Comparison of PD-L1, VISTA, LAG-3, and GAL-3 Expressions and Their Relationships to Mismatch Repair Protein and p53 Expression in 529 Cases of Endometrial Carcinoma.

The aim of this study is to evaluate the expressions of programmed death-ligand 1 (PD-L1), V-domain Ig suppressor of T-cell activation (VISTA), lymphocyte activation gene-3 (LAG-3), and galectin-3 (GAL-3), in mismatch repair-deficient (MMRd)/MMR-proficient and abnormal p53 expressing endometrial carcinomas and their relationship with clinical-histopathological features. Patients who underwent surgery for endometrial carcinoma between January 2008 and December 2018 were included in the study. Immunohistochemical analysis of MLH1, PMS2, MSH2, MSH6, p53, PD-L1, VISTA, LAG-3, and GAL-3 was performed on the tissue samples of microarray. A total of 529 patients were included. MMRd and p53-mutant tumors accounted for 31.5% and 11.5% of cases, respectively. PD-L1 and LAG-3 expressions in the MMRd and p53-mutant groups were higher than in the MMR-proficient group (P < 0.001). GAL-3 expression in the MMR-proficient group was statistically higher than in the MMRd and p53-mutant groups (P < 0.001). Mean age, grade, International Federation of Gynecology and Obstetrics stage, lymphovascular invasion, and lymph node metastasis were significantly higher in the p53-mutant group (P < 0.001). In the group with PD-L1 expression, nonendometrioid histologic type, tumor grade, and lymphovascular invasion were significantly higher (P < 0.001). Tumor grade, lymphovascular invasion, lymph node metastasis, and microcystic, elongated and fragmented pattern of invasion were significantly higher in the group with high VISTA expression (P < 0.05). Tumor grade was significantly higher in the group with LAG-3 expression (P < 0.001). Immunohistochemically determined subgroups and PD-L1, VISTA, LAG-3, and GAL-3 expression levels may be useful indicators of molecular features, and clinical outcomes also may have important implications for the development of targeted therapies in endometrial carcinoma.

Clinical, histopathological and immunohistochemical evaluation of ultraviolet A1 treatment in early-stage mycosis fungoides.

BACKGROUND/PURPOSE: Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas primarily involving the skin. Early-stage MF is characterised by non-specific skin lesions and non-diagnostic biopsies. While skin-focused treatments, such as PUVA and narrowband UVB (nbUVB), are the most frequently recommended treatments, the UVA1 efficacy has been researched in recent years. The purpose of this study was to evaluate the clinical, histopathological and immunohistochemical aspects of UVA1 treatment in patients with early-stage MF. METHODS: The modified severity weighted assessment scale (mSWAT) was used for total skin body scoring before and after treatment. Skin punch biopsies were taken from the patients before and after treatment. UVA1 therapy was performed five times each week. RESULTS: This study included 26 patients with early-stage MF. The total number of UVA1 sessions varied between 15 and 34. Complete response was observed in 8 (30.8%) of 26 patients (30.8%). The median mSWAT score decreased statistically significantly from 7.1 to 2.0 after treatment (p < .001). Histopathological complete response was observed in 2 (9.5%) of 21 patients. A statistically significant decrease in dermal interstitial infiltrate was observed on histopathological examination after treatment (p = .039). Epidermal CD4/CD8 levels decreased statistically significantly higher from a median of 2.5-1.2 in the complete clinical response group after treatment (p = .043). CONCLUSION: According to our results, UVA1 treatment has an effect on early-stage MF in terms of clinical, histopathological and immunohistochemistry.

The prevalence and distribution of human papillomavirus in 4267 Turkish women with or without cervical lesions: A hospital-based study.

In the present study, it was aimed to screen the genotypes of human papillomavirus (HPV) retrospectively in women with gynecological symptoms who were admitted to a tertiary care university hospital in Ankara, Turkey. A total of 4267 cervical swab samples of women aged 18-79 years were sent to Medical Virology Laboratory from January 2017 to November 2020. Nucleic acid extraction and amplification of samples were done by an automated system. The test can detect 14 high-risk HPV (HR-HPV) types in a single analysis that performs a real-time polymerase chain reaction, by providing individual results on the highest-risk genotypes HPV 16 and HPV 18 and pooled results on other high-risk genotypes (OHR-HPV) (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). HPV DNA positivity was detected in 14.2% (605/4267) of the samples. HPV type 16 and type 18 were detected in 2.4% and 0.7% of the samples, respectively. OHR-HPV types were found in 8.8% of the samples. Of the 1.9% and 0.4% samples had mixed types with type 16+ OHR-HPV and type 18+ OHR-HPV, respectively. The results of this study presented the rates of HR-HPV genotypes of a university hospital in Ankara, over a 4-year period. It was observed that the positivity rate of type 18 is decreasing and some OHR-HPV types are increasing. HPV vaccination is not in the national immunization program in Turkey yet, however, HPV vaccines are available and the vaccination rates for women are increasing.

Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study.

Endocervical adenocarcinomas (ECAs) have been recently reclassified according to their morphologic features linked to etiology by the International Endocervical Adenocarcinoma Criteria and Classification (IECC) and this system is adopted by WHO 2020. This classification separates the ECAs as human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) subtypes. According to WHO 2020, high risk (HR)-HPV association can be histologically recognized by the presence of luminal mitoses and apoptosis. Therefore, investigating the reproducibility of the morphologic criteria of this new classification will be important in observing the recognizability of tumor types. Full slide sets of 94 ECAs were collected from 4 institutions in Turkey and reclassified on the basis of IECC/WHO 2020 criteria and the presence or absence of HR-HPV. HR-HPV presence was confirmed by HPV DNA in situ hybridization, p16 immunohistochemistry and in conflicted cases with real time-polymerase chain reaction. The final diagnoses were given based on the combination of the histologic evaluation and ancillary test results. Our cohort consisted of 73.4% HPVA and 26.6% HPVI cases. According to the WHO 2020 criteria 92.7% of HPVAs and 88% of HPVIs were easily classified. HPV DNA in situ hybridization was positive in 91.3% of the HPVAs and p16 was positive in all HPVAs, and also positive in 8% of the HPVIs. In conclusion, most of the ECAs can be diagnosed by their characteristic morphologic features by the WHO 2020 criteria. However, we want to emphasize that mitosis/apoptosis criteria may not be helpful especially in mucinous ECAs and ancillary tests for HR-HPV should be used in challenging cases.

Subsequent IVF outcomes following antibiotic therapy for chronic endometritis in patients with recurrent implantation failure.

AIM: The aim is to identify the chronic endometritis (CE) incidence in recurrent implantation failure (RIF) patients undergoing in vitro fertilization (IVF) treatment and compare the IVF outcomes of RIF patients with CE following antibiotic therapy with RIF patients without CE. Another purpose is to compare the IVF outcomes of described RIF patients with patients undergoing the first cycle of IVF. METHODS: In this retrospective cohort study, CE was diagnosed with CD-138 immunohistochemical staining. Among RIF patients, two groups were formed as group 1, including patients diagnosed with CE and treated by antibiotics (n = 129), and group 2, including patients without CE (n = 103). Patients with the first IVF cycle having similar infertility etiologies with RIF patients were reviewed as group 3 (n = 932). RESULTS: CE was diagnosed in 55.6% of RIF patients. The number of oocytes retrieved was not different between groups. Implantation rates (IR) were similar after antibiotic treatment in RIF patients with or without CE. However, Group 3 had a higher IR (41.1%) than group 1 and 2 (23.1% and 30.1%, respectively) (p < 0.001). Clinical pregnancy (CPR) and live birth rates (LBR) were comparable between RIF groups. However, CPR and LBR were significantly higher in group 3 (48.6% and 40.5%) than group 1 (36.4% and 27.9%), and group 2 (37.9% and 30.1%) (p = 0.007 and p = 0.005, respectively). CONCLUSION: Unidentified endometrial factors except CE may also affect the implantation process, although CE is a frequent finding in patients with RIF. Reproductive outcomes may not be improved only with antibiotics in RIF patients with CE.

Prognostic role of maspin expression in patients with cervical dysplasia and cervical cancer.

AIM: Mammary serine protease inhibitor (maspin) acts as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are increased in some types of malignant cells. The aim of this study was to investigate the maspin expression in cervical dysplasia and cervical cancer, and to analyze its' relation with survival. METHODS: Maspin expression was detected by immunohistochemistry using labeled streptavidin biotin method to determine cytoplasmic and nuclear maspin expressions in cervical intraepithelial neoplasia grade 1 (CIN1), cervical intraepithelial neoplasia grade 2 (CIN2), cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer. RESULTS: A total of 89 patients with CIN (29 cases of CIN1, 30 cases of CIN2 and 30 cases of CIN3), and 27 patients with cervical cancer were included to the study. 7.8% of the patients with CIN had maspin staining positivity. On the other hand maspin staining was positive in 20 of 27 patients (74.1%) with cervical carcinoma (P = 0.001). Of these patients 20 (100%) had cytoplasmic, and 8 (40%) had nuclear maspin staining positivity. Cytoplasmic maspin immunoreactive scores were found to be significantly higher in carcinoma group when compared to the patients with CIN1/3 (respectively; P = 0.01, P = 0.02). No difference was noted for nuclear maspin expression. Significant overall survival advantage was detected for patients with nuclear maspin staining (P = 0.03). CONCLUSION: The current study shows that nuclear maspin expression is related with better overall survival in cervical cancer. Maspin staining can be a useful diagnostic marker to discriminate cervical intraepithelial neoplasia from cervical carcinoma.

Ultraviolet A1 Phototherapy in the Treatment of Early Mycosis Fungoides.

BACKGROUND: Phototherapy has been the mainstay of therapies for early mycosis fungoides (MF). The beneficial role of ultraviolet (UV) light on MF is suggested by the observation that lesions occur on non-sun-exposed areas. Therapeutic light sources that are available today are broadband UVB, psoralen and UVA, narrowband UVB, and long-wave UV (UVA1). Current literature provides increasing evidence on the use of UVA1 to treat MF. AIM: To investigate the treatment responses of early MF patients treated with fixed 30 J/cm2 doses of UVA1 phototherapy. MATERIAL AND METHODS: Nineteen patients with early MF, stage IA-IIA of the TNM staging system, received fixed 30 J/cm2 doses of UVA1, given 5 times weekly over 5 weeks. Therapeutic effectiveness was assessed by clinical examination and was confirmed by histological evaluation. RESULTS: Of the 19 patients, complete responses were achieved in 12 (63%) and partial responses were achieved in 7 (37%) patients after UVA1 radiation exposures. During the study, UVA1 therapy was well tolerated. During the follow-up, 7 (58%) of the 12 patients with complete response relapsed within 3 months of the UVA1 therapy. CONCLUSION: The current study provides clinical and histological evidence for the effectiveness of UVA1 (30 J/cm2 5 times a week for 5 weeks) as a skin-directed therapy in the treatment of early MF; however, such a treatment failed to maintain a long and sustained response. Thus, studies to identify the optimal dosing protocol regarding the therapeutic efficacy, the factors affecting relapse time/rate, and the necessity of maintenance treatment are needed.

The effect of levosimendan on lung damage after myocardial ischemia reperfusion in rats in which experimental diabetes was induced.

BACKGROUND: It is known that diabetic complications and lipid peroxidation are closely associated. During ischemia and reperfusion (IR), injury may occur in distant organs, as well as in tissues next to the region exposed to the ischemia, and the lungs can be one of the most affected of these organs. Therefore, this study investigated the effects of levosimendan on lung tissue and the oxidant-antioxidant system in diabetic rats. MATERIALS AND METHODS: The study was conducted in 24 Wistar albino rats that were separated into four groups (C, control; DC, diabetic control; DIR, diabetic IR; and DIRL, diabetic IR levosimendan). Diabetes was induced in 18 rats using streptozotocin (55 mg/kg), and the animals were randomly separated into three groups after the effects of the diabetes became apparent. After a left thoracotomy, ischemia was performed on the myocardial muscle with the left main coronary artery (LAD) for 30 min in the DIR and DIRL groups. After ischemia, the LAD ligation was removed, and reperfusion was applied for 120 min. Single-dose intraperitoneal 12 µg/kg levosimendan was administered to group DIRL before the ischemia. Group DC was evaluated as the diabetic control group, and six rats were considered to be the control group (group C), in which thoracotomy was performed and then closed with no induction of myocardial ischemia. We measured the levels of malondialdehyde, as a lipid peroxidation end product, as well as catalase and glutathione S-transferase activities, as antioxidant enzymes in the lung tissue. Tissue samples were also examined histopathologically. RESULTS: Neutrophil infiltration or aggregation in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.003, P = 0.026, and P = 0.026, respectively). Alveolar wall thickening in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.002, P = 0.002, and P = 0.006, respectively). In addition, the lung tissue damage score was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.001, P = 0.004, and P = 0.007, respectively). Finally, catalase and glutathione S-transferase activity levels were significantly higher in the DIR group compared with those observed in the C, DC, and DIRL groups. CONCLUSIONS: Although diabetes increases lipid peroxidation, it suppresses antioxidant activity. Our results showed that levosimendan had a protective effect against lung damage secondary to IR in the rats with induced diabetes. We recommend that experimental and clinical studies be conducted to examine the effects of levosimendan at different doses and different IR durations on various organs for clinical use.

A potential novel treatment strategy: inhibition of angiogenesis and inflammation by resveratrol for regression of endometriosis in an experimental rat model.

The aim of our study was to evaluate the effectiveness of resveratrol in experimentally induced endometrial implants in rats through inhibiting angiogenesis and inflammation. Endometrial implants were surgically induced in 24 female Wistar-Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were divided into resveratrol (seven rats), leuprolide acetate (eight rats), and control (seven rats) groups and medicated for 21 d. In the third surgery, the measurements of mean areas and histopathological analysis of endometriotic lesions, VEGF, and MCP-1 measurements in blood and peritoneal fluid samples, and immunohistochemical staining were evaluated. After treatment, significant reductions in mean areas of implants (p < 0.01) and decreased mean histopathological scores of the implants (p < 0.05), mean VEGF-staining scores of endometriotic implants (p = 0.01), and peritoneal fluid levels of VEGF and MCP-1 (p < 0.01, for VEGF and p < 0.01, for MCP-1) were found in the resveratrol and leuprolide acetate groups. Serum VEGF (p = 0.05) and MCP-1 (p = 0.01) levels after treatment were also significantly lower in the resveratrol and leuprolide acetate groups. Resveratrol appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting angiogenesis and inflammation. Further studies are needed to determine the optimum effective dose in humans and to evaluate other effects on reproductive physiology.

Clear cell adenocarcinoma of the uterine cervix: a case report and review of the literature.

We report an extremely rare case of a patient with clear cell carcinoma of the cervix who had no history of in utero diethylstilbestrol (DES) exposure. Although clear cell adenocarcinoma is an uncommon tumor, it must be considered in the differential diagnosis in young women and children who have cervico-vaginal lesions even without in utero DES exposure history. We present the case of 2 girls, a 14-year-old and a 16-year-old, who were admitted to hospital because of intermittent vaginal bleeding and the presence of a cervical mass diagnosed as clear cell cervix carcinoma. Neither of them had a history of exposure to DES.

Chronic bilateral hearing loss in an immunocompetent patient. An atypical course of tuberculous meningitis.

Congenital, infectious, toxic, and demyelinating disorders are common etiological causes of deafness. Tuberculous meningitis, as one of the infectious causes, should be considered in the differential diagnosis since tuberculosis represents an endemic public health problem in developing countries. Multiple cranial nerve palsies can be expected due to basal meningitis; however, presentation with bilateral hearing loss is quite rare. Early diagnosis and treatment are crucial to prevent mortality and residual neurologic deficits. The focus of this discussion is a 42-year-old female presenting with bilateral hearing loss and nonspecific complaints who was finally diagnosed with chronic tuberculous meningitis. We also demonstrate the characteristic radiological and histopathological findings.

Human papillomavirus DNA testing with the urine sample is not yet available: the accuracy of two distinct kits.

OBJECTIVE: The aim of this study was to assess the results and efficiency of two real-time polymerase chain reaction procedures for detecting human papillomavirus utilizing urine samples. METHODS: This study comprised 151 patients who had previously tested positive for human papillomavirus in their cervical samples. Two different commercial real-time polymerase chain reaction techniques were used for identification and genotyping human papillomavirus in urine specimens. The urine samples of 151 patients were evaluated via the Roche Cobas test, and the urine samples of 91 patients were also evaluated via the Qiagen test. RESULTS: The overall consistency of urine and cervical swab specimens for the identification of human papillomavirus in Roche Cobas and Qiagen tests were 44.8 and 44%, respectively. The rates of positive human papillomavirus results from urine samples were 57 and 70.3%, respectively. The overall concordance among Roche Cobas and Qiagen tests utilizing urine samples for human papillomavirus type 16/18 was 84.3% with a kappa value of 0.675, and for other high-risk-human papillomavirus, it was 75.60% with a kappa value of 0.535. Roche Cobas showed high concordance with Qiagen test. CONCLUSION: human papillomavirus positivity was not detected in all urine samples. It is still inappropriate to recommend the use of urine liquid biopsy for the accurate and reliable detection of human papillomavirus. Due to the lack of a standardized tool, the utilization of urine samples as a screening human papillomavirus test remains a challenge.

Acquired Perforating Dermatosis: Clinical and Histopathological Analysis of 95 Patients From One Center.

INTRODUCTION: Acquired perforating dermatosis (APD) is a disease group characterized by transepidermal elimination of dermal connective tissue materials such as collagen, elastic fibers, and keratin through the epidermis and observed with pruritic skin lesions. OBJECTIVES: In this study, we aim to clarify the clinical, histopathological, and dermoscopic characteristics of APD, identify the associated systemic disease, and figure out treatment options. METHODS: This study was designed as a single-center retrospective, observational, cross-sectional study. We evaluated all accessible APD cases between January 2004 and June 2022 in a tertiary care hospital. RESULTS: A total of 95 patients with confirmed APD were included in the study. Sixty percent of the patients were women and 40% were men. The median age at diagnosis was 63.1 years (35-85 years). The most common site of lesions was the lower extremities which were detected in 86.31% of the patients. The concomitant systemic disease was identified in 84.21% of the patients. The most common systemic disease was type 2 diabetes mellitus (65.26%). Antihistamines and topical corticosteroids were the most commonly prescribed treatment agents. CONCLUSIONS: Transepidermal elimination of dermal connective tissue components is a feature of APD and the disease usually presents with pruritic papules and nodules with central keratotic crust or plug. The diagnosis of APD requires a clinical examination and histological investigation. APD is usually accompanied by systemic comorbidities. There are several topical and systemic medications available for APD, however, sometimes the therapy might be challenging.

Evaluation of endometrial receptivity in recurrent pregnancy loss and recurrent implantation failure.

Objective: The cause of implantation defects in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) has not been clearly established. We aimed to evaluate the immunohistochemical changes in HOXA-11, ß1 integrin, focal adhesion kinase (FAK), cluster of differentiation 44 (CD44), and extracellular matrix protein 1 (ECM1) molecules during the receptive endometrial period in patients with RIF and RPL. Materials and Methods: This study was retrospectively conducted at a university hospital. After the exclusion of cases with pathology that may cause a change in the level of receptors in the endometrium, biopsies performed during the receptive period were selected, and the patients were categorized into RPL (n=15), RIF (n=16), control (n=16) groups. All preparations were immunohistochemically stained for HOXA-11, ß1 integrin, FAK, CD44, and ECM1. Results: HOXA-11 and ß1 Integrin expression changes were similar between the RIF and control groups. However, FAK expression was significantly increased in the RIF group (p<0.01). Additionally, ECM1 and CD44 expressions were significantly decreased in the RIF group compared with the control group (p<0.01). There was no significant difference in the endometrial staining of HOXA-11, FAK, and ECM1 in patients with a history of RPL. However, ß1 Integrin and CD44 levels were significantly decreased in the RPL group compared with the control group (p<0.05). Conclusion: Implantation is a complex process, and altered adhesion mechanisms involved in endometrial receptivity may be related to defective implantation in patients with RIF and RPL. Among the adhesion molecules, the expression of CD44, ß1 integrin, FAK, and ECM1 molecules varies in inappropriate implantation compared with the normal population.

Histopathologic Features for Overall Survival in Merkel Cell Carcinoma: A Case Series with Intact Mismatch Repair Protein Expression.

OBJECTIVE: In a study of Merkel cell carcinoma (MCC), a fusion transcript between MLH1 and SPATA4 was identified. This fusion has the potential to generate the inactive or dominant-negative form of the protein. Therefore, we aimed to investigate whether mismatch repair protein deficiency occurr in MCC cases or not, in addition to the overall survival association with histopathologic features. MATERIAL AND METHOD: A retrospective review of 15 patients diagnosed with a biopsy-proven Merkel Cell Carcinoma between 2012 and 2019 was performed. Mismatch repair (MMR) protein expressions were evaluated by immunohistochemistry. RESULTS: The median follow-up time was 36 months (mean 41, range 2-103 months). Six (40%) patients died during follow-up. The overall survival (OS) at 1 year, 2 years, 3 years, and 5 years were 87%, 80%, 62%, and 53%, respectively. The patients diagnosed at < 60 years had an improved OS compared to those ≥60 years of age (p=0.016). Patients in clinical stage I had better OS than patients in clinical stage IV (p=0.011). Cases with pathological tumor stage (pT) 1 had better OS than pT3 and pT4 (p=0.045). Adjuvant radiotherapy or adjuvant radiotherapy+chemotherapy treatment improved OS compared to adjuvant chemotherapy (p=0.003). MMR protein nuclear expression was intact in 12 cases available for immunohistochemical study. CONCLUSION: To the best of our knowledge, this is the second study that preferentially investigated the mismatch repair protein status of Merkel Cell Carcinoma. No mismatch repair protein deficiency of MCC cases was identified in the current study.

Krukenberg Tumor Presentation of Recurrent Gallbladder Cancer After a Decade.

BACKGROUND: Krukenberg tumors are among rare cases of metastatic ovary cancers. They are presented as a solid mass which generally has bilateral and sometimes cystic components and is also known through symptoms related to the mass effect and/or hormonal imbalance. However, they may present findings before the primary tumor or remain asymptomatic for a long time. CASE REPORT: We presented a patient, who was diagnosed with gallbladder cancer nine years ago and whose adjuvant treatment was completed, applied to the outpatient clinic with the complaint of vaginal bleeding. Surgery was recommended to the patient and the patient was diagnosed with metastatic signet ring cell gallbladder cancer. The patient was started on gemcitabine-capecitabine treatment after surgery. CONCLUSION: The case is important both due to the rareness of metastasis of gall bladder cancer on the ovaries and also the detection of metastasis following the nine-year recurrence-free period. This case shows that routine controls including a careful gynecological examination in a patient primarily detected to have gastrointestinal malignity are important for recognizing late metastases.

Association of Merkel Cell Polyomavirus Status With p53, RB1, and PD-L1 Expression and Patient Prognosis in Merkel Cell Carcinomas: Clinical, Morphologic, and Immunohistochemical Evaluation of 17 Cases.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, primary neuroendocrine carcinoma of the skin whose main risk factors are immunosuppression, UV radiation exposure, and Merkel cell polyomavirus. Programmed death-1/programmed death ligand-1 (PD-L1)-based immunotherapy is currently the first choice for treating patients with metastatic MCC. METHODS: MCC biopsies (17) were evaluated for their nucleus and cytoplasm characteristics and growth patterns, as well as for intratumor lymphocytes, mitotic number, and lymphovascular invasion. Paraffin-embedded tissue samples of the biopsies were stained with MCPyV large T-antigen (LTag), RB1, p53, and PD-L1. RESULTS: We observed MCPyV LTag expression in 9 out of the 17 tumors, and all 9 cases were positive for RB1 ( P <0.000). p53 staining was not significantly correlated with MCPyV LTag. We observed no relationship between p53 expression and any other parameters, and PD-L1 expression was low in the MCC samples. We evaluated PD-L1 using both the combined positive score and tumor proportion score (TPS), and found that TPS was correlated with MCPyV LTag expression ( P =0.016). Tumors with tumor-infiltrating lymphocytes showed a better prognosis than those without these lymphocytes ( P =0.006). DISCUSSION: Our data demonstrated that RB1 was effective for immunohistochemically investigating the MCPyV status of tumors. TPS was superior to the combined positive score in evaluating PD-L1 in MCC. Tumor-infiltrating lymphocytes were the only parameters that were associated with survival. Further studies with larger series are required to confirm these results.

Novel Compound Heterozygous Mutations of TGM1 Gene Identified in a Turkish Collodion Baby Diagnosed with Non-Bullous Congenital Ichthyosiform Erythroderma.

Autosomal recessive congenital ichthyosis (ARCI) is a group of diseases presenting as collodion baby at birth. ARCI is categorized as Harlequin ichthyosis, lamellar ichthyosis, and non-bullous congenital ichthyosiform erythroderma (NBCIE), bathing suit icthyosis (BSI) and others. We describe the case of a male newborn with NBCIE whose whole exome sequencing revealed two variants of TGM1 gene (NM_000359.3) in a compound heterozygous state: c.790C>T (p.Arg264Trp) in exon 5 and c.2060G>A (p.Arg687His) in exon 13. In the literature, the Arg264Trp variant has been reported as homozygous or compound heterozygous with other variants in patients with BSI. In contrast, the Arg687His variant has been reported only as homozygous in patients with BSI. To the best of our knowledge, this is the first case whose two compound heterozygous variants, exhibiting the NBCIE phenotype, instead of the BSI.