Delayed inflammatory leukoencephalopathy after gastric bypass surgery.

We describe an unusual leukoencephalopathy in a female who developed global language and memory difficulties as well as diffuse FLAIR lesions in the cerebral white matter (WM) ~ 30 months after bariatric surgery. She had no detectable nutritional deficiency. She died suddenly due to cardiovascular disease. The cerebral WM revealed perivascular T-cell infiltrations and strong immunoreactivity for the amyloid precursor protein limited to axons, without signs of myelin or neuronal injury. Unexplained WM lesions have been reported in post-bariatric-surgery patients. Our findings suggest that altered immunity and axonal dysfunction could be responsible for leukoencephalopathy in some patients undergoing bariatric procedures.
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Fatal coronary sinus thrombosis due to hypercoagulability in Crohn's disease.

A 27-year-old male, admitted to hospital for a psoas muscle abscess secondary to Crohn's disease, suddenly died while in hospital. A medicolegal autopsy showed coronary sinus thrombosis. Coronary sinus thrombosis is rare and is usually associated with invasive cardiac procedures. Coronary sinus thrombosis associated with Crohn's disease has not been reported. Autopsy examination of the coronary sinus is advocated, especially in individuals with hypercoagulable states.

Utility of cytokeratin 5/6, cytokeratin 20, and p16 in the diagnosis of reactive urothelial atypia and noninvasive component of urothelial neoplasia.

BACKGROUND: The utility of cytokeratin (CK)5/6 in distinguishing reactive urothelial atypia (RA) from urothelial carcinoma in situ (CIS) and from noninvasive component of high-grade papillary urothelial carcinoma (PUC) is unknown. DESIGN: Twenty RA with or without papillary hyperplasia and 90 noninvasive components of neoplastic urothelial lesions were submitted for immunostaining with CK5/6, CK20, and p16. RESULTS: Diffuse and strong reactivity involving the full or nearly full thickness of urothelium was observed with CK5/6 in 90% of RA cases. CK20 and p16 were negative in 90% and 85% of the RA cases, respectively. For CIS and noninvasive components of high-grade PUC without squamous differentiation, there was no CK5/6 staining or reactivity in the basal layer only. CK20 and p16 showed strong positivity in full thickness of urothelium in 75% to 85% of cases. CIS with weak/focal or negative reactivity for p16 or CK20 exhibited moderate cytologic atypia. Low-grade PUC displayed variable reactivity for CK5/6, CK20, and p16. Urothelial lesions with squamoid or basaloid features showed positive reactivity for CK5/6. Urothelial lesions with glandular differentiation showed negative reactivity for CK5/6. CONCLUSIONS: Diffuse CK5/6 reactivity in RA and negative CK5/6 reactivity in CIS and PUC may be helpful in distinguishing between these 2 entities.

Sudden death from superior mesenteric artery thrombosis in a cocaine user.

Cocaine-mediated tissue injury is well established, particularly myocardial ischemia and infarction. Gastrointestinal complications including mesenteric ischemia, ischemic colitis and intestinal perforation occur less frequently. Cocaine-induced visceral arterial thrombosis is a rare finding. We report a case of a 49-year-old chronic cocaine user with superior mesenteric artery (SMA) thrombosis. The patient presented with a 24-h history of abdominal pain, nausea and vomiting. Physical examination documented tachycardia and a soft, non-rigid abdomen with voluntary guarding. Abdominal X-ray did not show any evidence of peritoneal free air or bowel obstruction. Laboratory investigations revealed elevated white blood cells and a high anion gap; a blood gas analysis was not done. Three hours after initial presentation, the patient had a cardiac arrest and died. At autopsy, the jejunum was ischemic, without obvious infarction. The SMA was occluded at its origin by significant atherosclerosis with superimposed thrombus. The myocardium had fibrosis, without acute infarction, and severe triple coronary artery atherosclerosis. Toxicological blood analysis confirmed cocaine use. This report emphasizes the need to consider chronic stimulant drug abuse in accelerated atheroma and thrombosis of visceral arteries.

Myopericytoma: a pleural-based spindle cell neoplasm off the beaten path.

Myopericytoma is a recently described hemangiopericytoma-like neoplasm with myoid differentiation. These tumors are typically located in the subcutaneous and soft tissues of the extremities. The authors report a rare pleural-based pulmonary myopericytoma in a 58-year-old woman. The lesion was grossly homogeneous and well circumscribed. Microscopically, it was composed of densely packed spindle cells organized as whorls and short interlacing fascicles with a concentric perivascular distribution. Immunohistochemical reactions were positive for vimentin, smooth muscle actin (SMA), muscle-specific actin, and Bcl-2 and negative for desmin, h-caldesmon, cytokeratin, and CD34. Atypically, increased mitotic activity was noted, but no other malignant features were identified. The differential diagnoses are discussed with specific emphasis on solitary fibrous tumor of the pleura, which is the most common benign pleural-based spindle cell neoplasm and may be a diagnostic pitfall with potentially harmful consequences.

Comparative immunohistochemical study of the stroma of serous and mucinous cystic neoplasms: possible histopathogenetic relationship of the 2 entities.

OBJECTIVES: Serous and mucinous cystic neoplasms (SCNs/MCNs) are the most common true cystic neoplasms of the pancreas and occur more frequently in women. The aim of this study was to characterize the stroma of SCNs to compare its phenotype with that of MCNs. METHODS: A total of 12 SCNs and 5 MCNs were analyzed immunohistochemically using the following antisera: progesterone receptor (PR), estrogen receptor (ER), inhibin, CD10, and vimentin. Normal pancreatic tissue (17 cases) and ductal adenocarcinomas of the pancreas (3 cases) were used as controls. RESULTS: Eight of 12 patients with SCNs and all 5 patients with MCNs were women. For SCNs, the stroma was sclerotic and paucicellular and showed focal moderate to strong reactivity for PR. Estrogen receptor, CD10, and inhibin were virtually negative. For MCNs, the stroma was more cellular and ovarianlike and showed a larger number of PR-positive cells with focal expression of ER and inhibin. Vimentin was expressed in all stromal cells in both groups. CONCLUSIONS: Both SCNs and MCNs contain PR-positive stromal cells. In view of the aforementioned clinical and immunophenotypical similarities, we suggest that in SCNs and MCNs, the stromal framework is similar in origin and/or differentiation.

A serine/threonine-rich motif is one of three nuclear localization signals that determine unidirectional transport of the mineralocorticoid receptor to the nucleus.

The mineralocorticoid receptor (MR) is a tightly regulated nuclear hormone receptor that selectively transmits corticosteroid signals. Steroid treatment transforms MR from a transcriptionally inert state, in which it is distributed equally between the nucleus and cytoplasm, to an active completely nuclear transcription factor. We report here that MR is an atypical nuclear hormone receptor that moves unidirectionally from the cytoplasm to the nucleus. We show that nuclear import of MR is controlled through three nuclear localization signals (NLSs) of distinct types. Nuclear localization of naive MR was mediated primarily through a novel serine/threonine-rich NLS (NL0) in the receptor N terminus. Specific amino acid substitutions that mimicked phosphorylation selectively enhanced or repressed NL0 activity, highlighting the potential for active regulation of this new type of NLS. The second NLS (NL2) within the ligand-binding domain also lacks a recognizable basic motif. Nuclear transfer through this signal was strictly dependent on steroid agonist, but was independent of the interaction of MR with coactivator proteins. The third MR NLS (NL1) is a bipartite basic motif localized to the C terminus of the MR DNA-binding domain with properties distinct from those of NL1 of the closely related glucocorticoid receptor. NL1 acted in concert with NL0 and NL2 to stimulate nuclear uptake of the agonist-treated receptor, but also directed the complete nuclear localization of MR in response to treatment with steroid antagonist. These results present MR as a nuclear hormone receptor whose unidirectional transfer to the nucleus may be regulated through multiple pathways.

Discordant expression of HLA class II-associated co-chaperones and HLA-DRB alleles in cultured fibroblast-like synoviocytes.

Human leukocyte antigen (HLA)-DR-positive synovial fibroblasts are frequently observed in rheumatoid arthritis (RA) and may be implicated in the autoimmune reaction because RA is associated with certain HLA-DRB1* alleles. The question of whether components of the class II antigen presentation pathway and specific DRB alleles are efficiently expressed by synovial fibroblasts is germane to this hypothesis. To address this, cultured fibroblast-like synoviocytes (cFLS) were analyzed for constitutive and interferon (IFN)-gamma-induced expression of specific DRB alleles and class II-associated cochaperones. IFN-gamma induction of invariant chain, DM, and DR molecules was observed in all cFLS, but expression of specific DR allotypes was variable. Interestingly, DM-modulated epitopes on RA-associated DR molecules were either absent or delayed, despite strong DM expression and a paucity of major histocompatibility complex/class II-associated invariant chain peptide complexes. Altered expression of specific peptide-dependent epitopes on RA-associated HLA-DR molecules suggests differences in antigen presentation by cFLS, which may have implications for the immunopathogenesis of RA.