软组织肿瘤分级与分期简介ppt课件.pptx

软组织肿瘤的分级与分期简介,吴焕文,prognosis,Prognosis of STS is dominated by local recurrence and distant metastasis. Overall survival mainly depends on metastasis, but in some localizations, such as retroperitoneal areas, overall survival depends also on local recurrence. In most reported studies, quality of surgical margins is the most important factor for predicting local recurrence, whereas metastasis and overall survival are related mainly to histologic grade.,Histopathological grading favourable prognosis or poor prognosis; overall survival; appropriate treatment regimen selection (Surgical, chemotherapeutic, and radiation treatments),soft-tissue sarcomas,prognostic factors,Grading of soft tissue sarcomas was first proposed in 1939 by Broders, who used a combination of mitotic activity, tumor giant cells, and fibrous stroma in assigning a grade to fibrosarcomas. Broders also acknowledged the importance of cellular differentiation in grading. The rst coherent and effective prognostic classication of STS was proposed by Russell et al. in 1977. This system introduced a histologic grading applicable to all adult STSs, which was the most important factor. Some histological type of Tumors are definitionally high grade or low grade. A number of different grading systems have been proposed over the years for soft tissue sarcomas, utilizing 2 tiered, 3 tiered, and 4 tiered stratification schemes.French Federation of Cancer Centers (FNCLCC) system(37.3%) National Cancer Institute (NCI) (24%), Broders criteria (12%)Markhede system (1.3%) other (15.3%),PARAMETERS USED IN GRADING:Histological typeNecrosisMitotic activityTumour differentiationCellularityNuclear pleomorphismVascular invasion,The most widely used and clinically validated grading systems are ：National Cancer Institute (NCI) systemFrench Federation of Cancer Centers (FNCLCC) system Both of which are 3 tiered systems (Grade 1, Grade 2, Grade 3). At the present time, the FNCLCC grading system ease of use interobserver agreement predictive power,National Cancer Institute (NCI) grading system,Criteria for gradinghistologic diagnosis cellularitycellular pleomorphismmitotic rate necrosis ：necrosis emerged as a major discriminating variable. grade 2 and 3 tumors exhibiting moderate or marked necrosis (15%) had a significantly poorer prognosis. Three-grade system The respective 5-year survival rates 100% (Grade I) 73% (Grade II) 46% (Grade III),NATIONAL CANCER INSTITUTE GRADING SYSTEM (NCI分级系统）Grading in this system is based on histological type of tumour and tumour necrosis where histological type does not define grade.HISTOLOGICAL PARAMETER GRADEHISTOLOGICAL TYPE/SUBTYPE 1- Epithelioid haemangioendothelioma- Well differentiated liposarcoma- Myxoid liposarcoma- Infantile fibrosarcomaHISTOLOGICAL TYPE, MITOSIS, DIFFERENTIATION 1 - Well-differentiated leiomyosarcoma ( 6 mitosis /10HPF)- Well- differentiated fibrosarcoma ( 6 mitosis / 10HPF)- Malignant peripheral nervesheath tumour ( 6 mitosis/ 10HPF)- Extraskeletal myxoid chondrosarcoma (no mitoses) HISTOLOGICAL TYPE, NECROSIS 2- Any sarcoma not compulsorily grade 3 and less than 15% necrosis HISTOLOGICAL TYPE / SUBTYPE 3- Any sarcoma with more than 15% necrosis- Rhabdomyosarcoma (all subtypes)- Extraskeletal osteosarcoma- Ewings sarcoma /primitive neuroectodermal tumour- Mesenchymal chondrosarcoma- Pleomorphic liposarcoma- Alveolar soft part sarcoma,ASSIGNED HISTOLOGIC GRADE ACCORDING TO HISTOLOGIC TYPE IN THE NCI SYSTEM,Shortcomings,The amount of necrosis emphasized by the NCI system is potentially affected by preferential sampling of necrotic and non-necrotic tissue Not practical for evaluation of needle biopsy specimens. Moreover, retrospective analysis is complicated when an overall assessment of necrosis is not included in the gross description.,FNCLCC grading system,Criteria for gradingcellular differentiation mitotic ratetumor necrosis（镜下）reproducibility 81% for tumor necrosis,74% for tumor differentiation 73% for mitotic rate 75% for overall tumor grade61% for histologic typeThe respective 5-year survival rates 100% (Grade I) 73% (Grade II) 46% (Grade III),Differentiation score is defined as the extent to which a tumor resembles adult mesenchymal tissue (score 1) the extent to which the histologic type is known (score 2) the observation that the tumor is undifferentiated (score 3),TUMOR DIFFERENTIATION SCORE ACCORDING TO HISTOLOGIC TYPE IN THE UPDATED VERSION OF THE FNCLCC SYSTEM,NCI VS FNCLCCgrade discrepancies： 34.6% Use of the FNCLCC system resulted in： an increased number of grade 3 tumors a reduced number of grade 2 tumors a better correlation with overall and metastasis-free survival,MIB-1 system,The histological grade is the most useful factor for predicting the prognosis of soft-tissue sarcomas. Among others, histological grading on the basis of the MIB1 labeling index is advantageous, both in terms of objectivity and reproducibility.,Both NCI and the FNCLCC systems were developed using cohorts of predominantly adult patients.In children, grading of soft tissue sarcomas is compromised by the good prognosis of certain tumors such as infantile fibrosarcoma. In addition, testing of a grading system within the pediatric population is difficult because of the rarity of these neoplasms. Two systems are currently in use for grading pediatric nonrhabdomyosarcomatous soft tissue sarcoma (NRSTS) tumors. Pediatric Oncology Group(POG) grading systems The grading systems developed by the Childrens Oncology Group (COG) and the French Federation of Cancer Centers Sarcoma Group,To avoid modication by treatment, the histological grade should be evaluated in untreated primary tumor specimens. Some tumors (especially pediatric rhabdomyosarcomas) may appear much better differentiated after chemotherapy, but, in truth, this most likely reflects selection of chemoresistant clones of tumor cells rather than an indication of improved prognosis.Grading system by any other means can not substitute for distinction between benign and malignant tumors or diagnosis of the histological type of the tumors.The same grading system cannot be applied to the different types of sarcomas because the prognostic factors differ according to histologic type.The histological grade does not serve as a reliable prognostic factor for malignant peripheral nerve sheath tumors (MPNST) and tumors that often develop in children.It is also not useful in cases of alveolar soft-part sarcoma, clear cell sarcoma or epithelioid sarcoma as these sarcomas show histiotype-specic behavior. extraskeletal myxoid chondrosarcoma, “Low-grade” fibromyxoid sarcomaCutaneous angiosarcoma： the size of the primary tumorSynovial sarcoma：年龄、大小、是否存在低分化区域分为高危组和低危组Ewing sarcoma should be considered automatically as a Grade 3 sarcoma with a high metastatic potential.To talk about degree of differentiation in tumors that have no differentiated normal tissue equivalent, such as synovial sarcoma, epithelioid sarcoma, and alveolar soft part sarcoma, is clearly pointless.,Histological grading is useful for predicting the likelihood of distant metastases and prognosis in a given patient. It is less useful for predicting the likelihood of local recurrence, which is known to be more closely associated with the margin of resection. Furthermore, specimens xed well and obtained from a tumor-rich area should be used for this classication. appropriately xed and processed specimens must be used;the mitotic gures must be checked accurately; The mitotic rate in each visual eld is counted at a magnication level of 400, and the counts in 10 visual elds are totaled to yield the number of mitotic gures (per 10 high-power elds, HPF). an area of the specimen with a high cellularity and the apparently largest number of mitotic gures must be selected. These precautions are the same as those commonly applicable to measurement of the mitotic count in pathological specimens. Needle biopsies are not ideal for preoperative grading purposes. In gastrointestinal stromal tumor, the NIH consensus risk assessments reports were used as a surrogate for histologic grade.,Accurate histological typing of the tumour plays an important role in determining tumour prognosis in the following cases: HIGH GRADE TUMOURS Angiosarcoma Extraskeletal Ewings sarcoma/PNET Extraskeletal osteosarcoma round cell liposarcoma Mesenchymal chondrosarcoma Pleomorphic liposarcoma Rhabdomyosarcoma LOW GRADE TUMOURS Angiomatoid malignant fibrous histiocytoma Atypical fibroxanthoma Atypical lipomatous tumour/well differentiated liposarcoma Dermatofibrosarcoma protuberans Desmoid tumour Myxoid liposarcoma,The spectrum of grades observed among histologic subtypes of soft-tissue sarcoma. (From Enzinger FN and Weiss SW, editors. Soft Tissue Tumors.）,STS的分期,UICC/AJCC TNM分期 PRIMARY TUMOR (T) REGIONAL LYMPH NODES (N) DISTANT METASTASIS (M),The current AJCC STS staging system ：Unlike with other organ systems, the staging of soft tissue sarcomas is largely determined by grade. four criteria of tumor size(depth), nodal status, grade, and metastasis (TNGM).useful prognostic information selection of patients for adjuvant therapy and/or stratication for inclusion in clinical trials.,Past Editions of the AJCC Cancer Staging Manual Edition 1 published 1977 and went into effect 1978Edition 2 published 1983 and went into effect 1984Edition 3 published 1988 and went into effect 1989Edition 4 published 1992 and went into effect 1993Edition 5 published 1997 and went into effect 1998Edition 6 published 2002 and went into effect 2003Edition 7 published 2009 and went into effect 2010,Depth：Besides histologic grade, tumor depth (superficial versus deep) was another important prognostic parameter.,The TNM staging system for soft tissue tumors of the AJCC and UICC is recommended. The staging system applies to all soft tissue sarcomas, except Kaposi sarcoma gastrointestinal stromal tumors fibromatosis (desmoid tumor) infantile fibrosarcoma. not optimally staged by this system sarcomas arising within the confines of the dura mater, including the brain sarcomas arising in parenchymatous organs and from hollow viscera,Anatomic Stage/Prognostic GroupsAJCC Cancer Staging Manual. 7th ed.,Anatomic Stage/Prognostic GroupsAJCC Cancer Staging Manual. 6th ed.,Nodal involvement is rare, occurring in less than 5% of patients with sarcoma. Histologic subtypes of soft tissue sarcoma, such as rhabdomyosarcoma and epithelioid sarcoma, have the greatest predilection for lymph node involvement.,Patients with isolated lymph node metastasis had an estimated 4-year OS rate of 71%, which was equivalent to the survival of AJCC stage III patients. In contrast, those patients who had synchronous systemic and lymph node involvement had far worse outcomes that were comparable to those of stage IV. These suggest that isolated lymph node metastases are most likely to be associated with an AJCC stage III rather than stage IV survival pattern,Enneking分期肌肉骨骼肌协会分期系统 used primarily by orthopedic oncologists,Enneking分期,两种解剖学情况： T1：间室内，是指局限于容易辨认的解剖学结构（如功能性肌群、关节和皮下组织） T2：间室外，指来源于或继发性侵犯无自然解剖屏障区域的肿瘤两级(G1，G2)，其与外科手术的两种治疗方式（扩大切除、根治切除）相吻合。三期（I A/B, II A/B, III)适用软组织肉瘤及骨肉瘤，最适用于四肢病变。,The surgical grade may differ slightly from the purely histologic grade by consideration of clinical and radiographic features.,Staging of rhabdomyosarcoma,The process includes the following steps:Assigning a stage (consider site, size, Surgico-pathologic Group, and presence/absence of metastases). Assigning a local tumor Surgico-pathologic Group (status postsurgical resection/biopsy, with pathologic assessment of the tumor margin). Assigning a Risk Group (classified by Stage, Group, and histology).,Soft Tissue Sarcoma Committee of the Childrens Oncology Group Pretreatment Staging System,Soft Tissue Sarcoma Committee of the Childrens Oncology Group Surgico-pathologic Group System,Soft Tissue Sarcoma Committee of the Childrens Oncology Group Rhabdomyosarcoma Risk Group Classification,Prognostic parameters not currently included in the present AJCC STS staging system,Age Age was the most consistent adverse independent prognostic factor for survival.Neurovascular and bone invasion independent predictors: malignant brous histiocytomas; leiomyosarcomas; synovial sarcoma;,Histologic subtype children and adolescents non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): less responsive to radiotherapy rhabdomyosarcoma: radiotherapy can be used instead of surgery embryonal subtypes alveolar subtypes retroperitoneal sarcomas (RPSs) atypical lipomatous tumors(ALTs), non-ALT liposarcomas (LPSs) other,Site of primary disease：,Specic molecular prognostic markerslocal recurrenceMost analyses identify previous local recurrence as a major (if not the major) risk factor for subsequent local recurrence.,Margin status Positive surgical margins are the main predictors for local relapse. Grade, size, and TNM stage (UICC/AJCC) have stronger prognostic signicance for overall survival and distant recurrence than for local relapse.,It is believed generally that surgical margins of less than 1.5-2 cm in soft tissue sarcoma predispose to an increased risk of local recurrence unless further surgery or irradiation is undertaken. However if a surgical margin is bounded by an unbreached layer of fascia or periosteum this risk probably does not apply , but such margins should still be measured if close.,Multivariate Analysis of Prognostic Factors in Patients with Extremity Soft-Tissue Sarcoma,RECOMMENDATIONS FOR THE REPORTING OF SOFT TISSUE SARCOMA Diagnostic Information 1. Site and depth of tumor (e.g. dermal, subcutaneous, fascial, subfascial, intramuscular, visceral or more than one of these). 2. Histological type (use WHO system when possible ); if tumor type is unknown then the term unclassified sarcoma with a qualifier such as pleomorphic, spindle cell, myxoid or round cell is useful. 3. Maximal dimension of tumor (in cm) ; 4. Histologic grade; 5. Minimum distance(s) to resection margins - any margin less than 2 cm from the tumor should be specified in terms of location and distance;,6. Histologic evidence of a pre-existing benign lesion ( only applicable to nerve sheath neoplasms); 7. Lymph node status (if present); 8. Results of any special investigations (e.g. special stains, immunohistochemistry, electron microscopy, DNA flow cytometry, karyotype).,1. Mitotic rate, expressed as number of mitoses per 10 high power fields; 2. Extent of necrosis, as confirmed histologically; 3. Presence or absence of vascular invasion, irrespective of vessel type; 4. Character of lesional margin - e.g. circumscribed, focally infiltrative, diffusely infiltrative; 5. Presence, extent and type of inflammatory infiltrate.,Optional Features in Diagnostic Report,参考文献,1. Trojani M, Contesso G, Coindre JM, Rouesse J, Bui NB, de Mascarel A,Goussot JF, David M, Bonichon F, Lagarde C (1984). Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological