Search

Genital anomalies have been reported with VACTERL association but not considered a core feature. Acute and chronic complications stemming from unrecognized genital anomalies have been reported in adolescents and young adults with VACTERL association. We sought to determine the frequency and severity of genital anomalies in VACTERL patients and identify which core features were more frequently associated with genital anomalies. A retrospective chart review from January 2010 to October 2021 identified 211 patients with two or more core VACTERL features, 34% of whom had a genital anomaly. The majority of genital anomalies (83% of those in males and 90% in females) were classified as functionally significant (requiring surgical intervention or causing functional impairment). The frequency of genital anomalies in the VACTERL cohort was higher if anorectal malformations or renal anomalies were present in both males and females and if vertebral anomalies were present in females. Due to their functional significance, genital anomalies should be assessed in all patients with two or more core features of VACTERL association, especially in those with anorectal or renal anomalies. Most genital anomalies in males will be detected on physical examination but additional investigation is often needed to detect genital anomalies in females. The timing and type of investigation are subjects for future study., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Women with prenatal diethylstilbestrol exposure are excluded from less frequent cervical cancer screening because of their increased neoplasia risk. We report the results of a prospective follow-up study of prenatal diethylstilbestrol exposure and lower genital tract high-grade (grade 2 or higher) squamous intraepithelial lesions (HSIL). The age-adjusted risk of HSIL among diethylstilbestrol-exposed women (n=4,062) was higher than among the diethylstilbestrol unexposed (n=1,837) through age 44 years (hazard ratio 2.03, 95% CI, 1.31-3.14) but not age 45 years or older. Elevated HSIL risk remained higher in diethylstilbestrol-exposed women, after accounting for frequency of cervical cancer screening. Compared with unexposed women, HSIL risk was higher among women with earlier gestational and high-dose diethylstilbestrol exposure. These data confirm the appropriateness of more frequent screening among diethylstilbestrol-exposed women through age 44 years. Whether those aged 45 years or older should continue to have increased screening will require careful weighing of possible risks and benefits., Competing Interests: Financial Disclosure : Elizabeth Hatch disclosed receiving payment from UpToDate for being a coauthor on a chapter on diethylstilbestrol. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

As women age, hormonal changes set the stage for a variety of vulvovaginal pathologies. Health care providers in long-term care facilities should be able to recognize and treat these conditions, especially because residents may be unable to communicate their discomfort. The objective of this article is to highlight the major vulvovaginal conditions affecting older women and provide up-to-date information on treatment for providers in long-term care facilities., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest Source of Funding; Paid consultant to Sponsor; Study Investigator Funded by Sponsor; Employee of Sponsor; Board Membership with Sponsor; Stock Holder for Mentioned Product/Company; Patent Inventor for Mentioned Product; Any Financial Relationship to Competitors of Mentioned Product; Other: All others have no conflicts.

Background: Verruciform xanthoma (VX) is an uncommon, benign epithelial lesion of the oral mucosa. While this entity can also present extraorally, including on the skin and in anogenital areas, the variation in its histologic features in extraoral sites is not yet well defined. Differences in the demographics and morphologic features of oral versus extraoral VX were assessed to help facilitate the accurate diagnosis and management of this lesion., Methods: After obtaining IRB approval, 110 cases of diagnosed VX were retrospectively collected from our institutional archives spanning from 2000 to 2022. Patient age, gender, available medical history, lesion appearance, and duration were obtained for each case., Results: The median age was 55 years (range 13-86) with a male-to-female ratio of 1.2:1. The most common oral sites, in descending order, were the palate (n = 24, 22%), buccal mucosa (n = 18, 16%), gingiva (n = 16, 15%), and tongue (n = 13, 12%). Extraoral sites comprised 9% of all lesions, including the scrotum (9), vulva (2), cheek (1), wrist (1), gluteal region (1), and abdominal wall (1). The median size for all lesions was 6.0 mm, and extraoral lesions were associated with a 6.7 mm larger size compared to oral lesions (B ± SE: 6.7 ± 2.5 cm, p = 0.01). The lesions were most frequently pink or white in color and often described as papillary, pedunculated, verrucous, and/or exophytic. Microscopically, the presence of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated inflammation significantly differed between oral and extraoral lesions. Prominent wedge-shaped parakeratosis (p = 0.04) and keratin projections above the epithelium/epidermis (p < 0.001) were more prevalent in extraoral lesions. There was no significant link between keratin projections and epithelial atypia (p = 0.44)., Conclusions: Familiarity with the broad morphological spectrum of VX, including the presence and degree of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated underlying inflammation, will be helpful in diagnosing it in unusual locations., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Dermoscopy is a safe, rapid, and non-invasive tool that aids in the clinical examination of pigmented and non-pigmented lesions. The upward trend in the use of dermoscopy can be attributed to the availability of compact hand-held and sophisticated dermoscopes, that are small enough to be carried around in a pocket. The extent of dermoscopy is not only limited to the evaluation of cutaneous lesions but also involves its use in the assessment of mucosal lesions along with lesions of hair and nails., Methods: In a descriptive cross-sectional study, subjects (n = 100) with oral or genital mucosal lesions will be enrolled. Following a thorough clinical examination, a dermoscopy of the lesion will be performed with Dermlite DL4© Dermoscope, having a magnification of 10x. Images obtained would be stored and evaluated for observing specific morphologic patterns on dermoscopy which would be utilized to describe those patterns and arrive at a specific diagnosis. Descriptive statistics will include mean and standard deviation to summarise quantitative variation. Dermoscopic features of oral and genital mucosal lesions will be estimated in percentage., Purpose of Study: Mucosal lesions several times mimic each other morphologically. Performing a biopsy is not always feasible for oral and genital lesions because they may be difficult to reach and tend to bleed more profusely compared to the skin surface due to its rich vascular nature. Dermoscopy is a non-invasive tool that helps in the diagnosis that is used mostly for the evaluation of non-mucosal lesions. For the same reason, there is no or minimal information in the published literature with regard to dermoscopic patterns of mucosal lesions. The current study intends to describe dermoscopic patterns in oral and genital mucosal diseases so that this important information would assist the diagnosis in a non-invasive manner thereby reducing the need for invasive investigations like mucosal biopsy., Expected Clinical Outcomes: To summarize, this research is intended to add to the scarce literature on dermoscopic findings of oral and genital mucosal lesions. The study findings would establish the diagnosis and eliminate the need for unwarranted invasive biopsies of mucosal lesions and, if need be, help in the selection of the biopsy site., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dodeja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction and Objectives: The aim of the study was to evaluate genital sparing radical cystectomy surgery in female patients from the point of view of both oncologic and functional outcomes (with emphasis on urinary and sexual outcomes) in a single high-volume center for the treatment of muscular invasive bladder cancer., Materials and Methods: Between January 2014 and January 2018, 14 female patients underwent radical cystectomy with preservation of genital organs (the entire vagina, uterus, fallopian tubes, ovaries) and orthotopic urinary neobladder (Padua neobladder). Inclusion criteria were recurrent T1G3 tumors; refractory tumors after BCG therapy without associated carcinoma in situ (CIS); T2 or T3a tumors entirely resected at endoscopic transurethral resection of the bladder and not involving urethra/bladder trigone. Exclusion criteria were: T3b or higher bladder cancer, associated CIS and involvement of urethra or bladder trigone. Oncological and histopathological outcomes (Overall Survival - OS, Recurrence Free Survival - RFS), urinary outcomes (day and night incontinence, intermittent catheterization use, Sandvik Score) and sexual outcomes (Female Sexual Function Index 19 FSFI-19) were considered. The average follow-up time was 56 months., Results: Considering oncological outcomes, histologic examination reported urothelial carcinoma in 13/14 patients; 8/13 patients (61.5%) had high grade T1 stage, 3/13 patients (23%) had high grade T2 stage and finally 2/13 patients (15.5%) had high-grade T3 stage. One patient presented with embryonal rhabdomyosarcoma completely excised after surgery (PT2aN0M0). No patient developed local or metastatic recurrence (RFS 100%); OS was 100%. Considering urinary continence outcomes, 12/14 patients retained daytime and nighttime continence (85.5%); 2/14 (14.5%) complained of low stress urinary incontinence daily and nighttime urinary leakage. The Sandvik Score showed complete continence in 7/14 patients (50%); mild degree incontinence in 6/14 patients without use of incontinence devices (43%); moderate degree of incontinence in one patient (7%). The FSFI administered at 1 year from the surgery showed sexual desire in all patients (100%); subjective arousal, achievement of orgasm and sexual satisfaction in 12/14 patients (85.5%); sufficient lubrication in 11/14 patients (78.5%). Only one patient (7%) complained about dyspareunia during sexual intercourse., Conclusions: Our study aims to demonstrate that genital-sparing radical cystectomy is a safe surgery in terms of oncologic outcomes and, most importantly, that it is beneficial in terms of urinary and sexual function. Indeed, patients' quality of life together with their psychological and emotional health should be put on the same level as oncological safety. However, it is a treatment reserved for selected patients who are strongly motivated to preserve fertility and sexual function and thoroughly informed about the benefits and complications of such a procedure.

Objectives: To examine the oncological and urinary functional outcomes of reproductive organ-sparing radical cystectomy (ROS-RC) and U-shaped ileal neobladder construction in females compared with male patients., Methods: We retrospectively examined 357 patients (281 male and 76 female) with muscle-invasive bladder cancer who were treated with RC plus U-shaped ileal neobladder construction between May 1996 and July 2021. All female patients were treated with ROS-RC. We compared disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), and urinary functional outcomes between male and female patients. We evaluated the effect of gender on DFS, CSS, and OS. Furthermore, urinary functional outcomes were evaluated in 140 males and 48 females using a pressure-flow study at 3, 6, 9, and 12 months postoperatively., Results: Female patients were considerably older than male patients at the time of radical cystectomy. No significant difference was noted in the tumor stage preoperatively. The multivariable Cox regression analysis with an inverse probability treatment weighted model revealed that the female gender was not significantly related to DFS, CSS, and OS. Moreover, urinary functions at 12 months were not markedly different between males and females, except for the capacity of the neobladder, detrusor pressure, and maximum urethral closure pressure., Conclusions: This study demonstrates that female patients with ROS-RC and U-shaped ileal neobladder construction did not significantly correlate with worse oncological outcomes. The combination of ROS-RC and U-shaped ileal neobladder construction might attain adequate urinary function without sacrificing oncologic outcomes., Competing Interests: Conflict of interest The authors have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Neoplasia of the tubular genital tract in goats, while rarely described, is most commonly reported as uterine adenocarcinoma, leiomyoma, or leiomyosarcoma. In this retrospective, single-center, case series, medical records were searched for goats with a computed tomography (CT) diagnosis of tubular genital mass and a definitive histologic (surgical biopsy or necropsy) diagnosis of malignant neoplasia. Data recorded from CT images were presence of peritoneal/retroperitoneal fluid, urinary tract obstruction, abdominal lymphadenomegaly, additional abdominal nodules/masses, and pulmonary nodules. For masses, maximum cross-sectional area, contrast enhancement, and uterine luminal fluid accumulation were also recorded. Seven goats met the inclusion criteria (leiomyosarcoma n = 5, adenocarcinoma n = 2). Both goats with adenocarcinoma had upper urinary tract obstruction, moderate to severe regional lymphadenopathy, peritoneal fluid, and peritoneal or hepatic nodules/masses; one goat with adenocarcinoma was discharged and subsequently euthanized, and the other had palliative mass debulking and was lost to follow up. Goats with leiomyosarcoma had infrequent, mild peritoneal fluid and mild sublumbar lymphadenopathy. Of the goats with leiomyosarcoma, two were euthanized at or near the time of CT imaging, two were euthanized at the time of surgery due to perceived mass non-resectability, and one had mass regression approximately four months post ovariohysterectomy but was subsequently lost to follow up. Five goats had pulmonary nodules, three of which had pathologic confirmation (pulmonary metastasis in a single patient with adenocarcinoma, and lungworm granulomas in two goats with leiomyosarcoma). Severe sublumbar lymphadenopathy and obstructive uropathy were sequelae in the two caprine patients with genital adenocarcinoma, and in none with leiomyosarcoma., (© 2022 American College of Veterinary Radiology.)

Background: Ovotesticular disorder/difference of sex development (DSD) refers to the co-presence of testicular and ovarian tissue in one individual. Childhood management is challenging as there are many uncertainties regarding etiology, gonadal function, and gender outcome., Summary: Ovotesticular DSD should mainly be considered in 46,XX children with atypical genitalia and normal adrenal steroid profiles. Various underlying genetic mechanisms have been described. Histological assessment of ovotestes requires expert revision and has many pitfalls. Neonatal sex assignment is essential, but as gender outcome is unpredictable, this should be regarded as provisional until a stable gender identity has developed. Therefore, it is crucial not to perform any irreversible medical or surgical procedure in affected individuals until adolescents can give their full informed consent. Gonadal function mostly allows for spontaneous pubertal development; however, fertility is compromised, especially in boys. Specific long-term outcome data for ovotesticular DSD are lacking but can be extrapolated from studies in other DSD populations., Key Messages: Management of ovotesticular DSD has changed in recent years, prioritizing the child's future right for autonomy and self-determination. The benefits and pitfalls of this new approach have not been documented yet and require intensive monitoring on an international scale., (© 2021 S. Karger AG, Basel.)

Lichen planus (LP) is a chronic T-cell-mediated mucocutaneous inflammatory disease, largely recognized in adults. It is uncommon in children, and the literature present still lacks comprehensive understanding mainly due to underreporting of such cases. LP shows atypical clinical features, when seen in children, mainly affecting the flexor aspect of the wrists, legs, and the oral and genital mucosae. It is largely considered an autoimmune response of the body with various etiologic factors. Its association with vaccination is still an interesting field for research. The focus of the present systematic review was to discover the link of vaccine in the pathogenesis of juvenile LP. An electronic search was carried out using MEDLINE by PubMed, Google Scholar, and Web of Science databases. Articles that reported LP in children with prior records for vaccination were selected for the present systematic review. Twenty-three published articles in the English language were included for the quantitative and qualitative syntheses. The demographic data, specific vaccine history, and clinical details of the lesions were recorded. The existing evidence supports that vaccines could play an important role in etiopathogenesis of pediatric LP., (© 2021 the International Society of Dermatology.)

Background: Genital lichen sclerosus decreases the quality of life of women; 10-15% of cases occur in prepubertal girls., Methods: Retrospective and descriptive study on the characteristics of girls diagnosed with genital lichen sclerosus at the Hospital Universitario de Navarra (Pamplona, Spain) between 2019 and 2022., Results: Eleven girls aged between 4 and 14 year-old were diagnosed. Frequently, diagnostic delays were up to two years after the appearance of the lesions; the girl with a four-year delay showed a significant vulvar architectural alteration. All cases showed the typical sclerotic lesions on the genital area, and two of them also on the back. While six patients were asymptomatic, the rest reported pruritus and/or pain. Treatment with high/very high potency topical cortico-steroids achieved a good partial response, without complete remission of the lesions., Conclusion: Early diagnosis of genital lichen sclerosus is key to start early treatment, avoiding ireversible genital structural alteration.

Disseminated tuberculosis is a rare form of tuberculosis that can cause severe illness if diagnosed and treated late. We present the case of a young Senegalese woman who had a miscarriage due to a pelvic inflammatory disease, followed by the development of a left pleural effusion. Despite laparoscopic findings and a salpinx biopsy that revealed necrotizing granulomas, only microbiological examinations of pleural biopsies revealed the final diagnosis of disseminated, drug-sensitive tuberculosis.

Microperforate hymens are rare anatomical variants with an unknown incidence and very few reported cases. Borderline ovarian tumours are similarly uncommon, with an incidence of approximately 0.002%-0.006%. The concurrent presence of a microperforate hymen and a borderline ovarian tumour is therefore exceedingly unique with no documented cases to date. In this report, we review the case of a nulliparous woman in her late 20s who initially presented with an inability to have penetrative intercourse. A subocclusive hymenal variant was noted on examination and further imaging work-up resulted in the incidental discovery of a large ovarian mass subsequently noted to be a borderline ovarian tumour. Herein, we review contemporary approaches to the diagnosis and management of both hymenal variants and borderline ovarian tumours, and discuss fertility-sparing strategies for young women diagnosed with ovarian neoplasms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Early inflammatory lesions of lichen sclerosus are histopathologically difficult to diagnose until the hallmark of the disease i.e., papillary sclerosis becomes visible in histological sections. Pre-sclerotic and late or resolved phases of the disease have not been extensively studied. Methods We retrospectively reviewed all cases diagnosed as genital lichen sclerosus over a ten-year period from 2006 to 2016, correlating the clinical findings with the histological features. Results A total of 133 cases of genital lichen sclerosus (90 males and 43 females) were identified. Both genders demonstrated a similar histological spectrum. Fifty eight (44%) cases were identified as having pre-sclerotic lichen sclerosus, 64 (48%) as having progressive disease and 11 (8%) cases were classified as fully resolved with atrophy. Asymptomatic vitiligoid lesions were identified in 19 (14%) cases of which 12 were male. Low-grade squamous cell carcinoma was seen within the areas affected by long-standing lichen sclerosus, in four patients (3%, 2 male). Limitations We studied only haematoxylin and eosin stained sections. The presence of basement membrane thickening could have been better illustrated with the periodic acid-Schiff stain. Conclusion The pathogenesis of lichen sclerosus probably involves an immune reaction to the basement membrane at the epidermal interface and around the adnexa. The initial band of inflammation shifts gradually downwards from the epidermal interface into the dermis destroying the vascular channels and appendages, resulting in excessive deposition of altered extracellular matrix. Basilar infiltration of lymphocytes along with a grossly vacuolated or thickened basement membrane is proposed as the characteristic diagnostic feature of the pre-sclerotic stage. Greater awareness of the clinicopathological spectrum of lichen sclerosus should enable early diagnosis and treatment, thereby preventing structural damage and possible malignant transformation in chronic cases.

Importance: Herpes simplex virus type 1 (HSV-1) is the leading cause of first-episode genital herpes in many countries., Objective: To inform counseling messages regarding genital HSV-1 transmission, oral and genital viral shedding patterns among persons with first-episode genital HSV-1 infection were assessed. The trajectory of the development of HSV-specific antibody and T-cell responses was also characterized., Design, Setting, and Participants: Prospective cohort followed up for up to 2 years, with 82 participants followed up between 2013 and 2018. Participants were recruited from sexual health and primary care clinics in Seattle, Washington. Persons with laboratory-documented first-episode genital HSV-1 infection, without HIV infection or current pregnancy, were referred for enrollment., Exposures: First-episode genital HSV-1 infection., Main Outcomes and Measures: Genital and oral HSV-1 shedding and lesion rates at 2 months, 11 months, and up to 2 years after initial genital HSV-1 infection. Participants self-collected oral and genital swabs for HSV polymerase chain reaction testing for 30 days at 2 and 11 months and up to 2 years after diagnosis of genital HSV-1. Blood samples were collected at serial time points to assess immune responses to HSV-1. Primary HSV-1 infection was defined as absent HSV antibody at baseline or evolving antibody profile using the University of Washington HSV Western Blot. HSV-specific T-cell responses were detected using interferon γ enzyme-linked immunospot., Results: Among the 82 participants, the median (range) age was 26 (16-64) years, 54 (65.9%) were women, and 42 (51.2%) had primary HSV-1 infection. At 2 months, HSV-1 was detected from the genital tract in 53 participants (64.6%) and in the mouth in 24 participants (29.3%). Genital HSV-1 shedding was detected on 275 of 2264 days (12.1%) at 2 months and declined significantly to 122 of 1719 days (7.1%) at 11 months (model-predicted rate, 6.2% [95% CI, 4.3%-8.9%] at 2 months vs 3.2% [95% CI, 1.8%-5.7%] at 11 months; relative risk, 0.52 [95% CI, 0.29-0.93]). Genital lesions were rare, reported on 65 of 2497 days (2.6%) at 2 months and 72 of 1872 days (3.8%) at 11 months. Oral HSV-1 shedding was detected on 88 of 2247 days (3.9%) at 2 months. Persons with primary HSV-1 infection had a higher risk of genital shedding compared with those with nonprimary infection (model-predicted rate, 7.9% [95% CI, 5.4%-11.7%] vs 2.9% [95% CI, 1.7%-5.0%]; relative risk, 2.75 [95% CI, 1.40-5.44]). Polyfunctional HSV-specific CD4+ and CD8+ T-cell responses were maintained during the follow-up period., Conclusions and Relevance: Genital HSV-1 shedding was frequent after first-episode genital HSV-1, particularly among those with primary infection, and declined rapidly during the first year after infection.

Type I interferons (IFNs) present the first line of defense against viral infections, providing antiviral, immunomodulatory and antiproliferative effects. The type I IFN family contains 12 IFNα subtypes and IFNβ, and although they share the same receptor, they are classified as non-redundant, capable to induce a variety of different IFN-stimulated genes. However, the biological impact of individual subtypes remains controversial. Recent data propose a subtype-specificity of type I IFNs revealing unique effector functions for different viruses and thus expanding the implications for IFNα-based antiviral immunotherapies. Despite extensive research, drug-resistant infections with herpes simplex virus type 1 (HSV-1), which is the common agent of recurrent orogenital lesions, are still lacking a protective or curing therapeutic. However, due to the risk of generalized infections in immunocompromised hosts as well as the increasing incidence of resistance to conventional antiherpetic agents, HSV infections raise major health concerns. Based on their pleiotropic effector functions, the application of type I IFNs represents a promising approach to inhibit HSV-1 replication, to improve host immunity and to further elucidate their qualitative differences. Here, selective IFNα subtypes and IFNβ were evaluated for their therapeutic potential in genital HSV-1 infections. Respective in vivo studies in mice revealed subtype-specific differences in the reduction of local viral loads. IFNβ had the strongest antiviral efficacy against genital HSV-1 infection in mice, whereas IFNα1, IFNα4, and IFNα11 had no impact on viral loads. Based on flow cytometric analyses of underlying immune responses at local and peripheral sites, these differences could be further assigned to specific modulations of the antiviral immunity early during HSV-1 infection. IFNβ led to enhanced systemic cytokine secretion and elevated cytotoxic responses, which negatively correlated with viral loads in the vaginal tract. These data provide further insights into the diversity of type I IFN effector functions and their impact on the immunological control of HSV-1 infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schmitz, Schwerdtfeger, Westmeier, Littwitz-Salomon, Alt, Brochhagen, Krawczyk and Sutter.)

Background: Syphilis is known as the "great imitator" because of its polymorphic clinical manifestations. Condyloma lata are an uncommon mucocutaneous manifestation of secondary syphilis, generally localized in intertriginous areas, such as the genitals and anus. Extragenital localization of condyloma lata is considered unusual., Methods: A case study of extra-genital condylomata is presented. To contextualise the case, a literature review of extra-genital condylomata lata was subsequently undertaken. The authors searched MEDLINE/PubMed, Scopus and Excerpta Medica/EMBASE English-language sources using the following keywords: "condyloma lata", "condylomata lata", and "condyloma latum"., Results: Thirty-five papers (from 1940 to 2021) describing an extra-anogenital localization of condyloma lata were found and are summarized in Table 1. Patients were mainly males (82.1%), with a mean age of 31.9 years. Most of them showed other manifestations of secondary syphilis (53.9%). In a minority of cases (39.0%), concomitant anogenital condyloma lata were present, thus making the diagnosis easier. The toe web localization was the most documented (26.2%) followed by the oral cavity (23.8%)., Conclusion: In the presence of extra-genital condyloma lata, the differential diagnosis is not always clear, especially when no other muco-cutaneous lesions are observed. In the case of eroded or wet lesions involving any cutaneous fold, associated or not with other cutaneous manifestations, a sexual history should be obtained, and syphilis must be considered.

Chlamydia trachomatis ( CT ) genital tract infection is insidious, and patients often have no conscious symptoms.Delayed treatment after infection can lead to serious complications. Chlamydia muridarum ( CM ) genital tract infection in female mice can simulate CT genital tract infection in women, which is an ideal model to investigate the pathogenesis of CT . CM plasmid protein pGP3, chromosomal protein TC0237/TC0668, CM -specific CD8 + T cells, TNF-α, and IL-13 can induce genital tract inflammation, CD4 + T cells are responsible for CM clearance. However, tubal inflammation persists after genital tract CM is removed. Genital tract CM can spread spontaneously in vivo and colonize the gastrointestinal (GI) tract, but the GI tract CM cannot reverse spread to the genital tract. The survival time and number of CM transmitted from genital tract to GI tract are positively correlated with the long-term lesion of oviduct, while the CM inoculated directly into the GI tract has no pathogenicity in both the genital and GI tract. The double attack pattern of Chlamydia -induced genital tract inflammatory lesions is as follows: CM infection of oviduct epithelial cells initiates the process of oviduct repair as the first attack. After genital CM spreads to the GI tract, activated chlamydia-specific CD8 + T cells are recruited to the genital tract and secreted pro-fibrotic cytokines such as TNF-α and IL-13. This process is called the second attack which transform tubal repair initiated by the first attack into long-term tubal fibrosis/hydrosalpinx. Elucidating the pathogenic mechanism of Chlamydia infection can provide new ideas for the development of Chlamydia vaccine, which is expected to solve the problems of infertility caused by repeated CT infection in women.

Background: The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls)., Methods: Women (n = 251) from South Africa and Kenya were included. Twenty-seven cervicovaginal cytokines were measured by Luminex at baseline, and 1 and 6 months after contraceptive iTanko et alnitiation. In addition, cytokines were measured preseroconversion in HIV cases (n = 25) and controls (n = 100)., Results: At 6 months after contraceptive initiation, women using Cu-IUD had increased concentrations of 25/27 cytokines compared to their respective baseline concentrations. In contrast, women initiating DMPA-IM and LNG-implant did not experience changes in cervicovaginal cytokines. Preseroconversion concentrations of IL-1β, IL-6, and TNF-α, previously associated with HIV risk, correlated with increased HIV risk in a logistic regression analysis, although not significantly after correcting for multiple comparisons. Adjusting for contraceptive arm did not alter these results., Conclusions: Although Cu-IUD use broadly increased cervicovaginal cytokine concentrations at 6 months postinsertion, these inflammatory changes were found not to be a significant driver of HIV risk., Clinical Trials Registration: NCT02550067., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press for the Infectious Diseases Society of America 2022.)

Florid lymphoid hyperplasias of the lower female genital tract, also known as pseudolymphoma or lymphoma-like lesions, are benign lesions displaying histologic features which mimic aggressive B-cell lymphomas. Initially described by Young and colleagues in 1985, fewer than 100 cases have been published, making this lesion rather uncommon and subject to misdiagnoses. However, given that this entity has now been included in the World Health Organization's most recent classification, greater clarity would be beneficial for pathologists and physicians. Thus, our report aims to review these entities and provide all available data. We reviewed the available literature according to PRISMA guidelines. We found that lymphoma-like lesions, regardless of their localization, display numerous superficial lymphoid B cells admixed with a polymorphic small lymphocytic and plasmocytic background and, sometimes, superficial ulceration. Large lymphoid cells show prominent nucleoli and mitotic figures. Immunohistochemistry can usually exclude large cell lymphomas, such as high-grade follicular lymphoma and Burkitt lymphoma, when a starry sky pattern is found, as well as Hodgkin Lymphoma; however, the exclusion of diffuse large B-cell lymphoma or marginal zone lymphoma is more difficult. Explorations seeking infectious agents may show Epstein-Barr virus or, rarely, Borrelia burgdorferi involvement. Molecular study occasionally finds a monoclonal B-cell population, but without the subsequent follow-up which would otherwise be worrisome. Despite its somewhat aggressive histologic features, the benignity of this entity must be highlighted to avoid misdiagnosis and complications due to overtreating., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

Summary: Phyllodes tumours (PT) of the vulva are uncommon tumours. The gold standard treatment for these lesions is unknown but is intuitively presumed to be wide local excision. Incomplete resection is associated with recurrence although the time to recurrence is not known. Pregnancy is hypothesised to increase recurrence due to the production of steroid hormones oestrogen and progesterone. We report on a patient who had recurrence of a PT at a rare site (labia minora) and on the contralateral side from the original lesion, during pregnancy. These findings support that oestrogen and progesterone hormones could have played a role in the recurrence of the PT although margins were not free at the initial surgery., (Copyright© Authors.)

Female genital tuberculosis (FGTB) can be asymptomatic or even masquerade as other gynecological conditions. Conventional methods of FGTB diagnosis include various imaging, bacteriological, molecular, and pathological techniques that are only positive in a small percentage of patients, leaving many cases with undiagnosed condition. In the absence of a perfect diagnostic method, composite reference standards (CRSs) have been advocated in this diagnostic study. This study assesses the agreement between traditional diagnostic modalities using CRS and prevalent TB groups among different fallopian tube infertility manifestations. A total of 86 women with primary and secondary infertility were included in the study and subjected to bacteriological, pathological, and radiological examination for the diagnosis of FGTB. Results were evaluated statistically for concordance of the diagnostic tests to the CRS by sensitivity and specificity, while PPV and NPV were calculated for the performance of diagnostic tests of FGTB. We observed that 11.2% of women were found to be true positives by means of CRS. The positive findings by CRS were as follows: ultrasonography (13.9%), laparoscopy (14%), hysteroscopy (12%), GeneXpert (4.8%), culture (4.8%), polymerase chain reaction (4.8%), and histopathology (6.4%). GeneXpert and culture were found to have a perfect agreement with CRS. Hysterosalpingography, laparoscopy, and hysteroscopy have a fair agreement with CRS. Out of 43 women with tubal factor infertility, 6 women were found in the definitive TB group with mixed conditions of tubal manifestations. This study evaluates and demonstrates the reliability of the collective assessment of various diagnostic methods with CRS findings that help in identifying different TB groups of genital tuberculosis patients from all infertile patients by applying the criteria of CRS., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Riden Saxena et al.)

Background: Ewing's sarcoma (ES) within the genitourinary tract are relatively unheard of and those within the external male genitalia are even rarer. To our knowledge, this is the first known case of primary ES within the paratesticular region in an adult., Case Presentation: We present a case of a 24-year-old man with a right sided testicular mass on examination that was initially characterized as an adenomatoid tumor on ultrasound. After the patient was lost to follow up over the course of 9 months, the testicular mass grew significantly and was excised with pathology revealing primary paratesticular Ewing's sarcoma. This rare case emphasizes the importance of elucidating between the broad differentials of paratesticular masses, including the rare presentation of primary ES and adds a review of the literature of ES in the external male genitalia., Conclusions: Rare differentials such as this case should be considered in patients with paratesticular masses. Further diagnostic and management algorithms for extraosseous Ewing Sarcoma, particularly in the adult population, are warranted., (© 2022. The Author(s).)

Concurrent multiple primary extramammary Paget's disease (EMPD) is rare. Herein, we present two Chinese cases of concurrent primary EMPD involving both the genitalia and the axilla, and they also had a history of other malignancy. We also summarise the cases of multiple primary EMPD previously described in literature. Careful examination of all apocrine sweat gland-bearing sites and additional internal malignancies is recommended for patients with EMPD., (© 2022 The Australasian College of Dermatologists.)

Genital keratotic lesions include bowenoid papulosis (BP), which histologically resembles squamous cell carcinoma in situ containing high-risk HPV, condyloma acuminatum (CA) that is a genital wart containing mostly low-risk HPV, and genital seborrheic keratosis (GSK), which is a benign epidermal tumour lacking a clear etiologic relationship with HPV. This study compared HPV genotype distributions among BP, CA and GSK and revealed that BP and GSK were related to high-risk HPV whereas CA was related to low-risk HPV. It is plausible that GSK is a distinct epidermal tumour often related to high-risk HPV rather than merely a senescent form of CA considering the overall discrepancy in the frequency distribution of HPV genotypes along with histopathological differences, and the detection of high-risk HPV in GSK alerts physicians to consider more active treatment and continued follow-ups., (© 2022 The Australasian College of Dermatologists.)

Objective: The aim of the study was to define the incidence, prognosis, and treatment patterns associated with synchronous lower genital tract squamous cell carcinoma (LGTSCC) among women diagnosed with any LGTSCC., Materials and Methods: Surveillance, Epidemiology, and End Results (SEER) database patients diagnosed with synchronous cervical, vaginal, vulvar, and/or anal SCC from 2000 to 2016 were included. Incidence and mortality were evaluated using Kaplan-Meier curves. Multivariable Cox proportional hazards regression was used to identify treatment patterns, risk factors, and mortality associated with LGTSCC., Results: Among 15,424 women with LGTSCC, 138 had synchronous LGTSCC (0.89%). Vulvar and vaginal SCC was the most common combination (49.3%), and cervical with anal SCC was the least common (1.4%). Only one patient had 3 or more primary LGTSCC. Synchronous LGTSCC was independently associated with higher mortality compared with single-site LGTSCC (adjusted hazards ratio [aHR] = 1.67; p < .001). Synchronous LGTSCC was significantly associated with older age (63 vs. 58 years, p < .001) and lower stage (adjusted odds ratio [aOR] = 0.38; p < .001) and grade of disease (aOR = 0.32; p < .001). Patients with synchronous LGTSCC were more likely to receive radiation (aOR = 1.74; p = .005) and were more likely to receive adjuvant radiation after primary surgical resection compared with single-site LGTSCC (aOR = 1.88; p = .007). Receipt of any treatment including radiation (aHR = 0.85; p < .001), chemotherapy (aHR = 0.50; p < .001), and surgery (aHR = 0.70; p < .001) was independently associated with decreased mortality hazard., Conclusions: Synchronous LGTSCC is rare but is associated with increased mortality and higher rates of adjuvant radiation compared with single-site LGTSCC despite lower stage and grade at diagnosis. More research is needed to define optimal therapy for these patients., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

Background: As public awareness of health has increased and diagnostic and treatment options have improved, the survival of patients with malignant tumors has continued to extend, and the population has been aging, the number of multiple primary malignant neoplasms has gradually increased in recent years. There are few reports concerning female patients with multiple primary malignant neoplasms of breast cancer or genitalia malignancies. In this study, we aimed to analyze the clinical characteristics and prognosis of multiple primary malignant neoplasms in female patients with breast cancer or genitalia malignancies, as well as further explore the factors that affect the survival., Methods: We collected clinical data on 80 female patients diagnosed with multiple primary malignant neoplasms of the breast or genitalia, described their clinical features. Furthermore, we calculated the survival and prognostic factors for 52 participants., Results: In our study, the prevalence rate of multiple primary malignant neoplasms was 0.66% (367/55404). Corresponding to female patients with multiple primary malignant neoplasms of breast cancer or genitalia malignancies, it was 1.4% (80/5707). the median age of diagnosis for the first tumor was 48 years, and the median age of diagnosis for the second tumor was 52 years. Regarding the interval, 67.57% (50/74) of patients were within five years. Most tumors were located in the breast (44.68%), followed by the uterus (20.21%), the ovary (17.02%), and the cervix (15.96%). The overall 12-, 36-and 60-month survival rates of the patients were 86.4%, 74.3%, and 69.8%. For the female patients, the stage (III-IV) ( P  = 0.046), non-radical surgery ( P  = 0.002), and types of the last tumor (breast cancer or genitalia malignancies) ( P  = 0.019) were associated with the poor prognosis., Conclusions: Female patients with breast cancer or genital malignancies should pay attention to screening for the second tumor, especially within 4 years after the first tumor diagnosed. Furthermore, during tumor screening, it may be recommended for these patients to focus on colorectal cancer and lung cancer. Compared with previous studies, in addition to clinical staging and types of surgery, we found whether the last tumor was breast cancer or genitalia malignancies should also be considered a prognostic factor., Competing Interests: The authors declare there are no competing interests., (©2022 Xiao et al.)

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis bacteria. In the past years, it has emerged as a relevant infectious agent, mainly affecting men who have sex with men (MSM), frequently associated with other sexually transmitted infections as human immunodeficiency virus (HIV) and syphilis. Even though genital lesions correspond to the classical presentation of LGV, nowadays anorectal syndrome is more frequently reported. We present a MSM patient, HIV infected, being treated with antiretroviral drugs, with a history of recurrent genital herpes, also recently treated for a syphilis in a latent stage. He had no recent trips. He referred inguinal fistulized enlarged lymph nodes, associated with a painful genital ulcer, he denied anorectal or systemic symptoms. He had been treated with multiple antibiotic and antiviral drugs, with no clinical response. Molecular studies from the content of the fistulized lymph node identified C. trachomatis. The patient received doxycycline for 6 weeks, showing good clinical response.

Chlamydia trachomatis serovars A-L cause important diseases of the eyes and reproductive tract by infecting epithelium lining those organs. A major hurdle for vaccine trials is finding a surrogate biomarker for protective immunity. Investigational data argues for T-cell biomarker(s) reflecting mucosal adaption, cytokine polarization, B-cell help, antibacterial effector mechanisms, or some combination thereof. A human investigation and 2 mouse studies link IL-13 to protection from infection/immunopathology. We performed RNAseq on T cells resident in spleens and genital tracts of naturally immune mice. CD4 signatures were consistent with helper function that differed by site including a genital tract-specific Fgl2 signal. The genital tract CD8 signature featured IL-10 and promotion of healing/scarring with a unique transcription of granzyme A. The RNAseq data was used to refine previously published CD4γ13 and CD8γ13 transcriptomes derived from protective T-cell clones, potentially identifying practicable T-cell subset signatures for assessing Chlamydia vaccine candidates., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The prognostic value of SPRY4-Intronic transcript 1 (SPRY4-IT1) in women suffering from breast carcinoma and malignant tumors of the reproductive system remains to be ascertained. Therefore, this paper attempted to assess the relationship between SPRY4-IT1 with the clinicopathological indicators and survival analysis in women suffering from breast carcinoma and malignant tumors of their reproductive organs through meta-analysis., Method: Related literature retrieved from Cochrane Library, Ovid, Embase, PubMed, the CNKI, and the Web of Science databases were reviewed. The latest article search was updated to September 1, 2021. The outcome indicators included as effective measures in the study were hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI). The Stata 12.0 software was used to analyze the data., Results: The elevated SPRY4-IT1 levels were indicative of poor overall survival (OS) [HR = 2.44, 95% CI = 1.35-4.43, P < .05], and were not related to Disease-Free Survival (DFS) [HR = 1.61, 95% CI = 0.50-5.18, P = .43] in female patients suffering from malignant tumors. In terms of lymph node metastasis (LNM) for the association between long noncoding RNA SPRY4-IT1(LncRNA SPRY4-IT1) and OS, elevated LncRNA SPRY4-IT1 implied poor OS with LNM [HR = 2.79, 95% CI: 1.81-4.28, P < .001]. Based on the aspect of the LNM for the association between LncRNA SPRY4-IT1 and DFS, SPRY4-IT1 was not correlated with DFS [HR = 0.97, 95% CI: 0.73-1.28, P = .81]. SPRY4-IT1 in the TNM stage was not related to OS [HR = 1.43, 95% CI: 0.55-3.70, P = .46]. In the TNM stage, SPRY4-IT1 was not related to DFS [HR = 1.68, 95% CI: 0.92-3.06, P = .09]. SPRY4-IT1 was found to be associated with lymph node metastasis (OR = 4.15, 95% CI: 2.75-6.25, P = .000) and TNM stage (OR = 2.89, 95% CI: 1.51-7.27 P = .02). No significant correlation was noted between SPRY4-IT1 and the age of the patients (OR = 0.89, 95% CI: 0.61-1.29 P = .54)., Conclusions: Thus, this study provides evidence-based medical evidence for the target treatment of female breast carcinoma and malignant tumors of the reproductive system. The elevated level of SPRY4-IT1 was associated with poor prognosis of female breast cancer patients and of those having malignant tumors in their reproductive organs. In addition, the SPRY4-IT1 expression was also associated with the disease progression and metastasis., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Tissue-resident memory T (Trm) cells can trigger a secondary immune response when they encounter the same antigen, playing an important role in antitumor immunity. However, whether Trm cells are protective against female genital tract tumors remainunknown. Here, we show that cervicovaginal vaccination with HPV16 E7aa 43-62 peptide/CPG-1826 can generate CD103 + CD8 + Trm cells in the genital tract. These Trm cells can result in subsequent CD8 + T cell expansion and cytokine production when they encounter the same antigen. Importantly, this secondary response can control rechallenge with tumor cells. In vitro,BMDCs can promote the production of TGF-β, which induces CD103 expression in CD8 + T cells. In human cervical cancer samples, DCs were correlated with the Trm gene signature, which was positively associated with overall survival. Our results indicate that cervicovaginal Trm cells have the capacity tocontrol tumor growth and that BMDCs may induce Trm cell generation via the TGF-β signaling pathway., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The objective is to explore the treatment effect of mometasone furoate cream on lichen sclerosus et atrophicus (LSeA) of external genitalia in boys and its correlation with Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88)., Methods: A total of 100 boys treated in our hospital from January 2021 to January 2023 due to clinical manifestations in the external genitalia were selected as the study objects. All boys received redundant circumcision treatment, their protein expression of TLR4 and MyD88 in foreskin tissues was measured by BCA protein assay and western blot, and mometasone furoate cream was applied to those who were pathologically diagnosed with LSeA, so as to compare the levels of serum inflammatory factors and urodynamic indicators in the child patients before and after treatment., Results: The total clinical efficacy rate of LSeA child patients was up to 90.79%; after treatment, the maximum and mean urinary flow rates of child patients were significantly higher than before treatment ( P < 0.001); compared with the non-LSeA group, the protein expression of TLR4, MyD88, and NF- κ B was increased in the LSeA group ( P < 0.001), and the mRNA expression of TLR4, MyD88, and NF- κ B was significantly increased in the LSeA group ( P < 0.001); the results of ROC curves showed that TLR4 had the highest AUC value, and during treatment, the incidence rate of adverse reactions in child patients was 6.58%., Conclusion: LSeA will increase the inflammatory reactions in child patients, and its pathogenesis may be related to the upregulation of TLR4, MyD88, NF- κ B expression and thus activation of TLR4/MyD88/NF- κ B signaling pathways. Applying mometasone furoate cream to LSeA patients after redundant circumcision can effectively reduce the inflammatory reactions in the body and improve their urodynamic indicators, with exact efficacy. Further research will be conducive to establishing a better treatment scheme for such child patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Hong Sun et al.)

Introduction: Genital chronic graft-vs-host disease (cGvHD) is a common late effect after allogeneic stem cell transplantation. In a previous cross-sectional study, prevalence, signs and symptoms of genital and extra-genital cGvHD were accounted for in a cohort of 42 women. Classifications of cGvHD were performed as per the National Institutes of Health (NIH) 2005 criteria. In this follow-up study on surviving women, the aim was to assess genital and extra-genital cGvHD status after long period of time. Our hypothesis was that signs and symptoms of cGvHD alleviate over time., Material and Methods: All surviving women (n = 38) were re-examined by an ophthalmologist, a gynecologist and a hematologist. Signs and symptoms were classified according to the NIH 2014 criteria. Clinical scorings of affected organs were combined for estimating global score of cGvHD. To make possible comparisons between the two studies, data from the original study were re-classified as per the NIH 2014 criteria, and the four dead women were excluded. The same questionnaires were completed. Cervical smear, human papilloma virus test and vulvar photo-documentation were performed., Results: Median time after original study was 8.4 (5.8-12) years and after transplant 14.5 (10-19.3) years. The prevalence of genital cGvHD was similar in the original (50%) and follow-up (58%) studies (p = 0.646) as well as extra-genital cGvHD. Systemic corticosteroid treatment of cGvHD was ongoing in 34% and 29%, respectively (p = 0.805). Ocular cGvHD was found in 24 of 37 examined women (65%) in the follow-up study. Genital cGvHD had disappeared in three women and developed in two women 5-12 and 9-17 years, respectively, after transplantation. The severity of global cGvHD changed over time in 14 women, but was the same on group level (p = 0.345). Atrophic mucous membranes as in estrogen deficiency were seen in 66%. Three women had human papilloma virus genotypes associated with the risk of developing cervical cancer., Conclusions: Chronic GvHD did not alleviate over time. Allotransplanted women require early and continuous life-long contact with a gynecologist and an ophthalmologist for the detection of cGvHD. Specific attention should be given to the need for local estrogen and the risk of genital epithelial malignancies., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Purpose: Muscle invasive bladder cancer surgical management has been historically a radical cystoprostatectomy in males and an anterior exenteration in females. Uterine, ovarian, and vaginal preservation are utilized, but raise concerns regarding risk to oncologic control, especially in variant histopathology or advanced stage., Materials and Methods: A retrospective single institutional analysis identified radical cystectomies performed in women, including those with variant histology, which were defined as reproductive organ sparing (uterine, vaginal, and ovary sparing) or nonorgan sparing. The Kaplan-Meier method was used for recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in patients with advanced disease., Results: From 2000 to 2020, 289 women were identified, 188 underwent reproductive organ-sparing cystectomy. No statistical differences were noted for clinical parameters or presence of variant histology for organ-sparing (ROS) and nonorgan-sparing (non-ROS). Positive margin rates did not differ for ROS and non-ROS; 4.3% vs. 7.9%, P = .19, respectively. Median RFS was not statistically significantly different for ROS vs. non-ROS (26.1 vs. 15.3 months) P = .937 hazard ratio (HR) 1.024. CSS was not statistically different for ROS vs. non-ROS (36.3 vs. 28.6 months), P = .755 HR 0.9. OS was not statistically different for ROS vs. non-ROS (25.8 vs. 23.8 months), P = .5 HR = 1.178. Variant histology did not change survival (HR 1.1, P = .643)., Conclusion: In this analysis, ROS in women with advanced disease did not increase positive margin rates or decrease RFS, CSS, or OS compared to non-ROS. Variant histology did not decrease survival odds. Based on preoperative assessment and intraoperative findings, ROS in patients with variant histology and advanced disease should be considered., Competing Interests: Disclosure Nothing to disclose., (Copyright © 2021. Published by Elsevier Inc.)

EIF2S3 pathogenic variants have been shown to cause MEHMO syndrome - a rare X-linked intellectual disability syndrome. In most cases, DNA diagnostics of MEHMO syndrome is performed using exome sequencing. We describe two cousins with profound intellectual disability, severe microcephaly, microgenitalism, hypoglycemia, epileptic seizures, and hypertrichosis, whose clinical symptoms allowed us to suspect MEHMO syndrome. To confirm this diagnosis, we designed an mRNA analysis for the EIF2S3 gene. It is a cost-effective method to detect coding sequence variants in multi-exonic genes, as well as splicing defects and allelic imbalance. Our mRNA sequence analysis revealed a novel EIF2S3 variant c.820C>G in both cousins. We also found the same variant in female family members in the heterozygous state. To investigate the pathogenicity of the c.820C>G variant, we performed expression analysis, which showed that the DDIT3 transcript level was significantly increased in the patient relative to the controls. We, thus, demonstrate that mRNA analysis is an efficient tool for performing genetic testing in patients with distinct phenotypic features., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Oral human papillomavirus (HPV) is associated with increasing rates of HPV-associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection after a genital infection of the same type in the HPV infection in men study was investigated. Samples from 3140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58); and then also sequential, same-type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7-3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7-3.1) and 3.5 (95% CI: 1.9-6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections., (© 2021 UICC.)

WNT2B is a member of the Wnt family, a group of signal transduction proteins involved in embryologic development and stem cell renewal and maintenance. We recently reported homozygous nonsense variants in WNT2B in three individuals with severe, neonatal-onset diarrhea, and intestinal failure. Here we present a fourth case, from a separate family, with neonatal diarrhea associated with novel compound heterozygous WNT2B variants. One of the two variants was a frameshift variant (c.423del [p.Phe141fs]), while the other was a missense change (c.722 G > A [p.G241D]) that we predict through homology modeling to be deleterious, disrupting post-translational acylation. This patient presented as a neonate with severe diet-induced (osmotic) diarrhea and growth failure resulting in dependence on parenteral nutrition. Her gastrointestinal histology revealed abnormal cellular architecture particularly in the stomach and colon, including oxyntic atrophy, abnormal distribution of enteroendocrine cells, and a paucity of colonic crypt glands. In addition to her gastrointestinal findings, she had bilateral corneal clouding and atypical genital development later identified as a testicular 46,XX difference/disorder of sexual development. Upon review of the previously reported cases, two others also had anterior segment ocular anomalies though none had atypical genital development. This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein's putative involvement in multiple developmental and stem cell maintenance pathways.

Individuals mosaic for monosomy X and a cell line with Y chromosome material can have genitalia that appear phenotypical female, male, or ambiguous. Those with this karyotype and typical female genitalia are diagnosed with Turner syndrome; however, this definition specifically excludes those with genitalia other than typical female. There is limited information on whether medical and neurodevelopmental risks are similar among individuals with monosomy X and Y chromosome material across genital phenotypes. This multicenter retrospective study compared comorbidities and clinical management in individuals with monosomy X and Y material and male/ambiguous genitalia to those with typical female genitalia. Electronic medical records for all patients with monosomy X and Y material (n = 76) at two large U.S. pediatric centers were abstracted for predetermined data and outcomes. Logistic regression was used to compare the two phenotypic groups adjusting for site and duration of follow-up. The male/ambiguous genitalia group was just as likely to have congenital heart disease (RR 1.0, 95%CI [0.5-1.9]), autoimmune disease (RR 0.6 [0.2-1.3]), and neurodevelopmental disorders (RR 1.4 [0.8-1.2]) as those with female genitalia. Despite similar risks, they were less likely to receive screening and counseling. In conclusion, individuals with monosomy X and Y chromosome material have similar medical and neurodevelopmental risks relative to individuals with Turner syndrome regardless of genitalia, but there are notable differences in clinical management., (© 2021 Wiley Periodicals LLC.)