Heterogeneous genetic alterations in ovarian mucinous tumors: application and usefulness of laser capture microdissection.

Histologic observation of ovarian mucinous tumors suggests that there is a multistep transition through the accumulation of genetic alterations. We analyzed loss of heterozygosity (LOH) and replication error (RER) on TP53 and D17S855 as well as K-ras point mutations of the heterogeneous histologic areas of the same tumor in 26 cases of ovarian mucinous tumor. The laser capture microdissection (LCM) technique has been applied to the study of K-ras point mutation in 10 cases. As for genetic alterations for LOH or RER on TP53 and D17S855, 2 (1 borderline tumor and 1 carcinoma) of 14 cases and 4 (1 borderline tumor and 3 carcinomas) of 12 cases, respectively, showed genetic heterogeneities in different histologic areas. Six (2 borderline tumors and 4 carcinomas) of 18 cases showed heterogeneity of K-ras point mutation in the different histologic areas of the same tumor, and 5 (1 cystadenoma with Brenner tumor component, 2 borderline tumors, and 2 carcinomas) of 10 cases showed heterogeneous K-ras mutation pattern in the same tumor when the LCM technique was used. Atypical areas tended to show K-ras point mutations frequently. Out of 3 cases of mixed mucinous cystadenoma and Brenner tumor, 1 case showed K-ras point mutation in the Brenner tumor area but not in the area of mucinous cystadenoma. These preliminary results suggest that a subset of ovarian mucinous tumors occur through multistep carcinogenesis and show that LCM is useful for molecular pathologic studies.

Immunohistochemical study of Ki-67 (MIB-1), p53 protein, p21WAF1, and p27KIP1 expression in benign, atypical, and anaplastic meningiomas.

Histologic grading of meningiomas has prognostic and clinical therapeutic implications. Meningiomas were histologically classified into 3 different World Health Organization grades. Grade II, an atypical meningioma, was defined by major and various minor histologic criteria. However, these histologic criteria sometimes are not fulfilled, and other criteria are necessary. We studied and analyzed the immunohistochemical expression of MIB-1, p53, p21WAF1, p27KIP1 proteins in 146 cases of meningiomas, including 109 benign, 27 atypical, and 10 anaplastic meningiomas. Most of the benign meningiomas expressed low MIB-1 labeling index (mean, 1.5%), and fewer cases had p53 protein expression. In contrast, the anaplastic meningiomas had a high labeling index of MIB-1 (mean, 19.5%) and always expressed p53 protein, with a mean labeling index of 6.3%. The atypical meningiomas had MIB-1 and p53 labeling indexes in the range between benign and anaplastic meningiomas, with mean labeling indexes of 8.1% and 3.5%, respectively. These expressions were statistically significant among benign, atypical, and anaplastic meningiomas (P <.001). We conclude that the immunohistochemistry of MIB-1 and p53 protein will be valuable in discriminating atypical meningiomas from benign or anaplastic meningiomas, at least in histologically borderline cases. In addition, we also found direct correlation of p21 and inverse correlation of p27 expressions in meningiomas with increasing histologic grade and proliferative index.

Dysplastic glioneuronal lesion arising in the cerebellum: a clinicopathological, immunohistochemical and ultrastructural study.

We describe a case of dysplastic glioneuronal lesion in the right cerebellar hemisphere. A 13-year-old boy presented with headache since 1998. He had no neurological deficits. The computerized tomograph (CT) scan showed prominent calcification, and magnetic resonance imaging (MRI) revealed a non-enhancing mass of 15 x 15 x 5 cm in the right cerebellar hemisphere. The mass had low intensity in T1- and high intensity in T2-weighted images. Histologically, the lesion was composed of poorly defined small to intermediate sized cells arranged in fibrillar background. Although few neuronal cells having large nuclei with small nucleoli were present, no ganglion cells could be seen. Immunohistochemically, these poorly defined cells were non-reactive to various glial and neuronal markers. However, GFAP, synaptophysin, neurofilament and vimentin-reactive intercellular matrix and few nonneoplastic GFAP-positive glial cells and neurofilament-positive neuronal cells were seen. A very low MIB-1-labelling index of less than 0.1% was noted. Ultrastructurally, two different populations of the cells were seen. A few neuronal cells were larger and had an oval nucleus with small nucleolus and cytoplasm containing various cytoplasmic organelles, Golgi apparatus, mitochondria, ribosomes, lipofuscin, rough endoplasmic reticulum, microtubules and neurofilaments. Many other cells had a scant cytoplasm and thus poorly defined. Cytoplasmic processes with axono-dendritic synapses and foci of bundles of intermediate filaments were present in the intercellular areas of the lesion. Based on these radiological, histological and ultrastructural findings of the lesion of low proliferative potential, we considered it dysplastic in nature.

Idiopathic granulomatous meningoencephalitis presenting as an intracranial tumor.

A 2-year-old girl presented with a single episode of generalized seizure. Magnetic resonance imaging examination showed an intracranial mass with a diameter of 2.5 cm in the right parieto-occipital region of the cerebrum. These clinicoradiological findings were suggestive of intracranial tumor. Histologically, fibroblastic proliferation of storiform pattern was noted, associated with epithelioid granulomas. The etiological pathogens for the granulomas could not be detected even though investigation of special histochemical staining, immunohistochemical study and DNA analysis of Mycobacterium tuberculosis by polymerase chain reaction technique was performed. On electron microscopic examination, the area appearing as a storiform pattern consisted of fibroblasts showing much dilated rough endoplasmic reticulum and slender tappering cytoplasmic processes without cellular junctional complex. No organisms were identified in the granulomatous area of the lesion. From those findings the diagnosis as idiopathic granulomatous meningoencephalitis was made.