Soft tissue sarcomas are rare malignancies of mesenchymal origin, with an estimated annual incidence in the United States of 13,040, or fewer than 1% of all cancer diagnoses.1 Soft tissue sarcomas are often presumed to be benign and are resected without the typical preoperative workup, such as imaging or biopsy. These unplanned resections occur in approximately 30% of all cases and frequently require further morbid treatments, resulting in worse oncologic outcomes. They often present as a large, slow- or fast-growing mass, and they are not always accompanied by pain.2,3 Current recommendations suggest referral to a specialist when any of the following features are present: increasing size, size greater than 5 cm, or pain.4,5 Because they are so rare, many soft tissue masses are presumed to be benign and are resected without obtaining a complete preoperative workup, such as magnetic resonance imaging and biopsy. When the workup is not completed before tumor excision, the principles of sarcoma excision, such as meticulous hemostasis, wide resection, and extensile incisions, are not typically followed. Any tumor that is surgically manipulated without preoperative imaging or regard for the necessity to resect the tumor with a margin of normal tissue is referred to as an unplanned resection.6–8 Unplanned resections often leave patients with positive surgical margins and a widely contaminated field.9 In addition, improper incision placement can cause further soft tissue contamination. For any mass that is undergoing resection, the incision should be longitudinal. Transverse incisions risk contaminating adjacent muscles, resulting in the need for expanded subsequent wide resection. Unplanned resection can lead to a cascade of errors, with catastrophic consequences for the patient, including wide resection and limb amputation; however, the effect of local recurrence on mortality remains controversial.10,11 A significant financial burden can be associated with unplanned resection.12 Unfortunately, the rate of unplanned resection remains high, occurring in 18% to 71% of all reported cases.13–16
Materials and Methods
After institutional review board approval was obtained, a retrospective review was performed of all patients who presented to a tertiary sarcoma center with a diagnosis of sarcoma between 1996 and 2017. This search spanned 2 separate electronic medical records, including Epic (Epic Systems Corporation) and CareWeb (University of Michigan Health System), which is no longer used at the authors' institution. With use of an electronic medical record search engine (EMERSE; University of Michigan Health System), 2600 patients were identified and in-depth chart reviews were performed, including all pertinent documentation, imaging, and pathology reports. Inclusion criteria consisted of a primary diagnosis of soft tissue sarcoma in an upper or lower extremity. Included patients also had to have complete records, including known histologic type, size, and grade of soft tissue sarcoma. Exclusion criteria included incomplete data for these study variables (12 patients were excluded for unknown unplanned resection status) and a primary sarcoma site that was not in an extremity, such as the abdomen, retroperitoneum, thorax, pelvis, or axilla. Chart reviews for all 2600 patients were conducted by 1 of 6 members of the research team (P.G., J.N., N.W., C.M., C.R., J.K.). If the assigned member of the team did not find any of the individual data points that were being collected, a second member of the team performed a second, independent chart review. A similar process occurred for ambiguous data or multiple entries with differing information, until consensus was reached.
In total, 836 of the 2600 patients who were reviewed met the inclusion criteria. Data collected for each patient included demographic information, such as age at the time of referral and sex, in addition to tumor size, histologic type, and grade. Also recorded was whether an unplanned resection was performed. In attempting to discern whether a patient had undergone an unplanned resection, the authors searched the medical records. If a mass greater than 5 cm was excised without a preoperative biopsy or advanced imaging and was found to be a soft tissue sarcoma, it was determined that the patient had undergone an unplanned re-section. When a mass measuring less than 5 cm was excised and malignancy was found incidentally, this was also considered an unplanned resection, although current recommendations do not mandate advanced imaging for masses of this size. If a patient underwent advanced imaging and biopsy and the specimen was later found to have positive margins, this was not considered an unplanned resection.
The size of the tumor was measured in 3 dimensions, with the largest dimension documented as the tumor size for the purposes of this study. Measurements typically were obtained through radiology reports of advanced imaging, such as magnetic resonance imaging or computed tomography; however, if imaging with measurements was unavailable, pathology reports were used to determine the tumor size. If neither imaging nor pathology reports mentioned size, the size was recorded as unknown. In some cases, only 1 or 2 dimensions were recorded. In these cases, the largest dimensions were used as the documented size. Because of the current recommendations for tumor size and referral to a tertiary sarcoma center, tumor size was divided into 2 categories—5 cm or greater and less than 5 cm.
The histologic features of the soft tissue sarcomas were recorded based on in-house pathology reports. When diagnoses differed between an outside pathology report and the report completed at the authors' tertiary sarcoma center, the latter diagnosis was used. If only the outside report was available, that diagnosis was used. All pathology reports were generated from biopsy specimens, surgical specimens, or both. A total of 27 unique soft tissue sarcoma pathology types were identified for the purpose of this study (Table 1). Any histology category that included 5 or fewer patients was recorded as “other” because the sample was too small to allow calculation of statistical significance. If no pathology report included a definitive diagnosis, the rest of the medical record was searched to determine the diagnosis, including notes from oncology providers and orthopedic oncologists.
Histologic Findings and Unplanned Resection
Tumor grade was determined similarly by using the pathology reports and through chart review. If available, in-house pathology reports were preferred over reports from other institutions. If no pathology report from the authors' tertiary sarcoma center was found, the report from the other institution was used. Pathology reports from biopsy and/or surgical specimens were used. If the pathology report did not mention the tumor grade, the authors searched in other locations of the chart, including clinic notes from medical and surgical oncologists. Tumor grade was recorded as high (grade III), intermediate (grade II), or low (grade I).
Metastasis was recorded for all patients who were determined to have undergone unplanned resection and who underwent routine follow-up for 5 years. Patients who were lost to follow-up after surgery were not included. Mortality as a result of metastatic disease was recorded on the basis of documentation in the electronic medical record or obituaries written within 1 year of metastatic disease and cessation of treatment.
The authors examined their referral rate for unplanned resection vs planned resection from 1996 to 2006 and compared that rate with their referral rate for unplanned resection vs planned resection from 2007 to 2017.
Descriptive and inferential statistical analysis was performed with SPSS, version 25.0, software (IBM). First, the authors described demographic and related characteristics across included patients with raw counts, measures of central tendency (eg, mean, median, or mode), and measures of data dispersion (eg, 95% CI, standard error) where appropriate. The primary method of analysis was the chi-square test or Fisher's exact test to examine the association between unplanned resection and tumor grade, histologic type, and size.
Mean age of all patients was 54.1 years (range, 2–94 years). More men (n=487, 58.3%) than women (n=349, 41.7%) were included in the study.
After final screening, 848 patients had a primary diagnosis of soft tissue sarcoma of the upper or lower extremity. Of these 848, 12 patients had no other data that could be used for the purposes of this study and therefore were excluded, leaving a total of 836 patients to be analyzed. Of these 836 patients, 219 (26.2%) underwent unplanned resection.
Of the 219 patients who underwent unplanned resection, 31 were excluded because of incomplete data or unavailable operative reports, leaving 188 patients. General surgery referred 58 (30%) patients to the authors' institution. Orthopedic surgery was the referring specialty for 27 (14%) patients.
Histologic Features and Unplanned Resection
For the purposes of this study, the authors classified all histopathologic types of soft tissue sarcoma into 27 categories. Myxofibrosarcoma was the most common type to undergo unplanned resection (Table 1).
Tumor Grade and Unplanned Resection
Of the 836 patients, 783 had a known tumor grade (93.6%). Of the patients, 166 had a grade I tumor (21.2%), 32 had a grade II tumor (4.1%), and 585 had a grade III tumor (74.7%). Unplanned re-section was performed for 44 of 166 (26.5%) grade I tumors, 9 of 32 (28.1%) grade II tumors, and 144 of 572 (25.2%) grade III tumors. Pearson chi-square analysis determined that this finding was not significant (P=.806).
Morbid Re-Resection and Unplanned Resection
Of the previously reported 188 patients who underwent unplanned resection, 12.7% (24 of 188) had amputation, 33.0% (62 of 188) had flap coverage, and 11.7% (22 of 188) had skin grafting. When accounting for tumor grade, the authors noted that amputation occurred at a rate of 16.5% (23 of 139) for grade III tumors, 0% (0 of 9) for grade II tumors, and 2.5% (1 of 40) for grade I tumors. When accounting for tumor grade in flap coverage, the authors found a rate of 39.6% (55 of 139) for grade III tumors, 0% (0 of 9) for grade II tumors, and 17.5% (7 of 40) for grade I tumors. When accounting for grade in skin graft coverage, the authors found a rate of 13.7% (19 of 139) for grade III tumors, 1.1% (1 of 9) for grade II tumors, and 0.5% (2 of 40) of grade I tumors. Rates of morbid re-resection were significantly higher for grade II and III tumors (66.2%; 98 of 148) compared with grade I tumors (25.0%; 10 of 40) (P<.05).
Metastasis and Mortality Rate
Of the 188 patients who underwent unplanned resection, 34 were lost to follow-up after surgery. Except for 2 occurrences in grade II tumors, the authors observed metastasis only in grade III tumors. A total of 50.5% (53 of 105) patients who had a grade III tumor and underwent unplanned resection had metastatic disease within 5 years of re-section. Mortality occurred as a result of metastatic disease in 29.9% (32 of 107) of the patients, and 4 other patients died of other causes. The remaining patients who had metastatic disease were alive at the time of this writing.
Tumor Size and Unplanned Resection
Tumor size ranged from 0.4 to 54.0 cm. Of the 836 patients, 778 showed size measurements (93.1%). Of the 226 (27.0%) patients who had a tumor measuring less than 5 cm, 94 underwent unplanned resection (41.6%). Of the 552 (66.0%) patients who had a tumor measuring 5 cm or greater, 104 underwent unplanned resection (18.8%). The difference between these groups was tested with a 2-sided Pearson chi-square test and was statistically significant (P<.001), with smaller tumors more likely to undergo unplanned resection. Within the morbidity group, 73 patients with a grade III tumor measuring 5 cm or greater had undergone unplanned resection, with 58.9% (43 of 73) of patients requiring morbid re-resection surgery. Patients with a grade III tumor measuring less than 5 cm who underwent unplanned resection had a morbid re-resection rate of 60.6% (40 of 66). This difference was not statistically significant (P=.838). The rate of metastatic disease for patients with a grade III tumor measuring greater than 5 cm who underwent unplanned resection was 50.7% (37 of 73), whereas the rate of metastatic disease among patients with a grade III tumor measuring less than 5 cm who underwent unplanned resection was 19.7% (13 of 66) (P<.001).
Rates of Unplanned Resection During the Past Two Decades
The authors analyzed the rates of unplanned resection for patients who had been referred to their institution after an unplanned resection compared with that for patients who were referred to them for planned resection. A total of 296 referrals occurred between 1996 and 2006, and 531 referrals occurred between 2007 and 2017. Of the patients who were referred between 1996 and 2006, 30.0% (89 of 296) had undergone unplanned resection. In the group of patients referred between 2007 and 2017, 23.9% (127 of 531) had undergone unplanned resection. A chi-square test for independence found no significant difference between rates of unplanned resection in the 2 groups (P=.053).
Soft tissue sarcomas are rare malignancies; therefore, front-line clinicians often do not consider them in the differential diagnosis. As a result, there can be misdiagnosis and substandard initial treatment, including unplanned resection, which potentially can lead to worse oncologic outcomes. These patients often require morbid re-resection and have a higher likelihood of local recurrence, which has been well reported.17
In studies that controlled for tumor grade in unplanned resection, multiple authors have shown significantly increased rates of mortality and metastasis compared with planned resection. Grade III tumors with unplanned resection have significantly higher rates of mortality and metastasis compared with those with planned resection. Rates of metastasis in these studies ranged from 24% to 33% for grade III tumors.13,18,19 The current authors found that high-grade tumors accounted for most of the morbidity and all of the mortality among patients with unplanned resection. They found a significant difference in mortality rates among patients who underwent unplanned resection of a grade III sarcoma measuring 5 cm or greater (50.7%) compared with a tumor measuring less than 5 cm (19.7%) (P<.001). This finding is in keeping with other retrospective studies showing that larger sarcomas have higher metastatic potential than smaller sarcomas.20
In the current study, the authors defined morbid re-resection surgery as amputation, flap coverage, or skin grafting. When they combined grade II and II sarcomas and evaluated the rate of morbid re-resection against that for grade I sarcomas, the difference was statistically significant. They did not find a statistically significant difference between the rate of unplanned resection of grade III tumors measuring 5 cm or greater (58.9%) and that of those measuring less than 5 cm (60.6%) that required morbid reresection surgery. This finding highlights the idea that sarcomas measuring less than 5 cm that undergo unplanned resection still have a significant effect on morbidity rates.
Oncologic societies that specialize in sarcoma-type cancers have developed educational awareness campaigns to help front-line providers to recognize the warning signs of soft tissue sarcoma. However, unplanned resection still occurs in approximately one-third of all sarcomas. Among the current patients, the authors found a decrease in rates of referral for unplanned resection between the period of 2007 to 2017 compared with 1996 to 2006, although this difference was not statistically significant. They also found that general surgery made up a larger portion of the referral base (30%) compared with orthopedic surgery (14%). This finding indicates that although rates of unplanned resection are declining, more work is needed to decrease the rates further, and additional education is needed for both general and orthopedic surgeons.
Arguably, among the best educational awareness campaigns was the idea that clinicians should refer all soft tissue masses that are larger than a golf ball to a tertiary sarcoma center for evaluation and treatment. Part of the impetus to perform this study was to evaluate the effectiveness of that campaign. Golf balls are just smaller than 5 cm in diameter and are easily recognized by medical professionals. The authors found that the unplanned resection rate for masses larger than 5 cm was 18.8%, which was lower than that for many other sites, although still high. Their unplanned resection rate for masses that did not meet the golf ball criterion was 41.6%, with a statistically significant (P<.001) difference between the 2 groups. During the past 20 years, they had 296 referrals from 1996 to 2006 and 531 referrals from 2007 to 2017. Of the group of patients who were referred between 1996 and 2006, 30.0% (89 of 296) underwent unplanned resection. In the group of patients who were referred between 2007 and 2017, 23.9% (127 of 531) underwent unplanned resection. This difference approached statistical significance (P=.053). This finding could be interpreted as showing the success of the “golf ball campaign” in that clinicians more often recognized larger soft tissue sarcomas and referred the patients to specialists at cancer centers. However, this finding also indicated that simple rubrics, such as size larger than a golf ball, can lull providers into a false sense of security. Therefore, all treating surgeons should continue to have a high index of suspicion for soft tissue sarcomas and use their best clinical judgment, even when treating small tumors. Educating practicing clinicians about soft tissue sarcoma is likely necessary, especially for smaller soft tissue masses. Of course, this retrospective study had the limitation of being biased by the number of referrals for soft tissue sarcoma at the authors' institution. The authors recognize that many more benign masses measuring less than 5 cm are removed in their catchment area and never present to them for evaluation.
Nagano et al21 reported on the efficacy of ultrasound for the diagnosis of soft tissue sarcoma, with a scoring system based on size, echogenicity, internal texture, and Doppler pattern. They found that their scoring system had high sensitivity in screening for soft tissue sarcomas.21 Another study compared ultrasound findings when evaluating for high- vs low-grade malignancy in soft tissue masses.22 A significant difference in tumor margin, echo-genicity, and vascularity was observed when distinguishing between high- and low-grade sarcomas. Ultrasound could be an effective modality in screening for soft tissue sarcomas should further literature support its efficacy. The current data support the morbid effects of unplanned re-section on sarcomas measuring less than 5 cm. Guidelines supporting ultrasound imaging of all masses, regardless of size, before resection could be beneficial to patients in decreasing morbidity and mortality rates by preventing unplanned resection of soft tissue sarcomas.
The authors were intrigued by the relationship between unplanned resection and specific histologic subtype. This finding is likely a byproduct of the rarity of these tumors, although special attention should be paid to myxoid liposarcomas and myxofibrosarcomas. Myxoid liposarcomas can be easily confused with other lipomatous tumors, which may reflect the high rate of unplanned resection. Controversially, the authors distinguished between myxoid liposarcoma and myxoid round cell liposarcoma. Myxofibrosarcomas tend to grow in a more infiltrative pattern than other types of soft tissue sarcoma, and this tendency may contribute to a higher rate of unplanned resection with positive margins than is seen with other subtypes. For these reasons, more research is necessary to allow meaningful conclusions to be drawn about subtypes of soft tissue sarcoma.
Many factors are part of the evaluation and treatment of soft tissue masses of all sizes. Many patients do not want to travel to the nearest sarcoma center, which, in the authors' state, could involve a 10-hour drive. Many insurance companies do not approve advanced imaging studies for small masses and may hesitate to approve an image-guided biopsy for a small mass.
Limitations of this study included small samples for some pathology types. In addition, the study was performed at a single institution with a singular pathology evaluation (albeit by dedicated experts in the field). Also, the study was retrospective and was performed in a single region with a large, fragmented catchment zone, suggesting the possibility of poor follow-up.
Educational awareness campaigns have come a long way, but a national or international consensus about the treatment of all soft tissue masses, regardless of size, is needed. Although soft tissue sarcomas are rare, missing the diagnosis is disastrous for the patient in terms of morbidity and for insurance companies in terms of cost. National and international sarcoma societies should work toward developing an easy-to-follow consensus guideline for the evaluation and treatment of soft tissue masses that can be disseminated to all providers and set as the standard of care for all insurance companies. The authors have shown that simple rubrics, such as bigger than a golf ball, can lull practitioners into a false sense of security about smaller masses. The authors recommend studying the utility and cost-effectiveness of promoting ultrasound evaluation before resection of any mass measuring less than 5 cm.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68 (1):7–30. doi:10.3322/caac.21442 [CrossRef] PMID:29313949
- Han I, Kang HG, Kang SC, Choi JR, Kim H-S.Does delayed reexcision affect outcome after unplanned excision for soft tissue sarcoma?Clin Orthop Relat Res.2011;469(3):877–883. doi:10.1007/s11999-010-1642-8 [CrossRef] PMID:21046299
- Hussein R, Smith MA. Soft tissue sarcomas: are current referral guidelines sufficient?Ann R Coll Surg Engl.2005;87(3):171–173. doi:10.1308/1478708051658 [CrossRef] PMID:15901376
- Musculoskeletal Tumor Society. Information Statement: Inappropriate Excision of Unrecognized Soft Tissue Sarcoma. msts.org. Accessed November 19, 2018. http://msts.org/view/download.php/education/pdfs/inappropriate-excision-of-unrecognized-soft-tissue-sarcoma
- Dangoor A, Seddon B, Gerrand C, Grimer R, Whelan J, Judson I. UK guidelines for the management of soft tissue sarcomas. Clin Sarcoma Res. 2016;6(1):20. doi:10.1186/s13569-016-0060-4 [CrossRef] PMID:27891213
- Giuliano AE, Eilber FR. The rationale for planned reoperation after unplanned total excision of soft-tissue sarcomas. J Clin Oncol. 1985;3(10):1344–1348. doi:10.1200/JCO.19184.108.40.2064 [CrossRef] PMID:4045526
- Noria S, Davis A, Kandel R, et al. Residual disease following unplanned excision of soft-tissue sarcoma of an extremity. J Bone Joint Surg Am. 1996;78(5):650–655. doi:10.2106/00004623-199605000-00003 [CrossRef] PMID:8642020
- Tedesco NS, Henshaw RM. Unplanned re-section of sarcoma. J Am Acad Orthop Surg. 2016;24(3):150–159. doi:10.5435/JAAOS-D-15-00074 [CrossRef] PMID:26761037
- Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol. 1996;14(5):1679–1689. doi:10.1200/JCO.19220.127.116.119 [CrossRef] PMID:8622088
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- Potter BK, Adams SC, Pitcher JD Jr, Temple HT. Local recurrence of disease after unplanned excisions of high-grade soft tissue sarcomas. Clin Orthop Relat Res. 2008;466(12): 3093–3100. doi:10.1007/s11999-008-0529-4 [CrossRef] PMID:18818981
- Alamanda VK, Delisca GO, Mathis SL, et al. The financial burden of reexcising incompletely excised soft tissue sarcomas: a cost analysis. Ann Surg Oncol. 2013;20(9): 2808–2814. doi:10.1245/s10434-013-2995-5 [CrossRef] PMID:23636515
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- Rougraff BT, Davis K, Cudahy T. The impact of previous surgical manipulation of subcutaneous sarcoma on oncologic outcome. Clin Orthop Relat Res. 2005;438(438):85–91. doi:10.1097/00003086-200509000-00016 [CrossRef] PMID:16131874
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Histologic Findings and Unplanned Resection
|Histologic finding||No.||Unplanned resection|
|Total no.||Unplanned resection||No unplanned resection|
|Alveolar soft part||6||2||4||33.33%|
|Extraskeletal myxoid chondrosarcoma||7||1||6||14.29%|
|Myxoid round cell liposarcoma||12||4||8||33.33%|
|Peripheral nerve sheath tumor||20||7||13||35.00%|
|Undifferentiated pleomorphic sarcoma||190||50||140||26.32%|