Although the pathogenesis of BPH is not yet fully understood and several mechanisms seem to be involved in the development and progression, recent studies strongly suggest that BPH is an immune inflammatory disease. The T-cell activity and associated autoimmune reaction seem to induce epithelial and stromal cell proliferation. Further understanding of the role of inflammation in BPH and clinical detection of this inflammation will expand the understanding of BPH pathogenesis and its histologic and clinical progression, allow risk stratification for patients presenting with BPH-related LUTS, and suggest novel treatment strategies.
SUMMARY
BackgroundIrritable bowel syndrome is the most common disorder diagnosed by gastroenterologists. Although several randomized-controlled trials have assessed the therapeutic role of antidepressant drugs, there is insufficient evidence to support their use.
Introduction
Atypical hemolytic uremic syndrome (aHUS) is a prototypic thrombotic microangiopathy attributable to complement dysregulation. In the absence of complement inhibition, progressive clinical deterioration occurs. We postulated that a biopsy of normal skin could corroborate the diagnosis of aHUS via the demonstration of vascular deposits of C5b-9.
Materials and methods
Biopsies of normal skin from 22 patients with and without aHUS were processed for routine light microscopy as well as immunofluorescent studies. An assessment was made for vascular C5b-9 deposition immunohistochemically and by immunofluorescence. The biopsies were obtained primarily from the forearm and or deltoid.
Results
Patients with classic features of atypical HUS showed insidious microvascular changes including loose luminal platelet thrombi except in two patients in whom a striking thrombogenic vasculopathy was apparent in biopsied digital ulcers. Extensive microvascular deposits of the membrane attack complex (MAC)/ C5b-9 were identified excluding one patient in whom eculizumab was initiated prior to biopsy. In 5 of the 7 patients where follow-up was available, the patients exhibited an excellent treatment response to eculizumab. Patients without diagnostic clinical features of atypical HUS failed to show significant vascular deposits of complement except two patients with TTP including one in whom a Factor H mutation was identified.
Conclusion
In a clinical setting where aHUS is an important diagnostic consideration, extensive microvascular deposition of C5b-9 supports the diagnosis of either aHUS or a subset of TTP patients with concomitant complement dysregulation; significant vascular C5b-9 deposition predicts clinical responsiveness to eculizumab.
Background
We and others have noticed consistent staining of sebaceous glands with PReferentially expressed Antigen in MElanoma (PRAME). We aimed to determine whether PRAME was as sensitive, specific, and interpretable as adipophilin for distinguishing sebaceous neoplasms (SNs) from other neoplasms.
Methods
Twenty SNs and 32 control cases were stained for PRAME and adipophilin. Extent of staining was scored as follows: 0, no staining; 1, <5% positivity; 2, 5% to 50% positivity; and 3, >50% positivity. Intensity was scored as negative, weak, moderate, or strong. A composite score was determined by adding the scores for extent and intensity.
Results
PRAME had positive composite scores in all 20 SNs in the more differentiated areas, whereas adipophilin had positive composite scores in 19/20 cases. PRAME showed positivity in the basaloid cells in 15/16 cases, whereas adipophilin was positive in 14. Among controls, PRAME and adipophilin had positive composite scores in 3/32 cases and 6/32 cases, respectively.
Conclusions
PRAME and adipophilin are comparable in terms of distribution and intensity for staining sebocytes. In the basaloid cells, PRAME expression is often more diffuse and easier to detect than adipophilin. In comparing the SNs to the controls, PRAME was more sensitive and more specific than adipophilin. PRAME could be used as an additional marker of sebaceous differentiation in everyday practice.
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