2d:I[856015,["/_next/static/immutable/chunks/1xzisbplk9czp.js","/_next/static/immutable/chunks/3j2i1faptc_-9.js","/_next/static/immutable/chunks/0fma7nlq6immz.js","/_next/static/immutable/chunks/08tq8rmv423j5.js","/_next/static/immutable/chunks/1chr5wkk3j58k.js","/_next/static/immutable/chunks/37kmmh_zm4dov.js","/_next/static/immutable/chunks/311zvdjfxff-f.js","/_next/static/immutable/chunks/1a_hqhrsle_n_.js"],"default"] 2e:T6474,

Summary Table

Category	Detail
Risk Factors	Fair skin (Fitzpatrick I-II), chronic UV exposure, history of sunburns, immunosuppression, prior radiation therapy, advancing age, male sex, arsenic exposure, Gorlin syndrome (nevoid BCC syndrome)
Etiology	Dysregulated Hedgehog (Hh) signaling pathway, most commonly via loss-of-function mutation in PTCH1 tumor suppressor gene; UV-induced DNA damage in basal keratinocytes of the interfollicular epidermis and infundibulum
Patient Presentation	Slowly enlarging papule or nodule on sun-exposed skin (especially face), present for months to years, may bleed with minor trauma, usually painless
Classic Physical Exam	Pearly, translucent papule with rolled borders and arborizing telangiectasia; central ulceration or crusting in advanced lesions (ulcus rodens)
Key Diagnostic Results	Dermoscopy: arborizing vessels, blue-black globules/nests, leaf-like structures, spoke-wheel structures. Histopathology (gold standard): basaloid cell nests with peripheral palisading, retraction artifact (clefting) from fibromyxoid stroma
Management	Surgical excision with defined margins (3-4 mm low-risk, 5 mm or more high-risk); Mohs micrographic surgery for high-risk or cosmetically sensitive areas; Hedgehog inhibitors (vismodegib, sonidegib) for locally advanced or metastatic disease
Keywords	"Pearly papule," "rolled borders," "arborizing telangiectasia," "rodent ulcer," "sun-exposed area," "slow-growing," "locally invasive," "rarely metastasizes"

1. Pathophysiology

BCC originates from the basal layer of the epidermis, arising from stem cells in the interfollicular epidermis and the hair follicle infundibulum rather than the hair bulge as previously believed. It is the most common non-melanoma skin cancer and the most common malignancy overall in humans.

The central molecular driver is aberrant activation of the Hedgehog (Hh) signaling pathway. Under normal conditions, the transmembrane protein Patched-1 (PTCH1) tonically inhibits Smoothened (SMO), keeping the pathway silent. When PTCH1 undergoes a loss-of-function mutation, SMO becomes constitutively active, leading to unregulated nuclear translocation of GLI transcription factors. This drives unchecked proliferation of basal keratinocytes. UV radiation is the primary mutagen responsible for PTCH1 inactivation, which explains why BCC overwhelmingly occurs on chronically sun-exposed skin.

Despite being classified as a malignant neoplasm, BCC is locally invasive but rarely metastasizes (estimated metastatic rate below 0.5%). The clinical behavior is one of slow, relentless local tissue destruction. This is why the term "rodent ulcer" (ulcus rodens) exists: the tumor "gnaws" through tissue over time. Morfeaform and infiltrative subtypes carry a higher risk of subclinical extension and perineural invasion, making margin assessment more difficult.

The connection between pathophysiology and presentation is direct: the pearly, translucent quality of the papule reflects the basaloid cell clusters beneath a thin epidermis, while the arborizing telangiectasia results from tumor-associated angiogenesis. Central ulceration occurs when the tumor outgrows its blood supply.

2. Classification and Clinical Manifestation

Subtype	Clinical Features	Typical Location	Behavior / Risk
Nodular	Pearly translucent papule/nodule, rolled borders, telangiectasia; large lesions develop central necrosis (ulcus rodens)	Sun-exposed areas, especially face	Most common subtype (~60-80%); well-defined borders, lower recurrence after excision
Pigmented	Similar to nodular but with blue, black, or brown pigmentation due to melanin	Sun-exposed areas	Can mimic melanoma on clinical exam; dermoscopy helps distinguish
Superficial	Erythematous, scaly plaque; often multicentric	Trunk and extremities	Least aggressive subtype; tends to be multifocal; can mimic eczema or psoriasis
Morpheaform (Sclerosing)	White or yellow, shiny, scar-like plaque with ill-defined borders	Face	Most aggressive subtype; diffuse infiltrative growth with high recurrence; resembles morphea or scar tissue
Ulcerative	Includes ulcus rodens (superficial erosion) and ulcus terebrans (deep, destructive penetration)	Face	Associated with local tissue destruction into bone, cartilage
Other variants	Basosquamous, keratotic, fibroepithelioma of Pinkus (pink papule on lower back resembling a skin tag)	Variable	Basosquamous carries higher metastatic potential; Pinkus variant is indolent

EADO Classification and Staging

The European Association of Dermato-Oncology (EADO) classifies BCC by increasing difficulty-to-treat and recurrence risk:

Stage	Category	Description
I	Easy to Treat	Low-risk common BCC; recurrences only from blind treatments or insufficient margins
IIA	Common BCC	Somewhat difficult-to-treat; complexity from location, poor borders, prior recurrence, or patient factors
IIB	Common BCC	High number of common BCCs (more than 10) or multiple BCCs (more than 5), including Gorlin syndrome
IIIA	Advanced BCC	Locally advanced, difficult-to-treat BCC outside critical areas; curable without expected functional mutilation
IIIB	Advanced BCC	Locally advanced in critical or functionally important areas (periorbital, nose); curable by surgery but functional impairment and/or mutilation are inevitable
IIIC	Advanced BCC	Giant and/or deeply invasive tumors involving extracutaneous tissue (bone, muscle, vital structures); cure cannot be expected by surgery
IV	Metastatic BCC	Distant metastases; regardless of initial staging, any metastatic BCC is classified Stage IV

3. Diagnostic Workup

Test	Role	Key Findings
Dermoscopy (Best Initial Test)	Non-invasive screening tool for clinically suspicious lesions	Arborizing vessels, blue-black globules/nests, leaf-like structures, spoke-wheel structures, ulceration; may also show shiny white streak-strand-blotches and concentric globules
Histopathology / Biopsy (Gold Standard)	Confirmatory; determines subtype and guides treatment	Basaloid cell nests with scant cytoplasm, hyperchromatic nuclei, peripheral palisading, retraction clefting from fibromyxoid stroma, apoptotic cells
Immunohistochemistry	Differentiating BCC from trichoepithelioma or squamous cell carcinoma (SCC)	BCC: BCL2 (+), CD10 (+) diffusely, BerEP4 (+); Trichoepithelioma: CK15 (+), CK20 (+), podoplanin (+) at tumor periphery; SCC: EMA (+), BerEP4 (-)
CT scan / MRI	For advanced or aggressive lesions with suspected deep invasion	Indicated when clinical signs suggest bone, nerve, orbital, or parotid gland involvement

Dermoscopy is the best initial step when evaluating a suspicious skin lesion. The hallmark dermoscopic finding for nodular BCC is arborizing (tree-like branching) vessels, which are large-diameter focused vessels with multiple branching ramifications. Blue-grey globules and ovoid nests suggest nests of basaloid cells within the dermis. Leaf-like structures and spoke-wheel patterns are more characteristic of pigmented BCC. For superficial BCC, look for short fine telangiectasias, concentric structures, and multiple small erosions.

Histopathology via biopsy is the confirmatory test and is indicated for any lesion where clinical and dermoscopic assessment alone cannot establish the diagnosis. It is also required for lesions in high-risk zones (central face around the eyes, nose, ears, and mouth), large lesions, ulcerated lesions, and cases where subtype identification is needed to guide therapy. The classic histologic picture shows clusters of basaloid cells with peripheral palisading surrounded by a fibromyxoid stroma with characteristic retraction artifact (clefting between tumor nests and stroma). Apoptotic tumor cells, melanocyte colonization, and stromal amyloid deposition may also be present.

Immunohistochemistry becomes relevant when the histologic differential includes trichoepithelioma (a benign follicular tumor that closely mimics BCC). The key discriminator is that BCC expresses BCL2 and CD10 diffusely on tumor cells, while trichoepithelioma expresses CK15, CK20, and podoplanin at the tumor periphery. To differentiate BCC from SCC, BerEP4 is positive in BCC and negative in SCC, while EMA shows the reverse pattern.

4. Management and Treatment

Pharmacologic Therapy

Agent	Indication	Level of Evidence
Imiquimod (topical)	Small primary superficial and nodular BCC	1B (clinical), 2A (histologic improvement)
Sonidegib (Hedgehog inhibitor)	Locally advanced or metastatic BCC	1A
Vismodegib (Hedgehog inhibitor)	Locally advanced or metastatic BCC, difficult-to-treat cases	1A
5-Fluorouracil (5-FU) (topical)	Superficial BCC	2B
Tazarotene 0.1% (topical retinoid)	Superficial BCC (adjunctive)	1A
Zycure (0.005% solasodine glycosides)	Superficial BCC	1A

Surgical and Procedural Therapy

Modality	Indication	Evidence / Notes
Standard surgical excision	Primary BCC (first-line for most cases)	1C; margins 3-4 mm for low-risk, 5 mm or more for high-risk
Mohs micrographic surgery	High-risk BCC (recurrent, aggressive subtype, critical anatomic sites, ill-defined borders)	1C; 2% recurrence vs. 3% for standard excision at 30 months
Electrodesiccation and curettage	Low-risk, small BCC	1C
Cryosurgery	Low-risk BCC	1A
CO2 laser ablation	Low-risk BCC in low-risk areas only	1A; limitation: no histopathologic assessment possible post-ablation
Photodynamic therapy (PDT) with ALA or MAL	Superficial BCC, low-risk nodular BCC	1B; less effective than excision for nodular BCC but better cosmetic outcome with MAL-PDT
Radiotherapy	Patients who are not surgical candidates or who refuse surgery	Alternative therapy

First-line treatment for most BCC is standard surgical excision with predetermined margins. For low-risk BCC, margins of 3 to 4 mm are adequate. For high-risk BCC (large size, aggressive subtypes like morpheaform, location in the H-zone of the face), margins of at least 5 mm are recommended. Excision is more effective than both radiotherapy and PDT with 5-ALA for nodular BCC.

Mohs micrographic surgery is the preferred approach for high-risk lesions: recurrent BCC, aggressive histologic subtypes, tumors in cosmetically or functionally critical areas (periorbital, nasal, auricular), and lesions with clinically ill-defined borders. Mohs provides real-time, complete margin assessment through horizontal frozen sections, achieving a 2% recurrence rate at 30 months compared to 3% for standard excision. The tradeoff is that Mohs is more resource-intensive and costly.

Destructive techniques like electrodesiccation and curettage (ED&C), cryosurgery, and CO2 laser ablation are appropriate only for small, well-defined, low-risk BCCs. A notable limitation of CO2 laser ablation is that it destroys the tissue, making subsequent histopathologic evaluation impossible.

Photodynamic therapy (PDT) with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) is an option for superficial BCC and low-risk nodular BCC. While PDT provides a better cosmetic result than excision (particularly MAL-PDT), it is less effective at tumor clearance for nodular subtypes.

Hedgehog pathway inhibitors (vismodegib, sonidegib) represent the systemic therapy option for locally advanced BCC that is not amenable to surgery or radiotherapy, and for the rare metastatic BCC. These drugs work by inhibiting SMO, directly targeting the molecular driver of the disease. Side effects include muscle spasms, dysgeusia, alopecia, and weight loss.

Topical imiquimod (a toll-like receptor 7 agonist that stimulates local immune response) is used for small superficial and nodular BCC, though it carries a lower cure rate compared to surgery. Topical 5-FU is another option limited to superficial BCC.

Consultation

Radiotherapy referral is indicated when radiation is the chosen treatment modality. Hematology-Oncology referral is appropriate for cases requiring systemic chemotherapy or Hedgehog inhibitor therapy.

5. Differential Diagnosis and Distractors

Diagnosis	Why It's Similar	Key Discriminator
Squamous Cell Carcinoma (SCC)	Also occurs on sun-exposed skin; can present as a nodule or ulcerated lesion	SCC tends to be firm, keratinizing, with a "cutaneous horn" or thick crust; lacks the pearly translucent quality and arborizing vessels of BCC; grows faster; higher metastatic risk; immunohistochemistry: EMA (+), BerEP4 (-)
Melanoma	Pigmented BCC can mimic nodular melanoma	Melanoma shows irregular pigment network, asymmetric dots/globules, blue-white veil on dermoscopy; BCC shows arborizing vessels and leaf-like structures; biopsy is definitive
Actinic Keratosis	Sun-damaged skin, similar demographic	Actinic keratosis is a rough, scaly, flat lesion (pre-malignant for SCC, not BCC); lacks nodularity, translucency, and telangiectasia
Keratoacanthoma	Dome-shaped nodule on sun-exposed skin	Keratoacanthoma has a central keratinous plug ("volcano-like"), rapid growth over weeks, and may involute spontaneously; BCC grows slowly over months to years
Bowen Disease (SCC in situ)	Erythematous scaly plaque, can mimic superficial BCC	Bowen disease is typically a well-demarcated, uniformly erythematous plaque without the pearly or translucent quality; full-thickness epidermal dysplasia on histology without dermal invasion
Trichoepithelioma	Benign follicular tumor; flesh-colored papule on the face; histologically mimics BCC	Trichoepithelioma shows horn cysts and papillary mesenchymal bodies on histology; IHC: CK20 (+), podoplanin (+), BCL2 (-) in tumor cells
Seborrheic Keratosis	Pigmented, "stuck-on" lesion that can mimic pigmented BCC	Seborrheic keratosis has a waxy, verrucous surface with horn pseudocysts on dermoscopy; lacks arborizing vessels
Morphea / Localized Scleroderma	Morpheaform BCC mimics scar or morphea plaque	True morphea is bilateral/symmetric, has a lilac ring at the periphery during active phase, and lacks telangiectasia or subtle erosion that morpheaform BCC may show; biopsy differentiates
Dermatitis / Psoriasis	Superficial BCC can mimic a chronic eczematous or psoriatic patch	Dermatitis and psoriasis are typically bilateral, respond to topical steroids, and lack the fine telangiectasias and threadlike border of superficial BCC; persistent unilateral "eczema patch" that does not respond to treatment should raise suspicion for superficial BCC

6. Traps and High-Yield Pearls

The most common way students get BCC questions wrong is by confusing the subtype with the management approach. The vignette may describe a scar-like, ill-defined, whitish plaque on the nose, and the student selects standard excision with 3-4 mm margins. This is wrong because the description points to morpheaform BCC in a high-risk location, which requires either Mohs micrographic surgery or wide excision with at least 5 mm margins. The test is checking whether you can match the clinical subtype and anatomic location to the appropriate surgical strategy.

Another common trap involves superficial BCC mimicking benign dermatoses. The vignette gives a persistent, non-healing, erythematous scaly patch on the trunk that "has not responded to topical steroids." Students pick eczema or psoriasis. The key discriminator is the lack of response to standard dermatitis treatment plus unilateral distribution, which should trigger biopsy.

For pigmented BCC, the trap is selecting melanoma as the diagnosis. The giveaway in the vignette is the presence of arborizing telangiectasia and a pearly quality, which melanoma does not have. Dermoscopy findings in the question stem will often include "tree-like branching vessels" rather than an irregular pigment network.

On treatment questions, remember that Hedgehog inhibitors (vismodegib, sonidegib) are reserved for locally advanced unresectable or metastatic BCC, not for routine cases amenable to surgery. If the vignette describes a patient with a giant, inoperable facial BCC invading bone (Stage IIIC), the answer is a Hedgehog inhibitor, not wider excision.

Finally, do not forget that BCC rarely metastasizes but has a 30-50% chance of developing a second primary lesion within 5 years. Follow-up surveillance at 3 to 12 month intervals (based on risk category) is a tested concept. The prognosis for life (quo ad vitam) is generally favorable (dubia ad bonam), while prognosis for function and cure (quo ad functionam and quo ad sanactionam) are more guarded (dubia ad malam), especially for high-risk subtypes.

1e:["$","$L2d",null,{"article":{"id":"16bd1540-5418-4f89-83d3-e2452a832f6d","title":"Karsinoma Sel Basal","content":"$2e","category":"Dermatovenereologi","created_at":"2026-05-18T11:43:36.369553+00:00","status":"published","subcategory":null},"questionCount":2,"sections":[{"id":"section-pathophysiology","num":"01","title":"Pathophysiology"},{"id":"section-classification-and-clinical-manifestation","num":"02","title":"Classification and Clinical Manifestation"},{"id":"section-diagnostic-workup","num":"03","title":"Diagnostic Workup"},{"id":"section-management-and-treatment","num":"04","title":"Management and Treatment"},{"id":"section-differential-diagnosis-and-distractors","num":"05","title":"Differential Diagnosis and Distractors"},{"id":"section-traps-and-high-yield-pearls","num":"06","title":"Traps and High-Yield Pearls"}],"hasSummaryTable":true}]