Evaluation of the role of sampling technique and site of polyarteritis nodosa (PAN)-associated cutaneous ulcer in the yield of the histopathologic diagnosis.
Hematoxylin-eosin–stained biopsy specimens from clinically active cutaneous ulcers associated with polyarteritis nodosa (PAN). A, Incisional biopsy specimen from an ulcer periphery shows a medium-deep to deep dermal medium-sized muscular artery (arrow) with scant perivascular lymphocytic inflammation and intramural fibrosis but no necrotizing or other histologic feature of medium-sized vessel (MSV) vasculitis. Dense interstitial dermal fibrosis is also present (original magnification ×2.5). B, Greater magnification of the artery indicated by the arrow in panel A (original magnification ×40). C, Narrow incisional specimen containing subcutis and including nearby central tissue. The dermal-subcutaneous junction underlying the nearby central area of the ulcer reveals MSV vasculitis with necrotizing features, endothelial swelling, and a neutrophil-rich infiltrate with leukocytoclasia. The wedge-shaped area of skin overlying the affected MSV (arrow) that would normally be its blood supply reveals dermal necrosis (most evident in the upper dermis) and epidermal ulceration (original magnification ×2.5). D, Greater magnification of the MSV area indicated by the arrow in panel C (original magnification ×40).
Ricotti C, Kowalczyk JP, Ghersi M, Nousari CH. The Diagnostic Yield of Histopathologic Sampling Techniques in PAN-Associated Cutaneous Ulcers. Arch Dermatol. 2007;143(10):1331–1344. doi:10.1001/archderm.143.10.1334
Polyarteritis nodosa (PAN), a medium-sized vessel (MSV) vasculitis, may result in cutaneous ulcers.1 There is no specific serologic abnormality associated with PAN; therefore, the mainstay diagnosis consists of histologic evidence of MSV vasculitis in the context of pertinent clinical findings.2 Several factors may contribute to the potential low diagnostic yield of tissue biopsy specimens from MSV-vasculitic ulcers. The present study evaluates the role of tissue sampling in the histologic evaluation of PAN-associated cutaneous ulcers.
Retrospective analysis of de-identified archival biopsy specimens taken from skin ulcers and sural nerves of 29 patients with histologically proven PAN-associated MSV vasculitis. Patients met the classification and definitional criteria of the American College of Rheumatology3 and Chapel Hill Consensus Conference.4 Specimens were obtained from Johns Hopkins University, University of Pennsylvania, and Ameripath Inc. Biopsy technique, depth and site within the ulcer, and histologic findings were evaluated by the same dermatopathologist (C.H.N). Peripheral ulcer areas were defined to include the ulcer edge and surrounding nonulcerated skin, whereas nearby central ulcer areas included the areas near the ulcer center. Both areas were determined by the referring physician and histopathologically. Fisher exact and χ² tests were performed.
Of the 29 biopsy-proven cases of PAN-associated cutaneous ulcers, 26 were confirmed with skin specimens that included subcutaneous tissue and peripheral and nearby central areas of the ulcer (Figure 1). Sampling techniques ranged from incisional to deep punch biopsies and included the double trephine method.5 Peripheral and nearby central biopsy specimens were acquired by either a single elliptical incision or by multiple, separate, deep punch biopsies, both techniques performed along a radial trajectory (perpendicular to the ulcer edge).
Of the 26 patients with skin biopsy confirmation, 9 had to undergo repeated biopsies for diagnosis to be rendered. For 3 of the 29 patients, dermatopathologic confirmation could not be obtained despite repeated biopsy specimen evaluation, and histologic confirmation through sural nerve biopsies was required. Repeated skin biopsy specimens from only 1 of these 3 patients contained subcutis and were obtained from peripheral and nearby central areas. Specimens from the other 2 patients who underwent repeated skin biopsies contained subcutis but lacked nearby central ulcer tissue.
Owing to small sample size, Fisher exact and χ² tests were performed on 2 variables: (1) specimens containing subcutis and peripheral and nearby central ulcer areas (n = 27) vs (2) specimens with neither subcutis nor nearby central areas (n = 14), both variables yielding a histologic diagnosis of PAN. The χ² value (38.07), exceeded the critical threshold for .05 probability level (3.84); therefore, the difference in diagnostic yield between the 2 variables was significant. The Fisher exact test also yielded a nondirectional 2-tailed probability of P < .001.
Histologic evidence of MSV vasculitis in conjunction with pertinent clinical and ancillary study correlation are the gold standard diagnostic pillars for PAN. The present study shows that subcutis-containing specimens that include not only peripheral ulcer areas but also nearby central areas offer the best histologic yield for the diagnosis of PAN-associated ulcers (Figure 2). On the other hand, all initial and the vast majority of repeated nondiagnostic biopsy specimens were lacking subcutis and/or were obtained from only the ulcer periphery. Cutaneous MSVs are located in the dermal-subcutaneous junction, deep dermis, or subcutis. When MSVs are affected by a vasoocclusive process, ulcers can result in the wedge-shaped area of skin above the affected MSV that normally provides that skin's blood supply. This finding supports the notion that obtaining subcutis-containing specimens from nearby central areas of PAN-associated ulcers would increase diagnostic yield.
Polyarteritis nodosa–associated cutaneous ulcers carry a worse prognosis that other cutaneous presentations. Early diagnosis and prompt and effective therapy would reduce the high PAN-associated morbidity and mortality. The present study underscores the importance of adequate sampling as a factor in the early diagnosis of PAN-associated cutaneous ulcers.
Correspondence: Dr Nousari, Institute for Immunofluorescence, Dermpath Diagnostics South Florida, 895 SW 30th Avenue, Ste 101, Pompano Beach, FL 33069 (firstname.lastname@example.org).
Financial Disclosure: None reported.