Germline mutations in the human MSH2, MLH1, PMS2 and PMS1 DNA mismatch repair (MMR) gene homologues appear to be responsible for most cases of hereditary non-polyposis colorectal cancer (HNPCC; refs 1-5). An important role for DNA replication errors in colorectal tumorigenesis has been suggested by the finding of frequent alterations in the length of specific mononucleotide tracts within genes controlling cell growth, including TGF-beta receptor type II (ref. 6), BAX (ref. 7) and APC (ref. 8). A broader role for MMR deficiency in human tumorigenesis is implicated by microsatellite instability in a fraction of sporadic tumours, including gastric, endometrial and colorectal malignancies. To better define the role of individual MMR genes in cancer susceptibility and MMR functions, we have generated mice deficient for the murine homologues of the human genes MLH1, PMS1 and PMS2. Surprisingly, we find that these mice show different tumour susceptibilities, most notably, to intestinal adenomas and adenocarcinomas, and different mutational spectra. Our results suggest that a general increase in replication errors may not be sufficient for intestinal tumour formation and that these genes share overlapping, but not identical functions.

Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas that almost always arise in soft tissue. They can develop in pre-existing neurofibromas or schwannomas, de novo from peripheral nerves, or following radiation therapy. Primary intraosseous MPNST is rare and has been reported most frequently in the mandible. Of the reported cases involving the long bones, none has been associated with neurofibromatosis type 1 (NF-1). We report a case of MPNST arising in the femur in a patient with NF-1.

The case presented is an example of diffuse involvement of the female genital tract by neurofibromatosis in a patient without a family history of von Recklinghausen's disease and without other clinical manifestations of the disease.

Extraskeletal myxoid chondrosarcoma, an unusual soft tissue lesion which preferentially affects the extremities, is a prime candidate for "pathologist performed" fine-needle aspirates (FNA) because it preferentially affects the extremities [Enzinger and Shiraki, Hum Pathol 1972;3:421-435] and is usually an accessible lesion. Cytomorphologically, the neoplasm consists of clusters of fairly uniform cells, lacking cartilaginous differentiation, with a metachromatic matrix when stained with Diff-Quik (DQ). While subtle, this neoplasm has distinct features and must be distinguished for other neoplasms in the differential diagnosis because patient evaluation, prognosis, and therapy will vary greatly. We present a case characteristic of this tumor in which FNA derived material was subjected to light microscopy, X-ray microanalysis, and immunohistochemical studies; each modality provided data essential to the correct diagnosis.