Abdominal diffuse large B-cell lymphoma presenting in association with cutaneous granulomatous vasculitis

To the Editor: We report the case of a 72-year-old man who presented with cutaneous granulomatous vasculitis (CGV) in association with stage IVB diffuse large B-cell lymphoma. An exceptionally uncommon entity, CGV has only rarely been reported in conjunction with a primary malignant lymphoma. Although it has also been observed with various autoimmune disorders, infection, and inflammatory disorders, it has an especially poor prognosis when associated with lymphoproliferative disease. The patient was a 72-year-old man who originally presented in September 2005 with nonhealing upper extremity ulcers without constitutional symptoms. Antibiotic therapy was unsuccessful. One month later he presented to the emergency department with diffuse abdominal pain, vomiting, exertional dyspnea, and the same nonhealing ulcers. He was notably pancytopenic with new peripheral lymphadenopathy. Computed tomography of the abdomen/pelvis revealed bulky retroperitoneal lymphadenopathy and splenomegaly. Cytologic and flow cytometric analysis of a right inguinal lymph node fine-needle aspirate demonstrated a low-grade B-cell lymphoma. However, bone marrow biopsy specimen showed a diffuse CD20+ large B-cell lymphoma, raising concern for transformation of a low-grade small B-cell lymphoma to an intermediate-grade large B-cell lymphoma. Dermatology was consulted for the nonhealing cutaneous ulcers in the setting of likely rapidly advancing lymphoma. Overlying the right bicep were three 1- to 1.3-cm ulcers with a 2- to 3-mm thick hemorrhagic crust surrounded by a 3-mm ring of erythema and edema (Fig 1, A). Although there was a suggestion of a vasculitis causing a nonspecific pattern of full-thickness necrosis, the biopsy specimen was nondiagnostic. Meanwhile, cultures grew Staphylococcus aureus, prompting renewed antibiotic therapy. However, antibiotic therapy yielded no change in the lesion appearance. In November 2005, despite one course of chemotherapy, the lesions grew (Fig 1, B), prompting another punch biopsy specimen, which revealed a lymphohistiocytic infiltrate with associated granulomatous vasculitis and fibrinoid change of the medium dermal vessels (Fig 2). No atypical lymphoid infiltrates or malignant large B cells were present. Repeated cultures were sterile. Ultimately, the skin lesions resolved as the lymphoma regressed after successive cycles of chemotherapy. CGV is a rare histologic finding of unknown origin defined by vascular damage with fibrinoid change or hemorrhage in conjunction with a perivascular granulomatous infiltration.1Gibson L.E. el-Azhary R.A. Smith T.F. Reda A.M. The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation.J Cutan Pathol. 1994; 21: 437-445Crossref PubMed Scopus (26) Google Scholar Macroscopically, the condition manifests with papules, plaques, nodules, or ulcerations on the extremities although facial and truncal lesions have been observed.1Gibson L.E. el-Azhary R.A. Smith T.F. Reda A.M. The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation.J Cutan Pathol. 1994; 21: 437-445Crossref PubMed Scopus (26) Google Scholar, 2Gibson L.E. Winkelmann R.K. Cutaneous granulomatous vasculitis: its relationship to systemic disease.J Am Acad Dermatol. 1986; 14: 492-501Abstract Full Text PDF PubMed Scopus (38) Google Scholar Treatment involves treating the underlying disorder, but steroids are of some benefit.3Astudillo L. Recher C. Launay F. Lamant L. Brousset P. Arlet-Suau E. Malignant lymphoma presenting as cutaneous granulomatous vasculitis.Br J Dermatol. 2005; 152: 820-821Crossref PubMed Scopus (4) Google Scholar Our patient is one of a few cases reported in the literature of CGV in association with primary malignant lymphoma.1Gibson L.E. el-Azhary R.A. Smith T.F. Reda A.M. The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation.J Cutan Pathol. 1994; 21: 437-445Crossref PubMed Scopus (26) Google Scholar, 3Astudillo L. Recher C. Launay F. Lamant L. Brousset P. Arlet-Suau E. Malignant lymphoma presenting as cutaneous granulomatous vasculitis.Br J Dermatol. 2005; 152: 820-821Crossref PubMed Scopus (4) Google Scholar Like these cases,1Gibson L.E. el-Azhary R.A. Smith T.F. Reda A.M. The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation.J Cutan Pathol. 1994; 21: 437-445Crossref PubMed Scopus (26) Google Scholar, 3Astudillo L. Recher C. Launay F. Lamant L. Brousset P. Arlet-Suau E. Malignant lymphoma presenting as cutaneous granulomatous vasculitis.Br J Dermatol. 2005; 152: 820-821Crossref PubMed Scopus (4) Google Scholar our patient had no direct infiltration of malignant lymphocytes within the granulomatous lesion. Although it has been seen with autoimmune inflammatory disorders such as Crohn's disease4Sabat M. Leulmo J. Saez A. Cutaneous granulomatous vasculitis in metastatic Crohn's disease.J Eur Acad Dermatol Venereol. 2005; 19: 652-653Crossref PubMed Scopus (13) Google Scholar and sarcoidosis1Gibson L.E. el-Azhary R.A. Smith T.F. Reda A.M. The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation.J Cutan Pathol. 1994; 21: 437-445Crossref PubMed Scopus (26) Google Scholar and with infections including herpes virus,1Gibson L.E. el-Azhary R.A. Smith T.F. Reda A.M. The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation.J Cutan Pathol. 1994; 21: 437-445Crossref PubMed Scopus (26) Google Scholar, 5Snow J.L. el-Azhary R.A. Gibson L.E. Estes S.A. Espy M.J. Smith T.F. Granulomatous vasculitis associated with herpes virus: a persistent, painful, postherpetic papular eruption.Mayo Clin Proc. 1997; 72: 851-853Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar CGV is usually associated with systemic vasculitis and lymphoproliferative disease.1Gibson L.E. el-Azhary R.A. Smith T.F. Reda A.M. The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation.J Cutan Pathol. 1994; 21: 437-445Crossref PubMed Scopus (26) Google Scholar, 3Astudillo L. Recher C. Launay F. Lamant L. Brousset P. Arlet-Suau E. Malignant lymphoma presenting as cutaneous granulomatous vasculitis.Br J Dermatol. 2005; 152: 820-821Crossref PubMed Scopus (4) Google Scholar This latter association carries a particularly poor prognosis.2Gibson L.E. Winkelmann R.K. Cutaneous granulomatous vasculitis: its relationship to systemic disease.J Am Acad Dermatol. 1986; 14: 492-501Abstract Full Text PDF PubMed Scopus (38) Google Scholar In a review of 26 patients with CGV, Gibson et al2Gibson L.E. Winkelmann R.K. Cutaneous granulomatous vasculitis: its relationship to systemic disease.J Am Acad Dermatol. 1986; 14: 492-501Abstract Full Text PDF PubMed Scopus (38) Google Scholar showed that 5 of the 8 patients with lymphoproliferative disease died within 2 years of the onset of the skin lesions, whereas the 13 remaining patients with arthritis, gastrointestinal disease, sarcoidosis, and tuberculosis all had better outcomes. Cohen et al6Cohen Y. Amir G. Schibi G. Amariglio N. Polliack A. Rapidly progressive diffuse large B-cell lymphoma with initial clinical presentation mimicking seronegative Wegener's granulomatosis.Eur J Haematol. 2004; 73: 134-138Crossref PubMed Scopus (15) Google Scholar reported a patient with CGV whose therapy for misdiagnosed Wegener's granulomatosis ultimately masked a fatal chemo-resistant B-cell lymphoma. Thus, given the higher prevalence and mortality of CGV-associated lymphoproliferative disease, a diagnosis of CGV should prompt consideration of lymphoproliferative disorders, thereby allowing for better treatment options and response at a more treatable stage.