Penis Flashcards
Peyronie disease
- 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
- Proliferation of fibroblasts and myofibroblasts on or around the tunica albuginea of the penis, most often the dorsal aspect, that may lead to plaques
- May be related to microtrauma (coital, urethral instrumentation), which releases fibroblast related cytokines
- May arise secondary to urethritis as a sclerosing inflammatory process
Micro:
* Dense fibrous nodules, similar to those in Dupuytren contracture, fibromatosis and other desmoplastic conditions involving myofibroblasts
* More dense and less cellular than other types of superficial fibromatosis
* Disorganization of collagen of tunica albuginea with formation of nodules, often hyalinizing fibrosis
* Perivascular lymphoid infiltrate in early stages
* Fibrotic tunica albuginea with extension of fibrosis to corpus cavernosum
* Abnormal vessels with venous leakages
* Calcification or ossification may occur, linear band of calcification
Molecular:
* No somatic mutations of beta catenin genes unlike desmoid fibromatosis
* Etiology may be related to Parc protein or Wnt2
IHC
Vimentin
variable actin - muscle specific and smooth muscle actin, less frequently desmin
Lichen sclerosus (balanitis xerotica obliterans)
- Chronic inflammatory mucocutaneous condition
- Male equivalent of lichen sclerosus et atrophicus of vulva
- Chronic inflammatory and sclerotic benign condition
- Middle aged men
- Unknown etiology
- Associated with penile intraepithelial neoplasia (PeIN) and penile carcinomas
- Inner foreskin, coronal sulcus and glans mucosae
- Urethra may be affected
- Rarely extends to the shaft
Macro:
* grayish white plaques in foreskin, coronal sulcus or glans
Micro:
Squamous epithelium:
* Normal, atrophic or hyperplastic, the latter most common, with more than 10 cell epithelial layers
* Hyperkeratosis associated with hyperplasia
* Vacuolar degeneration of basal layer, landmark lesions in all types of lichen
* Tissue separation at the basal layer, which indices late epithelial ulceration
Lamina propria:
* Thickening and loss of structures
* Edema, hypervascularity and typically sclerosis
Molecular:
* p53, CDKN2A alterations suggest progression to neoplasia
IHC:
* Immunohistochemistry is not needed for diagnosis but can suggest progression to neoplastic lesions
* p53: 40% of cases adjacent to cancer showed positive parabasal cells in other organs
* Ki67: positive in basal epithelial cells
* MCM3 (mini chromosome maintenance 3 protein): positivity in long standing lichen sclerosus and correlates with Ki67 expression
* CD3, CD4, CD8: T cells marker are positive in the lymphocytic infiltrate
Angiokeratoma
- Benign vascular lesion characterized by superficial vascular ectasia and overlying epidermal hyperplasia (acanthosis or hyperkeratosis)
- Lesions may be solitary or multiple / diffuse
Five types with similar histology
- Angiokeratoma of Mibelli: seen in children and adolescents on dorsum of toes and fingers
- Angiokeratoma of Fordyce: scrotal skin of elderly
- Angiokeratoma corporis diffusum: clustered papules in a bathing suit distribution; associated with **Anderson-Fabry disease **(X-linked recessive lysosomal storage disease)
-
Angiokeratoma circumscriptum: least common type, usually congenital, associated with nevus flammeus, cavernous hemangioma
Idiopathic solitary or multiple angiokeratomas - Idiopathic solitary or multiple angiokeratomas
Macro:
* Small red to brown / black papule or nodule with verrucous surface, can be clustered
Micro:
* Vascular ectasia of the papillary dermis which may appear to extend into the epidermis
* Overlying epidermal hyperplasia characterized by acanthosis, elongation of the rete and hyperkeratosis, with the epidermis encircling the dilated vascular spaces
* Often thrombosis within the vascular ectasia
Bowenoid papulosis
- Human papillomavirus (HPV) related proliferation of atypical basaloid and koilocytic cells
- Characteristically involves the anogenital skin and mucosa
- Postulated to rarely progress to Bowen disease or invasive squamous cell carcinoma
Macro:
* Skin / mucosal punch or shave biopsy with superficial surface demonstrating papule(s), plaque or papillomatous lesion(s) that may be skin toned, violaceous or red-brown
Micro:
* Dysplastic changes with intact basement membrane, consistent with squamous cell carcinoma in situ
* Proliferation of atypical basaloid and koilocytic cells in squamous epithelium may range from scattered cells to full thickness involvement
* Often accompanied by acanthosis, parakeratosis and mitotic figures above the basal layer
* May demonstrate hyperkeratosis, dyskeratosis, lymphocytic infiltrate, loss of polarity and dilated, tortuous capillaries in dermal papillae
* Cannot definitively be distinguished from other forms of carcinoma in situ, Bowen disease and erythroplasia of Queyrat, based on histology alone
Molecular:
* DNA PCR and ISH may detect DNA of HPV
* Usually caused by HPV 16 infection or (less commonly) other HPV strains, including 18, 13, 33, 35, 39 and 53
IHC:
* p16
Penile intraepithelial neoplasia (PeIN)/ Bowen Disease
- Intraepithelial neoplastic proliferation with variable degree of dysplasia, keratinization and nuclear atypia
- Penile intraepithelial neoplasia (PeIN) is classified as HPV related / dependent or HPV unrelated / independent, similar to invasive carcinomas
- Considered a precursor of penile invasive carcinoma –> 5-10%
- PeIN is most commonly found in the glans and foreskin
- Differentiated PeIN, non-HPV related, preferentially involves the foreskin inner mucosal epithelium
- 40-60 years
Erythroplasia of Queyrat
* This disease is more aggressive than Bowen’s disease, with up to 33% of cases progressing to invasive SCC, and 20% of those cases resulting in metastasis. It’s usually seen in middle-aged to elderly men.
Macro:
Non-HPV related PeIN / differentiated
* Solitary white or pink macule, plaque or slightly elevated geographical lesion
* Affects the foreskin and glans and rarely the shaft
HPV related PeIN
* Lesions are flat or slightly elevated or papular, velvety, erythematous, dark brown or black
* Warty PeINs are granular or villous
* Borders are irregular or sharply delineated
Micro:
* Full-thickness dysplasia
* Hyperkeratosis, parakeratosis, hypergranulosis, acanthosis, elongation of rete ridges, abnormal squamous maturation and squamous cell atypia
* Prominent intercellular edematous bridges and intraepithelial keratinization
IHC:
Non-HPV related PeIN / differentiated
* Ki67: positive above the basal cell layer
* p53: may be positive in an irregular patchy pattern
HPV related PeIN / undifferentiated
* Ki67: positive in most cells, full thickness
* p16: 99% positive, en bloc for basaloid PeIN and ≤ 50% of epithelial thickness in warty basaloid and warty PeIN
Squamous cell carcinoma
- Malignant epithelial tumor composed of squamous cells; diagnosis often delayed
- Slow growing, exophytic/ulcerating penile mass
- Patients occasionally present with inguinal nodal metastases with occult penile cancer due to severe phimosis or very small primary tumor
- Local recurrence in 33% is due to insufficient surgery or positive margins, which also increases risk of regional inguinal and pelvic nodal metastases
- 10 year survival rate of 82%
Risk factors:
* Phimosis and long foreskin, paraphimosis
* Genital warts (6 times increased risk)
* Also HPV infection in general, particularly HPV 16 and related risk factors
* ~33% of non-HPV cases are associated with lichen sclerosus (balanitis xerotica obliterans)
* Penile injury, tears and chronic balanitis
* Smoking, psoriasis patients treated with UVB radiation, penile rash > 1 month, immunosuppression and radiation therapy
Macro:
* Superficial spreading: tumors are limited to lamina propria or superficial corpus spongiosum and usually extend horizontally through multiple anatomical compartments
* Vertical growth: tumors invade deep anatomical levels, surface is nonverruciform and frequently ulcerated
* Verruciform: tumors are exophytic and papillomatous with a cauliflower-like aspect, may be limited to surface (verrucous) or invade deep anatomical levels (cuniculatum)
* Mixed patterns: observed in 10 - 15% of all cases
* In some cases, multicentric tumors (2 or more independent foci of carcinomas) are identified
Micro:
* Usually keratinized with moderate differentiation
* Up to 50% of cases are heterogeneous (> 1 histological grade)
* Tumors composed exclusively of extremely well differentiated or poorly differentiated areas are uncommon
* Exophytic component –> often well-differentiated
* Endophytic component –> often poorly-differentiated
* In some cases, clear glycogenated cells may predominate (but must differentiate from koilocytes)
* Stroma has variable lymphoplasmacytic infiltrate
* Foreign body type giant cells are often seen in highly keratinized tumors
* Most are conventional (Keratinizing) varient
* OTher types –> basaloid, warty, warty-basaloid, papillary, sarcomatoid, mixed, adenosquamous, pseudoglandular, pseudohyperplastic
Molecular:
* Mutations in PIK3CA, HRAS or KRAS genes in 39%
* Epigenetic silencing (by methylation) of FHIT gene in 92%
IHC:
EGFR
Dense, en bloc p16 in HPV associated
Verrucous Carcinoma
- Middle aged men
- Most arise in the coronal sulcus
- Behaves as locally aggressive neoplasm
- No metastatic potential
- Not associated with HPV
Macro:
* Large, fungating, warty tumour
* Surface is frequently ulcerated
Micro:
* Endo and exophytic papillary growth
* Minimal cytologic atypia
* Rare mitotic activity
* Deep margin –> pushing, broad area of infiltration
* True koilocytosis
