Genital Intraepithelial Neoplasia & SCC In Situ: Mohs Indications

Undifferentiated PeIN is driven by high-risk HPV infection, predominantly HPV types 16 and 18, with HPV 16 accounting for approximately 60-80% of cases. This category includes the formerly named basaloid, warty (condylomatous), and mixed (warty-basaloid) subtypes. The basaloid subtype shows a monotonous population of immature basaloid cells throughout the full thickness of the epithelium with minimal keratinization. The warty subtype displays a distinctive undulating surface with koilocytotic changes (perinuclear clearing, nuclear irregularity) reflecting active viral cytopathic effect. The mixed warty-basaloid pattern is the most common undifferentiated subtype. Undifferentiated PeIN characteristically shows strong, diffuse block-type p16 positivity on immunohistochemistry, serving as a reliable surrogate marker for transcriptionally active HPV. The overall risk of progression to invasive SCC is approximately 3-5%, lower than the differentiated subtype. Undifferentiated PeIN accounts for approximately 40-50% of all PeIN cases and tends to occur in younger patients (40-60 years).

Differentiated PeIN (dPeIN) is an HPV-independent pathway strongly associated with chronic inflammatory conditions, most notably lichen sclerosus et atrophicus (LSA). This subtype arises through a TP53 mutation-driven pathway and represents the premalignant precursor for the majority of well-differentiated keratinizing invasive penile SCCs. Differentiated PeIN is characteristically p16-negative and shows aberrant p53 expression patterns. Either strong diffuse overexpression (missense mutation pattern) or complete loss of expression (null/deletion pattern). dPeIN is histologically subtle and can be difficult to distinguish from reactive atypia associated with lichen sclerosus, making it the more dangerous and diagnostically challenging subtype. It accounts for approximately 30-40% of PeIN cases and tends to occur in older patients (60-80 years). Critically, differentiated PeIN carries a significantly higher risk of progression to invasive SCC (estimated 33-50% over 5-10 years) and gives rise to more aggressive, deeply invasive tumors compared to the HPV-driven pathway.

The vulvar counterpart follows a parallel classification system. The ISSVD (International Society for the Study of Vulvovaginal Disease) 2015 classification divides vulvar intraepithelial neoplasia into usual-type VIN (uVIN, HPV-associated, equivalent to undifferentiated PeIN) and differentiated VIN (dVIN, HPV-independent, lichen sclerosus-associated). Usual-type VIN is further subdivided into warty, basaloid, and mixed patterns. The molecular and prognostic parallels to the penile classification are direct. DVIN carries a significantly higher risk of progression to invasive vulvar SCC (up to 33-86% in some series) compared to uVIN (approximately 5-9%). The concept of vulvar field cancerization is important: patients with one area of VIN may harbor multicentric disease, and careful examination of the entire vulvar, perianal, and vaginal mucosa is essential.

Bowen disease of the genital region presents as a well-demarcated, erythematous, scaly plaque on keratinized genital skin. The penile shaft, scrotum, inguinal folds, mons pubis, or perineum. The plaque is typically sharply bordered, erythematous to pink-brown, with variable scale or crusting. It grows slowly by radial extension and may be asymptomatic or mildly pruritic. Clinically, it can closely mimic eczema, psoriasis, lichen simplex chronicus, fixed drug eruption, or tinea cruris. The key clinical distinguishing feature is its fixed, persistent nature and resistance to topical anti-inflammatory or antifungal therapy. Any genital plaque that does not respond to appropriate topical therapy within 2-4 weeks warrants biopsy.

Erythroplasia of Queyrat presents as a well-demarcated, velvety, glistening, bright red plaque on the glans penis, coronal sulcus, or inner prepuce. The mucosal or modified mucosal surface. The surface may appear moist, eroded, or glazed. Uncircumcised men are at substantially higher risk, as the moist environment of the preputial space promotes HPV persistence and chronic inflammation. The differential diagnosis includes Zoon balanitis (plasma cell balanitis), contact dermatitis, candidal balanitis, lichen planus, and fixed drug eruption. Zoon balanitis can be clinically indistinguishable from erythroplasia of Queyrat, making biopsy essential. Erythroplasia of Queyrat is considered to have a higher risk of progression to invasive SCC compared to Bowen disease of keratinized skin, with progression rates of approximately 5-10%.

Bowenoid papulosis is an HPV-driven condition presenting as multiple small (2-10 mm), discrete, flat-topped papules that may be skin-colored, brown, erythematous, or violaceous. It occurs predominantly in sexually active young adults (20-40 years) and has a strong association with HPV 16 and 18. Unlike Bowen disease, the lesions of bowenoid papulosis are characteristically multifocal and papular rather than forming a single large plaque. Although histologically identical to SCC in situ (full-thickness epidermal atypia), bowenoid papulosis has a generally benign clinical course with spontaneous regression possible, particularly in immunocompetent patients. However, transformation to invasive SCC has been documented, and the HPV types associated with bowenoid papulosis (HPV 16, 18) are the same high-risk types implicated in cervical, anal, and penile carcinoma. Female sexual partners of men with bowenoid papulosis have an increased risk of cervical intraepithelial neoplasia (CIN) and should undergo cervical screening.

Vulvar SCC in situ may present as erythematous, leukoplakic (white), hyperpigmented, or mixed-color patches or plaques on the vulvar skin. Usual-type VIN (HPV-associated) tends to be multifocal, affecting younger women, and may appear as raised, verrucous, or pigmented papules. Differentiated VIN (dVIN) is more challenging to recognize clinically, often presenting as a focal area of thickening, hyperkeratosis, or erosion on a background of lichen sclerosus. dVIN is typically unifocal and may appear as a subtle white or erythematous plaque that is easily dismissed as part of the underlying lichen sclerosus. Pruritus is the most common symptom across all vulvar SCC in situ subtypes. Vulvoscopy with acetic acid application can enhance visualization of subclinical disease.

Perianal SCC in situ (formerly perianal Bowen disease) presents as a well-demarcated, erythematous, scaly or verrucous plaque in the perianal region. It is predominantly HPV-driven and shares epidemiologic associations with anal squamous neoplasia. Risk factors include HPV infection, receptive anal intercourse, HIV infection, and immunosuppression. The differential diagnosis includes condylomata acuminata, psoriasis, contact dermatitis, and Paget disease (extramammary). Perianal SCC in situ may be asymptomatic or cause pruritus, burning, or bleeding. Given the shared HPV etiology, patients with perianal SCC in situ should be evaluated for concurrent cervical, vaginal, vulvar, and anal intraepithelial neoplasia.

Undifferentiated PeIN shows full-thickness replacement of the epidermis by atypical keratinocytes with loss of normal maturation. The basaloid subtype demonstrates a monotonous population of small, dark, basaloid cells with a high nuclear-to-cytoplasmic ratio extending through all epithelial layers. The warty subtype shows a characteristic undulating (spiky) surface with koilocytic change. Perinuclear clearing with nuclear enlargement, irregularity, and hyperchromasia. Reflecting active HPV cytopathic effect. The mixed warty-basaloid pattern combines features of both. Mitotic figures, including atypical forms, are present throughout the epithelium. The dermal-epidermal junction is intact (no invasion into the dermis), distinguishing SCC in situ from invasive SCC. Parakeratosis is common.

Differentiated PeIN is histologically the most challenging subtype to diagnose. The atypia is characteristically subtle and confined to the basal and parabasal layers, with the upper epithelium showing apparent maturation. This gives a deceptively bland appearance on low-power examination. Key diagnostic features include: basal cell atypia with nuclear enlargement, prominent nucleoli, and irregular nuclear contours; abnormal keratinization with eosinophilic (glassy) cytoplasm in the lower epithelium; elongated and branching rete ridges; keratin pearl formation within the rete; and an abrupt transition between the atypical basal cells and the relatively normal-appearing suprabasal layers. The changes are often focal and can be subtle even for experienced dermatopathologists. The background dermis frequently shows the characteristic features of lichen sclerosus: homogenized collagen in the papillary dermis, a band-like lymphocytic infiltrate beneath the zone of homogenization, and epidermal atrophy with follicular plugging.

A targeted IHC panel is essential for accurate PeIN classification and should be performed on all genital SCC in situ biopsies. p16 is the most important single marker: undifferentiated (HPV-driven) PeIN shows strong, diffuse, continuous (block-type) p16 positivity throughout the full thickness of the epithelium, reflecting HPV E7-mediated Rb pathway inactivation. Differentiated PeIN is p16-negative or shows only patchy, non-block-type staining. p53 staining patterns are the key to diagnosing differentiated PeIN: aberrant p53 expression manifests as either strong diffuse overexpression throughout the basal layer and extending into the suprabasal layers (missense mutation pattern) or complete absence of staining (null/deletion pattern). Wild-type p53 shows a heterogeneous, scattered pattern. Ki-67 proliferation index is elevated in undifferentiated PeIN (full-thickness staining) and may show a parabasal-predominant pattern in differentiated PeIN. CK17 positivity has been reported as an additional marker for differentiated PeIN.

Undifferentiated PeIN/uVIN progresses to invasive SCC in approximately 3-5% of cases over extended follow-up (5-10 years). When progression does occur, the resulting invasive SCC tends to be of the basaloid or warty subtype, which generally carries a more favorable prognosis compared to conventional keratinizing SCC. The progression risk may be higher in older patients, immunosuppressed individuals, and those with persistent HPV infection. Bowenoid papulosis, while histologically identical to undifferentiated PeIN, has a particularly low progression risk and may undergo spontaneous regression, especially in immunocompetent young patients. However, the progression risk of bowenoid papulosis is not zero, and cases of progression to invasive SCC have been documented. The overall risk of progression for bowenoid papulosis is estimated at 1-3%.

Differentiated PeIN/dVIN carries a dramatically higher risk of progression to invasive SCC, estimated at 33-50% over 5-10 years in some series. Roughly 10 times higher than the undifferentiated pathway. This is one of the most important clinical facts about genital intraepithelial neoplasia. The invasive SCC arising from differentiated PeIN is typically a well-differentiated keratinizing SCC that tends to be deeply invasive at the time of diagnosis, with a higher propensity for lymph node metastasis compared to HPV-driven genital SCC. The insidious nature of differentiated PeIN. Its subtle histology, frequent underdiagnosis, and association with chronic lichen sclerosus that may mask early changes. Means that many cases are not diagnosed until invasive SCC has already developed. The concept of field cancerization is particularly relevant: the entire area of lichen sclerosus-affected genital skin may harbor TP53-mutant clones that represent a field effect, with multiple areas of dPeIN developing independently.

Several factors increase the risk of progression from genital SCC in situ to invasive disease across both pathways. Immunosuppression (HIV infection, solid organ transplantation, chronic immunosuppressive therapy) is a major risk factor, both increasing the likelihood of persistent HPV infection and impairing immune surveillance of premalignant clones. Older age is associated with higher progression risk, particularly for the differentiated pathway. Persistent or extensive lichen sclerosus without adequate treatment or surveillance increases the risk of dPeIN development and progression. Smoking is an independent risk factor for both cervical and penile carcinogenesis, likely through both immunosuppressive and direct mutagenic effects. Lack of circumcision increases the risk of penile SCC, likely through mechanisms including HPV persistence in the preputial environment and chronic inflammatory changes (phimosis, balanoposthitis). Multifocal disease and large lesion size may indicate a broader field effect and higher cumulative progression risk.

The genital region is classified as an H-zone (high-risk zone) in the NCCN risk stratification system, and genital SCC in situ meets multiple criteria for Mohs surgery. The rationale is particularly compelling. First, tissue conservation is paramount. Even a few millimeters of excess tissue removal on the glans, prepuce, or vulva can result in significant functional impairment, disfigurement, or sexual dysfunction. Mohs allows removal of the tumor with the narrowest possible margins while ensuring completeness of excision. Second, subclinical extension is common. Genital SCC in situ frequently extends beyond the clinically visible borders, with studies showing subclinical extension in 30-50% of cases. Standard clinical margins may be insufficient to capture these extensions, while Mohs provides complete peripheral margin assessment. Third, recurrence rates after standard excision are high. Reported recurrence rates after conventional wide local excision for genital SCC in situ range from 10-23%, compared to approximately 0-6% after Mohs surgery. Fourth, frozen section control allows real-time margin assessment without the need for overly wide margins that would increase morbidity.

The AAD/ACMS Appropriate Use Criteria (AUC) support Mohs micrographic surgery for SCC in situ in the genital region based on the anatomic location (H-zone) and the functional importance of tissue conservation. Genital SCC in situ in Area H is rated as appropriate for Mohs regardless of lesion size. Documentation should specify the H-zone location, functional considerations for tissue conservation, history of treatment failure (if recurrent), and any associated features such as background lichen sclerosus or immunosuppression. For patients with extensive or multifocal disease where complete excision by Mohs would result in unacceptable tissue loss, a staged approach combining Mohs for the most clinically significant lesion with topical therapy for remaining areas may be appropriate.

Mohs surgery in the genital region requires several technique modifications. Local anesthesia should be administered carefully with attention to distortion of landmarks. Nerve blocks (dorsal penile nerve block, pudendal nerve block) are preferred over local infiltration when feasible to avoid tissue distortion. The thin, delicate nature of genital skin (particularly the glans and vulvar mucosa) requires careful tissue handling to avoid crush artifact on frozen sections. Inking margins on thin mucosal specimens can be challenging, and meticulous orientation is critical. The Mohs layer should be taken at an appropriate depth. SCC in situ is an epidermal process, and the initial layer need not include deep subcutaneous tissue. However, if the initial biopsy showed any question of microinvasion, adequate deep margins are essential. Frozen section interpretation of genital skin requires familiarity with the normal histology of modified mucosal surfaces, which differs from keratinized skin. In situ SCC on the glans or vulvar mucosa can be more difficult to identify on frozen sections due to the thinner epithelium and different architecture.

For cases where Mohs is not available or for very large lesions where same-day completion is impractical, staged excision with complete circumferential and deep margin assessment (CCPDMA) on permanent sections (slow Mohs) is an effective alternative. The excised tissue is processed using the en face technique on formalin-fixed, paraffin-embedded sections, providing the same complete margin assessment as Mohs but without real-time frozen section analysis. This is particularly useful for large vulvar or penile lesions where multiple stages may be anticipated and the logistics of same-day Mohs may be challenging. The disadvantage is that the wound must be left open or managed with a temporary dressing between stages (typically 1-2 weeks apart), which may be uncomfortable in the genital area. Rush permanent sections (24-48 hour turnaround) can reduce the interval between stages.

When Mohs is unavailable, wide local excision (WLE) with predetermined margins is the standard surgical alternative. For genital SCC in situ, NCCN recommends clinical margins of 5-10 mm with histologic confirmation of clear margins. Peripheral margins should be assessed using permanent sections with complete margin evaluation when possible. Recurrence rates after WLE for genital SCC in situ are higher than after Mohs (10-23% vs. 0-6%), reflecting the inability of predetermined margins to account for irregular subclinical extension. Re-excision should be performed for positive margins. For extensive disease or multifocal disease, partial penectomy, glansectomy, or partial vulvectomy may be necessary, though these procedures carry significant functional and psychosocial morbidity.

5-fluorouracil 5% cream is one of the most widely used non-surgical treatments for genital SCC in situ and is considered first-line topical therapy by many experts. The mechanism involves selective destruction of rapidly proliferating neoplastic keratinocytes through inhibition of thymidylate synthase, disrupting DNA synthesis. For genital SCC in situ, 5-FU is typically applied once or twice daily for 4-6 weeks, though treatment protocols vary. Expected response includes progressive erythema, erosion, and crusting of the treated area, reflecting selective destruction of dysplastic epithelium. Complete clinical response rates range from 50-75%, with recurrence rates of approximately 10-20% at 5-year follow-up. Advantages include tissue preservation, self-application by the patient, and the ability to treat large or multifocal areas. Disadvantages include significant local irritation (erosion, pain, burning) that may limit compliance, inability to confirm complete clearance histologically, and the need for prolonged treatment courses. Zinc oxide or petroleum jelly applied to surrounding normal skin can reduce collateral irritation.

Imiquimod 5% cream is a topical immune response modifier that activates innate and adaptive immunity through toll-like receptor 7 (TLR7) stimulation, inducing interferon-alpha, tumor necrosis factor, and other cytokines that promote anti-tumor immune surveillance. For genital SCC in situ, imiquimod is typically applied 3-5 times per week for 6-16 weeks. Complete clinical response rates are reported at 50-73%, comparable to 5-FU. Imiquimod may be particularly well-suited for HPV-driven undifferentiated PeIN, as the immune response it induces may target HPV-infected cells specifically. Local side effects include erythema, erosion, edema, and flu-like systemic symptoms (particularly with genital application where systemic absorption may be higher). The combination of imiquimod with 5-FU (sequential or alternating) has been investigated for refractory cases.

Photodynamic therapy using aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) with red light illumination has been used for genital SCC in situ. The photosensitizer is preferentially absorbed by dysplastic keratinocytes and, upon light activation, generates reactive oxygen species that selectively destroy the neoplastic cells. PDT has the advantage of being well-tolerated with good cosmetic outcomes and preserving normal tissue architecture. However, response rates for genital SCC in situ are variable, with complete response rates of 40-80% depending on the study and treatment protocol. Multiple treatment sessions may be required. Pain during illumination is the primary side effect and can be significant in the genital region. Adequate analgesia (topical anesthesia, nerve blocks, or oral analgesics) is essential. PDT is particularly useful for multifocal disease and for lesions in cosmetically sensitive areas where surgical scarring would be undesirable.

Carbon dioxide (CO2) laser ablation vaporizes the dysplastic epithelium to a controlled depth, typically extending to the papillary or mid-reticular dermis. It is effective for superficial genital SCC in situ with reported clearance rates of 70-90%. Advantages include precise depth control, excellent hemostasis, and good healing in the genital region with minimal scarring. The primary disadvantage is the destruction of all tissue, eliminating the possibility of histologic margin assessment. Residual or recurrent disease at the deep margin (adnexal structures) is a concern, though this is less problematic in the genital area where follicular density is lower than the face. CO2 laser is often used for bowenoid papulosis and multifocal genital SCC in situ where excision of all lesions would be impractical.

Cryotherapy with liquid nitrogen can be used for small, well-defined genital SCC in situ, but has significant limitations in this anatomic location. The uncontrolled depth of destruction, high recurrence rates (approximately 20-40%), and risk of scarring with secondary phimosis, urethral stricture, or vulvar adhesions limit its utility. Cryotherapy is generally not recommended as primary treatment for genital SCC in situ except in very select cases (small, superficial, keratinized skin) where other treatments are unavailable. Two freeze-thaw cycles are recommended when cryotherapy is used. It may have a role as adjunctive treatment for small satellite foci of disease.

The AJCC 8th edition TNM staging for penile SCC classifies tumors by depth of invasion: T1a. Invasion into lamina propria without lymphovascular invasion (LVI) or perineural invasion (PNI) and not poorly differentiated; T1b. Invasion into lamina propria with LVI, PNI, or poorly differentiated histology; T2. Invasion into corpus spongiosum or dartos fascia; T3. Invasion into corpus cavernosum or urethra; T4. Invasion into adjacent structures (prostate, pubic bone). Nodal staging (N) incorporates the number and laterality of involved inguinal and pelvic lymph nodes. The prognosis is strongly stage-dependent: 5-year survival exceeds 85% for T1a disease but drops below 30% for T4 or N3 disease. Vulvar SCC staging follows a similar framework with tumor size, depth of invasion, and nodal involvement driving prognostication.

Mohs micrographic surgery has an established role in early-stage invasive genital SCC, particularly for T1a penile SCC where the tumor is confined to the lamina propria without adverse histologic features. In selected T1a tumors, Mohs provides the same tissue-sparing advantage as in SCC in situ while ensuring complete margin assessment. This allows organ preservation in many cases where traditional surgical management would require partial or total penectomy, with profound psychosocial and functional consequences. Studies of Mohs for penile SCC have shown local recurrence rates of approximately 0-11% for selected cases, comparing favorably to the 4-12% local recurrence rate after partial penectomy. Patient selection is critical. Mohs is most appropriate for well-defined, superficially invasive tumors on the glans or distal penile shaft. Tumors with deep invasion into the corpora, poor differentiation, or clinical lymphadenopathy require more extensive surgical management.

Lymph node assessment is a critical component of invasive genital SCC management. For penile SCC, the inguinal lymph nodes are the primary draining basin, and nodal status is the single most important prognostic factor. Dynamic sentinel lymph node biopsy (DSNB) is recommended for clinically node-negative patients with intermediate-risk (T1b-T2) penile SCC in experienced centers. DSNB has a sensitivity of approximately 88-95% in experienced hands and allows identification of occult nodal metastases without the significant morbidity of complete inguinal lymph node dissection (ILND). When DSNB is positive or when clinically palpable inguinal lymphadenopathy is confirmed by fine-needle aspiration biopsy, therapeutic inguinal lymph node dissection is indicated. For vulvar SCC, sentinel lymph node biopsy is well-established for tumors with depth of invasion greater than 1 mm.

Radiation therapy plays multiple roles in invasive genital SCC management. As primary treatment, radiation can achieve organ preservation in selected penile SCC cases (T1-T2 tumors <4 cm) with local control rates of 50-70%, though these are generally inferior to surgical approaches. Adjuvant radiation to the inguinal and pelvic lymph node basins is recommended after lymph node dissection when multiple nodes are involved, extranodal extension is present, or pelvic node involvement is identified. For vulvar SCC, adjuvant radiation to the inguinal and pelvic regions is standard after positive sentinel lymph node biopsy or when two or more lymph nodes are involved. Chemoradiation (cisplatin-based concurrent chemotherapy with radiation) is used for locally advanced, unresectable, or recurrent disease.

Systemic therapy for advanced genital SCC has been transformed by immune checkpoint inhibitors. Penile SCC, like cutaneous SCC, has shown responsiveness to anti-PD-1 therapy, and both cemiplimab and pembrolizumab are being evaluated in penile SCC through clinical trials and off-label use. The tumor mutational burden of penile SCC is variable. HPV-positive tumors may have a different immune microenvironment and potentially different response patterns compared to HPV-negative tumors, though data are still emerging. Traditional chemotherapy regimens (cisplatin-based combinations: TIP. Paclitaxel, ifosfamide, cisplatin) remain the standard first-line systemic therapy for metastatic penile SCC, with objective response rates of approximately 30-50%. For vulvar SCC, systemic therapy follows similar principles with PD-1 checkpoint inhibitors showing promise in the advanced/recurrent setting.

Recurrence rates after treatment of genital SCC in situ vary significantly by modality. Mohs micrographic surgery achieves the lowest recurrence rates at approximately 0-6% (5-year). Wide local excision with 5-10 mm margins has recurrence rates of 10-23%. Topical 5-FU and imiquimod have recurrence rates of 10-25%. CO2 laser ablation recurrence rates are approximately 10-15%. Cryotherapy has the highest recurrence rates at 20-40%. These recurrence rates underscore the importance of selecting the most appropriate treatment modality based on disease characteristics, patient factors, and available expertise. Recurrence after any treatment modality warrants re-evaluation including rebiopsy to reassess histologic subtype, rule out progression to invasive disease, and determine optimal retreatment strategy.

Following treatment of genital SCC in situ, clinical follow-up is recommended every 3-6 months for the first 2 years, then every 6-12 months thereafter for a minimum of 5 years, and ideally lifelong for patients with lichen sclerosus or persistent HPV infection. Each follow-up visit should include complete examination of the treated site for recurrence, examination of the entire genital region for new primary lesions, palpation of inguinal lymph nodes (to detect early progression to invasive disease), and assessment of the background condition (lichen sclerosus management, HPV-related disease elsewhere). Biopsy should be performed for any suspicious clinical finding. Post-treatment biopsy of the treated site to confirm clearance is recommended after non-surgical therapy (5-FU, imiquimod, PDT) and should be performed 4-8 weeks after completion of treatment.

Patients with HPV-associated genital intraepithelial neoplasia are at risk for multicentric HPV-related neoplasia at other anogenital sites. Screening recommendations include cervical cytology/HPV co-testing for female patients and female partners of affected males, anal cytology (Pap smear) for patients with perianal disease or high-risk features (HIV, MSM, immunosuppression), oropharyngeal awareness for HPV-related head and neck SCC risk, and examination of all genital and perianal skin for multicentric disease. Partner notification and counseling about HPV transmission, vaccination eligibility, and screening recommendations are important components of care. HPV vaccination (9-valent) should be offered to eligible patients and partners who have not been previously vaccinated, as vaccination may reduce the risk of new HPV-related lesions even in previously infected individuals (though data are evolving).

Patients with genital lichen sclerosus require lifelong dermatologic surveillance regardless of whether PeIN/VIN has been diagnosed. The cumulative lifetime risk of vulvar SCC in women with lichen sclerosus is estimated at 3-5%, and a similar risk exists for penile SCC in men with lichen sclerosus. Active management of lichen sclerosus with topical corticosteroids (clobetasol propionate) reduces the inflammatory milieu and may decrease the risk of malignant transformation, though definitive evidence for cancer prevention through LS treatment is still accumulating. Surveillance examinations should focus on identifying any focal change (new erythema, erosion, hyperkeratosis, nodularity, or architectural distortion) in the field of lichen sclerosus, which should prompt biopsy to evaluate for differentiated PeIN or early invasive SCC. Patient education about self-examination and the warning signs of malignant transformation is an important component of lichen sclerosus management.