Evaluation of Smooth Muscle Myosin Heavy Chain Isoform Expressions in a Buried Penis.

BACKGROUND: A buried penis (BP) is rare in which the penile body is retracted into the prepubic adipose tissue. This research focuses on differences in smooth muscle myosin heavy chain (SMMHC) isoform expressions in the dartos fascia. METHODS: A total of 82 children, 41 of whom had BPs, who applied for circumcision between May and November 2021, were included in the study. The cases were divided into four groups aged ≥6 years (NP6, n = 18) and aged ≤3 years (NP3, n = 17) with normal penile appearance, aged ≥6 years (BP6, n = 23) and aged ≤3 years (BP,n = 24) with a BP. SMMHC isoforms mRNA gene expression analyses were performed by quantitative PCR technique in dartos fascia obtained from foreskin removed by circumcision. RESULTS: Compared to the NP3 group, the SM1 mRNA expressed in the BP6 group was statistically significantly higher (p < 0.005). SM2 mRNA levels expressed in dartos fascia were considerably higher in NP6 and NP3 groups compared to BP6 and BP3 groups (p < 0.001). The SM2/SM1 ratio was 0.85 in the BP6 group and 1.46 in the NP6 group, which was statistically significant (p = 0.006) and increased from 0.87 in the BP3 group to 2.21 in the NP3 group (p < 0.001). CONCLUSION: In a buried penis, there is a difference in the expression of SMMHC isoforms. SM1 is highly expressed, while SM2 decreases, increasing the SM2/SM1 ratio. This causes increased contractility in the smooth muscle, leading to retraction of the penile body. The dartos fascia surrounding it resembles aberrant muscle tissue in boys with a BP. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Case-control study.

Granuloma annulare of the penis: a uncommon location for an usual disease.

The subcutaneous clinical variant of granuloma annulare (GA) is rare and tends to present more frequently in children, in locations unusual for conventional GA. Involvement of the penis is exceptional and has been rarely reported. Most cases are located in the shaft of the penis and tend to persist without spontaneous remission. Diagnosis is done only after biopsy, and surgical resection of the lesions is not unusual. We report a new case of subcutaneous GA of the penis in a 13-year-old boy with lesions persistent for the past year. Surgical excision of one of them allowed the correct diagnosis. No further treatment was done, and the condition has not remitted 1 year later. We stress the importance of clinical recognition of unusual presentations of GA to avoid overtreatment of lesions that do not need an aggressive approach.

Mechanisms of penile fibrosis.

INTRODUCTION: Penile fibrosis has been conceptually identified with the plaque that develops in the tunica albuginea in Peyronie's disease (PD), or with localized processes induced in the corpora cavernosa by ischemic or traumatic events. Recently, it has been proposed that a diffuse, progressive, and milder intracorporal fibrosis, which affects also the media of the penile arteries, is responsible for vasculogenic erectile dysfunction (ED) associated with aging, smoking, diabetes, hypertension, and post-radical prostatectomy. These processes differ in etiology, time course, target cells, and treatment, but have many features in common. AIM: To review the literature pertaining to fibrosis in the penis, related to PD and ED. METHODS: PubMed search for pertinent publications mainly during 2001-2008. RESULTS: This review focuses initially on PD and then deals with studies on ED in animal and cell culture models, discussing some of the pathophysiological similarities between tunical fibrosis in PD and corporal fibrosis in corporal veno-occlusive dysfunction (CVOD), and emerging therapeutic strategies. The role of profibrotic factors, the excessive deposit of collagen fibers and other extracellular matrix, the appearance of a synthetic cell phenotype in smooth muscle cells or the onset of a fibroblast-myofibroblast transition, and in the case of the corporal or penile arterial tissue the reduction of the smooth muscle cellular compartment, are discussed. This histopathology leads either to localized plaques or nodules in penile tissues, or to the diffuse fibrosis causing impairment of tissue compliance that underlies CVOD and arteriogenic ED. The antifibrotic role of the sustained stimulation of the nitric oxide/cyclic guanosine monophosphate pathway in the penis and its possible relevance to exogenous and endogenous stem cell differentiation is also briefly presented. CONCLUSIONS: Fibrotic processes in penile tissues share a similar cellular and molecular pathophysiology and common endogenous mechanisms of defense that have inspired novel pharmacological experimental approaches.

Immunohistochemical and ultrastructural features of Langerhans cells in condyloma acuminatum.

BACKGROUND: There are few studies on the abnormal morphology of Langerhans cells (LCs) in condyloma acuminatum (CA) lesions and the essence of the abnormal morphology of LCs in CA lesions is still not well elucidated. The aim of this study was to further investigate the morphological features of LCs in CA lesions. METHODS: CD1a(+) LCs in 13 CA lesions and in 13 normal controls were labeled using immunohistochemistry and examined by light microscopy. Ultrastructural investigation on LCs in six CA lesions and in six normal controls was performed by electron microscopy. RESULTS: Compared with those in normal controls, most CD1a(+) LCs in CA lesions exhibited dysplastic dendrities and abnormal distribution. The number of CD1a(+) LCs in CA lesions (26.31 +/- 18.84) was statistically lower (p < 0.001) than that in normal controls (72.00 +/- 27.40). Electron microscopy showed that the number of Birbeck granules within lesional LCs (4.00 +/- 2.94) was significantly decreased (p < 0.001) than that within normal LCs (10.80 +/- 4.78). The ultrastructures of most lesional LCs displayed degenerative changes. CONCLUSIONS: The morphology of most LCs in CA lesions shows degenerative changes, which suggest that these LCs have been functionally impaired.

Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma.

BACKGROUND: Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer. OBJECTIVES: To investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer. METHODS: By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients. RESULTS: HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS. CONCLUSIONS: Our study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.

Ectopic modified sebaceous glands in human penis.

The balanopreputial sulcus is believed to be the most frequent site of the so-called Tyson's glands. The intriguing feature of these anatomical structures is their mere existence, which has been doubted. Herein, the authors present a case of a 24-year-old man who underwent surgical treatment of his phimosis. On microscopic examination of the specimen, glands with morphological features similar to those described by Tyson were noted.

[Predicting cancerization of condyloma acuminatum by testing expression of p16].

BACKGROUND & OBJECTIVE: About 3%-10% of condyloma acuminatum (CA) may develop into cancer. Some studies indicated that homologous deletion of p16 gene is a major factor that causes cancerization of CA. This study was to detect expression of P16 protein in CA tissues and its cancerization tissues, and to investigate relationship of abnormal expression of P16 and cancerization of CA. METHODS: A total of 75 skin biopsy specimens were collected, including 30 normal skin samples (control group), 35 CA samples, and 10 cancerized CA samples. Expression of P16 was tested by LSAB immunohistochemistry, and relationship of P16 and cancerization of CA was statistically analyzed. RESULTS: CA and normal skin tissues showed weakly positive expression of P16, no significant difference exist (P< 0.05). Cancerized CA tissues showed positive or strongly positive expression of P16, significantly stronger than CA and normal skin tissues (P< 0.05). CONCLUSIONS: Positive and strongly positive expression of P16 in CA tissue implied risk of cancerization of CA. P16 may be a useful predictor for cancerization of CA.

[Experimental and clinical research of "Keyouling" on treatment of condyloma acuminata].

OBJECTIVE: To investigate the effects of traditional Chinese medicine "Keyouling" in treatment of condyloma acuminata (CA). METHODS: The effects of "Keyouling" at different concentrations on growth and proliferation of rabbits' prepuce epithelial cells and CA warts tissue were assessed by means of cellular primary culture and subculture, and the effects of "Keyouling" at different concentrations on the expression level of HPV6.11 DNA and expression level of HPV6.11 DNA of different area of CA patient's penis were quantitatively detected by means of FQ-PCR. RESULTS: "Keyouling" had no effect on growth and proliferation of rabbits' prepuce cuticle cells, but it had significant inhibition on CA warts tissue cells and expression of HPV6.11 DNA. Concentrations of "Keyouling" assumed negative correlated with cell proliferation rate of CA warts tissue and expression level of HPV6.11 DNA, and also had significant inhibition on expression of HPV6.11 DNA of negative cutaneous lesion area and cutaneous lesion area of CA patients. CONCLUSION: "Keyouling" had significant anti HPV6.11 effect, could significantly restrain growth and proliferation of CA warts tissue cells, while it had no damaging effect on normal organic cuticle cells. It was suggested that "Keyouling" was safe in clinical use and had good therapeutic effect on CA and subclinical infection.

In vivo fluorescence kinetics and photodynamic therapy in condylomata acuminata.

BACKGROUND: Topical application of 5-aminolaevulinic acid (ALA) to condylomata acuminata leads to accumulation of protoporphyrin IX (PpIX); therefore ALA-induced photodynamic therapy (ALA-PDT) appears to be a potential treatment. OBJECTIVES: To investigate in vivo the PpIX fluorescence time course after topical application of ALA in order to determine the optimal time for irradiation, and to assess the efficacy of subsequently performed ALA-PDT. METHODS: Fluorescence kinetics was studied in 12 male patients with condylomata acuminata. Confirmation of diagnosis was established with conventional histology and polymerase chain reaction. Lesions were treated with 20% ALA and irradiated at the optimal time with a dose of 70 J cm-2 or 100 J cm-2 light. An additional session with 100 J cm-2 was administered 1 week later to lesions that persisted. RESULTS: The in vivo study of fluorescence kinetics indicated that the optimal time for irradiation varied among patients from 6 to 11 h. The overall cure rate was 72.9%, 12 months after treatment. CONCLUSIONS: Topical ALA-PDT is a potentially effective treatment for condylomata acuminata.

Mucinous metaplasia of the penis.

AIMS: To determine the incidence of mucinous metaplasia occurring in the foreskin or glans penis and any associated clinical or histopathological features. METHODS AND RESULTS: Following the recognition of two index cases, 100 other foreskin specimens were retrieved from the histopathology archives at Southampton General Hospital. The haematoxylin and eosin-stained slides were examined by a single observer to detect the presence of mucin-producing cells in the surface epithelium. The absence of mucinous metaplasia in negative cases was confirmed with mucin histochemistry. In total, four cases of mucinous metaplasia were identified, three involving the foreskin and one involving the glans penis. The age range was 51-80 years. Three cases were associated with Zoon's balanitis and the fourth showed mild non-specific balanitis. All four cases showed positive staining with both diastase periodic acid-Schiff and alcian blue. No mucin-producing cells were identified in non-inflamed or minimally inflamed specimens. CONCLUSIONS: Mucinous metaplasia of the penis is an uncommon but under-recognized condition. It is seen in the elderly and appears to be a metaplastic change associated with severe chronic inflammation, and possibly more specifically with Zoon's balanitis. Our study identified a case affecting the glans penis, a site not previously recorded.

Lymphohistiocytic and granulomatous phlebitis in penile lichen sclerosus.

Lichen sclerosus (LS) is a chronic inflammatory disease of unknown etiology that may affect the genital and/or extragenital skin of individuals of either sex at all ages. In boys, the prepuce is the most common site of involvement. The diagnostic criteria of LS include the presence of inflammatory infiltrates mainly composed of T lymphocytes. We report on two cases of LS of the prepuce because of the unusual feature of lymphocytic (CD45RO+ and CD20+), histiocytic (CD68+), and granulomatous phlebitis. This lesion was not present in a group of another 18 cases of childhood penile LS. We have not been able to find any references describing and illustrating inflammatory involvement of the dermal vein walls in LS. Unlike the data reported in the literature, the dermal inflammatory infiltrates of these two cases showed a similar proportion of B and T lymphocytes in addition to frequent CD68+ histiocytes.

Immunohistochemical expression of glucose transporter-1 in human penile proliferative lesions.

Glucose transporters (GLUTs) are a family of membrane proteins responsible for the transport of glucose across cellular membranes. In terms of their mRNA levels, they have been reported to be expressed in some human tumours. However, the immunohistochemical localization of GLUTs in human urogenital lesions has rarely been studied. This study was performed to evaluate the expression of GLUT1 in penile proliferative lesions (18 cases of penile carcinoma and 13 cases of condyloma acuminatum). Using an isoform-specific anti-GLUT1 antibody, formalin-fixed paraffin-embedded sections were stained by the avidin-biotin complex method. In all cases of penile carcinoma, GLUT1 staining was diffusely recognized on the cell membrane of the carcinoma cells in the mainly infiltrating areas. However, the inner areas of the tumour were more weakly and focally stained. The intensity of staining for the penile carcinoma (staining score = 2.8 +/- 0.6) was stronger than that for condyloma acuminatum and that for adjacent non-proliferative areas. All cases of condyloma acuminatum showed a diffuse staining on the cell membrane in the basal and intermediate layers (staining score = 2.4 +/- 0.5). Non-proliferative (histologically normal) glans areas adjacent to the above lesions expressed the weakest GLUT1 staining only in the stratum basale (staining score = 1.8 +/- 0.5). These three areas showed significantly different staining scores from each other (p < 0.01). In conclusion, GLUT1 is expressed dominantly in penile proliferative lesions, especially in infiltrating areas of penile carcinoma.

Immunohistochemical detection of p53 protein expression in HPV-induced condyloma acuminatum.

Immunohistochemical peroxidase staining for p53 protein was performed on 22 condyloma acuminatum tissue samples from patients infected with human papillomavirus (HPV). The purpose of our study was to understand the benign character of this syndrome. The patients studied were infected by HPV type 6 and 11. Two monoclonal antibodies, PAbs DO-1 and 240, were used to detect the p53 protein. Overexpression of wild-type p53 was found in the nuclei of the basal cell layers. In healthy tissues and non-infected patients no p53 protein expression was detected. We would like to speculate that infection with HPVs and their viral protein E7, which is implicated in disruption of normal growth, may regulate the induction of wild-type p53 over-expression, as is known for DNA-damaging agents such as UV- or X-radiation.

[Immunohistochemical characterization of a median raphe cyst of the penis]. / Caractérisations immunohistochimiques d'un kyste du raphé médian de la verge.

Cysts and canals found on the ventral surface of the penis have been ascribed to minor dysembryoplasia of the male genitalia. These lesions occur almost exclusively on the ventral surface of the penis along the median raphe and can extend from the urethral meatus to the anus. They are lined by stratified urothelium or squamous epithelium and they do not communicate with the urethra. Most cases are noted in early adulthood, they are usually asymptomatic but may become infected. Surgical removal is the adapted treatment. In this report we describe a case in which the urothelial origin of the cyst was documented by immunohistochemistry for cytokeratin 13.

Collagen alterations in the corpus cavernosum of men with sexual dysfunction.

Previous studies have noted the abundance of collagen in human erectile tissues and the association of altered collagen content with erectile dysfunction. We investigated these notions by studying the collagen characteristics of biopsies from the corpus cavernosum of men who required surgical correction of their sexual dysfunction. Histologic analysis revealed abundant collagen within the erectile tissues. With the exception of patients with Peyronie's disease and priapism, only mild alterations in collagen architecture were noted in the remainder of the patients. Biochemical quantitation confirmed the histologic study. The mean collagen content represented 47% of total protein in most patients. The proportion rose to 68% and 73% in the patients with Peyronie's disease and priapism, respectively. No statistical difference in collagen content was noted in all the patients studied. Immunohistochemistry revealed collagen types I and IV to predominate in the corpus cavernosum, with type III making up the minority. There were no qualitative changes in collagen ratios with age and disease. We conclude that though collagen is a major component of the penis, there are no changes in its histologic characteristics that can be correlated to senescence or to the etiology of erectile dysfunction.

Ultrastructural visualization of human papillomavirus DNA in verrucous and precancerous squamous lesions.

Human papillomavirus (HPV) DNA was ultrastructurally localized by the non-isotopic in situ hybridization technique in formalin-fixed, paraffin-embedded specimens of verruca vulgaris of the skin, condyloma acuminatum of the penis and severe dysplasia of the uterine cervix. Biotinylated DNA probe cocktails were employed for the visualization of HPV-DNA, types 6 and 11 (HPV 6/11) and types 16 and 18 (HPV 16/18). The papillomavirus genus-specific antigen was also visualized by pre-embedding immunoelectron microscopy using rabbit antiserum. In verruca vulgaris, HPV antigen-positive 50-60 nm-particles of mature viral size were observed in the nuclei of the granular cells and parakeratotic cells with perinuclear haloes, whereas HPV 6/11 and HPV 16/18 DNA were negative. In condyloma acuminatum, the nuclei were positive for the HPV antigen and HPV 6/11 DNA, but were negative for HPV 16/18 DNA. More cells were labeled for the viral DNA than for the viral antigen. The ultrastructural observation indicated the presence of the naked (plasmid) viral DNA as fine particles sized 15-20 nm. In the dysplastic cervical mucosa, dot-like positivity of HPV 16/18 DNA was recognized. The HPV antigen and HPV 6/11 DNA were undetectable. HPV 16/18 DNA was localized in part of the nuclear chromatin. This pattern of localization may suggest integration of the viral DNA into the host cell DNA.

Sclerosing lipogranuloma of the penis: chemical analysis of lipid from the lesional tissue.

The origin of paraffin from penile granuloma tissue was determined first by field desorption mass spectrometry. A case of penile granuloma with histopathological findings of sclerosing lipogranuloma is presented. Chemical composition of the lesional lipid by elemental analysis and infrared absorption spectroscopy revealed paraffin hydrocarbon. Field desorption mass spectrometric analysis showed the paraffin to be a mixture of saturated hydrocarbons containing substantially 24 to 40 carbon atoms. On the basis of the chemical structure of naturally occurring lipids we concluded that this paraffin was exogenous and not endogenous material that was produced in the tissue following lipid degeneration.