Federation Nationale Des Centres De Research Articles

Role of Histopathology in diagnosis of Soft Tissue Tumors at Tertiary Care Center

Introduction: Soft tissue tumors (STTs) are a diverse group of neoplasms. It varies from the most common benign tumors to some self-limited lesions and rare malignant soft tissue tumors. Because of the overlap in their clinical and radiological characteristics, histopathology is crucial in determining their diagnosis.
 Objectives: To study the relative frequencies of types of soft tissue tumors (benign, intermediate and malignant) as well as their histological pattern in relation to age, gender and site of distribution.
 Methodology: This was a retrospective study conducted over a period of three years from January 2018 to December 2020 in the Department of Pathology, Dhulikhel Hospital, Kavre Nepal. This study included STTs of all the anatomical sites excluding STTs of the female reproductive system. The tumors were classified as benign, intermediate, or malignant using the WHO 2013 classification of soft tissue and bone tumors. The sarcomas were further graded into grades 1, 2, and 3 using the FNCLCC (French Federation Nationale des Centres de Lutte Contre le Cancer) grading system. Immunohistochemistry (IHC) and special staining procedures were also performed as and when required. 
 Result: A total of 198 STTs were studied, of which benign cases were 191 (96.45%), intermediate 03 (1.52%) and malignant 04 (2.03%) in number. The most common type of STTs was vascular tumors 77(38.89%) followed by adipocytic tumors 52(26.26%) and nerve sheath tumors 13(6.56%). STTs were most common in the third decade of life, with the head and neck region being the commonest site. All four malignant tumors were categorized using the FNCLCC grading system. There were three cases of Grade 2 sarcoma and one case of Grade 3 sarcoma.
 Conclusion: The most common benign tumors were vascular tumors followed by adipocytic tumors and nerve sheath tumors. STTs were most common in the third decade of life. Benign tumors were more common than malignant tumors. In comparison to malignant tumors, benign tumors were found at a younger age group. STTs were found mainly in the head and neck region followed by upper and lower limbs. Despite the fact that molecular diagnostics is gaining popularity in the field of soft tissue tumors, histopathology still remains the gold standard.

Comorbidity, body mass index, and performance status as prognostic factors in older patients with soft-tissue sarcoma

IntroductionSurgery, chemotherapy, and radiotherapy are the treatments for soft tissue sarcoma (STS) similar to those for other cancers. However, treatment is even more difficult in older patients because of aging-related weakness. The influence of aging-associated factors on prognosis in the patients with STS has not been fully elucidated. This study aimed to clarify the factors that impact prognosis in older patients with STS. Materials and MethodsThe present study retrospectively analyzed the data of 262 (≥60 years old) patients with STS. Moreover, this study investigated (1) tumor-associated parameters (e.g., tumor site, tumor size, depth, histological grade [Federation Nationale des Centres de Lutte le Cancer], American Joint Committee on Cancer [AJCC, eighth edition] stage, and histotype); (2) treatment-related factors (i.e., presence of surgery, neoadjuvant/adjuvant chemotherapy, adjuvant radiotherapy, and surgical margin); and (3) patient-dependent counterparts (e.g., age, gender, performance status [PS], body mass index [BMI], and Charlson comorbidity index [CCI]). Statistical analysis was conducted to evaluate the impact of each factor on overall survival (OS). ResultsAmong the 262 patients, 217 and 45 were 60–79 and ≥80 years old, respectively. A comparison of the sociodemographic background showed no significant difference other than surgical margin and PS between those groups. According to univariate analysis, the significant factors to impact OS were age, stage, tumor size, depth, surgical margin, PS, BMI, and CCI. Multivariate analysis indicated that advanced stage, poor PS, and low BMI were negative prognostic factors for OS. Intriguingly, multivariate analysis demonstrated that CCI was a not significant factor for OS in this study. DiscussionWhile AJCC stage is a well-known determinant, this study suggests that physicians should be alerted to poor PS and low BMI in older patients with STS.

Breast Primary Angiosarcoma: A Clinicopathologic and Imaging Study of a Series Cases.

The aim of our study is to provide clinicopathologic and imaging features of breast primary angiosarcoma. We retrospectively analyzed cases of primary angiosarcoma diagnosed at the Pathological Laboratory of Lomé over a period of 20 years (2000-2019). Eight cases of primary angiosarcoma of the breast were collected, including 6 from women and 2 from men. The median age was 41.63 years (range from 17 to 66 years). Depending on the location, there were 4 of 8 cases in the left breast. Ultrasound classifications were BI-RADS 4 and 5. Histology revealed a malignant vascular proliferation composed of small lumens lined by atypical endothelial cells, evident mitoses, and foci of necrosis. On immunohistochemistry, the lesional cells expressed CD31, CD34, and Factor VIII. Based on Federation Nationale des Centers de Lutte Contre Le Cancer (FNCLCC) grading, the cases were grade II and III. Overall survival at 6 months was estimated to be 25% in a woman.

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.

MR T1WI based radiomics and machine learning model for predicting the histopathological grades of soft tissue sarcomas

Objective To explore the value of T1WI based optimal radiomics and machine learning model in predicting histological grades of soft tissue sarcoma. Methods The preoperative MR T1WI data of 113 patients with soft tissue sarcoma in Affiliated Hospital of Qingdao University from May 2009 to November 2018 was analyzed retrospectively. The patients were divided into training set (n=80) and validation set (n=33) using randomly stratified sampling mothed. According to the French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system, the soft tissue sarcomas were divided into 3 pathological levels (grade Ⅰ-Ⅲ). Grade Ⅰ was defined as low grade, grade Ⅱ and Ⅲ were defined as high grade. In the training set, there were 18 cases with low-grade lesions, 62 cases with high-grade lesions. In the validation set, there were 7 cases with low-grade lesions and 26 cases with high-grade lesions. After a normalizationapproach applied on the image, the radiomics features were extracted in the regions of interest using A.K software. Based on different feature selection methods [with or without recursive feature elimination (RFE)], machine learning algorithm [random forest (RF) or support vector machine (SVM)] and sampling technology [without subsampling, with the synthetic minority oversampling technique (SMOTE) or with random oversampling examples], a total of 12 models were built and each machine-learning combination model was trained using leave-one-out cross validation. The receiver operating characteristic (ROC) curves were used to evaluate the efficacy of the model in predicting the pathological grade of soft tissue sarcoma. Results Among the 12 different machine learning models, the optimal classification model for the prediction of soft tissue sarcoma pathological grade was a combination of RF, RFE and SMOTE, with an area under the curve of 0.909 (95% confidence interval, 0.808-1.000) in the validation set, and the accuracy, sensitivity, and specificity were 84.85%, 86.21%, and 75.00%, respectively. Conclusion The radiomics based machine learning model can be used as an attractive application approach for predicting histological grades of soft tissue sarcoma. Key words: Magnetic resonance imaging; Soft tissue neoplasms; Sarcoma; Radiomics; Artificial intelligence

Distinguishing soft tissue sarcomas of different histologic grades based on quantitative MR assessment of intratumoral heterogeneity

PurposeTo explore the role of intratumoral heterogeneity on MRI assessed by histogram analysis in differentiating soft-tissue sarcomas (STS) of different grades. Materials and MethodsPatients with primary STS undergoing MRI prior to iatrogenic procedures were included retrospectively. The histologic grade was assigned according to Federation Nationale des Centres de Lutte Contre le Cancer grading system. T1WI and T2WI were normalized by dividing mean signal intensity (SI) of contralateral/near unaffected muscles. Contrast-enhanced T1WI was normalized by computing enhancement ratio (ER) map as (SIpost-SIpre)/SIpre×100, where SIpre and SIpost represent SI of each pixel before and after enhancement. A region of interest (ROI) was manually drawn to include entire tumor area on axial slice with largest tumor diameter. Mean, mode, standard deviation, kurtosis and skewness on ROIs were extracted with ImageJ software. ANOVA/Kruskal-Wallis test was used to determine the significance of differences. ROC curve was applied for statistically significant parameters. P value ≤0.05 was considered statistically significant. ResultsAmong involved 67 patients, 8 were assigned to grade 1, 38 to grade 2 and 21 to grade 3. Skewness (P = 0.022) and kurtosis (P = 0.035) on ER maps were significantly different among STS of different grades. The optimal cutoffs of skewness and kurtosis on ER maps were -0.488 (AUC[95% CI] 0.747[0.557–0.937]; sensitivity/specificity, 62.5%/86.4%) and 0.762 (AUC[95% CI] 0.684[0.548–0.821]; sensitivity/specificity, 76.2%/56.5%), respectively. ConclusionIntratumoral heterogeneity on MRI quantitatively displayed by histogram parameters can differentiate STS of different grades. Skewness and kurtosis on ER maps show the capacity.

Changing odds of survival over time among patients undergoing surgical resection of extremity soft tissue sarcoma.

While survival after surgical treatment of extremity soft tissue sarcoma (STS) is traditionally reported as actuarial survival, conditional survival (CS) may be more clinically relevant as it accounts for time already survived. We compared actuarial survival and CS of STS patients. We analyzed 567 patients who underwent surgery for localized extremity STS. Actuarial survival was estimated using the Kaplan-Meier method. Cox proportional hazards model was used to evaluate factors associated with disease-specific survival. Five-year CS (CS5) estimates at "χ" year(s) after surgery were calculated as CS5 = S(χ + 5)/S(χ). Whereas actuarial survival decreased over time, CS5 increased. The postsurgical 1-, 3-, and 5-year CS5 values were 84.5%, 90.0%, and 93.8%, respectively, whereas the 6-, 8-, and 10-year actuarial survival rates were 82.0%, 79.4%, and 78.5%, respectively. The calculated CS5 exceeded actuarial survival especially in patients with risk factors such as large tumor size and Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grades 2 and 3 tumors. Patients with tumor size ≥5 cm had an actuarial survival of 73.9% at 10 years compared to a CS5 of 95.4% in patients alive at 5 years. Likewise, patients with FNCLCC grade 3 tumors had an actuarial survival of 71.1% at 10 years compared to a CS5 of 96.0% in patients alive at 5 years. Survival estimation by determination of CS can be dynamic and accurate especially in high-risk patients. CS can be useful for survival prediction and clinical decision making in extremity STS patients.

Radiotherapy for retroperitoneal liposarcoma: A report from the Transatlantic Retroperitoneal Sarcoma Working Group.

BackgroundThe current study investigated the role of radiotherapy (RT) in patients with primary nonmetastatic retroperitoneal liposarcomas.MethodsA total of 607 patients with localized retroperitoneal well‐differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) underwent surgical resection with or without RT at 8 high‐volume sarcoma centers (234 patients with WDLPS, 242 patients with grade 1 to 2 DDLPS, and 131 patients with grade 3 DDLPS; grading was performed according to the National Federation of Centers for the Fight Against Cancer [Federation Nationale des Centres de Lutte Contre le Cancer; FNCLCC]). RT was administered in 19.7%, 34.7%, and 35.1%, respectively, of these 3 cohorts. Overall survival (OS) was estimated using the Kaplan‐Meier method, and the incidences of local recurrence and distant metastasis (DM) were estimated in a competing risk framework. To account for bias consistent with nonrandom RT assignment, propensity scores were estimated. Cox univariable analysis of the association between RT and oncological endpoints was performed by applying inverse probability of treatment weighting (IPTW) using propensity scores.ResultsAge, tumor size, and the administration of chemotherapy were found to be significantly imbalanced between patients who did and did not undergo RT in all cohorts. IPTW largely removed imbalances in key prognostic variables. Although the 8‐year local recurrence incidences in patients treated with surgery plus RT versus surgery only were 11.8% and 39.2%, respectively, for patients with WDLPS (P = .011;); 29.0% and 56.7%, respectively, for patients with grade 1 to 2 DDLPS (P = .008); and 29.8% and 43.7%, respectively, for patients with grade 3 DDLPS (P = .025), this significant benefit was lost after IPTW analyses. There were no significant differences noted with regard to DM and OS between irradiated and unirradiated patients across all 3 cohorts.ConclusionsPerioperative RT was found to be associated with better local control in univariable unadjusted analysis in all 3 cohorts, but not after accounting for imbalances in prognostic variables. RT did not impact on DM or OS. The appropriate selection of RT in this disease remains challenging. The results of the European Organization for Research and Treatment of Cancer (EORTC)–Soft Tissue and Bone Sarcoma Group (STBSG) 62092‐22092 prospective randomized trial are awaited.

Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma

ImportancePatients with soft tissue sarcoma are at risk for local recurrence and distant metastases despite optimal local treatment. Preoperative anthracycline plus ifosfamide chemotherapy improves outcome in common histological subtypes.ObjectiveTo analyze whether the previously reported improvement in local progression-free survival by adding regional hyperthermia to neoadjuvant chemotherapy translates into improved survival.Design, Setting, and ParticipantsOpen-label, phase 3 randomized clinical trial to evaluate the efficacy and toxic effects of neoadjuvant chemotherapy plus regional hyperthermia. Adult patients (age ≥18 years) with localized soft tissue sarcoma (tumor ≥5 cm, French Federation Nationale des Centers de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep) were accrued across 9 centers (6, Germany; 1, Norway; 1, Austria; 1, United States) from July 1997 to November 2006. Follow-up ended December 2014.InterventionsAfter stratification for tumor presentation and site, patients were randomly assigned to either neoadjuvant chemotherapy consisting of doxorubicin, ifosfamide, and etoposide alone, or combined with regional hyperthermia.Main Outcomes and MeasuresThe primary end point was local progression-free survival. Secondary end points included treatment safety and survival, with survival defined from date of randomization to death due to disease or treatment. Patients lost to follow-up were censored at the date of their last follow-up.ResultsA total of 341 patients were randomized, and 329 (median [range] age, 51 [18-70] years; 147 women, 182 men) were eligible for the intention-to-treat analysis. By December 2014, 220 patients (67%; 95% CI, 62%-72%) had experienced disease relapse, and 188 (57%; 95% CI, 52%-62%) had died. Median follow-up was 11.3 years. Compared with neoadjuvant chemotherapy alone, adding regional hyperthermia improved local progression-free survival (hazard ratio [HR], 0.65; 95% CI, 0.49-0.86; P = .002). Patients randomized to chemotherapy plus hyperthermia had prolonged survival rates compared with those randomized to neoadjuvant chemotherapy alone (HR, 0.73; 95% CI, 0.54-0.98; P = .04) with 5-year survival of 62.7% (95% CI, 55.2%-70.1%) vs 51.3% (95% CI, 43.7%-59.0%), respectively, and 10-year survival of 52.6% (95% CI, 44.7%-60.6%) vs 42.7% (95% CI, 35.0%-50.4%).Conclusions and RelevanceAmong patients with localized high-risk soft tissue sarcoma the addition of regional hyperthermia to neoadjuvant chemotherapy resulted in increased survival, as well as local progression-free survival. For patients who are candidates for neoadjuvant treatment, adding regional hyperthermia may be warranted.Trial Registrationclinicaltrials.gov Identifier: NCT00003052

A CORRELATIVE STUDY ON SPINDLE CELL SARCOMA WITH CYTO-HISTOLOGICAL GRADING BY CONVENTIONAL METHODS IN AN INDIAN TERTIARY CARE TEACHING HOSPITAL

Objective: Spindle cell sarcomas constitute an important component of soft tissue sarcomas, where accurate grading is more important than histologic subtypes to plan treatment strategies and determine prognosis. To assess whether histologic criteria for grading sarcomas could be applied to fine needle aspiration biopsy (FNAB) specimens of adult spindle cell sarcomas without knowledge of sarcoma subtypes. Furthermore, correlate this grading with histologic Federation Nationale Des Centres de lutte contre le cancer (FNCLCC) grading system and find out the percentage of accuracy of FNAB grading. Methods: Hundred cases were studied by fine needle aspiration cytology (FNAC), among them 50 cases found to be spindle cell sarcoma; in only 42 cases surgical specimens were available. Each aspiration being spread into two or more slides. Subsequently, biopsy was done and studied. Technique used - grading of FNAB specimens and corresponding surgical specimens. Result: Grading of FNAB specimens done taking into account four parameters - nuclear atypia, nuclear variation (nuclear contour, chromatin, nucleoli, and nuclear overlap), mitotic figure, and necrosis. Grading of surgical specimens done by FNCLCC system. The overall results were correlated for both FNAC and biopsy concordance and statistically analyzed. From there the sensitivity and specificity were calculated as 95.23% and 80.76%, respectively. Conclusion: Histologic criteria for grading sarcomas in adults could be applied to FNAC specimens of spindle cell sarcomas with 88% accuracy. While comparing the diagnosis given by FNAC and biopsy, it revealed the true positive were 40 cases, true negative 42 cases, false positive 10 cases, and false negative (FN) 2 cases.

Federation Nationale des Centers de Lutte Contre le Cancer grading of soft tissue sarcomas on needle core biopsies using surrogate markers

Needle core biopsy (NCB) of soft tissue sarcomas (STSs) presents problems for French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) histological grading because small sample size hinders determination of necrosis and mitotic activity. We graded 53 STSs on NCB using a modified FNCLCC grading system that substitutes Ki-67 immunoexpression for mitotic count and uses a radiological assessment of necrosis, and compared the results with those obtained by conventional FNCLCC grading of the corresponding untreated, surgically resected specimen. Forty-eight of the 53 tumors were classified as malignant on NCB (concordance = 91%). The modified FNCLCC grade correctly separated high-grade (grades II and III) from low-grade sarcomas in 70% of cases and predicted the traditional FNCLCC grade given to the resected specimen in 49% of cases. Ki-67 scores of 2 or 3 were observed in 5 tumors classified as low-grade neoplasms on NCB but upgraded to a high-grade dedifferentiated liposarcoma on resection. Underestimated NCB grades were commonly encountered with lipomatous tumors due to sampling error, whereas Ki-67 or radiologic necrosis scores higher than the corresponding histological scores were responsible for the vast majority of overestimated NCB grades. Our FNCLCC grading scheme replacing conventional mitosis counting and histologic assessment of necrosis with surrogate markers is useful in separating high- and low-grade STSs on NCB for STS treatment planning. High Ki-67 rate should raise suspicion of a higher-grade component, particularly with fatty tumors.

Primary leiomyosarcoma of the pancreas: report of a case treated by local excision and review of the literature.

BackgroundFirst described by Ross in 1951, primary pancreatic leiomyosarcoma is a rare mesenchymal tumour of the pancreas, with nonspecific clinical and radiological features and a poor prognosis, if unresectable.Case reportA 60-year-old woman presented with abdominal pain. Magnetic resonance imaging (MRI) and computed tomography (CT) scan detected a dishomogeneous egg-shaped 8-cm mass, arising from the pancreatic head, with duodenal compression, without dilation of the Wirsung duct. 18F-FDG positron-emission tomography (PET)-CT showed a moderate tracer uptake, and the endoscopic ultrasound (US) showed a hypoechoic lesion, arising from the duodenal wall, suspected to be a gastrointestinal stromal tumour (GIST). CEA, CA19-9, NSE, and chromogranin A were normal. At the surgical exploration, a 10-cm mass, adherent to the anterior aspect of the pancreatic head, was found. The lesion was easily separable from the duodenal wall and was totally excised. The frozen intraoperative examination showed a mesenchymal tumour, with spindle-shaped cells, suggesting that a GIST diagnosis was likely. Postoperative course was uneventful. Histology and immunohistochemistry demonstrated a well-differentiated leiomyosarcoma, with five to six mitotic counts per 10 high-power field (HPF) and proliferative index (MIB-1) 10 % (grade 2 according to Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC)), with positive smooth muscle actin, desmin, and caldesmon but negative CD117 (c-kit) and S-100. The patient is alive and asymptomatic 19 months after surgery, without evidences of disease.ConclusionsIn the English literature, only 44 cases of primary pancreatic leiomyosarcoma have been reported. If a pancreatic mass suspected for primary pancreatic leiomyosarcoma has no adjacent organ/vessel invasion or distant metastases, surgical resection is the therapy of choice.

Typing and Grading of Soft Tissue Tumors and their Correlation with Proliferative Marker Ki-67

Aim and Objective: The main aim of this study is to categorize, type, grade of soft tissue tumors & correlate it with Ki-67 proliferative index. Material and Methods: The present study was conducted in the Department of Pathology, PGIMS, Rohtak. The study group comprised of excised 44 cases of STT (soft tissue tumors) specimens. Tumor grade was assigned based on the FNCLCC (Federation Nationale des Centers de Lutte Contre le Cancer) grading system. According to the Ki-67 index the patients were divided into two groups: high index group (>50/10HPF) and low index group (<50/10HPF). These grades were correlated with proliferative activity using Ki-67 index. Results: Out of 44 soft tissue tumors in our study 12 (27.27%) were diagnosed as benign and 32 (72.72%) were diagnosed as malignant soft tissue tumors. Average size of benign tumors was 4.50 cm and that of malignant tumors was 10.33 cm. Maximum number of soft tissue tumor were located in the extremities i.e.10 (22.72%) in upper extremity and 24 (54.54%) in the lower extremity. The commonest site affected was thigh (18.2%). Out of the 32 cases of (STS) soft tissue sarcomas, 15 (46.87%) were Grade 2, 13 (40.63%) were Grade 3 and 4 (12.5%) were Grade 1. MPNST (malignant peripheral nerve sheath tumor) had the largest number of cases with Grade 3 (31.3%). All the benign STT had low Ki-67 index, while the Ki-67 index was low in 12 STS and high in 20 STS. The size as well as grade of the tumors showed a significant correlation with Ki-67 index. Conclusion: Grading based on assessment of morphologic variables is one of the most important factors for predicting the prognosis of the patients with STS. Therefore, it should be a part of the pathology report and should be adapted to the modern management of patients.

Fibrosarcoma of the temporomandibular joint area: benefits of magnetic resonance imaging and computed tomography

Here, we report a case of primary fibrosarcoma in the mandible of a 33-year-old woman with symptoms and radiologic signs mimicking temporomandibular disorder. We also present a literature review of fibrosarcomas in the jaw. CASE REPORT A 33-year-old woman presented with a 1-year history of trismus associated with a clicking noise in the left temporomandibular joint (TMJ). Her chin shifted to the right side when she opened her mouth (Figure 1). Panoramic radiographs (Figure 2, A, B) and magnetic resonance imaging (MRI) scans (Figure 3, A-H) of the TMJ regions showed signs of temporomandibular disorder (TMD), so conventional treatment for TMD was prescribed, including occlusal splints, mouth-opening exercises, and a muscle relaxant for 6 months. When the MRI scout images were analyzed retrospectively, the findings of 2 of 5 scout images were suggestive of tumor (see Figure 3, A, E). The patient was referred again 6 months after the initial visit for investigation of insomnia caused by spontaneous pain in the left TMJ area. She also had paralysis of the lower lip and left chin. She had herpes labialis and gastroenteritis caused by stress. Given the suspicion of malignancy, both MRI and computed tomography (CT) were performed. MRI showed a round, inhomogeneous mass in the pterygomandibular portion of the masticator space, which caused minimal medial narrowing of the left parapharyngeal space (Figure 4, A, B). CT found significant bony erosion of the inner cortex of the left ramus of the mandible (Figure 5). The patient was referred to another hospital for further management because the tumor grew toward the pharyngeal arches. An incisional biopsy was subsequently performed, and the initial diagnosis was a sarcoma based on the histopathologic examination of the biopsy. A definitive histologic diagnosis was reached by exclusion. The tumor was diagnosed as a grade 3 (poorly differentiated) fibrosarcoma using the FNCLCC (Federation Nationale des Centres de Lutte Contre le Cancer) grading system. Histopathologic examination found that the tumor contained spindle cells arranged in compact fascicles that were intersected by various amounts of delicate thin to dense keloid-like collagen. Cell bundles were arranged at acute angles to each other, whereas the presence of fascicles was subtler in other areas. A prominent storiform pattern was not seen (Figure 6). The fibrosarcoma was resected followed by postoperative radiotherapy and chemotherapy. The tumor was removed, along with the left ramus of the mandible, a portion of the left maxilla, a deep part of the parotid gland, and lymph nodes located superior to the omohyoid muscle. The cheek mucosa was reconstructed using a free anterolateral thigh flap (Figure 7). The patient recovered and got married afterward; however, lung metastasis with Fig. 1. Facial photograph. The patient’s chin shifted to the right side when she opened her mouth.

What make differences in the outcome of adjuvant treatments for resected gastric cancer?

After a long history of Dark Age of adjuvant chemotherapy for gastric cancer, definite evidences of survival benefit from adjuvant treatment have been reported since 2000s. These survival benefits are likely attributed to something new approach different from pervious studies. In 2001, South West Oncology Group INT0116 trial yielded survival benefit in curatively resected gastric cancer patients with postoperative chemoradiotherapy [5-fluorouracil (5-FU) + Leucovorin + radiotherapy], followed by positive result by MAGIC Trial, employing peri-operative(pre- and postoperative chemotherapy with Epirubicin, cisplatin (CDDP), 5-fluorouracil (ECF) regimen in patients with curative resection. A novel drug [S1: ACTS-GC (Adjuvant chemotherapy trial of TS-1 for gastric cancer) in 2007], or new drug combination chemotherapys [CDDP + 5-FU: FNCLCC/FFCD (Federation Nationale des Centres de Lutte contre le cancer/Federation Francophone de Cancerologie Digestive) in 2011, Capecitabine + Oxaliplatin: CLASSIC in 2012] also produced positive results in terms of improved prognosis. Neoadjuvant or perioperative chemotherapy, novel anti-cancer drugs, and chemoradiotherapy might be the key words to develop further improvement in the adjuvant treatment of resectable gastric cancer. Moreover, it is not new but still true to stress the importance of D2 surgery as the baseline treatment in order to minimize the amount of residual tumor after surgery.

Leiomyosarcoma of the Inferior Vena Cava: Clinicopathologic Study of 40 Cases

This report details the clinicopathologic features and follow-up data on 40 cases of inferior vena cava leiomyosarcoma, a rare sarcoma with a poor prognosis. Study cohort consisted of 31 females and 9 males (mean age, 53 y), whose material was accessioned to the Armed Forces Institute of Pathology between 1976 and 2008. Inferior vena cava leiomyosarcomas ranged in size from 3.5 to 15.0 (median, 8.5) cms, and most involved the middle segment of the vessel and grew extraluminally. Eleven leiomyosarcomas were French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade I; 21, grade II; and 5 were grade III. Eleven of 33 patients managed by complete or radical resection had involved surgical margins. Twenty of the 34 patients (59%) with clinical follow-up data (mean, 33.5; median, 51 mo) died of sarcoma-related complications and 9 (26%) of unknown causes. The 5-year and 10-year survival rates after resection without documented residual macroscopic disease were 50% and 22%, respectively. Two patients are alive without disease 9 and 18 years after last surgical intervention. Suprahepatic vena caval and right atrial involvement by tumor, predominant intraluminal tumor growth, and residual postsurgical macroscopic disease were factors that statistically correlate with death within 2 years. By univariate analysis, intraluminal tumor (P=0.03), liver injury or failure (compromised liver) (P=0.01), and moderate to poor tumor differentiation (P=0.03) were associated with increased tumor-related mortality, whereas a compromised liver (P=0.01) was the only factor correlated with mortality by multivariate analysis. Our study concludes that a macroscopic resection of localized inferior vena cava leiomyosarcoma provides the best chance for long-term survival, suprahepatic tumors often result in early death, and a compromised liver correlates with overall poor survival, but French Federation Nationale des Centres de Lutte Contre le Cancer grading does not affect prognosis.

Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Long Term Persistent Alopecia and Suboptimal Hair Regrowth after Adjuvant Chemotherapy for Breast Cancer: Alert for an Emerging Side Effect: ALOPERS Observatory.

Abstract Background: Since 2003, through the impetus given by Pr Erick Gamelin and the Regional Health Agency in Western France (Bretagne, Pays de Loire), a network called OMIT (Drugs and Emerging Therapeutics Observatory) has been created, including the Breast Cancer Forum. Anthracyclins and taxanes are the cornerstones of adjuvant chemotherapy for breast cancer. In France, since the PACS 01 publication1, FEC 100 followed by docetaxel 100 has been the standard adjuvant chemotherapy regimen in breast cancer. Long term toxicities like persistent alopecia or suboptimal hair regrowth have been observed.Methods: Over the last year, the first cases of persistent alopecia or suboptimal hair regrowth after adjuvant chemotherapy have been reported to the Breast Cancer Forum. Consequently, OMIT quickly drew up a case report form and mailed it to every oncologist in Western France to collect data.Results: From May 2008 to April 2009, 66 cases of persistent alopecia or suboptimal hair regrowth after adjuvant chemotherapy from 15 different institutions were declared to OMIT: median age: 60 years (35-78), hypothyroidia: 11, fine hair before treatment: 2. Alopecia was localized: 13, diffuse: 49, complete: 4. The time lapse between the end of chemotherapy and persisting alopecia has been more than 3 months: 5 patients, more than 6 months: 10, more than 12 months: 22, more than 24 months: 29. The chemotherapy regimens were various: schedule FEC (epirubicin 100 mg/msq), 3 courses followed by docetaxel 100 mg/msq, 3 courses: 54, docetaxel 100 mg/msq: 3, TCH (docetaxel-carboplatin-trastuzumab) or TH: 2, FEC 100: 2, epirubicin 75 mg/msq in association with docetaxel 75 mg/msq: 2. Hormonotherapy: letrozole: 13, anastrozole: 18, exemestane: 3, tamoxifene: 14, LH-RH agonist: 3. No hormonotherapy: 13. In some institutions, according to the ECOG trial2, some oncologists quickly decided to change their standard regimen from FEC 100 - docetaxel 100, to EC 100 4 courses followed by weekly paclitaxel for 12 weeks: forthcoming data on persistent alopecia, suboptimal hair regrowth or neuropathy after this ECOG adjuvant chemotherapy regimen will be presented at the symposium.Conclusion: For the first time in France, Western OMIT offers us data about persistent alopecia or suboptimal hair regrowth after adjuvant chemotherapy: it is an important side effect and must be considered by oncologists as optimal information to give to curable patients. The next step is to evaluate the real incidence of this phenomen on the population of patients treated by adjuvant chemotherapy for breast cancer: OMIT is currently working with the Federation Nationale des Centres de Lutte contre le Cancer (FNCLCC) to collect data from prospective trials such as PACS 01 (FEC versus FEC-docetaxel), PACS 04 (FEC versus epirubicin-docetaxel) and PACS 05 (FEC 6 courses versus 4 courses), to create the ALOPACS database.1- Roché H. Sequential Adjuvant Epirubicin-based Regimen and Docetaxel Chemotherapy for node-positive Breast Cancer Patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 dec 20; 24 (36) 5664-71.2- Sparano JA.Weekly Paclitaxel in the Adjuvant Treatment in Breast Cancer. N Engl J Med. 2008 Apr 17; 358(16): 1663-71. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3174.

Breast Cancer Prevention by Letrozole in Post Menopausal BRCA1/2 Mutations Carriers: The Onco-03/LIBER Trial.

Abstract Women carrying germline BRCA1/2 deleterious mutations are an extreme risk population for developing breast cancer, with a cumulative life-time risk of 56-80%. Prophylactic bilateral mastectomy provides a valid option for reducing the risk of breast cancer by nearly 90 %. Although it greatly affects the quality of life, breast prophylactic surgery in BRCA1/2 mutation carriers have increased in Europe and in US over the last decade.The major breast cancer prevention trials using tamoxifen and raloxifen showed an approximately 50% risk reduction in high risk women. The contralateral risk reduction in current adjuvant trials comparing aromatase inhibitors (AI) to tamoxifen therapies reveals a higher preventive efficacy of AI after menopause. Two ongoing randomized studies using exemestane (MAP3) or anastrozole (IBIS2) are assessing the risk reduction of breast cancer in menopausal women but none are designed for BRCA1/2 carriers.The French federation of cancer centres, "FNCLCC" (Federation Nationale des Centres de Lutte Contre le Cancer) has developed a randomized phase III study to determine the efficacy of the aromatase inhibitor letrozole to reduce the incidence of invasive breast cancer in post menopausal BRCA1/2 carriers. The ONCO-03 (LIBER) study is a double-blind, letrozole versus placebo, controlled study involving 28 centres in France. The study opened for recruitment in march 2008. The study design, procedures and first analysis of patients enrolment are presented.Based on the known preclinical and clinical profile of AI, a greater reduction in breast cancer incidence with fewer side effects is hypothesized with this class of agents than with tamoxifen or raloxifen. For postmenopausal women bearing a BRCA1/2 genetic predisposition, prevention of breast cancer risk by letrozole could provide a precious alternative to bilateral mastectomy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1048.

Clinicopathologic study of 24 patients with primary cardiac sarcomas: a 10-year single institution experience

Primary cardiac sarcomas are exceptionally rare. We present a 10-year, single-institution experience with 24 primary adult cardiac sarcomas. These cases were retrieved from the Department of Pathology data file of the Methodist Hospital at Houston, TX. Clinical presentation and pathologic features were analyzed. Histologic classification was followed according to the criteria set by the World Health Organization, and grading according to the system proposed by the Federation Nationale des Centres de Lutte Contrele Cancer. There were 14 men and 10 women (male/female, 1.4:1) with a mean age of 42.2 years (range 20-68 years). The tumors involved the right atrium in 14 cases, left atrium in 6 cases, right ventricle in 2 cases, and left ventricle in 2 cases. The tumor size ranged from 2.0 to 17.0 cm (mean 7.2 cm), and, histologically, there were 10 angiosarcomas, 9 unclassified sarcomas, 3 synovial sarcomas, and 2 leiomyosarcomas. All 10 angiosarcomas originated from the right atrium, whereas 5 of the unclassified sarcomas were from the left atrium. Although cases were limited, no predilection site was found for the other histologic types. All tumors were graded as 2 (5 cases) or 3 (19 cases) in differentiation. The prognosis was poor with a median survival time of 25 months after diagnosis. The grade was not statistically significant on survival (P = .14). In conclusion, angiosarcoma and unclassified sarcomas are the most common sarcomas of the heart accounting for 76%, but rare tumors such as synovial sarcoma and leiomyosarcoma may also occur in this organ. The survival of cardiac sarcomas is poor.