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  1. Int J Clin Exp Pathol 2016;9(8):8297-8307 www.ijcep.com /ISSN:1936-2625/IJCEP0031746 Original Article Clinical outcomes of undifferentiated sarcomas are similar with that of other spindle cell sarcomas of specific histologic types: an institutional experience Soyoung Im, Changyoung Yoo, Jihan Jung, Hyun Joo Choi, Jinyoung Yoo Department of Hospital Pathology, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea Received May 5, 2016; Accepted June 23, 2016; Epub August 1, 2016; Published August 15, 2016 Abstract:Background: Clinical, epidemiological and pathologic data about undifferentiated sarcoma (US) is not suf- ficient. This study aimed to provide the basic data including clinical outcomes about US. Materials and methods: For this study, we selected 135 cases of sarcomas including 49 cases of US and 86 cases of specific sarcomas diag- nosed from 2000 to 2012 at St. Vincent Hospital, The Catholic University of Korea. Among the specific sarcomas, we selected some high grade spindle cell sarcomas which grouped as non-US and used for comparison and analysis. We compared clinical and histological characteristics and overall survival between these two groups. Results: US oc- cupied 36.3% of sarcomas and occurred mainly in older ages more than 41 years (82%), and lower extremities were prevalent sites. 6 cases were accompanied by metastasis (12.2%), and lung and bone were major target organs. 22 cases (44.9%) were grade 2 by FNCLCC and 27 (55.1%) were grade 3. When compared with non-US, there were no significant differences. Clinically, presence of metastasis alone affected their overall survival not only in US but also in non-US. Conclusions: Because US and other spindle cell sarcoma showed similar clinical outcomes according to this study, clinical approaches for US could be followed safely that of other high grade sarcomas. Keywords: Undifferentiated sarcoma, epidemiology, immunohistochemistry, molecular pathology, overall survival Introduction coma, synovial sarcoma or fibrosarcoma are reckoned as principal entities for differential diagnosis with US, we aimed to know whether there were significant differences in their clini- cal courses between US and above mentioned sarcomas. Undifferentiated sarcoma (US) refers a soft tis- sue sarcoma showing no identifiable line of dif- ferentiation even though present available diagnostic tools such as immunohistochemis- try and tumor genetic assays are applied [1]. US includes several kinds of tumors, and US is diagnostic term used only after possible spe- cific entities are excluded as described in the definition of US. Therefore, this entity can be reckoned as a kind of wastebasket. In the cat- egory of US, dedifferentiated sarcomas of other specific soft tissue tumors are not included [1, 2]. Materials and methods For this study, we selected 135 cases of sarco- mas including 49 cases of US and, for compari- son, 86 cases of specific sarcomas diagnosed from 2000 to 2012 at St. Vincent Hospital, The Catholic University of Korea. Because the diag- nostic term of US was changed several times, diagnostic term of these cases were variable. Therefore, 49 US cases included 38 malignant fibrous histiocytomas, 2 undifferentiated pleo- morphic sarcomas, 2 high grade sarcomas, and 7 poorly differentiated sarcomas. Although some cases showed ambiguous diagnostic term, we grouped these cases as US according The clinical, epidemiological and pathologic data about US is not sufficient. This study aimed to provide the basic data about US such as clinical and histological characteristics, and its overall survival. Especially, because several sarcomas of specific types such as leiomyosar-

  2. Clinical outcomes of undifferentiated sarcoma Table 1. Clinical characteristics of sarcomas Sex Ages (years) 21-40 0 5 0 2 1 1 3 0 0 5 2 3 3 1 0 9 35 (25.9) 55 (40.7) Diagnosis No. (%) M 4 4 1 3 3 3 3 3 4 4 6 4 2 3 3 29 F 2 12 0 0 1 2 5 3 0 1 5 1 3 1 0 20 0-20 0 0 0 0 0 0 3 0 1 0 0 1 0 1 2 0 8 (5.9) 41-60 4 9 0 1 2 2 1 1 2 0 9 1 1 1 0 21 61-80 2 2 1 0 1 2 1 5 1 0 0 0 1 1 1 19 37 (27.5) Dedifferentiated liposarcoma Myxoid liposarcoma Pleomorphic liposarcoma Fibrosarcoma Myxofibrosarcoma Leiomyosarcoma Rhabdomyosarcoma Kaposi sarcoma Angiosarcoma MPNST Synovial sarcoma Epithelioid sarcoma Alveolar soft part sarcoma Clear cell sarcoma Extraskeletal Ewing sarcoma Undifferentiated sarcoma Tatal 6 (4.4) 16 (11.9) 1 (0.7) 3 (2.2) 4 (3.0) 5 (3.7) 8 (5.9) 6 (4.4) 4 (3.0) 5 (3.7) 11 (8.1) 5 (3.7) 5 (3.7) 4 (3.0) 3 (2.2) 49 (36.3) 135 (100.0) 79 (58.5) 56 (41.5) to the 2013 WHO classification [1], because these cases showed no definite line of differen- tiation histologically and immonohistochemi- cally in common. Among the specific sarcomas, we excluded well differentiated liposarcoma and dermatofibrosarcoma protuberans. is 1 if total score is 2 or 3, grade 2 if total score is 4 or 5, and grade 3 if total score is 6, 7, or 8 [1]. For the comparison of histologic grades and overall survival, we selected fibrosarcoma, myxofibrosarcoma, dedifferentiated liposarco- ma, leiomyosarcoma, MPNST and synovial sar- coma as a group of non-US because these tumors are most frequently referred diagnostic entities for the differential diagnosis of US. We compared overall survival between US and selected specific sarcomas above mentioned (non-US below). We used the chi-square test and Kaplan-Meier survival analysis to examine the statiatical significance of the results, using SAS software (version8; SAS Inc., Cary, NC, USA). A p-value of <0.05 was considered signifi- cant. This study was approved by the Clinical Study Medical Ethics Committee (VC15RISI- 0002). We considered following conditions before selection of US, the methods provided by Goldblum [3]: any kind of specific line of differ- entiation was not identified immunohistologi- cally, any possibility of dedifferentiated sarco- ma should be excluded, and the possibility of sarcomatous carcinoma from other body sites was not present. We selected the cases of US only after above mentioned criteria is fulfilled. For other specific sarcomas, we selected them according to the classification of 2013 WHO classification. We examined clinical characteristics such as age, sex, site, and metastatic rate of these sar- comas. We reviewed HE slides and immunohis- tochemical results of US and other sarcomas. Tumor grade were applied according to Fede- ration Nationale des Centres de Lutte Contre le Cancer (FNCLCC). This system consists with scoring system including tumor differentiation (score 1 to 3), mitotic count (score 1 to 3), and tumor necrosis (score 0 to 2). Histologic grade Results Among sarcomas diagnosed in this institute, US occupied 36.3%. Male to female ratio was about 1.5:1.0. US occurred mainly in older ages more than 41 years (82%). Other specific sarco- mas composed of various diagnoses. Their sex ratio was variable. As US, these sarcomas were also more frequent in older ages more than 41 years (61%) (Table 1). 8298 Int J Clin Exp Pathol 2016;9(8):8297-8307

  3. Clinical outcomes of undifferentiated sarcoma Following results are com- parisons between US and non-US as these were major concern of this study. For this comparison, we select- ed 34 sarcomas of specific histologic types including 3 fibrosarcomas, 4 myxofibro- sarcomas, 6 dedifferentiat- ed liposarcomas, 5 leiomyo- sarcomas, 5 malignant pe- ripheral nerve sheath tum- ors, and 11 synovial sarco- mas. Histologically, US could be divided into 24 pleomor- phic type (49.0%), 19 spin- dle cell type (38.8%), 5 epi- thelioid type (10.2%), and 1 round cell type (2.0%) (Table 4; Figure 1). In US, 22 cases (44.9%) were grade 2 and 27 (55.1%) were grade 3. Grade 1 tumor was not found. Among the 34 cases of non-US, 15 cases (41.7%) were grade 2 and 21 (58.3%) were grade 3. Grade 1 tumor was not found either. Sta- tistical difference of histo- Table 2. Metastatic rates of soft tissue sarcomas Rate of metastasis No (%) 0 (0.0)b 2 (12.5) 0 (0.0) 1 (33.3) 1 (25.0) 0 (0.0) 3 (37.5) 0 (0.0) 2 (50.0) 2 (40.0) 4 (36.4) 1 (20.0) 5 (100.0) 4 (100.0) Lung, bone, brain, regional lymph node 1 (33.3) 8 (16.3) Diagnosisa No. (%) Sites of metastasis DLS MLS PLS FS MFS LMS RMS KS AS MPNST SS ES ASPS CCS EES US Tatal 6 (4.4) 16 (11.9) 1 (0.7) 3 (2.2) 4 (3.0) 5 (3.7) 8 (5.9) 6 (4.4) 4 (3.0) 5 (3.7) 11 (8.1) 5 (3.7) 5 (3.7) 4 (3.0) 3 (2.2) 49 (36.3) 135 (100.0) - Liver, bone - Lung Lung - Lung, bone - Lung, brain Lung, bone Lung Lung Lung, bone Brain Lung, bone aDLS, dedifferentiated liposarcoma; MLS, myxoid liposarcoma; PLS, pleomorphic liposarcoma; FS, fibrosarcoma; MFS, myxofibrosarcoma; LMS, leiomyosarcoma; RMS, rhabdomyosarcoma; KS, kaposi sarcoma; AS, angiosarcoma; MPNST, malignant pe- ripheral nerve sheath tumor; SS, synovial sarcoma; ES, epithelioid sarcoma; ASPS, al- veolar soft part sarcoma; CCS, clear cell sarcoma; EES, extraskeletal Ewing sarcoma; US, undifferentiated sarcoma; bPercentage within individual sarcoma. These sarcomas showed various rates of metastasis from 0 to 100%. Angiosarcoma, alveolar soft part sarcoma and clear cell sar- coma showed high rate (more than 50%) of metastasis. Most frequent metastatic sites were lung and bone. Other sites included liver, brain and regional lymph node. Among 49 US, 6 cases were accompanied by metastasis (12.2%), and lung and bone were major target organs (Table 2). logic grade between US and non-US group was insignificant (P=0.827) (Table 4). We compared the sites of occurrence between US and non-US. More than 60.0% of US, fibro- sarcomas, myxofibrosarcomas, Leiomyosarco- mas, MPNST and synovial sarcomas occurred in the extremities. Dedifferentiated liposarco- mas occurred in intraabdominal area more fre- quently (66.7%). In US, 34 cases (69.4%) occ- urred in extremities, especially in lower extrem- ities - 5 (10.2%) in upper and 29 (59.2%) in lower extremities. 9 cases (18.4%) were found in the trunk, and 6 cases (12.2%) were found as intraabdominal tumor (Table 5). Immunohistochemistry was done in 49 cases of US. Generally performed items were cytoker- atin, vimentin, alpha 1-antitrypsin, desmin, ac- tin, lysozyme, myoglobin, S-100 protein, CD68 and CD34. Our cases showed nonspecific or occasional positive reactions to vimentin, alpha 1-antitrypsin, CD68 and lysozyme, but negative reactions to other items except 3 cases which showed weal or focal positive reaction to actin, and a case with faint reaction to S-100protein. Other antibodies such as HMB-45, c-kit, EMA, CD99, CD56 and beta-catenin were applied in certain cases, but showed negative reactions in majority cases (Table 3). In the aspects of overall survival, there was no difference between US and non-US (P= 0.362) (Figure 2A). Among the grade 2 tumors, there was no difference between them (P= 0.562) (Figure 2B) and showed same results among the grade 3 (P=0.552) (Figure 2C). Among non-US, there was no difference between grade 2 and 3 (p=0.378) (Figure 2D) and showed same result with US (P=0.392) 8299 Int J Clin Exp Pathol 2016;9(8):8297-8307

  4. Clinical outcomes of undifferentiated sarcoma Table 3. Immunohistochemical results of US Cases CK vim AT 1 -a P - 2 - P - 3 - P - 5 - P - 6 N P - 7 - P N 8 N P N 9 - P N 10 - - N 11 - - - 12 - - N 13 N P N 14 - - N 15 - P N 16 - P - 17 - P - 18 N P - 19 - - N 20 - P N 21 - - N 22 - P P 23 - P N 24 - P N 25 - P WP 27 - - N 28 - P N 29 - P N 30 - P N 31 - P N 32 N P - 33 N - - 34 N P - 35 N P - 36 N - WP 37 N P N 38 - P N 40 N - N 41 - - N 42 - P N 43 - - N 44 N - N 45 - P N 46 - P N 48 - P N 49 - - N CK, cytokeratin; vim, vimentin; AT, actin; DM, desmin, S-100, S-100protein; MG, myoglobin; LZ, lysozyme; A1A, alpha-1 antitryp- sin; BC, beta-catenin. a. N, negative; P, positive, WP, weak positive; FP, focal positive; -, not done. DM N N - N - N - - - - - N - N - - N N N - N N - N N N N - N - - N - N N N N N N N - - N N N S-100 - - - N - N N N N - N N N N N N N - N N N - N N N N N N N P N N - N N N N N N N N N N N N MG - N - - - - - - - - - N - - - - - - N - - N - N N - - - - - - N - - - - - - - - N - N - N LZ N P WP - P - - - - P P N - - P P - N N - P N N P - - - - N - - - - - - - N - P - N P P - - A1A - P P P P P - P - P P P - P P P - P - P - P P - - - N - - - - - - - - - - - - - - - P N P c-kit - - - - - - - - - - - P - - - - - N - - - - - - N - - - - - - - - - N - - N - - - - - - - CD34 - - - - - - N - N - - - N - - - - N - N - - - - - N N - - - - N - N N - - N - - - - - N N CD68 - - - - - - - - - - - - - - - - - - - - - - - - N P P - - - - N - - - - P P P - - - - - - HMB45 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N - N - - - - - - - - - - - - - CD56 CD99 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N - - - - - - - - - - - - - - - BC - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N - - - - - N - - - - - - - - 8300 Int J Clin Exp Pathol 2016;9(8):8297-8307

  5. Clinical outcomes of undifferentiated sarcoma Table 4. Histologic grades of US and sarcomas of control Histologic types No. (%) Tumor gradea 2 9 12 0 1 15 (30.6) 3 4 0 Total p-valued 1 0 0 0 0 3 15 7 5 0 US Pleomorphic Spindle Epithelioid Round Total 24 (49.0)b 19 (38.8) 5 (10.2) 1 (2.0) 49 (100.0) 3 (8.8)c 4 (11.8) 6 (17.6) 0 (0.0) 0 0 0 34 (69.4) 0 0 6 Fibrosarcoma Myxofibrosarcoma Dedifferentiated liposarcoma Leiomyosarcoma MPNST Synovial sarcoma Total a. Tumor grades were based on FNCLCC system; b. Percentage within US; c. Percentage within non-US including fibrosarcoma, myxofibrosarcoma, Leiomyosarcoma, MPNST and synovial sarcoma; d. Chi-square test. 0 0 0 3 0 5 2 5 6 5 (14.7) 5 (14.7) 11 (32.4) 34 (100.0) 0 (0.0) 15 (44.1) 19 (55.9) 0.827 Figure 1. Histologic types of undifferentiated sarcoma. Pleomorphic type shows bizarre cytology and multinucleated giant cells as dominant morphology (A). Spindle cell type is characterized by fascicular pattern of spindle cells (B). Epithelioid type is composed of tumor cells which are similar to metastatic carcinoma or mesothelioma (C). Round cell type is consisted with homogenous small round cell pattern (D). 8301 Int J Clin Exp Pathol 2016;9(8):8297-8307

  6. Clinical outcomes of undifferentiated sarcoma Table 5. Sites of US and sarcomas of control No. (%) DLS 2 (33.3) 0 (0.0) 2 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (66.7) 1 (16.7) 3 (50.0) 6 (100.0) Sites US FS MFS LMS 3 (60.0) 1 (20.0) 2 (40.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (40.0) 0 (0.0) 2 (40.0) 5 (100.0) MPNST 3 (60.0) 1 (20.0) 2 (40.0) 1 (20.0) 0 (0.0) 1 (20.0) 0 (0.0) 0 (0.0) 1 (20.0) 0 (0.0) 1 (20.0) 5 (100.0) SS Extremities Upper Lower Trunk Neck CW Back Abd IA O/M RP Total a. Percentage within individual sarcoma US, undifferentiated sarcoma; FS, fibrosarcoma; MFS, myxofibrosarcoma; DLS, dedif- ferentiated liposarcoma; LMS, leiomyosarcoma; MPNST, malignant peripheral nerve sheath tumor; SS, synovial sarcoma; CW, chest wall; Abd, abdominal wall; IA, intraabdominal; O/M, omentum/mesentery; RP, retroperitoneum. 34 (69.4)a 5 (10.2) 29 (59.2) 9 (18.4) 2 (4.1) 4 (8.2) 2 (4.1) 1 (2.0) 6 (12.2) 2 (4.1) 4 (8.2) 49 (100.0) 2 (66.7) 2 (66.7) 0 (0.0) 1 (33.3) 0 (0.0) 0 (0.0) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (100.0) 4 (100.0) 1 (25.0) 3 (75.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (100.0) 11 (100.0) 3 (27.3) 8 (72.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 11 (100.0) (Figure 2E). Survival difference between grade 2 and 3 among total sarcomas which included US and non-US was also insignificant (P=0.146) (Figure 2F; Table 6). undifferentiated epithelioid sarcoma, and undi- fferentiated sarcoma, NOS [1, 5]. US is known as aggressive sarcoma, and occu- py 20% of sarcomas, and most frequently aris- ed in extremities [1, 5]. Also, US is known as most common soft tissue sarcoma which occurs in older adult [6]. But, precise percent- age of this tumor is still in controversy [7]. Recent report from Syria listed the percen- tages of sarcomas as malignant fibrous histio- cytoma (23%), liposarcoma (22%), rhabdomyo- sarcoma (9%), leiomyosarcoma (8%), malignant schwannoma (5%), dermatofibrosarcoma pro- tuberans (5%), synovial sarcoma (10%), fibro- sarcoma (13%), extraskeletal chondrosarcoma (1%), and extraskeletal Ewing sarcoma (4%) [3]. When compared with this data, we could notice that diagnostic rate of US was somewhat high- er in this institute. According to the statistical data from Jamaica, sarcoma, not otherwise specified (NOS) occupied 20.1% and MFH was 17.9% [8]. If these cases were gathered in one category, it became similar diagnostic rate with that of our study. According to a report, pediat- ric US is characterized by predominant round cell type, but comparison with our case is not feasible because of small number of round cell type in our study [9]. Altogether, the epidemio- logic reports about US are not sufficient. Comprehensive statistical study in USA showed similar incidences of various sarcomas with our results [10]. Report in Nigeria showed that inci- dence of sarcomas was 11.3% of all sarcomas, As the overall survivals were examined in the aspect of metastasis, cases with metastasis showed worse prognosis than cases without metastasis among total sarcomas which includ- ed US and non-US (P=0.001) (Figure 3A). Among the cases without metastasis, there was no survival difference between US and non-US (P=0.305) (Figure 3B). Among the cases with metastasis, there was no survival difference between US and non-US too (P=0.218) (Figure 3C). Among non-US, cases with metastasis showed worse prognosis than cases without metastasis (P=0.036) (Figure 3D) and same result was found among US (P=0.009) (Figure 3E; Table 6). Discussion Diagnostic term of US changed several times. In the previous editions of WHO classification, malignant fibrous histiocytoma (MFH) and high grade undifferentiated pleomorphic sarcoma were used as diagnostic terms [4]. At 2013 edi- tion of WHO classification, these tumors are grouped under the term of undifferentiated sar- coma (US). Under the name of US, WHO classi- fication includes undifferentiated round cell sarcoma, undifferentiated spindle cell sarco- ma, undifferentiated pleomorphic sarcoma, 8302 Int J Clin Exp Pathol 2016;9(8):8297-8307

  7. Clinical outcomes of undifferentiated sarcoma 8303 Int J Clin Exp Pathol 2016;9(8):8297-8307

  8. Clinical outcomes of undifferentiated sarcoma Figure 2. In the aspects of overall survival, there was no difference between US and non-US (P=0.362) (A). Among the grade 2 tumors, there was no difference between them (P=0.562) (B) and showed same result among the grade 3 (P=0.552) (C). Among non-US, there was no difference between grade 2 and 3 (P=0.378) (D) and showed same result with US (P=0.392) (E). Survival difference between grade 2 and 3 among total sarcomas which included US and non-US was also insignificant (P=0.146) (F). sufficient. Other report insisted that more than 30% of metastatic rate could be estimated [12]. Overall sur- vival of US was not significantly dif- ferent with other high grade sarco- mas in this study. At present, progno- sis of these tumors may be more dependent on adequate surgical treatment [13]. Table 6. Comparisons of overall survival between US and non-US Histologic types No. (%) Non-US Mean survival (M) ± SD 141.968 ± 11.045 p-value 34 US 49 117.505 ± 13.496 0.362 Non-US, grade 2 15 152.000 ± 13.348 US, grade 2 15 127.250 ± 14.611 0.562 Non-US, grade 3 19 82.885 ± 11.130 There are some controversies about the diagnosis of US. For example, if Murine double-minute 2 (MDM2) amplification was identified by immu- nohistochemistry or by molecular method, this tumor should be con- sidered as dedifferentiated sarc- oma [14]. Even though US was fina- lly diagnosed, there still remain the possibility of other disease entity. As said before, presence of other spe- cific line of differentiation, possibility of dedifferentiated sarcoma, and possibility of non-mesenchymal neo- plasm, especially sarcomatoid carci- noma should be considered before diagnosis of US is made. In this study, although histological findings were matched with US, studies about the specific line of differentiation were not sufficiently done in some cases as seen in the immunohisto- chemical results. We think that the supplimentation of this point should be made. US, grade 3 34 111.296 ± 16.392 0.552 Non-US, grade 2 15 152.000 ± 13.348 Non-US, grade 3 19 82.885 ± 11.130 0.378 US, grade 2 15 127.250 ± 14.611 US, grade 3 34 111.296 ± 16.392 0.392 Non-US and US, grade 2 30 142.139 ± 12.278 Non-US and US, grade 3 53 117.645 ± 12.589 0.146 Non-US and US, without meta 66 142.391 ± 9.151 Non-US and US, with meta 17 45.094 ± 6.797 0.001 Non-US, without meta 25 157.000 ± 8.731 US, without meta 41 134.658 ± 12.542 0.305 Non-US, with meta 9 51.875 ± 9.331 US, with meta 8 32.688 ± 7.123 0.218 Non-US, without meta Non-US, with meta 25 157.000 ± 8.731 9 51.875 ± 9.331 0.036 US, without meta 41 134.658 ± 12.542 US, with meta 8 32.688 ± 7.123 0.009 US, undifferentiated sarcoma; non-US, spindle cell sarcomas other than US. and among them US occupied 21.1% of all sar- comas. Their prevalent sites were lower extrem- ities [11]. For the strict limitation of the ranges of US, we should provide some strategies. At first, clinical and pathological informations should be metic- ulously examined. For example, in the case of high grade sarcoma found in intraabdominal site without evidence of definite line of differen- tiation, the possibility of dedifferentiated sar- coma should be considered as a differential diagnosis. In this study, considerable portion of intraabdominal sarcomas were dedifferentiat- ed sarcoma. If there was history of carcinoma in certain case, the possibility of metastatic Clinically, age and sex distributions of US in this study were similar with other specific high grade sarcomas. This study showed 12.2% of metastatic ratio with lung and bone as domi- nant target organs. Comparisons of metastatic ratios with other sarcomas were not feasible because there were so many kinds of specific sarcomas and their numbers of cases were not 8304 Int J Clin Exp Pathol 2016;9(8):8297-8307

  9. Clinical outcomes of undifferentiated sarcoma Figure 3. As the overall survivals were examined in the aspect of metas- tasis, cases with metastasis showed worse prognosis than cases without metastasis among total sarcomas including US and non-US (P=0.001) (A). Among the cases without metastasis, there was no survival differ- ence between US and non-US (P=0.305) (B). Among the cases with metastasis, there was no survival difference between US and non-US too (P=0.218) (C). Among non-US, cases with metastasis showed worse prognosis than cases without metastasis (P=0.036) (D) and same result was found among US (P=0.009) (E). 8305 Int J Clin Exp Pathol 2016;9(8):8297-8307

  10. Clinical outcomes of undifferentiated sarcoma carcinoma in the form of high sarcomatoid car- cinoma should be considered. In this case, use of wide range immunohistochemical panel con- taining several antibodies for the detection of epithelial differentiation may be great help for the differential diagnosis. As shown in immuno- histochemical results, in many cases of this study, immunohistochemical studies for the epithelial differentiation were not done. We think some kind of cytokeratin should be includ- ed in the immunohistochemical panel to diag- nose US. If histologic findings such as myxoid change and complex capillary pattern were found, myxofibrosarcoma can be a possible diagnosis. Immunohistochemically, brand-new antibodies can be useful in the differential diagnosis. As mentioned above, MDM2 is known as associated with atypical lipomatous tumor and dedifferentiated liposarcoma which is closely related with atypical lipomatous tumor [14, 15]. In certain cases of myxofibro- sarcoma, AMACR amplification was identified [16]. Other report showed that LMP2/beta-1i and cyclin B1 can be useful for the diagnosis of uterine leiomyosarcoma [17], but the applica- tion for the cases of soft tissue leiomyosarco- ma is not known. Acknowledgements This work was performed with aids of the staffs of department of pathology, St. Vincent Hos- pital. Disclosure of conflict of interest None. Address correspondence to: Dr. Changyoung Yoo, Department of Pathology, The Catholic University of Korea, St. Vincent Hospital, 93-6, Jungbudaero, Paldal-gu, Suwon, Gyeonggi-do 442-723, Korea. Tel: 031-249-7646; Fax: 031-244-6786; E-mail: ppgg2@catholic.ac.kr References [1] Fletcher, CDM, Bridge JA, Hogendoorn PCW, Mertens F. WHO Classification of Tumours of Soft Tissue and Bone. 4th edition. Lyon: IARC Press; 2013. John R Goldblum, et al. Enzinger and Weiss’s Soft tissue tumors. 6th edition. Philadelphia: Elsevier Saunders; 2014. Reshadi H, Rouhani A, Mohajerzadeh S, Moosa M, Elmi A. Prevalence of malignant soft tissue tumors in extremities: an epidemiological study in syria. Arch Bone Jt Surg 2014; 2: 106- 10. Fletcher CDM, Unni KK, Mertens F. Pathology and genetics of tumors of soft tissue and bone. Lyon: IARC press; 2002. Delisca GO, Mesko NW, Alamanda VK, Archer KR, Song Y, Halpern JL, Schwartz HS, Holt GE. MFH and high-grade undifferentiated pleomor- phic sarcoma-what's in a name? J Surg Oncol 2015; 111: 173-7. Becerikli M, Wieczorek S, Stricker I, Nambiar S, Rittig A, Epplen JT, Tannapfel A, Lehnhardt M, Steinstraesser L, Jacobsen F. Numerical and structural chromosomal anomalies in undiffer- entiated pleomorphic sarcoma. Anticancer Res 2014; 34: 7119-27. Goldblum JR. An approach to pleomorphic sar- comas: can we subclassify, and does it mat- ter? Mod Pathol 2014; 27 Suppl 1: S39-46. Gibson TN, Hanchard B, Waugh N, McNaughton D. A fifty-year review of soft tissue sarcomas in Jamaica: 1958-2007. West Indian Med J 2012; 61: 692-7. Somers GR, Gupta AA, Doria AS, Ho M, Pereira C, Shago M, Thorner PS, Zielenska M. Pediatric undifferentiated sarcoma of the soft tissues: a clinicopathologic study. Pediatr Dev Pathol 2006; 9: 132-42. [10] Ng VY, Scharschmidt TJ, Mayerson JL, Fisher JL. Incidence and survival in sarcoma in the [2] [3] Recently, molecular pathology has appeared as important diagnostic method. Already, many important genetic translocations were identi- fied and used as diagnostic markers using fluo- rescent in situ hybridization (FISH). Not only the translocations, but also complex genetic abnor- malities were found [18, 19]. Some kind of genetic abnormalities were reported for US [20- 22], but their diagnostic values are investiga- tional. Collectively, US in this institute showed higher diagnostic rate than preexisting but lim- ited reports. To establish accurate epidemiolo- gy of US in stricter range, not only clinical and pathological examination, but also reinforce- ment and supplementation in the field of immu- nohistolochemistry and especially molecular pathology is mandatory. It may be certain that there will be no great changes in classification and differential diagnosis of US even though discrimination of specific sarcomas from US is important task of pathologists. Because US and other spindle cell sarcoma showed similar clinical outcomes according to this study, clini- cal approaches for US could be safely followed that of other high grade sarcomas. We hope this study could contribute to be a data base about US and useful data for further research. [4] [5] [6] [7] [8] [9] 8306 Int J Clin Exp Pathol 2016;9(8):8297-8307

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