Demonstration of epitope-spreading phenomena in bullous pemphigoid: results of a prospective multicenter study

Bullous pemphigoid (BP), the most common autoimmune subepidermal bullous disease, is associated with an autoantibody response to BP180 and BP230, two components of junctional adhesion complexes in human skin promoting dermo-epidermal cohesion. Retrospective analyses demonstrated that these autoantigens harbor several epitopes targeted by autoaggressive B and T cells. The aim of this prospective multicenter study was to assess the evolution of IgG autoantibodies in 35 BP patients over a 12-month observation period. Epitope-spreading (ES) events were detected in 17 of 35 BP patients (49%). They preferentially occurred in an early stage of the disease and were significantly related to disease severity at diagnosis. Moreover, in three patients, spreading of IgG reactivity to intracellular epitopes of BP180 and BP230 was preceded by recognition of the BP180 ectodomain. Finally, IgG reactivity with extracellular epitopes of BP180 and intracellular epitopes of BP230 correlated with the severity of BP in disease course. These findings support the idea that IgG recognition of the BP180 ectodomain is an early and crucial event in BP disease, followed by variable intra- and intermolecular ES events, which likely shape the individual course of BP.

Is there an indication for frozen section examination of the ureteral margins during cystectomy for transitional cell carcinoma of the bladder?

PURPOSE: We evaluated the incidence of pathological findings of the ureter at cystectomy for transitional cell carcinoma of the bladder and assessed the usefulness of intraoperative frozen section examination of the ureter. MATERIALS AND METHODS: Histopathological findings of ureteral frozen section examination were compared to the corresponding permanent sections and the diagnostic accuracy of frozen section examination was evaluated. These segments were then compared to the more proximal ureteral segments resected at the level where they cross over the common iliac arteries. The histopathological findings of the ureteral segments were then correlated for upper urinary tract recurrence and overall survival. RESULTS: Transitional cell carcinoma or carcinoma in situ was found on frozen section examination of the distal ureter in 39 of 805 patients (4.8%) and on permanent sections in 29 (3.6%). In 755 patients the false-negative rate of frozen section examination of the ureters was 0.8%. Of the patients with carcinoma in situ diagnosed on the first frozen section examination 80% also had carcinoma in situ in the bladder. Transitional cell carcinoma or carcinoma in situ in the most proximally resected ureteral segments was found in 1.2% of patients. After radical cystectomy there was tumor recurrence in the upper urinary tract in 3% of patients with negative ureteral frozen section examination and in 17% with carcinoma in situ on frozen section examination. CONCLUSIONS: Routine frozen section examination of the ureters at radical cystectomy is only recommended for patients with carcinoma in situ of the bladder, provided the ureters are resected where they cross the common iliac arteries.