Patient Presentation A 69-year-old Caucasian female presented to the dermatology clinic with a slow-growing pigmented lesion near her umbilicus that had been developing over the course of approximately 3 months. The lesion began as a small erythematous macule that enlarged and became more heavily pigmented. The patient denied pruritus, pain or bleeding. On physical exam, a shiny, irregularly shaped, asymmetric, firm purple to gray-black plaque measuring 2.5 cm by 2 cm with areas of brown-to-black speckled pigmentation was found on the left lower side of the umbilicus. The plaque had slightly elevated margins and areas of pigment spillage beyond the borders of the lesion itself. What is Your Diagnosis?Diagnosis: Pigmented Basal Cell Carcinoma (PBCC)Basal cell carcinoma (BCC) is the most common of all malignant skin tumors, with approximately 1 million new cases occurring annually and an increasing incidence in the United States.1 Most BCCs arise in the sun-exposed areas of the head and neck, and are more common in males, elderly patients and individuals with fair skin. Those with red hair or a family history of nonmelanotic skin cancers and significant UV exposure are likely at the greatest risk.2 Up to 5% of BCCs contain some melanin pigment, and Galloway first described these lesions as far back as 1898.3 For still uncertain reasons, pigmented basal cell carcinomas (PBCCs) are seen more commonly in African-American, Asian and Hispanic patients, and are frequently misdiagnosed as nevi, melanomas or actinic and seborrheic keratoses. Individuals of Japanese ancestry may have pigment present in BCCs in up to 84% of cases.4 When evaluating a suspicious pigmented lesion, clinicians may focus too heavily on its pigmented nature and ignore other features suggestive of BCC such as induration, ulceration, raised margins and mottled pigmentation.3,5,6 Clinical and Dermoscopic Characteristics of PBCCPBCCs often display the same characteristic features as non-pigmented BCCs, such as a pearly appearance, rolled borders and telangiectasias.7 Pigment deposition is most common in the nodular subtype of BCC and rarely observed in the morpheaform or infiltrating subtypes.8 Pigment is clinically visible in up to 8.5% of all BCCs8 and Goldberg et al. found that pigment “speckling” in discrete, solitary skin-colored tumors was consistent with a diagnosis of PBCC. Oftentimes a blue-black or grayish color (secondary to the dermal location of the neoplasm and the Tyndall effect) is observed within these neoplasms.9 The use of dermoscopy greatly improves the visualization of the pigment deposition pattern and is proven to increase the diagnostic accuracy of benign versus malignant lesions such as PBCC and melanoma.7 When compared to melanoma, PBCCs are relatively hypomelanotic lesions, with two-thirds of tumors having less than 50% of their area pigmented.8 A suspicious lesion having >75% of its surface area pigmented is much more indicative of melanoma.8 It is important to remember that PBCCs may also be large and/or ulcerated lesions like traditional BCCs, and that the presence of such features, while making the visual diagnosis more difficult, does not necessarily constitute a worse prognosis.2 The most sensitive morphologic feature in making the diagnosis of a PBCC is its lack of the organized pigment network often present in melanoma.8Histologic FeaturesWhile PBCC can be distinguished from melanoma clinically, excisional biopsy is often the sole means of establishing a definitive diagnosis. PBCCs display the traditional aggregates of basaloid cells with scant cytoplasm and peripheral palisading, often involving the dermis.10 Benign melanocytes in and around the tumor produce varying amounts of melanin. Recent studies comparing the melanocytes of PBCC and normal peri-lesional tissue showed a hyperactivity of melanogenesis in the PBCC melanocytes, as well as wide variability in their location compared to normal melanocytes.4 Traditionally, two theories have been considered regarding the source of the melanocytes present in PBCCs. Lao and Matz et al. have demonstrated morphologic evidence that the melanocytes present in PBCC originate from precursors already present in the hair follicle.2,4 Recently, others have hypothesized that the pigment may arise from a migration of melanocytes from the epidermis of adjacent normal skin via unknown chemotactic factors.3 The latter hypothesis would better explain the current observation that more heavily pigmented skin produces a darker neoplasm. Recent investigation of the pigmentation process in BCC identified enhanced endothelin-1 (ET-1) expression in pigmented tumors, which is postulated to be implicated in regulation of the pigmentation pathway.11 Regardless of the source, increased melanocytes may be seen histologically in up to 30% of BCCs, much greater than what is observed clinically.9 Melanin is generally seen in the superficial portion of the PBCC and may be contained within melanocytes or the surrounding tumor cells.8 Fontana stain of excisional biopsies is regularly performed to demonstrate the presence of melanin within these lesions. While melanocytes in PBCC often display ovoid nests of pigment deposition, they do not aggregate nor have organized networks as seen in melanoma.8Differential Diagnostic ConsiderationsSeveral cutaneous lesions must be considered in the differential diagnosis of PBCC, including intradermal nevi, seborrheic keratoses, hypertrophic scars, neurofibromas, dysplastic nevi and amelanotic malignant melanomas.9 Menzies suggests employing a two-step method for dermoscopic diagnosis of PBCC. First, a suspected PBCC must not have the negative feature of pigment network, and secondly must possess one or more of the following six positive characteristics: 1) large gray-blue ovoid nests (seen in 55% of PBCCs); 2) multiple gray-blue globules (seen in 27%); 3) maple-leaf like areas (seen in 17% but connote 100% specificity); 4) spoke-wheel areas (100% specificity); 5) ulceration (seen in 27%); 6) arborizing tree-like vessels (seen in 52%). By using this method, a 93% sensitivity and 89% to 92% specificity in diagnosing PBCC have been reported.8 This technique was independently reproduced and found to be similarly effective with little influence dictated by the test subjects’ experience in diagnosing suspicious lesions.7 Telangiectasia and milia-like cysts are also features useful in diagnosis. In addition, only 11% of PBCCs display multiple (up to five or six) colors, compared to 35% to 53% of invasive melanomas that have melanin deposited at various layers in the epidermis and dermis.8 Using these criteria an observant physician is better able to make an accurate diagnosis of PBCC.Prognosis and Treatment Although PBCC may appear more clinically ominous to the dermatologist, its prognosis is identical to that of normal BCC.3 Pigmented BCC has no more of an increased risk to metastasize than non-pigmented BCC, of which approximately 300 such cases have been reported in the literature.12 With such a low metastatic rate, the cancer is often treated successfully with initial therapy. If not treated appropriately or discovered early on, however, BCC can cause significant local destruction and disfigurement. Treatment options including excision, curettage and electrodessication, cryotherapy and radiotherapy generally halt tumor progression and provide a very low risk of recurrence. Surgical excision with 4-mm margins is necessary to achieve cure rates of 95%.13 While the cure rates with curettage and electrodessication are nearly as good, there is a significant amount of variability depending on physician experience with the technique. Radiotherapy and cryotherapy are also similarly dependent on operator experience and have fallen out of favor in recent years. On patient follow-up examinations, it is important to remember that patients who develop one BCC have a 30% chance of developing another BCC at a site separate from the initial cancer in the future.13 Because BCC is most commonly located on the sun-exposed regions of the head and neck, Mohs micrographic surgery (MMS) is frequently used as a skin sparing treatment in these areas. Recurrence rates are reported to be as low as 1% to 2% using MMS, as almost all of the tissue margins are immediately examined on frozen sections.14 Our patient’s PBCC was excised using 4mm margins following close clinical dermoscopic examinations. The margins were clear on histopathology. She was instructed to follow-up regularly and was given written information regarding skin malignancies and sun protection.