eMedicine Specialties > Dermatology > Internal Medicine

Sign of Leser-Trelat: Differential Diagnoses & Workup

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: May 29, 2009

Differential Diagnoses

Acanthosis Nigricans
Tuberous Sclerosis
Cowden Disease (Multiple Hamartoma Syndrome)
Warts, Genital
Nevi, Melanocytic
Warts, Nongenital
Nevoid Basal Cell Carcinoma Syndrome
Warty Dyskeratoma
Seborrheic Keratosis

Other Problems to Be Considered

The chemotherapeutic agent cytarabine may cause a rare reaction of inflammation of existing seborrheic keratoses, mimicking the sign of Leser-Trélat.34

Cupric keratoses have been described as green seborrheic keratoses secondary to external copper exposure.35

Regressing seborrheic keratoses may clinically and dermoscopically mimic a regressing melanoma.36

Workup

Laboratory Studies

  • Laboratory abnormalities are due to the associated malignancy.
  • Appropriate clinical tests should be performed, depending on the clinical setting. The author recommends the following:
    • Routine blood and chemistry studies, including a complete blood cell count with differential and absolute platelet counts
    • Examination of the stool for occult blood
    • Carcinoembryonic antigen test
    • Urinalysis with cytologic examination
    • Papanicolaou test in women
    • Cervical cytologic examination in women
    • Prostate-specific antigen testing in men

Imaging Studies

  • The following should be performed:
    • Chest radiography
    • Mammography in women
    • Upper and lower gastrointestinal radiographic studies
  • CT scanning of the abdomen and the pelvis should be considered.

Procedures

  • The author recommends that a biopsy specimen be obtained to confirm the diagnosis.
  • Complete colorectal and gastric endoscopic examinations should also be performed if no malignancy is detected.

Histologic Findings

In this syndrome, seborrheic keratoses are the same as the common type of seborrheic keratosis. Both types involve epidermal hyperkeratosis, papillomatosis, and acanthosis with cystic inclusion of keratinous material (eg, horn pseudocysts). Variants, such as adenoid-type seborrheic keratoses, have not yet been described.

More on Sign of Leser-Trelat

Overview: Sign of Leser-Trelat
Differential Diagnoses & Workup: Sign of Leser-Trelat
Treatment & Medication: Sign of Leser-Trelat
Follow-up: Sign of Leser-Trelat
Multimedia: Sign of Leser-Trelat
References
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References

  1. Leser E. Ueber ein die Krebskrankheit beim Menschen haufig begleitendes, noch wenig gekanntes Symptom. Munchener Med Wochenschr. 1901;51:2035-2036.

  2. De Bersaques J. Sign of Leser-Trelat. J Am Acad Dermatol. 1985;12:724.

  3. Hollander E. V. Beitrage zur Fruhdiagnose des Darmcarcinomas (Hereditatsverhaltnisse und Hautveranderungen. Deutsche Medicinische Wochenschrift. 1900;26:483-485.

  4. Dubreuilh W. Official Transactions. Des hyperkeratoses circonscrites. Third International Congress of Dermatology held in the examination hall of the conjoint Royal Colleges of Physicians and Surgeons, London: Waterlow & Sons Ltd; August 4-8, 1896.

  5. Freudenthal W. Verruca senilis und Keratoma senile. Arch F Dermat U Syph (Berlin). 1926;152:505-528.

  6. Garcia RL, Bishop ME. The rapid onset of seborrheic keratoses of the breasts during pregnancy. J Assoc Mil Dermatol. 1977;3 (2):13-4.

  7. Lindelöf B, Sigurgeirsson B, Melander S. Seborrheic keratoses and cancer. J Am Acad Dermatol. Jun 1992;26(6):947-50. [Medline].

  8. Kilmer SL, Berman B, Morhenn VB. Eruptive seborrheic keratoses in a young woman with acromegaly. J Am Acad Dermatol. Nov 1990;23(5 Pt 2):991-4. [Medline].

  9. Martin RW 3rd, Rady P, Arany I, Tyring SK. Benign Leydig cell tumor of the testis associated with human papillomavirus type 33 presenting with the sign of Leser-Trelat. J Urol. Oct 1993;150(4):1246-50. [Medline].

  10. Inamadar AC, Palit A. Eruptive seborrhoeic keratosis in human immunodeficiency virus infection: a coincidence or 'the sign of Leser-Trelat'?. Br J Dermatol. Aug 2003;149(2):435-6. [Medline].

  11. Millard LG, Gould DJ. Hyperkeratosis of the palms and soles associated with internal malignancy and elevated levels of immunoreactive human growth hormone. Clin Exp Dermatol. Dec 1976;1(4):363-8. [Medline].

  12. 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. Dec 17 1987;317(25):1582-7. [Medline].

  13. Horiuchi Y, Katsuoka K, Takezaki S, Nishiyama S. Study of epidermal growth activity in cultured human keratinocytes from peripheral-blood lymphocytes of a patient with Sezary syndrome associated with the Leser-Trelat sign. Arch Dermatol Res. 1985;278(1):74-6. [Medline].

  14. Ellis DL, Yates RA. Sign of Leser-Trelat. Clin Dermatol. Jan-Mar 1993;11(1):141-8. [Medline].

  15. Barron LA, Prendiville JS. The sign of Leser-Trelat in a young woman with osteogenic sarcoma. J Am Acad Dermatol. Feb 1992;26(2 Pt 2):344-7. [Medline].

  16. Westrom DR, Berger TG. The sign of Leser-Trelat in a young man. Arch Dermatol. Dec 1986;122(12):1356-7. [Medline].

  17. Schwengle LE, Rampen FH, Wobbes T. Seborrhoeic keratoses and internal malignancies. A case control study. Clin Exp Dermatol. May 1988;13(3):177-9. [Medline].

  18. Grob JJ, Rava MC, Gouvernet J, et al. The relation between seborrheic keratoses and malignant solid tumours. A case-control study. Acta Derm Venereol. 1991;71(2):166-9. [Medline].

  19. Kierland RR. Acanthosis nigricans: an analysis of data in twenty-two cases and a study of its frequency in necropsy material. J Invest Dermatol. 1947;9:299-305.

  20. Li M, Yang LJ, Zhu XH, et al. The Leser-Trelat sign is associated with nasopharyngeal carcinoma: case report and review of cases reported in China. Clin Exp Dermatol. Jan 2009;34(1):52-4. [Medline].

  21. Siedek V, Schuh T, Wollenberg A. Leser-Trelat sign in metastasized malignant melanoma. Eur Arch Otorhinolaryngol. Feb 2009;266(2):297-9. [Medline].

  22. Bedi TR. Familial congenital multiple seborrheic verrucae. Arch Dermatol. Oct 1977;113(10):1441-2. [Medline].

  23. Jadassohn J. Die benignen Epitheliome. Arch f Dermatol u Syph (Wien). 1913;116:117.

  24. Reiches AJ. Seborrheic keratoses; are they delayed hereditary nevi?. AMA Arch Derm Syphilol. May 1952;65(5):596-600. [Medline].

  25. Rongioletti F, Corbella L, Rebora A. Multiple familial seborrheic keratoses. Dermatologica. 1988;176(1):43-5. [Medline].

  26. Dasanu CA, Alexandrescu DT. Bilateral Leser-Trelat sign mirroring lung adenocarcinoma with early metastases to the contralateral lung. South Med J. Feb 2009;102(2):216-8. [Medline].

  27. Jemec GB. Hypertrichosis lanuginosa acquisita. Report of a case and review of the literature. Arch Dermatol. Jul 1986;122(7):805-8. [Medline].

  28. Hage E, Hage J. Malignant acanthosis nigricans--a para-endocrine syndrome?. Acta Derm Venereol. 1977;57(2):169-72. [Medline].

  29. Aylesworth R, Vance JC. Multiple hamartoma syndrome with endometrial carcinoma and the sign of Leser-Trelat. Arch Dermatol. Feb 1982;118(2):136-8. [Medline].

  30. Rubisz-Brzezinska J, Zebracka T, Musialowicz D. [Coexistence of 2 paraneoplastic syndromes - acrokeratosis bazex and Leser-Trelat syndrome - in a case of squamous-cell laryngeal cancer]. Przegl Dermatol. Mar-Apr 1983;70(2):205-8. [Medline].

  31. Kebria MM, Belinson J, Kim R, Mekhail TM. Malignant acanthosis nigricans, tripe palms and the sign of Leser-Trelat, a hint to the diagnosis of early stage ovarian cancer: a case report and review of the literature. Gynecol Oncol. May 2006;101(2):353-5. [Medline].

  32. Pembroke AC, Grice K, Levantine AV, Warin AP. Eruptive angiomata in malignant disease. Clin Exp Dermatol. Jun 1978;3(2):147-56. [Medline].

  33. Siedek V, Schuh T, Wollenberg A. Leser-Trelat sign in metastasized malignant melanoma. Eur Arch Otorhinolaryngol. Feb 2009;266(2):297-9. [Medline].

  34. Patton T, Zirwas M, Nieland-Fisher N, Jukic D. Inflammation of seborrheic keratoses caused by cytarabine: a pseudo sign of Leser-Trelat. J Drugs Dermatol. Sep-Oct 2004;3(5):565-6. [Medline].

  35. Peterson J, Shook BA, Wells MJ, Rodriguez M. Cupric keratosis: green seborrheic keratoses secondary to external copper exposure. Cutis. Jan 2006;77(1):39-41. [Medline].

  36. Pastar Z, Lipozencic J, Rados J, Stajminger G. Regressing seborrheic keratosis - clinically and dermoscopically mimicking a regressing melanoma. Acta Dermatovenerol Croat. 2007;15(1):24-6. [Medline].

  37. Stieler W, Plewig G. [Acanthosis nigricans maligna and Leser-Trélat sign in double malignancy of the breast and stomach]. Z Hautkr. Mar 1 1987;62(5):344-66. [Medline].

  38. Holdiness MR. A case of Leser-Trélat sign. J Am Acad Dermatol. Jan 1987;16(1 Pt 1):147-8. [Medline].

  39. Abeloff MD. Paraneoplastic syndromes: a window on the biology of cancer. N Engl J Med. Dec 17 1987;317(25):1598-600. [Medline].

  40. Achten G, Ledoux-Corbusier M, Goens J. [Classification and pathogenesis of cutaneous paraneoplastic syndromes]. Ann Med Interne (Paris). 1984;135(8):646-53. [Medline].

  41. Balo J. A verrucak es rak gyakori egyuttes elofordulasa. Orvosi Hetilop. 1933;77:797-798.

  42. Barth G, Basten O, Ruschoff J, Rompel R. [Clinical and histopathological characteristics of early Leser-Trelat syndrome]. Hautarzt. Jul 2001;52(7):649-52. [Medline].

  43. Bordeleau L, Weatherhead L. Eruptive seborrheic keratoses and Crohn's disease. Canadian J Dermatol. 1993;5:495-496.

  44. Brauer J, Happle R, Gieler U. The sign of Leser-Trelat: fact or myth?. J Europ Acad Dermatol Venereol. 1992;1:77-80.

  45. Carrera C, Segura S, Palou J, et al. Seborrheic keratosislike melanoma with folliculotropism. Arch Dermatol. Mar 2007;143(3):373-6. [Medline].

  46. Ceylan C, Alper S, Kilinc I. Leser-Trelat sign. Int J Dermatol. Oct 2002;41(10):687-8. [Medline].

  47. Curth HO. Skin lesions and internal carcinoma. In: Cancer of the Skin. Biology-Diagnosis-Management. Philadelphia, Pa: WB Saunders; 1976:1308-41.

  48. Curth HO. Skin manifestations of internal malignant tumors. Md State Med J. Dec 1972;21(12):52-6. [Medline].

  49. Dantzig PI. Sign of Leser-Trelat. Arch Dermatol. Nov 1973;108(5):700-1. [Medline].

  50. Darier J. Authorized translation from the second French edition edited with notes by S. Pollitzer. Philadelphia, Pa: Lea & Febinger; 1920:209-10.

  51. De Bersaques J, Dockx P. [Internal malignant tumors and cutaneous symptoms]. Arch Belg Dermatol. Jul-Sep 1974;30(3):117-58. [Medline].

  52. Dingley ER, Marten RH. Adenocarcinoma of the ovary presenting as acanthosis nigricans. J Obstet Gynaecol Br Emp. Dec 1957;64(6):898-900. [Medline].

  53. Flugman SL, McClain SA, Clark RA. Transient eruptive seborrheic keratoses associated with erythrodermic psoriasis and erythrodermic drug eruption: report of two cases. J Am Acad Dermatol. Dec 2001;45(6 Suppl):S212-4. [Medline].

  54. Follmann J. A naevusok gyakorisagarol valamint a naevusok es a kozotti osszefuggesekrol. Magyar Orvosi Archivum. 1939;40:53-71.

  55. Freudenthal W. Rumpfhautepitheliom (nebst Bemerkungen uber die Verruca senilis und das Keratoma senilis. Arch F Dermat U Syph (Berlin). 1929;158:539-544.

  56. Gheeraert P, Goens J, Schwartz RA, Lambert WC, Schroeder F, Debusscher L. Florid cutaneous papillomatosis, malignant acanthosis nigricans, and pulmonary squamous cell carcinoma. Int J Dermatol. Mar 1991;30(3):193-7. [Medline].

  57. Heng MC, Soo-Hoo K, Levine S, Petresek D. Linear seborrheic keratoses associated with underlying malignancy. J Am Acad Dermatol. Jun 1988;18(6):1316-21. [Medline].

  58. Hirano T, Yoshioka H, Manabe T. A case of pancreatic cancer with the sign of Leser-Trelat. Nippon Geka Hokan. Jul 1 1993;62(4):203-8. [Medline].

  59. Holdiness MR. Erythroderma, seborrheic keratoses and Leser-Trelat sign. Acta Derm Venereol. 1989;69(3):273-4. [Medline].

  60. Holdiness MR. On the classification of the sign of Leser-Trelat. J Am Acad Dermatol. Oct 1988;19(4):754-7. [Medline].

  61. Holdiness MR. The sign of Leser-Trelat. Int J Dermatol. Nov 1986;25(9):564-72. [Medline].

  62. Hollander E. Carcinom und Hautveranderungen. Centralblatt F Chirurg. 1902;29:457-459.

  63. Klimopoulos S, Kounoudes C, Pantelidaki C, Skrepetou K, Papoudos M, Katsoulis H. The leser-trelat sign in association with carcinoma of the ampulla of Vater. Am J Gastroenterol. May 2001;96(5):1623-6. [Medline].

  64. Micali G, Nasca MR, Pasquale R. Familial multiple seborrheic keratoses. Report of a kindred. Giornale Ital Dermatol Venerol. 2002;137:169.

  65. Moore RL, Devere TS. Epidermal manifestations of internal malignancy. Dermatol Clin. Jan 2008;26(1):17-29, vii. [Medline].

  66. Pentenero M, Carrozzo M, Pagano M, Gandolfo S. Oral acanthosis nigricans, tripe palms and sign of leser-trelat in a patient with gastric adenocarcinoma. Int J Dermatol. Jul 2004;43(7):530-2. [Medline].

  67. Rampen HJ, Schwengle LE. Erythroderma, seborrheic keratoses and Leser-Trelat sign. Response to Dr. Mark Holdiness' letter. Acta Derm Venereol (Stockh). 1989;60:273-274.

  68. Rampen HJ, Schwengle LE. The sign of Leser-Trelat: does it exist?. J Am Acad Dermatol. Jul 1989;21(1):50-5. [Medline].

  69. Ronchese F. Keratoses, cancer and "the sign of Leser-Trelat". Cancer. Aug 1965;18:1003-6. [Medline].

  70. Schwartz RA. Acanthosis nigricans, florid cutaneous papillomatosis and the sign of Leser-Trelat. Cutis. Sep 1981;28(3):319-22, 326-7, 330-1 passim. [Medline].

  71. Schwartz RA. Acanthosis nigricans. J Am Acad Dermatol. Jul 1994;31(1):1-19; quiz 20-2. [Medline].

  72. Schwartz RA. The sign of leser-trelat. In: Demis DJ, ed. Clinical Dermatology. 26A. 13th ed. Philadelphia, Pa: JB Lippincott; 1987:1-3.

  73. Schwartz RA. Florid cutaneous papillomatosis. Clin Dermatol. Jan-Mar 1993;11(1):89-91. [Medline].

  74. Schwartz RA. Sign of Leser-Trelat. J Am Acad Dermatol. Jul 1996;35(1):88-95. [Medline].

  75. Schwartz RA, Burgess GH. Florid cutaneous papillomatosis. Arch Dermatol. Dec 1978;114(12):1803-6. [Medline].

  76. Schwartz RA, Helmold ME, Janniger CK, Gascon P. Sign of Leser-Trelat with a metastatic mucinous adenocarcinoma. Cutis. Apr 1991;47(4):258-60. [Medline].

  77. Scully C, Barrett WA, Gilkes J, Rees M, Sarner M, Southcott RJ. Oral acanthosis nigricans, the sign of Leser-Trelat and cholangiocarcinoma. Br J Dermatol. Sep 2001;145(3):506-7. [Medline].

  78. Sebastinei F. Esame dello stato della cuti individui affetti da neoplasmi maligni. Diagnosi. 1932;12:95-113.

  79. Sneddon IB, Roberts JB. An incomplete from of acanthosis nigricans. Gut. Sep 1962;3:269-72. [Medline].

  80. Stone OJ. The sign of Leser-Trelat: a cutaneous sign of internal malignancy: weakened subepithelial matrix from the effect of neoplasms on the extracellular matrix of the host. Med Hypotheses. Jun 1993;40(6):360-3. [Medline].

  81. Vielhauer V, Herzinger T, Korting HC. The sign of Leser-Trelat: a paraneoplastic cutaneous syndrome that facilitates early diagnosis of occult cancer. Eur J Med Res. Dec 29 2000;5(12):512-6. [Medline].

  82. Williams MG. Acanthoma appearing after eczema. Brit J Dermatol Syph. 1956;68:268-271.

  83. Yaniv R, Servadio Y, Feinstein A, Trau H. The sign of Leser-Trelat associated with transitional cell carcinoma of the urinary-bladder--a case report and short review. Clin Exp Dermatol. Mar 1994;19(2):142-5. [Medline].

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Further Reading

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Keywords

multiple eruptive seborrheic keratoses, paraneoplastic syndromes, malignant acanthosis nigricans, seborrheic warts, keratosis pigmentosa, verruca senilis

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Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Takeji Nishikawa, MD, Emeritus Professor, Department of Dermatology, Keio University School of Medicine; Director, Samoncho Dermatology Clinic; Managing Director, The Waksman Foundation of Japan Inc
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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