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)

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Various classification schemes, similar to cervix

(a) High grade and low grade penile intraepithelial lesions, with and without HPV changes; (b) mild, moderate or severe dysplasia; (c) PIN I, II or III

High grade / severe dysplasia and PIN III are synonymous with carcinoma in situ

In Paraguay, most cases of PIN are associated with invasive squamous cell carcinoma

75-100% are associated with HPV

Gross: varied appearance - flat or slightly elevated pearly white or moist erythematous; or dark brown/black macule, papule or plaque; sharp or subtle borders or focal or diffuse; occasionally papillary

Micro: low grade lesions have atypical cells in lower third of epithelium; high grade lesions have full-thickness atypia; both have variable koilocytosis

Squamous, basaloid and warty patterns exist, which usually correspond to pattern of invasive component, if present

High grade squamous intraepithelial lesion: similar to lesions at other sites; most common type of carcinoma in situ; large irregular cells with eosinophilic keratinized cytoplasm (DD: urothelial carcinoma in situ)

High grade basaloid intraepithelial lesion: composed entirely of small, basophilic immature basal cells with prominent mitotic figures; resemble similar lesions in vulva and cervix; present in >50% of invasive basaloid carcinomas; related to HPV, coexists with warty lesions

High grade warty intraepithelial lesion: flat or slightly ulcerated papillary growth; hyperkeratosis, atypical parakeratosis, marked nuclear pleomorphism, abnormal mitotic figures, full thickness koilocytosis; related to HPV, coexists with basaloid lesions

 

Carcinoma in situ

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Also called Bowen’s disease, bowenoid papulosis and erythroplasia of Queyrat

All forms below are associated with HPV 16 (80% of cases)

 

Bowen’s disease

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Also called squamous cell carcinoma in situ

Age 35+; affects skin of shaft of penis and scrotum; also occurs in women

10% progress to invasive squamous cell carcinoma

1/3 may have unrelated visceral malignancy (lung, GI, urinary tract)

HPV positive

Gross: sharply demarcated, gray-white plaque with shallow ulcer and crusting

Micro: markedly dysplastic cells in all layers of epithelium, large hyperchromatic nuclei, multinucleated cells, dyskeratosis, vacuolization, acanthosis, hyperkeratosis, stroma with vascular proliferation and chronic inflammatory infiltrate; atypical mitoses but intact dermal epidermal junction

Virtual slides: carcinoma in situ

 

Bowenoid papulosis

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Sexually active young men (mean age 30), usually on skin of shaft, glans or scrotum

Associated with HPV 16 or 18

Almost never becomes invasive

May spontaneously regress

Gross: multiple, small, pigmented papular lesions, may resemble condyloma acuminatum

Micro: histologically resembles Bowen’s disease, but may have mild/heavy melanin pigmentation within the lesion; often spiky or flat appearance, may have less cytologic atypia

 

Erythroplasia of Queyrat

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Affects penile squamous mucosa

One or more shiny red, velvety plaques, usually on glans and prepuce

Histologically similar to Bowen’s disease (which affects penile shaft squamous epithelium), also HPV positive

No association with visceral malignancy

Virtual slides: Erytroplasia of Queryat

 

 

Squamous cell carcinoma and variants

Squamous cell carcinoma-general

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Rare in US (<1% of carcinomas in men vs. 10-20% in Asia [excluding Japan], Africa, South America)

Incidence: 0.29 per 100K in US whites vs. 4.2 per 100K in Paraguay vs. 4.4 per 100K in Uganda

Rare if circumcision at birth, more common if late circumcision (after age 10)

Risk factors: paraphimosis, phimosis and long foreskin (AJSP 2003;27:994), HPV 16 or 18 (although most cases are not related to HPV), smoking, psoriasis patients treated with UV B radiation, penile rash > 1 month (? Bowen’s disease)

1/3 of non-HPV cases are associated with lichen sclerosus (balanitis xerotica obliterans)

HPV: HPV positive cancers more likely to have high grade penile intraepithelial neoplasia than HPV negative cancers (AJCP 1992;97;272), HPV present in 42% of penile carcinomas, but frequency varies by histologic type: squamous cell 35%, verrucous 33%, basaloid 80%, warty 100% (AJPath 2001;159:1211)

Most tumors arise from glans or inner foreskin near coronal sulcus as slow growing, irregular mass; patients occasionally present with inguinal nodal metastases with occult penile cancer due to severe phimosis or very small primary tumor

Usually age 40-70 years, median age 58 years

Metastases: inguinal and pelvic lymph nodes, liver, lung, heart or bone; 15% have metastases at diagnosis

Note: nodes are often enlarged at clinical presentation due to infection, not metastases

5 year survival related to nodal involvement: 66% (not involved) vs. 27% (involved)

Histologic subtypes resemble those in vulva, anus, buccal mucosa; 70% are usual squamous cell carcinoma

Prognostic factors: histologic grade and depth of penetration into various anatomic compartments most important; poor prognostic factors are angiolymphatic invasion, vertical growth pattern, basaloid, sarcomatoid, solid, anaplastic and pseudoglandular subtypes; extension beyond foreskin and compromise of corpus cavernosum

Although prognosis related to depth of invasion (epithelium, lamina propria, corpus spongiosum, corpus cavernosum), anatomic variations exist (corpus cavernosum may not be located in glans in 25% of cases), AJSP 2001; 25:1091

Low grade: no regional metastases if only superficial invasion to 6 mm or less (Mod Path 2001;14:963)

[depth measured from deepest malignant cells to highest overlying dermal papilla, image]

High grade: deep invasion (8-10 mm) into corpus spongiosum, dartos or corpora cavernosa associated with 80% rate of metastases

Intermediate/high grade with invasion 5-10 mm have ~ 15% risk of metastases

Treatment: local resection, partial/total penectomy, National Cancer Institute page

 

Squamous cell carcinoma - NOS

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NOS: not otherwise specified; i.e. usual histologic pattern

70% of squamous cell carcinomas

Case reports: metastatic disease in pleural effusion, Archives 1992;116:198

Gross: exophytic (resembles condyloma acuminatum) or flat (epithelial thickening with gray fissures in mucosa, later ulcerated papule); cut surface shows tan-white solid irregular tumor with superficial or deep penetration

Gross images: red-tan ulcerated tumor #1, #2, fungating mass

Micro: classified according to growth pattern as superficial spreading, vertical growth, verruciform, multicentric or mixed (see below); usually keratinized with moderate differentiation; predominantly undifferentiated carcinomas are rare; unusual focal or diffuse patterns are acantholytic (pseudoglandular), spindle cell (sarcomatoid), lymphoepithelioma-like, trabecular, endocrine, giant cell pleomorphic and clear cell

Graded as 1 (well differentiated), 2 (moderated differentiated) or 3 (poorly differentiated)

Stroma has variable lymphoplasmacytic infiltrate; foreign-body type giant cells often seen in highly keratinized tumors; desmoplasia is unusual; most cases have associated penile intraepithelial neoplasia (high grade and low grade) and squamous hyperplasia; lichen sclerosus is associated with low grade foreskin carcinomas, especially verrucous carcinomas and multicentric tumors with pseudohyperplastic features

Micro images: grade 1, grade 2, grade 2, grade 3, finger like projections into dermis, vascular invasion, measuring depth of invasion

DD: pseudoepitheliomatous hyperplasia (elongated rete ridges, no atypia in separated nests, no keratinization, no stromal reaction); melanoma, epithelioid angiosarcoma, urothelial carcinoma (ventral surface of penis, no penile intraepithelial lesions, history of urothelial CIS or bladder tumor)

 

(a) Superficial spreading

Most common pattern; slow growing; involves mucosal and superficial layers of glans, coronal sulcus and foreskin; resembles melanoma subtype due to early horizontal phase and late vertical phase with deep invasion of corpus spongiosum and corpora cavernosum; histologic subtype is usual squamous cell carcinoma but verruciform tumors may show this growth pattern as well

Tends to recur if incompletely excised

Gross: slightly raised gray-white granular firm tumor

Micro: all in situ OR in situ plus invasive nodular component OR horizontal pattern of in-situ and invasive carcinoma; may involve resection margin

 

(b) Vertical growth

High risk of regional metastasis and death

Gross: large ulcerated or fungating mass; solid uniform cut surface with focal necrosis

Micro: high grade with prominent vascular invasion; may have satellite nodules in corpus spongiosum or corpora cavernosa; histologic subtypes are basaloid, sarcomatoid, anaplastic, solid and usual type

 

(c) Verruciform

25% of penile tumors; slow growing exophytic tumors with well-differentiated keratotic papillary configuration; usually superficial; histologic subtypes include verrucous, condylomatous (warty), papillary and usual type; may be difficult to differentiate benign from malignant tumors

 

(d) Multicentric

Two or more foci of carcinoma separated by benign tissue; behavior similar to superficial spreading carcinomas; patients prone to recurrences unless all anatomic compartments removed at surgery

 

Adenosquamous carcinoma

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Very rare

May originate in misplaced glandular cells in perimeatal region of penis

Case reports of superficial tumors at AJSP 1996;20:156

Gross: firm, gray-white, granular

Micro: squamous cell and glandular pattern, with squamous cell pattern usually predominating; glands produce mucin; squamous intraepithelial lesions present in glans mucosa

Positive stains: CEA in glandular portion

DD: adenoid squamous cell carcinoma (prominent acantholysis simulates glandular spaces but lining is composed of squamous epithelium and spaces with necrotic debris and keratin, not mucin); adenosquamous (mucoepidermoid) carcinoma of urethra (ventral in penis, restricted to periurethral tissue and corpus cavernosa); Littre gland adenocarcinoma (ventral in penis, restricted to periurethral tissue and corpus cavernosa)

 

Basaloid carcinoma

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Aggressive, high grade, deeply invasive

50% have enlarged inguinal nodes (due to metastasis) at diagnosis; 59% mortality

80% associated with HPV

5-10% of penile cancers

Median age 52 years

May arise from squamous-urothelial junction at urethral meatus

Gross: usually in glans; flat, ulcerated, irregular mass, with solid tan tissue replacing corpus spongiosum and invading tunica albuginea and corpus cavernosa

Micro: closely attached nests of tumor cells, often with central comedonecrosis; may have peripheral clefts due to retraction artifact; composed of small cells resembling basal cells with small nucleoli and numerous mitotic figures; prominent perineural and angiolymphatic invasion; occasionally peripheral pallisading and focal central keratinization; may have starry sky appearance due to apoptosis; may have associated basal cell hyperplasia or basaloid or warty carcinoma in situ

Micro images: figure 1C: nests of immature malignant squamous epithelium

DD: basal cell carcinoma of skin, poorly differentiated squamous cell carcinoma NOS, small cell carcinoma, neuroendocrine carcinoma.

 

Papillary carcinoma

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Exophytic, slow growing, low-grade squamous cell carcinoma without condylomatous features and with irregular infiltrating margin

Diagnosis of exclusion of other verruciform tumors

Inguinal nodal metastases are unusual

Gross: usually in glans; large gray-white exophytic destructive lesion, mean 6 cm, up to 14 cm; cut surface shows pearly white papillomatous tissue, poor demarcation between tumor and stroma

Micro: well differentiated papillary squamous neoplasm; prominent hyperkeratosis and acanthosis; variable papillae (long/short, variable fibrovascular cores); may have keratin cysts and intraepithelial abscesses; no prominent koilocytotic changes; irregular / infiltrative base

DD: squamous cell carcinoma NOS (no prominent papillary features, not as well differentiated); verrucous carcinoma (broad/bulbous boundary of tumor and stroma); warty carcinoma (pleomorphic cells with koilocytotic changes); pseudoepitheliomatous hyperplasia (no atypia, no keratinization, no desmoplastic stroma)

 

Sarcomatoid carcinoma

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Rare, aggressive, large tumors with predominance of anaplastic spindle cells

Median age 60 years

Frequent recurrences due to inadequate surgery

Gross: usually involves glans, large gray-white or red fungating mass, 5-7 cm; cut surface shows deep invasion of corpus spongiosum or corpora cavernosa; superficial or deep tumor nodules

Micro: predominantly anaplastic spindle cells, occasional giant cells, usual squamous cell carcinoma is either focal or absent; prominent necrosis and mitotic activity; variable leiomyosarcomatous, malignant fibrous histiocytoma-like or prominent myxoid changes, squamous cell carcinoma in situ, benign and malignant bone, osteoid, cartilaginous metaplasia

Positive stains: keratin

DD: sarcoma, malignant melanoma (HMB45+, S100+)

 

Verruciform carcinoma

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A pattern, not a diagnosis

Penile exophytic tumors with verruciform gross appearance and low/intermediate grade papillary microscopic features

Condylomatous: giant condyloma, warty carcinoma

Non-condylomatous: verrucous carcinoma, low grade papillary squamous cell carcinoma

 

Verrucous carcinoma

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Median age 57 years

Rare, slow growing, extremely well differentiated variant of squamous cell carcinoma with low malignant potential

Locally invasive, one third recur (due to inadequate surgery or multifocal tumor) but rarely/never metastasizes

33% of cases associated with HPV (usually HPV 6, 11)

Gross: exophytic, papillary (resembles condyloma acuminatum but larger), warty; white-gray, usually ~ 3  cm, involves all penile compartments (glans most common)

Micro: very well differentiated with prominent intercellular bridges, minimal atypia and minimal mitotic figures; penetrates through lamina propria with broad base and pushing borders; hyperkeratotic and acanthotic papillae with keratin cysts; orthokeratosis more prominent than parakeratosis; tumor cells are polygonal squamous cells with glassy cytoplasm, central vesicular nuclei, intercellular edema, may have superficial vacuolated clear cells but no koilocytosis; dense inflammatory infiltrate may obscure tumor-stroma boundary; intraepithelial abscess and crust formation is common; central fibrovascular cores are uncommon

Micro images: nests of well differentiated keratinized tumor cells, pushing border, minimal atypia, figure 1B: papillary architecture

DD: giant condyloma and warty carcinoma (koilocytotic change present), papillary carcinoma (invasive and jagged border, more atypia, potential for inguinal node metastases)

References: Mod Path 1992;5:48

 

Warty (condylomatous) carcinoma

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Rare, low-intermediate grade, slow growing carcinoma; identical to vulvar, uterine cervix or anal warty carcinoma

May have regional nodal metastases if deeply invasive

Intermediate behavior between low-grade verrucous or papillary carcinomas and usual squamous cell carcinomas of penis

Patients unlikely to die of disease, AJSP 2001;25:673, AJSP 2000;24:505

100% associated with HPV

Gross: verruciform; endophytic, white-tan, cauliflower-like, mean 5 cm; may have cobblestone surface; papillomatous cut surface, may penetrate deep into corpus spongiosum or corpora cavernosa with broad or irregular contours (but less likely than squamous cell carcinoma)

Micro: resemble condyloma due to HPV-related changes of cellular pleomorphism with clear cytoplasm resembling koilocytosis throughout entire tumor (not just surface); arborescent papillary pattern with long, rounded or spiky papillae with prominent fibrovascular cores; may have intraepithelial abscesses; prominent hyperkeratosis and atypical parakeratosis; early - sharply delineated interface between tumor and stroma with no invasion; later - jagged boundary between tumor and stroma;

DD: giant condylomas (benign, HPV changes only in superficial layers, no pleomorphism), verrucous carcinoma (no HPV changes), papillary carcinomas (no HPV changes)

 

 

Other malignancies

Basal cell carcinoma

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Arise in skin of shaft, may be multicentric

No metastatic potential

 

Clear cell sarcoma

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Case report in 10 year old boy, Hum Path 1986;17:423

Positive stains: S100

EM: melanosomes

 

Kaposi’s sarcoma

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Sporadic in older patients, associated with AIDS in younger patients

Most common sarcoma of penis

Case report in glans penis in bisexual man, Archives 1986;110:346

Gross: single or most commonly multiple small 2-6 mm bluish lesions in glans

Micro: slit like spaces with numerous red blood cells, intracytoplasmic grape-like clusters of PAS+ diastase resistant hyaline globules, prominent lymphoplasmacytic inflammatory infiltrate; may have patch-plaque-like changes at periphery of nodular mass

Positive stains: CD34, CD31

Negative stains: desmin

 

Leiomyosarcoma

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Very rare, < 50 cases reported, but still second most common sarcoma of penis (after Kaposi’s sarcoma)

Mean age 51 years, range 43-62 years

Sites: usually shaft or base of penis but can occur at any site

Superficial lesions (above tunica albuginea) are asymptomatic, deep seated lesions may cause dysuria or difficulty voiding

Often recur locally

Prognostic features: tumor depth (2 cm or less vs. more than 2 cm), tumor size (5 cm or less vs. more than 5 cm)

Treatment: wide local excision if superficial, excision as necessary for complete removal of deeper tumors

Gross: median 1.5 cm (range 0.5 to 6.0 cm), often superficial; white-tan-gray, firm, may form nodular mass

Micro: smooth muscle cells (abundant eosinophilic cytoplasm, blunt ended nuclei, juxtanuclear vacuoles) arranged in fascicles with nuclear atypia, nuclear pleomorphism, focal necrosis and mitotic activity

Positive stains: desmin, muscle specific actin

References: AJSP 2004;28:115

DD: sarcomatoid carcinoma, metastases

 

Malignant mesothelioma

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Rare; case report at Urology 2003;62:551

 

Melanoma

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Most common tumor in penis after squamous cell carcinoma, but still rare

Localized to glans, may involve foreskin, although 43% have inguinal nodal metastases at diagnosis

Poor prognosis

 

Metastases to penis

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Unusual; when it occurs, primary usually from urogenital region (urinary bladder, prostate, kidney) or distal colon

Other primaries are lung (small cell carcinoma), lymphoma, melanoma

Preferred site is corpus cavernosum; also Buck’s fascia and corpus spongiosum

Typically produces “malignant priapism”, due to massive replacement of corpora cavernosa by tumor

 

Mucoepidermoid carcinoma

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Case report in glans penis, Archives 2000;124:148

Aggressive

Micro: sheets and nests of cells with large nuclei, prominent nucleoli, abundant cytoplasm with well defined borders, mucin in 25% of cells; minor component of well-differentiated nonkeratinizing squamous cell carcinoma; resembles similar tumor of cervix

Micro images: sheets/nests of cells with prominent mucin, mucicarmine stain

 

Proximal type epithelioid sarcoma

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Aggressive tumor of men and women, median age 35 years old

Usually are metastatic and cause death

Resembles atypical epithelioid sarcoma, rhabdoid tumor, undifferentiated carcinoma

Usually pelvic/perineal, pubic region, buttocks; also penis, forearm, axilla, AJSP 1997;21:130

Micro: prominent large cell epithelioid or rhabdoid features, marked cytologic atypia, often multinodular pattern with necrosis, invasion of subcutaneous or deep soft tissues; usually no granuloma type pattern

Positive stains: keratin, EMA, vimentin, often desmin, CD34, smooth muscle actin; occasionally HMB45 or CEA

Negative stains: CD31, S100

 

Sclerosing epithelioid fibrosarcoma

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Rare, behaves as fully malignant sarcoma, AJSP 2001;25:699

Micro: small to moderate-size, round to ovoid, relatively uniform cells, often with clear cytoplasm, embedded in a hyalinized fibrous stroma; variable necrosis

Positive stains: vimentin (strong, diffuse)

EM: fibroblasts

DD: low grade fibromyxoid sarcoma, hyalinizing spindle cell tumor with giant rosettes

 

 

Miscellaneous

Staging of penile carcinoma

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Excludes melanomas

 

Primary tumor (T)

 

TX:  primary tumor cannot be assessed

T0:  no evidence of primary tumor

Tis: carcinoma in situ

Ta:  noninvasive verrucous carcinoma

T1:  tumor invades subepithelial connective tissue

T2:  tumor invades corpus spongiosum or corpus cavernosum

T3:  tumor invades urethra or prostate

T4:  tumor invades other adjacent structures

 

Regional lymph nodes (N)

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NX:  regional lymph nodes cannot be assessed

N0:  no regional lymph node metastases

N1:  metastasis in a single superficial, inguinal lymph node

N2:  metastasis in multiple or bilateral superficial inguinal lymph nodes

N3:  metastasis in deep inguinal or pelvic lymph node(s) unilateral or bilateral

 

Distant metastasis (M)

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MX:  distant metastasis cannot be assessed

M0:  no distant metastasis

M1:  distant metastasis

 

Stage:

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0:    Tis or Ta N0 M0

I:     T1 N0 M0

II:    T1 N1 M0  or  T2 N0-N1 M0

III:    T1-2 N2 M0  or  T3 N0-N2 M0

IV:    T4 any N M0  or  any T N3 M0  or  any T any N M1

 

Features to report in carcinomas

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Tumor site (glans, coronal sulcus, foreskin, skin of shaft or combinations)

Largest tumor size

Histologic type (squamous NOS, basaloid, verrucous, papillary, condylomatous (warty), sarcomatoid, mixed)

Growth pattern: superficial spreading, vertical growth, verruciform, multicentric

Histopathologic grade (well, moderately, poorly differentiated or undifferentiated)

Anatomic level of invasion: lamina propria, dartos skin in foreskin; lamina propria, corpus spongiosum, tunica albuginea and corpora cavernosa in glans tumors

Margin of resection: skin of shaft, corpora cavernosa, urethral epithelium and surrounding tissues (lamina propria, corpus spongiosum, tunica albuginea, penile fascia)

Depth of invasion from deepest malignant cells to highest overlying dermal papilla (micro image)

   Note: if tumor replaces most of penis, measure tumor thickness from non-keratinized tumor surface to deepest point of invasion

References: Mod Path 2001;14:963

 

Grossing penectomy specimens

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Fix specimen overnight in formalin

Separate glans from shaft by cutting along coronal sulcus

Take transverse sections of proximal resection margins: 1-corpora cavernosa and skin of the shaft, separated from 2-urethra and surrounding corpus spongiosum

Take longitudinal sections of shaft, centered along urethra, with additional parallel sections on both sides

The cut surface shows the tumor in relation to all anatomical compartments

References: AJSP 2001; 25:1091

 

Grossing circumcision specimens

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Pin  the 4 angles of the specimen with the mucosa oriented on one side and the skin on the other

Ink the coronal sulcus margin (the surgical cut section area)

Fix the specimen overnight in formalin.

Cut transversally 12 sections clockwise.

 

 

Scrotum

Scrotum - normal

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Covers testes, adnexae, distal spermatic cord

Layers are epidermis, dermis, tunic dartos (muscle bundles), three layers of Colles’ fascia (intercrural, cremasteric, infundibuliform), parietal layer of tunica vaginalis

Drawing #1, #2, inguinal ring

 

 

Non-neoplastic lesions of scrotum

Fat necrosis

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Due to cold exposure, presents as bilateral masses in lower scrotum

 

Idiopathic calcinosis

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Multiple nodules in skin, beginning in childhood/adolescence, tend to increase in size and number

May break through skin and discharge chalky material

May arise from keratinous cysts that have lost their lining

Micro: amorphous basophilic substance, may have foreign body giant cell reaction

Micro images: calcification in dermal soft tissue #1, #2, foreign body giant cell reaction #1, #2, calcification of preexisting cyst

 

Massive localized lymphedema in morbidly obese patients

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Associated with hypothyroidism

Huge masses resembling neoplasms (mean 50 cm, range 38-75 cm), of 9 months to 18 years duration

Scrotum affected; also thigh, popliteal fossa, abdomen, suprapubic and inguinal region

Gross: poorly defined, non-encapsulated; skin indurated and peau d’orange; marbled appearance with fibrous bands intersecting adipose tissue lobules

Micro: no atypical cells, no lipoblasts; lymphatic vascular ectasia, chronic inflammatory infiltrates, fibrosis, edema between collagen fibers, infarction and fat necrosis

References: Hum Path 2000;31:1162

 

Peritesticular fibrosis

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Typically involves tunica albuginea, may simulate tumor

May cause bowel wall perforation in infants with meconium periorchitis

Micro: associated with fibrinous or hyalinized loose bodies in cavity

 

Sclerosing lipogranuloma

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Rare, painless, usually affects adults in penis, scrotum, spermatic cord, perineum

Appears to be associated with paraffinomas (injection of exogenous material) in almost all cases

See also Tancho’s nodules

Micro: fat necrosis, histiocytes, giant cells with extensive fibrosis and hyalinization

DD: adenomatoid tumor, lymphangioma, sclerosing liposarcoma

References: Archives 1977;101:321

 

Tunica albuginea cysts

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Usually contain clear fluid, lined by low cuboidal or columnar cells, may be ciliated

 

 

Neoplastic lesions of scrotum

Aggressive angiomyxoma

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Locally aggressive but nonmetastasizing soft tissue tumor of pelvic soft tissue and perineum, almost always in adult women

Case report of tumors in 4 men at AJSP 1992;16:1059

Micro: infiltrative tumors composed of fibromyxoid matrix with occasional bland spindle cells with delicate cytoplasmic processes in background of scattered vessels of variable size, some with hypertrophy or hyalinization of vessel wall

Positive stains: vimentin, variable muscle specific actin

Negative stains: alpha smooth muscle actin, desmin, S100

 

Angiomyofibroblastoma

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Has features of vulvovaginal angiomyofibroblastoma and spindle cell lipoma

Involves scrotum or inguinal region in men with median age 57 years (range 39 to 88 years)

Treatment: simple excision usually sufficient

Gross: superficial, well circumscribed tumors, mean 7 cm

Micro: tapered spindled cells between small to medium-sized vessels in acid mucopolysaccharide-rich finely collagenous stroma; may have focal epithelioid stromal cells; minimal mitotic activity, minimal nuclear atypia

Positive stains: vimentin, PgR, often CD34, ER, desmin, muscle specific actin, smooth muscle actin

Negative stains: S100

 

Calcifying fibrous pseudotumor

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Extremities, trunk, scrotum, groin, neck, axilla; men and women with median ages of 19 years

Treatment: local excision

Gross: 2-15 cm in subcutaneous and deep soft tissue, well circumscribed with occasional infiltrative borders or entrapped structures

Micro: abundant hyalinized collagen, psammomatous or dystrophic calcification, lymphoplasmacytic infiltrate

References: AJSP 1993;17:502

 

Desmoplastic round cell tumor

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See also testis page

Rarely arises in scrotum, Hum Path 1993;24:850, AJSP 1998;22:1303

Usually arises in males, mean 27 years, within abdomen or pelvis

All sites - most patients die of metastatic disease, mean 25 months after diagnosis

Micro: epithelial, mesenchymal and neuroendocrine phenotypes

 

Leiomyoma

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Most common benign mesenchymal tumor of scrotum

May clinically resemble cyst

 

Leiomyoma with bizarre nuclei

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Very rare, <20 reported cases

Also called symplastic, atypical or pleomorphic leiomyoma

Benign with no local recurrence or distant metastases

Case report of 69 year old man with 6 year history of scrotal mass, Archives 2004;128:e37

Nuclear atypia most likely is degenerative (as in ancient schwannomas)

Gross: firm, well-delineated mass, tan-yellow, solid

Micro: unencapsulated but well circumscribed, multilobulated tumor with fascicles of spindle cells with cigar shaped nuclei, abundant eosinophilic cytoplasm; varying amounts of cells with hyperchromasia, pleomorphic nuclei and macronucleoli; no mitotic figures, no hypercellularity, no infiltrative margins, no necrosis

Micro images: smooth muscle cells with focal atypia

Positive stains: vimentin, desmin, smooth muscle actin, muscle specific actin, h-caldesmon

Negative stains: keratin, neurofilament, HMB45

DD: piloleiomyoma (arise from arrectores pilorum muscle, poorly delineated, dermal, painful), angioleiomyoma (arise from vessel musculature, encapsulated, highly vascular, painful), leiomyosarcoma (mitotic figures, necrosis)

References: Mod Path 1998;11:282

 

Liposarcoma

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See also testis page

 

Dedifferentiated subtype

Median age 61 years, usually retroperitoneum (2/3) but 20% in extremities/trunk and 8% in scrotum/spermatic cord

Usually resemble MFH or high grade fibrosarcoma; may have only low-grade areas

Aggressive (even if low grade features) with recurrence in 41%, metastases in 17%, death in 28%, AJSP 1997;21:271

 

Dual lineality

Case reports of tumors of older men (70 and 77 years) in scrotum and abdominal cavity with liposarcomatous and leiomyosarcomatous features, AJSP 1993;17:905

 

Malignant mesothelioma

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Most common primary malignant tumor of tunica vaginalis

Usually diffuse epithelial type

Presents as scrotal swelling

May locally invade dartos, epididymis, testis, skin

 

Paget’s disease

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Adenocarcinoma in situ of scrotal skin; usually not associated with underlying malignancy

Less frequent than in vulva or perianal region

Case report in patient with prior squamous cell carcinoma in situ (Bowen’s disease) of scrotum, Archives 2004;128:84.

Gross: erythematous plaque or raised lesion on scrotal or penile skin

Micro: intraepidermal clusters of large cells with abundant clear cytoplasm and large vesicular nuclei; may be associated with hyperkeratosis and parakeratosis

Micro images: low power, high power, CEA, PAS, with Bowen’s disease and stains

Positive stains: CK7, CAM 5.2, CEA, EMA, PAS, MUC1, MUC5AC

Negative stains: 34betaE12 (high molecular weight keratin), HMB45, MelanA/Mart1, S100, MUC2

DD: superficial spreading melanoma

References: AJSP 2001;25:1469

 

Posttraumatic spindle cell nodules

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Case reports in 22 and 67 year old men with scrotal lesions secondary to trauma, Archives 1994;118:709

No recurrence after local excision

Micro: monomorphic, dense, spindle cell proliferations forming irregular nodules in wall of hematoma

Positive stains: smooth muscle markers

 

Squamous cell carcinoma

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Associated with chimney sweeps, paraffin workers, tar workers, cotton mill workers

Treatment: wide local excision with bilateral lymphadenectomy

 

End of Penis and Scrotum chapter / outline

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