Multiple basal cell carcinoma in lymphoedema

Summary

Basal cell carcinoma is the most common malignant skin tumour, but rarely appears in more than one location. For these multiple basal cell carcinoma (MBCC), lymphoedema seems to be a predisposing factor. We report the case of a patient with secondary lymphoedema, presenting with a 3-year-history of ulcerations and papules on her lymphoedematous leg. Histology confirmed the clinical diagnosis of MBCC in all lesions.

Pathophysiologically, a strong risk factor for the development of MBCC in lymphoedema seems to be the local failure of immunosurveillance. In obstructive lymphoedema, an impairment of lymphocyte and Langerhans cell trafficking was observed, resulting in ineffective phagocytosis of foreign antigens. Consequently, lymphoedema is an immunologically vulnerable area, facilitating the development of MBCC. Nevertheless, other risk factors such as actinic skin damage and somatic mutations might also play a role in the development of MBCC in lymphoedema. Despite its rare occurrence, MBCC has to be taken into consideration in all suspicious skin lesions. Whenever in doubt, skin biopsy should be performed.

Zusammenfassung

Das Basalzellkarzinom ist der häufigste maligne Hauttumor. Nur selten wird es bei einem Patienten in mehreren Lokalisationen gleichzeitig gefunden. Eine mögliche Ursache für das Auftreten von solchen multiplen Basalzellkarzinomen (MBCC) ist das Lymphödem. Wir berichten über eine Patientin mit sekundärem Lymphödem, die sich mit seit drei Jahren bestehenden Ulzerationen und Papeln am lymphödematösen Unterschenkel vorstellte. Die histologische Untersuchung aller Hautveränderungen zeigte Basalzellkarzinome.

Pathophysiologisch scheint ein lokaler Immundefekt für die erleichterte Entwicklung von MBCC ausschlaggebend zu sein. Im Lymphödem konnte eine veränderte Aktivität der Langerhans-Zellen beobachtet werden, die eine ineffektive Phagozytose fremder Antigene zur Folge hat. Diese lokale Immunsuppression begünstigt die Entwicklung von MBCC im Lymphödem, aber auch andere Risikofaktoren wie Lichtschäden der Haut und somatische Mutationen dürfen nicht außer Acht gelassen werden. Trotz des seltenen Auftretens muss bei verdächtigen Läsionen an Basaliome gedacht und im Zweifel biopsiert werden.

Résumé

Le carcinome à cellules basales (BCC) est la tumeur maligne cutanée la plus fréquente. Cette lésion se développe en général à une seule localisation. Les auteurs décrivent ici le cas d’une patiente atteinte d’un carcinome multiloculaire à cellules basales (MBCC) en association avec un oedème lymphatique. La patiente, atteinte d’un lymphoedème, présentait depuis 3 ans des ulcérations et des papules à la jambe malade. L’examen histologique des lésions a permis de poser un diagnostic de carcinome multiloculaire à cellules basales. La pathologie de l’immunodéficience locale propre au lymphoedème semble se caractériser par une circulation réduite des cellules de Langerhans ainsi que par une phagocytose diminuée ou absente d’antigènes étrangers. Cette caractéristique paraît déterminante pour permettre le développement de tumeurs. En conclusion, le lymphoedème offre un milieu favorable au développement d’une immunodéficience locale, ce qui peut favoriser le développement de MBCC. D’autres facteurs (lésions actiniques, mutations diverses, etc.) peuvent contribuer au développement de ces tumeurs. Bien que les MBCC soient rares, il est nécessaire de rechercher ce type de tumeur en cas de lésions suspectes.

Keywords

Multiple basal cell carcinoma - lymphoedema - immunologically vulnerable area

Schlüsselwörter

Multiple Basalzellkarzinome - Lymphödem - lokaler Immundefekt

Mots clés

Carcinome multiloculaire à cellules basales ou carcinome baso-cellulaire - lymphoedème - immunodéficience locale

• References

• 1 Benson PM, Pessoa CM, Lupton GP. et al. Basal cell carcinomas arising in chronic lymphedema. J Dermatol Surg Oncol 1988; 14: 781-3.
• 2 Beswick SJ, Garrido MC, Fryer AA. et al. Multiple basal cell carcinomas and malignant melanoma following radiotherapy for ankylosing spondylitis. Clin Exp Dermatol 2000; 25: 381-3.
• 3 Dorfner B, Baum C, Voigtlander V. Multiple superficial basal cell carcinomas following chronic ingestion of sodium hydrogen carbonate containing arsenic. Hautarzt 2002; 53: 542-5.
• 4 Ekmekci P, Bostanci S, Anadolu R. et al. Multiple basal cell carcinomas developed after radiation therapy for tinea capitis: a case report. Dermatol Surg 2001; 27: 667-9.
• 5 Gailani MR, Stahle-Backdahl M, Leffell DJ. et al. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet 1996; 14: 78-81.
• 6 Gallagher RP, Hill GB, Bajdik CD. et al. Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma. Arch Dermatol 1995; 131: 157-63.
• 7 Gorlin RJ, Vickers RA, Kellen E. et al. Multiple Basal-Cell Nevi Syndrome. An analysis of a syndrome consisting of multiple nevoid basal-cell carcinoma, jaw cysts, skeletal anomalies, medulloblastoma, and hyporesponsiveness to parathormone. Cancer 1965; 18: 89-104.
• 8 Handa Y, Miwa S, Yamada M. et al. Multiple pigmented basal cell carcinomas arising in the normal-appearing skin after radiotherapy for carcinoma of the cervix. Dermatol Surg 2003; 29: 1233-5.
• 9 Happle R. Nonsyndromic type of hereditary multiple basal cell carcinoma. Am J Med Genet 2000; 95: 161-3.
• 10 Holikova Z, Massi D, Lotti T. et al. Insight into the pathogenesis of sporadic basal cell carcinoma. Int J Dermatol 2004; 43: 865-9.
• 11 Kim MY, Park HJ, Baek SC. et al. Mutations of the p53 and PTCH gene in basal cell carcinomas: UV mutation signature and strand bias. J Dermatol Sci 2002; 29: 1-9.
• 12 Klein E, Schwarz RA, Case RW. et al. Accessible tumors. In: Buglio Lo. (ed) Clinical immunotherapy. New York: Marcel Dekker Inc; 1980: 31-71.
• 13 Lear JT, Heagerty AH, Smith A. et al. Multiple cutaneous basal cell carcinomas: glutathione S-transferase (GSTM1, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) polymorphisms influence tumour numbers and accrual. Carcinogenesis 1996; 17: 1891-6.
• 14 Lear JT, Smith AG, Bowers B. et al. Truncal tumor site is associated with high risk of multiple basal cell carcinoma and is influenced by glutathione S-transferase, GSTT1, and cytochrome P450, CYP1A1 genotypes, and their interaction. J Invest Dermatol 1997; 108: 519-22.
• 15 Lear JT, Tan BB, Smith AG. et al. Risk factors for basal cell carcinoma in the UK: case-control study in 806 patients. J R Soc Med 1997; 90: 371-4.
• 16 Lotem M, Tamir G, Loven D. et al. Multiple basal cell carcinomas of the leg after recurrent erysipelas and chronic lymphedema. J Am Acad Dermatol 1994; 31: 812-3.
• 17 Lukas M, Stossel H, Hefel L. et al. Human cutaneous dendritic cells migrate through dermal lymphatic vessels in a skin organ culture model. J Invest Dermatol 1996; 106: 1293-9.
• 18 McGregor JM, Proby CM. Skin cancer in transplant recipients. Lancet 1995; 346: 964-5.
• 19 Michaelsson G, Olsson E, Westermark P. The Rombo syndrome: a familial disorder with vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, basal cell carcinomas and peripheral vasodilation with cyanosis. Acta Derm Venereol 1981; 61: 497-503.
• 20 Miller SJ. Biology of basal cell carcinoma (Part II). J Am Acad Dermatol 1991; 24: 161-75.
• 21 Olszewski WL, Engeset A, Romaniuk A. et al. Immune cells in peripheral lymph and skin of patients with obstructive lymphedema. Lymphology 1990; 23: 23-33.
• 22 Plosila M, Kiistala R, Niemi KM. The Bazex syndrome: follicular atrophoderma with multiple basal cell carcinomas, hypotrichosis and hypohidrosis. Clin Exp Dermatol 1981; 6: 31-41.
• 23 Ramsay HM, Fryer A, Strange RC. et al. Multiple basal cell carcinomas in a patient with acute myeloid leukaemia and chronic lymphocytic leukaemia. Clin Exp Dermatol 1999; 24: 281-2.
• 24 Rosso S, Zanetti R, Martinez C. et al. The multicentre south European study ‘Helios’. II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin. Br J Cancer 1996; 73: 1447-54.
• 25 Ruocco V, Pisani M, Astarita C. Stewart-Treves syndrome with local deficit of cellular immunity: pathogenic hypothesis. Ann Dermatol Venereol 1982; 109: 489-92.
• 26 Ruocco V, Schwartz RA, Ruocco E. Lymphedema: an immunologically vulnerable site for development of neoplasms. J Am Acad Dermatol 2002; 47: 124-7.
• 27 Schena D, Rosina P, Chieregato G. Onset of multiple basal cell carcinoma 60 years after X-ray treatment for tinea capitis. J Eur Acad Dermatol Venereol 2004; 18: 371-2.
• 28 Schon MP, Reifenberger J, von Schmiedeberg S. et al. Multiple basal cell carcinomas associated with hairy cell leukaemia. Br J Dermatol 1999; 140: 150-3.
• 29 Strossenreuther RH. Lymphedema--anatomy, pathophysiology and diagnosis. MMW Fortschr Med 2004; 146: 24-6.
• 30 Wallberg P, Kaaman T, Lindberg M. Multiple basal cell carcinoma. A clinical evaluation of risk factors. Acta Derm Venereol 1998; 78: 127-9.
• 31 Wei Q, Matanoski GM, Farmer ER. et al. DNA repair related to multiple skin cancers and drug use. Cancer Res 1994; 54: 437-40.
• 32 Weimar VM, Ceilley RI, Goeken JA. Aggressive biologic behavior of basal-and squamous-cell cancers in patients with chronic lymphocytic leukemia or chronic lymphocytic lymphoma. J Dermatol Surg Oncol 1979; 5: 609-14.
• 33 Wong SS, Tan KC, Goh CL. Cutaneous manifestations of chronic arsenicism: review of seventeen cases. J Am Acad Dermatol 1998; 38: 179-85.