Aberrant activation of nuclear factor of activated T cell 2 in lamina propria mononuclear cells in ulcerative colitis.

AIM: To investigate the role of nuclear factor of activated T cell 2 (NFAT2), the major NFAT protein in peripheral T cells, in sustained T cell activation and intractable inflammation in human ulcerative colitis (UC). METHODS: We used two-dimensional gel-electrophoresis, immunohistochemistry, double immunohistochemical staining, and confocal microscopy to inspect the expression of NFAT2 in 107, 15, 48 and 5 cases of UC, Crohn's disease (CD), non-specific colitis, and 5 healthy individuals, respectively. RESULTS: Up-regulation with profound nucleo-translocation/activation of NFAT2 of lamina propria mononuclear cells (LPMC) of colonic mucosa was found specifically in the affected colonic mucosa from patients with UC, as compared to CD or NC (P < 0.001, Kruskal-Wallis test). Nucleo-translocation/activation of NFAT2 primarily occurred in CD8+T, but was less prominent in CD4+ T cells or CD20+B cells. It was strongly associated with the disease activity, including endoscopic stage (tau = 0.2145, P = 0.0281) and histologic grade (tau = 0.4167, P < 0.001). CONCLUSION: We disclose for the first time the nucleo-translocation/activation of NFAT2 in lamina propria mononuclear cells in ulcerative colitis. Activation of NFAT2 was specific for ulcerative colitis and highly associated with disease activity. Since activation of NFAT2 is implicated in an auto-regulatory positive feedback loop of sustained T-cell activation and NFAT proteins play key roles in the calcium/calcineurin signaling pathways, our results not only provide new insights into the mechanism for sustained intractable inflammation, but also suggest the calcium-calcineurin/NFAT pathway as a new therapeutic target for ulcerative colitis.

Identification of collapsin response mediator protein-2 as a potential marker of colorectal carcinoma by comparative analysis of cancer cell secretomes.

The cancer cell secretome may contain many potentially useful biomarkers. We therefore sought to identify proteins in the conditioned media of colorectal carcinoma (CRC) cell lines but not in those from other cancer cell lines. The secretomes of 21 cancer cell lines derived from 12 cancer types were analyzed by SDS-PAGE combined with MALDI-TOF MS. Among the 325 proteins identified, collapsin response mediator protein-2 (CRMP-2) was chosen for evaluation as a potential CRC biomarker, since it was selectively detected in the CRC cell line secretome and has never been reported as a cancer biomarker. Immunohistochemical analysis of 169 CRC specimens showed that CRMP-2 was positively detected in 58.6% of the tumors, but weakly or not detected in >90% of the adjacent nontumor epithelial cells. Moreover, the CRMP-2-positive rate was significantly increased in earlier stage tumors and lymph node metastasis. Plasma CRMP-2 levels were significantly higher in CRC patients (N = 201) versus healthy controls (N = 201) (61.3 +/- 34.6 vs. 40.2 +/- 24.3 ng/mL, p = 0.001). Our results indicate that comparative analysis of cancer cell secretome is a feasible strategy for identifying potential cancer biomarkers, and that CRMP-2 may be a novel CRC biomarker.

Cellular neurothekeoma with melanocytosis.

Cellular neurothekeoma (CNT) is a benign dermal tumor mainly affecting the head and neck and the upper extremities. It is characterized histologically by interconnecting fascicles of plump spindle or epithelioid cells with ample cytoplasm infiltrating in the reticular dermis. The histogenesis of CNT has been controversial, although it is generally regarded as an immature counterpart of classic/myxoid neurothekeoma, a tumor with nerve sheath differentiation. Two rare cases of CNT containing melanin-laden cells were described. Immunohistochemical study with NKI/C3, vimentin, epithelial membrane antigen, smooth muscle antigen, CD34, factor XIIIa, collagen type IV, S100 protein and HMB-45 was performed. Both cases showed typical growth pattern of CNT with interconnecting fascicles of epithelioid cells infiltrating in collagenous stroma. One of the nodules contained areas exhibiting atypical cytological features. Melanin-laden epithelioid or dendritic cells were diffusely scattered throughout one nodule, and focally present in the peripheral portion of the other nodule. Both nodules were strongly immunoreactive to NKI/C3 and vimentin, but negative to all the other markers employed. CNT harboring melanin-laden cells may pose diagnostic problems because of their close resemblance to nevomelanocytic lesions and other dermal mesenchymal tumors. These peculiar cases may also provide further clues to the histogenesis of CNT.

Immunohistochemical expression of OCT4 in primary central nervous system germ cell tumours.

OCT4 is a POU-domain transcription factor that is expressed in embryonic stem cells and germ cells. OCT4 has been detected in specific types of testicular germ cell tumour (GCT), including seminoma and embryonal carcinoma. The aim of this study was to evaluate the role of OCT4 expression in the diagnosis of primary central nervous system (CNS) pure and mixed GCT. Seventeen formalin-fixed, paraffin-embedded tissues of primary CNS GCT were immunohistochemically studied. The 12 pure GCT samples comprised germinoma (5), yolk sac tumour (3), mature teratoma (2), and immature teratoma (2). The five cases of mixed GCT contained various components as follows: yolk sac tumour (4), embryonal carcinoma (3), mature teratoma (1), germinoma (2), polyembryoma (1) and immature teratoma (1). Diffuse and strong nuclear staining indicating OCT4 expression was detected in all cases of pure germinoma (5), and in all cases of mixed GCT containing embryonal carcinoma (3) and/or germinoma (2). There was no corresponding staining in pure GCT of yolk sac tumour, mature teratoma, or immature teratoma except in a primitive neuroectodermal component, or in mixed GCT containing components of yolk sac tumour, mature teratoma or immature teratoma. In conclusion, we found that OCT4 immunostaining is a useful diagnostic tool to assist in the identification of primary CNS embryonal carcinoma and germinoma. In CNS mixed GCT, OCT4 expression can be detected provided that the components include embryonal carcinoma and/or germinoma.

Long-term changes in trace elements in patients undergoing chronic hemodialysis.

Although the connection between aluminum intoxication and dialysis dementia was identified in the 1980s, understanding of trace element imbalances in hemodialysis patients is as yet incomplete. Recent application of newer inductively coupled plasma-mass spectrometry (ICP/MS) techniques has resulted in renewed study of this population. We used ICP/MS to evaluate serum concentrations of Cu, Se, Zn, Mn, and Ni in a relatively large population of hemodialysis patients compared with healthy age-matched controls. Comparisons were also done by duration of hemodialysis treatment to see whether length of treatment correlates with severity of imbalance. Patients had significantly lower concentrations of the three elements Se, Zn, and Mn. Patients had significantly higher concentrations of Ni, and there was a positive correlation between duration and severity of imbalance for this one element. There was no difference in Cu concentrations between patients and controls. Our findings confirm relative Ni excess and deficiencies of Se, Zn, and Mn in hemodialysis patients, documenting the value of ICP/MS in research work on trace element imbalances as well as clinical monitoring of individual patients.

Diagnosis of nodal Langerhans cell histiocytosis by fine needle aspiration cytology.

Langerhans cell histiocytosis (LCH) is a rare disease and disease confined to the lymph nodes is even more uncommon. Fine needle aspiration (FNA) cytology of LCH of the lymph nodes has rarely been described. A case study of LCH of the lymph nodes in a 23-year-old man is presented. FNA smears showed high cellularity composed of many isolated Langerhans cells (LCs) with nuclear grooves admixed with numerous eosinophils, lymphocytes, giant cells, macrophages, and neutrophils. Further immunohistochemical study of the excised lymph node sections revealed that the histiocytes were positively stained with CD1a. The presence of LCs with nuclear grooves and eosinophils suggests the possibility of LCH. FNA cytology is a valuable method for diagnosis.

Medial canthal tophus associated with gout.

PURPOSE: To report a case with a gouty tophus at the medial canthus. DESIGN: Observational case report. METHODS: Review of the clinical, laboratory, photographic, and pathologic records of a patient with a gouty tophus at the medial canthus. RESULTS: A 27-year-old man had a 3-year history of gouty arthritis and poorly controlled hyperuricemia. A medial canthal mass without discomfort developed gradually over 3 months. An excisional biopsy was performed, and the tissue was fixed in formalin for pathology. Analysis of a routine hematoxylin-and-eosin-stained section disclosed a multilobulated pseudocyst filled with amorphous eosinophilic material. Further staining with nonaqueous alcoholic eosin and viewed under a polarizing microscope indicated the presence of birefringent urate crystals. CONCLUSIONS: Gouty tophus can develop progressively at the medial canthus, especially in people with uncontrolled hyperuricemia. A formalin-fixed specimen, stained with nonaqueous alcoholic eosin, demonstrates abundant birefringent urate crystals under a polarizing microscope.

Macrocystic serous cystadenoma of the pancreas in a young patient resembling a pseudocyst: case report and literature review.

Macrocystic serous cystadenoma is an unusual and essentially benign pancreatic tumor. Ages of reported cases are usually 60 years and over, with a mean age of 54 years. Herein, we report on a 26-year-old man who presented with upper abdominal pain. A cystic lesion in the mid-portion of the pancreas was revealed by abdominal computed tomography, and a pseudocyst was suspected. A distal pancreatectomy was performed with a splenectomy due to intractable abdominal pain and being unable to rule out to be a mucinous cystic neoplasm, which has a malignant potential. The histopathological diagnosis was macrocystic serous cystadenoma of the pancreas. To our knowledge, this patient is the youngest person to present with such tumor. Clinical and pathologic features including complete immunohistochemical studies are presented, and we review the relevant literature.

Pathological analysis of congenital cervical cysts in children: 20 years of experience at Chang Gung Memorial Hospital.

BACKGROUND: Congenital cervical cysts are frequently encountered in pediatric populations, and constitute one of the most intriguing areas of pediatric pathology. This report analyzes cervical cysts in Taiwanese children diagnosed at Chang Gung Memorial Hospital (CGMH) over the past 20 years. The pathologic and clinical findings are reviewed. METHODS: Files on 331 patients under the age of 18 years, with a diagnosis of congenital cervical cyst at CGMH from January 1, 1983 to June 30, 2002, were retrieved from the Department of Pathology. There were 204 boys and 127 girls. We reviewed the histology of all cases and correlated it with clinical information in the medical records. RESULTS: Thyroglossal duct cysts, the most common congenital neck cyst, accounted for 54.68% of all cases, followed by cystic hygromas (25.08%), branchial cleft cysts (16.31%), bronchogenic cysts (0.91%), and thymic cysts (0.30%). Nine cases (2.72%) remained unclassified. CONCLUSIONS: This is the largest series regarding pediatric cervical cysts in the literature to date. Thyroglossal duct cysts were the most common congenital cervical cyst encountered. Our experience indicates that each type of cyst has its unique location in the neck and is highly associated with its embryonic origin. Complete and precise clinical information is a prerequisite in order for pathologists to make accurate diagnoses of congenital cervical cysts.