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Cutaneous Manifestations of Visceral Malignancy Postgrad Med J: first published as 10.1136/pgmj.46.541.678 on 1 November 1970. Downloaded from Postgraduate Medical Journal (November 1970) 46, 678-685. Cutaneous manifestations of visceral malignancy I. B. SNEDDON M.B., F.R.C.P. Consultant Physician for Diseases of the Skin, Rupert Hallam Department of Dermatology, The Hallamshire Hospital, Sheffield, 10 HEBRA (1868) was the first to suggest that pigmenta- has been found in several families to indicate a tion of the skin might indicate the presence of a congenital abnormality of the lower end of the visceral cancer. With gathering speed, more and oesophagus, which later developed carcinoma. more skin reactions which occur before or con- Howel-Evans et al. (1958) described two families currently with malignant disease have been observed. who suffered from tylosis, which is usually harm- Some suspected associations such as the presence of less and trivial, but of forty-eight affected members Campbell De Morgan angiomata, which were at one of the families eighteen developed carcinoma of the time considered harbingers of cancer, are now oesophagus early in life. recognized as incorrect. The more recent example of More recently, Shine & Allison (1966) described such negative evidence is the report (Rhodes, 1970) a family who suffered from mild tylosis of rather copyright. that seed keratoses on the palms and soles thought late onset together with hiatus hernia and a lower by Dobson, Young & Pinto (1965) to occur four oesophagus lined by gastric mucosa. A carcinoma times as frequently in patients with cancer, affect developed in the first patient to be recognized. The 62%4 of skin patients over 40 and indicate no greater son of this patient, who also had dysphagia, was proneness to internal neoplasia. treated by prophylactic removal of an oesophageal Many skin changes occur in elderly people in the stricture. The tylosis in this family was so mild that, cancer age and it is important therefore to avoid had it not been looked for, it would have been missed. ascribing normal aging effects or even skin disorders of old age to internal carcinoma when the relation- Peutz-Jeghers syndrome http://pmj.bmj.com/ ship may only be coincidental. There are, however, Moving a little further down the gastro-intestinal many very striking associations between skin lesions tract, hereditary polyposis of the small intestine and visceral cancer but it is easier to observe them may be associated with pigmentation on the lips, in the rare disorders such as acanthosis nigricans or the oral mucosa and sometimes on the fingers (Fig. the sudden sprouting of lanugo hair over the face of 1) and the umbilicus. This, the Peutz-Jeghers syn- an adult (Lyle & Whittle, 1951) than in the everyday drome, is rarely associated with malignancy in the complaints of generalized pruritus or urticaria. small intestine (Peutz, 1921; Jeghers, McKusick & on September 28, 2021 by guest. Protected Unfortunately by the time skin lesions such as acan- Katz, 1949). The pigmented skin changes occur in thosis nigricans have appeared the underlying neo- infancy and may fade at puberty, leaving only the plasm is far advanced and there is no opportunity oral pigmentation which persists throughout life. to alter the natural course of the disease. It is par- The pigmented freckles on the face are more profuse ticularly important, therefore, to recognize those than usual freckles and involve the red margin of conditions which may indicate the precancerous the lips. It is important to emphasize that in the state such as the genetic defect of an internal organ Peutz-Jeghers syndrome polyposis is mainly in the which may develop a neoplastic change at an early small intestine and symptoms usually arise from age. haemorrhage or intussusception. Malignant change has been recorded (Kutscher et al., 1959) but more Skin markers of intestinal defect recent reviewers (Dormandy, 1957; Morson, 1962; A number of syndromes involving the gastro- McKusick, 1962) ofthe evidence of malignant change intestinal tract have been recognized. Hyperkeratosis in the polyps have come to the conclusion that of the hands and feet, technically known as tylosis, the great majority are hamartomas and that the Postgrad Med J: first published as 10.1136/pgmj.46.541.678 on 1 November 1970. Downloaded from Cutaneous manifestations of visceral malignancy 679 subsequent course of those patients said to have dark, velvety thickening of the skin. This occurs malignant change has contradicted the diagnosis of constantly on the neck, axillae and groins and carcinoma. One recent report (Williams & Knudsen, frequently round the nipples and umbilicus. Pedun- 1965) claims to be the first to describe a true malig- culated papillomas and flat warts arise in the flexures. nant change in a polyp in the duodenum, with Velvety thickening of the palms is a useful con- metastasis. Whilst it is true that the risk of malig- firmatory sign (MacKenna, 1957) and the mucous nancy in the small intestine is low, many of these membranes of the mouth and anus are usually in- patients do have polyps in the stomach and colon volved by warty overgrowths. which do not have such a benign course (Dormandy, Curth, who has done more than anyone to recog- 1957). Pigmented macules on the lips do not always nize acanthosis nigricans, has emphasized that 9000 indicate gastro-intestinal polyposis and there have of the carcinomas underlying the disorder are in the been a number of instances reported (Calnan, 1960; abdomen and 61% arise from the stomach (Curth, Belisario, 1965) in which no gastro-intestinal ab- 1943; Curth, Hilberg & Machacek, 1962). Invariably normality was found. the growth is highly malignant and rapidly fatal. Only temporary regression of the acanthosis has Familial polyposis of the colon followed removal of a primary tumour. The obscure This is a far more dangerous disease. Malignancy relationship between acanthosis nigricans and a will occur in 50%o of those with symptoms (Dukes, neoplasm can best be demonstrated by a case re- 1958), but fortunately in some families those with ported in 1964 by Jenner: a woman who had acan- polyposis may be indicated by a variety of skin and thosis nigricans underwent laparotomy but evidence subcutaneous markers. Gardner and his associates of carcinoma in the abdomen and pelvis was not (1951, 1953) described the syndrome of polyposis found. She died 7 years later and at necropsy was and subcutaneous bony tumours of the maxilla, the found to have secondary nodules in the liver and in mandible and cranial bones. This syndrome now the lungs, and a possible primary in the body of the bears his name. There are now some seventy-five pancreas. reported examples of this condition, 30%° of them with carcinoma (Jones & Cornell, 1966). Seborrhoeic warty lesions copyright. Other authors have recorded a variety of sub- An occasional variant of acanthosis nigricans is cutaneous benign tumours such as lipoma (Laberge, the predominance of seborrhoeic wart-like lesions Saver & Mayo, 1957), osteoma (Weiner & Cooper, with minimal or absent change at the flexures 1955), desmoid tumours and epidermoid cysts (Old- (Sneddon & Roberts, 1962; Curth et al., 1962; field, 1954; Staley, 1961), which have appeared prior Gougerot & Duperrat, 1942). Some years ago I to colonic symptoms. Polyps occur only in those with stumbled across two such cases in men with skin lesions, which therefore serve a useful purpose carcinoma of the stomach. The second of them, in indicating those at risk. Dawborn and his col- a man of 58, was referred for treatment of warts leagues (1962) considered that the likelihood of on the arms and legs. He had noticed an increase http://pmj.bmj.com/ malignancy in the colonic polyps of Gardner's syn- in the number and size of the warts over a period drome was so great that co ectomy in early adult life of 6 months. His only other complaint was lack was justified. They based their opinion on fifty-six of energy. The warty growths were distributed in patients with Gardner's syndrome of whom eighteen profusion over the front and back of all the limbs were dead at the average age of 33 as a result of but the trunk was spared and, in particular, there cancer of the colon and rectum. A recent report of were no changes in the mouth, axillae and groins. familial polyposis (Weston & Wiener, 1967) includes, The warts varied in size from a few mm to 1 cm and as well as the sebaceous cysts, pigmented lesions on in appearance were indistinguishable from sebor- on September 28, 2021 by guest. Protected the surface of the chest and back. The Cronkhite and rhoeic warts. Interspersed between them were cafe- Canada syndrome is associated with skin and gut au-lait pigmented macules. He did not complain of changes but does not cause malignant disease dyspepsia but, because of the similarity of this man's (Cronkhite & Canada, 1955). warts to those in the earlier case, a barium meal examination was carried out which showed a filling Acanthosis nigricans defect, later proved by laparotomy to be due to an Acanthosis nigricans was the first true dermatosis adenocarcinoma of the stomach. At the time I was associated with malignancy; it is the condition not aware that this condition had previously been which, if found in an adult, denotes that the patient described by a French surgeon, Ulysse Trelat, some has or will shortly have an adenocarcinoma. One time before his death in 1890. The association is well cannot improve on the description of Pollitzer who, known on the Continent and is called the sign of in 1890, roted the combination of increased pig- Trelat (Belisario, 1965; Ronchese, 1965). mentation and hypertrophy which gives rise to a During the last year a case was demonstrated to Postgrad Med J: first published as 10.1136/pgmj.46.541.678 on 1 November 1970.
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