Atypical generalized granuloma annulare associated with two visceral cancers
Authors: Satoko Shimizu, Chikako Yasui, Kikuo Tsuchiya
Journal: Journal of the American Academy of Dermatology (2006)

To the Editor: Granuloma annulare (GA) is characterized by necrobiotic dermal papules with various clinical features, but the pathogenesis has not been fully elucidated. Several cases of GA associated with malignant neoplasia have recently been reported.1Stewart K.A. Cooper P.H. Greer K.E. Kersh C.R. Granuloma annulare temporally associated with carcinoma of the breast.J Am Acad Dermatol. 1989; 21: 309-311Abstract Full Text PDF PubMed Scopus (16) Google Scholar, 2Lo J.S. Guitart J. Bergfeld W.F. Granuloma annulare associated with metastatic adenocarcinoma.Int J Dermatol. 1991; 30: 281-283Crossref PubMed Scopus (7) Google Scholar, 3Vassileva S. Krasteva M. Marina S. Tsankov N. Widespread granuloma annulare and cervical adenocarcinoma.Int J Dermatol. 1992; 31: 819Crossref PubMed Scopus (13) Google Scholar, 4Cohen P.R. Granuloma annulare associated with malignancy.South Med J. 1997; 90: 1056-1059Crossref PubMed Scopus (45) Google Scholar, 5Antony F. Holden C.A. Sweet's syndrome in association with generalized granuloma annulare in a patient with previous breast carcinoma.Clin Exp Dermatol. 2001; 26: 668-670Crossref PubMed Scopus (19) Google Scholar, 6Akyol M. Kilicarslan H. Goze F. Emre S. Granuloma annulare associated with prostate carcinoma.J Eur Acad Dermatol Venereol. 2003; 17: 464-465Crossref PubMed Scopus (15) Google Scholar Here, we present an unusual case of generalized GA with atypical features, complicated by the development of two independent visceral neoplasia, from the ovary and stomach. A 68-year-old woman with a history of mild hypertension visited our hospital for generalized eruptions on her extremities and trunk during a 6-month period. On her first visit, approximately 100 asymptomatic yellow-brown to violaceous papules and plaques measuring from 0.5 to 3 cm were distributed predominantly over her extremities and chest (Fig 1, A). The skin biopsy specimens obtained from these distinct papules and plaques all basically showed similar histopathologic findings (Fig 1, B and C). A lymphohistiocytic infiltrate with epithelioid histiocytes and multinucleated giant cells presented in a diffuse or palisading pattern from the papillary to the reticular dermis. Granulomatous inflammation surrounding foci of altered collagen were occasionally seen. Although this case possesses some atypical features, we gave this patient a diagnosis of generalized GA on both clinical and pathologic grounds. Intralesional corticosteroids were moderately effective for some lesions; however, other treatments including tacrolimus ointment, systemic tranilast, minocycline, vitamin E, and UVB therapy were ineffective. Two and a half years after the initial visit, she had appetite loss. Detailed examination revealed the presence of an advanced ovarian cancer (mucinous cystadenocarcinoma) and stomach cancer (signet ring cell carcinoma), respectively. Both cancers were removed simultaneously, and followed by chemotherapy including paclitaxel and carboplatin treatments. The skin lesion completely disappeared leaving postinflammatory pigmentation 1 month after removal of both cancers. No similar cases of GA complicated by two visceral cancers were detected after an extensive search of the MEDLINE database literature from 1966 to 2005. There were 8 cases, including the current case, with GA associated with cancer, which were described in detail (Table I).1Stewart K.A. Cooper P.H. Greer K.E. Kersh C.R. Granuloma annulare temporally associated with carcinoma of the breast.J Am Acad Dermatol. 1989; 21: 309-311Abstract Full Text PDF PubMed Scopus (16) Google Scholar, 2Lo J.S. Guitart J. Bergfeld W.F. Granuloma annulare associated with metastatic adenocarcinoma.Int J Dermatol. 1991; 30: 281-283Crossref PubMed Scopus (7) Google Scholar, 3Vassileva S. Krasteva M. Marina S. Tsankov N. Widespread granuloma annulare and cervical adenocarcinoma.Int J Dermatol. 1992; 31: 819Crossref PubMed Scopus (13) Google Scholar, 4Cohen P.R. Granuloma annulare associated with malignancy.South Med J. 1997; 90: 1056-1059Crossref PubMed Scopus (45) Google Scholar, 5Antony F. Holden C.A. Sweet's syndrome in association with generalized granuloma annulare in a patient with previous breast carcinoma.Clin Exp Dermatol. 2001; 26: 668-670Crossref PubMed Scopus (19) Google Scholar, 6Akyol M. Kilicarslan H. Goze F. Emre S. Granuloma annulare associated with prostate carcinoma.J Eur Acad Dermatol Venereol. 2003; 17: 464-465Crossref PubMed Scopus (15) Google Scholar Mean age at GA onset was 56.9 years, which is older than that of typical age for GA, which is usually a disease of children and young adults.7Li A. Hogan D.J. Sanusi I.D. Smoller B.R. Granuloma annulare and malignant neoplasms.Am J Dermatopathol. 2003; 25: 113-116Crossref PubMed Scopus (88) Google Scholar The order of GA and cancers were variable. The time interval between GA and cancer could not be precisely evaluated, because both GA and cancer are usually asymptomatic at the early stages and are often overlooked. However, we emphasize that the resolution of GA occurred after the cancer removal operations in two cases, and after operation and chemotherapy in two cases. Cohen4Cohen P.R. Granuloma annulare associated with malignancy.South Med J. 1997; 90: 1056-1059Crossref PubMed Scopus (45) Google Scholar recently defined a new term, "malignancy-associated GA," in which the onset of GA lesions coincided with the discovery of a previously unsuspected visceral neoplasm or recurrent metastatic disease. It is speculated that GA results from an immunologic reaction stimulated by an unidentified tumor antigen.6Akyol M. Kilicarslan H. Goze F. Emre S. Granuloma annulare associated with prostate carcinoma.J Eur Acad Dermatol Venereol. 2003; 17: 464-465Crossref PubMed Scopus (15) Google Scholar In conclusion, GA complicated with two visceral cancers is rare. The review of the literature indicates that we should be aware of the possibility of underlying cancers, especially in elderly patients with GA and an atypical presentation.Table IGranuloma annulare associated with cancerYear of publicationAge, ySexOrganHistologyClinical typeOnsetCourseRef. no.198952FBreastInfiltrating ductal carcinomaErythematous plaque1mo before neoplasmDisappeared 1 mo after operation. Reappeared 1 mo before metastasis. Disappeared again after operation and chemotherapy.1Stewart K.A. Cooper P.H. Greer K.E. Kersh C.R. Granuloma annulare temporally associated with carcinoma of the breast.J Am Acad Dermatol. 1989; 21: 309-311Abstract Full Text PDF PubMed Scopus (16) Google Scholar199159MMetastatic colon cancerAdenocarcinomaPlaque26 mo after neoplasmDisappeared spontaneously in 6 wk2Lo J.S. Guitart J. Bergfeld W.F. Granuloma annulare associated with metastatic adenocarcinoma.Int J Dermatol. 1991; 30: 281-283Crossref PubMed Scopus (7) Google Scholar199242FCervixAdenocarcinomaGeneralized papulesSimultaneousDisappeared after operation and chemotherapy3Vassileva S. Krasteva M. Marina S. Tsankov N. Widespread granuloma annulare and cervical adenocarcinoma.Int J Dermatol. 1992; 31: 819Crossref PubMed Scopus (13) Google Scholar199238FCervixAdenocarcinomaGeneralized papules and plaques5 mo before neoplasmDisappeared 2 mo after operation3Vassileva S. Krasteva M. Marina S. Tsankov N. Widespread granuloma annulare and cervical adenocarcinoma.Int J Dermatol. 1992; 31: 819Crossref PubMed Scopus (13) Google Scholar199775MLungAdenocarcinomaGeneralized papules and nodulesSimultaneousDisappeared after chemotherapy4Cohen P.R. Granuloma annulare associated with malignancy.South Med J. 1997; 90: 1056-1059Crossref PubMed Scopus (45) Google Scholar200161FBreastNot writtenGeneralized erythematous papular eruption3 y after neoplasmNo change5Antony F. Holden C.A. Sweet's syndrome in association with generalized granuloma annulare in a patient with previous breast carcinoma.Clin Exp Dermatol. 2001; 26: 668-670Crossref PubMed Scopus (19) Google Scholar200360MProstateAdenocarcinomaLocalized papulesSimultaneousUnchanged 3 mo after operation6Akyol M. Kilicarslan H. Goze F. Emre S. Granuloma annulare associated with prostate carcinoma.J Eur Acad Dermatol Venereol. 2003; 17: 464-465Crossref PubMed Scopus (15) Google ScholarCurrent case68FStomach and ovaryMucinous cyst adenocarcinoma, signet ring cell carcinomaGeneralized papules and nodules2.5 y before detection of advanced tumorDisappeared after operation and chemotherapyF, Female; M, male. Open table in a new tab F, Female; M, male.