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FREDERIC B.ASKINMDWILLIAM H.WESTRAMD
Basal cell carcinoma is the most common skin cancer in the United States, with an estimated 900 000 cases per year.1 It represents 75% of all cutaneous neoplasms and outnumbers squamous cell carcinoma by 4:1.2,3 It has also become the most commonly diagnosed malignancy in the world, with the highest annual incidence in Australia. The incidence of BCC is higher in men than in women and increases with age, usually occurring between the ages of 40 and 60 years. However, there has been a rise in the number of cases among younger patients. Approximately 80% of BCCs occur in the head and neck. The nose is the most common site of occurrence, followed by the cheeks and forehead.4
There are several predisposing factors for BCC. Exposure to sunlight, particularly UV-B, has been accepted as the primary risk factor. The incidence of BCC increases near the equator and at high altitudes. Other risk factors include hereditary predisposition, fair complexion, multiple sunburns, and long-term exposure to chemicals. More recently, immunosuppression has been implicated in the pathogenesis of BCC.3 Immunocompromised patients who have undergone kidney transplantation are at greater risk for developing both premalignant and malignant cutaneous lesions. Similarly, patients with lymphoproliferative disorders are at greater risk for developing melanoma, BCC, and squamous cell carcinoma.3
There are 5 main clinical presentations of BCC.5 The morpheaform or fibrosing BCC is the most subtle and most dangerous clinical variant. It presents as a yellowish plaque with indistinct borders. It may progress unnoticed for years and may develop a scarlike appearance, telangiectasia, or ulcerations. The most common type is the noduloulcerative variant, which presents as a raised, pearly, waxy lesion. There is usually a central portion of ulceration, and its borders are well defined, making this the easiest variant to treat. Pigmented BCC is brown and may be mistaken for a nevus or melanoma. It is similar in behavior and appearance to the nodular type. The superficial multicentric BCC, which consists of scaly red patches with irregular borders, is uncommon in the head and neck region. Fibroepitheliomas, which occur mainly on the back, are another variant. They present as pedunculated lesions, resembling fibromas. Histologically, there are many forms of BCC, and various classification systems have been proposed. One large series classified BCC as nodular, superficial, micronodular, infiltrative, or morpheic, with a large portion having mixed histologic patterns.1 There is controversy over a metatypical form of BCC, also known as basosquamous carcinoma. Some authors believe that it is an intermediate form, between squamous cell and basal cell tumors; however, monoclonal antibody staining indicates that a true intermediate form probably does not exist. Others believe that it is simply a keratinizing form of BCC; hence, the term keratotic BCC.5 Whatever the terminology used, basosquamous (keratotic) carcinomas seem to have a greater tendency to metastasize.5,6 Figure 1 highlights some features of keratotic BCC, including deposits of keratin with focal squamous differentiation in the surrounding cells.
Although the well-trained clinician has no difficulty in recognizing primary BCC, recurrent BCC poses a greater challenge. Its varying clinical appearance may largely be influenced by its original treatment, as it may appear under a scar, in a suture line, or at the edge of a skin graft.4 Recurrent BCC also occurs more frequently in immunocompromised patients. One study reported a 17% recurrence rate of BCC in patients with lymphoma compared with an approximate recurrence rate of 10% (3%-20%, depending on the treatment modality) in patients with primary lesions.3 The average time to recurrence is approximately 1.7 years.6
Metastasis of BCC is rare, with reported incidences of 0.0028% to 0.4%.6 Of BCCs that metastasize, 70% to 86% occur in the head and neck region.2,6,7 Lesions in the ear and scalp region have been cited as the most likely to metastasize, perhaps owing to the thin skin and relatively large underlying vessels.7 Larger, more invasive tumors have a greater tendency to metastasize. One study reported a 1.9% metastatic rate for tumors larger than 3 cm and stated that large and deep tumors account for 75% of BCCs that metastasize.7 Tumors smaller than 1 cm rarely metastasize. A history of radiation therapy may also be a risk factor for metastasis. The BCC that is at risk for metastasizing is one that is large, infiltrative, locally aggressive, and with multiple recurrences despite surgical therapy or radiotherapy.5 However, there are no absolute prerequisites for metastasis.
Basal cell carcinoma disseminates through lymphatic and hematogenous routes. The tumor usually disseminates initially to regional lymph nodes, but it can spread to the lungs and bones as its first site of involvement.5 Metastasis to the skin, liver, and other internal organs has also been reported. The median time to metastasis is variable, ranging from 6 to 11 years, and metastasis may present 6 months to 45 years after initial diagnosis.2,6
The case described herein highlights the increased propensity toward aggressive BCC in the immunocompromised host. Indeed, our patient's BCC metastasized to a lymph node that was replaced by a low-grade lymphoma. Figure 2 demonstrates the obliteration of normal nodal architecture (lack of germinal centers) by a monotonous proliferation of small lymphocytes with a metastatic deposit of abnormal basaloid cells. A high-power micrograph (Figure 3) of the same specimen revealed cohesive nests of basaloid cells with the characteristic squamoid appearance of eosinophilic cytoplasm. These cells were surrounded by mixoid stroma and cleft artifacts typical of BCC.
The vast majority of primary BCCs are small and nonaggressive and appear in low-risk areas. They are highly responsive to electrodesiccation, cryosurgery, irradiation, or surgical excision. Radiation therapy, once a popular mode of treatment, has fallen slightly out of favor, as some authors believe that it may lead to metastasis and that the lack of a tissue specimen compromises the ability to assess the adequacy of treatment.2 For higher-risk tumors—those that are recurrent, histologically aggressive, large, and deeply infiltrative (>0.6-2 cm, depending on the location) and present in high-risk areas (eg, midface)—the Mohs procedure offers the best chance of microscopic tumor removal.8 Primary reconstruction is possible after Mohs surgery, but it should occasionally be delayed in those patients who are at high risk for recurrence, as residual tumor may grow along the lines of least resistance into deeper tissues before it is detected on the surface.2
While localized BCC has a high cure rate (93%-99%), the prognosis for patients with metastatic BCC is poor. Median survival time has been reported from 8 to 14 months after the diagnosis of metastasis.2,6 Patients with lymphatic metastasis have a slightly better prognosis than those with hematogenous spread. After distant metastasis to the lung, bones, or other organs, median survival time is approximately 10 months, whereas the average survival in patients with nodal spread is 3.6 years.9,10 Our patient has not shown any further evidence of recurrence and receives very close follow-up. Although BCC represents a seemingly nonaggressive disease, the tumor can metastasize. Given the variable time from presentation of initial disease to recurrence and metastasis, long-term follow-up is warranted.
Diagnosis Pathology Quiz Case 1. Arch Otolaryngol Head Neck Surg. 2002;128(1):77–78. doi:
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