Penis and scrotum
Last revised 4 October 2007
Copyright © 2002-2007, PathologyOutlines.com, Inc.
Reviewed by Antonio L. Cubilla, M.D., January 2004 (see Reviewers page)
Bold and underlined topics are hypertext links, and may open a new window
Penis
Anatomy, congenital anomalies, circumcision, priapism
Inflammatory lesions: accessory urethral canals, balanoposthitis, cellulitis, chancroid, cutaneous verruciform xanthoma, fungal infections, Fournier’s gangrene, gangrenous balanitis, granuloma inguinale, herpes simplex virus, HIV, inflammatory pseudotumor, lentiginous melanosis, lichen sclerosus (BXO), lymphogranuloma venereum, molluscum contagiosum, Mondor’s phlebitis, mucoid cyst, os penis, papillomatosis of glans corona, paraphimosis, Peyronie’s disease, phimosis, plasma cell balanitis, scabies, syphilis, Tancho’s nodules and paraffinomas
Benign tumors: condyloma acuminatum, epithelioid hemangioma, giant condyloma, leiomyoma, myointimoma, squamous hyperplasia, transitional papilloma
Dysplasia/carcinoma in situ: penile intraepithelial neoplasia, carcinoma in situ, Bowen’s disease, bowenoid papulosis, erythroplasia of Queryat
Squamous cell carcinoma and variants: general, squamous cell carcinoma NOS, adenosquamous, basaloid, papillary, sarcomatoid, verruciform, verrucous, warty
Other malignancies: basal cell carcinoma, clear cell sarcoma, Kaposi’s sarcoma, leiomyosarcoma, malignant mesothelioma, melanoma, metastases, mucoepidermoid carcinoma, proximal type epithelioid sarcoma, sclerosing epithelioid fibrosarcoma
Miscellaneous: staging, features to report, grossing penectomy specimens, grossing circumcision specimens
Scrotum
Non-neoplastic lesions: fat necrosis, Fournier’s gangrene, idiopathic calcinosis, massive localized lymphedema in morbidly obese, peritesticular fibrosis, sclerosing lipogranuloma, tunica albuginea cysts
Neoplastic lesions: aggressive angiomyxoma, angiomyofibroblastoma, calcifying fibrous pseudotumor, cutaneous verruciform xanthoma, desmoplastic round cell tumor, leiomyoma, leiomyoma with bizarre nuclei, liposarcoma, malignant mesothelioma, Paget’s disease, posttraumatic spindle cell nodules, squamous cell carcinoma
AJCC Cancer Staging Manual (6th Ed)
American Journal of Clinical Pathology (AJCP), Jan 1975 to Jan 2004 [no images]
American Journal of Pathology, (AJPath), Jan 1975 to Feb 2004
American Journal of Surgical Pathology (AJSP), Mar 1977 to Jan 2004
Archives of Pathology and Lab Medicine (Archives), Jan 1976 to Feb 2004
Human Pathology (Hum Path), Mar 1970 to Jan 2004
Modern Pathology (Mod Path), Jan 1988 to Feb 2004
Rosai, J: Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Sternberg, S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins, 1999
www.Webpathology.com - source of numerous beautiful GU images used in these outlines
Please refer to these primary references for more detailed discussions and photographs
Penis
Suspended from front and sides of pubic arch, contains majority of urethra
There are 3 main parts: the distal glans (head), the middle body (corpus or shaft) and the proximal root
Body is composed of three cylindrical masses of cavernous erectile tissue (specialized venous sinuses of variable diameter and widely interconnected) bound together by fibrous tunica albuginea
Orientation: the upper surface is termed dorsal, the undersurface is termed ventral
Drawings: compartments, transverse section, local anatomy #1, #2, arteries, veins, urethra
Micro images: transverse section, tunica albuginea
Virtual slides: cross section
Buck’s fascia
Fibroelastic and vascular membrane encasing and separating dorsal corpora cavernosa and ventral corpus spongiosum
Coronal sulcus
Narrow and circumferential cul de sac (in non-circumcised) behind glans corona; area of insertion of dartos and Buck’s fascia
Corpora cavernosa
Two lateral masses of erectile tissue that form bulk of penis; posterior portions are called crura, are connect to pubic arch
Micro images: vascularized tissue in fibrous stroma #1, #2, #3, #4, #5
Corpus spongiosum
Median mass of erectile tissue that contains most of urethra
Micro images: vascularized tissue with adjacent urothelium #1, #2, #3, #4, #5
Dartos
Smooth discontinuous muscle layer covering corpora and mid part of foreskin
Foreskin (prepuce)
Skin folded on itself covering the glans (clitoris in females)
In normal males, long foreskins cover the meatus and the glans is not visible
Layers are outer skin (squamous epithelium, lamina propria), dartos, inner mucosa
Micro images: outer and inner surface
Fossa navicularis
Terminal dilated portion of penile urethra, contains stratified, non-keratinized, squamous epithelium
Frenulum
Fibrous band of tissue attaching foreskin to ventral glans
Gross images: frenulum
Glans
Portion distal to coronal sulcus
Conical cup covering distal end of penile shaft
Layers are squamous epithelium, lamina propria, corpus spongiosum, tunica albuginea and corpora cavernosa
Glans corona
At base of glans, slightly elevated circumferential rim
Urethral meatus (meatus urethralis)
Urethral opening
Usually at central ventral glans penis
Vertical cleft, related to frenulum
Urethra
Divided into 3 portions in male: prostatic urethra (proximal, surrounded by prostate, contains urothelium), membranous urethra (from lower pole of prostate to bulb of corpus spongiosum, stratified or ciliated pseudostratified columnar epithelium), penile urethra (passes through corpus spongiosum, stratified or ciliated pseudostratified columnar epithelium)
Layers are surface columnar epithelium and basal stratified or pseudostratified epithelium
Occasional PSA positive glands are present, Hum Path 2002:33;905
Penile urethra contains plasma cells, T lymphocytes and macrophages, epithelium contains IgA secretory component and dendritic cells; protect against ascending infections, AJPath 1995;147:155
Regional lymph nodes
Superficial inguinal nodes (site of 1-3 sentinel nodes), deep inguinal, external iliac, internal iliac (pelvic nodes)
Periurethral glands
Cowper’s (bulbourethral) glands: mucinous acinar structures deep at level of membranous urethra
Intraepithelial glands (Morgagni’s lacunae): one-layer cylindrical intraepithelial glands, micro image
Littre’s glands: tubuloacinar mucinous glands present along entire length of corpus spongiosum; micro image
Miscellaneous:
Penile glycogenated epithelial cells indicate recent vaginal intercourse, AJCP 1985;84:524
Penile swabs after recent vaginal intercourse almost always contain female cells identifiable by FISH (image), Archives 2000;124:1080
Skin covering of penis is thin, stratified squamous epithelium, loosely connected to deeper parts of organ; non-keratinizing at glans penis; keratinized after circumcision
Skin at root of penis is continuous with skin over scrotum and perineum
Aphallia
Agenesis of penis
Only 70 cases reported; associated with other GU abnormalities
Chordae
Fibrous band associated with hypospadias or epispadias
Concealed penis
Penis is normally developed but hidden under fat in suprapubic region, scrotum, perineum, thigh
Diphallia
Duplication of penis
Associated with hypospadias, bifid scrotum, bladder duplication, renal agenesis
Epispadias
Urethra opens onto dorsal surface of penis
Penopubic epispadias (opening in penopubic junction) is most common, associated with urinary incontinence
Hypoplasia
Almost always associated with abnormalities of GU tract
Hypospadias
Urethra opens onto ventral surface of penis or scrotum
1/300 live male births
Due to failure of fusion of urethral folds
Hypospadias and epispadias are associated with abnormal descent of testes, urinary tract malformations, obstruction, urinary tract infections, possibly infertility if orifices are near base of penis
Lateral curvature
Due to hypo/hyperplasia of one corpora cavernosa
Median raphe cysts
Due to anomalies in development of urethral groove, trapped epithelial cells or migration of epithelial cells after closure of genital folds
Midline, usually translucent and subcutaneous masses in ventral shaft
Lined by squamous, columnar, mucus-producing or apocrine-like epithelium
Micropenis
Penis small, but normal ratio of shaft length to circumference
Torsion
Fibrous tissue surrounding corpus spongiosum or short urethra causes rotational defect of penile shaft
Webbed penis
Scrotal skin extends to ventral portion of penis and hides it
Excision of foreskin
Associated with reduced incidence of penile cancer and bacterial infections in children
Associated with reduced incidence of HIV infection, apparently due to CD4+ T lymphocytes on inner mucosa of foreskin (see HIV)
Prolongation of erection associated with pain
May have fever and difficulty voiding
Associated with impotence in 17% to 50%
Usually due to obstruction of the deep dorsal vein of penis due to sickle cell disease, leukemia, cancer, trauma, drugs, idiopathic
Common presenting sign of carcinomas metastatic to the penis.
Treatment: prompt intervention is important with drugs or surgical aspiration of blood / clots
May open near fossa navicularis, become inflamed and produce symptoms
Infection of glans and foreskin, usually due to Candida, anaerobes, Garderella, pyogenic bacteria
Common in uncircumcised newborns or uncircumcised men with poor hygiene and accumulation of smegma
Due to propensity of pathogenic bacteria to adhere to inner mucosal surface of foreskin
Causes phimosis
More common in newborns and immunosuppressed
Usually involves scrotum
Usually caused by group A streptococcus
Caused by Haemophilus ducreyi
Soft painful ulcer, may extend rapidly and be associated with ruptured inguinal abscess
May destroy external genitalia if superimposed Fusobacterium infection is present
Micro: zonation; upper layer is ulcer base with fibrin, neutrophils and necrosis; middle layer has granulation tissue, pallisading blood vessels and thrombosis; deep layer has marked lymphoplasmacytic infiltrate
Cutaneous verruciform xanthoma
Rare, uncertain etiology, usually in oral mucosa, rarely in scrotum, penis
Etiology: initial keratinocyte damage attracts neutrophils, then dermal dendrocytes phagocytosize necrotic keratinocyte debris; probably not due to HPV; foam cells most likely derived from dermal dendritic cells.
Gross: solitary, raised or polypoid with cup-shaped craters
Micro: foam cell aggregates in vascularized submucosa or papillary dermis, associated with verrucous epithelial hyperplasia; cup shaped craters filled with parakeratotic cells blending into keratinocytes; also neutrophilic infiltrate near surface of epidermis between plump parakeratotic cells and keratinocytes of varying intensity; bandlike plasma cell infiltrate at base of epidermis
Positive staining (foam cells): Factor VIIIa, CD68, Mac387, cytokeratin (weak)
Negative staining: S100
References: AJSP 1998;22:479
Superficial or deep
Superficial: dermatophytes, spores often in keratinized epithelium, often spreads locally from groin
Deep: rare, usually spreads via blood from other sites
Candida albicans: usually sexually transmitted, 15% of men are asymptomatic carriers, may reinfect women
Necrotizing fasciitis of genitalia and perineum
Usually due to Staph or Strep in children; gram negative rods or anaerobic bacteria in adults
Affects Buck’s fascia and foreskin, sparing glans
Risk factors: trauma, burns, anorectal disease, diabetes, leukemia, alcoholic cirrhosis
Also called Corbus’s disease
Rapidly progressing necrotizing inflammatory disease due to anaerobes in glans penis
May cause total necrosis of glans; although foreskin may be secondarily involved in advanced cases, the site of the lesion is the glans, sparing the penile fascia and foreskin (contrary to Fournier’s gangrene)
Penile necrosis in diabetic patients produces similar changes in the distal penis
Sexually transmitted disease caused by Calymmatobacterium granulomatis, a gram negative rod
Initially small painful nodule at infection site; nodule ulcerates; may have satellite lesions
Micro: massive plasma cell infiltrate without lymphocytes, large mononuclear cells with Donovan bodies (large, intracytoplasmic encapsulated bipolar bodies, highlighted with Warthin-Starry stain)
Sexually transmitted disease, usually caused by HSV2
Multiple small (1-2 mm) vesicles that rupture and cause painful ulcers
Micro: ground glass nuclei due to intranuclear virus; multinucleated giant cells
Human immunodeficiency virus (HIV)
Most HIV-1 positive men are infected via the penis
Lack of circumcision confers 8x increased risk, apparently due to high lymphocyte density in foreskin mucosa (HIV-1 targets CCR5 and CXCR4 receptors on CD4+ T cells), higher than uterine ectocervix, AJPath 2002;161:867
No infiltration by HIV-1 of foreskin outer surface
Associated with chronic condom catheterization
Frequent lesion of glans and foreskin
Benign, although associated with melanomas
Gross: flat pigmented macules with irregular borders
Micro: melanocytic hyperplasia, hyperpigmentation of basal epithelium, elongation of rete ridges, no atypia
Lichen sclerosus (Balanitis xerotica obliterans )
Male equivalent of lichen sclerosus et atrophicus of vulva, a chronic and atrophic mucocutaneous condition
Affects older men, may have autoimmune etiology
More frequent in foreskin, but coronal sulcus, glans and even urethra may be affected
May cause narrowing of urethral meatus or phimosis.
Atypical lichen sclerosus shows epithelial dysplastic changes (low grade or high grade)
Associated with low grade squamous cell carcinoma in glans and foreskin (non HPV variants-squamous cell NOS, verrucous, papillary); unusual in basaloid or condylomatous (warty) carcinomas
Treatment: circumcision, but may recur at scar
Gross: gray-white foci of atrophy in foreskin or perimeatal glans
Micro: thinning or thickening of epidermis with orthokeratotic (i.e. anuclear as in normal epidermis) hyperkeratosis, lamina propria thickening and loss of structures due to edema, sclerosis or hyalinization; vacuolar degeneration of basal layer, diffuse fibrosis, deep lymphocytic infiltrate; usually spares corpus spongiosum of glans and foreskin dartos
Micro images: orthokeratotic hyperkeratosis and epidermal atrophy, hyalinized lamina propria
References: AJSP 2003; 27:1448
Sexually transmitted disease caused by Chlamydia trachomatis
Painless papule or ulcer, followed by suppurative inflammation of inguinal lymph nodes, followed by lymphocytic hyperplasia and massive plasma cell infiltration; later get stellate abscess, then suppurative granuloma with sinuses and tracts
Caused by DNA pox virus; may be sexually transmitted
Gross: 3-6 mm dome shaped papule with central umbilication
Micro: prominent Henderson-Patterson bodies (intracytoplasmic eosinophilic inclusions containing virus particles) in stratum spinosum and granulosum
Micro images: low power, Henderson-Patterson bodies
Due to trauma or herpes simplex infections
Gross: firm, subcutaneous cord-like structures along dorsal shaft of penis or around coronal sulcus
Micro: massive thrombosis of superficial venous plexus of penis
Inflammatory lesion due to accessory urethral canals, on foreskin or glans, associated with intraepithelial mucous cells or glands
Heterotopic bone in penis, most commonly in elderly, also children
The majority of mammals have an intrapenile bone, except some primates including men
Associated with Peyronie’s disease
Papillomatosis of glans corona
Also called hirsutoid papillomas, pearly penile papules
Benign, asymptomatic
Associated with male sexual partners of women with cervical HPV lesions, although perhaps due to greater surveillance
Gross: multiple pearly gray white fibroepithelial papillomas, 1-2 mm, in dorsal glans corona; usually in 2-3 rows
Gross images: small papillary lesions
Micro: hyperkeratosis but no koilocytosis, no significant inflammation
DD: condyloma acuminatum
Forceful retraction of phimotic foreskin over glans may cause marked swelling which blocks replacement of foreskin
Painful, associated with urinary retention and constriction
Treat with circumcision
Fibrous thickening of dermis and Buck’s fascia between corpora cavernosa and tunica albuginea, causing curvature towards side of lesion and restricting movement of these structures during erection
May be associated with carcinoid syndrome, Dupuytren’s contracture
Usually considered a form of fibromatosis
By another theory, arises secondary to urethritis as a sclerosing inflammatory process
Treatment: may spontaneously regress, responds to small amounts of irradiation, steroids, excision
Micro: fibromatosis with dense fibrous nodules, calcification
Orifice of foreskin is too small to permit its retraction; usually due to scarring from repeated infection due to poor hygiene
May be congenital
Smegma (desquamated epithelial cells, debris) accumulates, causes secondary infections and possibly carcinoma
Micro: lymphoplasmacytic infiltrate in glans and foreskin
DD (requires liberal sampling of foreskin): carcinoma in situ, lichen sclerosus, atypical lichen sclerosus
Also known as balanitis circumscripta plasmacellularis, Zoon’s balanitis
Balanitis: inflammation of glans
Uncircumcised men
Etiology unknown, but probably reactive
Gross: well-defined brown/red plaques, solitary or multiple; resembles erythroplasia of Queyrat / Bowen’s disease
Micro: epidermal atrophy, band like infiltrate of plasma cells in dermis, pigment laden histiocytes, edema, numerous capillaries; rarely plasma cells are scant/absent
Micro images: low power, high power
Most common parasitic infection of penis, usually part of generalized infection
30% transmission rate from sexual intercourse
Caused by Treponema pallidum, humans are the only natural host
Sexually transmitted disease with primary, secondary and tertiary phases (not very infectious are tertiary stage)
Primary syphilis: painless hard chancre (ulcer with indurated and punched out base) at site of inoculation, often in glans
Secondary syphilis: bacteremic stage with greatest number of organisms in the body; widespread rash (small red macular lesions), including on palms and soles and mucous membranes; condyloma lata (flat, rose/gray maculopapules in scrotum)
Tertiary syphilis: gummatous form (granulomas with epithelioid and giant cells, obliterative endarteritis, necrosis); also cardiovascular form and neurosyphilis; accelerated time course occurs with HIV infection (1 year to neurosyphilis)
Diagnosis: Warthin-Starry stain, darkfield examination (corkscrew motility)
Gross images: primary syphilitic chancre #1, #2
Micro: plasma cells and lymphocytes underlying ulcer, endothelial cell proliferation and capillaritis
Virtual slides: chronic inflammatory infiltrate
DD: lymphoma, plasma cell myeloma.
Tancho’s nodules and paraffinomas
Injection or insertion of paraffin or other foreign material under skin of penis with foreign body reaction
Custom among some Asiatic populations
May require local surgical resection
Penile tumors
Benign tumor caused by HPV 6 and 11, related to verruca vulgaris (common wart)
Usually sexually transmitted, affects men and women
Often near coronal sulcus and inner surface of foreskin
Recurs but does not evolve into invasive cancer
Section lesions thoroughly to rule out verrucous carcinoma
Note: lesions with HPV 6 and 11 by in situ hybridization usually have perinuclear halos and nuclear atypia; lesions with HPV DNA by PCR only may contain only focally thickened granular layer associated with epithelial crevices, AJSP 1992;16:269
Gross: papillary, fungating, wart-like, often multiple lesions, 1 mm or larger
Gross images: cauliflower like lesion of foreskin, large scrotal lesion
Micro: complex papillary pattern with central fibrovascular cores, hyperplastic epithelium with preservation of orderly maturation; koilocytosis (vacuolization of cells of prickle cell layer near surface of papillae), T cells (CD4+), may have reactive atypia but no evidence of invasion
Micro images: low power, hyperkeratosis and koilocytosis, koilocytosis, scrotal lesion-low power
DD: pearly penile plaques (HPV negative, hyperkeratosis but no koilocytosis, no significant inflammation), verrucous carcinoma
Case reports in men ages 36 and 47 years, Archives 1985;109:51
Treatment: local excision
Gross: subcutaneous penile nodules
Micro: nests/cords of plump epithelioid cells in loose stroma with lymphocytes and eosinophils; also vascular areas and solid areas with cytoplasmic vacuoles and nuclear atypia
Positive stains: Factor VIII
Giant condyloma acuminatum
Also called Buschke-Lowenstein tumor
Very rare, benign, exophytic papillary growth of penis
Intermediate properties between condyloma and warty carcinoma
Gross: usually involves foreskin and coronal sulcus, also glans; 5-10 cm cauliflower-like verruciform tumors with cobblestone surface; cut surface shows papillomatous growth with sharp demarcation from underlying stroma
Micro: resembles condyloma (papillae with prominent fibrovascular cores, koilocytosis) with bulbous expansion into underlying tissue
DD: warty carcinoma (probably related, has clearly malignant histology and jagged borders with stroma), verrucous carcinoma (no koilocytosis, no prominent papillae with fibrovascular cores)
Very rare
Small, painless, slow-growing masses in adults
Micro: well demarcated smooth muscle tumors, no atypia, no mitotic activity
Myointimal proliferation of corpus spongiosum of glans penis
Mean age 29 (range, 2 to 61 years)
Treatment: conservative local excision
Gross: 0.5 to 2 cm mass
Micro: prominent fibrointimal proliferation with plexiform architecture involving the vasculature of the corpus spongiosum; stellate and spindled cells with minimal atypia embedded in abundant fibromyxoid matrix; cells occasionally are myxoid with abundant eosinophilic cytoplasm, blunt-ended nuclei, and juxtanuclear vacuoles; also areas of degenerative changes with "ghost cell" morphology
Positive stains: alpha-smooth muscle actin, muscle-specific actin (HHF-35), calponin
Negative stains: CD31, CD34, S100, keratin, Factor VIII, desmin (may have minimum staining)
DD: myofibroma, nodular fasciitis, vascular leiomyoma, plexiform fibrohistiocytic tumor
References: AJSP 2000;24:1524
Thickening of squamous epithelium (more than 15 cell layers) without atypia
Benign, but associated with squamous cell carcinoma, particularly verrucous and low grade papillary subtypes
Gross: involves glans, coronal sulcus, foreskin, urethra; flat, smooth and pearly white mucosal lesion, may be papillary; may merge with adjacent low grade carcinoma
Micro: flat, papillary or mixed; also pseudoepitheliomatous (downward florid but superficial proliferation of squamous cell nests, often detached, but with no keratinization, no stromal reaction, no desmoplasia); hyperkeratosis, acanthosis, normal maturing of squamous epithelium; no parakeratosis, no atypia, no koilocytosis
DD of pseudoepitheliomatous hyperplasia: low grade squamous cell carcinoma with pseudohyperplastic features
Transitional papilloma of fossa navicularis
Rare, case report at Virchows Arch 2003;442:601
Dysplasia / carcinoma in situ