Beneficial Use of the Combination of Gemcitabine and Dacarbazine in Advanced Soft Tissue Sarcomas: Real-World Data.

BACKGROUND: The combination of gemcitabine and dacarbazine has exhibited efficacy in terms of progression-free survival (PFS) and overall survival (OS) for aSTSs, albeit without robust confirmation from larger clinical trials. METHODS: We conducted a retrospective study in a single institution involving aSTS patients treated with gemcitabine and dacarbazine. RESULTS: 95 patients were assessed, pointing to a benefit in PFS of 3.5 months and an OS of 14.2 months. Patients with translocated histotypes had better PFS, while those with platelet-lymphocyte ratios (PLRs) surpassing a specific threshold or lower albumin levels had poorer overall survival. CONCLUSIONS: This study validates previous findings from three phase I-II trials, affirming the utility of this treatment approach in routine clinical practice.

[Alveolar rhabdomyosarcoma: Two fusion-negative cases lacking PAX3-FOXO1 and PAX7-FOXO1]. / Rabdomiosarcoma alveolar. Dos casos negativos para la fusión PAX3-FOXO1 y PAX7-FOXO1.

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and adolescence. Morphologically, two major forms are described: alveolar and embryonal rhabdomyosarcoma. The former is generally associated with a poorer prognosis and it usually harbors a characteristic fusion gene, PAX3/7-FOXO1, that is used to confirm the diagnosis. We present two cases, both of which exhibited the classic alveolar histology with immunohistochemical myogenic differentiation (Desmin, MYOD-1 and Myogenin expression) and lacked the characteristic fusion gene PAX3/7-FOXO1. The aim of this report is to highlight the importance of the molecular status in the study and diagnosis of these cases, as it seems to be not only a useful diagnostic tool, but also an important prognostic factor.

Rabdomiosarcoma alveolar. Dos casos negativos para la fusión PAX3-FOXO1 y PAX7-FOXO1 / Alveolar rhabdomyosarcoma: Two fusion-negative cases lacking PAX3-FOXO1 and PAX7-FOXO1

Los rabdomiosarcomas son los tumores de partes blandas más frecuentes en la edad pediátrica y en adultos jóvenes. Morfológicamente se distinguen dos subtipos principales: el rabdomiosarcoma alveolar y el rabdomiosarcoma embrionario. El subtipo alveolar se asocia generalmente con un peor pronóstico y presenta una fusión génica característica que clásicamente se ha utilizado para confirmar el diagnóstico: PAX3/7-FOXO1. Presentamos dos casos que fueron remitidos a nuestro centro. Ambos mostraron morfología alveolar clásica y diferenciación muscular basada en la inmunohistoquímica; no obstante, carecían de la fusión característica PAX3/7-FOXO1. El objetivo de este artículo es resaltar la importancia del estudio molecular de estos casos no solo como herramienta diagnóstica sino también como factor pronóstico importante.(AU)

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and adolescence. Morphologically, two major forms are described: alveolar and embryonal rhabdomyosarcoma. The former is generally associated with a poorer prognosis and it usually harbors a characteristic fusion gene, PAX3/7-FOXO1, that is used to confirm the diagnosis. We present two cases, both of which exhibited the classic alveolar histology with immunohistochemical myogenic differentiation (Desmin, MYOD-1 and Myogenin expression) and lacked the characteristic fusion gene PAX3/7-FOXO1. The aim of this report is to highlight the importance of the molecular status in the study and diagnosis of these cases, as it seems to be not only a useful diagnostic tool, but also an important prognostic factor.(AU)

Uncommon and peculiar soft tissue sarcomas: Multidisciplinary review and practical recommendations. Spanish Group for Sarcoma research (GEIS -GROUP). Part II.

Among all Soft Tissue sarcomas there are some subtypes with low incidence and/or peculiar clinical behaviour, that need to be consider separately. Most of them are orphan diseases, whose biological characteristics imply a clearly different diagnostic and therapeutic approach from other more common sarcoma tumors. We present a brief and updated multidiciplinary review, focused on practical issues, aimed at helping clinicians in decision making. In this second part we review these subtypes: Alveolar Soft Part Sarcoma, Epithelioid Sarcoma, Clear Cell Sarcoma, Desmoplastic Small Round Cell Tumor, Rhabdoid Tumor, Phyllodes Tumor, Tenosynovial Giant Cell Tumors, Myoepithelial Tumor, Perivascular Epithelioid Cell Neoplasms (PEComas), Extraskeletal Myxoid Chondrosarcoma, NTRK-fusions Sarcomas. Most of them present their own radiological and histopathological feautures, that are essential to know in order to achieve early diagnosis. In some of them, molecular diagnosis is mandatory, not only in the diagnosis, but also to plan the treatment. On the other hand, and despite the low incidence, a great scientific research effort has been made to achieve new treatment opportunities for these patients even with approved indications. These include new treatments with targeted therapies and immunotherapy, which today represent possible therapeutic options. It is especially important to be attentive to new and potential avenues of research, and to promote the conduct of specific clinical trials for rare sarcomas.

Ki-67 immunoexpression and radiological assessment of necrosis improves accuracy of conventional and modified core biopsy systems in predicting the final grade assigned to adult-soft tissue sarcomas. An international collaborative study.

Based on the French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, this study assesses the accuracy of conventional and modified core biopsy (CB) systems in predicting the final grade (low vs high) assigned to the resected specimen. Substituting Ki-67 immunoexpression for mitotic count, and radiological for histological assessment of necrosis, we used two modified FNCLCC CB grading systems: (1) Ki-67 immunoexpression alone, and (2) Ki-67 plus radiological assessment of necrosis. We graded 199 soft tissue sarcomas (STS) from nine centers, and compared the results for the conventional (obtained from local histopathology reports) and modified CB systems with the final FNCLCC grading of the corresponding resected specimens. Due to insufficient sample quality or lack of available radiologic data, five cases were not evaluated for Ki67 or radiological assessment of necrosis. The conventional FNCLCC CB grading system accurately identified 109 of the 130 high-grade cases (83.8%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (87.9%) of the 199 resected tumors; overestimating the final grade in three cases and underestimating in 21 cases. Modified system 1 (Ki-67) accurately identified 117 of the 130 high-grade cases (90.0%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (89.7%) of the 195 evaluated cases; overestimating seven and underestimating 13 cases. Modified system 2 (Ki-67 plus radiological necrosis) accurately identified 120 of the 130 high-grade cases (92.3%). This last matched the final FNCLCC grading (low vs high) in 177 (91.2%) of the 194 evaluated cases; overestimating seven and underestimating 10 cases. Modified system 2 obtained highest area under ROC curves, although not statistically significant. Underestimated CB grades did not correlate with histological subtypes, although many of the discrepant cases were myxoid tumors (myxofibrosarcomas or myxoid liposarcomas), leiomyosarcomas or undifferentiated pleomorphic/spindle cell sarcomas. Using modified FNCLCC CB grading systems to replace conventional mitotic count and histologic assessment of necrosis may improve the distinction between low and high-grade STS on CB. Our study confirms that classifying grade 1 as low grade and grades 2 and 3 as high grade improves correlation between CB and final grade by up to 21%, irrespective of CB system used. A higher than expected Ki-67 score in a low-grade sarcoma diagnosed on CB should raise concern that a higher-grade component may not have been sampled. Furthermore, correlation of all clinicopathological and radiological findings at multidisciplinary meetings is essential to assess the histological grade on CB as accurately as possible.

Control de calidad de la citología ginecológica: programa de calidad de la Sociedad Española de Citología. Resultados de la segunda ronda / The Spanish Society of Cytology: quality control program of gynecological cytology

Introducción. Las recomendaciones del cribado de cáncer de cérvix en España incluyen la participación en programas de control de calidad externos a los laboratorios de citología. La Sociedad Española de Citología (SEC) ha iniciado un programa de control de calidad de la citología ginecológica (CG). Objetivo. Presentar y analizar los resultados de la segunda ronda del control de calidad de la SEC. Material y métodos. Se incluyeron casos procesados mediante citología en medio líquido. Se escanearon las laminillas mediante la plataforma Aperio. Se seleccionaron 23 muestras procedentes de un banco de casos con al menos un 75% de acuerdo entre 4 expertos citopatólogos. Los diagnósticos de los casos para estudio incluyeron: uno negativo, 15 lesiones de bajo grado (4 ASCUS y 11 LSIL) y 7 lesiones de alto grado (uno ASCH y 6 HSIL). La CML correspondía a ThinPrep® en 16 casos y a SurePath® en 7. Se realizó el estudio de la correlación diagnóstica interobservador. Resultados. Participaron 16 hospitales. Las concordancias medias fueron: global 70,6% y por tipo de lesión 63,1%. En negativo 71,9%, en ASCUS 56,2%, en LSIL 69,5% y en HSIL 82,8%. Los casos discordantes correspondían con mayor frecuencia a negativos y a ASCUS. Se observó discordancia severa (HSIL/ASCH frente a negativo) en un 4,4% de los casos. Conclusiones. Nuestros resultados son similares a los descritos en la literatura, encontrando muy escasas discordancias severas (AU)

Introduction. In Spain, the guidelines for cervical cancer screening include a recommendation to enroll in external quality control programs. The Spanish Society of Cytology (SEC) has initiated its own quality control program of gynecological cytology (QCPGC). Aim. To describe and discuss the results of the second round of SEC¿s QCPGC. Material and method. The cases are selected by a group of expert cytologists. The cases with an agreement of 75% of four cytopathologists were used. The cases were scanned with Aperio. The scanned cases not available were excluded. We included a total of 23 cases, 1 negative, 15 low grade lesions (4 ASCUS and 11 LSIL) and 7 high grade lesions (1 ASCH and 6 HSIL). Sixteen cases were studied with ThinPrep™ platform and in 7 cases the SurePath™ platform was used. Results. Sixteen hospitals participated. The global mean concordance was 70.6%. The mean concordance in the type of lesion was 63.1%. The concordance was 71.9% in negative diagnoses, 56.2% in ASCUS, 69.5% in LSIL and 82.8% in HSIL The discordant cases were diagnosed more frequently as negative and ASCUS. 4.4% of cases had major discordances (HSIL or ASCH versus negatives). Conclusions: Our results are similar to those reported in the literature, with very little severe discordance. The method of exchanging slides does not allows continuous training, since the review of discordant cases can not be made. Therefore, methodological corrections are contemplated for future rounds (AU)

[The Spanish Society of Cytology: Quality control program of gynecological cytology]. / Control de calidad de la citología ginecológica: programa de calidad de la Sociedad Española de Citología. Resultados de la segunda ronda.

INTRODUCTION: In Spain, the guidelines for cervical cancer screening include a recommendation to enroll in external quality control programs. The Spanish Society of Cytology (SEC) has initiated its own quality control program of gynecological cytology (QCPGC). AIM: To describe and discuss the results of the second round of SECs QCPGC. MATERIAL AND METHOD: The cases are selected by a group of expert cytologists. The cases with an agreement of 75% of four cytopathologists were used. The cases were scanned with Aperio. The scanned cases not available were excluded. We included a total of 23 cases, 1 negative, 15 low grade lesions (4 ASCUS and 11 LSIL) and 7 high grade lesions (1 ASCH and 6 HSIL). Sixteen cases were studied with ThinPrep™ platform and in 7 cases the SurePath™ platform was used. RESULTS: Sixteen hospitals participated. The global mean concordance was 70.6%. The mean concordance in the type of lesion was 63.1%. The concordance was 71.9% in negative diagnoses, 56.2% in ASCUS, 69.5% in LSIL and 82.8% in HSIL The discordant cases were diagnosed more frequently as negative and ASCUS. 4.4% of cases had major discordances (HSIL or ASCH versus negatives). CONCLUSIONS: Our results are similar to those reported in the literature, with very few severe discordances.

mRNA expression profiles obtained from microdissected pancreatic cancer cells can predict patient survival.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies in developed countries because of its very poor prognosis and high mortality rates. By the time PDAC is usually diagnosed only 20-25% of patients are candidates for surgery, and the rate of survival for this cancer is low even when a patient with PDAC does undergo surgery. Lymph node invasion is an extremely bad prognosis factor for this disease. METHODS: We analyzed the mRNA expression profile in 30 PDAC samples from patients with resectable local disease (stages I and II). Neoplastic cells were isolated by laser-microdissection in order to avoid sample 'contamination' by non-tumor cells. Due to important differences in the prognoses of PDAC patients with and without lymph node involvement (stage IIB and stages I-IIA, respectively), we also analyzed the association between the mRNA expression profiles from these groups of patients and their survival. RESULTS: We identified expression profiles associated with patient survival in the whole patient cohort and in each group (stage IIB samples or stage I-IIA samples). Our results indicate that survival-associated genes are different in the groups with and without affected lymph nodes. Survival curves indicate that these expression profiles can help physicians to improve the prognostic classification of patients based on these profiles.