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Reviewers: Antonio Cubilla, M.D. and Alcides Chaux , M.D. (see Author page)
Revised: 24 February 2010
Last major update: February 2010 - in progress
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.
Penis
Anatomy, congenital anomalies, circumcision, priapism
Infectious disorders: balanoposthitis, cellulitis, chancroid, Fournier’s gangrene, fungal infections, gangrenous balanitis, granuloma inguinale, herpes simplex virus, HIV, lymphogranuloma venereum, molluscum contagiosum, scabies, syphilis
Inflammatory disorders: accessory urethral canal, cutaneous verruciform xanthoma, inflammatory pseudotumor, melanosis / lentiginosis, lichen sclerosus (BXO), Mondor’s phlebitis, mucoid cyst, os penis, paraphimosis, pearly pink papules, Peyronie’s disease, phimosis, plasma cell balanitis, Tancho’s nodules / 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, pseudohyperplastic, 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 (7th ed)
American Journal of Clinical Pathology
American Journal of Surgical Pathology
Archives of Pathology and Lab Medicine
Eble: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs, 2004
Websites: PathConsult, PathoPic, PEIR Digital Library, Webpathology.com
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
Penile intraepithelial neoplasia (PIN)
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
Also called Bowen’s disease, bowenoid papulosis and erythroplasia of Queyrat
All forms below are associated with HPV 16 (80% of cases)
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
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
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
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
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
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)
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.
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)
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+)
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
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
Other malignancies
Basal cell carcinoma
Arise in skin of shaft, may be multicentric
No metastatic potential
Case report in 10 year old boy, Hum Path 1986;17:423
Positive stains: S100
EM: melanosomes
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
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
Rare; case report at Urology 2003;62:551
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
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
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
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
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
Features to report in carcinomas
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
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
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
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
Non-neoplastic lesions of scrotum
Due to cold exposure, presents as bilateral masses in lower scrotum
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
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
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
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
Usually contain clear fluid, lined by low cuboidal or columnar cells, may be ciliated
Neoplastic lesions of scrotum
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
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
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
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
Most common benign mesenchymal tumor of scrotum
May clinically resemble cyst
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
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
Most common primary malignant tumor of tunica vaginalis
Usually diffuse epithelial type
Presents as scrotal swelling
May locally invade dartos, epididymis, testis, skin
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
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
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