Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson syndrome.

Two siblings from a consanguineous family presented with a poikiloderma of limbs and face, plantar keratoderma, and toenail pachyonychia. Neutropenia and neutrophil dysfunction with impairment of the respiratory burst and bacterial killing resulted in frequent respiratory tract infections. A bronchocentric granulomatous pneumonia was a fatal complication. The clinical presentation is consistent with Clericuzio type poikiloderma with neutropenia. Literature review identified several additional probable patients. Genetic linkage analysis excluded the locus of the RECQL4 gene, mutations in which have been described in some patients with the Rothmund-Thomson poikiloderma syndrome. This report confirms the clinical and genetic identity of the Clericuzio type of poikiloderma with neutropenia syndrome.

Primary peripheral PNET/Ewing's sarcoma of the dura: a clinicopathologic entity distinct from central PNET.

We describe two cases of peripheral primitive neuroectodermal tumor-Ewing's sarcoma (PNET-ES) arising intracranially in the leptomeninges. Both tumors exhibited a primitive undifferentiated round-cell morphology. Immunohistochemical stains revealed strong membrane expression of CD99 in both cases. A t(11;22)(q24;q12) could be demonstrated with reverse transcriptase-polymerase chain reaction in one case, whereas fluorescence in situ hybridization analysis performed in the second case showed a rearrangement of the EWS gene. The occurrence of PNET-ES at this site is very unusual. Immunophenotypical as well as genetic analysis play a key role in the diagnosis and the distinction from central PNET.

Loss of membranous expression of beta-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by exon 3 mutations.

beta-Catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also plays a role in the Wnt signaling pathway by activating T-cell factor- and lymphoid enhancer factor-regulated gene transcription. The level of beta-catenin in cells is tightly controlled in a multiprotein complex, and mutations in the glycogen synthase kinase 3beta (GSK-3beta) phosphorylation sites of the beta-catenin gene (CTNNB1) result in nuclear and/or cytoplasmic accumulation of beta-catenin and constitutive transactivation of T-cell factor and lymphoid enhancer factor target genes, a mechanism occurring in many cancers. Melanoma cell lines may harbor beta-catenin mutations; in vivo, however, cellular accumulation of beta-catenin is rarely caused by CTNNB1 mutations. In our study, 43 primary cutaneous melanoma and 30 metastases were screened for CTNNB1 exon 3 mutations by using a denaturing gradient gel electrophoresis technique and sequencing. beta-Catenin mutations were found in 2 primary melanomas and 1 metastatic melanoma and were not correlated with nuclear accumulation of beta-catenin in these cases. Cellular expression of beta-catenin was evaluated by immunohistochemistry and by reverse polymerase chain reaction (RT-PCR) in 80 and 70 cases, respectively. Immunohistochemistry revealed a significant loss of membranous beta-catenin staining between the primary and metastatic melanomas as well as between radial and vertical growth phase. RT-PCR showed a significant inverse correlation between the amount of RNA and the proportion of cells with membranous expression of beta-catenin (P =.0015); no correlation existed between the amount of RNA and the number of cells with nuclear or cytoplasmic expression of beta-catenin. In conclusion, nuclear expression of beta-catenin is seen in cutaneous melanoma but, in contrast to the case of many other cancers, does not correlate with tumor stage or mutation status. A combination of immunohistochemistry and RT-PCR showed that down-regulation of membranous beta-catenin was associated with an increased amount of beta-catenin RNA in primary or metastatic melanoma. Our results suggest that posttranslational events, rather than CTNNB1 mutations, are responsible for the altered distribution of beta-catenin in cutaneous melanoma.

BCL10 mutation does not represent an important pathogenic mechanism in gastric MALT-type lymphoma, and the presence of the API2-MLT fusion is associated with aberrant nuclear BCL10 expression.

Two recurrent translocations have been associated with mucosa-associated lymphoid tissue (MALT)-type lymphoma, t(11;18)(q21;q21) and t(1;14)(p22;q32). The first, t(11;18)(q21;q21), results in the fusion protein API2-MLT (API2-MALT1). Through t(1;14)(p22;q32), the BCL10 gene is entirely transferred to the IgH gene, resulting in its overexpression. Wild-type BCL10 is implicated in apoptosis, and it has been suggested that mutated forms gain oncogenic activity. The occurrence of genomic BCL10 mutations in 35 gastric MALT-type lymphomas with or without t(11;18)(q21;q21) (10 and 25 cases, respectively) was investigated. DNA extracted from either whole tissue sections or microdissected clusters of tumor cells was used. Five polymerase chain reactions amplifying the coding exons were performed and were followed by direct sequencing of the products. Twenty differences with the published BCL10 sequence, all single nucleotide substitutions, were detected in 16 cases. Of these, 12 represented known polymorphisms, either at codon 8, 213, or 5. Of the remaining 8 substitutions, 2 were silent and 6 resulted in amino acid substitutions. Mutation analysis results were correlated with the BCL10 expression pattern. Aberrant nuclear BCL10 expression was detected in 14 cases. No association could be demonstrated between the latter and the presence of BCL10 mutations. In contrast, all 10 cases carrying t(11;18)(q21;q21) showed nuclear expression, whereas this staining pattern was absent in 21 of 25 cases without t(11;18)(q21;q21). These results demonstrate that BCL10 mutations are rare in gastric MALT-type lymphoma and are not related to the aberrant nuclear expression of BCL10. In contrast, they indicate that the presence of the API2-MLT fusion protein is associated with aberrant nuclear BCL10 expression.