Report
Florid Cutaneous Papillomatosis, Malignant Acanthosis Nigricans, and Pulmonary Squamous Cell Carcinoma Patrick Gheeraert, M,D,, Jean Goens, M,D., Robert A. Schwartz, M,D,, M,P,H,, W, Clark Lambert, M,D,, Ph,D,, Fabienne Schroeder, M,D., and L, Debusscher, M,D,
Abstract: A 72-year-old man had florid cutaneous papillomatosis (FCP), which is an obligatory paraneoplastic syndrome always associated with an internal malignancy. The cancer, • which is usually intraabdominal and most often gastric in origin, evolves parallel to the FGP. This patient is the first case of FCP occurring In association with a lung malignancy. An association of FCP with other signs of internal cancer is common, with malignant acanthosis nigricans usually appearing many times with the sign of Leser-Trelat. FCP, malignant acanthosis nigricans, and the sign of Leser-Trelat are part of a continuum, developing by a common or similar pathogenic pathway due to an underlying malignancy producing a factor possibly similar to human epidermal growth factor.
Florid cutaneous papillomatosis (FCP) is a disease consisting of the rapid onset of numerous warty papules indistinguishable clinically from viral warts.'"'' These lesions develop on the trunk and extremities. FCP has been described in association with malignant aeanthosis nigricans and internal malignancy. We report a case associated with malignant acanthosis nigricans and a squamous cell carcinoma ofthe lungs. Report of a Case • A 72-year-old man was evaluated in December 1985 for the onset of multiple pruritic warty papules located predominately on the back of his hands and wrists, back, thighs, and knees of 3 months duration (Fig, 1), The papules gradually increased in size and number. He also noted fatigue, anorexia, and a weight loss of 12 kg in the previous year. Many years earlier he had a partial resec-
From the Departments of Dermatology, University Hospital SaintPierre, Brussels, Belgium, and New Jersey Medical School, Newark, New Jersey, and Institute J, Bordet, Brussels, Belgium, Address correspondence to: Robert A, Schwartz, M,D., Department of Dermatology, New Jersey Medieal School, 185 South Orange Avenue, Newark, NJ 07103-2757, March 1991, Vol. 30, No. 3
tion of the small bowel after a traumatic injury during an automobile accident. He also had a thyroidectomy. He smoked 20 cigarettes or more each day for over 50 years. Physical examination showed the presence of multiple papillomatous verrucous lesions. The largest lesions were up to 1 cm in diameter and were indistinguishable from viral warts. The smallest of them were 2-3 mm in diameter. There was also a diffuse palmoplantar keratoderma (Fig, 2), Multiple skin biopsies from these papillomas showed orthokeratotic hyperkeratosis, acanthosis, and papillomatosis (Fig, 3), There were no signs of viral inclusions or vacuolar degeneration of keratinocytes, Congo red staining was negative for amyloid, Ultrastructural microscopy also excluded the presence of viral inclusions and amyloid deposits, Papillomavirus serology was negative. Initial laboratory evaluation was remarkable for a sedimentation rate of 50 mm/h, fibrinogen (538 mg/dl), C reactive protein (4,45 mg/dl), immunoglobulin G (2,075 mg/dl), and mottled ANA (1/2,500). A serum immunoelectrophoresis showed a monoclonal kappa component. Urinary sediment examination showed kappa and lambda light chain traces. Chest, skull, and upper gastrointestinal roentgenograms were normal at this time. This first evaluation did not allow us to detect any internal malignancy despite a strong clinical suspicion and the suggestive paraneoplastic nature of the cutaneous lesions. The patient was interpreted as having only a benign monoclonal gammapathy. He was treated with etretinate 1 mg/kg/day for 1 month to improve his cutaneous hyperkeratotic lesions, but there was no benefit on the eruption or on his pruritus. Six months later, in July 1986, the patient reappeared complaining of deteriorating health and mental depression. His skin lesions were unchanged, except for the onset of velvety brown hyperkeratotic papillomatous papules in the axillary folds typical of acanthosis nigricans (Fig. 4). His gammopathy remained stable, but his chest roentenogram, chest CAT scan, mediastinoscopy, 193
194
International Journal of Dermatology • March 1991
Vol. 30
Figure 3, Histology of a warty papule, showing orthokeratotic hyperkeratosis, acanthosis, and papillomatosis (H&E, original magnilication X400), Figure 1, Myperkeratotic warty lesions on the back of the hands. Some of them are excoriated because of intense pruritus.
and bronchial fibroscopy with biopsy disclosed the presence of a sqtiamous cell carcinoma of right middle lobe with massive mediastinal involvement. Because the ttimor was considered tinresectable, the patient was started on radiotherapy with no significant clinical improvement of either the tumor or the cutaneous lesions. The patient died 9 months later from a secondary bacterial infection.
more commonly affected than women (14 men/9 women). In 20 of 23 patients, the diagnosis was made between 53 and 72 years of age (mean age, 58,5 years). Each patient had an underlying cancer, the most common being a gastric adenocarcinoma (15 of 23). One patient also had a second cancer, breast adenocarcinoma.^'' Of the eight remaining patients, 4 were associated with another intraabdominal tumor (urinary bladder, biliary ducts, ovary, uterus), 1 with a breast adenocarcinoma, 1 with a squarnous carcinotna of the lung, 1 with non-Hodgkin lymphoma,'^ and one
Discussion Florid cutaneous papillomatosis (FCP) is a rare condition.^"'' We have identified 22 cases in the literature (Table i),2.5-17,22-25 ^^^^ f^^.^^ ^^^^^ Pollitzer's description in 1891,^ In 1978 the name florid cutaneous papillomatosis was coined.^ Men appear to be two times
Figure 2. Velvety hyperkeratosis of the palms.
Figure 4, Brown hyperkeratosis of the axillary folds suriounclcci by verrucous papillomas.
Florid Cutaneous Papillomatosis • Gheeraert et al.
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International Journal of Dermatology • March 1991
of unknown origin.^ A most noteworthy feature of FCP is that its onset often preceded the diagnosis of the internal tumor (10 of 23) or was simultaneous with it (6 of 23). Clinically, the lesions of FCP are usually indistinguishable from common viral warts. They begin on the extremities, particularly on the backs ofthe hands and wrists, but may disseminate to the entire body including the face. Pruritus is an important symptom (13 of 23 cases). It may precede the onset ofthe papillomas. It can be located at the affected areas or it can be generalized. The histologic features of the cutaneous papillomas are uniform and display a pronounced hyperkeratosis, acanthosis, and papillomatosis. There was no evidence of epidermal vacuolization, parakeratosis, or eosinophilic inclusions suggestive of viral warts, except in one study." Search for HPV in the skin papillomas by ultrastructural evaluation,^'"'-'•"''^-^^-^^ immunofluorescence study,'" viral serology,'" and DNA hybridization^^ was always negative. Therefore, a viral origin as suggested by Jablonska et al.," Jablonska,'" Knapp,'^ and Milian et al.^^ appears to be unlikely. As mentioned, FCP may occur together with other signs of internal cancer. Although acanthosis nigricans and the sign of Leser-Trelat (eruptive seborrheic keratoses) are most frequently associated, other signs can be seen: hypertrichosis lanuginosa acquisita,** vitiligo,'' and acquired ichthyosis.'" Despite a lack of long period follow-up in most of the cases, a marked improvement of the cutaneous lesions has been observed in seven patients after surgical or chemotherapeutic treatment of the internal cancer.^'"''^"^''*'^ In one case local recurrence ofthe tumor was associated with recurrence of cutaneous papillomas.'^ In three other cases generalization ofthe cancer was associated with severe worsening ofthe cutaneous lesions."'^'^^ Palliative treatment ofthe cutaneous papillomas, either systemic (oral retinoid therapy, radiotherapy, or smallpox vaccination) or topical (steroids, vitamin A acid, urea, salicylic acid, liquid nitrogen), did not lead to any significant improvement, except in one case with topical 5-fluorouracil.'' The etiology of FCP in unknown, just as is the case with the other two eruptive paraneoplastic syndromes often seen with it, malignant acanthosis nigricans and the sign of Leser-Trelat. It appears highly likely that these three paraneoplastic syndromes are directly induced by their underlying neoplasms, most likely by a tumor-secreted growth factor.'""*'"" Millard and Gould^" found in two cases with tylosis (one with the sign of Leser-Trelat) high levels of immunoreactive human growth hormone. Another patient was de-
Vol. 30
scribed with a small cutaneous melanoma, acanthosis nigricans, the sign of Leser-Trelat, and multiple "acrochordons" in whom the cutaneous paraneoplastic syndrome lesions showed stimulation by the epidermal growth factor receptor.^' Increased epidermal staining for the epidermal growth factor receptor was initially observed in skin specimens of acanthosis nigricans, seborrheic keratoses, and cutaneous papillomas; this staining and the urine level of a-transforming growth factor both declined markedly after surgical removal of the primary nonmetastatic melanoma. Alpha-transforming growth factor is a 6,000-dalton protein structurally related to, but antigenically distinct from, epidermal growth factor. References 1. Achten G, Ledoux-Corbusier M, Goens J. Autonomie nosologiquc el pathogenic des syndromes paraneoplasiques cutanes. Ann Med Interne (Paris). 1984; 135:646-653. 2. Schwartz RA, Burgess GH. Florid cutaneous papillomatosis. Arch Dermatol. 1978;! 14:1803-1806. 3. Schwartz RA. Acanthosis nigricans, florid cutaneous papillomatosis, and the sign of Leser-Trelat. Cutis. l98I;28:319-334. 4. Schwartz RA. Florid cutaneous papillomatosis. In: Demis DJ, ed. Clinical Dermatology. 17th ed. Philadelphia: Harper & Row, 1990:1-3. 5. Pollitzer S. Acanthosis nigricans. In: Unna PG, Morris M, Besnier E, et al., eds. International Atlas of Rare Skin Diseases. London: H.K. Lewis, 1891:1-3. 6. Andreev VC, Boyanov L, Tsankov N. Generalized acanthosis nigricans. Dermatologica. 1981;183:19-24. 7. Clarke J. Malignant acanthosis nigricans. Clin Exp Dermatol. 1977;2:I67-17O. 8. Dingley ER, Marten RH. Adenocarcinoma ofthe ovary presenting as acanthosis nigricans. J Obstet Gynaec Br Emp. 1957;64:898-900. 9. Forman L. Acanthosis nigricans with discrete warts and marked mucous membrane changes in a patient with vitiligo. Proc R Soc Med. 1943;36:611. 10. Hage E, Hage J. Malignant acanthosis nigricans: a para-endocrine syndrome? Acta Derm Venereol (Stockh). 1977;57:169172. 11. Jablonska S, Kozminska A, Chorzelski T. Eine ungewohnliche Variante von Akanthosis nigricans (Zusammenhang zwischen Akanthosis nigricans und generalisierter Verrukose). Dermatol Wochenschr. 1965;151:177-185. 12. Knapp A. Zur Frage der Entstehung der Akanthosis nigricans. Dermatol Wochenschr. 1957; 135:313-327. 13. Misch KJ, Griffiths WAD, Eady RAJ. Warts as a presenting sign in acanthosis nigricans. Clin Exp Dermatol. 1983;8:651-656. 14. Navaratnam A, Hodgson GA. Acanthosis nigricans with carcinoma ofthe stomach. Br J Dermatol. I973;89:(suppl 9)46-50. 15. Sneddon IB, Roberts JBM. An incomplete form of acanthosis nigricans. Gut. I962;3:269-272. 16. White H. Acanthosis nigricans and wart-like lesions associated with metastatic carcinoma ofthe stomach. Cutis. 1976;17:931933. 17. Janier M, Blanchet-Bardon C, Bonvalet D, et al. Malignant acanthosis nigricans associated with non-Hodgkin's lymphoma. Dermatologica. 1988; 176:133-137.
No. 3
Florid Cutaneous Papillomatosis • Gheeraert et al.
18. Jablbriska S. Rogowacenie ciemne (acanthosis nigricans) zwiastunem zlbsliwego bujania nowotworowego w narzgdach wewn?trznych. Pol Tyg Lek. 1965;20:1355-1357. 19. Abeloff MD. Paraneoplastic syndromes. A window on the biology of cancer. N Engl J Med. 1987;317:1598-1600. 20. Millard LG. Gould DJ. Hyperkeratosis of the palms and soles associated with internal malignancy and elevated levels of immunoreaetive human growth hormone. Clin Exp Dermatol. 1976;l:363-368. 21. Ellis DL, Kafka SP, Chow JC, et al. Melanoma, growth factors, acanthosis nigricans, the sign of Leser-Trelat, and multiple acrochordons: a possible role for alpha-transforming growth factor in cutaneous paraneoplastic syndromes. N Engl J Med. 1987;317:1582-1587.
197
22. Milian G, Perin L. Babalian D. Condylomatose acuminee en nappe et acanthosis nigricans. Bull Soc Fr Dermatol Syph. 1934;41:1914-1916. 23. Gross G, Pfister H, Hcllcnthal B. et al. Acanthosis nigricans maligna; clinical and virologieal investigations. Dermatologica. 1984;168:265-272. 24. Stieler W. Plewig G. Acanthosis nigricans maligna und LeserTrelat-Zeichen be: Doppelmalignom von Mamma und Magen. Z Hautkr. 1987;62:344-366. 25. De Backer J, Kint A. Malignant acanthosis nigricans with multiple verrucous formations. Arch Beiges Dermatol Syphil. l971;27:3l7-322.
A verrucous photo allergic reaction in the red pigment years atter the tattoo was applied, but a few weeks after the soldier exposed it to the sun at the Waikiki Beach. From the World of Tattoos coliection, Honolulu, HI. Submitted by Norman Goldstein, M.D., Honoluiu, HI.
Florid Cutaneous Papillomatosis, Malignant Acanthosis Nigricans, and Pulmonary Squamous Cell Carcinoma Patrick Gheeraert, M,D,, Jean Goens, M,D., Robert A. Schwartz, M,D,, M,P,H,, W, Clark Lambert, M,D,, Ph,D,, Fabienne Schroeder, M,D., and L, Debusscher, M,D,
Abstract: A 72-year-old man had florid cutaneous papillomatosis (FCP), which is an obligatory paraneoplastic syndrome always associated with an internal malignancy. The cancer, • which is usually intraabdominal and most often gastric in origin, evolves parallel to the FGP. This patient is the first case of FCP occurring In association with a lung malignancy. An association of FCP with other signs of internal cancer is common, with malignant acanthosis nigricans usually appearing many times with the sign of Leser-Trelat. FCP, malignant acanthosis nigricans, and the sign of Leser-Trelat are part of a continuum, developing by a common or similar pathogenic pathway due to an underlying malignancy producing a factor possibly similar to human epidermal growth factor.
Florid cutaneous papillomatosis (FCP) is a disease consisting of the rapid onset of numerous warty papules indistinguishable clinically from viral warts.'"'' These lesions develop on the trunk and extremities. FCP has been described in association with malignant aeanthosis nigricans and internal malignancy. We report a case associated with malignant acanthosis nigricans and a squamous cell carcinoma ofthe lungs. Report of a Case • A 72-year-old man was evaluated in December 1985 for the onset of multiple pruritic warty papules located predominately on the back of his hands and wrists, back, thighs, and knees of 3 months duration (Fig, 1), The papules gradually increased in size and number. He also noted fatigue, anorexia, and a weight loss of 12 kg in the previous year. Many years earlier he had a partial resec-
From the Departments of Dermatology, University Hospital SaintPierre, Brussels, Belgium, and New Jersey Medical School, Newark, New Jersey, and Institute J, Bordet, Brussels, Belgium, Address correspondence to: Robert A, Schwartz, M,D., Department of Dermatology, New Jersey Medieal School, 185 South Orange Avenue, Newark, NJ 07103-2757, March 1991, Vol. 30, No. 3
tion of the small bowel after a traumatic injury during an automobile accident. He also had a thyroidectomy. He smoked 20 cigarettes or more each day for over 50 years. Physical examination showed the presence of multiple papillomatous verrucous lesions. The largest lesions were up to 1 cm in diameter and were indistinguishable from viral warts. The smallest of them were 2-3 mm in diameter. There was also a diffuse palmoplantar keratoderma (Fig, 2), Multiple skin biopsies from these papillomas showed orthokeratotic hyperkeratosis, acanthosis, and papillomatosis (Fig, 3), There were no signs of viral inclusions or vacuolar degeneration of keratinocytes, Congo red staining was negative for amyloid, Ultrastructural microscopy also excluded the presence of viral inclusions and amyloid deposits, Papillomavirus serology was negative. Initial laboratory evaluation was remarkable for a sedimentation rate of 50 mm/h, fibrinogen (538 mg/dl), C reactive protein (4,45 mg/dl), immunoglobulin G (2,075 mg/dl), and mottled ANA (1/2,500). A serum immunoelectrophoresis showed a monoclonal kappa component. Urinary sediment examination showed kappa and lambda light chain traces. Chest, skull, and upper gastrointestinal roentgenograms were normal at this time. This first evaluation did not allow us to detect any internal malignancy despite a strong clinical suspicion and the suggestive paraneoplastic nature of the cutaneous lesions. The patient was interpreted as having only a benign monoclonal gammapathy. He was treated with etretinate 1 mg/kg/day for 1 month to improve his cutaneous hyperkeratotic lesions, but there was no benefit on the eruption or on his pruritus. Six months later, in July 1986, the patient reappeared complaining of deteriorating health and mental depression. His skin lesions were unchanged, except for the onset of velvety brown hyperkeratotic papillomatous papules in the axillary folds typical of acanthosis nigricans (Fig. 4). His gammopathy remained stable, but his chest roentenogram, chest CAT scan, mediastinoscopy, 193
194
International Journal of Dermatology • March 1991
Vol. 30
Figure 3, Histology of a warty papule, showing orthokeratotic hyperkeratosis, acanthosis, and papillomatosis (H&E, original magnilication X400), Figure 1, Myperkeratotic warty lesions on the back of the hands. Some of them are excoriated because of intense pruritus.
and bronchial fibroscopy with biopsy disclosed the presence of a sqtiamous cell carcinoma of right middle lobe with massive mediastinal involvement. Because the ttimor was considered tinresectable, the patient was started on radiotherapy with no significant clinical improvement of either the tumor or the cutaneous lesions. The patient died 9 months later from a secondary bacterial infection.
more commonly affected than women (14 men/9 women). In 20 of 23 patients, the diagnosis was made between 53 and 72 years of age (mean age, 58,5 years). Each patient had an underlying cancer, the most common being a gastric adenocarcinoma (15 of 23). One patient also had a second cancer, breast adenocarcinoma.^'' Of the eight remaining patients, 4 were associated with another intraabdominal tumor (urinary bladder, biliary ducts, ovary, uterus), 1 with a breast adenocarcinoma, 1 with a squarnous carcinotna of the lung, 1 with non-Hodgkin lymphoma,'^ and one
Discussion Florid cutaneous papillomatosis (FCP) is a rare condition.^"'' We have identified 22 cases in the literature (Table i),2.5-17,22-25 ^^^^ f^^.^^ ^^^^^ Pollitzer's description in 1891,^ In 1978 the name florid cutaneous papillomatosis was coined.^ Men appear to be two times
Figure 2. Velvety hyperkeratosis of the palms.
Figure 4, Brown hyperkeratosis of the axillary folds suriounclcci by verrucous papillomas.
Florid Cutaneous Papillomatosis • Gheeraert et al.
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International Journal of Dermatology • March 1991
of unknown origin.^ A most noteworthy feature of FCP is that its onset often preceded the diagnosis of the internal tumor (10 of 23) or was simultaneous with it (6 of 23). Clinically, the lesions of FCP are usually indistinguishable from common viral warts. They begin on the extremities, particularly on the backs ofthe hands and wrists, but may disseminate to the entire body including the face. Pruritus is an important symptom (13 of 23 cases). It may precede the onset ofthe papillomas. It can be located at the affected areas or it can be generalized. The histologic features of the cutaneous papillomas are uniform and display a pronounced hyperkeratosis, acanthosis, and papillomatosis. There was no evidence of epidermal vacuolization, parakeratosis, or eosinophilic inclusions suggestive of viral warts, except in one study." Search for HPV in the skin papillomas by ultrastructural evaluation,^'"'-'•"''^-^^-^^ immunofluorescence study,'" viral serology,'" and DNA hybridization^^ was always negative. Therefore, a viral origin as suggested by Jablonska et al.," Jablonska,'" Knapp,'^ and Milian et al.^^ appears to be unlikely. As mentioned, FCP may occur together with other signs of internal cancer. Although acanthosis nigricans and the sign of Leser-Trelat (eruptive seborrheic keratoses) are most frequently associated, other signs can be seen: hypertrichosis lanuginosa acquisita,** vitiligo,'' and acquired ichthyosis.'" Despite a lack of long period follow-up in most of the cases, a marked improvement of the cutaneous lesions has been observed in seven patients after surgical or chemotherapeutic treatment of the internal cancer.^'"''^"^''*'^ In one case local recurrence ofthe tumor was associated with recurrence of cutaneous papillomas.'^ In three other cases generalization ofthe cancer was associated with severe worsening ofthe cutaneous lesions."'^'^^ Palliative treatment ofthe cutaneous papillomas, either systemic (oral retinoid therapy, radiotherapy, or smallpox vaccination) or topical (steroids, vitamin A acid, urea, salicylic acid, liquid nitrogen), did not lead to any significant improvement, except in one case with topical 5-fluorouracil.'' The etiology of FCP in unknown, just as is the case with the other two eruptive paraneoplastic syndromes often seen with it, malignant acanthosis nigricans and the sign of Leser-Trelat. It appears highly likely that these three paraneoplastic syndromes are directly induced by their underlying neoplasms, most likely by a tumor-secreted growth factor.'""*'"" Millard and Gould^" found in two cases with tylosis (one with the sign of Leser-Trelat) high levels of immunoreactive human growth hormone. Another patient was de-
Vol. 30
scribed with a small cutaneous melanoma, acanthosis nigricans, the sign of Leser-Trelat, and multiple "acrochordons" in whom the cutaneous paraneoplastic syndrome lesions showed stimulation by the epidermal growth factor receptor.^' Increased epidermal staining for the epidermal growth factor receptor was initially observed in skin specimens of acanthosis nigricans, seborrheic keratoses, and cutaneous papillomas; this staining and the urine level of a-transforming growth factor both declined markedly after surgical removal of the primary nonmetastatic melanoma. Alpha-transforming growth factor is a 6,000-dalton protein structurally related to, but antigenically distinct from, epidermal growth factor. References 1. Achten G, Ledoux-Corbusier M, Goens J. Autonomie nosologiquc el pathogenic des syndromes paraneoplasiques cutanes. Ann Med Interne (Paris). 1984; 135:646-653. 2. Schwartz RA, Burgess GH. Florid cutaneous papillomatosis. Arch Dermatol. 1978;! 14:1803-1806. 3. Schwartz RA. Acanthosis nigricans, florid cutaneous papillomatosis, and the sign of Leser-Trelat. Cutis. l98I;28:319-334. 4. Schwartz RA. Florid cutaneous papillomatosis. In: Demis DJ, ed. Clinical Dermatology. 17th ed. Philadelphia: Harper & Row, 1990:1-3. 5. Pollitzer S. Acanthosis nigricans. In: Unna PG, Morris M, Besnier E, et al., eds. International Atlas of Rare Skin Diseases. London: H.K. Lewis, 1891:1-3. 6. Andreev VC, Boyanov L, Tsankov N. Generalized acanthosis nigricans. Dermatologica. 1981;183:19-24. 7. Clarke J. Malignant acanthosis nigricans. Clin Exp Dermatol. 1977;2:I67-17O. 8. Dingley ER, Marten RH. Adenocarcinoma ofthe ovary presenting as acanthosis nigricans. J Obstet Gynaec Br Emp. 1957;64:898-900. 9. Forman L. Acanthosis nigricans with discrete warts and marked mucous membrane changes in a patient with vitiligo. Proc R Soc Med. 1943;36:611. 10. Hage E, Hage J. Malignant acanthosis nigricans: a para-endocrine syndrome? Acta Derm Venereol (Stockh). 1977;57:169172. 11. Jablonska S, Kozminska A, Chorzelski T. Eine ungewohnliche Variante von Akanthosis nigricans (Zusammenhang zwischen Akanthosis nigricans und generalisierter Verrukose). Dermatol Wochenschr. 1965;151:177-185. 12. Knapp A. Zur Frage der Entstehung der Akanthosis nigricans. Dermatol Wochenschr. 1957; 135:313-327. 13. Misch KJ, Griffiths WAD, Eady RAJ. Warts as a presenting sign in acanthosis nigricans. Clin Exp Dermatol. 1983;8:651-656. 14. Navaratnam A, Hodgson GA. Acanthosis nigricans with carcinoma ofthe stomach. Br J Dermatol. I973;89:(suppl 9)46-50. 15. Sneddon IB, Roberts JBM. An incomplete form of acanthosis nigricans. Gut. I962;3:269-272. 16. White H. Acanthosis nigricans and wart-like lesions associated with metastatic carcinoma ofthe stomach. Cutis. 1976;17:931933. 17. Janier M, Blanchet-Bardon C, Bonvalet D, et al. Malignant acanthosis nigricans associated with non-Hodgkin's lymphoma. Dermatologica. 1988; 176:133-137.
No. 3
Florid Cutaneous Papillomatosis • Gheeraert et al.
18. Jablbriska S. Rogowacenie ciemne (acanthosis nigricans) zwiastunem zlbsliwego bujania nowotworowego w narzgdach wewn?trznych. Pol Tyg Lek. 1965;20:1355-1357. 19. Abeloff MD. Paraneoplastic syndromes. A window on the biology of cancer. N Engl J Med. 1987;317:1598-1600. 20. Millard LG. Gould DJ. Hyperkeratosis of the palms and soles associated with internal malignancy and elevated levels of immunoreaetive human growth hormone. Clin Exp Dermatol. 1976;l:363-368. 21. Ellis DL, Kafka SP, Chow JC, et al. Melanoma, growth factors, acanthosis nigricans, the sign of Leser-Trelat, and multiple acrochordons: a possible role for alpha-transforming growth factor in cutaneous paraneoplastic syndromes. N Engl J Med. 1987;317:1582-1587.
197
22. Milian G, Perin L. Babalian D. Condylomatose acuminee en nappe et acanthosis nigricans. Bull Soc Fr Dermatol Syph. 1934;41:1914-1916. 23. Gross G, Pfister H, Hcllcnthal B. et al. Acanthosis nigricans maligna; clinical and virologieal investigations. Dermatologica. 1984;168:265-272. 24. Stieler W. Plewig G. Acanthosis nigricans maligna und LeserTrelat-Zeichen be: Doppelmalignom von Mamma und Magen. Z Hautkr. 1987;62:344-366. 25. De Backer J, Kint A. Malignant acanthosis nigricans with multiple verrucous formations. Arch Beiges Dermatol Syphil. l971;27:3l7-322.
A verrucous photo allergic reaction in the red pigment years atter the tattoo was applied, but a few weeks after the soldier exposed it to the sun at the Waikiki Beach. From the World of Tattoos coliection, Honolulu, HI. Submitted by Norman Goldstein, M.D., Honoluiu, HI.
