PATHOPHYSIOLOGY

BCCs arise from basal keratinocytes of the epidermis and adnexal structures (hair follicles, eccrine sweat ducts). Ultraviolet B (UVB) radiation (sunburn spectrum, 290 to 320 nm) is important for the induction of BCC. UVB radiation damages DNA and its repair system and alters the immune system. Depletion of ozone in the earth's atmosphere results in higher levels of UVB radiation at the earth's surface. Longer wavelength UVA radiation damages DNA and is also carcinogenic. BCC grows by direct extension and appears to require the surrounding stroma to support its growth. This may explain why the cells are not capable of metastasizing through blood vessels or lymphatics. The course of BCC is unpredictable. BCC can remain small for years with little tendency to grow, particularly in the elderly, or it may grow rapidly or proceed by successive spurts of extension of tumor and partial regression. BCC occurs at the site of previous trauma, such as scars, thermal burns, and injury. BCC occurs years later at sites treated with ionizing radiation. The tumor appears 3 months to 7 or more years later at the site of a well-remembered injury.

HISTOLOGY

The cells of a BCC resemble those of the basal layer of the epidermis. They are basophilic, have a large nucleus, and appear to form a basal layer by forming an orderly line around the periphery of tumor nests in the dermis, a feature referred to as palisading

There are five major histologic patterns.

1. Nodular (21%): a rounded mass of neoplastic cells with well-defined peripheral contours. Peripheral palisading is well developed.
2. Superficial (17%): contains buds of atypical basal cells extending from the basal layer of the epidermis
3. Micronodular (15%): small, rounded nodules of tumor about the size of hair bulbs. Tumor islands are rounded, well demarcated, and demonstrate peripheral palisading.
4. Infiltrative (7%): tumor islands vary in size and show a jagged configuration.
5. Morpheaform (1%): numerous small, elongated islands containing a few cells that appear as strands or cords in a fibrous stroma.

A mixed pattern (two or more major histologic patterns) is present in 38.5% of cases.

Management and risk of recurrence

There are several factors to consider before choosing the best treatment modality.   The most important are clinical presentation, cell type, tumor size, and location.

Clinical type.

Nodular and superficial BCCs are the least aggressive and can be completely removed by electrodesiccation and curettage or by simple surgical excision.

Histologic type.

The micronodular, infiltrative, and morpheaform BCCs have a higher incidence of positive tumor margins (18.6%, 26.5%, and 33.3%, respectively) after excision and have the greatest recurrence rate. [10] Clinically, BCCs with these patterns have poorly defined borders and are not apparent during physical examination. [24] They subtly extend into surrounding tissue and are easily missed by blind treatment techniques such as surgical excision. An average of 7.2 mm of subclinical tumor extension was found in mopheaform BCCs in one study, compared with 2.1 mm of extension in well-circumscribed nodular lesions.Routine pathologic examination of surgically excised BCCs may not detect a small nodule or strand of BCC on the other side of the excision margin. These tumors need more aggressive treatment with wide excision or microscopically controlled surgery.

Tumor size.

In general, electrodesiccation and curettage afford excellent results for small (less than 2 cm) nodular BCCs located on the forehead and cheeks. Nodular BCCs on the forehead and cheek that are larger and have well-defined margins should be excised and closed; electrosurgery for large tumors may result in large, unsightly scars. The margins of sclerosing BCCs cannot be determined by inspection, and either excision or, preferably, Mohs' micrographic surgery should be performed. Superficial BCCs of any size can be adequately removed by electrosurgery.

Location.

Tumors about the nose, eye, and ear require special consideration. BCCs of the medial canthus are particularly dangerous. The skin rests close to bone and cartilage, and tumor cells initially invade and proceed to migrate undetected along periosteum or perichondrium. Healing occurs over inadequately treated tumors, and deep invasion and lateral extension can remain undetected, resulting in a tumor of massive proportions. Extension to the eye and brain is possible.

Relative risk and follow-up.

Patients treated for BCC should be followed periodically for 5 or more years.   Patients with one BCC often develop another. Of patients with one BCC, 36% to 50% develop a second BCC during the 5 years after treatment. [26] [27] In another series, 41% of patients who had two or more previous skin cancers developed another BCC.

Recurrent BCC
Clinical presentation.

Inadequately treated BCC may recur. The tumor may be superficial in the scar tissue, on the border, or deep in the dermis or subcutaneous fat (Figure 21-17) . The clinical presentation of recurrent BCC sometimes differs from the original tumor. A tumor that infiltrates scar tissue produces a subtle change in color and consistency that is easily missed. Erosions that appear spontaneously at the border or in the scar are suspicious. The characteristic pearly white border is often absent, but biopsy of the erosion with the curette can reveal the soft, amorphous, gelatinous tissue of BCC extending deep and laterally well beyond the border of the erosion. Deep recurrences show a normal or a brownish erythematous surface and can be confused with epidermal cysts.

Histologic picture, anatomic location, and size are factors in predicting recurrence.

HISTOLOGIC TYPE.

Tumors of the morpheaform and basosquamous varieties have the greatest recurrence rate. BCCs that histologically show poor palisading or have a micronodular (islands of tumor) and/or infiltrating strand pattern without sclerotic stroma clinically have poorly defined borders and are not apparent during physical examination.  They subtly extend into surrounding tissue and are easily missed by blind treatment techniques such as surgical excision. An average of 7.2 mm of subclinical tumor extension was found in mopheaform BCCs in one study, compared with 2.1 mm of extension in well-circumscribed nodular lesions. As mentioned earlier, routine pathologic examination of surgically excised BCCs may not detect a small nodule or strand of BCC on the other side of the excision margin. These tumors need more aggressive treatment with wide excision or microscopically controlled surgery.

LOCATION.

Increasing diameter of the lesion and location of the lesion on various sites of the head, especially the nose and ear, are associated with an increased risk of recurrence, whereas location on the neck, trunk, limbs, or genitalia is associated with a decreased risk of recurrence with curettage-electrodesiccation, radiation therapy, and surgical excision.   BCCs on the nose or perinasal area may infiltrate along the perichondrium or penetrate into the embryonic fusion plane of the nasolabial fold, resulting in subclinical extension.

SIZE.

The larger the tumor, the greater the chance of recurrence; increased subclinical extension is seen with larger tumors.