Improved discrimination of melanotic schwannoma from melanocytic lesions by combined morphological and GNAQ mutational analysis

The histological differential diagnosis between melanotic schwannoma, primary leptomeningeal melanocytic lesions and cellular blue nevus can be challenging. Correct diagnosis of melanotic schwannoma is important to select patients who need clinical evaluation for possible association with Carney complex. Recently, we described the presence of activating codon 209 mutations in the GNAQ gene in primary leptomeningeal melanocytic lesions. Identical codon 209 mutations have been described in blue nevi. The aims of the present study were to (1) perform a histological review of a series of lesions (initially) diagnosed as melanotic schwannoma and analyze them for GNAQ mutations, and (2) test the diagnostic value of GNAQ mutational analysis in the differential diagnosis with leptomeningeal melanocytic lesions. We retrieved 25 cases that were initially diagnosed as melanotic schwannoma. All cases were reviewed using established criteria and analyzed for GNAQ codon 209 mutations. After review, nine cases were classified as melanotic schwannoma. GNAQ mutations were absent in these nine cases. The remaining cases were reclassified as conventional schwannoma (n = 9), melanocytoma (n = 4), blue nevus (n = 1) and lesions that could not be classified with certainty as melanotic schwannoma or melanocytoma (n = 2). GNAQ codon 209 mutations were present in 3/4 melanocytomas and the blue nevus. Including results from our previous study in leptomeningeal melanocytic lesions, GNAQ mutations were highly specific (100%) for leptomeningeal melanocytic lesions compared to melanotic schwannoma (sensitivity 43%). We conclude that a detailed analysis of morphology combined with GNAQ mutational analysis can aid in the differential diagnosis of melanotic schwannoma with leptomeningeal melanocytic lesions

Hemangiopericytomas of the spine: case report and review of the literature

We describe a rare case of a primary intracranial meningeal hemangiopericytoma (HPC) with late metastasis to the cervical spine. A 36-year-old woman had a left occipital lesion that was histopathologically identified as HPC. Fourteen years after resection, the tumor recurred and was treated with radiotherapy. Three years later, CT imaging showed a large mass in the liver consistent with metastatic HPC, and MRI of the cervical spine showed an extensive lesion of the C3 vertebral body. The patient underwent C3 corpectomy with en-bloc tumor removal and follow-up radiation with no local recurrence or other spinal metastasis for the following 4 years. Regardless of the subtype of spinal HPC, complete surgical removal and radiotherapy appear to be treatment of choice

Incidence of Sarcoma Histotypes and Molecular Subtypes in a Prospective Epidemiological Study with Central Pathology Review and Molecular Testing

International audienceBACKGROUND: The exact overall incidence of sarcoma and sarcoma subtypes is not known. The objective of the present population-based study was to determine this incidence in a European region (Rhone-Alpes) of six million inhabitants, based on a central pathological review of the cases. METHODOLOGY/PRINCIPAL FINDINGS: From March 2005 to February 2007, pathology reports and tumor blocks were prospectively collected from the 158 pathologists of the Rhone-Alpes region. All diagnosed or suspected cases of sarcoma were collected, reviewed centrally, examined for molecular alterations and classified according to the 2002 World Health Organization classification. Of the 1287 patients screened during the study period, 748 met the criteria for inclusion in the study. The overall crude and world age-standardized incidence rates were respectively 6.2 and 4.8 per 100,000/year. Incidence rates for soft tissue, visceral and bone sarcomas were respectively 3.6, 2.0 and 0.6 per 100,000. The most frequent histological subtypes were gastrointestinal stromal tumor (18%; 1.1/100,000), unclassified sarcoma (16%; 1/100,000), liposarcoma (15%; 0.9/100,000) and leiomyosarcoma (11%; 0.7/100,000). CONCLUSIONS/SIGNIFICANCE: The observed incidence of sarcomas was higher than expected. This study is the first detailed investigation of the crude incidence of histological and molecular subtypes of sarcomas

Description of the immune microenvironment of chondrosarcoma and contribution to progression

International audienceChondrosarcoma (CHS) is a rare bone malignancy characterized by its resistance to conventional systemic and radiation therapies. Whether immunotherapy targeting immune checkpoints may be active in these tumors remains unknown. To explore the role of the immune system in this tumor, we analyzed the immune environment of chondrosarcomas both in human sample, and in a syngeneic rat model, and tested the contribution of T lymphocytes and macrophages in chondrosarcoma progression. Immunohistochemical stainings were performed on human chondrosarcoma samples and on Swarm rat chondrosarcoma (SRC) model. Selective immunodepletion assays were performed in SRC to evaluate immune population's involvement in tumor progression. In human and rat chondrosarcoma, immune infiltrates composed of lymphocytes and macrophages were identified in the peritumoral area. Immune infiltrates composition was found correlated with tumors characteristics and evolution (grade, invasiveness and size). In SRC, selective depletion of T lymphocytes resulted in an accelerated growth rates, whereas depletion of CD163+ macrophages slowed down tumor progression. Splenocytes isolated from CHS-bearing SRC showed a specific cytotoxicity directed against chondrosarcoma cells (27%), which significantly decreased in CD3-depleted SRC (11%). The immune environment contributes to CHS progression in both human and animal models, suggesting that immunomodulatory approaches could be tested in bone chondrosarcom