Leser-Trelat sign is a rare cutaneous disorder that appears by sudden emergence of seborrheic keratoses and increase in their numbers and size just in weeks or months. Its cooccurence with many kinds of malignancies, especially with adenocarcinoma and lymphoma, has been reported in literature. In this case report, a patient having Leser Trélat sign, without any detected malignancy in spite of a detailed examination and 18 months of follow-up, is presented. The current literature is being discussed whether Leser-Trélat is a paraneoplastic syndrome or not

Enver Turan

Nurdan Yurt

Sezen Koçarslan

Yavuz Yesilova

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128 ACTA DERMATOVENEROLOGICA CROATICALeser-Trélat Sign: Does It Really Exist?Acta Dermatovenerol Croat   2013;21(2):128-130                                          CASE REPORTInTRoDucTIonA great number of skin manifestations have been related to the underlying internal malignancy (1). Skin changes can often be the first sign of a serious problem. A relationship of some dermatoses with malignancy has been frequently determined and the associated dermatoses are accepted as paraneoplas-tic. The clinical manifestations of these dermatoses may precede, coincide with or follow the diagno-sis of internal malignancy. In the current literature, many cases are presented with sudden appearance of multiple pruritic seborrheic keratoses related to the underlying internal malignancy (2-7). Although some authors have accepted that the sign of Leser-Trélat is a cutaneous marker of internal malignancies, it is still a matter of debate whether the syndrome is a paraneoplastic disorder or not (8-13). A patient with the sign of Leser-Trélat presented to our clinic, but no internal malignancy could be determined despite de-tailed examination.caSE REpoRTA 37-year-old female patient was admitted to our clinic because of serpigo on her neck that had ap-peared less than a month before and increased in number rapidly. Her past medical history and family history were unremarkable. On dermatological exam-ination, 2-10 mm sized brown and slightly verrucous papules were observed on the neck and upper chest (Fig. 1). Histopathology of the lesion showed acan-thosis, hyperkeratosis and papillomatosis (Fig. 2).The patient was examined for internal malignan-cy. Laboratory analyses for liver and kidney function, electrolytes, protein electrophoresis, blood and urine Enver Turan1, Yavuz Yesilova1, Nurdan Yurt2, Sezen Koçarslan3 1Department of Dermatology, Faculty of Medicine, University of Harran, Sanliurfa; 2Der-matology Clinic, Gumushane Government Hospital, Gumushane, 3Department of Pa-thology, Faculty of Medicine, University of Harran, Sanliurfa, Turkey corresponding author:Assist. Prof. Enver Turan, MD Department of Dermatology Faculty of Medicine, University of Harran63200-SanliurfaTurkey enverturan@gmail.comReceived: July 5, 2012Accepted: February 26, 2013SummaRy Leser-Trélat sign is a rare cutaneous disorder that manifests with sudden emergence of seborrheic keratoses and increase in their numbers and size within weeks or months. Its concurrence with many types of malignancies, especially adeno-carcinoma and lymphoma, has been reported in the literature. In this case report, a patient having Leser-Trélat sign, without any detected malignancy in spite of detailed examination and 18 months of follow up, is presented. Current literature is reviewed in relation to the debate whether Leser-Trélat is a paraneoplastic syndrome or not. KEy woRDS: Leser-Trélat sign, seborrheic keratoses, paraneo-plastic syndrome129ACTA DERMATOVENEROLOGICA CROATICAtests were all within the normal range. Chest x-ray and abdominal ultrasonography revealed no patho-logic signs. Erythrocyte sedimentation rate was 30 mm/hour and tests for viral hepatitis, HIV and syphilis were negative. No abnormality was detected on ab-dominal, cranial and thorax tomography. Otolaryn-gological examination was normal. Esophagogastro-duodenoscopy and colonoscopy were also normal. The patient was healthy and no change was observed on seborrheic keratoses during one-year follow up.DIScuSSIonParaneoplastic syndromes are a group of clini-cal manifestations that are associated with a malig-nancy and can progress without being related to a primary tumor or metastases. Characteristically, their progresses show parallelism with tumor progresses. Although their mechanism is not fully known, bioac-tive substances (such as polypeptide hormones, hor-mone-like peptides, antibodies or immune complex-es, cytokines, or growth factors), which are released by the tumor or as a response to tumor, are consid-ered responsible (1).The sign of Leser-Trélat is characterized by the pro-gression of new seborrheic keratoses in an eruptive way, or increase in their size within weeks or months. According to some researchers, this cutaneous dis-order is a paraneoplastic syndrome (2). The most frequently reported malignancies associated with Leser-Trélat sign are stomach cancer, gastrointestinal adenocarcinoma and lymphoma. In the literature, leukemia, lymphoma, mycosis fungoides, Sezary syn-drome, and breast, lung and prostate carcinomas and sarcomas (neurofibrosarcoma) associated with Leser-Trélat sign have also been reported (14).The sign of Leser-Trélat has been reported even in situations where no malignancy was detected, such as in heart transplant recipients, erythrodermic pity-riasis rubra pilaris, and HIV infection (15-17). Leser-Trélat sign was defined separately by Edmund Leser and Ulysse Trélat and was first described together with eruptive cherry angiomas in patients having in-ternal malignancy (14). However, Holländer was the first to show the relationship of seborrheic keratoses and cancer (18,19), but the name of Leser-Trélat was given to this sign.The criteria for Leser-Trélat sign defined by Ron-chese are rapid increase in seborrheic keratoses on lesion-free skin, pruritus and an accompanying inter-nal malignancy (20). Heaphy et al. have suggested to use the term of Leser-Trélat syndrome to describe the cases with accompanying internal malignancy (21). The pathomechanism of the sign of Leser-Trélat is unknown. The cause of the increase in size and number of seborrheic keratoses is thought to be an induction of epidermal proliferation associated with a growth factor that originates from the tumor and is swept into the circulation (22). Schwengle et al. studied 36 cancer patients, many of whom had adenosarcomas, and they found that the sizes and numbers of seborrheic keratoses in the cancer patient group were not different from those in the control group (12). Grob et al. determined the sign of Leser-Trélat in only one patient out of 82 pa-tients with solid organ cancers and again in only one Figure 2. Marked acanthosis of predominantly ba-saloid cells, papillomatosis, hyperkeratosis and horn cysts (HE; x40)Figure 1. Multiple seborrheic keratoses on the neck scattering to the upper chest. Turan et al. Acta Dermatovenerol CroatLesser-Trelat sign 2013;21(2):123-127130 ACTA DERMATOVENEROLOGICA CROATICApatient in the control group consisting of 82 patients (11). Similar findings were obtained in another study of 150 oncology patients compared with 150 healthy people (13). These researchers suggested that this sign was coincidental (11-13). For the Leser-Trélat sign, even if the term “paraneo-plastic” is used widely, we think that it is controversial because the incidence of both seborrheic keratoses and cancer is increased in old-aged population and the probability of this concurrence being coinciden-tal is pretty high, as stated by Schwengle et al. (12) and Fink et al. (13). Remission of paraneoplastic dermatosis should be expected after the tumor has been cured if ma-lignancy and paraneoplastic dermatosis show paral-lel progression (23). A real paraneoplastic dermatosis reappears when cancer recurs or metastasizes. In the literature, this fact is not introduced clearly, and after treatment of primary cancer, recession is observed only in one-third of seborrheic keratoses (21). A sudden increase of seborrheic keratoses is com-pletely based on subjective evaluation of the patient, and it is hardly reliable. This sudden increase can be related with the consciousness/awareness level of the patient who had cancer diagnosis, as mentioned by Schwengle et al. (12). Additionally, Brauer states that there is no plausible definition of distinction between eruptive seborrheic keratosis and common seborrheic keratosis (24).concLuSIonBy reviewing literature data, the results of stud-ies on the relation between Leser-Trélat sign and malignancy are inconsistent and there is no strong evidence for the presence of the sign. Almost all pub-lications that claim coincidence of this sign with ma-lignancy consist of case reports. Studies investigating the etiopathogenesis could not show any substance released by or in response to tumor. In our opinion, eruptive seborrheic keratoses do not require search-ing for an underlying internal malignancy. However, to be able to understand whether the Leser-Trélat sign really exists, the presence of malignancy should be searched in a broad case series consisting of pa-tients with eruptive seborrheic keratoses. References1. Cohen PR. Paraneoplastic dermatopathology: cu-taneous paraneoplastic syndromes. Adv Dermatol 1996;11:215-52; discussion 253.2. Schwartz RA. Acanthosis nigricans, florid cuta-neous papillomatosis and the sign of Leser-Trelat. Cutis 1981;28:319-22, 326-317, 330-311 passim.3. Holdiness MR. On the classification of the sign of Leser-Trelat. J Am Acad Dermatol 1988;19:754-7.4. Yavasoglu I, Kadikoylu G, Bolaman Z. The Leser-Trelat sign is associated with acute myeloid leuke-mia. Ann Hematol 2011;90:363.5. Cohn MS, Classen RF. The sign of Leser-Trelat asso-ciated with adenocarcinoma of the rectum. Cutis 1993;51:255-7.6. Barth JH, Dawber RP. Leser-Trelat sign associated with Sezary syndrome. Cutis 1986;38:42.7. Dasanu CA, Alexandrescu DT. Bilateral Leser-Trelat sign mirroring lung adenocarcinoma with early metastases to the contralateral lung. South Med J 2009;102:216-8.8. Halevy S, Feuerman EJ. The sign of Leser-Trelat. A cutaneous marker for internal malignancy. Int J Dermatol 1985;24:359-61.9. Rampen HJ, Schwengle LE. The sign of Leser-Trelat: does it exist? J Am Acad Dermatol 1989;21:50-5.10. Chung VQ, Moschella SL, Zembowicz A, Liu V. Clinical and pathologic findings of paraneoplastic dermatoses. J Am Acad Dermatol 2006;54:745-62; quiz 763-746.11. Grob JJ, Rava MC, Gouvernet J, Fuentes P, Piana L, Gamerre M, et al. The relation between seborrheic keratoses and malignant solid tumours. A case-control study. Acta Derm Venereol 1991;71:166-9.12. Schwengle LE, Rampen FH, Wobbes T. Seborr-hoeic keratoses and internal malignancies. A case control study. Clin Exp Dermatol 1988;13:177-9.13. Fink AM, Filz D, Krajnik G, Jurecka W, Ludwig H, Steiner A. Seborrhoeic keratoses in patients with internal malignancies: a case-control study with prospective accrual of patients. J Eur Acad Der-matol Venereol 2009;23:1316-9.14. Schwartz RA. Sign of Leser-Trelat. J Am Acad Der-matol 1996;35:88-95.15. Inamadar AC, Palit A. Eruptive seborrhoeic kerato-sis in human immunodeficiency virus infection: a coincidence or ‘the sign of Leser-Trelat’? Br J Der-matol 2003;149:435-6.16. Gleeson CM, Chan I, Griffiths WA, Bunker CB. Er-uptive seborrhoeic keratoses associated with Turan et al. Acta Dermatovenerol CroatLesser-Trelat sign 2013;21(2):123-127

Leser-Trélat sign: Does it really exist?

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