Hemorrhagic shock and encephalopathy syndrome in a patient with a de novo heterozygous variant in KIF1A.

INTRODUCTION: KIF1A, a gene that encodes a neuron-specific motor protein, plays important roles in cargo transport along neurites. Variants in KIF1A have been described in three different disorders, and neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment syndrome (NESCAVS) is the severest phenotype. CASE REPORT: A 3-year-old girl was born at term with a birth weight of 2590 g. At five months of age, she visited our hospital due to developmental delay. An EEG showed multiple epileptic discharge, and a nerve conduction study showed severe axonopathy of both motor and sensory nerves. We performed exome sequencing and identified a de novo heterozygous missense variant in KIF1A (NM_001244008.1: c. 757G > A, p.E253K). At six months of age, she developed acute encephalopathy, multiple organ failure and disseminated intravascular coagulation, necessitating intensive care. Her brain CT showed severe brain edema, followed by profound brain atrophy. We diagnosed hemorrhagic shock and encephalopathy syndrome (HSES) according to the clinico-radiological features. Currently, she is bed-ridden, and requires gastrostomy because of dysphagia. CONCLUSION: The clinical course of our case confirmed that p.E253K is associated with severe neurological features. Severe KIF1A deficiency could cause thermoregulatory dysfunction and may increase the risk of acute encephalopathy including HSES.

Immunohistochemical expression of myoepithelial markers in adenomyoepithelioma of the breast: a unique paradoxical staining pattern of high-molecular weight cytokeratins.

To determine which immunohistochemical markers are useful for the identification of neoplastic myoepithelial cells in adenomyoepithelioma of the breast, the expression of seven myoepithelial markers (α-smooth muscle actin (α-SMA), calponin, p63, CD10, cytokeratin 5/6, cytokeratin 14, and S-100) was examined in 19 lesions from 16 patients. The lesion consisted of seven spindle and 12 clear cell lesions. For normal myoepithelial cells, α-SMA, calponin, and p63 were significantly more sensitive than cytokeratin 5/6, cytokeratin 14, and S-100. There was no significant difference in the expression of α-SMA, calponin, p63, and CD10 in neoplastic myoepithelial cells of adenomyoepithelioma regardless of spindle or clear cell types. In spindle cell lesions, high-molecular weight cytokeratins (HMWCK; cytokeratin 5/6 and cytokeratin 14) tended to show higher staining scores and S-100 showed lower staining scores than other markers. In clear cell lesions, HMWCK showed significantly lower staining scores than the other five markers. There was no significant difference in staining scores among the other five markers. HMWCK showed a unique paradoxical staining pattern in clear cell lesions, with diffusely positive inner epithelial cells and completely negative outer myoepithelial cells. Although the sensitivity of HMWCK in clear cell lesions is low, with this unique paradoxical staining pattern and relatively high sensitivity in spindle cell lesions, HMWCK could be useful in diagnosing adenomyoepithelioma. In choosing immunohistochemical markers, any of the seven markers are useful, but combining HMWCK and any one of α-SMA, calponin, and p63 would be a good panel for the diagnosis of adenomyoepithelioma.

Gamma knife radiosurgery of brain metastasis from malignant pleural mesothelioma--report of three cases with autopsy study in a case.

The median survival time of malignant pleural mesothelioma (MPM) has been 9 months. Given the short survival, there have been only few cases in which brain metastases have been diagnosed and treated before death. Three cases of brain metastases treated by gamma knife radiosurgery (GKR) are reported. Case I showed a metastatic lesion in the right frontal lobe which was treated by GKR two years after diagnosis of MPM. The lesion markedly reduced and the symptoms were improved, But the patient died of progression of pleural tumor four months after GKR. A year and three months after the diagnosis, asymptomatic bifrontal lesions were treated with GKR. However, Case 2 died of abdominal mass a month after. Case 3 showed headache one and half year after the diagnosis. Three brain lesions were treated by GKR, which disappeared in 4 months. The patient died of new multiple brain metastases and periventricular dissemination seven months after. The autopsy revealed a MPM occupying the left pleural cavity. No neoplastic lesion was found in gamma knife-treated sites. The cause of death was the mass effect by new metastatic lesions. GKR was found effective also for the treatment of brain metastasis of MPM.

Squamous cell components in a thyroid follicular adenoma: significant evidence of follicular cell origin by histomorphological, immunohistochemical and molecular analyses.

Squamous cells in the thyroid appear in a variety of conditions, including adenomatous goiters, malignant neoplasms, inflammatory diseases, and embryonic remnants. However the origin of the squamous cells is still under dispute. Here we report a case of an encapsulated follicular cell tumor consisting of follicular cells, basaloid squamous cells, and morphologically intermediate cells. The patient was a 66-year-old man presenting with a progressively enlarged painless lump in the right side of his neck. A solid tumor with encapsulation in the right lobe was confirmed by simple right lobe thyroid lobectomy. This tumor demonstrated heterogeneous immunoreactions for Ki-67, thyroglobulin, thyroid transcription factor-1, and pan-cytokeratin (AE1/AE3), in that the intermediate cells had intermediate immunoreactivity between follicular and basaloid squamous cells. p63 was positive in the periphery layer of tumor cell nests of the intermediate and squamous cells. A completely negative immunoreaction was noted for high molecular weight cytokeratin (34ßE12), calcitonin, CEA, p53, CD5, and rearranged in transformation (RET). Mutational analysis of BRAF and RAS were negative. These results strongly suggest that this tumor is a follicular adenoma, and that the squamous component originated from follicular cells undergoing squamous metaplasia. The patient has been disease free more than 40 months after surgery.

High incidence of colonic perforation during colonoscopy in hemodialysis patients with end-stage renal disease.

BACKGROUND & AIMS: Colonic perforation is a rare but life-threatening complication of colonoscopy. We evaluated the incidence of colonic perforation that resulted from colonoscopy in patients who underwent hemodialysis compared with those who did not have this procedure (controls). METHODS: Data from a total of 15,098 consecutive patients who underwent colonoscopy from January 2001 to December 2008 in Nagoya Kyoritsu Hospital were analyzed retrospectively. Patients were divided into 2 groups: 1106 hemodialysis patients and 13,992 controls. The incidence of colonic perforation, patient characteristics, and locations of perforation during colonoscopy were compared between the 2 groups. Furthermore, perforated mucosa samples from colons were examined by pathology analysis. RESULTS: Colonic perforations occurred in 5 hemodialysis patients and 3 controls. The incidence of colonic perforation was markedly higher in the hemodialysis group than in the control group (0.45% vs 0.02%; odds ratio, 21.17; 95% confidence interval, 5.05-88.73; P < .0001). Even after multivariate analysis of age, sex, and patients who received polypectomies, hemodialysis still was associated independently with the risk of colonic perforation during colonoscopy (odds ratio, 19.91; 95% confidence interval, 4.61-85.93; P < .0001). Pathologic examination of perforated mucosa was performed in 3 hemodialysis patients and 3 control patients. beta2-microglobulin deposition was observed in all 3 hemodialysis patients. In contrast, beta2-microglobulin deposition was not detected in control patients. CONCLUSIONS: There is a higher risk of colonic perforation during colonoscopy among patients who received hemodialysis compared with those who did not. beta2-microglobulin deposition might have a role in perforation in patients who receive hemodialysis.

IL-10 and RANTES are elevated in nasopharyngeal secretions of children with respiratory syncytial virus infection.

BACKGROUND: Respiratory syncytial virus (RSV) infection causes asthma-like symptoms in infants and young children. Although an increase in several mediators in the airway during RSV infection has been reported, the mechanisms involved in airway inflammation are not fully understood. The aim of this study was to investigate the immunological deviation associated with airway inflammation by measuring cytokine and chemokine levels in the airway during RSV infection. METHODS: One hundred and ten children under 3 years of age with respiratory symptoms were enrolled in this study from November 2004 through January 2005. Nasopharyngeal secretions (NPAs) were gently aspirated and analyzed with RSV antigen, thereafter the concentrations of IL-4, IL-10, IFN-gamma, and RANTES were measured using an ELISA kit. We also investigated the prognosis of each child after 1 year by reference to clinical records or by interviews and re-evaluated the cytokine and chemokine levels. RESULTS: Of the subjects, 70 children were RSV positive and 40 were negative. Only 4 children were given a diagnosis of asthma by the pediatrician when NPAs were collected. The levels of IL-4, IL-10, and RANTES were significantly higher in the RSV-positive patients than RSV-negative patients with P values at 0.0362, 0.0007, and 0.0047, respectively. In contrast, there was no significant difference in the levels of IFN-gamma. Furthermore, there was a significant positive correlation between IL-10 and RANTES. CONCLUSIONS: The increased production of IL-4, IL-10, and RANTES in the airway may play an important role in the pathophysiological mechanisms of RSV infection.