Case 1 -

Necrotizing Granulomatous Dermatitis and Panniculitis Associated with Inflammatory Bowel Disease Victor G. Prieto UT-MD Anderson Cancer Center Houston TX

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Clinical history: A 51-year-old white woman with a history of rheumatoid arthritis, steroid-dependent ulcerative colitis, and diabetes mellitus was hospitalized with fever and red painful subcutaneous nodules on both inner thighs. An initial biopsy was thought to represent an abscess but she did not improve with broad-spectrum oral and intravenous antibiotics. The sites became necrotic, were debrided multiple times, and required administration of hyperbaric oxygen therapy. Physical exam revealed two opposing, large ulcers on the inner surface of both thighs. The biopsy was interpreted as consistent with T-cell lymphoma and the patient was referred to MDACC for treatment. Case 1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 1 - Figure 1 Case 1 - Figure 2 Case 1 - Figure 3 Case 1 - Figure 4 Case 1 - Figure 5 Histologic features: The punch biopsy shows skin to the upper subcutaneous tissue. The dermis and subcutaneous tissue contain large areas of confluent necrosis with macrophages and granulomatous infiltrate. There is also a superficial and deep infiltrate with large and small lymphocytes, some with convoluted contours, diffusely infiltrating the subcutaneous tissue, accompanied by neutrophils, plasma cells and scattered eosinophils. Some of the lymphocytes in the subcutaneous tissue are located around fat vacuoles ("rimming"). Special stains are negative for microorganisms. Immunohistochemical studies reveal a predominance of CD3 cells with approximately similar numbers of CD4 and CD8. Anti-TIA and granzyme B are essentially negative. Diagnosis: Necrotizing granulomatous dermatitis and panniculitis associated with inflammatory bowel disease Differential diagnosis: Subcutaneous T-cell lymphoma Granulomatous mycosis fungoides Infection Other granulomatous processes Discussion: After our diagnosis of "granulomatous dermatitis, no evidence of lymphoma or infection", further questioning revealed the patient had a previous diagnosis of steroid-dependent ulcerative colitis. Cutaneous manifestations, most commonly erythema nodosum and pyoderma gangrenosum, are seen in approximately 10 to 20 % of patients with Crohn disease (CD) and ulcerative colitis (UC). Other shared cutaneous associations include aphthous stomatitis, finger clubbing, cutaneous polyarteritis nodosa, psoriasis, pyostomatitis vegetans, erythema multiforme and vitiligo. Granulomatous changes have been described in skin lesions from patients with inflammatory bowel disease (IBD). Metastatic CD is the term referring to extraintestinal Crohn, as red to violaceous papules, nodules and plaques that often ulcerate. Histologically, it usually has non-caseating granulomas. Also seen are necrobiosis, panniculitis, and granulomatous perivasculitis and vasculitis, similar to the findings seen in this case. In particular, giant cells have been reported in pyoderma gangrenosum associated with inflammatory bowel disease. Also reported in inflammatory bowel disease are neutrophilic cutaneous processes (pyoderma gangrenosum, vesicopustular eruptions, erythema elevatum diutinum, Sweet syndrome, linear IgA bullous disease and neutrophilic lobular panniculitis). The differential diagnosis in a patient with large ulcers and history of immunosuppression includes infection and malignancy. Special stains for microorganisms and cultures ruled out an infectious etiology. Granulomatous inflammation may be seen in patients in multiple lymphoid processe, particularly mycosis fungoides / granulomatous slack skin, subcutaneous panniculitic T-cell lymphoma, and primary cutaneous anaplastic (CD30+) large cell lymphoma. Rarely, cutaneous B-cell lymphomas, both primary and secondary, can show granulomatous reactions. In evaluating these cases, immunohistochemical studies can help to characterize the inflammatory infiltrate. In summary, this case illustrates that inflammatory bowel disease should be included in the differential diagnosis for lesions showing "rimming" of lymphocytes, particularly when accompanied by granulomas and neutrophilic infiltrates. Clinical-pathologic correlation will be essential in such cases. References: Berkowitz EZ, Lebwohl M. Cutaneous manifestations of inflammatory bowel disease. J Eur Acad Dermatol Venereol 2000; 14: 349-350. Hackzell-Bradley, M, Hedbald, MA, Stephansson, EA. Metastatic Crohn's disease: three cases with unusual clinical and histopathologic features in men. Arch Dermatol 1996; 132: 928-32. LeBoit, PE, Zackheim HS, White CR Jr. Granulomatous variants of cutaneous T-cell lymphoma. The histopathology of granulomatous mycosis fungoides and granulomatous slack skin. Am J Surg Pathol 1998; 12: 83-95. Montemarano, AD, Rowe JE, Benson PM et al. Ki-1 (CD30+) positive anaplastic large cell lymphoma mimicking an infectious granuloma. Int J Dermatol 1995; 34: 790-793. Sabat M, Luelmo J, Saez A. Cutaneous granulomatous vasculitis in metastatic Crohn's disease. J Eur Acad Dermatol Venereol 2005; 19: 652-3. Scarabello A, Leinweber B, Ardigo M, et al. Granulomatous lymphomas with prominent granulomatous reaction. A potential pitfall in the histologic diagnosis of cutaneous T- and B-cell lymphomas. Am J Surg Pathol 2002; 26: 1259-1268. Shoji T, Ali S, Gateva E, Leytin A, and Phelps RG. A granulomatous dermatitis associated with idiopathic ulcerative colitis. Int J Dermatol 2000; 39: 205-217. Trost LB, McDonnell JK. Important cutaneous manifestations of inflammatory bowel disease. Postgrad Med J 2005; 81: 580-585.