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The Ubiquitous Basal Cell Epithelioma
The Ubiquitous Basal Cell Epithelioma JOHN F. FRITZ, JR., M.D.*
The basal cell epithelioma is a common epithelial tumor and represents a comparatively benign variety of carcinoma. Some clinicians would prefer to call this tumor a basal cell carcinoma. They point out that, left untreated, it would in most instances continue slowly to enlarge, tend to develop a central necrosis and have the potential to invade adjacent soft tissue, cartilage and bone, and in rare cases metastasize to other organs or locations. Some would prefer to use the word epithelioma for those tumors that, over a period of time, behave benignly in showing little tendency to invade or to develop necrosis within themselves, and to reserve the word carcinoma for those tumors showing invasive characteristics. It is not necessary to take issue with such terminology as long as the physician understands that the terms are used interchangeably, and that all such tumors have certain similar characteristics and potentials whatever the differences in clinical appearance may be. Many years ago the basal cell epithelioma was so named because histologically it resembled cells of the basal layer of the skin, and was at that time, and today, thought to originate from these cells. During the years it has been studied, different investigators have ascribed its origin not only to the basal cells of the epidermis but to the prickle cells, the sweat glands, the sebaceous glands, the hair follicle, and to pluripotential cells of the skin that have the potential and ability to differentiate to sebaceous, sweat and hair structures. I , 3, 7-9, 11-13 This variation in point of origin undoubtedly has an influence in the formation of the different clinical types as seen by the clinician and in the variation of histology as seen by the pathologist. AllenI has pointed out that these clinical and histologic variations do not indicate the potential of the basal cell epithelioma in terms of invasiveness, destruction of tissue or metastasis. The diagnosis of, or an aroused suspicion of, basal cell epithelioma is directly proportional to the number of patients examined and to the knowledge of the examining physician regarding the variety of clinical • Director of Dermatology, Hunterdon Medical Center, Flemington, New Jersey; Teaching Assistant in Clinical Dermatology, New York University School of Medicine, New York, N.Y.
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forms encountered. Today more persons are presenting themselves for opinion and aid regarding skin lesions, partly because of increased cancer education and fears. They are more aware of skin lesions, seek consultation earlier, and are more critical of lack of interest or knowledge on the physician's part, procrastination in treatment, and the results of therapy. Only a certain proportion of these patients will at first hand get to see a dermatologist or one trained in the diagnosis of epidermal lesions. The majority are seen by general practitioners, internists and surgeons. Thus it is necessary that the physician recognize the basal cell epithelioma in all its different clinical forms so that he may direct the patient into proper channels for correct and adequate therapy. A good number of such tumors are discovered by the examining physician during a periodic physical examination, or while examining primarily for some other condition. Of less importance, but still a factor in bringing some patients to the physician, is the increasing desire to achieve and maintain the best appearance cosmetically. Adequate therapy necessitates complete destruction of the epithelioma. Except for plastic surgery, which is not necessarily always indicated, adequate therapy produces a certain amount of scarring. Very often this scarring is in direct proportion to the size of the lesion. It accordingly behooves us as physicians to recognize such lesions as early as possible in order to initiate proper therapy to insure complete eradication of the lesion as well as to produce minimal and cosmetically acceptable scarring. The basal cell epithelioma is the most recognizable of skin malignancies and characteristically develops and enlarges slowly. There is always a slow invasive and destructive rate, and proven metastases2 have been recorded in rare instances. This slowness of development has resulted at times in leading the physician into a "laissez faire" attitude. However, since the tumor is locally invasive, therapy should be prompt and adequate. Since it can be recognized early and is accessible to easy biopsy for confirmation, it is possible to achieve complete destruction in nearly all instances. This tumor is chiefly seen in the middle-aged to elderly adult but is found occasionally in much younger individuals. There are, in fact, several instances of its development in the 20-year age period. The darker skinned races have a relative resistance, it being quite uncommon in the Negro. There is an increased incidence in blonde or light-complexioned, blue-eyed persons, especially when exposed to sunlight for longer or shorter periods. It can arise on any portion of the skin but almost never develops on the mucous membrane. However, it may extend onto the mucosal surface if it has arisen near or at a mucocutaneous junction. It has been noted in such unlikely places as the sole4 and palm. 5 Although this tumor can arise anywhere on the skin, there are areas of increased incidence, and these may be used as rough guidelines in making the diagnosis. The vast majority will be found on the face, between and including the upper lip, to and including the forehead. The neck, covered parts of the trunk, and extremities are less common sites.
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Once necrosis develops it is slowly progressive and practically never heals. It can invade neigh boring soft tissue, cartilage and bone. Such complications are usually seen in cases of local recurrence following treatment or when therapy has been delayed for years as in instances of basal cell epithelioma of the ear or scalp. In the latter location detection is often late. The tumor does not ordinarily develop in antecedent disorders of the skin excepting irradiation dermatitis. Trauma is associated with its development more frequently than in any other carcinoma and, in some states, is acceptable compensation-wise as the exciting factor or cause. Sunlight does not seem to be as important a factor in its development as it is in some other malignancies such as squamous cell carcinoma. It has been associated with the intake of arsenic. TYPES OF BASAL CELL EPITHELIOMA
The basal cell epithelioma can be divided clinically and morphologically into different types, their distinguishing features being determined by the location on the body, the type of cell giving rise to the tumor, the individual response of the patient to the tumor, and the various other known or unknown factors that go to make up what is known as "cancer immunity." Such a classification is an aid to dermatologists and investigators in their studies of the tumor's origin and biologic behavior. To other physicians this division is of value principally in distinguishing the clinical forms of this malignancy, as an aid in its early detection. In 1959 Witten and Kop{l5 divided basal cell epithelioma into the various clinical and morphologic types whose descriptions follow. I have added one other category which I cannot readily place in this grouping, namely the superficial, ulcerative type (No. 5). 1. Nodular (Figs. 1 and 2)
This, the commonest type, is usually found on the head and neck. It customarily begins as a 2- to 3-mm. whitish to pinkish papule that has a translucent quality producing a pearly effect. Other similar papules develop near the periphery, and, as the slow growth proceeds, the newer papules coalesce with the first to produce a nodule. As growth continues, there usually develops a small central depression which becomes crusted and/or ulcerated. The malignant tissue is very friable so that removal of the crust often causes bleeding. Typically, there becomes evident about the edge a raised, somewhat uneven, firm, finely nodular, pearly border. At this time telangiectatic vessels often appear over and about the advancing edge. According to host resistance, tissue reaction and other factors, there may be partial healing in the center of the epithelioma evident as a fibrosis and atrophy. Although this self-healing factor may be of considerable clinical magnitude, it never completely eliminates or destroys the malignant cells.
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Fig. 1
Figure 1. Three small nodular type basal cell epitheliomas, two of which are showing central depressions and beginning crusting. The lowest one shows the distinctive "pearly border." Figure 2. A nodular type with a different morphology due to fibrosis evident in the lower boundary of the tumor.
Fig. 2
The tumor is asymptomatic unless in the uncommon case there is secondary infection to the ulceration. It may be single or multiple. In those persons who have multiple, nodular, basal cell epithelioma of the face, one can, after frequent periodic examinations, learn to detect this tumor when it is but a small, single translucent papule. 2. Cystic (Fig. 3) This is no doubt a variety of the nodular type, but its appearance is so characteristic that perhaps it deserves a place as a different morphologic form. Its location and development are the same as for the nodular type. However, in this case it assumes a globular, cystic shape, is usually translucent, and is made up of one to several cysts which contain a gelatinous fluid. It is often found as part of or associated with the nodular type. 3. Morphea-like or Sclerosing (Fig. 4) This type is usually found on the head and neck, but may be on the body. It is an intracutaneous type that tends to extend in ,a lateral direction with little inclination to grow downward to involve subdermal fatty tissue.
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THE UBIQUITOUS BASAL CELL EPITHELIOMA
There is a self-healing quality that nearly keeps up with the slowly expanding edges to produce a lesion that has a flat, smooth, pale center which can resemble morphea or a localized scleroderma. At some point of, or on nearly all the circumference, one can make out a threadlike to larger, pearly border. If the edges are indistinct, examination through a glass slide pressed down on the lesion enough to push out dermal blood may then show the faint border. It rarely ulcerates and may have some telangiectatic vessels near the periphery. This type is the one most commonly overlooked by the examining physician. 4. Superficial Multicentric (Fig. 5)
This type is chiefly found on the trunk and extremities. It is an intraepidermal carcinoma that develops from multicentric, near foci in the skin to produce a superficial, flat, erythematous, eczematous, often scaling, oval plaque. The plaque tends to grow to a 2- to 4-cm. size with little inclination generally to enlarge further. Neighboring plaques may coalesce to form larger ones. It shows little tendency to invade and destroy, and is asymptomatic. It may show varying degrees of healing or atrophy in the center and Fig. 3
Figure 3. A basal cell epithelioma showing a cystic structure in its lower pole. Figure 4. A morphea or sclerosing type on the back. The border is evident on the right hand side of the lesion. The dark area represents the site of a biopsy that should have been taken for better microscopic interpretation from the edge rather than the center of the tumor.
Fig. 4
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JOHN F. FRITZ, JR.
Fig. 5
Figure 5. On the back there are seven basal cell epitheliomas of the superficial multicentric type. Note the sharp boundaries of the lesions and faint pearly borders in some areas. The two most lateral lesions both show increased pigmentation and beginning nodularity. Figure 6. A moist erythematous seborrheic type lesion on the face, after a loose crust had been wiped off. The edge is quite sharply outlined. The biopsy showed a basal cell epithelioma.
Fig. 6
the edges are sometimes scalloped and usually fairly sharply demarcated from normal skin. There is often a threadlike border which may require magnification to visualize. Its appearance suggests psoriasis, Bowen's disease, and some types of senile keratoses and in these conditions a biopsy may be necessary for differentiation. It may be single and is often mUltiple. As time goes on there may develop within its borders nodules which can go on to crusting and ulceration, and may show some invasive qualities. 5. Superficial. Ulcerative Type (Fig. 6) This I have added as a separate morphologic type. I have found it almost entirely on the face. It is a sharply marginated, very superficially ulcerated, flat, erythematous lesion that tends to develop a loose crust which is easily wiped away. It generally is from 5 to 10 mm. in size and there is a slight induration of its base. It resembles most a moist, seborrheic plaque. Usually there is a threadlike border that may require magnification to visualize. It probably is a variety of the superficial multicentric type.
6. Pigmented As the name indicates, this is a basal cell epithelioma containing pigment. It is chiefly seen in the nodular and cystic types and has been reported
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in the superficial multicentric type. It is very probable that all types of epithelioma may be pigmented. The coloration or pigmentation, which may be evenly distributed or scattered, varies from light to dark brown to coal black. As has been pointed out,lO the presence or amount of pigment bears no relationship to the biologic or malignant activity. Most of these pigmented tumors are found on the trunk although they may develop anywhere on the skin. The tumor can look like a pigmented seborrheic keratosis or a melanoma from which it can be differentiated at times only by biopsy. Multiple lesions, slowness of growth and a waxy appearance may help in this differentiation. If the tumor bears enough clinical resemblance to a melanoma to make the differential diagnosis difficult, it is, of course, necessary to manage it as a melanoma until it is proved to be otherwise. It has been reported l4 as an infrequent finding in verrucous nevi, especially of the scalp. 7. Rodent fficer This type is not seen as frequently today as it was in past generations, probably owing to earlier diagnosis, more prompt and improved therapy, and the refusal of patients to allow this destructive type to continue untreated. It is reported that this type generally started on previously damaged skin, whether from prolonged exposure to the sun or damage by a chronic skin disorder. It generally is seen on the face, ears, or dorsum of the hand, but may develop on other parts of the body. It is said to develop as a macular erythema in which several waxy papules or nodules form to produce a larger nodule that breaks down to form an ulcer. The ulcer progresses slowly and steadily, often in an irregular manner. In time large areas of the skin and underlying tissue are destroyed to produce large, unsightly areas of destruction. There is usually no pain. Frequent crusts are formed and at times there is a slight tendency for the tumor surface to bleed. Present day acumen and prompt, adequate treatment should never again permit patients to develop the disfigurements which were seen in the past. 8. FibroepitheIiaI Tumor of Pinkus This type is generally seen on the trunk as a superficial nodule that usually contains follicular plugs. It resembles mostly a seborrheic keratosis. It represents a fibrous tissue proliferation that encircles strands of epithelial cells that grow down from the skin and communicate with each other. It is considered as a premalignant lesion but may represent an unusual or different type of basal cell epithelioma.
9. Basal-Squamous Cell Carcinoma This type is also known as "transitional cell epithelioma" or "metaphysical carcinoma." One cannot distinguish it from the nodular type clinically. Histologically it is a different type and represents a tumor com-
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posed of cells that bear resemblance to both basal and squamous, or prickle cells of the epidermis. TREATMENT
Basal cell epithelioma can be correctly diagnosed clinically in about
75 per cent of all cases. However, prior to establishing therapy, there should
be a positive microscopic diagnosis. Small bits of tumor tissue and specimens obtained by a small punch biopsy provide adequate biopsy material. If carefully done, the performance of a biopsy should not add to the scarring from subsequent treatment. Even though the different morphologic types often follow characteristic clinical patterns of behavior, it is best to consider that, except for an occasional case, all of them have a similar prognosis. There is no doubt that a few basal cell epitheliomas of different types could be left untreated without jeopardizing the life of the patient. However, the behavior of anyone epithelioma does not guarantee that a similar one, even in the same patient, will follow the same pattern. Accordingly, all basal cell epitheliomas should be adequately treated with possibly a few exceptions. There may be instances in the elderly, debilitated or chronically ill patient when treatment may be justifiably palliative. Inasmuch as the amount of scarring from therapy is often proportional to the size of the lesion, early diagnosis and treatment make for more complete destruction of the tumor and a better cosmetic result. There will be for each tumor a one best method of treatment, keeping in mind that the goal of good therapy encompasses complete destruction by the simplest means plus obtaining the best cosmetic result. Guides to select the best modality of therapy have been well summarized by Witten and Kopf15 and are as follows: SOME GUIDES IN SELECTION OF PROPER THERAPY FOR BASAL CELL EPI'I'HELIOMAS
Age, sex and occupation Depth of invasion Histologic characteristics of the tumor Anticipated radiosensitivity of the tumor Anatomic location Contiguity to vital structures Underlying bone or cartilage Response to previous therapy Characteristics of adjacent skin Healing and scarring potential Physician experience Available equipment Ability of patient to carry through with therapy
The most commonly used methods of therapy are desiccation and curettage (D & C), irradiation, surgery and chemosurgery. Each of the
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methods has its own usefulness and disadvantages, and in every case should be judged accordingly. A majority of basal cell epitheliomas are amenable to treatment by D & C as developed and practiced by the dermatologist. This combined procedure is applicable to the entire tumor plus a 2- to 3-mm. margin beyond the visible edge of the lesion as well as enough depth to be beyond the estimated base. This is a simple office procedure, requires a minimum of office visits, rarely produces complications or becomes secondarily infected, has a cosmetic effect much like that following irradiation and, in experienced hands, has an excellent cure rate. Knox, Lyles, Shapiro and Martin 6 report a 98.3 per cent five-year cure rate after this type of therapy. It is especially useful in the nodular and cystic types under 2 cm. in size and not showing particularly invasive characteristics. It is not the method of choice in most lesions larger than 2 cm., in those that show fibrosis whether it be from being a sclerosing type or in cases of recurrence following previous D & C, surgery or irradiation therapy. It should not be used where there is an invasiveness of cartilage and bone, where the tumor is on the eyelid or is situated in the postauricular or nasolabial folds. In the latter locations this tumor often sends out strands of malignant cells that make complete eradication by D & C virtually impossible. It is useful in eradicating small, superficial, multicentric lesions. At times it is a useful palliative procedure in the elderly, ill patient although complete destruction of the tumor is not accomplished. Minor disadvantages of this method are the longer length of healing time compared to excision and the possibility of producing keloids or hypertrophic scars in some individuals. The morphea or sclerosing type of epithelioma has been most often treated by excision, but is amenable at times to irradiation therapy. Those tumors that have invaded neighboring tissue or are potentially able to do so, as in the nasolabial and postauricular folds, or have destroyed bone or cartilage are best managed by excision. The pigmented variety of tumor is best excised when conveniently possible inasmuch as irradiation, although satisfactorily destructive of the malignant cells, generally leaves the pigment present after healing. Certain of the pigmented variety can be adequately destroyed by D & C. Small lesions can be excised in certain locations where there is a laxness of skin producing natural folds in the skin. In such cases the line of excision is so placed that, on closure with a subcuticular suture, the scar becomes part of the fold aJready present. Irradiation is useful for those lesions on the eyelids and can be used for tumors over cartilage, as on nose and ear, by proper dosage without damaging these structures. It is useful in some cases of tumors arising in the folds about ears and nose and in those instances in which D & C or surgery is difficult. The superficial multicentric epithelioma can be treated with a single dose of irradiation provided there is no nodularity within its borders. This latter type of tumor seldom should be excised inasmuch as direct closure may be so difficult that grafting of skin becomes necessary. Chemo-
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surgery is best entrusted to those few adequately trained in the use of this modality. It has been well used in recurrent and unusually destructive lesions.
SUMMARY More than a cursory knowledge of skin tumors, more specifically basal cell epitheliomas, is required of the examining physician. He must be aware of the various clinical and morphologic forms in which this common, malignant, epithelial tumor can become manifest. An attempt has been made to describe the variations in appearance of the various clinical types, a knowledge of which will contribute to earlier and more frequent diagnoses. Guides are offered in the selection of proper therapy, which must be individualized according to the type of tumor and characteristics of the patient.
REFERENCES 1. AlIen, A. C.: The Skin: A Clinicopathologic Treatise. St. Louis, C. V. Mosby Co.,
1954. 2. Binkley, G. W. and Rauschkolb, R. R.: Epithelioma metastasizing to lymph nodes. A.M.A. Arch. Dermat. 86: 332,1962. 3. Eichenlaub, F. J. and Osbourn, R. A.: Studies in the histogenesis of the epidermis. A.M.A. Arch. Dermat. & Syph. 64: 700, 1951. 4. Hyman, A. B. and Michaelides, P.: Basal cell epithelioma of the sole. A.M.A. Arch. Dermat. 87: 481, 1963. 5. Johnson, D. E.: Basal cell epithelioma of the palm. A.M.A. Arch. Dermat. 82: 145, 1960. 6. Rnox, J. M., Lyles, T. W., Shapiro, E. M. and Martin, R. D.: Curettage and electrodesiccation in the treatment of skin cancer. A.M.A. Arch. Dermat. 82: 197, 1960. 7. Lever, W. F.: Pathogenesis of benign tumors of cutaneous appendages and of basal cell epithelioma: n. Basal cell epithelioma. Arch. Dermat. & Syph. 57: 709, 1948. 8. Montgomery, H.: Histogenesis of basal cell epithelioma. Radiology 25: 8, 1935. 9. Pinkus, H.: Premalignant fibroepithelial tumor of skin. Arch. Dermat. & Syph. 67: 598, 1953. 10. Smith, L. M., Garrett, H. D. and Hart, M. S.: Pigmented basal cell epithelioma. A.M.A. Arch. Dermat. 81: 133,1960. 11. Swerdlow, M.: Histogenesis of basal cell carcinoma. A.M.A. Arch. Dermat. 78: 563,1958. 12. Teloh, H. A. and Wheelock, M. C.: Histogenesis of basal cell carcinoma. Arch. Path. 48: 447, 1949. 13. Willis, R. A.: Pathology of Tumors. 2nd Ed. St. Louis, C. V. Mosby Co., 1953. 14. WiDer, L. H. and Levis, G. H.: Pigmented basal-cell carcinoma in verrucous Devi. A.M.A. Arch. Dermat. 83: 960, 1961. 15. Witten, V. H. and Ropf, A. W.: Some common misconceptions regarding nevi and skin cancers. M. CLIN. NORTH AMERICA 43: 731, 1959.
The basal cell epithelioma is a common epithelial tumor and represents a comparatively benign variety of carcinoma. Some clinicians would prefer to call this tumor a basal cell carcinoma. They point out that, left untreated, it would in most instances continue slowly to enlarge, tend to develop a central necrosis and have the potential to invade adjacent soft tissue, cartilage and bone, and in rare cases metastasize to other organs or locations. Some would prefer to use the word epithelioma for those tumors that, over a period of time, behave benignly in showing little tendency to invade or to develop necrosis within themselves, and to reserve the word carcinoma for those tumors showing invasive characteristics. It is not necessary to take issue with such terminology as long as the physician understands that the terms are used interchangeably, and that all such tumors have certain similar characteristics and potentials whatever the differences in clinical appearance may be. Many years ago the basal cell epithelioma was so named because histologically it resembled cells of the basal layer of the skin, and was at that time, and today, thought to originate from these cells. During the years it has been studied, different investigators have ascribed its origin not only to the basal cells of the epidermis but to the prickle cells, the sweat glands, the sebaceous glands, the hair follicle, and to pluripotential cells of the skin that have the potential and ability to differentiate to sebaceous, sweat and hair structures. I , 3, 7-9, 11-13 This variation in point of origin undoubtedly has an influence in the formation of the different clinical types as seen by the clinician and in the variation of histology as seen by the pathologist. AllenI has pointed out that these clinical and histologic variations do not indicate the potential of the basal cell epithelioma in terms of invasiveness, destruction of tissue or metastasis. The diagnosis of, or an aroused suspicion of, basal cell epithelioma is directly proportional to the number of patients examined and to the knowledge of the examining physician regarding the variety of clinical • Director of Dermatology, Hunterdon Medical Center, Flemington, New Jersey; Teaching Assistant in Clinical Dermatology, New York University School of Medicine, New York, N.Y.
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forms encountered. Today more persons are presenting themselves for opinion and aid regarding skin lesions, partly because of increased cancer education and fears. They are more aware of skin lesions, seek consultation earlier, and are more critical of lack of interest or knowledge on the physician's part, procrastination in treatment, and the results of therapy. Only a certain proportion of these patients will at first hand get to see a dermatologist or one trained in the diagnosis of epidermal lesions. The majority are seen by general practitioners, internists and surgeons. Thus it is necessary that the physician recognize the basal cell epithelioma in all its different clinical forms so that he may direct the patient into proper channels for correct and adequate therapy. A good number of such tumors are discovered by the examining physician during a periodic physical examination, or while examining primarily for some other condition. Of less importance, but still a factor in bringing some patients to the physician, is the increasing desire to achieve and maintain the best appearance cosmetically. Adequate therapy necessitates complete destruction of the epithelioma. Except for plastic surgery, which is not necessarily always indicated, adequate therapy produces a certain amount of scarring. Very often this scarring is in direct proportion to the size of the lesion. It accordingly behooves us as physicians to recognize such lesions as early as possible in order to initiate proper therapy to insure complete eradication of the lesion as well as to produce minimal and cosmetically acceptable scarring. The basal cell epithelioma is the most recognizable of skin malignancies and characteristically develops and enlarges slowly. There is always a slow invasive and destructive rate, and proven metastases2 have been recorded in rare instances. This slowness of development has resulted at times in leading the physician into a "laissez faire" attitude. However, since the tumor is locally invasive, therapy should be prompt and adequate. Since it can be recognized early and is accessible to easy biopsy for confirmation, it is possible to achieve complete destruction in nearly all instances. This tumor is chiefly seen in the middle-aged to elderly adult but is found occasionally in much younger individuals. There are, in fact, several instances of its development in the 20-year age period. The darker skinned races have a relative resistance, it being quite uncommon in the Negro. There is an increased incidence in blonde or light-complexioned, blue-eyed persons, especially when exposed to sunlight for longer or shorter periods. It can arise on any portion of the skin but almost never develops on the mucous membrane. However, it may extend onto the mucosal surface if it has arisen near or at a mucocutaneous junction. It has been noted in such unlikely places as the sole4 and palm. 5 Although this tumor can arise anywhere on the skin, there are areas of increased incidence, and these may be used as rough guidelines in making the diagnosis. The vast majority will be found on the face, between and including the upper lip, to and including the forehead. The neck, covered parts of the trunk, and extremities are less common sites.
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Once necrosis develops it is slowly progressive and practically never heals. It can invade neigh boring soft tissue, cartilage and bone. Such complications are usually seen in cases of local recurrence following treatment or when therapy has been delayed for years as in instances of basal cell epithelioma of the ear or scalp. In the latter location detection is often late. The tumor does not ordinarily develop in antecedent disorders of the skin excepting irradiation dermatitis. Trauma is associated with its development more frequently than in any other carcinoma and, in some states, is acceptable compensation-wise as the exciting factor or cause. Sunlight does not seem to be as important a factor in its development as it is in some other malignancies such as squamous cell carcinoma. It has been associated with the intake of arsenic. TYPES OF BASAL CELL EPITHELIOMA
The basal cell epithelioma can be divided clinically and morphologically into different types, their distinguishing features being determined by the location on the body, the type of cell giving rise to the tumor, the individual response of the patient to the tumor, and the various other known or unknown factors that go to make up what is known as "cancer immunity." Such a classification is an aid to dermatologists and investigators in their studies of the tumor's origin and biologic behavior. To other physicians this division is of value principally in distinguishing the clinical forms of this malignancy, as an aid in its early detection. In 1959 Witten and Kop{l5 divided basal cell epithelioma into the various clinical and morphologic types whose descriptions follow. I have added one other category which I cannot readily place in this grouping, namely the superficial, ulcerative type (No. 5). 1. Nodular (Figs. 1 and 2)
This, the commonest type, is usually found on the head and neck. It customarily begins as a 2- to 3-mm. whitish to pinkish papule that has a translucent quality producing a pearly effect. Other similar papules develop near the periphery, and, as the slow growth proceeds, the newer papules coalesce with the first to produce a nodule. As growth continues, there usually develops a small central depression which becomes crusted and/or ulcerated. The malignant tissue is very friable so that removal of the crust often causes bleeding. Typically, there becomes evident about the edge a raised, somewhat uneven, firm, finely nodular, pearly border. At this time telangiectatic vessels often appear over and about the advancing edge. According to host resistance, tissue reaction and other factors, there may be partial healing in the center of the epithelioma evident as a fibrosis and atrophy. Although this self-healing factor may be of considerable clinical magnitude, it never completely eliminates or destroys the malignant cells.
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JOHN F. FRITZ, JR.
Fig. 1
Figure 1. Three small nodular type basal cell epitheliomas, two of which are showing central depressions and beginning crusting. The lowest one shows the distinctive "pearly border." Figure 2. A nodular type with a different morphology due to fibrosis evident in the lower boundary of the tumor.
Fig. 2
The tumor is asymptomatic unless in the uncommon case there is secondary infection to the ulceration. It may be single or multiple. In those persons who have multiple, nodular, basal cell epithelioma of the face, one can, after frequent periodic examinations, learn to detect this tumor when it is but a small, single translucent papule. 2. Cystic (Fig. 3) This is no doubt a variety of the nodular type, but its appearance is so characteristic that perhaps it deserves a place as a different morphologic form. Its location and development are the same as for the nodular type. However, in this case it assumes a globular, cystic shape, is usually translucent, and is made up of one to several cysts which contain a gelatinous fluid. It is often found as part of or associated with the nodular type. 3. Morphea-like or Sclerosing (Fig. 4) This type is usually found on the head and neck, but may be on the body. It is an intracutaneous type that tends to extend in ,a lateral direction with little inclination to grow downward to involve subdermal fatty tissue.
1545
THE UBIQUITOUS BASAL CELL EPITHELIOMA
There is a self-healing quality that nearly keeps up with the slowly expanding edges to produce a lesion that has a flat, smooth, pale center which can resemble morphea or a localized scleroderma. At some point of, or on nearly all the circumference, one can make out a threadlike to larger, pearly border. If the edges are indistinct, examination through a glass slide pressed down on the lesion enough to push out dermal blood may then show the faint border. It rarely ulcerates and may have some telangiectatic vessels near the periphery. This type is the one most commonly overlooked by the examining physician. 4. Superficial Multicentric (Fig. 5)
This type is chiefly found on the trunk and extremities. It is an intraepidermal carcinoma that develops from multicentric, near foci in the skin to produce a superficial, flat, erythematous, eczematous, often scaling, oval plaque. The plaque tends to grow to a 2- to 4-cm. size with little inclination generally to enlarge further. Neighboring plaques may coalesce to form larger ones. It shows little tendency to invade and destroy, and is asymptomatic. It may show varying degrees of healing or atrophy in the center and Fig. 3
Figure 3. A basal cell epithelioma showing a cystic structure in its lower pole. Figure 4. A morphea or sclerosing type on the back. The border is evident on the right hand side of the lesion. The dark area represents the site of a biopsy that should have been taken for better microscopic interpretation from the edge rather than the center of the tumor.
Fig. 4
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JOHN F. FRITZ, JR.
Fig. 5
Figure 5. On the back there are seven basal cell epitheliomas of the superficial multicentric type. Note the sharp boundaries of the lesions and faint pearly borders in some areas. The two most lateral lesions both show increased pigmentation and beginning nodularity. Figure 6. A moist erythematous seborrheic type lesion on the face, after a loose crust had been wiped off. The edge is quite sharply outlined. The biopsy showed a basal cell epithelioma.
Fig. 6
the edges are sometimes scalloped and usually fairly sharply demarcated from normal skin. There is often a threadlike border which may require magnification to visualize. Its appearance suggests psoriasis, Bowen's disease, and some types of senile keratoses and in these conditions a biopsy may be necessary for differentiation. It may be single and is often mUltiple. As time goes on there may develop within its borders nodules which can go on to crusting and ulceration, and may show some invasive qualities. 5. Superficial. Ulcerative Type (Fig. 6) This I have added as a separate morphologic type. I have found it almost entirely on the face. It is a sharply marginated, very superficially ulcerated, flat, erythematous lesion that tends to develop a loose crust which is easily wiped away. It generally is from 5 to 10 mm. in size and there is a slight induration of its base. It resembles most a moist, seborrheic plaque. Usually there is a threadlike border that may require magnification to visualize. It probably is a variety of the superficial multicentric type.
6. Pigmented As the name indicates, this is a basal cell epithelioma containing pigment. It is chiefly seen in the nodular and cystic types and has been reported
THE UBIQUITOUS BASAL CELL EPITHELIOMA
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in the superficial multicentric type. It is very probable that all types of epithelioma may be pigmented. The coloration or pigmentation, which may be evenly distributed or scattered, varies from light to dark brown to coal black. As has been pointed out,lO the presence or amount of pigment bears no relationship to the biologic or malignant activity. Most of these pigmented tumors are found on the trunk although they may develop anywhere on the skin. The tumor can look like a pigmented seborrheic keratosis or a melanoma from which it can be differentiated at times only by biopsy. Multiple lesions, slowness of growth and a waxy appearance may help in this differentiation. If the tumor bears enough clinical resemblance to a melanoma to make the differential diagnosis difficult, it is, of course, necessary to manage it as a melanoma until it is proved to be otherwise. It has been reported l4 as an infrequent finding in verrucous nevi, especially of the scalp. 7. Rodent fficer This type is not seen as frequently today as it was in past generations, probably owing to earlier diagnosis, more prompt and improved therapy, and the refusal of patients to allow this destructive type to continue untreated. It is reported that this type generally started on previously damaged skin, whether from prolonged exposure to the sun or damage by a chronic skin disorder. It generally is seen on the face, ears, or dorsum of the hand, but may develop on other parts of the body. It is said to develop as a macular erythema in which several waxy papules or nodules form to produce a larger nodule that breaks down to form an ulcer. The ulcer progresses slowly and steadily, often in an irregular manner. In time large areas of the skin and underlying tissue are destroyed to produce large, unsightly areas of destruction. There is usually no pain. Frequent crusts are formed and at times there is a slight tendency for the tumor surface to bleed. Present day acumen and prompt, adequate treatment should never again permit patients to develop the disfigurements which were seen in the past. 8. FibroepitheIiaI Tumor of Pinkus This type is generally seen on the trunk as a superficial nodule that usually contains follicular plugs. It resembles mostly a seborrheic keratosis. It represents a fibrous tissue proliferation that encircles strands of epithelial cells that grow down from the skin and communicate with each other. It is considered as a premalignant lesion but may represent an unusual or different type of basal cell epithelioma.
9. Basal-Squamous Cell Carcinoma This type is also known as "transitional cell epithelioma" or "metaphysical carcinoma." One cannot distinguish it from the nodular type clinically. Histologically it is a different type and represents a tumor com-
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JOHN F. FRITZ, JR.
posed of cells that bear resemblance to both basal and squamous, or prickle cells of the epidermis. TREATMENT
Basal cell epithelioma can be correctly diagnosed clinically in about
75 per cent of all cases. However, prior to establishing therapy, there should
be a positive microscopic diagnosis. Small bits of tumor tissue and specimens obtained by a small punch biopsy provide adequate biopsy material. If carefully done, the performance of a biopsy should not add to the scarring from subsequent treatment. Even though the different morphologic types often follow characteristic clinical patterns of behavior, it is best to consider that, except for an occasional case, all of them have a similar prognosis. There is no doubt that a few basal cell epitheliomas of different types could be left untreated without jeopardizing the life of the patient. However, the behavior of anyone epithelioma does not guarantee that a similar one, even in the same patient, will follow the same pattern. Accordingly, all basal cell epitheliomas should be adequately treated with possibly a few exceptions. There may be instances in the elderly, debilitated or chronically ill patient when treatment may be justifiably palliative. Inasmuch as the amount of scarring from therapy is often proportional to the size of the lesion, early diagnosis and treatment make for more complete destruction of the tumor and a better cosmetic result. There will be for each tumor a one best method of treatment, keeping in mind that the goal of good therapy encompasses complete destruction by the simplest means plus obtaining the best cosmetic result. Guides to select the best modality of therapy have been well summarized by Witten and Kopf15 and are as follows: SOME GUIDES IN SELECTION OF PROPER THERAPY FOR BASAL CELL EPI'I'HELIOMAS
Age, sex and occupation Depth of invasion Histologic characteristics of the tumor Anticipated radiosensitivity of the tumor Anatomic location Contiguity to vital structures Underlying bone or cartilage Response to previous therapy Characteristics of adjacent skin Healing and scarring potential Physician experience Available equipment Ability of patient to carry through with therapy
The most commonly used methods of therapy are desiccation and curettage (D & C), irradiation, surgery and chemosurgery. Each of the
THE UBIQUITOUS BASAL CELL EPITHELIOMA
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methods has its own usefulness and disadvantages, and in every case should be judged accordingly. A majority of basal cell epitheliomas are amenable to treatment by D & C as developed and practiced by the dermatologist. This combined procedure is applicable to the entire tumor plus a 2- to 3-mm. margin beyond the visible edge of the lesion as well as enough depth to be beyond the estimated base. This is a simple office procedure, requires a minimum of office visits, rarely produces complications or becomes secondarily infected, has a cosmetic effect much like that following irradiation and, in experienced hands, has an excellent cure rate. Knox, Lyles, Shapiro and Martin 6 report a 98.3 per cent five-year cure rate after this type of therapy. It is especially useful in the nodular and cystic types under 2 cm. in size and not showing particularly invasive characteristics. It is not the method of choice in most lesions larger than 2 cm., in those that show fibrosis whether it be from being a sclerosing type or in cases of recurrence following previous D & C, surgery or irradiation therapy. It should not be used where there is an invasiveness of cartilage and bone, where the tumor is on the eyelid or is situated in the postauricular or nasolabial folds. In the latter locations this tumor often sends out strands of malignant cells that make complete eradication by D & C virtually impossible. It is useful in eradicating small, superficial, multicentric lesions. At times it is a useful palliative procedure in the elderly, ill patient although complete destruction of the tumor is not accomplished. Minor disadvantages of this method are the longer length of healing time compared to excision and the possibility of producing keloids or hypertrophic scars in some individuals. The morphea or sclerosing type of epithelioma has been most often treated by excision, but is amenable at times to irradiation therapy. Those tumors that have invaded neighboring tissue or are potentially able to do so, as in the nasolabial and postauricular folds, or have destroyed bone or cartilage are best managed by excision. The pigmented variety of tumor is best excised when conveniently possible inasmuch as irradiation, although satisfactorily destructive of the malignant cells, generally leaves the pigment present after healing. Certain of the pigmented variety can be adequately destroyed by D & C. Small lesions can be excised in certain locations where there is a laxness of skin producing natural folds in the skin. In such cases the line of excision is so placed that, on closure with a subcuticular suture, the scar becomes part of the fold aJready present. Irradiation is useful for those lesions on the eyelids and can be used for tumors over cartilage, as on nose and ear, by proper dosage without damaging these structures. It is useful in some cases of tumors arising in the folds about ears and nose and in those instances in which D & C or surgery is difficult. The superficial multicentric epithelioma can be treated with a single dose of irradiation provided there is no nodularity within its borders. This latter type of tumor seldom should be excised inasmuch as direct closure may be so difficult that grafting of skin becomes necessary. Chemo-
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F. FruTZ, JR.
surgery is best entrusted to those few adequately trained in the use of this modality. It has been well used in recurrent and unusually destructive lesions.
SUMMARY More than a cursory knowledge of skin tumors, more specifically basal cell epitheliomas, is required of the examining physician. He must be aware of the various clinical and morphologic forms in which this common, malignant, epithelial tumor can become manifest. An attempt has been made to describe the variations in appearance of the various clinical types, a knowledge of which will contribute to earlier and more frequent diagnoses. Guides are offered in the selection of proper therapy, which must be individualized according to the type of tumor and characteristics of the patient.
REFERENCES 1. AlIen, A. C.: The Skin: A Clinicopathologic Treatise. St. Louis, C. V. Mosby Co.,
1954. 2. Binkley, G. W. and Rauschkolb, R. R.: Epithelioma metastasizing to lymph nodes. A.M.A. Arch. Dermat. 86: 332,1962. 3. Eichenlaub, F. J. and Osbourn, R. A.: Studies in the histogenesis of the epidermis. A.M.A. Arch. Dermat. & Syph. 64: 700, 1951. 4. Hyman, A. B. and Michaelides, P.: Basal cell epithelioma of the sole. A.M.A. Arch. Dermat. 87: 481, 1963. 5. Johnson, D. E.: Basal cell epithelioma of the palm. A.M.A. Arch. Dermat. 82: 145, 1960. 6. Rnox, J. M., Lyles, T. W., Shapiro, E. M. and Martin, R. D.: Curettage and electrodesiccation in the treatment of skin cancer. A.M.A. Arch. Dermat. 82: 197, 1960. 7. Lever, W. F.: Pathogenesis of benign tumors of cutaneous appendages and of basal cell epithelioma: n. Basal cell epithelioma. Arch. Dermat. & Syph. 57: 709, 1948. 8. Montgomery, H.: Histogenesis of basal cell epithelioma. Radiology 25: 8, 1935. 9. Pinkus, H.: Premalignant fibroepithelial tumor of skin. Arch. Dermat. & Syph. 67: 598, 1953. 10. Smith, L. M., Garrett, H. D. and Hart, M. S.: Pigmented basal cell epithelioma. A.M.A. Arch. Dermat. 81: 133,1960. 11. Swerdlow, M.: Histogenesis of basal cell carcinoma. A.M.A. Arch. Dermat. 78: 563,1958. 12. Teloh, H. A. and Wheelock, M. C.: Histogenesis of basal cell carcinoma. Arch. Path. 48: 447, 1949. 13. Willis, R. A.: Pathology of Tumors. 2nd Ed. St. Louis, C. V. Mosby Co., 1953. 14. WiDer, L. H. and Levis, G. H.: Pigmented basal-cell carcinoma in verrucous Devi. A.M.A. Arch. Dermat. 83: 960, 1961. 15. Witten, V. H. and Ropf, A. W.: Some common misconceptions regarding nevi and skin cancers. M. CLIN. NORTH AMERICA 43: 731, 1959.