We report a case of desmoplastic small-cell tumor occurring in the CNS in relation to the tentorium in a 24-year-old man. Morphologically, the neoplasm had the typical appearance of small, round tumor cells of primitive appearance growing as well-defined nests separated by abundant desmoplastic stroma. The diagnosis was confirmed through the demonstration of immunoreactivity for keratin, desmin, and neuron-specific enolase and the detection by Southern blot analysis of a unique gene resulting from the fusion of the WT1 gene in chromosome 11 and the EWS gene in chromosome 22. This is the first documented instance of the occurrence of this tumor type at a distance from a mesothelial-lined surface.

The molecular basis of advanced systemic mastocytosis (SM) is not fully understood and despite novel therapies the prognosis remains dismal. Exome sequencing of an index-patient with mast cell leukemia (MCL) uncovered biallelic loss-of-function mutations in the SETD2 histone methyltransferase gene. Copy-neutral loss-of-heterozygosity at 3p21.3 (where SETD2 maps) was subsequently found in SM patients and prompted us to undertake an in-depth analysis of SETD2 copy number, mutation status, transcript expression and methylation levels, as well as functional studies in the HMC-1 cell line and in a validation cohort of 57 additional cases with SM, including MCL, aggressive SM and indolent SM. Reduced or no SETD2 protein expression—and consequently, H3K36 trimethylation—was found in all cases and inversely correlated with disease aggressiveness. Proteasome inhibition rescued SETD2 expression and H3K36 trimethylation and resulted in marked accumulation of ubiquitinated SETD2 in SETD2-deficient patients but not in patients with near-normal SETD2 expression. Bortezomib and, to a lesser extent, AZD1775 alone or in combination with midostaurin induced apoptosis and reduced clonogenic growth of HMC-1 cells and of neoplastic mast cells from advanced SM patients. Our findings may have implications for prognostication of SM patients and for the development of improved treatment approaches in advanced SM.

A 70-year-old immunocompetent woman who had been radiologically diagnosed with a left parasagittal meningioma 5 years previously developed a palpable subgaleal mass and underwent neurosurgery. Histologically the tumor was composed of thickened fibrotic dural tissue, infiltrated by a follicular lymphoma, of grade IIIB. A coexistent transitional meningioma had been infiltrated by the neoplastic lymphoid tissue. Two months after surgery, the patient developed evidence of extracranial dissemination of the lymphoma to the cervical lymph nodes and was treated with polychemotherapy plus Rituximab and intrathecal methotrextate. The patient is alive and recurrence-free at 1-year follow up. A review of the literature indicates that lymphomas developing primarily in the meninges, have an indolent course and tend to be localized in areas rich in meningothelial cells.

Context.—Gliosarcoma is a rare tumor of the central nervous system characterized by a biphasic histologic pattern, consisting of a gliomatous and a sarcomatous component, respectively. In most instances the sarcomatous component is represented by a fibrosarcoma, but other stromal malignancies have also been described. Osteosarcomatous differentiation in gliosarcoma has been rarely reported. Objective.—To review characteristic radiologic and histopathologic features of this rare neoplasm, to debate about possible differential diagnoses that should be taken into consideration, and to provide an overview of the potential histopathogenesis of gliosarcomas. Data Sources.—Relevant articles indexed in PubMed (National Library of Medicine) and reference medical texts. Conclusions.—Recent molecular studies suggest that sarcomatous and gliomatous components of gliosarcoma might be derived from a single precursor cell clone, progressing in 2 subclones with distinct morphologic features during tumor evolution. Nonetheless, events determining splitting of the original clone into 2 histologic populations remain to be investigated.

Sentinel lymph node (SLN) analysis allows the detection of occult metastases in patients with melanoma. The use of serial sections and immunohistochemical investigations (ICH) increases the chance of identifying metastases. Nevertheless, detection of mRNA of the tyrosinase gene through reverse transcription-polymerase chain reaction (RT-PCR) is the most sensitive tool for detection of occult melanoma cells in SLN. From September 1999 to August 2001, in the Anatomic Pathology Unit of M. Bufalini Hospital of Cesena, 489 SLNs from 332 patients with primary melanoma in clinical stages I and II (according to AJCC) were examined. There were 66 (13.5%) SLNs and 58 (17.4%) cases with metastasis revealed by histology and ICH. A single case with metastatic SLN was found in patients with melanomas < or = 1 mm in thickness. The percentage of cases with metastases in SLN correlated with thickness of the primary melanoma (p < 0.0001). RT-PCR for tyrosinase was carried out in 448 SLNs from of 308 cases. Overall, the RT-PCR results were positive in 149 (48.4%) patients and in 169 SLNs (37.9%). RT-PCR results showed a strong positive correlation with tumor thickness of primary melanoma (p < 0.0001) and with the clinical stage (p < 0.0001). Of the RT-PCR-positive cases, 18 showed intracapsular aggregates of nevus cells. Besides the percentage of positive cases, once those with nevus aggregates were excluded, overall, the RT-PCR revealed the presence of tyrosinase mRNA in 34.5% of patients with negative histology and ICH. Ongoing monitoring is necessary to define the real prognostic implication of the presumed presence of occult melanoma deposits disclosed by RT-PCR in SLNs.