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

Mapping the zonal organization of tumor perfusion and permeability in a rat glioma model by using dynamic contrast-enhanced synchrotron radiation CT.

International audiencePURPOSE: To depict and analyze in vivo the tumor zone organization of C6 gliomas depicted on quantitative parametric maps obtained with dynamic contrast material-enhanced synchrotron radiation computed tomography (CT) in a tightly controlled data-processing protocol. MATERIALS AND METHODS: Animal use was compliant with official French guidelines and was assessed by the local Internal Evaluation Committee for Animal Welfare and Rights. Fifteen Wistar rats with orthotopically implanted gliomas were studied at monochromatic synchrotron radiation CT after receiving a bolus injection of contrast material. The iodine concentration maps were analyzed by using a compartmental model selected from among a package of models. Choice of model and assessment of the relevance of the model were guided by quality criteria. Tissue blood flow (F(T)), tissue blood volume fraction (V(T)), permeability-surface area product (PS), artery-to-tissue delay (D(A-T)), and vascular mean transit time (MTT) maps were obtained. Parametric map findings were compared with histologic findings. Local regions of interest were selected in the contralateral hemisphere and in several tumor structures to characterize the tumor microvasculature. Differences in parameter values between regions were assessed with the Wilcoxon method. RESULTS: Whole-tumor parameters were expressed as means +/- standard errors of the mean: Mean F(T), V(T), PS, and D(A-T) values and MTT were 61.4 mL/min/100 mL +/- 15.3, 2.4% +/- 0.4, 0.37 mL/min/100 mL +/- 0.11, 0.24 second +/- 0.06; and 3.9 seconds +/- 0.83, respectively. MTT and mean PS were significantly lower (P < .01) in the normal contralateral tissue: 1.10 seconds +/- 0.06 and < or = 10(-5) mL/min/100 mL, respectively. Tumor regions were characterized by significantly different (P < .05) F(T) and V(T) pairs: 108 mL/min/100 mL and 3.66%, respectively, at the periphery; 45.9 mL/min/100 mL and 1.91%, respectively, in the intermediate zone; 5.1 mL/min/100 mL and 0.42%, respectively, in the center; and 210 mL/min/100 mL and 6.82%, respectively, in the maximal value region. CONCLUSION: Fine mapping of the glioma microcirculation is feasible with dynamic contrast-enhanced synchrotron radiation CT performed with well-controlled analytic protocols. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2501071929/DC1

Primary epithelioid sarcoma of bone: report of a unique case, with immunohistochemical and fluorescent in situ hybridization confirmation of INI1 deletion.

International audienceWe report the clinical and pathologic features of, what is to the best of our knowledge, the first case of epithelioid sarcoma of bone. A 31-year-old woman with an unremarkable past medical history presented with pelvic pain and was found by computed tomography scan to have a destructive 5 cm, partially calcified intraosseous lesion of the iliac bone. Histologically, the tumor consisted of relatively uniform but clearly malignant-appearing epithelioid cells, with scattered rhabdoid-appearing cells. A hyalinized to partially calcified matrix was present between the tumor cells, with a "chickenwire" pattern of calcification. By immunohistochemistry, the neoplastic cells expressed cytokeratins, vimentin, epithelial membrane antigen and CD34, and showed complete loss of INI1 protein expression. Fluorescence in situ hybridization showed homozygous deletion of the INI1 gene. An extensive clinical and radiographic workup did not show evidence of a soft tissue tumor, and the diagnosis of a primary epithelioid sarcoma of bone was made. After this, the patient underwent a complete resection of her tumor, and is currently disease free, 6 months after surgery. These extremely rare tumors must be rigorously distinguished from other more common tumors of bone, in particular, chondroblastoma and osteosarcoma. Awareness that epithelioid sarcoma may occur in bone, careful histologic evaluation and ancillary immunohistochemistry for epithelial markers, CD34 and INI1 protein should allow for recognition of such tumors. Study of additional cases of primary epithelioid sarcoma of bone will be necessary to better understand its clinical behavior

Ex vivo confocal microscopy imaging to identify tumor tissue on freshly removed brain sample

Confocal microscopy is a technique able to realize "optic sections" of a tissue with increasing applications. We wondered if we could apply an ex vivo confocal microscope designed for dermatological purpose in a routine use for the most frequent brain tumors. The aim of this work was to identify tumor tissue and its histopathological hallmarks, and to assess grading criteria used in neuropathological practice without tissue loss on freshly removed brain tissue. Seven infiltrating gliomas, nine meningiomas and three metastases of carcinomas were included. We compared imaging results obtained with the confocal microscope to frozen sections, smears and tissue sections of formalin-fixed tissue. Our results show that ex vivo confocal microscopy imaging can be applied to brain tumors in order to quickly identify tumor tissue without tissue loss. It can differentiate tumors and can assess most of grading criteria. Confocal microscopy could represent a new tool to identify tumor tissue on freshly removed sample and could help in selecting areas for biobanking of tumor tissue

PD-L1 expression in pleomorphic, spindle cell and giant cell carcinoma of the lung is related to TTF-1, p40 expression and might indicate a worse prognosis.

Lung sarcomatoid carcinoma of the lung is a rare tumor with a poor prognosis. More than 90% of them are pleomorphic, spindle cell and giant cell carcinoma (PSCGCC). This rare subtype of lung cancer is thought to be more resistant to chemotherapy, and a small subset of them seems to exhibit targetable mutations. Immunotherapy against PD1/PDL-1 is a new emerging treatment, and might be of interest in PSGSCC because they frequently express PD-L1. The aim of our work is to evaluate PD1 and PDL-1 expression in a surgical series of lung PSCGCC and their relationship with morphological and immunohistochemical parameters and prognosis. Thirty-six patients who underwent surgical resection of a PSGSCC were included. PD-L1 (E1L3N) expression on tumor cells and PD1 (NAT105) expression by tumor infiltrating lymphocytes (TILs) were performed by immunohistochemistry. Results were compared to immunohistochemistry tests of TTF1, Napsin A, p40 and to molecular study of EGFR, KRAS, BRAF and HER2. Seventy-five % of PSCGCC were considered as positive for PD-L1.PD-L1 expression in PSGSCC is associated with TTF-1 and/or Napsin A expression (47.2%, p = 0.039). Few p40 positive PSCGCC expressed PD-L1 (8.3%, p = 0.013). PD1 expression was not related to TTF-1 and/or Napsin A expression (p = 0.47), p40 expression (p = 0.68) or survival (p = 0.14). PD-L1 or PD1 expression were not related to the age, gender, pT, pN, stage, visceral pleura invasion, histopathological subtype, the presence of giant cell component, the predominance of sarcomatoid component, and the presence of EGFR or BRAF or HER2 or PIK3CA mutation (p>0.05). PD-L1 expression was correlated with a worse overall survival in PSCGCC (p = 0.045). PD-L1 expression is frequent in PSCGCC and might be associated with the expression of adenocarcinoma markers (TTF-1, Napsin A) or the lack of expression of squamous cell carcinoma marker (p40)

Distribution of molecular subtypes for sarcoma with specific gene abnormality (N = 362).

<p>GIST, gastrointestinal stromal tumors; PNET, primitive neuroectodermal tumor.</p>1<p>CIR: Crude incidence rate/100,000/year.</p>2<p>Molecular biology analysis not performed in France.</p>3<p>Detection of rearrangement of ALK gene.</p>4<p>Possible fusion transcript: TLS-CHOP; EWS-CHOP.</p>5<p>Possible fusion transcript: EWS-FLI1; EWS-ERG; EWS-FEV; EWS-EIAF; EWS-ETV1.</p>6<p>Possible fusion transcript: PAX3-FKHR; PAX7-FKHR.</p

Description of GIST stratification risk.

<p>NIH, National Institutes of Health ; AFIP, Armed Forces Institute of Pathology.</p>1<p>Grade was not evaluated due to limited material or too undifferentiated tumor.</p

Crude incidence of histological subtypes.

<p>GIST, gastrointestinal stromal tumor; PNET, primitive neuroectodermal tumor.</p>1<p>Crude incidence rate/100,000/year.</p>2<p>Unclassified sarcomas were divided in subtypes according to morphological features based on experts' advice.</p

Rare histological types of sarcoma.

1<p>MPNST, malignant peripheral nerve sheath tumor.</p>2<p>PEComa, neoplasm with perivascular epithelioid cell differentiation.</p