CYTOLOGICAL APPROACH TO DIAGNOSISFOR LARGE CELL NEUROENDOCRINE CARCINOMA

Clinical data or investigation of large cell neuroendocrine carcinoma (LCNEC) have accumulated, some of which however, can be flawed by erroneous cytological diagnosis. In this report, we present a case of LCNEC suspected of originating in the lung, and discuss cytological features Qr differential diagnosis. Aspiration cytology showed clusters of tumor cells with large and polymorphic nuclei and distinct nucleoli. The cytoplasm was positive for some markers for neuroendocrines, is similarly as demonstrated in histological findings of metastasis in the cervical lymph node. LCNEC rapidly develops and often reaches an advanced stage, and we have sometirnes found that fine needle biopsy or cytology is the only tool for pathological suggestion or diagnosis. Therefore, it is necessary to accumulate case reports as presented here and confirm cytological features, which might help us to make an accurate diagnosis of LCNEC and to distinguish it from other neuroendocrine neoplasms including small cell carcinoma or poorly differentiated tumors

CYTOLOGIC CHARACTERISTICS OF A MALIGNANT PROLIFERATING TRICHILEMMAL CYST

The proliferating trichilemmal cyst (PTC)is a tumor that originates from hair follicles. It is almost always benign, but rare lesions have been reported with malignant potential. In the present case, the patient had a mass on the right side of her neck for a few years, which suddenly increased in size. Cytologic examination revealed many atypical squamous cells staining well with orange G and light green, suggestive of a squamous cell carcinoma. Total extirpation was performed under general anesthesia, gross pathology revealing a focally cystic tumor approximately 5 cm in diameter. The final diagnosis was malignant PTC from the characteristic features. We here report cytologic findings for this case with regional lymph node metastasis

Molecular pathogenesis of pediatric astrocytic tumors1

Astrocytomas are the most common pediatric brain tumors, accounting for 7%–8% of all childhood cancers. Relatively few studies have been performed on their molecular properties; therefore, classification of pediatric astrocytic tumors into genetic subtypes similar to that of adult tumors remains to be defined. Here, we report an extensive characterization of 44 pediatric astrocytomas—16 diffuse astrocytomas (WHO grade II), 10 anaplastic astrocytomas (WHO grade III), and 18 glioblastomas (WHO grade IV)—in terms of genetic alterations frequently observed in adult astrocytomas. Some form of p53 mutation was found in three diffuse astrocytomas, in three anaplastic astrocytomas, and in six glioblastomas examined; PTEN mutations were detected only in two glioblastomas. EGFR amplification was detected in only one anaplastic astrocytoma and two glioblastomas, but no amplification was observed for the PDGFR-α gene. Loss of heterozygosity (LOH) on 1p/19q and 10p/10q was less common in pediatric astrocytic tumors than in those seen in adults, but the frequency of LOH on 22q was comparable, occurring in 44% of diffuse astrocytomas, 40% of anaplastic astrocytomas, and 61% of glioblastomas. Interestingly, a higher frequency of p53 mutations and LOH on 19q and 22q in tumors from children six or more years of age at diagnosis was found, compared with those from younger children. Our results suggest some differences in children compared to adults in the genetic pathways leading to the formation of de novo astrocytic tumors. In addition, this study suggests potentially distinct developmental pathways in younger versus older children

c-Jun NH2 Terminal Kinase Activation and Decreased Expression of Mitogen-Activated Protein Kinase Phosphatase-1 Play Important Roles in Invasion and Angiogenesis of Urothelial Carcinomas

We here examined whether c-Jun NH2 terminal kinase (JNK) might be involved in the progression of urothelial carcinomas. In vitro and in vivo invasion assays using Matrigel and chick embryo chorioallantoic membrane approaches showed constitutive activation of JNK to significantly increase two processes, invasion and angiogenesis, in the human urothelial carcinoma cell line kU-7, this being suppressed by a JNK inhibitor, SP600125, or cell-permeable peptides. In addition, we found that mitogen-activated protein kinase phosphatase (MKP)-1 functions as an endogenous inhibitor of JNK-mediated signals in urothelial carcinoma cells: chorioallantoic membrane assays showed UMUC14 cells with low MKP-1 expression to be more invasive and have pronounced angiogenesis compared to UMUC6 cells with high MKP-1. Furthermore, knockdown of the MKP-1 gene by siRNA transfection enhanced JNK activation in UMUC6 cells to the UMUC14 level. Immunohistochemically, JNK was found to be highly phosphorylated in high-grade and invasive carcinomas (≥pT2) as well as carcinoma in situ but not in low-grade and noninvasive phenotypes (pTa, pT1). In contrast, MKP-1 was much more expressed in low-grade/noninvasive cancers than with the high-grade/invasive phenotype, reversely correlating with phosphorylated JNK. Taken together, JNK activation and decreased expression of MKP-1 may play important roles in progression of urothelial carcinoma