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)

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Table of Contents

Primary references

 

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

Normal

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

 

 

Primary references

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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

Anatomy

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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

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Fibroelastic and vascular membrane encasing and separating dorsal corpora cavernosa and ventral corpus spongiosum

 

Coronal sulcus

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Narrow and circumferential cul de sac (in non-circumcised) behind glans corona; area of insertion of dartos and Buck’s fascia

 

Corpora cavernosa

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Two lateral masses of erectile tissue that form bulk of penis; posterior portions are called crura, are connect to pubic arch

Drawing of microanatomy

Micro images: vascularized tissue in fibrous stroma #1, #2, #3, #4, #5

 

Corpus spongiosum

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Median mass of erectile tissue that contains most of urethra

Micro images: vascularized tissue with adjacent urothelium #1, #2, #3, #4, #5

 

Dartos

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Smooth discontinuous muscle layer covering corpora and mid part of foreskin

 

Foreskin (prepuce)

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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

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Terminal dilated portion of penile urethra, contains stratified, non-keratinized, squamous epithelium

 

Frenulum

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Fibrous band of tissue attaching foreskin to ventral glans

Gross images: frenulum

 

Glans

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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

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At base of glans, slightly elevated circumferential rim

 

Urethral meatus (meatus urethralis)

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Urethral opening

Usually at central ventral glans penis

Vertical cleft, related to frenulum

 

Urethra

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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

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Superficial inguinal nodes (site of 1-3 sentinel nodes), deep inguinal, external iliac, internal iliac (pelvic nodes)

 

Periurethral glands

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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:

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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

 

Congenital anomalies

Aphallia

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Agenesis of penis

Only 70 cases reported; associated with other GU abnormalities

 

Chordae

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Fibrous band associated with hypospadias or epispadias

 

Concealed penis

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Penis is normally developed but hidden under fat in suprapubic region, scrotum, perineum, thigh

 

Diphallia

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Duplication of penis

Associated with hypospadias, bifid scrotum, bladder duplication, renal agenesis

 

Epispadias

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Urethra opens onto dorsal surface of penis

Penopubic epispadias (opening in penopubic junction) is most common, associated with urinary incontinence

 

Hypoplasia

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Almost always associated with abnormalities of GU tract

 

Hypospadias

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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

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Due to hypo/hyperplasia of one corpora cavernosa

 

Median raphe cysts

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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

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Penis small, but normal ratio of shaft length to circumference

 

Torsion

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Fibrous tissue surrounding corpus spongiosum or short urethra causes rotational defect of penile shaft

 

Webbed penis

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Scrotal skin extends to ventral portion of penis and hides it

 

Circumcision

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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)

 

Priapism

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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

 

 

Inflammatory lesions

Accessory urethral canals

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May open near fossa navicularis, become inflamed and produce symptoms

 

Balanoposthitis

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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

 

Cellulitis

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More common in newborns and immunosuppressed

Usually involves scrotum

Usually caused by group A streptococcus

 

Chancroid

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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

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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

 

Fungal infections

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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

 

Fournier’s gangrene

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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

 

Gangrenous balanitis

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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

 

Granuloma inguinale

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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)

 

Herpes simplex virus

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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)

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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

 

Inflammatory pseudotumor

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Associated with chronic condom catheterization

 

Lentiginous melanosis

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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 )

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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

 

Lymphogranuloma venereum

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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

 

Molluscum contagiosum

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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

 

Mondor’s phlebitis

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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

 

Mucoid cyst

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Inflammatory lesion due to accessory urethral canals, on foreskin or glans, associated with intraepithelial mucous cells or glands

 

Os penis

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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

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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

 

Paraphimosis

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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

 

Peyronie’s disease

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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

 

Phimosis

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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

 

Plasma cell balanitis

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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

 

Scabies

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Most common parasitic infection of penis, usually part of generalized infection

 

Syphilis

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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

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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

Condyloma acuminatum

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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

 

Epithelioid hemangioma

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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

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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)

 

Leiomyoma

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Very rare

Small, painless, slow-growing masses in adults

Micro: well demarcated smooth muscle tumors, no atypia, no mitotic activity

 

Myointimoma

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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

 

Squamous hyperplasia

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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

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Rare, case report at Virchows Arch 2003;442:601

 

 

Dysplasia / carcinoma in situ

Penile intraepithelial neoplasia (PIN)