Complicated Whipple's disease and endocarditis following tumor necrosis factor inhibitors

AIM: To test whether treatment with tumor necrosis factor inhibitors(TNFI) is associated with complications of Tropheryma whipplei(T. whipplei) infection. METHODS: Because unexplained arthritis is often the first Whipple’s disease(WD) symptom, patients may undergo treatment with TNFI before diagnosis. This may influence the course of infection with T. whipplei, which causes WD, because host immune defects contribute to the pathogenesis of WD. A literature search and cross referencing identified 19 reports of TNFI treatment prior to WD diagnosis. This case-control study compared clinical data in patients receiving TNFI therapy(group Ⅰ, n = 41) with patients not receiving TNFI therapy(group Ⅱ, n = 61). Patients from large reviews served as controls(group Ⅲ, n = 1059).RESULTS: The rate of endocarditis in patient group Ⅰ was significantly higher than in patient group Ⅱ(12.2% in group Ⅰ vs 1.6% in group Ⅱ, P 【 0.05), and group Ⅲ(12.2% in group Ⅰ vs 0.16% in group Ⅲ, P 【 0.01). Other, severe systemic or local WD complications such as pericarditis, fever or specific organ manifestations were increased also in group Ⅰ as compared to the other patient groups. However, diarrhea and weight loss were somewhat less frequent in patient group Ⅰ. WD istypically diagnosed with duodenal biopsy and periodic acid Schiff(PAS) staining. PAS-stain as standard diagnostic test had a very high percentage of false negative results(diagnostic failure in 63.6% of cases) in group I. Polymerase chain reaction(PCR) for T. whipplei was more accurate than PAS-stainings(diagnostic accuracy, rate of true positive tests 90.9% for PCR vs 36.4% for PAS, P 【 0.01).CONCLUSION: TNFI trigger severe WD complications, particularly endocarditis, and lead to false-negative PAS-tests. In case of TNFI treatment failure, infection with T. whipplei should be considered.

Neuroendocrine differentiation in ovarian mucinous tumors

OBJECTIVE: To investigate the relationship between neuroendocrine differentiation in ovarian mucinous tumors and its genesis. METHODS: A morphologic study of seventy-three cases of ovarian mucinous tumors (32 benign, 20 borderline, 21 malignant) using immunohistochemical and immunohistochemical/histochemical double staining techniques. RESULTS: The study showed that in tumors of benign, borderline and malignant types, the incidence of chromogranin A (CgA) positive cells was 62.5%, 75%, 76% and that of 5-hydroxytryptamine (5-HT) positive cells was 31.3%, 40% and 39%, respectively. Neuroendocrine cells (NEC) were not evenly distributed in any tumor. In four cases of the benign tumors, the number of CgA positive cells was more than 30 percent, localizing between the glandular basement membrane and the mucinous epithelial cells, with many intermediate cells containing both CgA and periodic acid-schiff (PAS) positive granules. CONCLUSION: The occurrence of both neuroendocrine and exocrine granules within the same cell has been previously described as 'intermediate' in pancreatic hyperplasia, pancreatic tumors and lung signet-ring cell carcinoids. This has not previously been observed in benign ovarian mucinous tumors. Finding both endocrine and exocrine granules within a single cell seems to indicate a histogenetic relationship between the ovarian endocrine and exocrine cells. The four cases of the benign tumors might be originated from a common stem cell, such as the so-called amphocrine cell. The relationship between these four tumors and neuroendocrine differentiation in ovarian mucinous tumors needs to be further clarified.