CASE REPORT Malignant Acanthosis Nigricans Associated with Squamous Cell Carcinoma of Bronchus H. P. Gautam, M.S., F.R.C.S. M alignant acanthosis nigricans is actually a misnomer, as the dermatosis itself never assumes a malignant character. Nevertheless, it is a useful term referring to the association of the dermatosis with a malignant internal tumor. Malignant acanthosis nigricans is a cancer clue of such reliability that if one is confronted with an adult who has recently developed this dermatosis, one can state with certainty that the patient has already had or will soon have an internal carcinoma. Although it has been associated with usual sites of primary carcinoma, in over 90% of cases the neoplasm is intraabdominal, and in at least 60% it is gastric in origin [3]. The histology of the cancer is not unique but seems to fall into one pattern-adenocarcinoma-in spite of the various sites of the origin of the tumor [4]. However, there are well-documented cases of malignant acanthosis nigricans associated with lymphoma [13, 141, sarcoma [l], and squamous cell carcinoma [2, 4, 7,9, 111. Bronchial carcinoma associated with acanthosis nigricans was first reported by Pertrini de Galatz [8]. Since then, 8 more cases of this association have been described [4, 6, 7, 10, 12, 151. No details of the histological features of the primary tumor are known in the cases of de Galatz [8], Levin and Behrman [lo], and Readett and Glyn Hughs [12]. Of the From the Department of Thoracic Surgery, Royal Infirmary, Manchester, England. The author would like to thank Mr. W. F. Nicholson and Dr. M. Garretts for the permission to publish the details of this case. -4ccepted for publication Nov. 22, 1968. VOL. 7, NO. 5, MAY, 1969 481
GAUTAM two Ellenboger cases [6], 1 was adenocarcinoma and the other an anaplastic tumor. Spear s case [15] was an anaplastic carcinoma, and both the cases of Curth and associates [4] were mucus-secreting adenocarcinomas. Fox and Gunn [7] described the first and only case of squamous cell carcinoma of bronchus associated with acanthosis nigricans. Adding to the 9 total cases, including the 1 of squamous cell carcinoma reported to date, the clinical features of 1 further case of squamous cell carcinoma of bronchus associated with malignant acanthosis nigricans are presented. W. P., a 65-year-old man, attended the dermatological outpatient clinic in June, 1968. For the previous six months he had noticed a progressive roughness and thickening of his palms and the appearance of warty lesions on the backs of his hands. He was a heavy smoker and had no symptoms apart from the dermatosis. Discrete, firm, and pigmented warty excrescences were present on the backs of his hands and the flexure surface of the forearms. There was diffuse symmetrical yellowish brown hyperkeratosis of fingers, palms, soles, and feet, accompanied by intense itching (Figure). The oral cavity was normal, but there was slight pigmentation in the perineal region. Clinically, the patient had marked finger clubbing and poor air entry in the left lower chest. Supraclavicular lymph nodes were not enlarged, and no intraabdominal mass was discovered. Chest x-ray revealed a large lobulated mass in the region of the left lower lobe. Bronchoscopy showed a narrow and relatively fixed left main and lower lobe bronchus, with thickened and congested mucosa. No direct evidence of a growth was seen. An exploratory left thoracotomy was performed in July. A large growth occupying the center of the lower lobe was found. The upper lobe was found on palpation to contain numerous small hard nodules about the size of a big pea. Left paratracheal, tracheobronchial, and subcarcinal lymph nodes were enlarged and involved in the growth. An extrapericardial palliative pneumonectomy was performed. Many involved lymph nodes were removed en bloc with the specimen, but most of the subcarcinal mass was left behind, as it was intimately blended with Hyperkeratosis of fingers, palm, and sole. 482., THE ANNALS OF THORACIC SURGERY
CASE REPORT: Acanthosis Nigricans with Bronchogenic Carcinoma outer coats of the esophagus. On microscopic examination, the tumor was seen as a poorly differentiated squamous cell carcinoma. Multiple nodules in the upper lobe were secondary deposits of the tumor, and the lymph nodes contained metastatic carcinoma. The patient made a good recovery following the operation. There was a marked initial improvement in his symptoms, and a regression in dermatosis was noted. A chest x-ray just before his discharge showed the appearance of two discrete metastatic shadows in the region of the right upper lobe. When last seen, he was well, asymptomatic, and had no itching; although he had residual persistent dermatosis, this was of such little significance that he was not much bothered with it. The last chest x-ray showed appearance of a few more secondary deposits in the right lung field. DISCUSSION Acanthosis nigricans has been known to occur in all races and in most parts of the world [3]. The clinical features of benign and malignant acanthosis nigricans are similar in most respects and differ only in degree and extent. Benign acanthosis nigricans may be present at birth or may appear later in childhood or, more commonly, at puberty. If it appears before, it becomes more intensified at puberty. The activation of the cutaneous process is probably due to hormonal inbalance occurring at puberty. After puberty, it either subsides or becomes stationary. Usually, it is not accompanied by any endocrine disorders or obesity. A variant of the benign condition is a pseudoacanthosis nigricans. It is found in obese individuals. Obesity may have a nutritional, constitutional, or endocrine basis, and the dependence of the dermatosis on obesity is obvious, as the lesion starts at the development of pronounced obesity and disappears with the patient s return to normal weight. The incidence of the malignant form increases with advancing age and is particularly high in persons over the age of 40. Occasionally, it has been noted to occur in younger persons, even in children [3]. A symmetrical verrucose and papillary quality together with varying degrees of pigmentation limited in particular to flexural areas are the cardinal cutaneous findings. Pigmentation is variable and is usually of moderate intensity and limited to the site of involvement. Hyperkeratosis of palms and soles and intense pruritis, as observed in the reported case, frequently accompany the malignant variety. Involvement of oral and other mucus membranes, though not noticed in this case, has been estimated to occur in 50% of cases of both varieties [2]. The histological picture presents a distinctive pattern based on the presence of hyperkeratosis, papillomatosis, and the areas of acanthosis that frequently alternate with areas of atrophy. The outstanding feature of malignant acanthosis nigricans is its association with an internal malignant tumor, which in most instances appears to have a direct influence on the dermatosis. With regard to the sequence of events, the dermatosis may appear either before, at the time VOL. 7, NO. 5, MAY, 1969 483
GAUTAM of, or even after the manifestation of cancer. The lesions usually regress or may completely disappear [2] after excision or irradiation of the primary tumor and may reappear when metastases develop. This observation justifies the conclusion that the tumor possesses properties that activate the dermatosis. It is entirely possible, however, that these as yet unidentified properties of the tumor are essential for even the earliest beginning of the dermatosis. A hypothetical substance secreted by the tumor may incite the skin to form acanthosis nigricans. This substance is effective in either small or large quantities. Its qualitative or quantitative thresholds may, in some instances, be reached at such an early stage of tumor growth that any clinical signs of the cancer are still absent, and in other instances may occur so late that the cancer has already become clinically evident. In the reported case, regression of the dermatosis was evident after palliative pneumonectomy for carcinoma, but its persistence may well be due to the growth left behind in the mediastinal lymph nodes and to the development of secondary deposits in the contralateral lung. The associated tumor is usually highly malignant, which is evidenced by its early metastasis, inoperability, and a fatal outcome after a relatively short time. The only recorded five-year survival is in a patient with an adenocarcinoma of the ovary [5]. Whether an association with acanthosis nigricans makes the tumor more malignant or the tumor itself is more invasive is not known. SUMMARY Malignant acanthosis nigricans is a reliable and occasionally an early clue to an internal malignancy. Clinical features of a case of squamous cell carcinoma of bronchus associated with malignant acanthosis nigricans are described. The tumor is usually highly malignant, with early metastasis, and carries a poor prognosis. REFERENCES 1. Belisario, J. C. Cancer of the Skin. London: Butterworth, 1959. P. 35. 2. Brown, J., and Winkelmann, R. K. Acanthosis nigricans. Medicine (Balt.) 47:33, 1968. 3. Curth, H. 0. Cancer associated with acanthosis nigricans. Review of literature and report of a case of acanthosis nigricans with cancer of the breast. Arch. Surg. 47:517, 1943. 4. Curth, H. O., Hilberg, A. W., and Machacek, G. F. The site and histology of the cancer associated with malignant acanthosis nigricans. Cancer 15: 364, 1962. 5. Dingley, E. R., and Marten, R. H. Adenocarcinoma of ovary presenting as acanthosis nigricans. J. Obstet. Gynaec. Brit. Comm. 64:898, 1957. 6. Ellenboger, B. K. Acanthosis nigricans associated with bronchial carcinoma, report of two cases. Brit. J. Derm. 61:251, 1949. 484 THE ANNALS OF THORACIC SURGERY
CASE REPORT: Acanthosis Nigricans with Bronchogenzc Carcinoma 7. 8. 9. 10. 11. Fox, H., and Gunn, A. D. G. Acanthosis nigricans and bronchial carcinoma. Brit. J. Dis. Chest 59:47, 1965. Galatz, P. de. Contribution A 1 Ctude clinique et histopathologique de la dystrophie pappillaire et pigmentaire (acanthosis nigricans) associc a un cancer pulmonaire. Ann. Derrn. Syph. (Paris) 5:321, 1914. Ive, F. A. Metastatic carcinoma of cervix with acanthosis nigricans, bullous pemphigoid and hypertrophic pulmonary osteoarthropathy. Proc. Roy. SOC. Med. 56:910, 1963. Levin, 0. L., and Behrman, H. T. Acanthosis nigricans associated with carcinoma of the lung. Arch. Derm. 46:54, 1942. Miller, T. R., and Davis, J. D. Acanthosis nigricans occurring in association with squamous cell carcinoma of hypopharynx. New York J. Med. 54:2333, 1954. Readett, M. D., and Glyn Hughs, F. Extensive acanthosis nigricans with bronchial carcinoma. Arch. Derm. (Chicago) 83:850, 1961. 12. 13. Rosenberg, S. A., Diamond, H. D., Jaslowitz, B., and Craven, L. F. Lymphosarcoma. A review of 1269 cases. Medicine (Balt.) 40:31, 1961. 14. Sanderson, K. V. Hodgkins disease. Acanthosis nigricans and tinea of the palms and soles and nails. Proc. Roy. SOC. Med. 55:960, 1962. 15. Spear, P. W. Acanthosis nigricans associated with carcinoma of lung. J. Thorac. Surg. 20:304, 1950. NOTICE FROM THE SOCIETY OF THORACIC SURGEONS Abstracts for papers to be presented at the 1970 Annual Meeting of The Society of Thoracic Surgeons are now being accepted. The meeting is to be held at the Regency Hyatt House, Atlanta, Georgia, January 12-14, 1970. The deadline for receipt of abstracts is September 15, 1969. An original and eight copies should be submitted to John C. Callaghan, M.D. (Chairman, Program Committee) 8409 112th Street, Suite 550, Edmonton, Alberta, Canada. Abstracts must summarize an original contribution not presented or submitted elsewhere. It must not exceed 200 words in length. Abstracts received after the deadline or exceeding 200 words will not be considered. The program committee reserves the right to select papers for either regular or forum-type presentations. Essayists are reminded that the complete manuscript must be submitted in duplicate either to the Editor of The Annals of Thoracic Surgery before the meeting or to the Secretary of the Society at the meeting, immediately prior to presentation. RALPH D. ALLEY, M.D. Secretary