Massive extracellular tryptase from activated bladder mast cells in interstitial cystitis

Abstract

W report the case of a 51-year-old woman who presented with clinical symptoms of pelvic and bladder pain, urinary frequency, and bloating and irritability of 3 years’ duration. Her symptoms were often precipitated by stress or occurred during ovulation. The pertinent medical history included type I diabetes mellitus treated with insulin. Skin biopsies of suspected pigmented areas performed at the Massachusetts General Hospital in 1998 identified urticaria pigmentosa. However, the bone marrow biopsy for the possible diagnosis of systemic mastocytosis was negative for increased mast cells. The serum total tryptase level (measured at the Virginia Commonwealth University in 2000) was more than 100 ng/mL (normal considered to be less than 5 ng/mL) on two occasions. Cystoscopy under general anesthesia (performed at St. Bernadine Medical Center, California in 2000 and 2001) revealed glomerulations in about 50% of the bladder. Thus, interstitial cystitis was diagnosed according to the criteria established by the National Institutes of Health.1 Bladder biopsies of this patient, processed for routine pathologic examination and stained with toluidine blue, evidently contained few or no mast cells on two occasions. Increased bladder mast cells have emerged as the most consistent pathologic finding in interstitial cystitis.2 Unfortunately, routine formalin fixation of biopsy specimens leads to understaining of mucosal mast cells with toluidine blue, which also cannot recognize fully activated (degranulated) mast cells.2 Immunocytochemical staining for the unique mast cell protease, tryptase, adequately recognizes both connective tissue and mucosal mast cells.2 Bladder biopsy specimens from this patient obtained from the same areas sent for routine pathologic examination were stained for tryptase, as previously described.3 Figure 1 reveals massive extracellular tryptase, indicated by red staining. This technique also identifies the extreme mast cell activation (Fig. 1C).