The significance of histologic subtype lies in its correlation with biologic aggressiveness. The infiltrative and micronodular types are the most likely to be incompletely removed by conventional excision. Rates of incomplete excision vary from 5 to 17 % with a recurrence rates of 33–39 %. Recurrences after radiotherapy (RT) show a tendency toward infiltrative histology and evidence of squamous transformation, and even recurrent BCC after excision may become metatypical. In general, recurrences are more frequent in BCCs with infiltrative and micronodular histology, when clear margins are less than 0.38 mm, and in the presence of squamous differentiation. Incompletely excised BCCs should be removed completely, preferably by Mohs micrographic surgery (MMS), especially if they occur in anatomically critical areas [16].

Adequate treatment of BCC requires appreciation of the histopathologic pattern of the neoplasm. Though some BCCs are small and superficial and behave in essentially a “biologically benign” manner as long as they are conservatively removed, others behave more aggressively and thus require more aggressive treatment. Examples of the latter include clinical BCCs that ulcerate and those located in the central face or on the ear. Furthermore, BCCs that show an aggressive-growth pattern histologically require definitive treatment with confirmation of histologically negative margins. Occasionally, it may appear that a BCC has been adequately removed by biopsy alone, leading to the question of whether to render further treatment. In one study, 41 consecutive patients with 42 BCCs apparently removed by biopsy were treated by MMS, and blocks of tissue, sectioned consecutively until exhausted, were examined for the presence of residual tumor. In 28 of 42 cases (66 %), residual cancer was identified. The presence of residual cancer was not related to age, site, histologic subtype, or extent of surrounding inflammation. The results indicate that patients with small BCCs that appear to be completely removed by initial biopsy may be at risk for recurrence if not treated further [22].

BCCs may demonstrate unique characteristics based on anatomic site. The nose is the most common site for cutaneous malignancies (30 %), and BCCs involving the nose may be aggressive. A study of 193 cases of infiltrative BCC involving the nose confirmed that the majority of infiltrating and recurrent BCCs affect the ala. Analysis of the recurrences’ aggressive local behavior indicated that recurrent lesions were subjected to inadequate therapy initially 23. In one study, 26 recurrences were identified in 71 nasal skin cancers at an average of 36 months after non-MMS excision. This suggests that MMS may be the treatment of choice for all BCCs involving the nose, especially those exhibiting aggressive-growth characteristics. Periocular BCC represents a significant therapeutic challenge. In one study, periocular BCC accounted for 7.3 % of 3192 BCCs treated over a 10-year period. Of these, 48.5 % involved the medial canthus, 22.35 % involved the lower eyelid, 10.7 % involved the upper eyelid, and 5.6 % involved the lateral canthus. BCC is the most common tumor affecting the eyelid. In a series of 97 cases of BCC involving the eyelid, 69 % were nodular, 13 % were infiltrative, 1 % were ulcerated, and 12 % were mixed (defined as having a significant nodular or ulcerative component in addition to an infiltrative component). Follow-up of 8 of 12 patients with mixed tumors revealed 3 recurrences. In one patient, orbital exenteration was required. This suggests that mixed tumors of the eyelid with aggressive-growth histology warrant thorough treatment with complete margin control. In a review of 24 eyelid tumors treated by MMS, high clearance rates were shown (100 %), although follow-up was short (14.6 months) [23, 24].

In addition, 50 % of patients were left with intact posterior lamellae, highlighting conservation of normal tissue. The results suggest that MMS followed by oculoplastic reconstruction, if necessary, is the preferred strategy in the management of periocular BCC.

Approximately 6 % of BCCs involve the ear, a site notable for high rates of recurrence. In a recent study, nine patients with BCC involving the conchal bowl were treated by an interdisciplinary approach. In each case, tumor extirpation was accomplished by MMS, and an otolaryngologist was available in the event of temporal bone involvement. There were no cases of recurrence at mean follow-up of 1 year. It must be stressed that BCC can occur anywhere, even in non-sun-exposed areas, and has been reported to occur on the vulva, penis, scrotum, and perianal area. In one series of vulvar BCC, mean age at presentation was 74 years. Patients have been seen with a history of local irritation that had been present for a few months to several years.

In order to make a diagnosis of malignant transformation from a CLU (especially in the absence of a previous positive histology) and to differentiate it from a primary cutaneous carcinoma, the CLU should be present for at least 3 years. However, the definite guidelines are lacking and the subject is still debatable. Abnormal excessive granulation tissue at the wound edges has been appreciated as a sensitive parameter for the diagnosis of CLU-associated malignancies in a recently published prospective study (done on CLUs that failed to improve even after 3 months of optimum treatment). Other specific parameters included abnormal bleeding and a high clinical suspicion of ulcerated skin malignancy or malignant transformation.

Basal cell carcinoma like many other malignancies may also develop secondary to the long-standing ulcers particularly squamous cell carcinomas developing in chronic venous ulcer or even a scar tissue (a burn scar). This can be explained by increased proliferative activity around the ulcer [2]. Carcinomas may arise in open wounds, but also at the site of remitting/relapsing ulcers. Ninety percent of the ulcers were found to be of venous origin or from mixed origin with a venous predominance in a published study. Exophytic irregular growth of the wound edges and/or bed, excess tissue granulation extending beyond the margins, increase in pain or bleeding, absence of healing despite adequate treatment, and unusual extension have also been reported as clinical features of malignant transformation [14, 15] .

Although many NMSCs present with classic clinical findings such as nodularity and erythema, definitive diagnosis can only be made by biopsy. Adequate tissue obtained in a nontraumatic fashion is critical to histopathologic diagnosis. Skin biopsies may be performed by shave, punch, or fusiform excision. The type of biopsy performed should be based on the morphology of the primary lesion. A shave biopsy usually is adequate for raised lesions such as nodular BCC, SCC, or tumors of follicular origin. Punch biopsy is effective for sampling flat, broad lesions for which shave or fusiform excision would be technically inappropriate. An excisional biopsy may be used to sample deep dermal and subcutaneous tissue. Excision is appropriate when it is necessary to distinguish between a benign lesion such as a dermatofibroma and a malignant tumor such as a dermatofibrosarcoma protuberans.