Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma.

It is now known that gene mutation of beta-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of beta-catenin with genetic mutation. This prompted us to further investigate the state of beta-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with l-FLAC/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adenocarcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of beta-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of beta-catenin in the epithelial component, and absent or focal N/C expression of beta-catenin in the mesenchymal component. Mutational analysis of exon 3 of the beta-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that beta-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of beta-catenin. Immunostaining for beta-catenin is useful for the discrimination.

Biotin-rich, optically clear nuclei express estrogen receptor-beta: tumors with morules may develop under the influence of estrogen and aberrant beta-catenin expression.

Recent studies have indicated that aberrant beta-catenin expression may be a common denominator for the morular formation of tumors from various anatomic sites. The evidence for the influence of female sex hormones in the formation of morules has been circumstantial, most previous studies having failed to demonstrate female sex hormone receptors in the morular cells. We investigated a possible role of estrogen receptor (ER)-beta in the occurrence of tumors that form morules with biotin-rich optically clear nuclei (BROCN)(BROCN-family tumors) and its possible relationship with aberrant nuclear/cytoplasmic (N/C) beta-catenin expression. We immunostained 14 BROCN-family tumors, including 6 low-grade adenocarcinomas of the fetal lung type, 3 papillary thyroid carcinomas of cribriform-morular variant (CMV), 2 ovarian endometrioid tumors, 2 colonic adenocarcinomas, and 1 gallbladder adenoma, as well as 4 cases of endometrial tissue with BROCN during gestation, for ERbeta, ERalpha, progesterone receptor (PgR), beta-catenin, and, on a subset of cases, c-Fos and MIB-1 as well. BROCN in all 18 cases expressed ERbeta but not ERalpha or PgR. In the BROCN-family tumors, the morular cells and budding glandular cells expressed ERbeta in the cytoplasm and BROCN, which overlapped with the N/C expression pattern of beta-catenin. Beta-catenin showed only membranous expression in the endometrial glands during gestation. In CMV and ovarian endometrioid tumors, nuclear expression of ERalpha and PgR were observed in association with N/C beta-catenin expression only in the glandular component. C-Fos was also constantly and strongly expressed in BROCN in all cases examined. The MIB-1 labeling index was low in the morular area, ranging from 1% to 3%. The present study indicates that N/C co-localization of ERbeta and beta-catenin is a feature common to the morules with BROCN that appear in the BROCN-family tumors from various anatomic sites. Whether the estrogen-signaling pathway and the Wnt-signaling pathway have crosstalk, cooperating in the development of the BROCN-family tumors, awaits further study.

The coincidence of pure lipoma, leiomyoma, and endometrial cancer. A case report of the uterine tumor triplicity.

A different tumor concurrence of the uterine body is usually encountered as a coincidence of leiomyoma and endometrial cancer. Pure lipomatous tumors or fatty change in the leiomyoma or endometrium are rare affections with some diagnostic peculiarities. We present a case of association of the pure uterine lipoma, leiomyoma, and endometrial cancer as a tumor triplicity, which may contribute, to the pathogenesis of mesenchymal tumors in this location.

[Diagnosis and surgical treatment of bronchial carcinoid]. / Diagnostika a chirurgická lécba bronchiálního karcinoidu.

The purpose of this study was to look at the clinical behaviour of bronchial carcinoids and clarify a surgical approach. Over 30 years 61 patients with a final histological diagnosis of carcinoid tumours were assessed for surgery. All patients were retrospectively reviewed for clinicopathological variables, surgical management and outcome. Tumours were considered typical and atypical based on histological features. The mean age at presentation was 46 years (range 11-69). Overall survival in the group of typical carcinoids was 96%, and 67% in the group of atypical carcinoids.

Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules.

The salient histopathologic features of low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA) include complex glandular structures and morules with biotin-rich optically clear nuclei. Interestingly, these characteristic features are shared by the cribriform-morular variant of papillary thyroid carcinoma, whose morphology is identical to that of familial adenomatous polyposis (FAP)-associated thyroid carcinoma. Furthermore, the single reported case of lung cancer associated with FAP was L-FLAC/WDFA. These observations lead us to hypothesize that up-regulation of the Wnt signaling pathway underlies the development of L-FLAC/WDFA. To verify this hypothesis, 11 cases of L-FLAC/WDFA, including the one FAP-associated case, eight cases of high-grade adenocarcinoma of the fetal lung type (H-FLAC), 24 cases of conventional pulmonary adenocarcinoma (CAC), and 13 fetal lungs were immunostained for beta-catenin. All cases of L-FLAC/WDFA showed predominantly aberrant nuclear/cytoplasmic expression, especially in budding glands and morules, whereas six of eight cases (75%) of H-FLAC and all but one case (96%) of CAC showed predominantly membranous expression. Fetal lungs showed nuclear/cytoplasmic expression restricted to the distal branching airway epithelium. Mutational analysis of exon 3 of the beta-catenin gene in five sporadic cases of L-FLAC/WDFA showed a point mutation at codon 34 and codon 37 in two cases, respectively. The present study indicates that up-regulating disturbances in the Wnt signaling pathway, including mutation of the beta-catenin gene, underlie tumorigenesis of L-FLAC/WDFA. The expression pattern of beta-catenin in L-FLAC/WDFA resembles that of the developing fetal lung airway. With the expression pattern of beta-catenin as a marker, most cases of H-FLAC as well as CAC appear to have different oncogenic pathways from cases of L-FLAC/WDFA. The present study together with other available data also suggests that abnormal up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors with morular formation from a variety of anatomic sites.