndrome.

The aim of this cross-sectional study was to show relations between activity impairment and salivary gland involvement for patient empowerment in primary Sjogren's syndrome (pSS). In the study, 86 patients with pSS were included. The data were collected through clinical examinations and a questionnaire regarding Work Productivity and Activity Impairment (WPAI), EULAR Sjogren's syndrome patient-reported index (ESSPRI) and Oral Health Impact Profile-14 (OHIP-14). Relations were analysed by using mediation and moderation analyses. In simple mediation analysis, an independent variable (X) influences outcome variable (Y) through a mediator variable (M) whereas a moderator variable (W) affects the direction of the relationship between the dependent (Y) and independent variables (X). Increases in ESSPRI-Dryness score (X) (p = 0.0189) and OHIP-14 score (M) (p = 0.0004) were associated with the poor WPAI activity impairment score (Y) in the first mediation analysis. The WPAI activity impairment score was mediated by the elevated ESSPRI-Fatigue score (X) (p = 0.03641) and low U-SFR (M) (p = 0.0000) in the second mediation analysis. In addition, ESSPRI-Pain score (W) was the significant moderator for WPAI activity impairment (Y) in patients without hyposalivation in the moderation analysis (p = 0.0010). WPAI activity impairment was affected by both ESSPRI-Dryness with OHRQoL and ESSPRI-Fatigue with SFR in glandular involvement.

Trouble-makers in cytologic interpretation of the uterine cervix.

The development and standardization of cytologic screening of the uterine cervix has dramatically decreased the prevalence of squamous cell carcinoma of the uterine cervix. Advances in the understanding of biology of human papillomavirus have contributed to upgrading the histologic diagnosis of the uterine cervix; however, cytologic screening that should triage those that need further management still poses several difficulties in interpretation. Cytologic features of high grade intraepithelial squamous lesion (HSIL) mimics including atrophy, immature metaplasia, and transitional metaplasia, and glandular lesion masquerades including tubal metaplasia and HSIL with glandular involvement are described with accentuation mainly on the differential points. When the cytologic features lie in a gray zone between the differentials, the most important key to the more accurate interpretation is sticking to the very basics of cytology; screening the background and cellular architecture, and then scrutinizing the nuclear and cytoplasmic details.