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Cutaneous Manifestations of Internal Malignancy

Diagnosis And Management

  • Therapy In Practice
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Abstract

An association between systemic malignancy and cutaneous manifestations has long been recognized. The cutaneous features that can occur are numerous and heterogeneous, and many different etiologic mechanisms are represented — from direct tumor invasion of skin or distant metastases to a wide variety of inflammatory dermatoses that may occur as paraneoplastic phenomena. In addition, there are a number of inherited syndromes that carry an increased risk of cutaneous as well as internal malignancies. While some of these inherited syndromes and paraneoplastic phenomena are exceedingly rare, all clinicians will be aware of the common cutaneous manifestations of advanced malignant disease such as generalized xerosis and pruritus.

This review classifies these wide-ranging cutaneous manifestations of internal malignancy into five basic groups and provides practical advice regarding diagnosis and screening of patients who initially present with a cutaneous complaint. Also included is up-to-date information on two rapidly expanding and exciting areas of research that are likely to have far-reaching clinical implications: (i) clarification of underlying humoral mechanisms, for example, in the malignant carcinoid syndrome; and (ii) identification of an increasing number of specific genetic defects that confer a susceptibility to malignancy.

Increased clinician awareness regarding the associations between these lesions and internal malignancy or inherited syndromes will facilitate screening and early diagnosis.

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References

  1. Lookingbill DP, Spangler N, Sexton FM. Skin involvement as the presenting sign of internal carcinoma: a retrospective study of 7316 cancer patients. J Am Acad Dermatol 1990; 22: 19-26

    Article  PubMed  CAS  Google Scholar 

  2. Spencer PS, Helm TN. Skin metastases in cancer patients. Cutis 1987; 39: 119-21

    PubMed  CAS  Google Scholar 

  3. Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4020 patients. J Am Acad Dermatol 1993; 29: 228-36

    Article  PubMed  CAS  Google Scholar 

  4. Weedon D. Cutaneous metastases. In: Weedon D, editor. Skin pathology. Edinburgh: Churchill Livingstone, 1997: 855-64

    Google Scholar 

  5. Brownstein MIL Helwig EB. Patterns of cutaneous metastases. Arch Dermatol 1972; 105: 862-8

    Article  PubMed  CAS  Google Scholar 

  6. Brenner S, Tamir E, Maharshak N, et al. Cutaneous manifestations of internal malignancies. Clin Dermatol 2001; 19: 290-7

    Article  PubMed  CAS  Google Scholar 

  7. Granter TI, Dhawan SS, Phillips MG, et al. Cutaneous metastases of colonic adenocarcinoma. Cutis 1990; 46: 66-8

    Google Scholar 

  8. McLean DI. Cutaneous paraneoplastic syndromes. Arch Dermatol 1986; 122: 765-7

    Article  PubMed  CAS  Google Scholar 

  9. Barnes BE, Mawr B. Dermatomyositis and malignancy: a review of the literature. Ann Intern Med 1976; 84: 68-76

    PubMed  CAS  Google Scholar 

  10. Henriksson KG, Sandstedt P. Polymyositis: treatment and prognosis: a study of 107 patients. Acta Neurol Scand 1982; 65: 280-300

    Article  PubMed  CAS  Google Scholar 

  11. Airio A, Pukkala E, Isomali H. Elevated cancer incidence in patients with dermatomyositis: a population based study. J Rheumatol 1995; 22: 1300-3

    PubMed  CAS  Google Scholar 

  12. Sigurgeiersson B, Lindelof B, Edhag O, et al. Risk of cancer in patients with dermatomyositis or polymyositis. N Engl J Med 1992; 326: 363-7

    Article  Google Scholar 

  13. Kalmanti M, Athanasion A. Neuroblastoma occurring in a child with dermatomyositis. Am J Pediatr Hematol Oncol 1985; 7: 387-8

    PubMed  CAS  Google Scholar 

  14. Graham RM, Cox NH. Systemic disease and the skin. In: Burns T, Breathnach S, Cox N, et al., editors. Rook’s textbook of dermatology. 7th ed. Oxford: Blackwell Science, 2004: 59.1-59.75

  15. Cox NH, Lawrence CM, Langry JA, et al. Dermatomyositis: disease associations and an evaluation of screening investigations for malignancy. Arch Dermatol 1990; 126: 61-5

    Article  PubMed  CAS  Google Scholar 

  16. Callen JP. When and how should the patient with dermatomyositis or amyopathic dermatomyositis be assessed for possible cancer? Arch Dermatol 2002; 138: 969-71

    Article  PubMed  Google Scholar 

  17. Sparsa A, Liozon E, Hermann F, et al. Routine vs extensive malignancy search for adult dermatomyositis and polymyositis. Arch Dermatol 2002; 138: 885-90

    Article  PubMed  Google Scholar 

  18. Woo TY, Callen JP, Voorhees JJ, et al. Cutaneous lesions of dermatomyositis are improved by hydroxychloroquine. J Am Acad Dermatol 1984; 10: 592-600

    Article  PubMed  CAS  Google Scholar 

  19. Gelber AC, Nousari HC, Wigley FM. Mycophenolate mofetil in the treatment of severe skin manifestations of dermatomyositis: a series of 4 cases. J Rheumatol 2000; 27: 1542-5

    PubMed  CAS  Google Scholar 

  20. Choy EHS, Hoogendijk JE, Lecky B, et al. Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. Cochrane Database Syst Rev 2005; (3): CD003643.pub2

  21. Bolognia JL, Brewer YP, Cooper DL. Bazex syndrome (acrokeratosis paraneoplastica): an analytic review. Medicine (Baltimore) 1991; 70: 269-80

    CAS  Google Scholar 

  22. Bolognia JL. Bazex syndrome: acrokeratosis paraneoplastica. Semin Dermatol 1995; 14: 84-9

    Article  PubMed  CAS  Google Scholar 

  23. Akhyani M, Mansoori P, Taheri A, et al. Acrokeratosis paraneoplastica (Bazex syndrome) associated with breast cancer. Clin Exp Dermatol 2004; 29: 429-30

    Article  PubMed  CAS  Google Scholar 

  24. Weedon D. Miscellaneous conditions. In: Weedon D, editor. Skin pathology. Edinburgh: Churchill Livingstone, 1997: 482-87

    Google Scholar 

  25. Cohen PR, Kurzrock R. Sweet’s syndrome revisited: a review of disease concepts. Int J Dermatol 2003; 42: 761-78

    Article  PubMed  Google Scholar 

  26. Chan HL, Lee YS, Kuo TT. Sweet’s syndrome: clinicopathologic study of eleven cases. Int J Dermatol 1994; 33: 425-32

    Article  PubMed  CAS  Google Scholar 

  27. Soppi E, Nousiainen T, Seppa A, et al. Acute febrile neutrophilic dermatosis (Sweet’s syndrome) in association with myelodysplastic syndromes: a report of three cases and a review of the literature. Br J Haematol 1989; 73: 43-7

    Article  PubMed  CAS  Google Scholar 

  28. Fitzpatrick TB, Johnson RA, Wolff K, et al. Miscellaneous inflammatory disorders. In: Fitzpatrick TB, Johnson RA, Wolff K, et al., editors. Color atlas and synopsis of clinic dermatology. New York (NY): McGraw-Hill, 2001: 106-51

  29. Graham JA, Hansen KK, Rabinowitz LG, et al. Pyoderma gangrenosum in infants and children. Pediatr Dermatol 1994; 11: 10-7

    Article  PubMed  CAS  Google Scholar 

  30. Kurzrock R, Cohen PR. Mucocutaneous paraneoplastic manifestations of hematologic malignancies (review). Am J Med 1995; 99: 207-16

    Article  PubMed  CAS  Google Scholar 

  31. Chow RKP, Ho VC. Treatment of pyoderma gangrenosum. J Am Acad Dermatol 1996; 34: 1047-60

    Article  PubMed  CAS  Google Scholar 

  32. Lindelof B, Islam N, Eklund G, et al. Pemphigoid and cancer. Arch Dermatol 1990; 126: 66-8

    Article  CAS  Google Scholar 

  33. Venning VA, Wojnarowska F. The association of buttons pemphigoid and malignant disease: a case control study. Br J Dermatol 1990; 123: 439-45

    Article  PubMed  CAS  Google Scholar 

  34. Egan CA, Lazarova Z, Darling TN, et al. Antiepiligrin cicatricial pemphigoid and relative risk for cancer. Lancet 2001; 357: 1850-1

    Article  PubMed  CAS  Google Scholar 

  35. Kimyai-Asadi A, Jin MIL Paraneoplastic pemphigus. Int J Dermatol 2001; 40: 367-72

    Article  PubMed  CAS  Google Scholar 

  36. Anhalt GJ, Kim SC, Stanley JR, et al. Paraneoplastic pemphigus: an autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med 1990; 323: 1729-35

    Article  PubMed  CAS  Google Scholar 

  37. Bronnimann M, von Felbert V, Streit M, et al. Progressive respiratory failure in paraneoplastic pemphigus associated with chronic lymphocytic leukemia. Dermatology 2004; 208: 251-4

    Article  PubMed  CAS  Google Scholar 

  38. Kaplan I, Hodak E, Ackerman L, et al. Neoplasms associated with paraneoplastic pemphigus: a review with emphasis on non-hematologic malignancy and oral mucosal manifestations. Oral Oncology 2004; 40: 553-62

    Article  PubMed  Google Scholar 

  39. Weedon D. The vesicobullous reaction pattern. In: Weedon D, editor. Skin pathology. Edinburgh: Churchill Livingstone, 1997: 109-59

    Google Scholar 

  40. White JW, Perry HO. Erythema perstans. Br J Dermatol 1969; 81: 641-51

    Article  PubMed  CAS  Google Scholar 

  41. Skolnick M, Mainman ER. Erythema gyratum repens with metastatic adenocarcinoma. Arch Dermatol 1975; 111: 227-9

    Article  PubMed  CAS  Google Scholar 

  42. Barber PV, Doyle L, Vickers DM, et al. Erythema gyratum repens with pulmonary tuberculosis. Br J Dermatol 1978; 98: 465-8

    Article  PubMed  CAS  Google Scholar 

  43. Breathnach SM, Wilkinson JD, Black MM. Erythema gyratum repens-like figurate eruption in buttons pemphigoid. Clin Exp Dermatol 1982; 7: 401-6

    Article  PubMed  CAS  Google Scholar 

  44. Eubanks LE, McBumey E, Reed R. Erythema gyratum repens. Am J Med Sci 2001; 321: 459-81

    Article  Google Scholar 

  45. Kawakami T, Saito R. Erythema gyratum repens unassociated with underlying malignancy. J Dermatol 1995; 22: 587-9

    PubMed  CAS  Google Scholar 

  46. Caux F, Lebbe C, Thomine E, et al. Erythema gyratum repens: a case studied with immunofluorescence, immunoelectron microscopy and immunohistochemistry. Br J Dermatol 1994; 131: 102-7

    Article  PubMed  CAS  Google Scholar 

  47. Holt PJ, Davies MG. Erythema gyratum repens: an immunologically mediated dermatosis? Br J Dermatol 1977; 96: 343-7

    Article  PubMed  CAS  Google Scholar 

  48. Weedon D. Vasculopathic reaction pattern. In: Weedon D, editor. Skin pathology. Edinburgh: Churchill Livingstone, 1997: 408-9

    Google Scholar 

  49. Chastain MA. The glucagonoma syndrome: a review of its features and discussion of new perspectives. Am J Med Sci 2001; 321: 306-20

    Article  PubMed  CAS  Google Scholar 

  50. Weedon D. Metabolic and storage diseases. In: Weedon D, editor. Skin pathology. Edinburgh: Churchill Livingstone, 1997: 109-59

    Google Scholar 

  51. El Rassi Z, Partensky C, Valette PJ, et al. Necrolytic migratory erythema, first symptom of a malignant glucagonoma: treatment by long-acting somatostatin and surgical resection: report of three cases. Fur J Surg Oncol 1998; 24: 562-7

    Google Scholar 

  52. Blanco R, Martinez-Taboada VM, Rodriguez-Valverde V. Cutaneous vasculitis in children and adults: associated diseases and etiologic factors in 303 patients. Medicine 1998; 77: 403-18

    Article  PubMed  CAS  Google Scholar 

  53. Greer JM, Longley S, Edwards NL, et al. Vasculitis associated with malignancy: experience with 13 patients and literature review. Medicine (Baltimore) 1988; 67: 220-30

    CAS  Google Scholar 

  54. Trent IT, Kirsner RS. Vasculitis: a precis. Adv Skin Wound Care 2001: 14: 64-70

    Article  PubMed  CAS  Google Scholar 

  55. Longley S, Caldwell JR, Panush RS. Paraneoplastic vasculitis: unique syndrome of cutaneous angftis and arthritis associated with myeloproliferative disorders. Am J Med 1986; 80: 1027-30

    Article  PubMed  CAS  Google Scholar 

  56. Sanchez-Guerrero J, Gutierrez-Urena S, Vidaller A. Vasculitis as a paraneoplastic syndrome: report of 11 cases and review of the literature. J Rheumatol 1990; 17: 1458-62

    PubMed  CAS  Google Scholar 

  57. Agarwala SS. Paraneoplastic syndromes. Med Clin North Am 1996; 80: 173-84

    Article  PubMed  CAS  Google Scholar 

  58. Highet A. Urticarial vasculitis and IgA myeloma. Br J Dermatol 1980; 102: 355-7

    Article  PubMed  CAS  Google Scholar 

  59. Lewis JE. Urticarial vasculitis occurring in association with visceral malignancy. Acta Derm Venereol 1990; 70: 345-7

    PubMed  CAS  Google Scholar 

  60. Sprossman A, Muller RP. Urticaria-vasculitis syndrome in metastatic malignant testicular teratoma. Hautarzt 1994; 45: 871-4

    Article  Google Scholar 

  61. Wilson D, McCluggage WG, Wright GD. Urticarial vasculitis: a paraneoplastic presentation of B-cell non-Hodgkin’s lymphoma. Rheumatology 2002; 41: 476-7

    Article  PubMed  CAS  Google Scholar 

  62. Ducarme G, Rey D, Bryckaert PE, et al. Paraneoplastic urticarial vasculitis and renal carcinoma. Prog Urol 2003; 13: 495-7

    PubMed  Google Scholar 

  63. Kurzrock R, Cohen PR, Markowitz A. Clinic manifestations of vasculitis in patients with solid tumors: a case report and review of the literature. Arch Intern Med 1994; 154: 334-40

    Article  PubMed  CAS  Google Scholar 

  64. Lacour JP, Castanet J, Perrin C, et al. Cutaneous leukocytoclastic vasculitis and renal cancer: two cases. Am J Med 1993; 94: 104-8

    Article  PubMed  CAS  Google Scholar 

  65. Odeh M, Misselevich I, Oliven A. Squamous cell carcinoma of the lung presenting with cutaneous leukocytoclastic vasculitis: a case report. Angiology 2001; 52: 641-4

    Article  PubMed  CAS  Google Scholar 

  66. Schwartz RA, Williams ML. Acquired ichthyosis: a marker for internal disease. Am Fam Physician 1984; 29: 181-4

    PubMed  CAS  Google Scholar 

  67. Aram H. Acquired ichthyosis and related conditions. Int J Dermatol 1984; 23: 458-61

    PubMed  CAS  Google Scholar 

  68. Ameen M, Chopra S, Darvay A, et al. Erythema gyratum repens and acquired ichthyosis associated with transitional cell carcinoma of the kidney. Clin Exp Dermatol 2001; 26: 510-2

    Article  PubMed  CAS  Google Scholar 

  69. Kato N, Yasukawa K, Kimura K, et al. Anaplastic large-cell lymphoma associated with acquired ichthyosis. J Am Acad Dermatol 2000; 42: 914-20

    Article  PubMed  CAS  Google Scholar 

  70. Roselino AM, Souza CS, Andrade JM, et al. Dermatomyositis and acquired ichthyosis as paraneoplastic manifestations of ovarian tumor. Int J Dermatol 1997; 36: 611-4

    Article  PubMed  CAS  Google Scholar 

  71. DiGiovanna JJ. Ichthyosiform dermatoses. In: Freedberg IM, Eisen AZ, Wolff K, et al., editors. Fitzpatrick’s dermatology in general medicine. New York (NY): McGraw Hill, 1999: 594-5

  72. Engin H, Akdogan A, Altundag O. Non-small-cell lung cancer with nonfamilial diffuse palmoplantar keratoderma. J Exp Clin Cancer Res 2002; 21: 45-7

    PubMed  CAS  Google Scholar 

  73. Smith CH, Barker IN, Hay RJ. Diffuse plane xanthomatosis and acquired palmoplantar keratoderma in association with myeloma. Br J Dermatol 1995; 132: 286-9

    Article  PubMed  CAS  Google Scholar 

  74. Cruz P, Hud J. Excess insulin binding to insulin-like growth factor receptors: proposed mechanism for acanthosis nigricans. J Invest Dermatol 1992; 98: 82-5

    Article  Google Scholar 

  75. Pentenero M, Carrozzo M, Pagano M, et al. Oral acanthosis nigricans, tripe palms and sign of Leser-Trelat in a patient with gastric adenocarcinoma. Int J Dermatol 2004; 43: 530-2

    Article  PubMed  CAS  Google Scholar 

  76. Sabai G, Grant JM, Kurtz R, et al. Cutaneous manifestation of internal malignancies (I). Acanthosis nigricans. Int J Dermatol 1978; 17: 312-5

    Article  Google Scholar 

  77. Moller H, Eriksson S, Holen O, et al. Complete reversibility of paraneoplastic acanthosis nigricans after operation. Acta Med Scand 1978; 203: 245-6

    Article  PubMed  CAS  Google Scholar 

  78. Dantzig PI. Sign of Leser-Trelat. Arch Dermatol 1973; 108: 700-1

    Article  PubMed  CAS  Google Scholar 

  79. Williams MG. Acanthomata appearing after eczema. Br J Dermatol 1956; 68: 268-71

    Article  PubMed  CAS  Google Scholar 

  80. Feingold KR, Elias PM. Endocrine-skin interactions: cutaneous manifestations of adrenal disease, pheochromocytomas, carcinoid syndrome, sex hormone excess and deficiency, polyglandular autoimmune syndromes, multiple endocrine neo plasia syndromes, and other miscellaneous disorders. J Am Acad Dermatol 1988; 19: 1-20

    Article  PubMed  CAS  Google Scholar 

  81. Zeitlin IJ, Smith AN. 5-Hydroxyindoles and kinins in the carcinoid and dumping syndromes. Lancet 1966; 2: 986-91

    Article  PubMed  CAS  Google Scholar 

  82. Smith AG, Greaves MW. Blood prostaglandin activity associated with noradrenaline-provoked flush in the carcinoid syndrome. Br J Dermatol 1974; 90: 547-51

    Article  PubMed  CAS  Google Scholar 

  83. Greaves MW. Flushing and flushing syndromes, rosacea and perioral dermatitis. In: Champion RH, Burton JL, Burns DA, et al., editors. Rook/Wilkinson/Ebling textbook of dermatology. 6th ed. Oxford: Blackwell Science, 1998: 2099-2113

  84. Altman AR, Tschen JA, Rice L. Treatment of malignant carcinoid syndrome with a long-acting somatostatin analogue. Arch Dermatol 1989; 125: 394-6

    Article  PubMed  CAS  Google Scholar 

  85. Shah GM, Shah RG, Veilette H, et al. Biochemical assessment of niacin deficiency among carcinoid cancer patients. Am J Gastroenterol 2005; 100: 2307-14

    Article  PubMed  CAS  Google Scholar 

  86. Zarafonetis CID, Lorber SM, Manson SM. Association of functioning carcinoid syndrome and scleroderma. I: case report. Am J Med Sci 1958; 236: 1-14

    Article  PubMed  CAS  Google Scholar 

  87. Ratnavel RC, Burrows NP, Pye RJ. Scleroderma and the carcinoid syndrome. Clin Exp Dermatol 1994; 19: 83-5

    Article  PubMed  CAS  Google Scholar 

  88. Seuwen K, Magnaldo I, Pouyssegur J. Serotonin stimulates DNA synthesis in fibroblasts acting through 5-HTIB receptors coupled to a Gi-protein. Nature 1988; 335: 254-6

    Article  PubMed  CAS  Google Scholar 

  89. Rajamannan NM, Caplice N, Anthikad F, et al. Cell proliferation in carcinoid valve disease: a mechanism for serotonin effects. J Heart Valve Dis 2001; 10: 827-31

    PubMed  CAS  Google Scholar 

  90. Handley J, Walsh M, Armstrong K, et al. Malignant carcinoid syndrome associated with cutaneous scleroderma. Br J Dermatol 1993; 129: 222-3

    Article  PubMed  CAS  Google Scholar 

  91. Pavlovic M, Saiag P, Lotz P, et al. Regression of sclerodermatous skin lesions in a patient with carcinoid syndrome treated by octreotide. Arch Dermatol 1995; 131: 1207-9

    Article  PubMed  CAS  Google Scholar 

  92. Mallory SB. Other genodermatoses. In: Bolognia JL, Jorizzo JL, Rapini RP, et al., editors. Dermatology. Toronto (Canada): Elsevier Limited, 2003: 892-3

  93. Lynch HT, Fusaro RM, Roberts L, et al. Muir-Torre syndrome in several members of a family with a variant of the cancer family syndrome. Br J Dermatol 1985; 113: 295-301

    Article  PubMed  CAS  Google Scholar 

  94. Lynch HT, Lynch PM, Pester J, et al. The cancer family syndrome: rare cutaneous phenotypic linkage of Torre’s syndrome. Arch Intern Med 1981; 141: 607-11

    Article  PubMed  CAS  Google Scholar 

  95. Popnikolov NK, Gatalica Z, Colome-Grimmer MI, et al. Loss of mismatch repair protein in sebaceous gland tumors. J Cutan Pathol 2003; 30: 178-84

    Article  PubMed  Google Scholar 

  96. Serleth HI, Kisken WA. A Muir-Torre syndrome family. Am Surg 1998; 64 (4): 365-9

    PubMed  CAS  Google Scholar 

  97. Schwartz RA, Torre DP. The Muir-Torre syndrome: a 25-year retrospect. J Am Acad Dermatol 1995; 33: 90-104

    Article  PubMed  CAS  Google Scholar 

  98. Nakadi B, Nouwynck C, Salhadin A. Combined therapeutic approach for extraorbital sebaceous carcinoma in a Torre’s syndrome. Eur J Surg Oncol 1995; 21: 321-2

    Google Scholar 

  99. Schwartz RA, Goldberg DJ, Mahmood F, et al. The Muir-Torre syndrome: a disease of sebaceous and colonic neoplasms. Dermatologica 1989; 178: 23-8

    Article  PubMed  CAS  Google Scholar 

  100. Cohen PR, Kohn SR, Davis DA, et al. Muir-Torre syndrome. Dermatol Clin 1995; 13: 79-89

    PubMed  CAS  Google Scholar 

  101. Inoshita T, Youngberg GA. Keratoacanthomas associated with cervical squamous cell carcinoma. Arch Dermatol 1984; 120: 123-4

    Article  PubMed  CAS  Google Scholar 

  102. Yohay K. Neurofibromatosis types 1 and 2. Neurologist 2006; 12: 86-93

    Article  PubMed  Google Scholar 

  103. Barker D, Wright E, Nguyen K, et al. A genomic search for linkage of neurofibromatosis to RFLPs. J Med Genet 1987; 24: 536-8

    Article  PubMed  CAS  Google Scholar 

  104. Collins FS, Ponder BA, Seizinger BR, et al. The von Recklinghausen neurofibromatosis region on chromosome 17: genetic and physical maps come into focus. Am J Hum Genet 1989; 44: 1-5

    PubMed  CAS  Google Scholar 

  105. Raevaara TE, Gerdes AM, Lonnqvist KE, et al. HNPCC mutation MLHI P648S makes the functional protein unstable, and homozygosity predisposes to mild neurofibromatosis type 1. Genes Chromosomes Cancer 2004; 40: 261-5

    Article  PubMed  CAS  Google Scholar 

  106. Hasanreisoglu B, Or M, Akbatur H. Neurofibromatosis associated with retinoblastoma: case report. Br J Ophthalmol 1988; 72: 139-41

    Article  PubMed  CAS  Google Scholar 

  107. Duve S, Rakoski J. Cutaneous melanoma in a patient with neurofibromatosis: a case report and review of the literature. Br J Dermatol 1994; 131: 290-4

    Article  PubMed  CAS  Google Scholar 

  108. Friedman SM, Margo CE. Choroidal melanoma and neurofibromatosis type 1. Arch Ophthalmol 1998; 116: 694-5

    PubMed  CAS  Google Scholar 

  109. Bernadis V, Sorrentino D, Snidero D, et al. Intestinal leiomyosarcoma and gastroparesis associated with von Recklinghausen’s disease. Digestion 1999; 60: 82-5

    Article  Google Scholar 

  110. Martinez-Lage IF, Salcedo C, Corral M, et al. Medulloblastomas in neurofibromatosis type 1: case report and literature review. Neurocirugia (Astur) 2002; 13: 128-31

    CAS  Google Scholar 

  111. Hope DG, Mulvihill JJ. Malignancy in neurofibromatosis. Adv Neurol 1981; 29: 33-56

    PubMed  CAS  Google Scholar 

  112. Rosser T, Packer RJ. Intracranial neoplasms in children with neurofibromatosis 1. J Child Neurol 2002; 17: 630-7

    Article  PubMed  Google Scholar 

  113. Ceccaroni M, Genuardi M, Legge F, et al. BRCAI-related malignancies in a family presenting with von Recklinghausen’s disease. Gynecol Onco12002; 86: 375-8

  114. al-Gazali LI, Arthur RJ, Lamb IT, et al. Diagnostic and counselling difficulties using a fully comprehensive screening protocol for families at risk for tuberous sclerosis. J Med Genet 1989; 26: 694-703

    Google Scholar 

  115. Connor JM, Sampson J. Recent linkage studies in tuberous sclerosis: chromosome 9 markers. Ann N Y Acad Sci 1991; 615: 265-73

    Article  PubMed  CAS  Google Scholar 

  116. Kandt RS, Haines JL, Smith M, et al. Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nat Genet 1992; 2: 37-41

    Article  PubMed  CAS  Google Scholar 

  117. Rose VM. Neurocutaneous syndromes. Mo Med 2004; 101: 112-6

    PubMed  Google Scholar 

  118. Harper JI, Trembath RC. Genetics and genodermatoses. In: Burns T, Breathnach S, Cox N, et al., editors. Rook’s textbook of dermatology. 7th ed. Oxford: Blackwell Science, 2004: 12.1-12.85

  119. Smith HC, Watson GH, Patel RG, et al. Cardiac rhabdomyomata in tuberous sclerosis: their course and diagnostic value. Arch Dis Child 1989; 64: 196-200

    Article  PubMed  CAS  Google Scholar 

  120. Blute ML, Malek RS, Segura JW. Angiomyolipoma: clinical metamorphosis and concepts for management. J Urol 1988; 139: 20-4

    PubMed  CAS  Google Scholar 

  121. Devroede G, Lemieux B, Masse S, et al. Colonic hamarromms in tuberous sclerosis. Gastroenterology 1988; 94: 182-8

    CAS  Google Scholar 

  122. Roach ES, DiMario FJ, Kandt RS, et al. Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Tuberous Sclerosis Association. J Child Neurol 1999; 14: 401-7

    Article  PubMed  CAS  Google Scholar 

  123. Robbins TO, Bernstein J. Renal involvement. In: Gomez MR, editor. Tuberous sclerosis. New York (NY): Raven Press, 1988: 133-146

    Google Scholar 

  124. Pasyk KA, Argenta LC. Argon laser surgery of skin lesions in tuberous sclerosis. Ann Plast Surg 1988; 20: 426-33

    Article  PubMed  CAS  Google Scholar 

  125. Barax CN, Lebwohl M, Phelps RG. Multiple hamartoma syndrome. J Am Acad Dermatol 1987; 17: 342-6

    Article  PubMed  CAS  Google Scholar 

  126. Vega A, Torres J, Torres M, et al. A novel loss-of-function mutation (N48K) in the PTEN gene in a Spanish patient with Cowden disease. J Invest Dermato12003; 121: 1356-9

    Google Scholar 

  127. Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997; 275: 1943-7

    Article  PubMed  CAS  Google Scholar 

  128. Schaller J, Rohwedder A, Burgdorf WH, et al. Identification of human papillomavirus DNA in cutaneous lesions of Cowden syndrome. Dermatology 2003; 207: 134-40

    Article  PubMed  CAS  Google Scholar 

  129. Starink TM. Cowden’s disease: analysis of fourteen new cases. J Am Acad Dermatol 1984; 11: 1127-41

    Article  PubMed  CAS  Google Scholar 

  130. Fistarol SK, Anliker MD, Itin PH. Cowden disease or multiple hamartoma syndrome -cutaneous clue to internal malignancy. Fur J Dermatol 2002; 12: 411-21

    Google Scholar 

  131. Gorlin R. Nevoid basal cell carcinoma syndrome. Dermatol Clin 1995; 13: 113-25

    PubMed  CAS  Google Scholar 

  132. Winkler PA, Guyuron B. Multiple metastases from basal cell naevus syndrome. Br J Plast Surg 1987; 40: 528-31

    PubMed  CAS  Google Scholar 

  133. Schultz-Butulis BA, Gilson R, Farley M, et al. Nevoid basal cell carcinoma syndrome and non-Hodgkin’s lymphoma. Cutis 2000; 66: 35-8

    Google Scholar 

  134. Gailani MR, Bale SJ, Leffell DJ, et al. Developmental defects in Gorlin syndrome related to putative tumor suppressor gene on chromosome 9. Cell 1992; 69: 111-7

    Article  PubMed  CAS  Google Scholar 

  135. Xie J, Johnson RL, Zhang X, et al. Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors. Cancer Res 1997; 57: 2369-72

    PubMed  CAS  Google Scholar 

  136. Kopera D, Cerroni L, Fink-Puches R, et al. Different treatment modalities for the management of a patient with the nevoid basal cell carcinoma syndrome. J Am Acad Dermatol 1996; 34: 937-9

    Article  PubMed  CAS  Google Scholar 

  137. Gardner EJ. A genetic and clinic study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum. Am J Hum Genet 1951; 3: 167-76

    PubMed  CAS  Google Scholar 

  138. Narisawa Y, Kohda H. Cutaneous cysts of Gardner’s syndrome are similar to follicular stem cells. J Cutan Pathol 1995; 22: 115-21

    Article  PubMed  CAS  Google Scholar 

  139. Greenberg D, McIntyre H, Ramsaroop R, et al. Aggressive fibromatosis of the breast: a case report and literature review. Breast 12002; 8: 55-7

  140. Nandakumar G, Morgan JA, Silverberg D, et al. Familial polyposis coli: clinic manifestations, evaluation, management and treatment. Mt Sinai J Med 2004; 71: 384-91

    PubMed  Google Scholar 

  141. Cruz-Correa M, Giardiello FM. Diagnosis and management of hereditary colon cancer. Gastroenterol Clin North Am 2002; 31: 537-49

    Article  PubMed  Google Scholar 

  142. Schreibman IR, Baker M, Amos C, et al. The ham artomatous polyposis syndromes: a clinic and molecular review. Am J Gastroenterol 2005; 100: 476-90

    Article  PubMed  Google Scholar 

  143. Hemminki A. The molecular basis and clinic aspects of Peutz-Jeghers syndrome. Cell Mol Life Sci 1999; 55: 735-50

    Article  PubMed  CAS  Google Scholar 

  144. Westerman AM, Wilson JH. Peutz-Jeghers syndrome: risks of a hereditary condition. Scand J Gastroenterol 1999; 230 Suppl.: 64S-70S

  145. Harper PS, Harper RMJ, Howell-Evans AN. Carcinoma of the oesophagus with tylosis. Q J Med 1970; 39: 317-33

    PubMed  CAS  Google Scholar 

  146. Griffiths WAD, Judge MR, Leigh IM. Disorders of keratinization. In: Champion RH, Burton JL, Burns DA, et al., editors. Rook/Wilkinson/Ebling textbook of dermatology. 6th ed. Oxford: Blackwell Science, 1998: 1483-1588

  147. Adreev VC, Petkov I. Skin manifestations associated with tumours of the brain. Br J Dermatol 1975; 92: 675-8

    Article  PubMed  CAS  Google Scholar 

  148. Mercadante S, Villari P, Fulfaro F. Rifampicin in opioid-induced itching. Support Care Cancer 2001; 9: 467-8

    Article  PubMed  CAS  Google Scholar 

  149. Portenoy RK, Thaler HT, Komblith AB, et al. Symptom prevalence, characteristics and distress in a cancer population. Qual Life Res 1994; 3: 183-9

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Dr Davin Lim of Clatterbridge Hospital (Wirrall, UK) and Dr Jonathan Sowden of Wrexham Hospital (Wrexham, UK) for generously contributing clinical photographs.

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of the review.

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Correspondence to C. Elise Kleyn.

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Kleyn, C.E., Lai-Cheong, J.E. & Bell, H.K. Cutaneous Manifestations of Internal Malignancy. Am J Clin Dermatol 7, 71–84 (2006). https://doi.org/10.2165/00128071-200607020-00001

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