IMMUNOSUPPRESSION Suppression of defensive immune surveillance by immunosuppressive medication, as in renal trasplantation or cancer treatment, increast the risk of skin

cancers as well as their aggressiveness. Gupta et al have studied this phenomenon in 523 renal transplant patients. While squamous cell carcinoma is most common,basal cell carsinoma do occur. Local immunosuppression also occurs in areas of the skin exposed to UVB through the damaging action of ultraviolet light on the langerhans cells. It is theorized that this may lead to a susceptibility to skin cancer formation, because not only are immune responses diminished, but langerhans cells become tolerant to antigens to which they are exposed after UVB damage. Thus if tumor antiagens are present in skin exposed to chronic UVB, they may not respond to these altered antigens, and thus allow the cancer to grow. INCIDENCE AND PREVALENCE As already indicated under etiology, the incidence of cancer is highest among middle aged and elderly people who have been exposed to considerable sunlight. Basal cell carcinoma is the most common tumor of light complexioned people. It occurs tree to four times as frequently as squamous cell carcinomas, and is more common in men. Approximately 30 to 40 percent of patiens with a basal cell carcinoma will develop one or more similar lesions within 10 years. PATHOGENESIS Pinkus indicated that the basal cell carcinoma belongs to the group of organoid adnexal tumors and that it is the least mature member of this group. It appears that the basal cell carcinomas arise from immature pluripotential cells.these tumors usually originate from the surface epidermis however, they may also originate from the outer root sheath of the hair follicle. Some recent observations support the view that the cells of the tumor are arrested in the early stages of epidermal differenntation. Antikeratin stains reveal a lack or decrease of large keratin molecules, which are associated with mature keratinizing epithelium. Also the basement membrane zone is altered, stanley et al have reported a loss of bullous pemphigoid antigen from this area in basal cell carcinomas. Grimwood et al have now provied and animal model for studying this tumor, with the transplantation of basal cell carcinoma into athymic mice. HISTOPATHOLOGY The early lesion shows small, darkjly staining, polyhedral cells resembling those of the stratum germinativum, with swollen nuclei and small nucleoli. These occur within the epidermis as thickenings or immediately beneath the epidermis as downgrowths connected with it. After the growth has progressed, regular compact columns of these cells fill the tissue spaces of the dermis, and a connection with the epidermismay be difficult to demonstrate. At the periphery of the masses of cells, the columnar cells may be characteristically arranged like fence paling (palisading). This may

be absent when the tumor cells are in cord arrangement or in small nests.a few mitases are usually present.cyst may from. The interlacing strands of tumor cells may present a latticelike pattern. Subtypes occurs histologically in which in the immature cells differentiation toward a type of more mature tumor. Pilar, eccrine, apocrine, sebaceous, and squamous types of differentiation may be seen. Pinkus indicated that the dermal stroma is anintegral and important part of the basal cell carcinoma. The tumor does not terminate at the bottom of the epithelial nests but actually extends into its own newly formed connective tissue matrix to constitute a fibroepithelial neoplasm. Electron microscopic studies show that the cells of the basal cell carcinoma have a greater nuclear/cytoplasmic ratio, fewer filaments, and fewer desmosomes than normal basal cells. No half desmosomes facing the basement membrane are found in the tumor. On the other hand, the tumor cells are quite similiar to the undifferentiated matrix of the human hair follicle. DIFFERENTIATION Occasionally a basal cell carcinoma occurs which has differentition into structure resembling sweat ducts, hair follicles,or sebaceous gland acini. These are reported under varying names such as the by sanchez et al of an eccrine epithelioma, or the tumor reported by sakamoto et al, entiled apocrine epithelioma. DIFFERENTIAL DIAGNOSIS Distinguishing between small basal cell and small squamous cell carcinomas is largely an intelectual exercise, of little practical importance. Both are caused chiefly by sunlight, neither is likely to metastasize, neither is likely to be amenable to ordinary topical therapy with 5-fluorouracil, and both will have to be removed, usually by simple surgical excision or curettage. Generalizations about location are both helpful and misleading. Both types of lesions may occur anywhere on the skin. However, the basal cell lesions are found chiefly on the face, especially on the nose, forehead, eyelids, temples, and upper lip,whereas the squamous cell growths are found principally on the face, at the mucocutaneous junctions, an on the extremities. Carcinoma primary on the vermilion surface of the lower lip is of the squamous cell thype. The lesions on the backs of the hands are usually actinic keratoses,keratoacanthomas,or squamous cell carcinomas. Basal cell carcinomas rarely occur at this site. The duration of the lesion may serve to differentiate the basal and squamous cell thype of carcinoma from keratoacanthoma. If a lesion attains a diameter of 1cm in less than three months, a diagnosis of squamous cell carcinoma or keratoacanthoma. Honry material is usually clinically undetectable in basal cell lesion. A waxy nodular rolled edge is fairly characteristic of basal cell growths. The squamous cell carcinoma is a dome shaped, elevated, hard, and infiltrated lesion. The early basal cell carcinoma may easily and confused with sbaceous hyperplasia, which has a depressed center with yellowish small nodules surrounding the lesion. These lesions never bleeds and do not become crusted.

Bowens disease, pagets disease, and actinic and seborrheic keratosis may also simulated basal cell carcinoma. Ulcerated basal cell carcinoma on the shins is frequently considered to be a stasis ulcer, and a biopsy ,may be the only way to differentiate the two. Pigmented basal cell epithelioma is frequently misdiagnosed as melanoma or as a pigmented nevus. The superficial basal cell carcinoma is easly mistaken for psoriasis. The careful search for the rolled edge of the peripheral nodules is important in differentiating basal cell carcinoma from all other lesions.

TREATMENT Each lesion of basalcell carcinoma must be thoroughly evaluated individually. Age, sex, and the size, site and type of lesion are important factor to be considered when choosing the proper method of treatment for an advabced lesion. No single treatment method is ideal for a lesion, be that excision, ionizing radiation, chemosurgery, cryosurgery, currettage, or alectrosurgery. The choice of treatment will also be influenced by the experiences and ability of the treating physician in the various treatment modalities. The aim in treatment is for a permanent cure with the best cosmetic result. This is important because the most frequent site of the basal cell carcinoma is the face. Recurrences result from inadequate treatment and are usually seen during the first four to 12 months after treatment. Cure rates are still calculated in five year periods, however, it is rare to see recurences later than one year after treatment. Five year follow up is indicated, however, to continue a search for new lesions, since the development of a second basal cell carcinoma will occur in 35 to 40 percent of patients, as reported by epstein, and confirmed by robinson. PROPHYLAXIS All light skinned individuals, especially those with blue eyes and light hair, should avoid unnecessary exposure to the sun from childhood to old age. Sunscreen lotions and creams that are helful and effective are available for those regularly exposed. They should be applied every morning and reapplied after swimming or virgorous outdoor activity.

BIOPSY A biopsy should be performed in all these lesions. When the lesion is small enough to be amenable to surgical removal, a biopsy excision is preferable. EXCISION The ideal treatment method for carcinomas over 5 to 7mm in diameter is simple elliptical excision with suturing,in those areas where this method is feasible. The scalp, ear rim, forehead, cheeks, chin, neck, and the remainder of the body are sites where simple elliptical excision may be indicated. Wedge excision is a method that is ideally performed on the lips, ears, and nostril rims, and even on the eyelids.

When lesion are munch too large for simple elliptical excision or where closure is not feasible, excision and skin grafting or the use of skin flaps may be necessary . the skin grafts are either split thickness or full thicness graft. Whether the split thickness graft is to be thin,intermediate, or thick depends upon the area to be covered. It is reemphasized that the choice of treatment method depends on the probability of achieving a cure with the best possible cosmetic result. Speciments should be examined histologically to confirm that the margins are clear. If the margins of the excision are involved, reexcision is necessary. The minimal margin generally necessary to totaly eradicated the tumor in more than 95 percent of cases with tumors less than 2cm in size is 4mm, as reported by wolf. Ionizing radiation therapy. The indications for radiations therapy are continually being modified, as chemosurgery evolves and becomes more available. In general, skin cancer should be treated by a modality which insures margin control, such as excision or chemosurgery. For individuals unable to tolerate surgical procedures, such as those with multiple medical problems, or in some cases the extremely elderly, radiation therapy offers an excellent alternative. In cases where surgery would be multilating this modality may also be considered however , the ultimate consideration should be the probability of cure, which often the favors surgical intervention. The amount of x-ray exposure for the treatment of carcinoma is dependent upon the size, depth, and thickness of the lesion and also the type of radiation used. As a rule, ionizing radiation theraphy to the ears requires great caution because of possible post radiation necrosis of the cartilage. Cancers of the scalp and forehead are near to the skull, and the proximity of the bone to the lesion, as well as the probability of permanent alopecia, modifies the choice of therapy. Heavy radiation exposure is contraindicates because of the danger of bone necrosis. Most carcinomas of the scalp and forehead can be readily treated by surgical measures if these hazards are recognized. Treatment failurs are probably are the result of errors in estimating the size and depth of tumors. Recurrence at the periphery of the lesions indicates inadequate field size of irradiation; recurrence in the center of the field results from insufficient tumor depth dose. Radiation should not be used in areas where recurrences might be catastrophic, as in the inner canthus, as discussed by Rosen, or in young patients where radiation sequelae in the treated area will compromise the cosmetic result. Pseudorecidive. This is a term used to describe the appearance of a pseudoepitheliomatous reaction at the site of previously irradiated basal cell carcinoma. This reaction occurs some two to four weeks after ionizing radiation therapy has been performed ; it may persist for as long as two months before spontaneous disappearance occurs. The lesions may resemble a seborrheic keratinosis or as reported by Poyzer and Delauney, a keratoacanthoma.

Electrosurgery Many skin cancers are treated satisfactorily with a good cure rate and good cosmetic results by curettage and fulguration. In the hands of an able and experienced operator this form of treatment is probably superior to most other methods. The proper use of various-sized dermal curretes in connection with the fulguration permits the easy seeking out of the cancerous tumor. The large multiple superficial carcinomas found on the trunk are effectively and easily treated by trorough curettage and fulguration. Small lesions, 5 to 20 mm, of the nodular or cystic type, may be treated satisfactorily by this method in most locations. A pliable, inconspicuous scar is formed with this method and a high cure rate attained. Knox and his associates and spiller et al report cure rates of over 96 per cent. Adam and salasche have both reviewed this method of treatment . studies by Salasche, dAubermont et al, Dubin et al, Lang et al, Roenigk et al , among others, indicate that central facial basal cell carcinomas and those of an infiltrating, micronodular or morpheiform histologic type are prone to recurrence if treated with curettage and desiccation.these lesions are thuse better treated by methods with permit examination of the margins such as excision or chemosurgery. Curettage McDaniel treated 437 basal cell carcinomas with curettage alone and has followed 328 treatment sites for over five years. Cosmetic results have been excellent. Twenty-eight treatment failures were noted. He avoided utilizing this technique on the eyelids and lips and with morphea type or infiltrating lesions. We recommend this technique in elderly patients with small, wellcircumscribed, nodular or superficial lesions. Dermal curettes of varying diameters are necessary. Mohs Surgery This method for the removal of accessible forms of cancer under microscope control was introduced by Mohs. His pioneering work began in the late 1930s. For 30 years his microscopically controlled the surgery by fixing the neoplastic tissue in situ with zinc chloride paste, excising a layer of tissue, carefully marking, mapping, and color-coding, the margins, cutting horizontal sections, examining them microscopically, and repeating the process until all cancer was removed. This method is time consuming, but the cure rate is high, determined by Mohs to be 99.3 per cent of 9351 lesions. In 1970 Tromovitch modified the technique by eliminating the fixative paste and doing the procedure on fresh tissue. Tromovitch and Stegman, and others, have done much to popularize this so-called fresh-tissue technique. It allows multiple sections to be taken each day, and allows for immediate repair, if desired. This type of surgery has an extremely high cure rate, usually in the range of over 99 per cent for primary basal cell carcinomas, and over 96 per cent for recurrent lesions. The indications for this type of surgery have been expanding, due to its proven cure rate and winder availability. Mohs himself embraced the fresh-tissue modification. Consideration for Mohs surgery should be allowed for primary tumors occurring in the H zone of the face (the nasolabial fold, nasal alae, periorbital region, and periauricular area) and certain scalp tumors, the histologic variants of more aggressive type such as morphheiform or sclerosing types and basal-squamous types, for large lesions (over 2 cm), and for clinical situations such as these lesions occurring in immunosuppressed patients. Recurrent basal cell carcinomas,

especially in difficult areas are also candidates for Mohs surgery. Swansons wrote an excellent review of this subject, in 1983. Topical Cytotonic Therapy The topical application of 5-fluorouracil in various concentrations has been reported to be effective in the treatment of basal cell carcinomas, especially the superficial, multicentric type. Some have applied 5-FU after thorough curettage of the lesion. Mohs and associates warn that topical fluorouracil treatment of invasive basal cell carcinoma of the face can result in partial or complete healing of the skin overlying deeper extensions of the neoplasm. This method is not accepted treatmen. Cryosurgery Cryotherapy for basal cell carcinomas as well as other benign and malignant neoplasms has been used since solid carbon dioxide became available. Since liquid nitrogen has become almost universally available, this modality has found increasing application for treatment of basal cell carcinomas. Because nitrogen boils at -195.8 C, a deep penetrating action is attained in a short time when the liquid is applied to the surface of the skin. Zacarian, Torre, and Gloria Graham have all reported on this type of refrigeration therapy. Graham has successfully combined it with curettage. Charles Sheard has recommended the Foster apparatus for administering liquid nitrogen through a shortened 16-gauge needle. He recommends a 90-second freeze, a 60-second thaw, and a 30second refreeze for a basal cell carcinoma up to 1 cm in diameter. However, cryosurgery is an essentially blind approach, and in general is not indicated except when excision is not feasible and irradiation does not appear to be advisable. Laser Therapy Goldman and his associates have pioneered laser beam therapy. Wheeland et al reported their results treating 52 patients with 370 basal cell carcinomas of the superficial type with curettage and carbon dioxide laser vaporization. They had excellent results with the advantages of rapid healing, diminished postoperative pain, and excellent field visualization. Other Modalities Greenway et al reported preliminary results in the use of intralesional interferon for treatment. Tse et al have used a hematoporphyrin derivative which localizes the neoplastic tissue and initiates cytotoxic responses after exposure to red light. Guthrie et al reportered on the use of cisplatin and doxorubicin for advanced lesions. These methods are all experimental. PREVENTION Peck et al reported preliminary results using isotretinoin as a chemopreventative approach. A large trial is underway to study this questions . sunscreens should be used by all basal cell cancer patients on a daily basis to prevent further solar damage.