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Aims. Chondroid lipoma (CL) is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16). Here, we analyze CL and its histological mimics. Methods. CL (n = 4) was compared to a variety of histological mimics (n = 83) for morphological aspects and immunohistochemical features including cyclinD1(CCND1). Using FISH analysis, CCND1 and FUS were investigated as potential translocation partners. Results. All CLs were strongly positive for CCND1. One of 4 myoepitheliomas, CCND1, was positive. In well-differentiated lipomatous tumors and in chondrosarcomas, CCND1 was frequently expressed, but all myxoid liposarcomas were negative. FISH analysis did not give support for direct involvement of CCND1 and FUS as translocation partners. Conclusions. Chondroid lipoma is extremely rare and has several and more prevalent histological mimics. The differential diagnosis of chondroid lipomas can be unraveled using immunohistochemical and molecular support.
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Liposarcomas are separated into clinicopathological entities with a characteristic morphological spectrum and mutually exclusive genetic alterations. Therefore, the rare occurrence of cases with combined patterns of well-differentiated liposarcoma and myxoid liposarcoma designated as mixed-type liposarcoma pose a conceptual problem. Moreover, this feature may have consequences for treatment choice and prognosis. Here, we have dissected the molecular relation of tumor components in cases of mixed-type liposarcoma. On the basis of heterogeneous preoperative magnetic resonance image (MRI) features, eight cases of mixed-type liposarcoma were selected. Preoperative biopsy samples and resection specimens were analyzed including molecular and immunohistochemical analysis on all components. As controls, cases with homogeneous MRI features and uniform aspects of myxoid liposarcoma (n = 5), round cell liposarcoma (n = 5) and well-differentiated liposarcoma (n = 5) were studied. All patients with heterogeneous MRI features showed morphological components of myxoid liposarcoma and well-differentiated liposarcoma. Real-time polymerase chain reaction showed FUS-DDIT3 fusion in both components in five of eight cases in the absence (zero of five) of MDM2 and CDK4 amplification. In three of eight patients, MDM2 and/or CDK4 were overexpressed, and amplification was shown by multiplex ligation-dependent probe amplification (MLPA) in the absence of myxoid liposarcoma translocations. All control patients showed a molecular pattern consistent with their morphological features. Therefore, mixed-type liposarcomas should not be regarded as collision tumors, but as an extreme variant of the morphological spectrum within a single biological entity, explaining the biological contradiction of mixed-type liposarcoma. For treatment stratification, detailed classification including molecular support should be performed in tumors with heterogeneous MRI features.
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Biomarcadores de Tumor/genética , Liposarcoma Mixoide/clasificación , Liposarcoma Mixoide/patología , Imagen por Resonancia Magnética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Proteínas de Unión a Calmodulina/genética , Proteínas de Unión a Calmodulina/metabolismo , Estudios de Cohortes , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 4 Dependiente de la Ciclina/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Liposarcoma Mixoide/genética , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , ARN Mensajero/genética , Proteína EWS de Unión a ARN , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Neoplasias Retroperitoneales/genética , Neoplasias Retroperitoneales/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Treatment decisions and prognosis assessment for liposarcoma is based on a classification that depends on morphological and genetic features. Revisions by experienced referral pathologists are often advocated. METHODS: The process of histopathological classification in referring hospitals and subsequently in a referral center in relation to molecular biological information is evaluated. A total of 331 consecutive liposarcoma patients were evaluated for the added value of histological review at time of referral. Subsequently, cases were reclassified with implementation of present-day molecular information. For all patients, complete data on staging, treatment, and follow-up were available. RESULTS: Upon histological revision, 15/54 (28%) diagnoses were reclassified in the first decade, 14/65 (22%) in the second, and 14/53 (26%) in the last decade. Molecular biological analysis enabled well-differentiated liposarcoma with or without dedifferentiated component to be better recognized as such and distinguished from myxoid liposarcoma and pleomorphic liposarcoma. Inclusion of cytogenetic information resulted in reclassification after revision in 4/18 (22%) cases in the first decade, 10/38 (26%) cases in the second decade, and 19/75 (25%) cases in the last decade. CONCLUSIONS: This study indicates that liposarcomas are heterogeneous tumors. Expert assessment and implementation of molecular biological analysis are valuable for adequate classification as a basis for treatment decisions.
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Liposarcoma/clasificación , Liposarcoma/diagnóstico , Cromosomas Humanos Par 12/genética , Técnicas de Laboratorio Clínico , Estudios de Cohortes , Quinasa 4 Dependiente de la Ciclina/genética , ADN de Neoplasias/genética , Diagnóstico Diferencial , Femenino , Humanos , Liposarcoma/terapia , Masculino , Proteínas de Fusión Oncogénica/genética , Reacción en Cadena de la Polimerasa , Pronóstico , Tasa de SupervivenciaRESUMEN
Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum.
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Inmunohistoquímica , Liposarcoma Mixoide/patología , Reacción en Cadena de la Polimerasa , Neoplasias Retroperitoneales/patología , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de Unión a Calmodulina/genética , Diferenciación Celular , Cromosomas Humanos Par 12 , Quinasa 4 Dependiente de la Ciclina/análisis , Quinasa 4 Dependiente de la Ciclina/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Liposarcoma Mixoide/química , Liposarcoma Mixoide/clasificación , Liposarcoma Mixoide/genética , Liposarcoma Mixoide/terapia , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas c-mdm2/análisis , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteína EWS de Unión a ARN , Proteína FUS de Unión a ARN/genética , Proteínas de Unión al ARN/genética , Neoplasias Retroperitoneales/química , Neoplasias Retroperitoneales/clasificación , Neoplasias Retroperitoneales/genética , Neoplasias Retroperitoneales/terapia , Terminología como Asunto , Factor de Transcripción CHOP/genética , Translocación GenéticaRESUMEN
The spectrum of lipomatous lesions ranges from benign to highly malignant disease. Differentiation between these lesions is important to indicate prognosis and choose the most appropriate treatment. Hemosiderotic fibrohistiocytic lipomatous lesion (HFLL) is a rare subtype of lipomatous tumor. The diagnosis is usually based on clinical, histological, and immunohistochemical information. Where magnetic resonance (MR) imaging is a suitable modality to assess fatty tumors, no data is reported on MR imaging of HFLL. Here, the MR characteristics are described in correlation with pathologic findings in a case of HFLL in the left thigh, an unusual location.
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PURPOSE: Surgery and adjuvant radiotherapy (RT) have long been the standard treatment for most deep-seated sarcomas; however, since the randomized trial from the National Cancer Institute of Canada, which described similar local control for pre- vs. postoperative RT, both modalities are now widely accepted. As a group, sarcomas are classified as radiation resistant. The subgroup of myxoid liposarcoma (MLS), a sarcoma with a typical vascular crow's feet pattern, is highly radiosensitive, but a mechanism for this phenomenon is unknown. Here we describe our results with preoperative RT and propose a mechanism explaining the high sensitivity based on the distinctive vascularization pattern of MLS. METHODS AND MATERIALS: Between 2002 and 2006, 31 sarcoma patients, including 10 with MLS, underwent preoperative RT at our institute. Resected specimens were histologically evaluated, focusing on classification, grade, and vascularization patterns. RESULTS: Twenty sarcomas showed more than 80% pathologic response after preoperative RT. A pathologic complete response was found in all "pure" MLS specimens after preoperative RT (n = 8). There were no pathologic complete responses in the remaining sarcoma patients (n = 23), although 12 showed 80% to 90% pathologic response. In contrast to the remaining RT-resistant sarcomas, the highly responding specimens contained branching vasculature, partial thrombus formation and inflammation of medium sized arterioles, similar to the vascular changes in MLS. CONCLUSIONS: Both MLS and sarcomas with MLS-like vasculature are highly radiosensitive. Radiation sensitivity may be explained by changes in medium-sized arterioles, obstructing the specific crow's feet vascularization and inducing hypoxia with secondary tumor cell death.