Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas with a significant susceptibility to metastasize early in their course. Pathogenesis is yet to be fully elucidated. Recently, the essential role of mast cells in the tumor onset of neurofibromatosis type 1 (NF1)-associated neurofibromas and MPNSTs was confirmed in both experimental and human studies. In this study, we investigate mast cell density (MCD), microvascular density (MVD), and proliferation index (Ki-67) in MPNST. A secondary aim was to correlate histological staining to clinical data and survival in patients with and without NF1. In total, 34 formalin-fixed paraffin-embedded MPNST tissues from 29 patients were eligible. MCD, MVD, and Ki-67 labeling index (LI) were analyzed in all stained tissues by a computer-based quantitative algorithm (Aperio ImageScope). In addition, chart review was performed for clinical data and survival analysis. Overall, MCD, MVD, and Ki-67 LI were evenly distributed throughout tumor tissue. There was a negative correlation of NF1 status (affected, P = 0.037), tumor size (>10 cm, P = 0.023), and MVD in the tumor periphery (higher tercile, P = 0.002) to survival. Multivariate analysis confirmed the association of MVD in the tumor periphery (higher tercile, P = 0.019) with a decreased overall survival. Diverse mast cell and microvascular distributions suggest that angiogenesis in MPNST occurs independently. The role of mast cells in tumor progression is unclear and lacks prognostic value. Higher MVD has prognostic significance with possible therapeutic implications in MPNST.

Malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1.

OBJECTIVE: In this study, we review the institution's experience in treating malignant peripheral nerve sheath tumors (MPNSTs). A secondary aim was to compare outcomes between MPNSTs with and without neurofibromatosis type 1 (NF1). METHODS: Ninety-two patients with MPNSTs, over a period of 20 years, were reviewed. A retrospective chart review was performed. The median age was 43.5 years (range, 3-84 years) and 55.4% were female; 41 patients (44.6%) had NF1-associated tumors. RESULTS: Mean tumor sizes were 15.8 ± 8.2 cm and 10.8 ± 6.3 cm for patients with and without NF1, respectively. Combined two- and five-year overall survival was 48.5% and 29%. Multivariate analysis confirmed the association of tumor size greater than 10 cm (hazard ratio (HR) 2.99; 95% confidence interval (CI) 1.14-7.85; p = 0.0258) and presence of NF1 (HR 3.41; 95%CI 1.88-6.19; p < 0.001) with a decreased overall survival. CONCLUSION: Tumor size and NF1 status were the most important predictors of overall survival in our population.

Malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1 / Tumor maligno da bainha de nervo periférico com e sem Neurofibromatose tipo 1

ABSTRACT Objective In this study, we review the institution’s experience in treating malignant peripheral nerve sheath tumors (MPNSTs). A secondary aim was to compare outcomes between MPNSTs with and without neurofibromatosis type 1 (NF1). Methods Ninety-two patients with MPNSTs, over a period of 20 years, were reviewed. A retrospective chart review was performed. The median age was 43.5 years (range, 3–84 years) and 55.4% were female; 41 patients (44.6%) had NF1-associated tumors. Results Mean tumor sizes were 15.8 ± 8.2 cm and 10.8 ± 6.3 cm for patients with and without NF1, respectively. Combined two- and five-year overall survival was 48.5% and 29%. Multivariate analysis confirmed the association of tumor size greater than 10 cm (hazard ratio (HR) 2.99; 95% confidence interval (CI) 1.14–7.85; p = 0.0258) and presence of NF1 (HR 3.41; 95%CI 1.88–6.19; p < 0.001) with a decreased overall survival. Conclusion Tumor size and NF1 status were the most important predictors of overall survival in our population.

RESUMO Objetivo Relatamos a experiência institucional no tratamento de tumores malignos da bainha de nervo periférico (TMBNP) e comparamos o prognóstico entre pacientes com e sem neurofibromatose tipo 1 (NF1). Métodos Foram incluídos neste estudo 92 pacientes num período de 20 anos. Foi realizada uma análise retrospectiva dos prontuários, das características do tumor e do tratamento. A idade mediana era 43,5 anos (variação 3–84 anos) e 55,4% dos pacientes eram mulheres; 41 pacientes (44,6%) tinham tumores associados à NF1. Resultados O diâmetro médio dos tumores era 15,8 ± 8,2cm e 10,8 ± 6,3cm para pacientes com e sem NF1, respectivamente. A sobrevida combinada em 2 e 5 anos foi de 48,5% e 29%. A análise multivariada confirmou que o tamanho do tumor acima de 10cm (hazard ratio (HR) 2.99; 95% intervalo de confiança (IC) 1.14–7.85; p = 0.0258) e a presença de NF1 (HR 3.41; 95%IC 1.88–6.19; p < 0.001) estão associados a uma pior sobrevida. Conclusões O tamanho do tumor e a associação com NF1 foram os preditores mais importantes de sobrevida na nossa população.

Reconstrução de extremidades com retalho livre de fíbula após ressecções oncológicas / Extremity reconstruction using a free fibula flap after oncological resection

INTRODUÇÃO: O tumor primário de ossos longos é raro, correspondendo de 0,2% a 1% dos tumores malignos. No passado, a amputação era o tratamento padrão, ocasionando grande impacto na morbidade e na mortalidade desses pacientes. Com o avanço das técnicas cirúrgicas e o envolvimento multidisciplinar, a cirurgia conservadora dos membros tornou-se o tratamento de escolha, sendo a reconstrução com retalho microcirúrgico de fíbula a mais utilizada. Este trabalho tem como objetivo apresentar a experiência do Instituto Nacional de Câncer (INCA) nas reconstruções de membros com retalho microcirúrgico de fíbula após ressecções de tumores de ossos longos. MÉTODO: Foi realizada análise retrospectiva de 7 casos de retalho livre de fíbula operados no INCA, no período de 1997 a 2009, para reconstrução de defeitos de extremidades após ressecções de tumores ósseos. Foram avaliados os seguintes parâmetros: sexo, idade, diagnóstico, localização do tumor, tipo e tamanho da ressecção, tipo e tamanho da reconstrução, vasos utilizados para anastomose, complicações pós-operatórias, estado da doença na última consulta, seguimento e tempo até deambulação. RESULTADOS: No total, 7 pacientes com média de idade de 11,8 anos (variando de 5 anos a 14 anos) foram submetidos a reconstrução de extremidades com retalho livre de fíbula, com 100% de viabilidade e consolidação óssea. As lesões eram localizadas em fêmur, tíbia ou úmero. O tumor mais comum foi o osteossarcoma. O tempo médio de retorno à deambulação foi de 14,7 meses. CONCLUSÕES: O uso do retalho livre de fíbula é uma excelente alternativa para reconstrução de membros, apresentando alta taxa de consolidação óssea, deambulação precoce, boa funcionalidade e baixa taxa de complicações.

BACKGROUND: Primary tumors of the long bones are rare, accounting for 0.2-1% of malignant tumors. In the past, amputation was the standard treatment and had a large impact on patient morbidity and mortality. With advances in surgical techniques and multidisciplinary involvement, conservative surgery of the limbs has become the treatment of choice, and reconstruction using a microsurgical fibula flap is the most commonly used technique. In this study, we aimed to present the experience of the National Cancer Institute (INCA) with limb reconstruction using a microsurgical fibula flap following tumor resection from the long bones. METHODS: We retrospectively analyzed 7 cases of free fibular flap surgery at the INCA from 1997 to 2009 for the reconstruction of defects of the extremities after bone tumor resection. We evaluated the following parameters: gender, age, diagnosis, tumor location, resection size and type, reconstruction size and type, vessels used for the anastomosis, postoperative complications, disease status at the last visit, follow-up, and time to ambulation. RESULTS: Seven patients with a mean age of 11.8 years (range, 5-14 years) underwent extremity reconstruction with a free fibula flap with 100% bone viability. The lesions were located within the femur, tibia, or humerus. Osteosarcoma was the most common tumor type. The average return to ambulation was 14.7 months. CONCLUSIONS: The use of a free fibula flap is an excellent alternative for limb reconstruction and features a high bone healing rate, early ambulation, good functionality, and a low complication rate.