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Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) shows potent preclinical anticancer activity in pediatric solid tumors such as Ewing sarcoma, rhabdomyosarcoma and neuroblastoma, but responses in clinical trials have been modest. In this work, we aimed to discover a rational biomarker-based approach to select the right candidate patients for this treatment. We assessed the efficacy of nab-paclitaxel in 27 patient-derived xenografts (PDX), including 14 Ewing sarcomas, five rhabdomyosarcomas and several other pediatric solid tumors. Response rate (partial or complete response) was remarkable in rhabdomyosarcomas (four of five) and Ewing sarcomas (four of 14). We addressed several predictive factors of response to nab-paclitaxel such as the expression of the secreted protein acidic and rich in cysteine (SPARC), chromosomal stability of cancer cells and expression of antiapoptotic members of the B-cell lymphoma-2 (Bcl-2) family of proteins such as Bcl-2, Bcl-xL, Bcl-W and Mcl-1. Protein (immunoblotting) and gene expression of SPARC correlated positively, while immunoblotting and immunohistochemistry expression of Bcl-2 correlated negatively with the efficacy of nab-paclitaxel in Ewing sarcoma PDX. The negative correlation of Bcl-2 immunoblotting signal and activity was especially robust (r = 0.8352; P = 0.0007; Pearson correlation). Consequently, we evaluated pharmacological strategies to inhibit Bcl-2 during nab-paclitaxel treatment. We observed that the Bcl-2 inhibitor venetoclax improved the activity of nab-paclitaxel in highly resistant Bcl-2-expressing Ewing sarcoma PDX. Overall, our results suggest that low Bcl-2 expression could be used to select patients with Ewing sarcoma sensitive to nab-paclitaxel, and Bcl-2 inhibitors could improve the activity of this drug in Bcl-2-expressing Ewing sarcoma.

Resumen El sarcoma histiocitico es un tumor maligno infrecuente, de patogenia incierta, caracterizado por una proliferacion de celulas neoplasicas con morfologia e inmunofenotipo de los histiocitos tisulares maduros. Aunque existen pocas referencias bibliograficas, afecta a pacientes de ambos sexos, de amplio rango de edad y afectacion nodal y/o extranodal. Se ha senalado la existencia en muchos casos de una estrecha relacion entre esta entidad y varias neoplasias hematolinfoides en un mismo paciente, lo que ha dado lugar a multiples estudios para esclarecer su etiologia y su patogenia. Su curso suele ser rapidamente progresivo y no se conoce una pauta terapeutica eficaz. Actualmente su diagnostico sigue siendo por exclusion. Presentamos el caso de un paciente de 82 anos con perforacion de un asa yeyunal con una tumoracion maligna que infiltra transmuralmente la pared y solo expresa CD68, CD45RO, CD163, lisozima y vimentina, junto con un reordenamiento clonal linfoide B con escasa amplificacion.

[EN]: Soft tissue myoepithelial carcinomas (STMM) are clinically aggressive tumors that arise in the extremities and limb girdles of young patients. Histologically, they show moderate to severe atypia and infiltrative margins. EWSR1-gene rearrangements are present in 45% of cases and are associated with increased malignancy.A large mass in the right hip of a 26-year-old male that had been surgically removed showed strands of cells embedded in a hyalin-myxoid matrix without ductal differentiation. Cells expressed cytokeratins, EMA, S-100 protein and calponin. STMM was diagnosed. Although the tumor did not have an EWSR1 gene rearrangement, it behaved aggressively and the patient died from multiple metastases 18 months after diagnosis. © 2011 SEAP y SEC., [ES]: Los carcinomas mioepiteliales de partes blandas (STMM), afectan a las extremidades o cinturas de pacientes jóvenes y evolucionan agresivamente. Muestran una marcada atipia y bordes infiltrantes y su pronóstico empeora con el reordenamiento del gen EWSR1, presente en el 45% de los casos. Presentamos el caso de un varón de 26 años al que se le extirpó un STMM situado en la cadera derecha, compuesto por cordones y nidos sólidos de células atípicas rodeadas de un estroma mixoide-hialino, sin diferenciación ductal. Expresaban citoqueratinas, EMA, S100 y calponina. La hibridación in situ fluorescente (FISH) no reveló reordenamientos del gen EWSR1. Tras recibir cuidados paliativos, el paciente murió por múltiples metástasis a los 18 meses del diagnóstico. Se trata de un caso de STMM sin reordenamiento del gen EWRS1 pero inusualmente agresivo., Partially supported by the Ministry of Science and Innovation of Spain-FEDER (PI081828, RD06/0020/0059).

Desmoplastic spindle cell tumor of the liver is a recently described and extremely unusual neoplasm that affects children and young adults. We report 1 case in a 33-year-old man. The patient had abdominal pain and dyspepsia. Abdominal examination showed that the liver was enlarged and palpable until umbilical region. Laboratory studies demonstrated positive serologic markers to hepatitis B virus. All other analytical studies were irrelevant. Computed tomography revealed a large tumor mass in left hepatic lobe showing heterogeneous densities, with hyperdense peripheral areas, as multiple nodular calcifications of less than 1 cm. In the central part of the mass, a big hypodense area was observed. There was no evidence of extrahepatic disease. Grossly, the tumor was well circumscribed with multiple nodular calcifications. The tumor was characterized by the presence of cohesive nests of bland spindle cells arranged in short fascicles and surrounded by desmoplastic stroma, intermixed with epithelioid cells. Mitotic activity was very low. Extensive osteoid formation was seen inside the cell nests. The tumor cells showed cytoplasmic reactivity for vimentin and pan-cytokeratin. The cells of desmoplastic stroma were immunoreactive for actin. The biologic behavior is still uncertain with only 5 published cases, but current information suggests that they are low-grade tumors with an indolent course. The clinical and morphologic features of this tumor are very similar to those of tumors previously reported as >nested stromal-epithelial tumor of liver> and >ossifying stromal-epithelial tumor of liver.> We describe the histologic, immunohistochemical, and molecular genetic features of a case of desmoplastic spindle cell tumor of the liver and review the literature. © 2010.

Sarcomas and Gastrointestinal Stromal Tumors: Presentations From the 2008 European Society for Medical Oncology International Symposium.-- et al., Despite complex genetics, aneuploid tumors like dedifferentiated liposarcoma have specific and reproducible chromosomal changes such as amplification of HDM2 and CDK4 that represent potential targets for systemic therapy. In addition, there are cancer cell survival pathways that may not be the target of chromosomal translocations or mutations that are still estimable targets for new systemic therapeutics, be it pathways involved in angiogenesis or apoptosis. In this review, we examine target selection for specific sarcoma subtypes, and demonstrate with a few examples new techniques being used to delineate novel therapeutic inroads for patients with sarcoma. © 2009 Elsevier Inc. All rights reserved., Enrique de Alava is supported by the European Commission (NoE EuroBoNet), Ministry of Science and Innovation of Spain-FEDER (PI052524, RD06/0020/0059). Silvana Pilotti is supported by Associazione Italiana per la Ricerca sul Cancro (AIRC). Robert G. Maki is supported by Program Project Grant No. P01-CA47179; Cycle for Survival. David M. Thomas is supported by the Victorian Cancer Agency Clinician Researcher fellowship, and Cancer Australia.

Resumen Caso clinico Los autores presentan un sarcoma de partes blandas cervicales que por su forma de presentacion clinica, localizacion yuxtatiroidea y aspecto histologico simulaba un tumor maligno de glandula tiroides. Resultados Aunque la histologia podia ser compatible con varias formas de carcinoma tiroideo, especialmente con un carcinoma medular, los resultados del estudio inmunohistoquimico y las alteraciones moleculares del gen EWS mediante FISH en parafina correspondieron a un tumor maligno de celulas redondas de estirpe mesenquimal, concordante con sarcoma de Ewing/ PNET. Conclusion Este caso, de gran dificultad diagnostica, sirve para recordar que en el diagnostico diferencial de tumores tiroideos pobremente diferenciados hemos de considerar la posibilidad de afectacion secundaria del mismo por tumores de estructuras vecinas, ya que los sarcomas primarios de la glandula tiroides son muy infrecuentes y en su mayoria corresponden a formas sarcomatoides de carcinomas tiroideos.

We report 4 cases of pseudomesotheliomatous carcinoma of the lung, which has clinical and microscopic features similar to malignant mesothelioma, but with ultrastructural, immunohistochemical, and molecular characteristics suggestive of a histogenesis from type II pneumocytes. Neoplasm grows as a diffuse or solid pattern of large polygonal cells with sharply defined borders. Hale's colloidal iron is positive in the cytoplasm of small groups of cells and, focally, in some intercellular spaces. Ultrastructure showed short microvilli in the surface. Immunohistochemically, tumor cells were positive for thyroid transcription factor-1, podoplanin, mesothelin, pan-cytokeratin, CK-7, CK-19, Ber-EP4, epithelial membrane antigen, apoprotein surfactant A, epidermal growth factor receptor, Leu-M1, carcinoembryonic antigen, E-cadherin, and CD-44 and negative for mesothelioma markers thrombomodulin and calretinin. In some areas, there were small cysts which contained a concentric fibrilar basophilic material apoprotein surfactant A positive. Chromosomal imbalances with comparative genomic hybridization technique were identified with a median of 15 abnormalities per case (range, 1-26): 51 gains, 6 losses, and 1 high-level amplification. The most frequent aberrations among the cases were gains on chromosomes regions 1q, 3q, 5p, 8q, 16p, and 18q and losses in 17p11-13 and 17q 22-q25. High-level amplifications were detected on 7p13-p21. In all cases, there was a characteristic association between the gains on 16p and those on 18q. The 4 cases resulted in death in less than 14 months, in spite of complete surgery and chemotherapy in 2 cases. Our aim is to complement the current understanding of this pseudomesotheliomatous >pneumocytic> carcinoma and alert pathologists to this rare entity to avoid misdiagnosis. © 2007 Elsevier Inc. All rights reserved.

Resumen Introduccion El sarcoma sinovial es un tumor de partes blandas poco frecuente en cabeza y cuello y excepcional en la mandibula. Presentacion del caso Presentamos un caso de un paciente de 74 anos previamente diagnosticado y tratado de osteosarcoma mandibular, que muestra una tumoracion en el remanente mandibular con extension infratemporal. El diagnostico con microscopia optica, tecnicas inmunohistoquimicas y ultraestructura fue de sarcoma sinovial monofasico. Se realizo estudio genetico para la traslocacion t (x;18) que resulto positiva, confirmandose el diagnostico de recidiva local por sarcoma sinovial. La biopsia previa estaba erroneamente diagnosticada. Conclusiones El sarcoma sinovial monofasico requiere diagnostico diferencial con otras entidades. Es una tumoracion que recidiva en mas de la mitad de los casos y presenta un riesgo elevado de metastasis. Su diagnostico exacto necesita un buen procesamiento tisular, tecnicas inmunohistoquimicas, ultraestructurales y estudio genetico.

alpha-Interferon therapy normalizes aminotransferase levels in approximately 50% of the patients with chronic hepatitis C, but post-therapy relapses are common and predictive factors of sustained response remain largely unknown. We retrospectively assessed several parameters as predictors of sustained remission after a 12-month course of lymphoblastoid alpha-interferon: the Knodell histological activity index, serum levels of procollagen type III peptide, serum HCV-RNA, anti-alpha-interferon antibodies, and anti-HCV antibodies (C-100-3), all at month 12. Thirty-seven patients were studied. Fourteen patients were non-responders (38%), 15 patients experienced a sustained response (40.5%) and eight patients responded similarly but relapsed after alpha-interferon withdrawal (21.5%). A decrease in the histological activity index above 5, normalization of procollagen type III peptide levels (< 12 ng/ml) and the absence of viremia after treatment were all significantly associated with a sustained response (p = 0.008, p = 0.007 and p = 0.037, respectively). Anti-interferon antibodies were detected in only one non-responder patient. Anti-C-100-3 antibodies became undetectable at month 12 in 5 of the 15 sustained responders. The best prediction of sustained response was obtained from the three variables independent of multivariate analysis according to the following equation: F = 0.872 + 0.067 x K (decrease of histological index) -0.052 x P (procollagen type III peptide levels at month 12) -0.28 x R (HCV-RNA at month 12; R = 2 when present and R = 1 when absent). A score higher than 0 predicted sustained remission with a 100% sensitivity and specificity in this series of patients.

Soft tissue sarcomas (STS) constitute a rare heterogeneous group of tumours that include a wide variety of histological subtypes, which require a multidisciplinary and, frequently specialized and complex management. Despite advances in our understanding of the pathophysiology of the disease, there are no consensus multidisciplinary recommendations about its diagnosis and treatment in our country. The objective of these guidelines is to provide practical therapeutic recommendations that may contribute to improve the therapeutic results of this disease in our environment. With this purpose, the Spanish Group for Research in Sarcomas (GEIS) held a meeting with a multidisciplinary group of experts for the study and management of sarcomas. The results of this meeting are compiled in this document, in which recommendations on diagnosis, treatment and monitoring of soft tissue sarcomas are included. In summary, these guidelines aim to facilitate the identification and management of STS for clinical practice in Spain.