Genital calcinosis cutis: Microscopic evidence supporting a dystrophic origin.

Calcinosis cutis (CC) is characterized by the deposition of calcium salts in the skin and subcutaneous tissues. CC involving the vulva or foreskin (prepuce) is uncommon. We present a 9-year-old female with vulvar CC and a 15-year-old male with preputial CC. Microscopic review of excisional specimens revealed calcification associated with follicular cysts in the vulvar case and lichen sclerosus in the preputial case, suggesting a dystrophic origin to a subset of cases of genital CC that might otherwise be classified as idiopathic. The clinical implication of these findings is the need for close histopathologic scrutiny and ongoing clinical surveillance of patients with genital CC initially deemed idiopathic.

Primary preputial reconstruction following surgical excision of cutaneous mast cell tumours without penile amputation in eight dogs.

CASE HISTORY: Medical records from a single referral hospital (Davies Veterinary Specialists, Hitchin, UK) were reviewed to identify dogs (n = 8) with preputial cutaneous mast cell tumours (CMCT) that underwent surgical excision and primary preputial reconstruction, preserving the penis and urethra, after clients declined alternatives such as penile amputation and urethrostomy, from June 2017-June 2022. CLINICAL FINDINGS: Tumours had a median diameter of 21.5 (min 15, max 30) mm, were located cranioventrally (3/8), caudoventrally (1/8), laterally (2/8) and dorsally (2/8) relative to the prepuce and were diagnosed as CMCT based on cytology. No dogs had hepatic or splenic metastasis on cytology but inguinal lymph node metastasis was identified in 3/4 dogs sampled. TREATMENT AND OUTCOME: The owners of all dogs had declined penile amputation and scrotal urethrostomy. The CMCT were excised and primary reconstruction of the prepuce performed. Surgical lateral margins of 10, 20 or 30 mm were used and the deep margin excised the inner preputial lamina or underlying muscular fascia. The deep margin for caudoventral CMCT involved excision of the underlying SC adipose tissue. Preputial advancement was performed in 3/8 dogs to achieve adequate penile coverage. Histopathology confirmed all CMCT were Kiupel low grade, Patnaik grade II with complete margins in 6/8 dogs but identified metastasis only in one inguinal lymph node from one dog. Two dogs encountered minor complications (infection and a minor dehiscence) and one dog had a major complication (infection with major dehiscence). Median follow-up duration was 125 weeks, excluding one dog with 4 weeks of follow-up. None of the dogs experienced local recurrence or died of mast cell disease during the available follow-up period. CLINICAL RELEVANCE:  This clinical study evaluated a surgical alternative to penile amputation and advanced reconstructive techniques for Kuipel low/Patnaik grade II preputial CMCT when these procedures were declined by owners. Surgical excision of preputial CMCT with lateral margins of 10, 20 or 30 mm with primary preputial reconstruction is achievable with low morbidity and a good outcome when penile amputation and scrotal urethrostomy is not an option.

Tumors of the Urogenital Tract.

Neoplasia has been reported to involve the majority of the urinary system of the horse, with tumors affecting the kidneys and bladder most comprehensively described. Primary tumors of the external genitalia are relatively common in the horse and are easily identified on clinical examination while primary tumors of the upper urogenital tract are uncommon. This article will highlight the common tumors, their clinical presentations, and discuss potential medical and surgical treatment options available. The less common neoplasms will be mentioned but not discussed in depth.

Hypospadias with Intact Prepuce: A Spectrum of Anomalies and their Reconstruction.

Aims: The aim of the study was to perform a detailed analysis of the clinical characteristics of megameatus with intact prepuce (MIP) and to audit our results of reconstructive surgeries on MIP. Materials and Methods: Design: Retrospective analysis. Setting: Pediatric surgery department of tertiary level. Subjects, methods: Hospital records and pictures of MIP operated over a 9-year period. Age, size of penis, circumcised or not, shape of glans, external urethral meatus (EUM), urethral plate (UP), chordee, distal urethra, reconstructive surgery, and complications were analyzed. Postoperative result was objectively assessed by Hypospadias Objective Scoring Evaluation (HOSE). Results: Twelve of 254 hypospadias were MIP (incidence = 4.72%). The mean age at operation was 38.25 months (12-87 m). Patients sought circumcision or surgical correction of anomaly. Two patients were precircumcised. MIP was coronal 7, subcoronal 3, and glanular 2. Meatus was wide in 10 and normal in 2. Glans penis was wide in 9 and conical in 3. UP was wide (9), moderately wide (2), or narrow and shallow (1). In two cases of wide deep UP, distal septum was present. Distal urethra was nondilated in all but 1, which had megalourethra. Reconstructive surgery was Tubularized Urethral Plate Urethroplasty (7 cases) or classical Snodgrass (Tubularised incised plate urethroplasty (TIPU), with superimposed vascular dartos flap (5 cases). The megalourethra underwent partial excision and TIPU. Distal UP-septum was incised. Urethral injury (2 cases) and UP injury (1 case) were intraoperative complications. One postoperative complication (ventral glans necrosis) resulted. The mean follow-up period was 4.79 months (1-12 m). In the postoperative follow-up, 11 (92%) had HOSE score 14-16, whereas one had HOSE 13. Conclusion: Some hypospadias cases which have intact prepuce have no megameatus; hence, they cannot be termed MIP. All cases of hypospadias having intact prepuce can be covered by the umbrella term "Hypospadias with Intact Prepuce (HIP);" MIP is a large subgroup under HIP. HIP presents with a spectrum of anomalies of glans, EUM, and UP. Repair by tubularization of UP without or with midline incision gives excellent results.

Single-cell analysis of human prepuce reveals dynamic changes in gene regulation and cellular communications.

BACKGROUND: The cellular and molecular dynamics of human prepuce are crucial for understanding its biological and physiological functions, as well as the prevention of related genital diseases. However, the cellular compositions and heterogeneity of human prepuce at single-cell resolution are still largely unknown. Here we systematically dissected the prepuce of children and adults based on the single-cell RNA-seq data of 90,770 qualified cells. RESULTS: We identified 15 prepuce cell subtypes, including fibroblast, smooth muscle cells, T/natural killer cells, macrophages, vascular endothelial cells, and dendritic cells. The proportions of these cell types varied among different individuals as well as between children and adults. Moreover, we detected cell-type-specific gene regulatory networks (GRNs), which could contribute to the unique functions of related cell types. The GRNs were also highly dynamic between the prepuce cells of children and adults. Our cell-cell communication network analysis among different cell types revealed a set of child-specific (e.g., CD96, EPO, IFN-1, and WNT signaling pathways) and adult-specific (e.g., BMP10, NEGR, ncWNT, and NPR1 signaling pathways) signaling pathways. The variations of GRNs and cellular communications could be closely associated with prepuce development in children and prepuce maintenance in adults. CONCLUSIONS: Collectively, we systematically analyzed the cellular variations and molecular changes of the human prepuce at single-cell resolution. Our results gained insights into the heterogeneity of prepuce cells and shed light on the underlying molecular mechanisms of prepuce development and maintenance.

One-stage tubularized urethroplasty using the free inner plate of the foreskin in the treatment of proximal hypospadias.

OBJECTIVE: This study summarizes the short-term efficacy of the one-stage tubularized urethroplasty using the free inner in proximal hypospadias. METHODS: A retrospective analysis was conducted on 42 patients with proximal hypospadias. All cases were treated with one-stage tubularized urethroplasty from January 2020 to June 2021. The postoperative complications like urethral fistula, urethral stricture, diverticulum, and split penis head were recorded. RESULTS: Patients were followed up for 3 to 15 months (an average of 8.5 months). A total of 26 cases (62%) were repaired without any complication. Five patients (11.9%) developed urinary fistulas and underwent secondary repair: three cases with anastomotic fistulas and two cases of coronal fistulas. Nine patients (21.4%) had stenosis of the head segment of the penis, six (14.3%) had stenosis that was relieved by urethral dilatation combined with topical mometasone furoate 1 month after urethral catheter removal. Two patients (4.8%) had severe stenosis with secondary surgical stenosis incision, and one (2.4%) had combined urethral diverticulum in which urethral stenosis incision and diverticulectomy were performed. CONCLUSIONS: Tubularized urethroplasty using the free inner bears the advantages of easy access, reduced short-term complications, low incidence of diverticula.

Cornification and classical versus nonclassical androgen receptor signaling in mouse penile/preputial development.

Mouse penile development is androgen-dependent. During development of male and female external genitalia, an internal ectodermal epithelial structure forms called the preputial lamina. At puberty the male preputial lamina canalizes to create the preputial space, effectively splitting into two layers: (a) the epithelial lining of the prepuce and (b) the surface epithelium of the penis. The female preputial lamina does not canalize, and instead remodels into the inverted U-shaped clitoral lamina of the adult female mouse. Androgen-dependent penile development was studied in transgenic mice with pathway-selective AR mutant transgenes through which AR signaling was activated either via the classical (AR-C) or the nonclassical pathway (AR-NC). Penile development and canalization of the preputial lamina was observed in AR-C and wild-type male mice naturally having both AR-C and AR-NC pathways. Conversely, clitoral development occurred in AR null (lacking both AR-C and AR-NC pathways) and AR-NC mice. The process of canalization of the preputial lamina seen in wild-type, AR-C and AR-C/AR-NC male mice involved cornification of the preputial lamina which involved up-regulation of keratin 10 and loricrin. Such up-regulation of these epidermal proteins was absent in the developing and adult clitoral lamina seen in wild-type female mice and AR-NC and AR null male (XY) mice. Thus, signaling through AR-C is sufficient to initiate and promote penile development and canalization of the preputial lamina, a process involving epithelial cornification.

Sensory innervation of the human male prepuce: Meissner's corpuscles predominate.

Meissner's corpuscles are the most abundant sensory corpuscles in the glabrous skin of the male prepuce. They are type I, rapidly adapting, low-threshold mechanoreceptors, and their function is linked to the expression of the mechanoprotein piezo-type mechanosensitive ion channel component 2 (PIEZO2). Stimulation of genital Meissner's corpuscles gives rise to sexual sensations. It has been recently demonstrated that digital Meissner's corpuscles, Meissner-like corpuscles, and genital end bulbs have an endoneurium-like capsule surrounding their neuronal elements; that is, the axon and glial lamellar cells, and their axons, display PIEZO2 immunoreactivity. It is unknown whether this is also the case for preputial Meissner's corpuscles. Furthermore, the expression of certain proteins that have been found in Meissner's corpuscles at other anatomical locations, especially in the digits, has not been investigated in preputial Meissner's corpuscles. Here, we used immunohistochemistry to investigate the expression of axonal (neurofilament, neuron-specific enolase), glial (S100 protein, glial fibrillary acidic protein, vimentin), endoneurial (CD34), and perineurial (glucose transporter 1) markers in the preputial and digital Meissner's corpuscles of male participants aged between 5 and 23 years. Furthermore, we investigated the occurrence of the mechanoprotein PIEZO2 in male preputial Meissner's corpuscles. Human male prepuce contains numerous Meissner's corpuscles, which may be grouped or isolated and are regularly distributed in the dermal papillae. Lamellar glial cells display strong expression of S100 protein and vimentin but lack expression of glial fibrillary acidic protein. In addition, they show axonal PIEZO2 expression and have an endoneurial capsule, but no perineurial. Our results indicate that human male preputial Meissner's corpuscles share the immunohistochemical profile of digital Meissner's corpuscles, which is considered to be necessary for mechanotransduction. These data strongly suggest that the structure and function of Meissner's corpuscles are independent of their anatomical location.

Microbiome Profile in Patients with Adult Balanoposthitis: Relationship with Redundant Prepuce, Genital Mucosa Physical Barrier Status and Inflammation.

Balanoposthitis is a common inflammatory condition of male genitalia, while the overall microbiota spectrum and its relevance to contributing factors have yet to be determined. This case-control study included patients with balanoposthitis (n = 26) and matched healthy controls (n = 29), both uncircumcised. Overt fungal infection in balanoposthitis was excluded, swab samples were collected, 16S rRNA gene sequenced and analysed. The profile of the microbiome was further analysed in relation to the clinical severity of the disease and the physical barrier status of the glans penis, including mucosa pH, transepidermal water loss, and mucosa hydration. In general, the microbiota composition was similar between patients with balanoposthitis and healthy controls, while it was different between patients with balanoposthitis and healthy controls with redundant prepuce. Decreased hydration of the mucosa and increased pH were found in patients with balanoposthitis. Staphylococcus warneri and Prevotella bivia are the 2 most abundant balanoposthitis-associated species and are positively correlated with disease severity.

Anatomy of the mouse penis and internal prepuce.

This paper addresses a confusing issue of preputial anatomy of the mouse. The term "internal prepuce" was used in 2013 to describe a preputial structure integral to the mouse glans penis. Subsequently in 2015 the same term was applied by another group to describe entirely different morphology, generating confusion in the literature. Because it is inappropriate to use the same term to describe entirely different structures, we take this opportunity to provide further descriptive information on the internal prepuce of the mouse employing gross dissection, analysis of serial histologic section sets, three-dimensional reconstruction, scanning electron microscopy and immunohistochemistry. For this purpose, we review and illustrate the relevant literature and provide some additional new data using standard morphological techniques including immunohistochemistry. The mouse internal prepuce is integral to the glans penis and clearly is involved in sexual function in so far as it contains a major erectile body innervated by penile nerves. The development of the mouse internal prepuce is described for the first time and related to the development of the corpus cavernosum glandis.

Development of the human prepuce and its innervation.

Development of the human prepuce was studied over the course of 9-17 weeks of gestation in 30 specimens. Scanning electron microscopy revealed subtle surface features that were associated with preputial development, namely the appearance of epidermal aggregates that appeared to be associated with formation of the preputial fold. Transverse and sagittal sections revealed that the epidermis of the glans is considerably thicker than that of the penile shaft. We described a novel morphogenetic mechanism of formation of the preputial lamina, namely the splitting of the thick epidermis of the glans into the preputial lamina and the epidermis via the intrusion of mesenchyme containing red blood cells and CD31-positive blood vessels. This process begins at 10-11 weeks of gestation in the proximal aspect of the glans and extends distally. The process is likely to be androgen-dependent and mediated via androgen receptors strategically localized to the morphogenetic process, but signaling through estrogen receptor may play a role. Estrogen receptor alpha (ESR1) has a very limited expression in the developing human glans and prepuce, while estrogen receptor beta (ESR2) is expressed more broadly in the developing preputial lamina, epidermis and urethra. Examination of the ontogeny of innervation of the glans penis and prepuce reveals the presence of the dorsal nerve of the penis as early as 9 weeks of gestation. Nerve fibers enter the glans penis proximally and extend distally over several weeks to eventually reach the distal aspect of the glans and prepuce by 14-16 weeks of gestation.

[A comparative study of three different circumcision devices for redundant prepuce and phimosis].

OBJECTIVE: To compare the clinical effects of disposable titanium nail circumcision stapler (TNCS), one-off circumcision stapler (Shang Ring) and disposable double-handle circumcision suture device (DHCSD) in the treatment of redundant prepuce and phimosis. METHODS: We reviewed the clinical data on 150 cases of redundant prepuce or phimosis treated with the TNCS (n = 50), DHCSD (n = 50) or Shang Ring (n = 50) from September 2018 to July 2020. We compared the operation time, intraoperative blood loss, wound healing time, Visual Analogue Scale (VAS) scores during and at 1 hour and 7 days after operation, postoperative complications and the patients' satisfaction with postoperative penile appearance among the three groups. RESULTS: The operation time was significantly longer (P < 0.05) but the wound healing time remarkably shorter (P < 0.05) in the TNCS and DHCSD groups than in the Shang Ring group. The intraoperative blood loss was markedly less in the TNCS and Shang Ring groups than in the DHCSD group (P < 0.05). No statistically significant difference was observed in the patients' satisfaction with postoperative penile appearance among the three groups (P > 0.05). The VAS scores during and at 1 hour and 7 days after operation and the incidence rate of postoperative complications were significantly higher in the Shang Ring and DHCSD groups than in the TNCS group (P < 0.05). CONCLUSIONS: The disposable titanium nail circumcision stapler is superior to disposable double-handle circumcision suture device and Shang Ring in the treatment of redundant prepuce and phimosis and deserves clinical promotion and application.?

A Novel Procedure of Prepuce Reconstruction Customized to the Religious Needs of Some Individuals.

Background Authors describe a novel procedure in a group of patients for prepuce reconstruction, ensuring complete glans penis coverage who had either been circumcised in childhood or had congenitally short prepuce. Methods Case records of all cases done by the novel method which involved penile degloving and maintenance of neoprepuce, with the help of de-epithelization of glans penis and a few key sutures performed over the period from January 2010 to December 2019 were reviewed retrospectively. A total of 46 patients, 32 had congenitally short prepuce and 14 had previous circumcision. Results All the patients had complete glans penis coverage. None of the patients had complications like urinary infection, meatal stenosis, collection in neoprepucial sac, balanitis, or posthitis. The mean followup was 23.24 months in 37 patients. Nine lost to followup. Conclusions The procedure is simple, gives reliable results, and is customized to the needs of the patients. It does not interfere with penile erections.

Reproductive tract biology: Of mice and men.

The study of male and female reproductive tract development requires expertise in two separate disciplines, developmental biology and endocrinology. For ease of experimentation and economy, the mouse has been used extensively as a model for human development and pathogenesis, and for the most part similarities in developmental processes and hormone action provide ample justification for the relevance of mouse models for human reproductive tract development. Indeed, there are many examples describing the phenotype of human genetic disorders that have a reasonably comparable phenotype in mice, attesting to the congruence between mouse and human development. However, anatomic, developmental and endocrinologic differences exist between mice and humans that (1) must be appreciated and (2) considered with caution when extrapolating information between all animal models and humans. It is critical that the investigator be aware of both the similarities and differences in organogenesis and hormone action within male and female reproductive tracts so as to focus on those features of mouse models with clear relevance to human development/pathology. This review, written by a team with extensive expertise in the anatomy, developmental biology and endocrinology of both mouse and human urogenital tracts, focusses upon the significant human/mouse differences, and when appropriate voices a cautionary note regarding extrapolation of mouse models for understanding development of human male and female reproductive tracts.

Two case reports of unusual phimosis in rhesus monkeys (Macaca Mulatta).

Phimosis is the inability of the penis to protrude from the prepuce. In the present report, we present two cases of phimosis in two rhesus monkeys. Surgical enlargement of preputial orifice was performed for unrestricted movement of penis. The exact cause of this condition is unknown to us.

The distribution of Preputial vessels in different severity of rat congenital hypospadias model: imaging study using micro-computerized tomography.

BACKGROUND: Micro-computerized tomography (micro-CT) is considered as an innovative non-invasive and high-resolution imaging technology. The current research aims to reconstruct the distribution of preputial vessels in different severity of rat congenital hypospadias model by micro-CT, and to provide an anatomic basis for the selection of preputial vessel pedicle flaps in surgery. METHODS: Pregnant rats were exposed to finasteride from gestational day 12 to 17. Depending on the position of the urethral meatus, the pups were divided into normal, mild hypospadias and severe hypospadias groups. Six months after birth, the preputial blood vessels were observed in vascular perfusion with Microfil (a silicone-based polymer) and scanned by micro-CT. CTvox and NRecon were utilized to reconstruct 3-dimentional (3D) images. A pathological analysis of the specimen was taken in order to determine the position of Microfil. RESULTS: The normal group and the mild hypospadias group had similar preputial image characteristics. At the junction of the inner and outer prepuce, the deep layer vessels of the superficial fascia were transversely distributed and formed a vascular ring-like structure. Among the severe hypospadias group, five had sufficient blood circulation while six had insufficient blood circulation. In sufficient blood circulation type, the ring-like vessels were found at the junction of the inner and outer prepuce similar to that of the normal and mild hypospadias group. However, only a small amount of capillary supply to this area in the insufficient type. CONCLUSION: The junction of the inner and outer prepuce with abundant blood circulation was suitable to be a vascular pedicle flap. The tubularized preputial island flaps were consistent with the ring-like vessels area, and the original blood supply was retained to the greatest extent.

Human glans and preputial development.

The urethra within the human penile shaft develops via (1) an "Opening Zipper" that facilitates distal canalization of the solid urethral plate to form a wide urethral groove and (2) a "Closing Zipper" that facilitates fusion of the epithelial surfaces of the urethral folds. Herein, we extend our knowledge by describing formation of the human urethra within the glans penis as well as development of the prepuce. Forty-eight normal human fetal penile specimens were examined using scanning electron microscopy and optical projection tomography. Serial histologic sections were evaluated for morphology and immunohistochemical localization for epithelial differentiation markers: Cytokeratins 6, 7, 10, FoxA1, uroplakin and the androgen receptor. As the closing zipper completes fusion of the urethral folds within the penile shaft to form a tubular urethra (~ 13 weeks), canalization of the urethral plate continues in proximal to distal fashion into the glans penis to directly form the urethra within the glans without forming an open urethral groove. Initially, the urethral plate is attached ventrally to the epidermis via an epithelial seam, which is remodeled and eliminated, thus establishing mesenchymal confluence ventral to the glanular urethra. The morphogenetic remodeling involves the strategic expression of cytokeratin 7, FoxA1 and uroplakin in endodermal epithelial cells as the tubular glanular urethra forms. The most ventral epithelial cells of the urethral plate are pinched off from the glanular urethra and are reabsorbed into the epidermis ultimately losing expression of their markers, a process undoubtedly regulated by androgens. The prepuce initially forms on the dorsal aspect of the glans at approximately 12 weeks of gestation. After sequential proximal to distal remodeling of the ventral urethral plate along the ventral aspect of glans, the prepuce of epidermal origin fuses in the ventral midline.

Contrasting mechanisms of penile urethral formation in mouse and human.

This paper addresses the developmental mechanisms of formation of the mouse and human penile urethra and the possibility that two disparate mechanisms are at play. It has been suggested that the entire penile urethra of the mouse forms via direct canalization of the endodermal urethral plate. While this mechanism surely accounts for development of the proximal portion of the mouse penile urethra, we suggest that the distal portion of the mouse penile urethra forms via a series of epithelial fusion events. Through review of the recent literature in combination with new data, it is unlikely that the entire mouse urethra is formed from the endodermal urethral plate due in part to the fact that from E14 onward the urethral plate is not present in the distal aspect of the genital tubercle. Formation of the distal portion of the mouse urethra receives substantial contribution from the preputial swellings that form the preputial-urethral groove and subsequently the preputial-urethral canal, the later of which is subdivided by a fusion event to form the distal portion of the mouse penile urethra. Examination of human penile development also reveals comparable dual morphogenetic mechanisms. However, in the case of human, direct canalization of the urethral plate occurs in the glans, while fusion events are involved in formation of the urethra within the penile shaft, a pattern exactly opposite to that of the mouse. The highest incidence of hypospadias in humans occurs at the junction of these two different developmental mechanisms. The relevance of the mouse as a model of human hypospadias is discussed.

Accessory fold of skin on the ventral surface of the penis: Is it a redundant prepuce?

Variations in the skin of the prepuce are very rare. We report here a variation of the penile skin as observed in an adult male cadaver aged approximately 65 years. The penis was covered by thin nonhairy skin. The glans was not covered with prepuce. There was no evidence of circumcision. The ventral surface of the penis, adjacent to the glans, had a huge fold of skin. This fold resembled the prepuce and had a hole in it. The glans penis had a normal urethral meatus. There was no evidence of hypospadias as the entire ventral surface of the penis was covered completely by the skin. We discuss the clinical importance of this accessory fold of skin.

[Pathogenesis, prevention and management of edema after prepuce surgery].

Prepuce diseases are very common conditions in urology and andrology, and quite a few cases need to be treated by surgery. Preputial edema is a common complication after prepuce surgery, with a higher incidence rate in children than in adults. Although preputial edema is just moderate symptom and does not affect urination, it worries or even distresses the patient both physically and psychologically. In recent years, rapid achievements have been made in prepuce surgery, as in prepuce circumcision, preputial neoplasm excision, and penile degloving repair, which can now be accomplished with shorter time and higher efficiency. Despite constant improvement in the methods and techniques for prepuce surgery, postoperative edema remains difficult to be totally prevented. Pathogenic factors for postoperative preputial edema vary from disturbance of blood circulation to inflammatory factor-induced change in capillary permeability, lymphatic circulation disorders, and neurogenic edema. Elimination of the pathogenic factors and precautionary measures after surgery count significantly to the prevention and management of postoperative preputial edema. This review focuses on the pathogenesis, prevention and treatment of edema after prepuce surgery.