Optic nerve and spinal cord manifestations of malignant atrophic papulosis (Degos disease).

A fatal case of malignant atrophic papulosis (Degos disease) with optic nerve and spinal cord involvement is described. Magnetic resonance imaging (MRI) of the optic nerve showed abnormal signal enhancement on fat suppressed T1 weighted images after intravenous meglumine gadopentetate infusion. On T2 weighted sagittal images, a sawtooth pattern was observed over seven vertebral segments of the spinal cord. On necropsy, a severe loss of myelinated nerve fibres in the left optic nerve was seen, with thrombotic obstruction of the central retinal artery. Spongy degeneration was observed in all levels of the spinal cord, with patchy and motheaten patterns caused by thromboses and endothelial proliferation in subarachnoid vessels. Findings on MRI were consistent with findings on pathological examination.

Heterogeneity of p53 mutational status in the superficial spreading type of early gastric carcinoma.

BACKGROUND: The superficial spreading type of gastric carcinoma may originate from either a single cellular clone or from several different clones; this issue remains controversial. Indeed, the p53 gene has been shown to play an important role in gastric carcinogenesis, but there have been only a few reports on the heterogeneity of gastric carcinoma with respect to the p53 gene. METHODS: We analyzed seven cases of the superficial spreading type of gastric submucosal carcinomas (80 lesions; 10 to 17 per case) which showed different histological types and/or different p53 protein staining patterns. Direct sequences of polymerase chain reaction products were used for the analysis. RESULTS: p53 Gene heterogeneity in mucosal carcinoma lesions was detected in three cases. However, in all of the cases, the p53 mutational pattern was identical to that found in the submucosal carcinoma lesions. In the heterogeneous cases, the mutation in the submucosal carcinoma was one of the mutation patterns found among the mucosal carcinoma lesions. More precisely, the mutational pattern of both submucosal carcinoma lesions and the mucosal lesions located just above them, was identical. CONCLUSION: These data suggest that, with regard to the p53 gene, in some superficial spreading types of gastric carcinomas, there are various subclones in the mucosal carcinoma; one of these subclones becomes predominant through clonal selection, and, thus, invades the submucosa.

Mutations of p53 in morphologically non-neoplastic mucosa of long-standing ulcerative colitis.

Two cases of ulcerative colitis (UC)-associated carcinoma or dysplasia and morphologically non-neoplastic mucosa with p53 protein overexpression (MNNM-p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions and exons 5 - 8 of the p53 gene were analyzed by PCR and direct sequencing. In addition, mutations in K-ras codon 12 were analyzed by PCR-RFLP methods. MNNM-p53OE was located surrounding and adjoining a coexisting carcinoma and / or dysplasia. A p53 mutation was detected in 12 / 22 (54.5%) MNNM-p53OE samples, 4 / 8 (50%) dysplasia samples and 8 / 8 (100%) carcinoma samples. The p53 mutations detected in MNNM-p53OE were identical to those demonstrated in the adjoining carcinoma and / or dysplasia. No K-ras codon 12 mutation was detected in any of the samples. These results indicate that MNNM-p53OE may share an identical clonal linkage with a coexisting carcinoma and / or dysplasia, and may be an initial and submorphological form of UC-associated neoplasia. Recognition of MNNM-p53OE in biopsy specimens may help to identify patients with UC at risk of developing colorectal carcinoma.

Heterogeneity of p53 mutational status in intramucosal carcinoma of the colorectum.

The aim of this study was to elucidate whether or not p53 genetic heterogeneity would occur while colorectal carcinoma was limited to the mucosa. Eight cases of endoscopically resected colorectal intramucosal carcinomas were analyzed to determine the p53 gene sequence (exons 5 to 8). Six out of 8 cases showed p53 gene mutations, and in all of them, the mutational status was heterogeneous. In 4 cases, mutated codons were heterogeneous as well. These data indicate that p53 gene alterations in colorectal carcinomas occur and diverge at the stage of intramucosal carcinoma, supporting our previously proposed hypothesis that colorectal carcinomas can be composed of various subclones as regards p53 gene mutation, while the carcinoma is limited to the mucosa, and one of these subclones commences invasion to the submucosa after clonal selection, thus generating a monoclonal invasive carcinoma.

Early colorectal cancer with special reference to the superficial nonpolypoid type from a histopathologic point of view.

The incidence and histopathologic characteristics of nonpolypoid (superficial type) early colorectal carcinomas were studied and compared with those of the polypoid type. The superficial type was subclassified as elevated (type IIa), type IIa with central depression (type IIa + IIc), plain (type IIb), depressed (type IIc), and IIc with marginal elevation (type IIc + IIa). The superficial type comprised 22% and 27% of intramucosal and submucosal carcinomas, respectively. Pure type IIb was not found, and there were only three pure type IIc lesions. Type IIa + IIc and IIc + IIa (and IIc) showed a significantly higher rate of submucosal invasion among the small tumors (59% and 71% less than 20 mm, respectively) compared to the polypoid type; type IIa showed no significant difference. The incidence of lymph node metastasis among submucosal carcinomas showed no significant difference between the superficial type and the polypoid type. About 64% and 52% of type IIa and IIa + IIc tumors accompanied residual adenoma, suggesting that they originated from small, flat adenomas through the adenoma-carcinoma sequence, whereas type IIc + IIa (and IIc) did not have an adenomatous component, implying that they arose de novo or originated through an adenoma-carcinoma sequence at a smaller size than the type IIa and IIa + IIc lesions. Superficial-type early colorectal carcinomas are not rare, and they are not uniform in nature. Rapid growth and invasion to the submucosa is characteristic of superficial-type lesions with a central depression, and only superficial depressed (type IIc + IIa, IIc) lesions can arise de novo. Although they grow rapidly to invade the submucosa, it cannot be said that they show more aggressive behavior than the polypoid type.