Grade Soft Tissue Sarcoma Research Articles

Comparison of the diagnostic performances of core needle biopsy in myxoid versus non-myxoid tumors

BackgroundDespite the overall diagnostic utility of core needle biopsy (CNB) comparable to incisional biopsy, increased diagnostic errors have been suggested of CNB for myxoid soft tissue tumors. This study compared the diagnostic performance of CNB between myxoid and non-myxoid soft tissue tumors. Methods369 patients who underwent ultrasound-guided CNB prior to resection for soft tissue tumors were classified into two groups according to resection pathology; myxoid group (n = 75) and non-myxoid group (n = 294). One-hundred and ninety-three patients were male and the median age of the patients was 40 years. Two-hundred and sixty-three tumors were malignant. ResultsCNB correctly diagnosed malignancy in 84% (58 of 69) for the myxoid group and 95% (184 of 194) for the non-myxoid group. For diagnosing histologic grade of soft tissue sarcoma, CNB correctly identified high grade in 78% (18 of 23) for the myxoid group and 74% (94 of 128) for the non-myxoid group. Correct diagnosis rate of histological type was significantly lower in the myxoid group (63% [47 of 75] in the myxoid group and 83% [242 of 294] in the non-myxoid group, p = 0.013). ConclusionOur study suggests that CNB is useful for myxoid soft tissue tumors of the extremity, with regard to diagnosing malignancy and histologic grade. However, CNB was less useful for identifying histologic subtype in myxoid tumors than in non-myxoid tumors.

The impact of antecedent primary malignancy in soft tissue sarcoma patients.

It is unclear whether antecedent primary malignancies (APMs) have any negative impact on the prognosis of soft tissue sarcoma (STS). We retrospectively reviewed STS patients with APMs (STS-APM) and compared their survival to those of STS only (STS-O). Twenty-one cases of STS-APM from 2008 to 2017 in our institution were analyzed. One hundred and seventy cases of STS-O at the same period were compared as a control group. Overall survival was estimated using Kaplan-Meier survival curves and prognostic factors were analyzed using logistic regression analyses and contingency table analyses. As the final status of STS-APM patients, 12 patients were in disease-free survival, 5 were alive with disease, 3 have died of disease, and 1 has died of another disease. There was no case that died of APM. The 5-year overall survival rates were 88% in STS-APM and 78% in STS-O, showing no statistical significant ( p = 0.65). The 5-year overall survival rates in each stage of STS-APM and STS-O were 100/100% in stage I, 100/85% in stage II, 86/72% in stage III, and the 3-year overall survival rates were 67/51% in stage IV, with no statistical significance. With regard to prognostic factor, histological grade of STS was the only significant factor. Although antecedent radiotherapy tended to show a high odds ratio, the association was not statistically significant. Antecedent chemotherapy did not show any estimated prognostic risk. Our study suggested that APM in STS patient would not be a negative prognostic factor.

DNA-cytometric characteristics of primary soft tissue sarcomas

Aim. Determination of deoxyribonucleic acid (DNA) content and cell distribution in mytotic cycle phases in the groups of patients with primary soft tissue sarcomas. 
 Methods. Study material was the tumours of patients with primary soft tissue sarcomas. Study methods included histological, DNA cytometric and statistical methods. 
 Results. Differences in proliferative activity and proliferation index in primary sarcomas depending on the tumor differentiation grade and disease stage were revealed. Differences in the numbers of diploid, aneuploid and polyploid cells depending on the cell cycle phases were determined in each group and between groups. Depending on the differentiation grade of soft tissue sarcoma, parameters of the cell cycle in soft tissue sarcomas were as follows: well-differentiated tumors (G1) were diploid in 100% of cases, and moderately differentiated tumors (G2) were aneuploid in 50% of cases. Poorly differentiated tumors (G3) were characterized by significantly higher content of aneuploid cells, in comparison with G2 tumors (33.1±5.2 and 16.5±6.8, respectively). Analysis of kinetic parameters of cell cycle demonstrated decreased proportion of cells in G1/G0 cell cycle phase from G1 to G3, accompanied by a statistically significant increase of the proportion of cells in S phase (p ˂0.05). 
 Conclusion. DNA cytometric study of cell cycle parameters demonstrated high biological potential of primary soft tissue sarcomas; high malignant potential can probably be determined by two parameters: proportion of the cells in G2+М phase and cell loss factor.

Interdisciplinary treatment of soft tissue sarcoma of the extremities

Soft tissue sarcomas are a rare and heterogeneous group of tumors. Surgery clearly remains the standard therapy of non-metastatic soft tissue sarcoma. A pretreatment biopsy is necessary to determine the histology and grade of soft tissue sarcomas and to diagnose entities that can be treated by targeted therapies, such as dermatofibrosarcoma protuberans or alveolar soft tissue sarcoma once they are in a metastatic stage. Nevertheless, locally advanced disease requires multimodal treatment and interdisciplinary treatment decisions. Limb sarcoma of borderline resectability (encasement of vessels, invasion of joints or close proximity to motor nerves) may profit from isolated limb perfusion with recombinant tumor necrosis factor and melphalan. Preoperative chemotherapy may be applied in locally advanced high grade tumors when clear resection margins are difficult to achieve. Deep wave hyperthermia has proven to be a useful addition to systemic chemotherapy in such a neoadjuvant setting. Also preoperative radiation therapy has proven to be effective in controlling locally advanced sarcoma despite higher perioperative morbidity which pays off in the long run by better limb function. Postoperative adjuvant external beam irradiation therapy with the best available technique is recommended for any tumor larger than 5cm with (FNLCC) grades 2 and 3 (American Joint Committee on Cancer stage IIb/III). Given all these therapeutic options, it is absolutely crucial that interdisciplinary decision-making starts early in the therapeutic process. Patients are often seen first by the surgeon. For an optimal treatment surgeons need to know the efficacy and toxicity of the multimodal treatment options described.

Grading of soft tissue sarcomas: from histological to molecular assessment

Several histological grading systems for soft tissue sarcomas have been described since the early 1980s. Their main objective is to select patients for adjuvant chemotherapy. Two histological grading systems are used in daily practice, the National Cancer Institute (NCI) and the French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems. They have been devised by combining histological parameters: number of mitoses per high-power field, the presence of necrosis, cellular and nuclear morphology and the degree of cellularity for the NCI grading; and tumour differentiation, mitotic index and extent of necrosis for the French system. Histological grading is far more appropriate to assess the risk of metastasis. However, several limitations prevent its use: grade cannot be applied to all histological types, its reproducibility is not perfect, a three-grade system generates an intermediate grade with undetermined prognosis, and finally the core needle biopsy, now widely used for the diagnosis of soft tissue sarcoma, is not the best sample to assess the grade. The development of molecular grading in addition to histological grading probably represents the next step. Molecular signatures based on quantitative evaluation of chromosomal complexity such as CINSARC (complexity index in sarcomas) appear as a strong independent predictive factor for metastasis in several types of sarcoma, and even in several other types of cancer. When they can be instituted in daily practice on formalin fixed, paraffin embedded material, molecular signatures will not only provide information on risk of metastasis, but also better understanding of cancer development, response or resistance to evaluated drugs, and potential targets for future treatments.

Thromboembolic Events Associated with Thalidomide and Multimodality Therapy for Soft Tissue Sarcomas: Results of RTOG 0330

Introduction. RTOG 0330 was developed to address the toxicity of RTOG 9514 and to add thalidomide (THAL) to MAID chemoradiation for intermediate/high grade soft tissue sarcomas (STSs) and to preoperative radiation (XRT) for low-grade STS. Methods. Primary/locally recurrent extremity/trunk STS: ≥8 cm, intermediate/high grade (cohort A): >5 cm, low grade (cohort B). Cohort A: 3 cycles of neoadjuvant MAID, 2 cycles of interdigitated THAL (200 mg/day)/concurrent 22 Gy XRT, resection, 12 months of adjuvant THAL. Cohort B: neoadjuvant THAL/concurrent 50 Gy XRT, resection, 6 months of adjuvant THAL. Planned accrual 44 patients. Results. 22 primary STS patients (cohort A/B 15/7). Cohort A/B: median age of 49/47 years; median tumor size 12.8/10 cm. 100% preoperative THAL/XRT and surgical resection. Three cycles of MAID were delivered in 93% cohort A. Positive margins: 27% cohort A/29% cohort B. Adjuvant THAL: 60% cohort A/57% cohort B. Grade 3/4 venous thromboembolic (VTE) events: 40% cohort A (1 catheter thrombus and 5 DVT or PE) versus 0% cohort B. RTOG 0330 closed early due to cohort A VTE risk and cohort B poor accrual. Conclusion. Neoadjuvant MAID with THAL/XRT was associated with increased VTE events not seen with THAL/XRT alone or in RTOG 9514 with neoadjuvant MAID/XRT.

14 Genomic versus histological grading in soft tissue sarcomas

14 Genomic versus histological grading in soft tissue sarcomas

Intense accumulation of 18F-FDG, not enhancement on MRI, helps to guide the surgical biopsy accurately in soft tissue tumors

Soft tissue sarcomas are a highly heterogeneous group of malignancies that arise from mesenchymal tissues. Grading of soft tissue sarcomas is an important prerequisite for the choice of therapy and estimation of prognosis. However, incisional biopsy of huge soft tissue sarcoma lesions frequently fails to provide an accurate diagnosis when there is a benign component, cystic changes and/or necrosis. MRI is helpful in evaluating the extent of the sarcoma lesion, vascularization, invasiveness and integrity of surrounding tissue, but definitive differentiation of benignity and malignancy is not possible with it. In this study, positron emission tomography using [(18)F]-2-fluoro-2-deoxy-D-glucose successfully guided surgeons to identify the most hypermetabolic and, therefore, the most suitable biopsy sites of huge soft tissue sarcoma.

Grading of soft tissue sarcomas on fine‐needle aspiration cytology smear

In this present study we have attempted to grade soft tissue sarcomas on fine-needle aspiration cytology (FNAC) material and then subsequently correlated our findings on histology section.A total of 44 cases of primary soft tissue sarcomas (STS) were graded and correlated with the subsequent histopathology sections.FNAC successfully diagnosed 40 cases and four cases were reported as benign. There were 11 grade I, 32 grade II and one grade III cases on histopathology. Out of the 11 grade I cases, only three cases were graded correctly on cytology. On FNAC, 31 sarcomas were diagnosed correctly as grade II tumors and one case was under diagnosed as benign. There was a single case of grade III sarcoma on histopathology which was correctly diagnosed and graded on FNAC.In majority of the STS it is possible to grade on FNAC. Grade I STS is relatively difficult to grade than grade II STS.

Grading of Soft Tissue Sarcomas: Review and Update

Histologic grading is the most important prognostic factor and the best indicator of metastatic risk in adult soft tissue sarcomas. The most commonly used systems are the French grading and the National Cancer Institute grading. Both are 3-grade systems and are mainly based on histologic type and subtype, tumor necrosis, and mitotic activity. Rules for using grading should be strictly respected and limitations of grading should be known to obtain the best performance. The most controversial point is the respective values of histologic typing and grading. Histologic typing should be clearly defined before any attempt at grading, and grading should not be used on tumors of intermediate malignancy such as atypical fibroxanthoma and on some sarcomas such as dedifferentiated liposarcoma. However, grading is useful in more than 90% of adult soft tissue sarcomas and has been adapted to pediatric nonrhabdomyosarcomatous sarcomas. Current grading is not suitable for core needle biopsies. To review the current value and limitations of histologic grading in soft tissue sarcomas. The reviews on grading and original studies on prognostic factors in soft tissue sarcomas were analyzed. Grading is the best predictor of metastasis outcome in adult soft tissue sarcomas and should be part of the pathologic report. Grading should be adapted to the modern management of patients and complemented by radiologic and molecular parameters.

Proteomic signatures corresponding to histological classification and grading of soft-tissue sarcomas

We performed a global protein expression study on soft-tissue sarcoma in order to develop novel diagnostic biomarkers and allow molecular classification. 2-D difference gel electrophoresis was used to generate the global protein expression profiles of 80 soft-tissue sarcoma samples with seven different histological backgrounds. We found that 67 protein spots distinguished the subtypes of soft-tissue sarcoma. Hierarchical clustering with these 67 protein spots resulted in the grouping of all 80 sarcoma samples corresponding to the histological classification. We found that the expression pattern of tropomyosin isoforms was different in conventional and pleomorphic leiomyosarcomas. We also identified five proteins, including alpha-1-antitrypsin, alpha-actinin 1, HSP27, and elongation factor 2, that could differentiate between malignant fibrous histiocytomas and leiomyosarcomas in grade III into low-risk and high-risk groups, which differed significantly with respect to survival. These results establish proteomics as a powerful tool to develop novel biomarkers for diagnosis and molecular classification of soft-tissue sarcomas. Identification of proteins associated with survival in grade III sarcoma will allow delineation of a high-risk group that may benefit from adjuvant therapy and the exclusion of low-risk patients in whom additional therapies are unlikely to exhibit clinical benefit.

High incidence of metastatic disease in primary high grade and large extremity soft tissue sarcomas treated without chemotherapy

BackgroundThe risk of metastasis and the survival in patients with primary extremity soft tissue sarcomas is worse when tumour size is large and the grade of malignancy is high. Such tumours may receive chemotherapy and/or radiation therapy (RTX) for optimising local control. Irradiation can either be applied preoperatively or after tumour resection. The question arises if the kind of RTX in the absence of chemotherapy influences the outcome concerning local control, metastatic disease, survival and complications.MethodsWe retrospectively reviewed the clinical outcome of 233 patients with a primary extremity soft tissue sarcoma treated between 1990 – 2000 with a mean follow-up of 35.8 (4–120) months in our institute. 41 patients had high grade, deep and large tumours (>8 cm), an AJCC stage III (no evidence of metastasis prior to treatment) and were treated with limb salvage surgery and irradiation but stayed without additional chemotherapy. Two groups of patients were compared: the first group received postoperative RTX after tumour resection (n = 33); the second group was treated with preoperative RTX (n = 8). Both groups did not differ concerning clinical parameters. We analysed primary and secondary outcomes.Results56% (23/41) of the population developed metastatic disease, 24% (10/41) local recurrence. The risk of metastasis was higher in the group with preoperative irradiation (p = 0.046). The overall (p = 0.0248) and relapse free survival (p = 0.104) were worse in this group. The delay to tumour resection amounted 8 weeks on average in the preoperative group. Local control was not different (p = 0.38) in both study groups. Wound infections and other combined therapy related complications were equally distributed (p = 0.22).ConclusionWithout chemotherapy there remains a high risk of metastasis in AJCC grade 3 patients. In high risk patients treated without chemotherapy the elapsed time to tumour resection after preoperative radiation might contribute to the development of metastasis. This outcome may support the thesis that a combination of RTX and offensive multimodal treatment protocols is advantageous in such a subset of patients

Grading of soft tissue sarcomas: the challenge of providing precise information in an imprecise world

By identifying patients at greatest risk for distant metastasis and, hence, most likely to benefit from adjuvant therapy, the grading of sarcomas has been one of the most important contributions pathologists have made to the treatment of sarcomas. Over the years, many grading schemes have been proposed and validated as efficacious. The three-tier system proposed by the French Federation of Cancer Centres is precisely defined, easy to use, and is the most widely employed. However, no system performs perfectly on all sarcomas. Sarcomas that do not lend themselves well to grading include (i) those in which grade provides no incremental information over histological subtypes (e.g. well-differentiated liposarcoma/atypical lipomatous neoplasm, Ewing's sarcoma); (ii) tumours traditionally considered "ungradable" (e.g. epithelioid sarcoma, clear cell sarcoma, angiosarcoma); and (iii) sarcomas that customarily have been graded but in which grade has recently been shown not to correlate well with outcome (e.g. malignant peripheral nerve sheath tumour). Consequently, several sarcoma-specific risk stratification schemes have been proposed. The future may well witness a synthesis of these two approaches. Nomograms, which incorporate clinical, histological and demographic findings, have proved accurate in predicting disease-specific survival in sarcomas. Diagnosis and grading are increasingly based on tissue obtained by core needle biopsy, which poses new challenges for pathologists, particularly if neoadjuvant therapy is to be given. Grading on needle biopsies may require a two-tier grading system (i.e. low versus high grade) and a close dialogue with clinicians to resolve ambiguities.

Detection and grading of soft tissue sarcomas of the extremities with (18)F-3'-fluoro-3'-deoxy-L-thymidine.

The aim of the study was to investigate the feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine positron emission tomography (FLT-PET) for the detection and grading of soft tissue sarcoma (STS). Nineteen patients with 20 STSs of the extremities were scanned, using attenuation corrected whole-body FLT-PET. Standardized uptake values (SUVs) and tumor:nontumor ratios (TNTs) were compared with histopathological parameters using French and Japanese grading systems. Mean SUV, maximal SUV, and TNT could differentiate between low-grade (grade 1; n = 6) STS and high-grade (grade 2 and 3; n = 14) STS according to the French grading system (P = 0.001). Mean SUV, max SUV, and TNT correlated with mitotic score, MIB-1 score, the French and Japanese grading system (* = 0.550-0.747). FLT-PET is able to visualize STS and differentiate between low-grade and high-grade STS. The uptake of FLT correlates with the proliferation of STS.

Cytopathology of bone and soft tissue tumors

Cytopathology of Bone and Soft Tissue Tumors provides the practising pathologist with a single reference for describing and illustrating the cytologic features of musculoskeletal tumours. Using fine-needle aspiration (FNA), the approach of this work is encyclopedic: both common and rare lesions are depicted. The chapters on soft-tissue lesions are organized by direction of differentiation. Summaries of clinical findings are given along with the histopathologic and cytologic description. Key diagnostic points (in table form) and a discussion of the differential diagnosis complete each section. The section on skeletal lesions is organized along predominant cell type seen in smears. This approach facilitates grouping of lesions into diagnostically useful categories, allowing the pathologist faced with an unfamiliar lesion to rapidly access the portion of the text most useful for differential diagnosis. Within each chapter, the organization is similar to that within the soft tissue chapters. The introduction discusses technical concerns, limitations of the technique, and a diagnostic approach in both tabular and narrative form. Information on grading of soft tissue sarcomas completes the introduction.

Subgrouping and grading of soft-tissue sarcomas by fine-needle aspiration cytology: a histopathologic correlation study.

To evaluate the accuracy and reproducibility of subgrouping and grading soft-tissue sarcomas by fine-needle aspiration biopsy (FNAB), a blind review was conducted of 84 FNAB specimens from 77 malignant and 7 benign soft-tissue lesions. Cytomorphologic subgroups included 31 spindle-cell, 24 pleomorphic, 11 myxoid, 7 epithelioid/polygonal, 3 small round cell, and 8 nondiagnostic cases. Malignancies included one lymphoma and 41 primary, 15 recurrent, and 20 metastatic soft-tissue sarcomas. Adequacy was defined as a majority of slides with at least 5 clusters of 10 unobscured cells. Five originally false-negative cases were considered nondiagnostic on review. Sarcoma was recognized in 59 of 64 adequate cases (92%) with available histology; however, the specific histopathologic subtype was identified in only 9 cases (14%). Benign myxoid and spindle-cell lesions were difficult to separate from low-grade sarcomas in 4 cases, and a B-cell lymphoma with sclerosis mimicked a low-grade myxoid sarcoma. The assigned cytologic grade accurately reflected the histologic grade in 90% of sarcomas when segregated into high and low grades. Pleomorphic, small round cell, and epithelioid/polygonal subgroups corresponded to high-grade sarcomas in all cases with only minor noncorrelations. Major grading noncorrelations occurred in 50% of myxoid and 9% of spindle-cell sarcomas. Therefore, attention should be given to specimen adequacy, and caution should be exercised when attempting to grade myxoid and spindle-cell sarcomas by FNAB.

Problems in grading soft tissue sarcomas.

Clinicians, particularly medical oncologists, place increasing importance on histologic grading as a means of informing their treatment decisions in patients with soft tissue sarcoma. Numerous different grading systems (with a variable number of grades) have been described. Although these have often used different parameters, it is nevertheless generally accepted that histologic grade, however derived, is probably the best prognostic indicator in these sarcoma patients. Unfortunately, however, there is no consensus as to the best grading system, and even those schemes that are most widely applied (those of the French National Cancer Centers and the National Cancer Institute in the United States) have important and acknowledged limitations. Furthermore, assessment of many of the most popular grading parameters is necessarily subjective, and, to date, potentially more objective measures of proliferative activity and ploidy (eg, using immunohistochemistry or DNA flow cytometry) have not improved on experienced morphologic grading. In addition, the confounding (and often misleading) effect on histologic grade of preoperative therapy, which is increasingly used, has not been addressed in any meaningful way. This overview highlights the limitations, problems, and concerns regarding histologic grading of soft tissue sarcomas.

Histologic prognostication in soft tissue sarcomas: grading versus subtyping or both? A comprehensive review of the literature with proposed practical guidelines.

Despite the validation of many histologic grading systems for soft tissue sarcomas, none have been universally accepted. Because of the overall rarity of specific histologic sarcoma subtypes, evaluation of grading systems and their prognostic significance have tended to base the results on sarcomas as a general group, diminishing the value and significance of histologic subtyping. A representative review of the literature regarding histologic grading of soft tissue sarcomas and its relationship to histologic subtype, stage, and prognosis is analyzed and discussed. Histologic grading of many soft tissue sarcomas appears to be a valuable predictor of patient survival, as confirmed by the literature. However, accurate histologic subtyping is essential for accurate histologic grading. Histologic grading in some sarcoma subtypes is probably not applicable and may underestimate biologic behavior. Clinicians and pathologists should be aware of the limitations, prognostic significances, and relationships of histologic subtyping and histologic grading in the therapeutic management and prognostication of soft tissue sarcomas.

How Should We Grade Soft Tissue Sarcomas and What Are the Limitations?

Histologic grade has been shown repeatedly to be the most important prognostic factor in adult soft tissue sarcomas with regard to metastasis development and tumor morrality, although tumor size and tumor location (superficial versus deep) are also important parameters to consider. In this review, the advantages and limitations of histrologic grade are exposed, focusing on the grading system of the Fédération Nationale des Centres de Lutte Contre fe Cancer. The reproducibility issue and the impact of histologic grade on patient management are also discussed.

Tumor size as a prognostic indicator of histologic grade of soft tissue sarcoma.

Tumor size is one of the independent factors affecting prognosis of patients with soft tissue sarcoma (STS). We evaluated the significance of tumor size in combination with tumor depth in each histologic grade. A total of 162 adult patients with localized STS in the extremities and trunk were selected. Patient ages ranged from 15 to 84 (median 46.5) years with a male-to-female ratio of 1.19. Histologic grade of tumors was low in 53 cases, intermediate in 51, and high in 58. Two types of categorization were set, and their significance in predicting the prognosis of patients in each grade was evaluated. In the first category (intermediate grade), tumors were dichotomized at 10 cm: Group A comprised patients with deeply seated tumors measuring > 10 cm; Group B comprised patients other than those in Group A. In the second category (high grade), tumors were dichotomized at 5 cm: Group C comprised patients with deeply seated tumors measuring > 5 cm; Group D comprised patients other than those in Group C. Categorization was not useful in the prognosis of low grade tumors. In the intermediate grade group, the 5-year-survival rate of Group B patients (78%) was higher than in Group A patients (59%) (P < 0.05), showing that dichotomization at 10 cm was useful. In the high grade group, the 5-year survival rate in Group C patients (32%) was lower than in Group D patients (56%), showing that dichotomization at 5 cm was useful. These findings show that tumor size for the prognosis of patients with STS differs according to each histologic grade.