Raised, dark, enlarging lesion

Case #1Basal cell carcinoma (BCC) is a slow-growing, locally invasive malignant skin tumor originating from basal keratinocytes in the epidermis. The risk of metastasis is low, ranging from 0.003% to 0.6%.1 When metastasis does occur, it is most frequently to the...

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Case #1

Basal cell carcinoma (BCC) is a slow-growing, locally invasive malignant skin tumor originating from basal keratinocytes in the epidermis. The risk of metastasis is low, ranging from 0.003% to 0.6%.¹ When metastasis does occur, it is most frequently to the lymph nodes or the lungs.

The major histologic subtypes of BCC are nodular, superficial, micronodular, infiltrative, and morpheaform. Pigmented BCC is a variation of the nodular subtype. In the United States, the lifetime risk of BCC is approximately 30%.² BCC is the most common form of all cancers, with more than one million cases identified every year.¹ 

Exposure to light in the ultraviolet B (UVB) spectrum leads to development of BCC. Mutations in the cell cycle regulator protein, p53, caused by UVB radiation are found in half of all BCCs.³ Additionally, development of BCC involves changes to the hedgehog signaling pathway and alterations in the patched 1 (PTCH1) and smoothened, frizzled class receptor (SMO) genes in 90% and 10% of BCCs, respectively.⁴ In contrast to squamous cell carcinoma, in which cumulative sun exposure is the main contributing factor, the development of BCC rests heavily on intermittent sun exposure or sunburns.¹ 

Exposure to UV radiation is the greatest risk factor for the development of BCC. The use of tanning beds increases the chance for the development of BCC by 1.5 times.⁵ Additionally, males have a two-fold increased risk for developing BCCs, compared with females.⁶ Other risk factors include fair complexion, ability to freckle, increased age, immunosuppression, arsenic exposure, and chronic local inflammation.⁷ Furthermore, there are genetic syndromes, such as Bazex-Dupré-Christol or Rombo syndromes, with a predisposition for BCC.

The average age at which BCCs develop is 62 years, but approximately 20% of these tumors occur in individuals aged less than 50 years.⁸ Pigmented BCC is most common in dark-skinned individuals and may be difficult to distinguish from nodular melanoma.⁹ 

BCCs typically develop on sun-exposed areas. Lesions most commonly develop on the nose, periorbital region, and cheek.⁶ They appear as one or more brown, black, or blue waxy, pearly, and typically translucent papules surrounding a central indentation or ulceration.⁹ The discrete border of these lesions frequently has a rolled appearance.¹ Telangiectasias are frequently seen.

The differential diagnosis for pigmented BCC includes melanoma, compound nevus, and blue nevus.¹Dermoscopy criteria for BCC include the lack of a pigmented network along with one additional finding, such as leaf-like regions, branching vessels, or ulceration.⁷ 

Definitive diagnosis of BCC is obtained with biopsy, with shave biopsy being the preferred method. Histopathology shows tumor nests composed of uniform cells with large basophilic nuclei. Histologically, pigmented BCC shows melanin in the tumor cells. The pigmentation in pigmented BCC is derived from melanophages in the tumor and the phagocytosis of melanosomes by the tumor.⁷ 

Following biopsy, BCCs can be removed via standard surgical excision, curettage and desiccation, radiation, cryotherapy, or Mohs surgery. Curettage and desiccation is most effective when used for low-risk tumors that are less than 2 cm on the trunk or extremities. Cryotherapy is reserved for lesions that are less than 3 mm in depth.¹⁰ Surgical excision is recommended for primary tumors that are less than 2 cm in diameter on the trunk or extremities.¹¹ To achieve a cure rate of 95%, appropriate margins for excision are 4 mm for tumors that are less than 2 cm in diameter.¹² Mohs micrographic surgery is reserved for tumors on the face, high-risk subtypes, or recurrent tumors.¹ 

The recurrence rate for BCC ranges from 5% to 14%.⁶ The major risk factor for recurrence is the histopathologic subtype; nodular BCC are considered to be the low-risk subtypes for recurrence.¹⁰ Recurrence rates are lowest following Mohs microscopic surgery.

BCC generally has a very good prognosis. However, in individuals who develop a BCC, the chance of developing another primary BCC within the following 5 years is as high as 50%.¹ 

For the patient in our case, a shave biopsy was taken of the lesion, and a diagnosis of pigmented BCC was confirmed. He then underwent Mohs microscopic surgery for removal of the lesion. At his 6-month follow-up appointment, the patient had no recurrence.

Case #2

Melanoma is a malignant cancer derived from the malignant transformation of melanocytes. Nodular melanomas originate at the interface between the dermis and epidermis. They rapidly grow vertically into the dermis.¹³ 

Although malignant melanomas are the least prevalent skin cancers, they are the most deadly, causing approximately 75% of all skin cancer deaths.¹⁴ In the United States, melanoma is the fifth most common cancer in males and the seventh most common cancer in females.¹⁵ Rates of melanoma have been steadily increasing, with the current lifetime risk estimated at greater than 1:30 for the development of melanoma.¹³ 

There are 7 subtypes of malignant melanoma. In order of decreasing prevalence, these subtypes are superficial spreading melanoma, nodular melanoma, lentigo maligna and lentigo maligna melanoma, amelanotic melanoma, acral lentiginous melanoma, and subungual melanoma.¹⁶ Although only 10% to 15% of melanomas are nodular melanomas, nodular melanomas are responsible for more than 35% of deaths associated with melanoma.^16,17Nodular melanomas are 1.5 times more likely to be fatal than superficial spreading melanomas, and they grow four times faster than other subtypes.^18,19 

Most melanomas develop following a sequence of events in which a benign melanocytic nevus progresses to have atypical characteristics. The atypical nevi may grow radially before progressing to a stage of vertical growth. Following the vertical growth state, the melanoma may metastasize. The vertical growth phase is a time of aggressive growth. This vertical growth pattern is rapidly displayed by nodular melanomas. Furthermore, in contrast to the other melanoma subtypes, nodular melanomas frequently do not arise from pre-existing nevi.

Nodular melanomas display mutations in the B-Raf proto-oncogene (serine/threonine kinase; BRAF), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), hypoxia-inducible factor 1 alpha subunit (basic helix-loop-helix transcription factor; HIF1A), and vascular endothelial growth factor (VEGF). These mutations are not found in other types of melanomas and contribute to the poor prognosis of nodular melanomas.²⁰ 

The most significant risk factor for development of melanoma is exposure to excessive ultraviolet radiation, specifically a history of intermittent blistering sunburns.¹³ Individuals who use tanning beds have a 1.25 increased risk for the development of melanoma.²¹ The most common age of diagnosis of melanoma is 52 years.¹³ Risk factors for the development of melanoma include fair complexion, age, personal or family history of skin cancer, and presence of numerous moles or dysplastic nevi.¹⁶ 

The ABCDE mnemonic helps clinicians screen for melanomas. These criteria are asymmetry, irregular border, variation in color, diameter greater than 6 mm, and evolving morphology of the lesion.¹⁶ The “E” criterion is particularly of use when diagnosing nodular melanomas for which the other criteria are not notable. Approximately 78% of nodular melanomas display evolving characteristics.²² An evolving lesion is one with any change in color, structure, or symptoms. A new development of bleeding, pain, or itching from the lesion fulfills this criterion.

The differential diagnosis for pigmented nodular melanoma includes pigmented basal cell carcinoma, pigmented Spitz nevus, blue nevus, or common nevus.¹³ Nodular melanoma typically presents as a fast-growing nodule on the head, neck, or trunk.¹⁶ The diagnosis of nodular melanoma is obtained through histopathology showing atypical melanocytes in the dermis.¹³ Elliptical excisional biopsy is the gold standard of diagnosis.¹⁶ Following biopsy, the tumor is staged based on Breslow’s thickness, mitotic rate, and the presence of ulceration.

Breslow’s thickness determines the appropriate margins for excision. If Breslow’s thickness is greater than 2 mm, a 2-cm margin can be used. If Breslow’s thickness is 1.01 mm to 2 mm, a margin of 1 cm to 2cm can be used.¹⁶ For lesions with a Breslow’s thickness that is less than 1 mm, a 1-cm margin is considered appropriate. Patients with a Breslow’s thickness of 1 mm or greater should undergo a sentinel node biopsy. Ulceration and presence of micrometastasis to the sentinel lymph node are the two most important indicators for poor prognosis.²⁰ 

Following surgical excision of the tumor with appropriate margins, the tumor is staged using the TNM staging system. This system takes into account the depth of the primary tumor, lymph node involvement, and the presence of metastatic disease. Follow-up and additional studies are based on the TNM stage of the cancer.¹⁶ 

For the patient in our case, a diagnosis of pigmented nodular melanoma was made following an excisional biopsy. The melanoma displayed a 1.69-mm Breslow’s thickness, mitosis of less than 1, and no ulceration. The patient underwent surgical excision and sentinel lymph node biopsy. The sentinel lymph node biopsy was negative. The patient shows no sign of recurrence at the 6-month follow up.

Danielle Brown, BA, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston.

References

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All electronic documents accessed on February 2, 2016.