Commentary
CLASSIFICATION OF ACANTHOSIS NIGRICANS HELEN OLLENDORFF CURTH, M.D.
From the Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York
Acanthosis nigricans occurs in many countries, climates and races and it may be seen in various forms. It is important to know to which type of the disease a case of acanthosis nigricans belongs, in order to comprehend its significance. Malignant Type The most important type is malignant acanthosis nigricans, or acanthosis nigricans, which always represents a benign dermatosis in association with a malignant internal adenocarcinoma. This association is causal and not coincidental, since both processes usually start at the same time an dtake a parallel course. Actually, the dermatosis and the cancer start simultaneously in 6 1 % of patients; cancer precedes acanthosis nigricans in 22% and acanthosis nigricans precedes cancer in 17%. In one instance,^ the patient had the dermatosis for 16 years before the cancer became manifest. The tumor usually is a highly malignant adenocarcinoma of the stomach, esophagus, cystic duct, hepatic ducts, colon, pancreas, mammary gland, uterus, ovaries, testes, lung or thyroid (?).2 The disease usually is fatal. In only 2 instances of cancer of the sigmoid colon did the patients survive. The patients are nonobese adolescents and adults, but the disease has also been reported in children.
The dermatosis is usually progressive; it also affects the mucous membranes with nonpigmented papillary lesions. The patients may complain of itching. They may develop keratoma of the palms and soles. Keratosis of the nipples and umbilicus may be present but keratoses may also be present in benign acanthosis nigricans. Since the various components of malignant acanthosis nigricans—hyperkeratosis, acanthosis and hyperpigmentation —do not always develop simultaneously, it may happen that hyperkeratotic papillary growths (sign of LeserTrelat) become prominent. Therefore, the Leser Trelat sign usually represents an early stage of acanthosis nigricans. There are a few instances in which the transition from Leser Trelat to malignant acanthosis nigricans was observed.'^''' Moreover, seborrheic keratoses on the body or extremities have almost always accompanied characteristic lesions of acanthosis nigricans. I have lately seen a Negro patient who showed only distinct hyperpigmentation, another component of acanthosis nigricans, over large areas of the body in addition to typical cutaneous changes in the axillae and a gastric carcinoma. Benign Types Acanthosis nigricans not associated with an internal carcinoma occurs in several types. Benign acanthosis nigricans, a genodermatosis, is Irregularly dominantly inherited. It is present at birth, or begins in childhood or at puberty. After that time it either regresses or remains sta-
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tionary. It is not accompanied by endocrine disturbances. In dark-skinned obese individuals of both sexes pseudo acanthosis nigricans' may start at any age. The obesity may be due to endocrine disturbances, overeating or constitutional factors. The process is reversible if the overweight can be considerably reduced. In acromegaly and gigantism, a reversal of the cutaneous process is impossible. In the tropics, pseudo acanthosis nigricans is due to sweating and maceration. Lately, a number of genetic conditions have been found associated with acanthosis nigricans. Such conditions are Bloom's, Down's and Crouzon's syndromes; lipodystrophy, phenylketonuria, and others now known. Acanthosis nigricans also occurred in siblings of 3 sisters .with nerve deafness and absent gastric motility.'' The dermatosis is present at birth or begins in childhood. It sometimes disappears at puberty.
Curth
593
until after puberty; some cases regress spontaneously. In widespread cases, dermabrasion has proved satisfactory. If pseudo acanthosis nigricans is caused by obesity, the excessive body weight should be reduced. If acanthosis nigricans is part of a syndrome, the other components are usually more disturbing than the acanthosis nigricans. In some syndromes, acanthosis nigricans disappears spontaneously. The significant of the various types is vastly different. In malignant acanthosis nigricans, the dermatosis is an important cancer clue. Benign acanthosis nigricans, a genodermatosis, can be greatly disfiguring and the patients may require genetic counseling. Pseudo acanthosis nigricans points to an overlying disturbance such as obesity, Cushing's syndrome, gigantism, acromegaly and others. Acanthosis nigricans as part of a syndrome may help in the recognition of the overall syndrome. References
Characteristics The clinical appearance of the dermatosis is the same in all 4 types. The body folds show hyperpigmented, confluent, verrucous skin. The nipples and the umbilicus may become keratotic. Sometimes palms and soles become thickened. In malignant acanthosis nigricans, the mucous membranes may be affected with nonpigmented verrucous growths. The histology of all 4 types is the same. It shows hyperkeratosis, acanthosis and hyperpigmentation. The sexes are about equally affected. Treatment of the malignant type involves earliest recognition and eradication of the tumor. Treatment of benign acanthosis nigricans should be deferred
1. Freund, E., Cas d'acantbosis nigricans; apparition d'un carcinome apres seize annees. Rev. Fr. Dermatol. Venereol. 7:450, 1931. 2. Curfb, H. C , Hilberg, A. W., and Macbacek, G. F., Tbe site and bistology of the cancer associated with malignant acantbosis nigricans. Cancer 15:364, 1962. 3. Roncbese, F., Keratoses, cancer and "tbe sign of Leser-Trelat." Cancer 18:1003, 1965. 4. Curtb, H. O., Tovell, H. M. M., and Janovski, N., Malignant acantbosis nigricans associated witb endometrial adenocarcinoma. Bull. Sloane Hosp. Women 8:141, 1962. 5. Curtb, H. O., Pseudo acantbosis nigricans. Ann. Dermatol. Sypbilol. 78:417, 1951. 6. Hirscbowitz, B. I., Groll, A., and Ceballos, R., Hereditary nerve deafness in tbree sisters witb absent gastric mobility, small bowel diverticulitis and ulceration and progressive sensory neuropatby. Birtb Defects 8:27, 1972.
CLASSIFICATION OF ACANTHOSIS NIGRICANS HELEN OLLENDORFF CURTH, M.D.
From the Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York
Acanthosis nigricans occurs in many countries, climates and races and it may be seen in various forms. It is important to know to which type of the disease a case of acanthosis nigricans belongs, in order to comprehend its significance. Malignant Type The most important type is malignant acanthosis nigricans, or acanthosis nigricans, which always represents a benign dermatosis in association with a malignant internal adenocarcinoma. This association is causal and not coincidental, since both processes usually start at the same time an dtake a parallel course. Actually, the dermatosis and the cancer start simultaneously in 6 1 % of patients; cancer precedes acanthosis nigricans in 22% and acanthosis nigricans precedes cancer in 17%. In one instance,^ the patient had the dermatosis for 16 years before the cancer became manifest. The tumor usually is a highly malignant adenocarcinoma of the stomach, esophagus, cystic duct, hepatic ducts, colon, pancreas, mammary gland, uterus, ovaries, testes, lung or thyroid (?).2 The disease usually is fatal. In only 2 instances of cancer of the sigmoid colon did the patients survive. The patients are nonobese adolescents and adults, but the disease has also been reported in children.
The dermatosis is usually progressive; it also affects the mucous membranes with nonpigmented papillary lesions. The patients may complain of itching. They may develop keratoma of the palms and soles. Keratosis of the nipples and umbilicus may be present but keratoses may also be present in benign acanthosis nigricans. Since the various components of malignant acanthosis nigricans—hyperkeratosis, acanthosis and hyperpigmentation —do not always develop simultaneously, it may happen that hyperkeratotic papillary growths (sign of LeserTrelat) become prominent. Therefore, the Leser Trelat sign usually represents an early stage of acanthosis nigricans. There are a few instances in which the transition from Leser Trelat to malignant acanthosis nigricans was observed.'^''' Moreover, seborrheic keratoses on the body or extremities have almost always accompanied characteristic lesions of acanthosis nigricans. I have lately seen a Negro patient who showed only distinct hyperpigmentation, another component of acanthosis nigricans, over large areas of the body in addition to typical cutaneous changes in the axillae and a gastric carcinoma. Benign Types Acanthosis nigricans not associated with an internal carcinoma occurs in several types. Benign acanthosis nigricans, a genodermatosis, is Irregularly dominantly inherited. It is present at birth, or begins in childhood or at puberty. After that time it either regresses or remains sta-
592
No. 8
ACANTHOSIS NIGRICANS
tionary. It is not accompanied by endocrine disturbances. In dark-skinned obese individuals of both sexes pseudo acanthosis nigricans' may start at any age. The obesity may be due to endocrine disturbances, overeating or constitutional factors. The process is reversible if the overweight can be considerably reduced. In acromegaly and gigantism, a reversal of the cutaneous process is impossible. In the tropics, pseudo acanthosis nigricans is due to sweating and maceration. Lately, a number of genetic conditions have been found associated with acanthosis nigricans. Such conditions are Bloom's, Down's and Crouzon's syndromes; lipodystrophy, phenylketonuria, and others now known. Acanthosis nigricans also occurred in siblings of 3 sisters .with nerve deafness and absent gastric motility.'' The dermatosis is present at birth or begins in childhood. It sometimes disappears at puberty.
Curth
593
until after puberty; some cases regress spontaneously. In widespread cases, dermabrasion has proved satisfactory. If pseudo acanthosis nigricans is caused by obesity, the excessive body weight should be reduced. If acanthosis nigricans is part of a syndrome, the other components are usually more disturbing than the acanthosis nigricans. In some syndromes, acanthosis nigricans disappears spontaneously. The significant of the various types is vastly different. In malignant acanthosis nigricans, the dermatosis is an important cancer clue. Benign acanthosis nigricans, a genodermatosis, can be greatly disfiguring and the patients may require genetic counseling. Pseudo acanthosis nigricans points to an overlying disturbance such as obesity, Cushing's syndrome, gigantism, acromegaly and others. Acanthosis nigricans as part of a syndrome may help in the recognition of the overall syndrome. References
Characteristics The clinical appearance of the dermatosis is the same in all 4 types. The body folds show hyperpigmented, confluent, verrucous skin. The nipples and the umbilicus may become keratotic. Sometimes palms and soles become thickened. In malignant acanthosis nigricans, the mucous membranes may be affected with nonpigmented verrucous growths. The histology of all 4 types is the same. It shows hyperkeratosis, acanthosis and hyperpigmentation. The sexes are about equally affected. Treatment of the malignant type involves earliest recognition and eradication of the tumor. Treatment of benign acanthosis nigricans should be deferred
1. Freund, E., Cas d'acantbosis nigricans; apparition d'un carcinome apres seize annees. Rev. Fr. Dermatol. Venereol. 7:450, 1931. 2. Curfb, H. C , Hilberg, A. W., and Macbacek, G. F., Tbe site and bistology of the cancer associated with malignant acantbosis nigricans. Cancer 15:364, 1962. 3. Roncbese, F., Keratoses, cancer and "tbe sign of Leser-Trelat." Cancer 18:1003, 1965. 4. Curtb, H. O., Tovell, H. M. M., and Janovski, N., Malignant acantbosis nigricans associated witb endometrial adenocarcinoma. Bull. Sloane Hosp. Women 8:141, 1962. 5. Curtb, H. O., Pseudo acantbosis nigricans. Ann. Dermatol. Sypbilol. 78:417, 1951. 6. Hirscbowitz, B. I., Groll, A., and Ceballos, R., Hereditary nerve deafness in tbree sisters witb absent gastric mobility, small bowel diverticulitis and ulceration and progressive sensory neuropatby. Birtb Defects 8:27, 1972.
