Pelvic Leiomyosarcoma With Splenic Metastasis and Response Assessment by 18F-FDG PET/CT.

The pelvis is a rare site for the origin of soft tissue sarcomas, and leiomyosarcoma remains the most common soft tissue sarcoma arising in the pelvis. Pelvic leiomyosarcomas are frequently aggressive tumors, and metastatic recurrence rates are high, with the lung, peritoneum, bone, and liver being the most frequent sites. We describe the findings of serial F-FDG PET/CT in a 53-year-old woman having pelvic leiomyosarcoma with uncommon site of metastasis, emphasizing the role of F-FDG PET/CT in response assessment.

Characterizing the efficacy and trends of adjuvant therapy versus observation in women with early stage (uterine confined) leiomyosarcoma: a National Cancer Database study.

OBJECTIVE: The utility of adjuvant therapy for women with uterine confined leiomyosarcoma remains uncertain. We sought to identify trends, analyze efficacy, and assess survival impact of adjuvant therapy in this patients. METHODS: We performed an observational cohort study of 1030 women with early stage leiomyosarcoma from the 2008-2014 National Cancer Database. Multi-nominal logistic regression was used to identify trends in receipt of adjuvant treatment. Demographic and clinical characteristics were compared. Kaplan-Meier curves were used to estimate survival. RESULTS: There were 547 who (53.1%) received observation, 79 (7.7%) received radiation alone, 340 (33.0%) received chemotherapy alone, and 64 (6.2%) received chemoradiation. Patients were more likely to be observed if tumor size was <5 cm (hazard ratio [HR]=0.97; 95% confidence interval [CI]=0.95-0.99; p=0.017) and less likely to be observed if lymphovascular space invasion (LVSI) was present (HR=0.60; 95% CI=0.41-0.89; p=0.010). Patients were more likely to receive chemotherapy if they were younger (HR=0.78; 95% CI=0.65-0.94; p=0.010) and if they had LVSI (HR=1.47; 95% CI=1.01-2.16; p=0.040). There was an independent association between older age, tumor size >5 cm, and LVSI with worsened survival, with the strongest predictor of mortality being the presence of LVSI. With a median survival of 61.9 months, there was no difference in estimated overall survival at 1 and 3 years based on receipt of adjuvant treatment as compared to observation (p=0.500). CONCLUSION: Although women with uterine confined leiomyosarcoma experience high recurrence rates and poor survival outcomes, adjuvant treatment does not appear to confer a survival benefit.

Oncological outcome, functional results and costs after unplanned excision of musculoskeletal soft tissue sarcoma.

BACKGROUND: Treatment of soft tissue sarcomas (STS) should only be initiated once the diagnosis is fully established. Resection of tumors of unknown nature should be avoided. Nevertheless, specialized centers continue to face numbers of unplanned excisions (UPE) in STS. AIM: To compare oncologic and functional outcomes, number of surgeries, length of hospital stay and treatment costs of UPE versus planned excision (PE) in STS. METHOD: A retrospective single tertiary center study was performed on 201 patients. Survival, local and distant recurrence rates were compared between PE (n = 137) and UPE (n = 64). In a subgroup analysis of 60 patients, functional outcome (MSTS and TESS scores), and socio-economic impact (number of surgeries, length of hospital stay and treatment costs) in "functional planned excision" (fPE) group (n = 30) and "functional unplanned excision" (fUPE) group (n = 29) were compared. RESULTS: There was no significant difference in oncological outcome between PE and UPE. In the subgroup analysis, we found a non-significant difference in functional outcome. Patients in the fUPE had significantly more surgeries (3.5 vs. 1.4; p < 0.00001) and costs of their management was 64% higher than fPE (p = 0.048). Hospital stay was longer after fUPE but not statistically significant (18.3 days vs. 11.8 days; p = 0.13). CONCLUSION: Even though oncological and functional outcomes are comparable after PE and UPE of STS, the number of surgeries, length of hospital stay and treatment costs were higher in patients with UPE. Our data underscore the importance of specialized STS treatment centers including multidisciplinary management.

The Adequacy of Core Biopsy in the Assessment of Smooth Muscle Neoplasms of Soft Tissues: Implications for Treatment and Prognosis.

The grading of soft tissue sarcomas is one of the most important prognostic factors and determines patient management. Although grading of most adult-type soft tissue sarcomas on biopsies correlates highly with the final grading on the excision specimen, it appears less reliable for tumors of smooth muscle. We assessed the pathologic findings for smooth muscle neoplasms diagnosed by core biopsy at our tertiary sarcoma center, and compared them with those in the subsequent excision specimens. A total of 100 patients with leiomyosarcoma first diagnosed on core biopsy and with a subsequent excision were identified and the accuracy of the biopsy grade determined by comparison with the excision grade. Differences in other salient histologic parameters were also noted. A grade difference between biopsy and excision specimens of leiomyosarcomas was found in 68% of cases, with all these cases showing an increase in grade from biopsy to excision specimen. Of the 3 parameters used for grading using the French Federation of Cancer Centers Sarcoma Group Grading System (FNCLCC), necrosis was the score that most commonly differed between biopsy and excision specimen (55%), closely followed by the mitotic count (51%). The grading of soft tissue smooth muscle tumor biopsies has a lower accuracy compared with other adult soft tissue sarcomas and should therefore be taken with caution, particularly as this may be an underrepresentation of the true tumor grade.

Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response Score.

PURPOSE: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). METHODS AND MATERIALS: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. RESULTS: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). CONCLUSION: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.

Updates in uterine fibroid tissue extraction.

PURPOSE OF REVIEW: Safety concerns regarding morcellation of presumed benign fibroid disease have led to an increase in recent research activity on this topic, as well as advances in surgical technique. RECENT FINDINGS: The prevalence of occult leiomyosarcoma is debated; however, estimates from a robust meta-analysis suggest it may be in the range of 1 case per 1960-8300 fibroid surgeries. Advancing age is an important clinical risk factor for occult malignancy. The impact of tumor morcellation may vary by mode of tissue removal, though tissue fragmentation is consistently associated with poorer outcomes. Decision and cost analyses continue to support laparoscopic hysterectomy as a low-morbidity and cost-effective approach. The increased scrutiny on fibroid procedures in the past few years may lead to changes in surgical approach; however, alternative tissue extraction options are evolving, including incorporation of contained morcellation. SUMMARY: Although the incidence of occult leiomyosarcoma is low, outcomes are poor and may be worsened by morcellation. By addressing risk factors for malignancy and incorporating evolving surgical techniques into practice, gynecologists can continue to offer patients a minimally invasive approach for fibroid management.

Assessment of MR Imaging as a Tool to Differentiate between the Major Histological Types of Uterine Sarcomas.

OBJECTIVES: We retrospectively compared and quantified magnetic resonance (MR) images to distinguish major histological types of uterine sarcomas and malignant and benign tumors. METHODS: MR images were obtained from patients who underwent preoperative examinations. We compared 25 pathologically confirmed uterine sarcomas (8 leiomyosarcomas, 11 carcinosarcomas, 6 endometrial stromal sarcomas) with 25 uterine leiomyomas. MR findings included tumor size, location, contour, signal intensity (SI), and contrast enhancement. Analysis focused on the contrast ratio (CR) of SI in T2-weighted images for the areas of lowest, highest, and main SI of each tumor as well as the contrast-enhanced ratio (CER) for the main solid part of each tumor in contrast-enhanced T1-weighted images. We evaluated diffusion-weighted (DW) images and apparent diffusion coefficient (ADC) values in 18 tumors (4 sarcomas, 14 leiomyomas). RESULTS: Uterine sarcomas and leiomyomas differed significantly in tumor location, contour, hemorrhaging, necrotic and cystic components, CR for the area of lowest SI (P < 0.05), CR for the area of main SI (P < 0.01), and CER (P < 0.05). Leiomyosarcomas were larger than carcinosarcomas or endometrial stromal sarcomas, and the CR for the area of lowest SI of leiomyosarcomas (P < 0.05) was significantly lower. The CER for endometrial stromal sarcomas (P < 0.05) showed the most homogeneous enhancement. Hemorrhagic or necrotic and cystic components were found more often in larger tumors, although there was no significant difference in their occurrence between sarcoma types. All uterine sarcomas showed high intensity on DW images. The ADC values were lower of uterine sarcomas than leiomyomas, although the difference was not statistically significant. CONCLUSION: Quantitative assessment using the CR or CER was useful for distinguishing benign and malignant uterine tumors as well as major histological types of uterine sarcomas.

Trends in the treatment of uterine leiomyosarcoma in the Medicare population.

OBJECTIVE: Uterine leiomyosarcoma (LMS) is a relatively rare malignancy that is associated with a poor prognosis. The rarity of LMS has led to a lack of consensus regarding appropriate treatment. The goal of this study was to identify the role that chemotherapy and radiotherapy have played in the treatment of uterine LMS in the United States as well as the effectiveness of adjuvant treatment. MATERIALS/METHODS: We used the SEER (Surveillance, Epidemiology, and End Results)-Medicare database to gather information on uterine LMS patients older than the age of 66 years diagnosed between 1992 and 2009. Basic demographic and clinical characteristics were collected. A logistic regression model analysis was performed to determine predictors of treatment. Cox proportional hazards models were used to identify clinical parameters and treatment strategies associated with survival differences. RESULTS: Our final study group included 230 patients. We found that the rate of use of chemotherapy and radiotherapy in the treatment of patients with uterine LMS increased over the period investigated. However, we identified no significant survival advantage associated with either mode of therapy. The strongest predictor of survival was stage at diagnosis. The logistic regression model analysis revealed that age at diagnosis, treatment year, stage, and underlying health status were all independent predictors of chemotherapy. Age at diagnosis was also a predictor of radiation therapy. CONCLUSIONS: The increasing rates of chemotherapy and radiotherapy use in this population seem to be unfounded given the lack of survival benefit. Further investigation into alternative treatment regimens is merited. The prognostic significance of stage at diagnosis indicates the importance of improving early detection of uterine LMS.

Regional Radiation Pneumonitis After SIRT of a Subcapsular Liver Metastasis: What is the Effect of Direct Beta Irradiation?

We herein present a patient undergoing selective internal radiation therapy with an almost normal lung shunt fraction of 11.5%, developing histologically proven radiation pneumonitis. Due to a predominance of pulmonary consolidations in the right lower lung and its proximity to a large liver metastases located in the dome of the right liver lobe a Monte Carlo simulation was performed to estimate the effect of direct irradiation of the lung parenchyma. According to our calculations direct irradiation seems negligible and RP is almost exclusively due to ectopic draining of radioactive spheres.

Racial Disparities in Extremity Soft-Tissue Sarcoma Outcomes: A Nationwide Analysis.

BACKGROUND: Racial disparities in access and survival have been reported in a variety of cancers. These issues, however, have yet to be explored in detail in patients with soft-tissue sarcomas (STS). The purpose of this paper was to investigate the independent role of race with respect to survival outcomes in STS. METHODS: A total of 7601 patients were evaluated in this study. A SEER registry query for patients over 20 years old with extremity STS diagnosed between 2004 and 2009 (n=7225) was performed. Survival outcomes were analyzed after patients were stratified by race. Multivariable survival models were used to identify independent predictors of sarcoma-specific death. The Wilcoxon rank-sum test was used to compare continuous variables. Statistical significance was maintained at P<0.05. RESULTS: This study showed that African American patients were more likely to die of their STS. They were younger at presentation (P=0.001), had larger tumors (P<0.001), had less surgery (P=0.002), received radiotherapy less frequently (P=0.024), had higher family income (P<0.001), and were less likely to be married (P<0.001). African American race by itself was not an independent predictor of death. CONCLUSIONS: African Americans encounter death due to STS at a much larger proportion and faster rate than their respective white counterparts. African Americans frequently present with a larger size tumor, do not undergo surgical resection, or receive radiation therapy as frequently as compared with their white peers. Barriers to timely and appropriate care should be further investigated in this group of at-risk patients.

Correlation between radiological assessment and histopathological diagnosis in retroperitoneal tumors: analysis of 291 consecutive patients at a tertiary reference sarcoma center.

OBJECTIVES: Aim of study was to assess the correlation between computed tomography scan (CT) findings and histopathology. MATERIAL AND METHODS: Data were collected on consecutive patients with suspected retroperitoneal sarcoma (RPS) referred to a tertiary sarcoma center. Patients underwent contrast enhanced multi-detector CT scans. Radiological features of lesions were classified according to the presence of a fatty (Group A) mass, or non-fatty (Group B) mass, both subdivided according to homogeneity and intralesional high-contrasted appearance. Radiological classification was compared with histopathological diagnosis. Sensitivity, specificity, positive/negative predictive value (PPV, NPV) were analyzed. RESULTS: Of 291 patients, 103/291 (35.4%) masses were classified in Group A and 188/291 (64.6%) in Group B. Diagnosis of mesenchymal tumor was obtained in 231/291 cases (79%) and non-mesenchymal tumor in 60/291 (21%). Sensitivity and specificity of Group A for liposarcoma were 76.7% and 92.0%; PPV and NPV were 86.4% and 85.6%. Sensitivity of Group B for a mesenchymal tumor was 55.4% and specificity was 0%; PPV and NPV were 68.1% and 0%. CONCLUSIONS: None of radiological criteria were sufficient to anticipate a specific diagnosis, with the only exception of well differentiated liposarcoma and angiomyolipoma. In a series of suspected RPS, 21% of the lesions were finally non-mesenchymal tumors.

[Assessment of the proliferative activity of tumor cells based on long-term phase-contrast microscopy CELL-IQ].

This work presents results of long-term phase-contrast microscopy research of proliferative potential of tumor cell lines utilizing live-cell imaging technology Cell-IQ (Chip-Man Technologies Ltd, Finland). It was found that the machine vision technology allowed to obtain sufficient body of evidence about high-quality and quantitative changes of proliferative activity of the tumor cells cultivated in static conditions. The present study demonstrates that modeling of time interval of maximum proliferative activity of tumors cells increases information efficacy and reliability of the analysis of dividing cell patterns using Cell-IQ technology. The models of exponential growth of various tumor cell lines, describing their quantitative and dynamic changes of expansion potential have been received. Modeling of maximum tumor cells proliferative activity can be applied for development of test-system of individual cell sensitivity to anticancer drugs in vitro.

Validity and reproducibility of Ki-67 assessment in gastrointestinal stromal tumors and leiomyosarcomas.

With the aim of standardizing Ki-67 immunohistochemistry, we assessed interobserver and interlaboratory variability of the Ki-67 labeling index and Ki-67 score among eight general pathologists for 24 gastrointestinal stromal tumors (GISTs) and 12 leiomyosarcomas, which were predominantly of the gastrointestinal (GI) tract, mesentery and retroperitoneum, based on a review of a tissue microarrays subjected to immunohistochemistry with antibodies for Ki-67. For Ki-67 immunostaining of mesenchymal tumors of the GI tract, including GISTs, differences were seen in the scores given by regional hospitals. Conversely, for two categories of the Ki-67 labeling index, namely <10% and ≥10%, concordance of the Ki-67 score between microscopic observation and image analysis, and between the observers, was good, but it was not good for the other four categories of the index for <5%, 5-9%, 10-29%, and ≥30%. The concordance of the Ki-67 scores between the observers in two categories was higher using the Ki-67 pre-stained tissue microarrays (TMAs) within each participating institute than that using the Ki-67 stained TMAs between the participating institutes. The reproducibility of a 10% cut-off value for the Ki-67 labeling index to predict the prognosis of GISTs was relatively high, but there is an urgent need to standardize the staining technique.

Mitosis-specific marker phospho-histone H3 in the assessment of mitotic index in uterine smooth muscle tumors: a pilot study.

SUMMARY: The assessment of an accurate mitotic index (MI) is one of the major parameters in the proper classification of uterine smooth muscle tumors. This assessment can be hampered by the presence of increased number of apoptotic bodies or piknotic nuclei, which frequently mimic mitoses. Phospho-histone H3 (PHH3) is a recently described immunomarker specific for cells undergoing mitoses. In this study, we evaluated the MI of 2 subsets of uterine smooth muscle tumors--6 leiomyosarcomas (LMS) and 6 smooth muscle tumors of undetermined malignant potential (STUMP)--using PHH3-labeled sections and hematoxylin and eosin (H&E)-stained slides. In the STUMP group, the MI on H&E ranged from 0 to 9 mitoses/10 high-power fields (HPFs) (mean, 3.2), and in the LMS group, it ranged from 0 to 37 mitoses/10 HPFs (mean, 19). PHH3 showed 0 to 16 mitoses/10 HPFs (mean, 3.8) in the STUMP group and 0 to 61 mitoses/10 HPFs (mean, 26) in the LMS group. In 7 cases, the MI difference (MID) between H&E-stained and PHH3-stained slides varied from 0 to 3 mitoses (mean, 1.6). In only one LMS, the PHH3 MI was lower than on H&E-stained slides (MID 7). The MI on H&E-stained and PHH3-stained slides were comparable in 7 cases, 5 of which were STUMPs. In 4 other cases, 3 of which were LMS, the PHH3 MI was significantly higher than the one obtained on H&E. The higher MI obtained with PHH3-labeled sections in some cases is most likely due to the recognition of true mitoses by the antibody, which were initially misinterpreted as apoptotic bodies and/or piknotic nuclei on H&E and not included in the formal count, and the fact that the phosphorilation of histone H3 starts just before the prophase and at this stage mitoses cannot be identified by H&E.

Oral leiomyosarcoma: review of the literature and report of two cases with assessment of the prognostic and diagnostic significance of immunohistochemical and molecular markers.

Leiomyosarcoma of the oral cavity is a very rare tumor that is associated with aggressive clinical behavior and low survival. In this paper, we report two new cases of leiomyosarcoma affecting the mandibular gingiva and mandible of a 35-year-old male and the mandible of a 51-year-old female. Given the difficulty in the histopathologic discrimination between benign and malignant smooth muscle tumors and the absence of reliable histologic parameters for prognostication of leiomyosarcomas, we evaluated the diagnostic and prognostic value of various immunohistochemical and molecular markers. By means of immunohistochemistry and quantitative real-time PCR analysis, we detected protein expression of PCNA, bcl-2, CDK4, p53 and MDM2 in both our cases and MDM2 amplification in our second case. The literature, pertinent to oral leiomyosarcoma and to molecular analysis of smooth muscle tumors, is reviewed.

Correlation of CT-guided fine-needle aspiration biopsy of the liver with fluoride-18 fluorodeoxyglucose positron emission tomography in the assessment of metastatic hepatic abnormalities.

Imaging studies using the fluoride-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan have recently become available for patient neoplasia evaluation. Fine-needle aspiration (FNA) biopsy is a well-described diagnostic method for hepatic lesion evaluation. Correlation of these testing modalities in hepatic abnormalities has not been previously reported. Pathology files of Saint Louis University Hospital were retrospectively searched for patients with FNA biopsy of the liver. Thirty-one patients with a total of 32 FNA biopsies of the liver with corresponding FDG-PET scans were identified. Twenty-five patients had 25 cases of metastatic malignant neoplasia diagnosed by FNA biopsy. Of these cases, all but one had an FDG-PET scan positive for malignancy, yielding a sensitivity of 96% (24/25) for the FDG-PET scan. Combined positivity of the two testing modalities yielded a sensitivity of 100% (24/24). Seven patients did not demonstrate neoplasia by FNA biopsy, and the FDG-PET scan was negative in 6 of these 7 cases. The FDG-PET scan is an important imaging technique and, combined with FNA biopsy, can provide reliable diagnostic results and assist in the guidance of oncologic patient management.

The combination of a decision tree technique with the computer-assisted microscope analysis of Feulgen-stained nuclei to assess aggressiveness in lipomatous and smooth muscle tumors.

The present study describes a computer-assisted methodology whose purpose is to reduce the degree of subjectivity in the diagnosis of soft tissue tumors. This methodology associates three complementary techniques, namely digital cell image analysis, the discretisation of numerical data and a Decision Tree technique (DT). The first technique relies on the use of the digital cell image analysis of Feulgen-stained nuclei, a technique which makes possible a quantitative and thus objective description of nuclei with the help of 24 numerical parameters (15 morphonuclear and 9 DNA content- (ploidy level and proliferation activity) related). The second technique transforms each numerical parameter into an ordinal one with a small number of values (2 to 4) so that only the relevant physical significance of the parameters is retained. The Decision Tree technique generates classification rules on the basis of the discretised parameters quoted above. This methodology was applied to 53 human soft tissue tumors which included 26 lipomatous tumors (13 malignant liposarcomas and 13 benign lipomas) and 27 smooth muscle tumors (11 malignant leiomyosarcomas and 16 benign leiomyomas). The results show that a distinction between benign (lipoma) and malignant (liposarcoma) lipomatous tumors can easily be made by means of simple logical rules depending on only four discretised cytological parameters (two ploidy- and two morphonuclear-related). In contrast, no stable or predictive characterisation can be obtained with respect to the difference between leiomyosarcomas and the leiomyomas. Hence, while lipomas and liposarcomas appeared to be two completely distinct biological entities, leiomyomas and leiomyosarcomas seem to involve a continuous biological process.

Morphometry and cytophotometric assessment of DNA in smooth-muscle tumors (leiomyomas and leiomyosarcomas) of the gastrointestinal tract.

The difficulties in predicting the biologic behavior of gastrointestinal (GI) smooth-muscle tumors (leiomyomas and leiomyosarcomas) based on the usual criteria of malignancy are discussed. In order to evaluate the prognostic importance of the nuclear DNA content and nuclear dimensions, measurements were performed on Feulgen-stained sections of GI smooth-muscle tumors from 66 patients. The best discrimination between benign and malignant tumors was obtained by using DNA index and tumor size as descriptors in a linear discriminate analysis. This method separated 79% of the benign and 97% of the malignant smooth-muscle tumors. However, as with conventional criteria for malignancy, there remained a group of tumors close to the discriminating line with an indeterminate malignant potential. In an attempt to reduce the number of such indeterminate tumors, future studies will include the use of several descriptors in a multivariate analysis system and the application of flow cytometric studies to all tumors.