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Sign of Leser-Trélat: Report of two cases and review of the literature
Sign of Leser-Tr61at: Report of two cases and review of the literature Pierre Y. Venencie, M.D.,* and Harold O. Perry, M.D.
Rochester, MN The sudden appearance of multiple seborrheic keratoses in the two patients could be related to adenocarcinoma of the breast. Despite other isolated reports, this disorder is still controversial as a marker of malignancy. (JAM ACAD DERMATOL10:83-88, 1984.)
From the Department of Dermatology, Mayo Clinic and Mayo Foundation. Accepted for publication May 3, 1983. Reprint requests to: Dr. P. Y. Vencncie, c/o Section of Publications, Mayo Clinic, Rochester, MN 55905. *A visiting clinician from the Clinique Dermatologique, Hbpital Saint-Louis, Paris, France,
In 1965, Ronchese I reported a case of multiple seborrheic keratoses occuning suddenly in a patient with uterine adenocarcinoma and credited two surgeons, a German, Edmund Leser (18531916), and a Frenchman, Ulysse Tr61at (18281890), for the hypothesis that the sudden appear-
Fig. 1. Case 1. A and B, Multiple seborrheic keratoses that appeared over a 3- to 4-week period 1 month after diagnosis of grade 3 metastatic adenocarcinoma of the breast. 83
84
Journal of the American Academy of Dermatology
Venencie and Pert 3'
Table I. Sign of Leser-Tr~lat: Summary o f the reported cases [ Source
Seborrheiekeratosis
Onset period
Sites involved
I Histology*
Josserand et al," 1948
F
32
Sudden
Mammary region
Schwartz, :3 1952
M
45
6 mo
Forearms
Dingley and Marten, 4 1957
F
56
"Sudden"
Trunk, arms, legs
Sneddon and Roberts, ~ 1962
M
46
Few mo
M
58
Face, neck, forearms, hands, thighs, legs Shoulders, arms, forearms, thighs, legs Trunk, extremities
SK SK
Curth, ~ 1962 Ronchese, x 1965 Walter, r 1972
F
54
Increase in 6 mo 1 mo
F
84
3 wk
Back, abdomen, forearms
Dantzig, 8 1973
M
55
4 mo
Chest, back, shoulders
M
72
3 mo
Chest, back, shoulders
F
67
6 mo
Trunk
M
71
6 mo
Trunk
M
64
Sudden increase
Back
Liddell et al, ~ 1975
Gitlin and Pirozzi, TM 1975
VH
AN AN
*AN: Acanthosisnigricans;SCC: squamouscell carcinoma;SK: seborrheickeratoses; VH: verrucal hyperplasia. ance of multiple seborrheic keratoses could be a marker of internal malignancy. Since then, numerous instances associated with various types of malignancies have been reported.
CASE REPORTS Case 1 A 56-year-old white woman was seen at the Mayo Clinic in January, 1970, because of multiple seborrheic keratoses that had appeared suddenly over the preceding 3 to 4 weeks (Fig. 1). A grade 3 metastatic adenocarcinoma of the breast had been diagnosed 2 months before this visit, and she had been receiving diethylstilhestrol for 1 month before the appearance of the seborrheic keratoses. On clinical examination, multiple seborrheic keratoses were noted on the back and the extremities, with disseminated freckles and typical acanthosis nigricans in the axillae, neck, nipples, and mouth. Histologic examination confirmed the clinical impression of mul-
tiple seborrheic keratoses. In early February the estrogens were stopped, and palliative treatment for the breast carcinoma with 5-fluorouracil was instituted. No regression of the seborrheic keratoses was noted subsequently. The patient died in August, 1970. No autopsy was performed.
Case 2 A 58-year-old white woman was examined at the Mayo Clinic in October, 1975, because of the sudden appearance of multiple pruritic seborrheic keratoses within the preceding 2 months. The patient had undergone bilateral mastectomy in March, 1975, for a breast adenocarcinoma and had been receiving conjugated estrogens for a month before the appearance of the multiple seborrheic keratoses. On clinical examination, multiple seborrheic keratoses were noted on the back and chest and some on the abdomen, with a mild hyperpigmentation in the neck and the axillae. In October, 1975, and again in 1978,
Volume 10 Number 1 January, 1984
Associated dermatologic symptoms
AN, contact dermatitis of forearms AN, lanugo hair
Caf6 au lait macules AN freckles, pruritus Pruritus Pruritus, erythroderma for 4 yr
Pruritus
Sign of Leser-Trdlat 85
Associated malignancy
Course of multiple seborrheic keratoses
Mammary adenocarcinoma diagnosed 4 mo before
Fading of the "warts" together with improvement of adenocarcinoma after pregnancy
Carcinoma of stomach discovered 2 mo later Ovarian adenocarcinoma discovered in the next mo Simultaneous progression of gastric adenocarcinoma Simultaneous discovery of gastric adenocarcinoma Uterine adenocarcinoma removed 1 mo before Simultaneous discovery of an adenocarcinoma of cecum Simultaneous discovery of S6zary syndrome Simultaneous discovery of carcinoma of the transverse colon Rectal adenocarcinoma discovered 6 mo later Adenocarcinoma of the sigmoid colon (chronology'?) Simultaneous discovery of recurrence of prostatic adenocarcinoma
After surgery and radiotherapy, decrease of old SK but appearance of new SK Died 1 wk after diagnosis
Died 4 mo after dissemination of her adenocarcinoma Large fading after surgery
Regression after radiotherapy, regrowth with progression of tumor Persistence of SK after surgery
colltlntled
an extensive evaluation for a possible metastasis of her breast adenocarcinoma was negative. No regression of the seborrheic keratoses was noted after withdrawal of the estrogen therapy. The patient has not been examined by us since 1978. She was apparently well from 1975 until December, 1982. At that time, a parotid gland tumor that had metastasized to the right cervical nodes was found. The primary lesion and secondarily involved nodes were excised, and x-ray therapy was directed to the nodebearing areas of the right side of the neck. The patient reported that warty lesions developed on the neck where the x-ray therapy had been administered. COMMENT The cases previously reported have been reviewed carefully (Table I). In the absence of the original descriptions of Leser and Trglat, the definition of the sign of Leser-Tr61at is controversial; nevertheless, the sudden appearance of sebor-
rheic keratoses, as in our two cases, or at least the sudden increase in number and size of previous seborrheic keratoses, is a universally accepted and obligatory feature, ls,19 The occurrence of seborrheic keratoses in previously normal skin has been emphasized by Brown, 2~ who believes that erythrodermatous or eczematous states could promote their appearance. ~1,22 Thus, seborrheic keratoses appearing in sites involved by contact dermatitis:~ or erythrodermic conditionss'12'la could be of rather doubtful significance. In this regard, the relative role of previous topical treatments, including mechlorethamine hydrochloride, t2 in the appearance of seborrheic keratoses must be assessed. The association of the sign of Leser-Tr61at with acanthosis nigricans (typical in Case 1; incomplete in Case 2) has been reported 1':1'4"~and has led some authors to consider the sign of Leser-Tr~lat, even when isolated, as a form of acanthosis nigri-
86
Journal of the American Academy of Dermatology
Venencie and Perry
Table I. Cont'd
E Source
Seborrheic keratosis
Onset period
Sites involved
] Histology*
Harrington,t~ 1976
M
72
6 wk
Chest, back
Doll et al, r" 1977
M
69
1-2 mo
Trunk
Greer et al, la 1978
M
72
3 days
Neck, chest, back
SK
Safai et al, 14 1978
M
73
"Sudden"
Face, trunk
SK
M
61
2 mo
Face, chest, back
M
87
Days
Chest, back
SK
M
49
Weeks
Chest, back, abdomen
--
Halevy et al, TM 1980
M
63
Face, chest, back, abdomen
SK
Curry and King,17 1980
M
63
Trunk
Present report
F
56
Sudden increase Increase in I yr 4 wk
Back, extremities
SK
F
58
2 mo
Chest, back, abdomen
--
Lambert et al, 15 1980
*AN: Acanthosisnlgricans; SCC: squamouscell carcinoma; SK: seborrheic keratoses; VH: verrucal hyperplasia, cans, ~''-':~ from which hyperkeratotic forms of seborrheic keratoses are sometimes difficult to differentiate histologically.24 The association with pruritus not related to an erythroderma, as in Case 2, has been reported. 1.6.7.9 The sudden appearance (or increase) of multiple seborrheic keratoses has been reported in association with gastric, a'a duodenal, 17 colonic, ~'~ rectosigmoidal, 9 prostatic, 1~ ovarian, 4 and uterine 1"6 carcinomas. In the classic case of Josser et al, 2 breast adenocarcinoma was associated with "warts" whose clinical description was consistent with seborrheic keratoses. After the end of a pregnancy, the warts faded and there was partial spontaneous improvement of the adenocarcinoma. Other malignancies associated with the appearance of seborrheic keratoses have been reported, including squamous cell carcinomas of the lungs,,2.,~ acute leukemia, TM mycosis fungoides, 14,1~ and S6zary syndrome, s
There are cases 7 in which the simultaneous occurrence of seborrheic keratoses and malignancy, and regression of the sebon'heic keratoses after treatment for the malignancy, seem to indicate a relationship between the two conditions. However, in some of these cases the regression of the seborrheic keratoses could have been a direct effect of chemotherapy or radiotherapy. In our first case, multiple seborrheic keratoses occurred after the diagnosis of an adenocarcinoma, as has been reported in other cases. '~''~ Diethylstilbestrol has been recognized as producing acanthosis nigricans, 2'~ and consequently the possible role of estrogen therapy in our two cases must be considered. However, in our two cases the seborrheic keratoses remained unchanged after withdrawal of the estrogen therapy. The appearance of multiple seborrheic keratoses after mastectomy in Case 2, with no evidence of metastasis, might be related to an immunodeficient state
Volume 10 Number 1 January, 1984
Associated dermatologic symptoms
Symptoms consistent with porphyria cutanea tarda Erythematous, pruritic, ichthyosiform rash for 2 mo Intertrigo due to Candida
albicans Ichthyosiform dermatitis, pruritus
Erythroderma and pruritus for 1 wk
Hemangiomas Pruritus AN, freckles Mild flexural hyperpigmentation
Sign of Leser-Trdlat
Associated malignancy
Simultaneous discovery of isotopic and arterial hepatic defect Simultaneous discovery of SCC of lung Acute leukemia diagnosed 3 days before Well-differentiated lymphoma Mycosis fungoides diagnosed 2 mo before Mycosis fungoides diagnosed simultaneously Simultaneous discovery of metastasis to brain from SCC of the lung diagnosed 5 mo before Simultaneous diagnosis of lymphocytic lymphoma Adenocarcinoma of duodenum Grade 3 metastatic breast adenocarcinoma diagnosed 2 mo before Mastectomy for breast adenocarcinoma 5 mo before
promoting both the seborrheic keratoses and the malignancy. In cases in which seborrheic keratoses appear after a cancer, the hypothetic immunodeficient state might have occurred as a side effect of chemotherapy or radiotherapy. Unfortunately, studies of immunocompetence were not performed on our patients. The sign of Leser-Tr~lat is controversial because various investigators are not in agreement that the isolated presence of eruptive seborrheic keratoses is indicative of an internal malignancy. Many of the cases reported (Table I) occun'ed in elderly patients, in whom the simultaneous appearance of multiple seborrheic keratoses and malignancies could be coincidental. '~ Thus, review of our two cases and of the previously reported cases leads us to conclude that further reports--including the previous state of the skin, histologic findings, and previous topical and general treatments--and a statistical analysis are
87
Course of multiple seborrheie keratoses
Regression after pneumonectomy
Died 1 mo later, with partial involution of SK Decreased with chemotherapy
Decrease of SK after electron beam therapy No decrease with palliative treatment and appearance of hepatic metastasis
No regression with palliative treatment, died 8 mo after No regression noted during 3-yr follow-up
needed to assess the relevance of the sign of Leser-Tr~lat. On the other hand, clinical experience in some patients who present with sudden appearance or sudden increase of seborrheic keratoses must alert physicians to the possibility that these cutaneous phenomena may indicate associated malignant disease. 1~,J8 REFERENCES
1. Ronchese F: Keratoses, cancer and "the sign of LeserTr~lat," Cancer 18:1003-1006, 1965. 2. JosserandA, Dargent M, Mayer M: t~volutionet involution simultan~esde carcinose du sein et de ven:ues de la r6gion mammaire. Presse m~d 2:674-675, 1948. 3. Schwartz B: Acanthosis nigricans. Proc R Soe Med 45:466, 1952. (Abst.) 4. Dingley ER, Marten RH: Adenocarcinomaof the ovary presenting as acanthosisnigricans. J Obstet GynaecolBr Emp 64:898-900, 1957. 5. Sneddon IB, Roberts JBM: An incompleteform of aeanthosis nigricans. Gut 3:269-272, 1962. 6. Curth HO: The necessityof distinguishingt~ee types of
88
7. 8. 9.
10. 11. 12. 13. 14. 15. 16,
Venencie a n d P e r r y
acanthosis nigricans. Exeerpta Mediea International Congress Series No. 55, 1962, p. 335. Walter JA: Eruptive basal cell papillomata with carcinoma of caecum. Proc R Soc Med 65:595-596, 1972. Dantzig PI: Sign of Leser-Tr~lat. Arch Dermatol 108: 700-701, 1973. Liddell K, White JE, Caldwell IW: Seborrhoeie keratoses and carcinoma of the large bowel: Three cases exhibiting the sign of Leser-Tr61at. Br J Dermato192:449-452, 1975. Giflin MC, Pirozzi DJ: The sign of Leser-Tr61at. Arch Dermatol 111:792-793, 1975, (Letter to Editor.) Harrington CI: Leser-Tr61at sign with porphyria cutanea tarda and malignant hepatoma. Arch Dermatol 112:730, 1976. (Letter to Editor.) Doll DC, McCagh MF, Welton WA: Sign of LeserTr61at. JAMA 238:236-237, 1977. Greer KE, Hawkins H, Hess C: Leser-Tr61at associated with acute leukemia. Arch Dermatol 114:1552, 1978. (Letter to Editor,) Safai B, Grant JM, Good RA: Cutaneous manifestation of internal malignancies. II. The sign of Leser-Tr61at. Int I Dermatol 17:494-495, 1978. Lambert D, Fort M, Legoux A, Chapuis J-L: Le signe de Leser-Tr61at: Apropos de 2 observations. Ann Dermatol Venereol 107:1035-1041, 1980. Halevy S, Halevy J, Feuerman EJ: The sign of LeserTr61at in association with lymphocytic lymphoma. Dermatologica 161'183-186, 1980.
Journal of the American Academy of Dermatology 17. Curry SS, King LE: The sign of Leser-Tr~lat: Report of a case with adenocarcinoma of the duodenum. Arch Dermatol 116:1059-1060, 1980. 18. Roberts SOB, Rook A: The skin in systemic disease, in Rook AJ, Wilkinson DS, Ebling FJG, editors: Textbook of dermatology. Oxford, 1979, BlackweU Scientific Publications, vol. 2, ed. 3, p. 2107. 19. Braverman IM: Skin signs of systemic disease, ed. 2. Philadelphia, 1981, W. B. Saunders Co., pp. 66-67. 20. Brown FC: Sign of Leser-Tr~lat. Arch Dermatol 110: 129, 1974. (Letter to Editor.) 21. Williams MG: Acanthomata appearing after eczema.Br J Den~atol 68:268-271, 1956. 22. Sanderson KV: The structure of seborrhoeic keratoses. Br J Dermatol 80:588-593, 1968. 23. Sneddon IB: Cutaneous manifestations of visceral malignancy, in Bagshawe KD, editor: Medical oncology: Medical aspects of malignant disease. Oxford, 1975, Blackwell Scientific Publications, p. 165. 24. Lever WF, Schaumburg-Lever G: Histopathology of the skin, ed. 5. Philadelphia, 1975, J. B. Lippincott Co., pp. 409-410. 25. Banuchi SR, Cohen L, Lorincz AL, Morgan J: Aeanthosis nigricans following diethylstilbestrol therapy: Occurrence in patients with childhood muscular dystrophy. Arch Dermatol 109:545-546, 1974. 26. Kierland RR: Cutaneous signs of internal malignancy. South IVied J 65:563-568, 1972.
Rochester, MN The sudden appearance of multiple seborrheic keratoses in the two patients could be related to adenocarcinoma of the breast. Despite other isolated reports, this disorder is still controversial as a marker of malignancy. (JAM ACAD DERMATOL10:83-88, 1984.)
From the Department of Dermatology, Mayo Clinic and Mayo Foundation. Accepted for publication May 3, 1983. Reprint requests to: Dr. P. Y. Vencncie, c/o Section of Publications, Mayo Clinic, Rochester, MN 55905. *A visiting clinician from the Clinique Dermatologique, Hbpital Saint-Louis, Paris, France,
In 1965, Ronchese I reported a case of multiple seborrheic keratoses occuning suddenly in a patient with uterine adenocarcinoma and credited two surgeons, a German, Edmund Leser (18531916), and a Frenchman, Ulysse Tr61at (18281890), for the hypothesis that the sudden appear-
Fig. 1. Case 1. A and B, Multiple seborrheic keratoses that appeared over a 3- to 4-week period 1 month after diagnosis of grade 3 metastatic adenocarcinoma of the breast. 83
84
Journal of the American Academy of Dermatology
Venencie and Pert 3'
Table I. Sign of Leser-Tr~lat: Summary o f the reported cases [ Source
Seborrheiekeratosis
Onset period
Sites involved
I Histology*
Josserand et al," 1948
F
32
Sudden
Mammary region
Schwartz, :3 1952
M
45
6 mo
Forearms
Dingley and Marten, 4 1957
F
56
"Sudden"
Trunk, arms, legs
Sneddon and Roberts, ~ 1962
M
46
Few mo
M
58
Face, neck, forearms, hands, thighs, legs Shoulders, arms, forearms, thighs, legs Trunk, extremities
SK SK
Curth, ~ 1962 Ronchese, x 1965 Walter, r 1972
F
54
Increase in 6 mo 1 mo
F
84
3 wk
Back, abdomen, forearms
Dantzig, 8 1973
M
55
4 mo
Chest, back, shoulders
M
72
3 mo
Chest, back, shoulders
F
67
6 mo
Trunk
M
71
6 mo
Trunk
M
64
Sudden increase
Back
Liddell et al, ~ 1975
Gitlin and Pirozzi, TM 1975
VH
AN AN
*AN: Acanthosisnigricans;SCC: squamouscell carcinoma;SK: seborrheickeratoses; VH: verrucal hyperplasia. ance of multiple seborrheic keratoses could be a marker of internal malignancy. Since then, numerous instances associated with various types of malignancies have been reported.
CASE REPORTS Case 1 A 56-year-old white woman was seen at the Mayo Clinic in January, 1970, because of multiple seborrheic keratoses that had appeared suddenly over the preceding 3 to 4 weeks (Fig. 1). A grade 3 metastatic adenocarcinoma of the breast had been diagnosed 2 months before this visit, and she had been receiving diethylstilhestrol for 1 month before the appearance of the seborrheic keratoses. On clinical examination, multiple seborrheic keratoses were noted on the back and the extremities, with disseminated freckles and typical acanthosis nigricans in the axillae, neck, nipples, and mouth. Histologic examination confirmed the clinical impression of mul-
tiple seborrheic keratoses. In early February the estrogens were stopped, and palliative treatment for the breast carcinoma with 5-fluorouracil was instituted. No regression of the seborrheic keratoses was noted subsequently. The patient died in August, 1970. No autopsy was performed.
Case 2 A 58-year-old white woman was examined at the Mayo Clinic in October, 1975, because of the sudden appearance of multiple pruritic seborrheic keratoses within the preceding 2 months. The patient had undergone bilateral mastectomy in March, 1975, for a breast adenocarcinoma and had been receiving conjugated estrogens for a month before the appearance of the multiple seborrheic keratoses. On clinical examination, multiple seborrheic keratoses were noted on the back and chest and some on the abdomen, with a mild hyperpigmentation in the neck and the axillae. In October, 1975, and again in 1978,
Volume 10 Number 1 January, 1984
Associated dermatologic symptoms
AN, contact dermatitis of forearms AN, lanugo hair
Caf6 au lait macules AN freckles, pruritus Pruritus Pruritus, erythroderma for 4 yr
Pruritus
Sign of Leser-Trdlat 85
Associated malignancy
Course of multiple seborrheic keratoses
Mammary adenocarcinoma diagnosed 4 mo before
Fading of the "warts" together with improvement of adenocarcinoma after pregnancy
Carcinoma of stomach discovered 2 mo later Ovarian adenocarcinoma discovered in the next mo Simultaneous progression of gastric adenocarcinoma Simultaneous discovery of gastric adenocarcinoma Uterine adenocarcinoma removed 1 mo before Simultaneous discovery of an adenocarcinoma of cecum Simultaneous discovery of S6zary syndrome Simultaneous discovery of carcinoma of the transverse colon Rectal adenocarcinoma discovered 6 mo later Adenocarcinoma of the sigmoid colon (chronology'?) Simultaneous discovery of recurrence of prostatic adenocarcinoma
After surgery and radiotherapy, decrease of old SK but appearance of new SK Died 1 wk after diagnosis
Died 4 mo after dissemination of her adenocarcinoma Large fading after surgery
Regression after radiotherapy, regrowth with progression of tumor Persistence of SK after surgery
colltlntled
an extensive evaluation for a possible metastasis of her breast adenocarcinoma was negative. No regression of the seborrheic keratoses was noted after withdrawal of the estrogen therapy. The patient has not been examined by us since 1978. She was apparently well from 1975 until December, 1982. At that time, a parotid gland tumor that had metastasized to the right cervical nodes was found. The primary lesion and secondarily involved nodes were excised, and x-ray therapy was directed to the nodebearing areas of the right side of the neck. The patient reported that warty lesions developed on the neck where the x-ray therapy had been administered. COMMENT The cases previously reported have been reviewed carefully (Table I). In the absence of the original descriptions of Leser and Trglat, the definition of the sign of Leser-Tr61at is controversial; nevertheless, the sudden appearance of sebor-
rheic keratoses, as in our two cases, or at least the sudden increase in number and size of previous seborrheic keratoses, is a universally accepted and obligatory feature, ls,19 The occurrence of seborrheic keratoses in previously normal skin has been emphasized by Brown, 2~ who believes that erythrodermatous or eczematous states could promote their appearance. ~1,22 Thus, seborrheic keratoses appearing in sites involved by contact dermatitis:~ or erythrodermic conditionss'12'la could be of rather doubtful significance. In this regard, the relative role of previous topical treatments, including mechlorethamine hydrochloride, t2 in the appearance of seborrheic keratoses must be assessed. The association of the sign of Leser-Tr61at with acanthosis nigricans (typical in Case 1; incomplete in Case 2) has been reported 1':1'4"~and has led some authors to consider the sign of Leser-Tr~lat, even when isolated, as a form of acanthosis nigri-
86
Journal of the American Academy of Dermatology
Venencie and Perry
Table I. Cont'd
E Source
Seborrheic keratosis
Onset period
Sites involved
] Histology*
Harrington,t~ 1976
M
72
6 wk
Chest, back
Doll et al, r" 1977
M
69
1-2 mo
Trunk
Greer et al, la 1978
M
72
3 days
Neck, chest, back
SK
Safai et al, 14 1978
M
73
"Sudden"
Face, trunk
SK
M
61
2 mo
Face, chest, back
M
87
Days
Chest, back
SK
M
49
Weeks
Chest, back, abdomen
--
Halevy et al, TM 1980
M
63
Face, chest, back, abdomen
SK
Curry and King,17 1980
M
63
Trunk
Present report
F
56
Sudden increase Increase in I yr 4 wk
Back, extremities
SK
F
58
2 mo
Chest, back, abdomen
--
Lambert et al, 15 1980
*AN: Acanthosisnlgricans; SCC: squamouscell carcinoma; SK: seborrheic keratoses; VH: verrucal hyperplasia, cans, ~''-':~ from which hyperkeratotic forms of seborrheic keratoses are sometimes difficult to differentiate histologically.24 The association with pruritus not related to an erythroderma, as in Case 2, has been reported. 1.6.7.9 The sudden appearance (or increase) of multiple seborrheic keratoses has been reported in association with gastric, a'a duodenal, 17 colonic, ~'~ rectosigmoidal, 9 prostatic, 1~ ovarian, 4 and uterine 1"6 carcinomas. In the classic case of Josser et al, 2 breast adenocarcinoma was associated with "warts" whose clinical description was consistent with seborrheic keratoses. After the end of a pregnancy, the warts faded and there was partial spontaneous improvement of the adenocarcinoma. Other malignancies associated with the appearance of seborrheic keratoses have been reported, including squamous cell carcinomas of the lungs,,2.,~ acute leukemia, TM mycosis fungoides, 14,1~ and S6zary syndrome, s
There are cases 7 in which the simultaneous occurrence of seborrheic keratoses and malignancy, and regression of the sebon'heic keratoses after treatment for the malignancy, seem to indicate a relationship between the two conditions. However, in some of these cases the regression of the seborrheic keratoses could have been a direct effect of chemotherapy or radiotherapy. In our first case, multiple seborrheic keratoses occurred after the diagnosis of an adenocarcinoma, as has been reported in other cases. '~''~ Diethylstilbestrol has been recognized as producing acanthosis nigricans, 2'~ and consequently the possible role of estrogen therapy in our two cases must be considered. However, in our two cases the seborrheic keratoses remained unchanged after withdrawal of the estrogen therapy. The appearance of multiple seborrheic keratoses after mastectomy in Case 2, with no evidence of metastasis, might be related to an immunodeficient state
Volume 10 Number 1 January, 1984
Associated dermatologic symptoms
Symptoms consistent with porphyria cutanea tarda Erythematous, pruritic, ichthyosiform rash for 2 mo Intertrigo due to Candida
albicans Ichthyosiform dermatitis, pruritus
Erythroderma and pruritus for 1 wk
Hemangiomas Pruritus AN, freckles Mild flexural hyperpigmentation
Sign of Leser-Trdlat
Associated malignancy
Simultaneous discovery of isotopic and arterial hepatic defect Simultaneous discovery of SCC of lung Acute leukemia diagnosed 3 days before Well-differentiated lymphoma Mycosis fungoides diagnosed 2 mo before Mycosis fungoides diagnosed simultaneously Simultaneous discovery of metastasis to brain from SCC of the lung diagnosed 5 mo before Simultaneous diagnosis of lymphocytic lymphoma Adenocarcinoma of duodenum Grade 3 metastatic breast adenocarcinoma diagnosed 2 mo before Mastectomy for breast adenocarcinoma 5 mo before
promoting both the seborrheic keratoses and the malignancy. In cases in which seborrheic keratoses appear after a cancer, the hypothetic immunodeficient state might have occurred as a side effect of chemotherapy or radiotherapy. Unfortunately, studies of immunocompetence were not performed on our patients. The sign of Leser-Tr~lat is controversial because various investigators are not in agreement that the isolated presence of eruptive seborrheic keratoses is indicative of an internal malignancy. Many of the cases reported (Table I) occun'ed in elderly patients, in whom the simultaneous appearance of multiple seborrheic keratoses and malignancies could be coincidental. '~ Thus, review of our two cases and of the previously reported cases leads us to conclude that further reports--including the previous state of the skin, histologic findings, and previous topical and general treatments--and a statistical analysis are
87
Course of multiple seborrheie keratoses
Regression after pneumonectomy
Died 1 mo later, with partial involution of SK Decreased with chemotherapy
Decrease of SK after electron beam therapy No decrease with palliative treatment and appearance of hepatic metastasis
No regression with palliative treatment, died 8 mo after No regression noted during 3-yr follow-up
needed to assess the relevance of the sign of Leser-Tr~lat. On the other hand, clinical experience in some patients who present with sudden appearance or sudden increase of seborrheic keratoses must alert physicians to the possibility that these cutaneous phenomena may indicate associated malignant disease. 1~,J8 REFERENCES
1. Ronchese F: Keratoses, cancer and "the sign of LeserTr~lat," Cancer 18:1003-1006, 1965. 2. JosserandA, Dargent M, Mayer M: t~volutionet involution simultan~esde carcinose du sein et de ven:ues de la r6gion mammaire. Presse m~d 2:674-675, 1948. 3. Schwartz B: Acanthosis nigricans. Proc R Soe Med 45:466, 1952. (Abst.) 4. Dingley ER, Marten RH: Adenocarcinomaof the ovary presenting as acanthosisnigricans. J Obstet GynaecolBr Emp 64:898-900, 1957. 5. Sneddon IB, Roberts JBM: An incompleteform of aeanthosis nigricans. Gut 3:269-272, 1962. 6. Curth HO: The necessityof distinguishingt~ee types of
88
7. 8. 9.
10. 11. 12. 13. 14. 15. 16,
Venencie a n d P e r r y
acanthosis nigricans. Exeerpta Mediea International Congress Series No. 55, 1962, p. 335. Walter JA: Eruptive basal cell papillomata with carcinoma of caecum. Proc R Soc Med 65:595-596, 1972. Dantzig PI: Sign of Leser-Tr~lat. Arch Dermatol 108: 700-701, 1973. Liddell K, White JE, Caldwell IW: Seborrhoeie keratoses and carcinoma of the large bowel: Three cases exhibiting the sign of Leser-Tr61at. Br J Dermato192:449-452, 1975. Giflin MC, Pirozzi DJ: The sign of Leser-Tr61at. Arch Dermatol 111:792-793, 1975, (Letter to Editor.) Harrington CI: Leser-Tr61at sign with porphyria cutanea tarda and malignant hepatoma. Arch Dermatol 112:730, 1976. (Letter to Editor.) Doll DC, McCagh MF, Welton WA: Sign of LeserTr61at. JAMA 238:236-237, 1977. Greer KE, Hawkins H, Hess C: Leser-Tr61at associated with acute leukemia. Arch Dermatol 114:1552, 1978. (Letter to Editor,) Safai B, Grant JM, Good RA: Cutaneous manifestation of internal malignancies. II. The sign of Leser-Tr61at. Int I Dermatol 17:494-495, 1978. Lambert D, Fort M, Legoux A, Chapuis J-L: Le signe de Leser-Tr61at: Apropos de 2 observations. Ann Dermatol Venereol 107:1035-1041, 1980. Halevy S, Halevy J, Feuerman EJ: The sign of LeserTr61at in association with lymphocytic lymphoma. Dermatologica 161'183-186, 1980.
Journal of the American Academy of Dermatology 17. Curry SS, King LE: The sign of Leser-Tr~lat: Report of a case with adenocarcinoma of the duodenum. Arch Dermatol 116:1059-1060, 1980. 18. Roberts SOB, Rook A: The skin in systemic disease, in Rook AJ, Wilkinson DS, Ebling FJG, editors: Textbook of dermatology. Oxford, 1979, BlackweU Scientific Publications, vol. 2, ed. 3, p. 2107. 19. Braverman IM: Skin signs of systemic disease, ed. 2. Philadelphia, 1981, W. B. Saunders Co., pp. 66-67. 20. Brown FC: Sign of Leser-Tr~lat. Arch Dermatol 110: 129, 1974. (Letter to Editor.) 21. Williams MG: Acanthomata appearing after eczema.Br J Den~atol 68:268-271, 1956. 22. Sanderson KV: The structure of seborrhoeic keratoses. Br J Dermatol 80:588-593, 1968. 23. Sneddon IB: Cutaneous manifestations of visceral malignancy, in Bagshawe KD, editor: Medical oncology: Medical aspects of malignant disease. Oxford, 1975, Blackwell Scientific Publications, p. 165. 24. Lever WF, Schaumburg-Lever G: Histopathology of the skin, ed. 5. Philadelphia, 1975, J. B. Lippincott Co., pp. 409-410. 25. Banuchi SR, Cohen L, Lorincz AL, Morgan J: Aeanthosis nigricans following diethylstilbestrol therapy: Occurrence in patients with childhood muscular dystrophy. Arch Dermatol 109:545-546, 1974. 26. Kierland RR: Cutaneous signs of internal malignancy. South IVied J 65:563-568, 1972.