Staining For Neuron-specific Enolase Research Articles

Central granular cell odontogenic tumor: The first reported case in Oriental people and literature review

The central granular cell odontogenic tumor (CGCOT) is a rare odontogenic neoplasm, usually occurring in the mandible of middle-aged women. Previous studies have reported only 34 cases, all of whom were white or black individuals. The present study reports an additional case of CGCOT, occurring in the posterior mandible of a 69-year-old Taiwanese man. To the authors' knowledge, this is the first reported case in Oriental people. The odontogenic epithelium exhibited strong positive immunoreactivity for pan-cytokeratin, and focal weak staining for bcl-2. The granular cells showed strong positivity for vimentin and α1-antichymotrypsin, and focal weak staining for carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and CD68. These features indicated a mesenchymal origin and possible histiocytic lineage for the granular cells. This study also presents a literature review and describes immunohistochemical features of the tumor.

Primary Clear Cell Carcinoid Tumors of the Vulva

Neuroendocrine tumors are uncommon in the female genital tract and have been described in the ovary, uterus, cervix, and vagina. Primary carcinoid tumors have not been described in the vulva. We report 3 cases in 3 middle-aged women who presented with a solitary vulvar nodule without any other associated symptoms. All were treated with simple local excision. Two tumors were composed exclusively of clear cells arranged in nests separated by fibrovascular septae. The third tumor predominantly exhibited nests of eosinophilic granular cells with scattered areas of cells showing clear cytoplasm. Immunohistochemical staining for chromogranin and neuron-specific enolase confirmed neuroendocrine differentiation in all cases. Follow-up of 5.5 to 16 years showed no evidence of recurrence or metastasis. Primary clear cell carcinoid tumors of the vulva need to be considered in the differential diagnosis of vulvar masses with clear cell features. Immunohistochemistry plays an important role in the diagnosis of these lesions.

Sporadic Hemangioblastoma of the Kidney: a rare renal tumor

Hemangioblastoma is a benign and morphologically distinctive tumor that can occur sporadically or in association with von Hippel-Lindau disease in approximately 25% of the cases, and which involves the central nervous system in the majority of the cases. Rare occurrences of hemangioblastoma in peripheral nerves and extraneural tissues have been reported. This report describes one case of sporadic renal hemangioblastoma happened in a 16-year-old Chinese female patient, presenting with hematuria, and low back pain. Histologically, the tumors were circumscribed, and composed of sheets of large polygonal cells traversed by arborizing thin-walled blood vessels. The diagnosis of hemangioblastoma was confirmed by negative immunostaining for cytokeratin, and positive staining for α-inhibin, S100 and neuron-specific enolase (NSE). This benign neoplasm which can be mistaken for various malignancies such as renal cell carcinoma, epithelioid hemangiopericytoma and epithelioid angiomyolipoma, deserves wider recognition for its occurrence as a primary renal tumor.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5445834246942699

Neuroendocrine prostate cancer (NEPC) after androgen deprivation therapy (ADT): Clinical characteristics.

190 Background: NEPC is an aggressive variant of PC that may arise de novo or, more commonly, from existing prostate adenocarcinoma following the use of ADT. With additional agents targeting the AR signaling pathway, NEPC transformation may become more commonly clinically significant. Methods: With IRB approval, we retrospectively identified 48 metastatic (met) PC patients (pts) who met NEPC (or anaplastic) criteria for trial enrollment: a) PC with >50% immunohistochemical (IHC) staining for NE markers chromogranin (CgA), synaptophysin, or neuron specific enolase (NSE) OR Histological/cytological confirmed adenocarcinoma with clinical progression despite medical/surgical castration and at least one of the following: b) Predominant liver or brain mets c) Serum CgA > 5x upper limit of normal (ULN) or NSE > 2x ULN d) Short interval (<6 months) to development of CRPC following ADT. Results: Overall 48 pts met the criteria of NEPC. All pts received prior ADT, 54.2% received prior chemotherapy (84.6% docetaxel). The table demonstrates overall and subgroup demographics and survival from time of NEPC diagnosis. One pt with a history of long-term ADT including abiraterone after docetaxel demonstrated complete transformation to small cell phenotype, losing AR, PSA, PSMA, and Erg expression on IHC, only retaining FISH evidence of Erg rearrangement (along with AURKA and MYCN amplifications), confirming prostate origin of his emergent liver and lung metastases. Conclusions: NEPC arising from prostatic adenocarcinoma is an emerging issue, leading to one of the most lethal forms of PC. As we further refine clinical and molecular diagnostic criteria, therapeutic studies targeting this population warrant further exploration. [Table: see text]

Clinical and Pathological Predictor Factors of Fellow Eye Affliction in Patients with an Initial Unilateral Retinoblastoma

Objective:To identify the clinical and pathological predictor factors for the fellow eye affliction (asynchronous bilateralization) in patients who were initially diagnosed with unilateral retinoblastoma. Methods:The present study was conducted in the Department of Ophthalmology of the Faculty of Medicine at Zagazig University in Zagazig, Egypt. All patients initially diagnosed with unilateral retinoblastoma from January 2005 to December 2007 were followed up meticulously for at least 32 months for the development of metastatic disease and/or fellow eye affliction. At pathological examination, all specimens were stained with hematoxylin (HX) and eosin (E). The specimens also underwent special immunohistochemical staining for neuron-specific enolase (NSE). Care was given to detect optic nerve invasion by the tumor, tumor focality, and tumor differentiation during pathological examination. Results: Only 3 (16.7%) of the 18 patients initially diagnosed with unilateral retinoblastoma developed a fellow eye affliction, asynchronous bilateralization of retinoblastoma, during the follow-up period. The time lapse to fellow eye affliction ranged from 3 to 14 months. All 3 patients (100%) were diagnosed at less than 12 months of age (mean, 6.3 months; P 0.05). Of the 3 patients, 2 (66.7%) had a positive family history of retinoblastoma (P < 0.05). Optic nerve invasion and poor tumor differentiation were found in 2 (66.7%) and 1 (33.3%), respectively, of the 3 patients with asynchronous bilateralization. A statistically significant correlation was found between negative NSE staining and asynchronous bilateralization of retinoblastoma (P < 0.05). Conclusions:This study suggests that earlier age at diagnosis (less than 1 year), positive family history, and negative immunohistochemical staining with NSE are possible predictor factors for the development of fellow eye affliction in patients initially diagnosed with unilateral retinoblastoma.

Particulate matter neurotoxicity in culture is size-dependent

Exposure to particulate matter (PM) air pollution produces inflammatory damage to the cardiopulmonary system. This toxicity appears to be inversely related to the size of the PM particles, with the ultrafine particle being more inflammatory than larger sizes. Exposure to PM has more recently been associated with neurotoxicity. This study examines if the size-dependent toxicity reported in cardiopulmonary systems also occurs in neural targets. For this study, PM ambient air was collected over a 2 week period from Sterling Forest State Park (Tuxedo, New York) and its particulates sized as Accumulation Mode, Fine (AMF) (>0.18–1μm) or Ultrafine (UF) (<0.18μm) samples. Rat dopaminergic neurons (N27) were exposed to suspensions of each PM fraction (0, 12.5, 25, 50μm/ml) and cell loss (as measured by Hoechst nuclear stain) measured after 24h exposure. Neuronal loss occurred in response to all tested concentrations of UF (>12.5μg/ml) but was only significant at the highest concentration of AMF (50μg/ml). To examine if PM size-dependent neurotoxicity was retained in the presence of other cell types, dissociated brain cultures of embryonic rat striatum were exposed to AMF (80μg/ml) or UF (8.0μg/ml). After 24h exposure, a significant increase of reactive nitrogen species (nitrite) and morphology suggestive of apoptosis occurred in both treatment groups. However, morphometric analysis of neuron specific enolase staining indicated that only the UF exposure produced significant neuronal loss, relative to controls. Together, these data suggest that the inverse relationship between size and toxicity reported in cardiopulmonary systems occurs in cultures of isolated dopaminergic neurons and in primary cultures of the rat striatum.

Metastatic Melanomas in Young Broiler Chickens (Gallus gallus domesticus)

Four young broiler chickens affected by multiple melanotic tumors are described. Grossly, there were multiple tumors composed of melanocytes within the skin, skeletal muscle, and multiple visceral organs. Tumors ranged from flattened macules to masses that extensively replaced viscera. Microscopically, melanocytes were often well pigmented, and while there was moderate nuclear anisokaryosis, mitotic rates were low. Immunohistochemical staining of some melanomas with antibodies to S100 proteins, Melan-A, vimentin, or neuron-specific enolase after bleaching of tumor cells with potassium permanganate revealed lack of immunostaining of tumor cells with antibodies to S100, strong positive staining of tumor cells for neuron-specific enolase, moderate staining with antibodies to vimentin, and faint staining for Melan-A. Only neuron-specific enolase staining was evident in unbleached tumor cells. Attempts to identify exogenous avian leukosis viruses in these tumors were unsuccessful.

Neuroendocrine differentiation as an indicator of chemosensitivity and prognosis in nonsmall cell lung cancer

Context: Nonsmall cell lung cancers with neuroendocrine differentiation (NSCLC-ND) may demonstrate biologic behavior intermediate between NSCLC and small cell lung cancer (SCLC) with impact on prognosis.Methods: We analyzed 116 consecutive patients with Stage III and IV NSCLC who were diagnosed and treated between 2001 and 2006. Using immuno-histochemical staining for neuron-specific enolase (NSE), chromogranin A (ChrA), and synaptophysin (Syn), 29 (25%) NSCLC-ND were identified.Results: Expression of NSE was present in 22.4%, ChrA in 15.5% and Syn in 14.8% of patients with NSCLC. Therapeutic response was significantly better in the NSCLC-ND group and specimens with > 30% neuroendocrine (NE)-differentiated tumor cells showed favourable therapeutic response (P < 0.05). Multivariate binary logistic regression showed that percentage of NE positive tumor cells was a significant independent prognostic factor associated with a favourable outcome. Receiver operating characteristic (ROC) curves and areas under ROC curves confirmed that percentage of NE-differentiated tumor cells could be useful prediction factor of therapeutic response. Moreover, according to percentage of NE-differentiated tumor cells, optimal cutoffs and related sensitivities and specificities were determined for each markers.Conclusion: Advanced-stage NSCLC with NE tumor cells are clinically less aggressive tumors. Percentage of NE-differentiated tumor cells identifies patients with favourable therapy response to paclitaxel-cisplatin

Sporadic Hemangioblastoma of the Kidney

Verine, Jérôme MD, PhD; Sandid, Wissam MD; Miquel, Catherine MD, PhD; Vignaud, Jean-Michel MD, PhD; Mongiat-Artus, Pierre MD, PhD Author Information

Large Dermal Non Neural Granular Cell Tumor on the Surgical Wound Site

Granular cell tumors (GCTs) can be divided into neural type with S-100 reactivity and non-neural type without that. The latter has not been widely recognized and there are only fewer reports available when compared to conventional GCT. A 65-year-old man was presented with the presence of a painless mass on his back. The mass had developed into a small nodule on the scar developed because of previous surgery carried out 2 years ago. The tumor consisted of large, polygonal cells comprising of an enormous number of faintly eosinophilic small granules in the cytoplasm. The cytoplasmic granules were stained positively for periodic acid-Schiff stain. Immunohistochemical stains for S-100 protein and neuron-specific enolase were found to be negative. Herein, we report the appearance of a very rare case of non neural GCT developed on the surgical scar in support with relevant literature reviews.

Extraosseous Ewing's sarcoma arising from the pterygomandibular space

Extraosseous Ewing’s sarcoma (EES) arising in head and neck is extremely rare. We report on a rare case of EES originating from the pterygomandibular space. A 15-year-old boy was seen with a rapidly growing mass in the right upper neck, difficulty in opening mouth, dysphagia, numbness in the right lower lip and buccal skin. Clinical and radiological examinations indicated that a soft tissue mass origi-nated from the pterygomandibular space with the submandibular space and mouth floor extension. Histological and immunohistochemical evaluations of the biopsy specimen revealed poorly differentiated small blue round cells with positive stains for CD99 and neuron-specific enolase. According to the clinical manifestation, CT and MRI findings, histological pattern and the results of the immunohistochemical studies, the final diagnosis was EES. Our patient was treated with chemotherapy and radiotherapy. The lesion recurred locally after 10 months and he died of multiple distant metastases 22 months later. Early and confident diagnosis coupled with combined surgical excision and modern chemotherapy/radiotherapy appears to be the most effective treatment plan.

Sporadic Hemangioblastoma of the Kidney: An Underrecognized Pseudomalignant Tumor?

Hemangioblastoma is a benign tumor that can occur sporadically, or in association with von Hippel-Lindau disease in approximately one-quarter of the cases. Only exceptionally does it occur outside the central nervous system. This report describes 2 cases of sporadic renal hemangioblastoma, with 1 patient presenting with hematuria and polycythemia, and the other low back pain. Histologically, the tumors were circumscribed, and composed of sheets of large polygonal cells traversed by arborizing thin-walled blood vessels. Many of the tumor cells showed pleomorphic nuclei, but the mitotic figures were rare. The cytoplasm was eosinophilic, and occasionally finely vacuolated indicating the presence of lipid. The diagnosis of hemangioblastoma was confirmed by negative immunostaining for cytokeratin, and positive staining for α-inhibin, S100, and neuron-specific enolase. This benign neoplasm which can be mistaken for various malignancies such as renal cell carcinoma, epithelioid angiomyolipoma, adrenal cortical carcinoma, and paraganglioma, deserves wider recognition for its occurrence as a primary renal tumor.

Histopathological study of retrolental membranes secondary to persistent hyperplastic primary vitreous

To study the pathological characteristics of retrolental membranes (RLMs) secondary to persistent hyperplastic primary vitreous (PHPV), and to discuss the possible pathogenesis of PHPV. Experimental study. Six RLMs obtained from six patients with PHPV during vitrectomy were examined by light microscopy (HE & PAS staining). All of them were observed with proliferating cell nuclear antigen (PCNA) immunostaining, together with collagen I, factor VIII related antigen, smooth muscle actin (SMA), epithelial membrane antigen (EMA), neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP) staining. Apoptosis were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL). Light microscopy showed that the RLM was a dense connective tissue with numerous inflammatory cells including mast cells and lymphocytes. PAS staining showed that RLMs contained a larger amount of polysaccharides. Histopathology and immunohistochemistry showed that there were vascular channels, smooth muscle cells, nervous cells and epithelial cells scattered in RLMs. Collagen I was the main component of RLMs. PCNA-positive nuclei were widely found in RLMs. TUNEL-positive nuclei were also found in all RLMs, as well as in the posterior subcapsular epithelial cells of lens. The cell types of RLMs secondary to PHPV are similar to those of the primary vitreous. It is possible that the mechanism of the progression of RLMs is the over-development and incomplete regression of the retrolental vascular system. Inflammation may play an important role in the regression of RLMs.

Pineal parenchymal tumor of intermediate differentiation showing malignant progression at relapse

Pineal parenchymal tumors of intermediate differentiation (PPTID) are extremely rare tumor entities and only limited data are available regarding their pathologic features and biologic behavior. In this report, we describe a case of PPTID transformed into pineoblastoma at relapse in a 47-year-old woman, focusing on the comparison of histologic and immunohistochemical features between the first and recurred tumors. The first tumor in February 2004 exhibited diffuse sheets of relatively uniform, small cells with moderately high cellularity and mild nuclear atypia, and no mitoses or necrosis. Immunohistochemically, the tumor cells showed diffuse staining for neuron-specific enolase (NSE), synaptophysin and chromogranin, and the MIB-1 labeling index was 3%. The diagnosis was PPTID. On the other hand, 4 years later, the recurred tumor had morphologic features of undifferentiated small cell histology with high mitotic activity and prominent necrosis. Immunohistochemically, the tumor cells showed only focal, weak staining for NSE, synaptophysin and chromogranin, and the MIB-1 labeling index was 19%, all of which were the features of pineoblastoma. This case clearly indicates that PPTID can be transformed without limit into pineoblastoma at relapse in a clinical aspect, and PPTID is closely related to pineoblastoma on a continuous spectrum in a histogenetic aspect.

Neuron-specific enolase-like immunoreactivity in human Leydig cells

Using the peroxidase anti-peroxidase immunocytochemical technique, neuron-specific enolase (NSE)-like immunoreactivity (NSE-LI) was revealed in Leydig cells of adult human testes at the light microscopic level. Differences in the NSE staining intensity were observed between the individual Leydig cells, separate cell groups within a testis and between the testes of individual patients. Together with the already established substance P-like immunoreactivity (SP-LI), the results obtained provided further evidence for the possible neuroectodermal origin of human Leydig cells and their presumable relation to the APUD- or the Diffuse Neuroendocrine System (DNES).

Pure red-cell aplasia as the presenting feature of the carcionoid tumor of the thymus: case report

Acquired pure red-cell aplasia (PRCA) is an uncommon disorder of erythrocytopoiesis that can develop in association with thymic tumors. We present the very rare case of a severely anemic 62-year-old man with PRCA and a concurrent neuroendocrine carcinoid tumor of the thymus. The anterior mediastinal thymus tumor was completely excised, and following histological and immunohistochemical analyses (showing positive staining for cytokeratin, chromogranin A, synaptophysin, and neuron-specific enolase) the diagnosis of a (grade I; T(1)N(0)M(0)) typical carcinoid tumor of the thymus was made. Postoperatively the anemia persisted despite no signs of residual tumor on CT chest. A hematological work up found: normocellularity with <0.5% erythroblasts and preserved megakaryocytopoiesis and granulocytopoiesis in a trephine biopsy; reduced numbers of Colony Forming Unit Erythroid (CFU-E) and normal numbers of Burst-Forming Unit Erythroid (BFU-E) in bone marrow colony-forming assays; a markedly increased level of serum erythropoietin; normal T and B-cell numbers with a normal CD4/CD8 ratio; and no clonal T-cell receptor -gamma and -delta gene rearrangement) The patient responded favorably to a therapeutic trial of glucocorticoid immunosuppressive treatment (prednisone 1 mg/kg/day) with a normalization of the reticulocyte count and hematocrit, suggesting an immunologic mechanism for the PRCA. Though the exact mechanisms underlying the association between the PRCA and the carcinoid tumor of the thymus remain unknown.

Chitosan Scaffold Enhances Nerve Regeneration within the in vitro Reconstructed Bladder Wall: An Animal Study

Introduction: The function of reconstructed bladder depends on the contracting bladder wall. This can be obtained with a proper innervating segment. Polyglycolic acid (PGA) is used as cell vehicle. Chitosan supported the adhesion and differentiation of neurons. The aim of the study was to compare PGA with PGA/chitosan ‘sandwich’ grafts for bladder regeneration. Methods: 3T3 fibroblasts were seeded on 6 PGA and on 3 chitosan scaffolds and incubated for 3 days at 37°C in 5% CO₂before implantation. Three rats underwent bladder reconstruction with PGA cell-seeded grafts and 3 with PGA grafts covered with chitosan cell-seeded grafts (‘sandwich’ graft). Three rats in the control group were not operated. After 6 months, reconstructed tissue was stained with hematoxylin and eosin. Neurons were identified by synaptophysin and neuron-specific enolase staining. Results: No complications were noticed. PGA/chitosan grafts were evaluated as (+++) and (++), while PGA grafts were evaluated as (++) and (+) with use of synaptophysin antibody. The control group was evaluated as (+). PGA/chitosan grafts were evaluated as (++) and (+), while PGA grafts were evaluated as (++) and (+) in neuron-specific enolase staining. The control group was evaluated as (+). Conclusion: Chitosan improved PGA’s abilities as a cell matrix and in guiding neurons into the graft.

Paralyzing Diarrhea

Purpose: When patients present with several symptoms including extraintestinal problems, a unitary diagnosis is occasionally possible. A 28 year-old white female reported one year of diarrhea with more than 10 watery bowel movements daily. There was mild bilateral lower quadrant abdominal pain without associated or alleviating factors. During the preceding two months, she lost 10 pounds. She denied dysentery, hematochezia, fever, chills or laxative use. She had been receiving potassium supplements for chronic hypokalemia and had several episodes of generalized weakness, followed by “paralysis” that had required hospitalization for the treatment of profound hypokalemia. The evaluation included negative results for stool cultures, stool Clostridium difficile toxin, amoeba serology, sedimentation rate, C reactive peptide level, thyroid stimulating hormone level, serum gastrin level, calcitonin level, tissue transglutaminase IgA, serum protein electrophoresis with quantitative immunoglobulins, urine laxative screen, and complete blood cell count. Metabolic panel was remarkable for serum potassium level of 1.8 and a serum bicarbonate level of 20 in the face of a non-anion gap metabolic acidosis. Colonoscopy with terminal ileum intubation showed no mucosal lesions and random biopsies were normal mucosa. CT scan with thin cuts through the pancreas revealed a 7.3 × 6.9 cm mass in the tail of the pancreas. Vasoactive intestinal peptide level was elevated at 1055 pg/mL. Diarrhea and hypokalemia-associated symptoms abated on octreotide. She underwent a laparoscopic subtotal pancreatectomy, splenectomy and lymph node resection. Light microscopy of the pancreatic mass demonstrated a well-differentiated pancreatic endocrine neoplasm with no extension through the tumor capsule. Associated lymph nodes were negative for malignancy. Immunohistochemical analysis had positive staining for anti-cytokeratin (CAM 5.2), neuron-specific enolase (NSE), and synaptophysin (SYP) in the tumor cells, consistent with a neuroendocrine tumor of the pancreas. This case demonstrates the importance of considering pancreatic neuroendocrine tumors in patients presenting with watery diarrhea and periodic hypokalemia-associated paralysis. Methods: Results: Conclusion:

Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

Lamotrigine (LTG), an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD) in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen). LTG was administered intraperitoneally with the doses of 5, 10, 20, and 40 mg/kg 3 h after operation and the dose of 20 mg/kg 1 h before and 3 h, 6 h after operation. Blood and brain were sampled 24 h after operation. Nissl staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), and neuron-specific enolase (NSE) immunohistochemical staining were used for morphological studies. Water content in left cortex and NSE concentration in serum were determined. LTG significantly reduced water content in the cerebral cortex, as well as the number of TUNEL staining neurons in the dentate gyrus and cortex in hypoxic-ischemia (HI) model. Furthermore, LTG significantly decreased the NSE level in serum and increased the number of NSE staining neurons in the cortex. These effects, except that on water content, were dose-dependent and were more remarkable in the pre-treated group than in the post-treated groups. These results demonstrate that LTG may have a neuroprotective effect on acute HIBD in neonates. The effect is more prominent when administrated with higher doses and before HI.

Small cell carcinoma of the prostate treated with amrubicin

We describe the use of amrubicin hydrochloride to treat small cell carcinoma of the prostate in a 23-year-old man. Initial radiological examinations of the patient revealed a pelvic tumor associated with bilateral hydronephrosis, pelvic lymph node swelling, and lumbar vertebral bone metastases. The pathological diagnosis was small cell carcinoma originating in the prostate, based on positive immunohistochemical staining for neuron-specific enolase, synaptophysin, and myoglobulin; and negative staining for CD3e, CD20, leukocyte common antigen, and CD99. The clinical stage was T4N1M1. A bilateral nephrostomy was performed to improve renal function, and an ileostomy was established to prevent ileus. The first induction chemotherapy consisted of amrubicin 35 mg/m(2) (days 1, 2, 3, monthly). The amrubicin regimen caused a dramatic reduction in tumor size, but could not be continued, because of the occurrence of grade 4 diarrhea. A different regimen was then administered, consisting of one cycle of a 50% dose and a second cycle of a 75% dose of etoposide (100 mg/m(2) days 1, 2, 3), coadministered with carboplatin (AUC 5, plasma concentration curve). Five months after the induction of chemotherapy, the patient suffered respiratory arrest and died.