Basal Cell Carcinoma Diagnosis and Treatment
Primary Care Visit Report
A 50-year-old female with no past medical history presented with a rash on her left upper arm that had been there, per the patient, “for at least 10 years.” She said it changed in appearance sometimes but was always dry, scaly, and often itchy. The patient said she tried her best not to scratch it. She also reported that the lesion occasionally bled spontaneously. In the past, she had applied hydrogen peroxide and apple cider vinegar with no effect. She had also tried over-the-counter hydrocortisone cream and moisturizer, both of which made the scab and scale go away, revealing a red base.
Vitals were normal. On exam, on her left upper arm, there was a 2.5 cm × 2.5 cm erythematous, scaly plaque with irregular borders and peripheral scab.
The lesion was suspected to be psoriasis as the patient previously had a rash in her intergluteal cleft, which was diagnosed and treated as inverse psoriasis. However, she was referred to dermatology for further evaluation. At the dermatology clinic, the arm lesion was biopsied and found to be basal cell carcinoma. She subsequently underwent Mohs surgery to remove it.
Discussion from Dermatology Clinic
Differential Dx
• Basal cell carcinoma
• Amelanotic melanoma
• Bowen’s disease
• Extramammary Paget’s disease
• Squamous cell carcinoma
• Lichenoid keratosis
Favored Dx
In this case, biopsy was diagnostic of basal cell carcinoma (BCC). Psoriatic lesions would typically be more thickened. Long-standing pruritic, scaly lesions located in sunexposed areas and accompanied by spontaneous bleeding, as well as the patient’s fair skin and age, are aspects of the history and physical examination that would raise clinical suspicion of BCC in the absence of biopsy results. This patient’s BCC appears to belong to the superficial subtype (discussed in more detail below), as the lesions are fl at and scaly.
Overview
Skin cancers are the most commonly occurring type of cancer, with over one million diagnoses per year in the USA [ 1 , 2 ]. BCC is a neoplasm of keratinocytes (an epi-dermal cell that produces keratin) of the lowest, or basal, layer of the epidermis, and accounts for 75–80 % of non-melanoma skin cancers [ 1 , 2 ]. It affects men more commonly than women, and is considered a cancer of the elderly, although inci-dence is increasing overall particularly among younger women [ 1 – 4 ]. BCC pre-dominantly affects fair-skinned people [ 2 ]. The actual incidence of BCC is diffi cult to estimate as non-melanoma skin cancers may not be included in cancer registry statistics [ 1 , 5 ]. Additionally, in some countries only the fi rst instance of BCC is reported, and recurrence as well as multiple lesions are common [ 3 ].
The pathogenesis of BCC is complex, and represents an interaction between genetic, phenotypic and environmental factors [ 5 ]. The main genetic abnormality in BCC is thought to be upregulation of the Hedgehog (HH) signaling pathway found on the PTCH1 gene, which is responsible for normal tissue maintenance in adult life. UV radiation appears to induce mutations that inactivate PTCH1 , p53 and other tumor sup-pressor genes [ 2 ]. PTCH1 mutations are present in 68–90 % of sporadic BCCs [ 2 , 5 ].
Unlike squamous cell carcinoma which is related to cumulative sun exposure , BCC is believed to be associated with intermittent, intense sun exposure, and expo-sure early in life [ 1 , 2 , 4 ]. Although BCC most often presents on sun-exposed areas, UV exposure is not entirely predictive of lesion location, as BCC can also arise on areas of the body that are not typically sun-exposed [ 4 ]. The tendency to develop mul-tiple lesions has a genetic link and may be suggestive of basal nevus syndrome [ 2 ]. Other risk factors for developing BCC include age, male sex, fair complexion, light-colored eyes, red hair, immunosuppressed status, and exposure to ionizing radiation [ 1 , 2 ].
Presentation
Basal cell carcinomas typically present as dry, crusting, non-healing plaques that are pink to red in color. They can be pearly and translucent. They often feature small dilated blood vessels called telangiectasias and raised edges. Patients may complain of pruritus. Pain is associated with ulceration, depth of invasion, and the morphea-form variant of BCC—a variant with innocuous surface characteristics but deep, wide extension [ 6 ]. BCCs typically appear on sun-exposed areas of the head, neck, trunk, and extremities; however, they can occur anywhere. Patients may describe healing followed by recurrence of lesion, and bleeding spontaneously or after slight trauma. Larger lesions may feature partial necrosis. BCC tends to be destructive of local tissue and is usually not metastatic; however, long-standing, untreated BCC can invade subcutaneous layers, muscle, and bone.
There are fi ve clinical subtypes of BCC, each presenting slightly differently. The most common subtype is nodular BCC , which typically occurs on the head and neck [ 2 ]. Pigmented BCC presents as a hyperpigmented, translucent nodule. Superfi cial BCCs are fl at plaques that tend to occur on the trunk and resemble eczema. They are the second most common variant. Morpheaform BCC (also called infi ltrating or sclerosing BCC) is a more aggressive variant that appears as a shiny, hypopigmented fi rm plaque most often located on the head and neck. This variant tends to be more painful [ 6 ]. Patients presenting with a scar without history of trauma should be evaluated for morpheaform BCC. Fibroepithelioma of Pinkus is a variant that looks similar to a skin tag, and usually presents on the lower back [ 2 ].
Workup
BCCs are diagnosed by shave or punch biopsy . Histopathology varies between sub-types and reveals basal cells with large nuclei, little cytoplasm, and stromal retraction.
Treatment
The goal of treatment is ensuring full removal of malignant tissue. Cryosurgery, topical chemotherapy such as imiquimod 5 %, electrodessication and curettage, sur-gical excision , and Mohs micrographic surgery are the main treatment modalities. Surgical treatment has the lowest failure rate and Mohs surgery specifi cally has the lowest recurrence rate [ 1 , 2 ]. Treatment approach usually depends on the size, loca-tion, and depth of lesion.
Any lesions that generate suspicion of BCC should be biopsied, and if the lesion is small enough full removal should be attempted. Initial biopsy of the lesion may be performed in a primary care setting if the treating physician has experience performing biopsies. Patients can be referred to dermatology to discuss biopsy results that are confi rmed BCC, or to perform the initial biopsy if needed. Any sub-sequent treatment should be undertaken by a dermatologist.
Follow-Up
Histologically confi rmed complete excision of BCC is associated with <2 % local recurrence after 5 years [ 5 ]. Factors that are associated with recurrence, metastasis, and poor prognosis are lesions greater than 5 cm in size, location on ears or centro-facially, morpheaform subtype, poor delineation, incomplete excision , and histo-logical features of infi ltration, micronodular appearance, and perivascular or perineural involvement.
Patients with BCCs on the trunk are more likely to develop future lesions anywhere on the body, but especially on the trunk [ 7 ]. Other factors associated with poor prognosis are immunocompromised status, presence of multiple lesions, and involvement of lymph nodes, or metastasis [ 1 , 2 , 5 ]. Metastasis is very unlikely, occurring in fewer than 0.55 % of cases [ 2 ]. When it does occur, it usually affects sentinel nodes, or the lungs.
Patients with a history of BCC should be screened for new lesions twice yearly. Some precautions may be taken to help prevent new lesions, including wearing SPF daily, avoiding prolonged exposure to the sun or tanning beds, and wearing protec-tive clothing.
Questions for the Dermatologist
– What is the natural course of basal cell carcinoma if left untreated?
The lesion persists and there is slow local tissue destruction.
The patient reported having the lesion for 10 years. Is it common for BCC to go
undiagnosed for that long?
It is fairly uncommon. Progression of lesions in this case are slower than average.
Typically lesions are more painful and bleed spontaneously 6 months after they appear.
– Does the process (i.e., inactivation of tumor suppressor genes) that gave rise to
the BCC on her arm make it more likely for BCC to occur in other parts of her
skin, like her leg?
Patients with one BCC are more likely to develop others. Genetic changes to
tumor suppressor genes are probably happening locally, and the lesions develop
independently. However, they may be refl ective of an environmental exposure such
as UV radiation , which would affect multiple sites on the body. If those changes are
happening in one area, they are more likely to happen in another.
– If the patient gets more lesions in the future, would they be more likely to be
BCC?
Correct. A patient with primary BCC is at increased risk for developing subsequent
BCC lesions.
– Is there anything in the patient’s history that is indicative of BCC, e.g. the lesions
spontaneously bleeding?
Irritation, bleeding, and the persistence of lesions would raise suspicion of BCC
Reference
1. Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med. 2005;353(21):2262–9.
2. Carucci JA, Leffell DJ, Pettersen JS. Chapter 115. Basal cell carcinoma. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick’s dermatology in general medicine. 8th ed. New York: McGraw-Hill; 2012. p. 1294–303.
3. de Vries E, Micallef R, Brewster DH, Gibbs JH, Flohil SC, Saksela O, Sankila R, Forrest AD, Trakatelli M, Coebergh JW, Proby CM, EPIDERM Group. Population-based estimates of the occurrence of multiple vs fi rst primary basal cell carcinomas in 4 European regions. Arch Dermatol. 2012;148(3):347–54.
4. Xiang F, Lucas R, Hales S, Neale R. Incidence of nonmelanoma skin cancer in relation to ambi-ent UV radiation in white populations, 1978–2012. JAMA Dermatol. 2014;150(10):1063–71.
5. Madan V, Lear JT, Szeimies RM. Non-melanoma skin cancer. Lancet. 2010;375(9715): 673–85.
6. Yosipovitch G, Mills KC, Nattkemper LA, Feneran A, Tey HL, Lowenthal BM, Pearce DJ, Williford PM, Sangueza OP, D’Agostino Jr RB. Association of pain and itch with depth of invasion and infl ammatory cell constitution in skin cancer: results of a large clinicopathologic study. JAMA Dermatol. 2014;150(11):1160–6.
7. Ramachandran S, Fryer AA, Smith A, Lear J, Bowers B, Jones PW, Strange RC. Cutaneous basal cell carcinomas: distinct host factors are associated with the development of tumors on the trunk and on the head and neck. Cancer. 2001;92(2):354–8.