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Acanthosis nigricans and bronchial carcinoma
Brit. 07. Dis. Chest (x965) 59, 47.
ACANTHOSIS NIGRICANS AND BRONCHIAL CARCINOMA BY H. Fox Department of Pathology, University of Manchester AND
A~.~XANDER D. G. GuNN Darbishire House Health Centre, Manchester
ACANTHOSIS nigricans may occur together with a gastro-intestinal adenocarcinoma (Curth et al., 1962) and a few cases of acanthosis nigricans occurring together with a bronchial carcinoma have been reported. Another example of this association is reported and the cases previously recorded are reviewed.
Case Report A man of 57 was seen in September i963. He gave a i5-year history of bronchitis and recurrent chest infections. These were becoming more frequent and more severe and when seen he had lost 7 lb. in weight and had a recrudescence of pulmonary infection that was proving slow to respond to antibiotics. Chest X-ray showed an opacity in the left upper lobe. This was considered to be a virus pneumonia and periodic observation was recommended. In October I963 the patient was seen again complaining of generalized itching. He was noted to have well marked brownish pigmentation of the nipples, umbilicus, perianal region, and perineum. Discrete, firm, deeply pigmented warty excrescences were present symmetrically in the axill~e and on the forearms. All the pigmented areas itched and although the patient had not noticed the pigmentation he was able to recall that the warty lesions had appeared 2 months previously. A clinical diagnosis of acanthosis nigricans was made and one of the warty lesions was taken for histological examination. Histologically this showed localized hyperkeratosis, acanthosis, and basal pigmentation, confirming the diagnosis of acanthosis nigricans (Fig. I). The patient was found to be gaining weight and a new chest X-ray was reported as being clear. Although given a follow-up appointment the patient did not reattend as he felt well enough to return to work. The patient was not seen again until March 1964, when he returned with a chest infection. The chest X-ray now showed what was considered to be a carcinoma at the left hilum. He was admitted to Park Hospital, Davyhulme, where bronchoscopy confirmed the presence of a carcinoma obstructing the left upper lobe bronchus. Thoracotomy was performed in April I964. Because of carcinomatous infiltration of the hilar nodes and of the left lower lobe, left pneumonectomy was carried out, with dissection of the involved paraortic glands. (Receivedfor publication, Wo~ember 1964)
48
F o x AND GUNN
The resected lung showed a tumour obstructing the left upper lobe bronchus - - t h e upper lobe beyond the tumour was consolidated. Sections of the tumour showed this to be a poorly differentiated squamous cell carcinoma. Metastatic tumour was present in the hilar lymph nodes. The patient died on the seventh day after operation. Autopsy by Dr. B. L. Williams showed no residual tumour in the chest, nor were there metastatic deposits elsewhere in the body. There was no other tumour, and in particular the gastro-intestinal tract was normal. There was a purulent pericarditis and a left hydropneumothorax. Discussion
Acanthosis nigricans was first described by Pollitzer in 1890. In this condition there are areas of brown or black pigmentation and papillary hypertrophy. Nodules, papillomatous growths, or diffuse warty excrescences are found in the pigmented areas. The lesions are usually symmetrical and occur most commonly in the axillm, the neck, the external genitalia, and the groins. Less commonly the inner aspects of the thighs, the forearms, the flexor surface of the elbows, the umbilical area, the face and perianal area are involved. Lesions of the hands, breasts or buttocks are rare. Occasionally the whole skin surface may be involved, and lesions of the mucous membranes of the mouth, oesophagus, vagina and anus have also been recorded (Curth et al., 1962). On histological examination absolute and relative hyperkeratosis, acanthosis, and pigmentation of the basal layer of the epidermis are seen. The dermal papilla~ are hypertrophied and this may give an impression of epithelial atrophy. Pigment containing melanophores and a mild degree ofperivascular lymphocytic infiltration may be seen in the dermis. The condition may be subdivided into three subgroups: (Curth, 1936, 195 I, and 1952) : I. Benign acanthosis nigricans. 2. Malignant acanthosis nigricans. 3. Pseudo-acanthosis nigricans. There is no macroscopic or microscopic difference between the benign and malignant varieties of the disease. The benign type, however, appears either in childhood or at puberty; after puberty the lesions either become stationary or else subside. This type of lesion is not associated with malignant disease. The malignant variant of acanthosis nigricans appears for the first time in adult life and is always associated with an internal carcinoma. The skin lesions may precede the discovery of the tumour by several years (Gunn and Fox, 1964) ; may appear at the same time as the tumour, or may not appear until after the tumour has become clinically apparent. As the tumour grows, the skin lesions usually become both more numerous and more deeply pigmented. Removal of the tumour may occasionally produce partial or complete regression of the skin lesion and development of metastatic deposits may be heralded by a fresh crop of lesions. Incomplete forms of malignant acanthosis nigricans have been described (Snedden and Roberts, 1962) in which the lesions present solely on the
PLATE V
FIG. I.--Biopsy of skin lesion. This shows the typical histological appearances of acanthosis nigricans. (H & E X 9o)
To face p. 48.
ACANTHOSIS NIGRICANS AND BRONCHIAL CARCINOMA
49
limbs as small itching warts which rapidly become pigmented. The third variant of acanthosis nigricans is pseudo-acanthosis nigricans. This is found in fat women and is related to obesity. The skin lesions appear with weight gain and disappear with weight loss. Histologically the changes in pseudo-acanthosis nigricans are similar to those of true acanthosis nigricans b u t are less pronounced. There is no association between this lesion and malignant disease. Although acanthosis nigricans has been reported in association with a wide variety of tumours, the vast majority of cases have been gastro-intestinal carcinomata--and particularly gastric tumours. The first case to be reported in association with a bronchial carcinoma was that of Petrini de Galatz in IgI 4, and in the same year Dore briefly mentioned a case during a discussion at the Royal Society of Medicine. Since that date only six more cases of this association have been reported (Levin and Behrman, i942; Ellenbogen, I949; Spear, i95o; Curth et al., I962 ). Curth (i953) has suggested that the tumour is invariably an adenocarcinoma. Adenocarcinoma is a relatively rare form of bronchial carcinoma and it would help to explain the rarity of the association with acanthosis nigricans. In the case we report, however, there is no doubt that the tumour was a squamous cell carcinoma. No details of the histological appearances of the primary tumour are recorded in the cases described by Dore, Petrini de Galatz, and Levin and Behrman. O f the two cases reported by Ellenbogen one was an anaplastic tumour and the other an adenocarcinoma. Spear's case was an anaplastic carcinoma and both of Curth's cases were mucus secreting adenocarcinomata. It seems therefore that the bronchial tumour may be any of the common histological types--though the case in this paper appears to be the first reported one of squamous cell carcinoma. Acanthosis nigricans may be much more common than is generally thought (Gunn and Fox, I964) , and cases may be unnoticed amidst the more prominent visceral symptoms produced by the carcinoma. If acanthosis nigricans is recognized it should be a signal for immediate investigation for malignant disease. In the case we have reported acanthosis nigricans was diagnosed five months before the diagnosis of bronchial carcinoma was confirmed. O n reviewing the X-rays it is clear that there was in fact some evidence o f a hilar carcinoma in the X-ray film taken shortly before the skin lesions appeared. If bronchoscopy had been undertaken at the time at which the diagnosis of acanthosis nigricans was made the patient might have come to operation at a much earlier stage of his disease.
Summary A case of acanthosis nigricans in association with bronchial carcinoma is reported. Previous examples of this association are reviewed and the significance of acanthosis nigricans is discussed. ACKNOWLEDGEMENTS We would like to thank Mr. W. K. Douglas of Park Hospital, Davyhulme for permission to quote the surgical findings in this case: Dr. B. L. Williams for the autopsy report and Dr.
5°
FOX AND GUNN
J. G. Goburn of the Manchester and Salford Hospital for Skin Disease for reviewing the histological sections of the skin lesions. We are indebted to Mr. B. W. Figg of the Department of Obstetrics, Manchester University for the photomicrograph. REFERENCES
GURTH, H. O. (1936). Arch. Derm. Syph., 34, 353GURTH, H. O. (i951). Ann. Derm. Syph. (Paris), 78, 417. CugwH, H. O. (1952). Arch. Derm., 66, 80. CURTH, H. O., HILLBERG, A. W., • MAGHACHEK,G. F. (1962). Cancer, 15, 364 . DOPE, S. E. (1914). Brit. J. Derm., 26, 94. ELLnNBOG~N, B. K. (1949). Brit. 07. Derm., 61, 251. GALATZ, P. D~ (1914). Ann. Derm. Syph. (Paris), 5, 32I. GUNN, A. D. G. & Fox, H. (1964). Practitioner, I92, 396. LEVlN, O. L. & BEHRMAN, H. T. (I962). Arch. Derm. Syph. (Chic.), 46, 54. POLLITZER, S.(I890 ). In Internatlonal Atlas ofRare Skin Diseases, ed. M. Morris, P. G. Unna, H. Leloir and L. A. Duhring. No. XI. London, Lewis. SNEDDON, I. B. & ROBERTS, J . B. M. (I962). Gut, 3, 269.
ACANTHOSIS NIGRICANS AND BRONCHIAL CARCINOMA BY H. Fox Department of Pathology, University of Manchester AND
A~.~XANDER D. G. GuNN Darbishire House Health Centre, Manchester
ACANTHOSIS nigricans may occur together with a gastro-intestinal adenocarcinoma (Curth et al., 1962) and a few cases of acanthosis nigricans occurring together with a bronchial carcinoma have been reported. Another example of this association is reported and the cases previously recorded are reviewed.
Case Report A man of 57 was seen in September i963. He gave a i5-year history of bronchitis and recurrent chest infections. These were becoming more frequent and more severe and when seen he had lost 7 lb. in weight and had a recrudescence of pulmonary infection that was proving slow to respond to antibiotics. Chest X-ray showed an opacity in the left upper lobe. This was considered to be a virus pneumonia and periodic observation was recommended. In October I963 the patient was seen again complaining of generalized itching. He was noted to have well marked brownish pigmentation of the nipples, umbilicus, perianal region, and perineum. Discrete, firm, deeply pigmented warty excrescences were present symmetrically in the axill~e and on the forearms. All the pigmented areas itched and although the patient had not noticed the pigmentation he was able to recall that the warty lesions had appeared 2 months previously. A clinical diagnosis of acanthosis nigricans was made and one of the warty lesions was taken for histological examination. Histologically this showed localized hyperkeratosis, acanthosis, and basal pigmentation, confirming the diagnosis of acanthosis nigricans (Fig. I). The patient was found to be gaining weight and a new chest X-ray was reported as being clear. Although given a follow-up appointment the patient did not reattend as he felt well enough to return to work. The patient was not seen again until March 1964, when he returned with a chest infection. The chest X-ray now showed what was considered to be a carcinoma at the left hilum. He was admitted to Park Hospital, Davyhulme, where bronchoscopy confirmed the presence of a carcinoma obstructing the left upper lobe bronchus. Thoracotomy was performed in April I964. Because of carcinomatous infiltration of the hilar nodes and of the left lower lobe, left pneumonectomy was carried out, with dissection of the involved paraortic glands. (Receivedfor publication, Wo~ember 1964)
48
F o x AND GUNN
The resected lung showed a tumour obstructing the left upper lobe bronchus - - t h e upper lobe beyond the tumour was consolidated. Sections of the tumour showed this to be a poorly differentiated squamous cell carcinoma. Metastatic tumour was present in the hilar lymph nodes. The patient died on the seventh day after operation. Autopsy by Dr. B. L. Williams showed no residual tumour in the chest, nor were there metastatic deposits elsewhere in the body. There was no other tumour, and in particular the gastro-intestinal tract was normal. There was a purulent pericarditis and a left hydropneumothorax. Discussion
Acanthosis nigricans was first described by Pollitzer in 1890. In this condition there are areas of brown or black pigmentation and papillary hypertrophy. Nodules, papillomatous growths, or diffuse warty excrescences are found in the pigmented areas. The lesions are usually symmetrical and occur most commonly in the axillm, the neck, the external genitalia, and the groins. Less commonly the inner aspects of the thighs, the forearms, the flexor surface of the elbows, the umbilical area, the face and perianal area are involved. Lesions of the hands, breasts or buttocks are rare. Occasionally the whole skin surface may be involved, and lesions of the mucous membranes of the mouth, oesophagus, vagina and anus have also been recorded (Curth et al., 1962). On histological examination absolute and relative hyperkeratosis, acanthosis, and pigmentation of the basal layer of the epidermis are seen. The dermal papilla~ are hypertrophied and this may give an impression of epithelial atrophy. Pigment containing melanophores and a mild degree ofperivascular lymphocytic infiltration may be seen in the dermis. The condition may be subdivided into three subgroups: (Curth, 1936, 195 I, and 1952) : I. Benign acanthosis nigricans. 2. Malignant acanthosis nigricans. 3. Pseudo-acanthosis nigricans. There is no macroscopic or microscopic difference between the benign and malignant varieties of the disease. The benign type, however, appears either in childhood or at puberty; after puberty the lesions either become stationary or else subside. This type of lesion is not associated with malignant disease. The malignant variant of acanthosis nigricans appears for the first time in adult life and is always associated with an internal carcinoma. The skin lesions may precede the discovery of the tumour by several years (Gunn and Fox, 1964) ; may appear at the same time as the tumour, or may not appear until after the tumour has become clinically apparent. As the tumour grows, the skin lesions usually become both more numerous and more deeply pigmented. Removal of the tumour may occasionally produce partial or complete regression of the skin lesion and development of metastatic deposits may be heralded by a fresh crop of lesions. Incomplete forms of malignant acanthosis nigricans have been described (Snedden and Roberts, 1962) in which the lesions present solely on the
PLATE V
FIG. I.--Biopsy of skin lesion. This shows the typical histological appearances of acanthosis nigricans. (H & E X 9o)
To face p. 48.
ACANTHOSIS NIGRICANS AND BRONCHIAL CARCINOMA
49
limbs as small itching warts which rapidly become pigmented. The third variant of acanthosis nigricans is pseudo-acanthosis nigricans. This is found in fat women and is related to obesity. The skin lesions appear with weight gain and disappear with weight loss. Histologically the changes in pseudo-acanthosis nigricans are similar to those of true acanthosis nigricans b u t are less pronounced. There is no association between this lesion and malignant disease. Although acanthosis nigricans has been reported in association with a wide variety of tumours, the vast majority of cases have been gastro-intestinal carcinomata--and particularly gastric tumours. The first case to be reported in association with a bronchial carcinoma was that of Petrini de Galatz in IgI 4, and in the same year Dore briefly mentioned a case during a discussion at the Royal Society of Medicine. Since that date only six more cases of this association have been reported (Levin and Behrman, i942; Ellenbogen, I949; Spear, i95o; Curth et al., I962 ). Curth (i953) has suggested that the tumour is invariably an adenocarcinoma. Adenocarcinoma is a relatively rare form of bronchial carcinoma and it would help to explain the rarity of the association with acanthosis nigricans. In the case we report, however, there is no doubt that the tumour was a squamous cell carcinoma. No details of the histological appearances of the primary tumour are recorded in the cases described by Dore, Petrini de Galatz, and Levin and Behrman. O f the two cases reported by Ellenbogen one was an anaplastic tumour and the other an adenocarcinoma. Spear's case was an anaplastic carcinoma and both of Curth's cases were mucus secreting adenocarcinomata. It seems therefore that the bronchial tumour may be any of the common histological types--though the case in this paper appears to be the first reported one of squamous cell carcinoma. Acanthosis nigricans may be much more common than is generally thought (Gunn and Fox, I964) , and cases may be unnoticed amidst the more prominent visceral symptoms produced by the carcinoma. If acanthosis nigricans is recognized it should be a signal for immediate investigation for malignant disease. In the case we have reported acanthosis nigricans was diagnosed five months before the diagnosis of bronchial carcinoma was confirmed. O n reviewing the X-rays it is clear that there was in fact some evidence o f a hilar carcinoma in the X-ray film taken shortly before the skin lesions appeared. If bronchoscopy had been undertaken at the time at which the diagnosis of acanthosis nigricans was made the patient might have come to operation at a much earlier stage of his disease.
Summary A case of acanthosis nigricans in association with bronchial carcinoma is reported. Previous examples of this association are reviewed and the significance of acanthosis nigricans is discussed. ACKNOWLEDGEMENTS We would like to thank Mr. W. K. Douglas of Park Hospital, Davyhulme for permission to quote the surgical findings in this case: Dr. B. L. Williams for the autopsy report and Dr.
5°
FOX AND GUNN
J. G. Goburn of the Manchester and Salford Hospital for Skin Disease for reviewing the histological sections of the skin lesions. We are indebted to Mr. B. W. Figg of the Department of Obstetrics, Manchester University for the photomicrograph. REFERENCES
GURTH, H. O. (1936). Arch. Derm. Syph., 34, 353GURTH, H. O. (i951). Ann. Derm. Syph. (Paris), 78, 417. CugwH, H. O. (1952). Arch. Derm., 66, 80. CURTH, H. O., HILLBERG, A. W., • MAGHACHEK,G. F. (1962). Cancer, 15, 364 . DOPE, S. E. (1914). Brit. J. Derm., 26, 94. ELLnNBOG~N, B. K. (1949). Brit. 07. Derm., 61, 251. GALATZ, P. D~ (1914). Ann. Derm. Syph. (Paris), 5, 32I. GUNN, A. D. G. & Fox, H. (1964). Practitioner, I92, 396. LEVlN, O. L. & BEHRMAN, H. T. (I962). Arch. Derm. Syph. (Chic.), 46, 54. POLLITZER, S.(I890 ). In Internatlonal Atlas ofRare Skin Diseases, ed. M. Morris, P. G. Unna, H. Leloir and L. A. Duhring. No. XI. London, Lewis. SNEDDON, I. B. & ROBERTS, J . B. M. (I962). Gut, 3, 269.