In the most literal sense, granulomatosis indicates a condition characterized by multiple granulomas. Sarcoidosis is an archetype granulomatosis, although the term granulomatosis is rarely used in discussing or writing about sarcoidosis. In fact, the term granulomatosis is most often used Rapamycin supplier in the medical literature in the context of GPA (WG). Especially in the acute lesions of GPA

(WG), the predominant pattern of inflammation is not granulomatous, but purulent. Thus, the inflammation has the appearance of an abscess more than a granuloma (Fig. 2). Often, the only feature in the acute inflammatory lesions that is reminiscent of granulomatous inflammation is the presence of scattered multi-nucleated giant cells. As lesions age, they often develop Panobinostat manufacturer a central zone of necrosis that seems to evolve from extensive karyorrhectic (leucocytoclastic) debris to a central zone with a slightly basophilic hue, and finally to a central zone of amorphous acidophilic material (Fig. 3). Concurrent with this degeneration of the central zone of neutrophils, the periphery of the lesion accrues palisades of elongated macrophages and scattered multi-nucleated giant cells that justify being called granulomatous inflammation. Mark et al. [6] concluded that in GPA (WG):

‘Micronecrosis, usually with neutrophils (microabscesses), constitutes the early phase in the development of the pathognomonic organized palisading granuloma.’ They suggested that the multi-nucleated giant cells might be a secondary reactive response to the acute necrotizing lesions. This is supported PAK5 by the finding of engulfed apoptotic and necrotic neutrophil debris that can be seen occasionally within the multi-nucleated giant cells at sites of necrotizing inflammation in GPA (WG) (Fig. 2b). This prominence of neutrophilic

infiltrates (microabscesses) in the acute phase of the disease and the atypicality of the granulomatous inflammation that follows have been reported in detail in the literature [6,7] but probably, in part because of the term ‘granulomatosis’ in the name, concepts and theories about the pathogenesis of the extravascular inflammation in GPA (WG) have drawn analogies to typical granulomatous inflammation as seen in sarcoidosis or tuberculosis, which has little or no resemblance to the granulomatosis of GPA (WG). In a careful pathological study of pulmonary specimens from 35 patients with GPA (WG), Mark et al. [6] concluded that: ‘Compact granulomas of tuberculoid or sarcoidal type did not occur in the cases of Wegener’s granulomatosis.