gms | German Medical Science

GMS German Plastic, Reconstructive and Aesthetic Surgery – Burn and Hand Surgery

Deutsche Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC)
Deutsche Gesellschaft für Verbrennungsmedizin (DGV)

ISSN 2193-7052

Tumor type resulting in upgrade: An analysis based on 333 low grade soft tissue sarcoma

Eine Analyse des Gradingwechsels auf Basis von 333 chirurgisch therapierten niedrigmalignen Weichgewebssarkomen

Research Article

  • corresponding author Stefan Langer - Department of Plastic and Hand Surgery, Burn Center, University Hospital Bergmannsheil, Ruhr University Bochum, Germany; Department of Plastic Surgery, University Hospital Leipzig, Germany
  • Nick Spindler - Department of Plastic and Hand Surgery, Burn Center, University Hospital Bergmannsheil, Ruhr University Bochum, Germany; Department of Plastic Surgery, University Hospital Leipzig, Germany
  • Hans Ulrich Steinau - Department of Plastic and Hand Surgery, Burn Center, University Hospital Bergmannsheil, Ruhr University Bochum, Germany
  • Andrea Tannapfel - Department of Pathology, BG University Hospital Bergmannsheil, Ruhr University Bochum, Germany
  • Ingo Stricker - Department of Pathology, BG University Hospital Bergmannsheil, Ruhr University Bochum, Germany

GMS Ger Plast Reconstr Aesthet Surg 2014;4:Doc08

doi: 10.3205/gpras000027, urn:nbn:de:0183-gpras0000277

Veröffentlicht: 27. November 2014

© 2014 Langer et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Introduction: Soft tissue sarcomas (STS) are rare tumors. Based on histopathological criteria, three grades are distinguished from low (G1) to intermediate (G2) and high grade (G3). After complete initial surgical resection, some G1 STS recur as lesions with an upgrade of a previous G1 STS to a recurrent G2 STS. This upgrade indicates higher malignancy of the STS. Our aim was to find possible risk factors for these upgrades including age, localization of tumor and tumor type.

Methods: This retrospective case-control study evaluated 333 patients. Of these 333, 54.7% were male and 45.3% female. All patients underwent R0 resections and among these, 10% subsequently upgraded. The processed data include age, gender, tumor type, tumor localization, local recurrence and upgrade.

Results: Patients with upgrades have a higher mean age of 5.5 years than our reference collective. The tumor type has a significant effect on upgrades. Patients with fibrosarcomas are at a threefold risk of an upgrade compared to patients with other G1 STS.

Conclusion: Our results indicate that age and tumor type play a key role in upgrades in G1 STS. Patients, age 60 and above and diagnosed with G1 fibrosarcomas, are three times as likely to upgrade compared to patients younger than 60 with other G1 STS. We discuss the significance of these risk factors and whether aside from complete tumor resection, additional therapies (e.g. irradiation) may be applied to improve therapeutic outcome.


Problem: Weichgewebssarkome gehören zu den seltenen malignen Neubildungen. Die chirurgische Resektion mit mikroskopisch tumorfreiem Resektionsrand stellt bei niedrigmalignen Weichgewebssarkomen bisher die Therapie der Wahl dar. Aufgrund ihrer niedrigen Inzidenz sind grundlegende Aspekte in der Ursache, Entstehung und Therapie dieser Tumoren noch weitgehend ungeklärt. Einige Patienten entwickeln zudem trotz chirurgischer Resektion Lokalrezidive, welche im Verlauf zu einer Prognoseverschlechterung führen können. Es gilt die Ursachen solcher Rezidive zu klären sowie Parameter zu ermitteln, welche diese möglicherweise begünstigen.

Methode: Es erfolgte eine retrospektive Analyse histopathologischer Befunde aller im Zeitraum von 1996 bis 2011 in der Klinik für Plastische Chirurgie, Bergmannsheil Bochum an niedrigmalignen Weichgewebssarkomen operativ behandelter Patienten. Untersuchte Daten umfassten Alter bei Diagnosestellung, Geschlecht, Tumorlokalisation sowie Tumorsubtyp.

Ergebnis: Patienten mit der Diagnose Fibrosarkom haben ein dreifach erhöhtes Risiko im Vergleich zu Patienten mit anderen Sarkomsubtypen an einem Lokalrezidiv mit Dedifferenzierung, einem sog. Gradingwechsel, zu erkranken.

Diskussion: Patienten, welche Risikofaktoren bezüglich Gradingwechseln aufweisen, müssen bei der Therapieplanung in besonderem Maße berücksichtigt werden. Zu solchen Risikofaktoren zählen neben der Diagnose Fibrosarkom auch ein fortgeschrittenes Lebensalter. Neben einer weiten chirurgischen Resektion stehen hier zusätzliche therapeutische Maßnahmen wie die Radiotherapie im Vordergrund.


Soft tissue sarcomas (STS) are a heterogeneous tumor group derived from non-epithelial extra skeletal tissue, striated muscle cells and connective tissue [1]. Embryologically, STS are mesenchyme derived tumors [2]. Unlike carcinomas, STS have a low incidence at 2.4 per 100,000 per year [3]. Preferred localizations of STS are lower extremity, thorax, upper extremity as well as the head and neck region [4]. Local recurrence and distant metastasis have a clear impact on patients’ prognosis. Thus, accurate grading and adequate therapy are essential to patients’ survival and quality of life [5]. STS show locally aggressive, destructive and invasive growth, a high recurrence rate, and distant metastasis. According to the guidelines of Trojani et al., tumor grading of STS is based on tumor type, tumor differentiation, mitosis count, and tumor necrosis [3]. A standard three grade system is defined by low malignant, intermediate malignant and high malignant STS (G1–G3) [3]. Due to the rare occurrence patients with low malignant STS often lack accurate diagnosis. Healthcare professionals may mistake low grade liposarcomas for benign lesions [5]. They may increase in size, infiltrate adjacent structures and produce distant metastasis [6]. Patients oftentimes consult a clinic when they are already suffering from secondary symptoms due to displacement of neighboring structures. At this point, the tumor may have changed its morphology to a higher grade and R0 resection crucial for curative therapy may have become impossible because of large, local infiltration. Moreover, if STS are not fully surgically resected (i.e. R1 or R2), patients may develop recurrences from remaining tumor cells [7]. Some patients with recurrences may then have an upgrade of their tumor. These patients have an increased chance of mortality, as distant metastasis is more likely [8]. Upgrades involve, amongst other factors, a dedifferentiation with a grading shift towards higher malignancy in a recurrent tumor. As a result of the low incidence of STS, it is quite difficult to gather a sufficiently large collective of patients to carry out studies. The university hospital Bergmannsheil Bochum is a German reference center for STS, which offers sufficient data to study STS. The aim of this study is to analyze patients who develop a local recurrence with an upgrade and to detect possible risk factors.

Patients and methods

We conducted a retrospective case control study that investigated data over a period of 15 years. For our data, we incorporated all patients who were diagnosed with a low grade STS (G1) and received surgical therapy from 1996 to 2011. A total of 333 patients were then closely analyzed. All of these patients received a pathological review at a single institution – the Department of Pathology, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum – and data was analyzed according to standards of the ethical committee of the Ruhr University Bochum.

We divided our study group into patients with upgrades in local recurrencies and those without. We labeled patients without upgrades as our reference collective. For our study we did not exclude any patients and did not deliberately pick any grading changers. Therefore, we regard our data as randomly sampled. We analyzed main parameters which we evaluated as relevant for upgrades. These parameters were age at diagnosis, gender, localization of tumor and specific STS type.


Data was evaluated by χ2 test, independent sample t test, logistic regression and regression coefficient using SPSS. Both univariate and multivariate analysis were conducted to reduce bias. Results are presented using p value and confidence interval at 5%. Results were considered to be significant at p<0.05.


Mean age (in years) of both collectives was at 54.3 years ± 16.6. 182 patients were male (54.7%) and 151 patients were female (45.3%). Preferred localization was lower extremity (53.2%; n=177), followed by thorax (17.1%; n=57), upper extremity (15.3%; n=51), pelvis (10.2%; n=34) and head (4.2%; n=14) (Table 1 [Tab. 1]). Preferred STS was liposarcoma (53.8%; n=179), followed by fibrosarcoma (17.7%; n=59), malignant peripheral nerve sheath tumor (MPNST) (4.5 %; n=15), chondrosarcoma (3.9 %; n=13) and others (20.1%; n=67) (Table 1 [Tab. 1]).

Of 333 patients, 23.4% developed a recurrent tumor (n=78). The specification of the different tumor types is shown in Table 2 [Tab. 2]. Of those patients who suffered from such recurrences, 42.3% upgraded (n=33).

9.9% of the entire collective (n=333) upgraded (n=33), labeled as upgraders as opposed to our reference collective (n=300) who did not (non upgraders).


In patients with upgrades, mean age was 5.5 years higher than in the reference group (53.8 years compared to 59.3 years). Preferred localization was again lower extremity (54.5%; n=18), followed by thorax (18.2%; n=6), upper extremity (12.1%; n=4), pelvis (12.1 %; n=4) and head (3%; n=1). Preferred STS were liposarcoma (42.4%; n=14), fibrosarcoma (36.4%; n=12), MPNST (9.1%; n=3), chondrosarcoma (3%; n=1) and others (9.1%; n=3).

Figure 1 [Fig. 1], Figure 2 [Fig. 2] and Figure 3 [Fig. 3] show examples with typical histopathological patterns of three different low grade soft tissue sarcoma patients with their initial tumor (left column, G1) and their recurrent upgraded tumor (right column, G2).

Mean age difference (p=0.072) and age above 60 (p=0.068) show no significant statistical effect on upgrades. Also, gender (p=0.71) and localization (p1=0.678, p2=0.814) are not statistically significant (see Table 1 [Tab. 1]). Fibrosarcoma show significant effect on upgrades (p=0.013). The risk that a patient with a fibrosarcoma will upgrade is three times higher than patients with other STS (Odds Ratio = 3.1) in both univariate and multivariate analysis.


Low grade STS are very heterogeneous in their appearance and show high variety in terms of recurrence rates and malignancy. All patients had a complete surgical resection with tumor free margins,however, among all low-grade G1 STS patients, 23.4% developed a local recurrent tumor (Table 2 [Tab. 2]). Such a recurrent tumor may require a second surgery, which has a clear impact on the patients’ outcome. Additionally, some of these STS that locally recur show an upgrade, a phenomenon we described in the first part of this study. Upgrades describe a change in the tumor toward a higher malignant entity, which is associated with a poorer prognosis. Among all of our patients, 10% had an upgrade of their STS.

The aim of this study was to find risk factors that enable us to analyze which patients are more at risk of an upgrade. After statistically analyzing possible risk factors such as age, gender, tumor type and tumor localization, we discovered one parameter that is clearly linked to an upgrade (Table 1 [Tab. 1]). The tumor type fibrosarcoma – in other words, a patient diagnosed with a low grade G1 fibrosarcoma – is three times as likely to upgrade. G1 Fibrosarcoma are a 3-fold risk to upgrade if local recurrence occurs. Almost 40% of all our fibrosarcoma patients developed a recurrent tumor.

Additionaly, 20% of our fibrosarcoma patients suffered from recurrent tumors with upgrades. These are remarkably high numbers and emphasize the importance of an adequate first line therapy, which is clearly related to a patient’s prognosis [9].

Similar results showing high recurrence tendencies were found in Merck’s study which found the local recurrence of, in this case myxofibrosarcomas, to be 38%, 48%, 51% and 61% for G 1, 2, 3 and 4 tumors, respectively [10].

When considering these high recurrence rates, the question of whether the current therapy plan of complete surgical resection with tumor free margins is sufficient arises. We need to discuss whether, at least in patients who may exhibit specific risk factors, additional therapeutic options should be applied. There is no clear evidence whether adjuvant radiotherapy is beneficial to the patients [11]. Until now, the only strong risk factor leading to significantly higher recurrence rates is the tumor type fibrosarcoma. In this respect, the option of radiotherapy in addition to surgical resection in patients with fibrosarcomas could be discussed [4], [7], [10]. The option of radiotherapy depends on each individual case, as there is no standardized protocol for sarcoma treatment. The use of irradiation often depends on the therapist’s attitude towards radiotherapy and the patients’ individual decision.

Irradiation is not a postoperative standard for low grade STS. The majority of patients benefit greatly from a sole surgical resection [9]. Side effects and long term destruction of other soft tissue should also be put into account when considering radiotherapy [11]. Due to the high number of upgrades associated with a poorer prognosis, patients with low grade fibrosarcomas may benefit from irradiation.

Currently, there are no international standards or guidelines for the treatment and follow up of low grade STS. There is also a lack of evidence as to whether an adjuvant therapy such as chemotherapy or irradiation is indicated for these patients [11].



The investigators would like to thank Professor Hans-Ulrich Steinau for enabling this research. This paper is dedicated to his retirement from the chairmanship of the Department of Plastic Surgery of the Bergmannsheil Bochum. We would like to thank the ethics committee of the Ruhr University Bochum for their support. Part of these data will be used for the thesis of T. Khosrawipour, Bochum. The authors thank her for proofreading the manuscript.

Competing interests

The authors declare that they have no competing interests.


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