Subcutaneous Soft Tissue Sarcomas Research Articles

Long-Term outcome following surgical excision of large, low to intermediate grade soft tissue sarcomas in dogs.

Soft tissue sarcomas (STS) represent a heterogeneous group of tumours, with varying mesenchymal cell origin, size and histological grade. Large soft tissue sarcomas pose a surgical challenge due to feasibility of excision, and are often dismissed as good surgical candidates due to an anticipated poor prognosis. To evaluate the long-term outcome of dogs that underwent surgical excision of large (≥5 cm), low to intermediate grade, soft tissue sarcomas. Medical records of dogs that presented for STS excision between 2009 and 2021 were reviewed. Information was obtained regarding signalment, tumour location and size, preoperative cytology and histology, preoperative imaging, surgical findings, postoperative histological diagnosis and outcome. Dogs were included in the study if they underwent surgical excision of a de novo cutaneous or subcutaneous STS, which measured at least five centimeters in one plane, and was histologically diagnosed as low-intermediate grade. Long-term follow-up data were obtained via consultation, telephone or email. Thirty-nine dogs with large, low-intermediate grade STS were included. Most tumours were Grade 1 (28/39), located predominantly on the thigh and thorax (17/39). Tumours were removed by at least a narrow margin excision (≥1 cm) and deep fascial plane in all cases. Histological margins were deemed complete in 15/39, close (1-3 mm) in 8/39, incomplete in 4/39, and unknown in 12/39. All sites were closed primarily, either directly (22/39) or with flap reconstruction (17/39). Long-term follow-up (median 1064 days) reported good postoperative function, with owner reported local recurrence in 2/39. Minor complications occurred in 10/39 and major complications requiring surgical intervention occurred in 5/39. Large, low-intermediate grade STSs can be surgically excised with good long-term function and outcome, where consideration is given to appropriate case selection and planning. If skin flap reconstruction is required, owners should be made aware of the possible complications associated with their use.

RETROSPECTIVE REVIEW OF MORBIDITY AND MORTALITY IN A POPULATION OF CAPTIVE BUDGERIGARS (MELOPSITTACUS UNDULATES).

This retrospective study reviews the diseases associated with morbidity and mortality in 221 budgerigars (Melopsittacus undulates) from a captive population from 2013 to 2019. The study aimed to evaluate the health status of a flock of budgerigars typical of today's zoologic collections. Based on previous literature, it was hypothesized that age-related conditions such as neoplasia would be common, whereas metabolic and nutritional disorders would be less common. Neoplasia was widespread among the population, affecting 34% of birds (75/221). Carcinomas made up most neoplastic processes and most commonly affected the renal system (n = 22), followed by the proventriculus (n = 7). Pituitary, adrenal, and hepatocellular carcinomas were less commonly diagnosed. Sarcomas affected the population less often than carcinomas and were found within the coelom (undifferentiated four cases), within the spleen (three cases), within the kidney (two cases), and one subcutaneous soft tissue sarcoma. There were five cases of multicentric lymphoma found most commonly affecting the spleen and liver. Benign neoplasms affected the pituitary most commonly (nine cases), followed by the reproductive system, with seminomas (seven cases) being most common. Macrorhabdus ornithogaster (MO) was found in 56 cases. The majority (38 cases) were found in conjunction with a range of comorbidities, but several birds experienced MO infections alone, and it was thought to have been the cause of death in these birds (22 cases). In contrast to our hypothesis, disease associated with nutritional or metabolic disorders impacted a substantial portion of the population; hepatic lipidosis (26 cases) was the most common along with obesity (26 cases), followed by atherosclerosis, xanthomas, and gout (8, 7, and 4 cases, respectively). Traumatic lesions were noted in 41 cases and were most commonly characterized by head trauma and cerebral hemorrhage. Toxicity was rare; five total cases caused by a single carbon monoxide event were identified.

Marginal excision of cutaneous mast cell tumors in dogs was not associated with a higher rate of complications or prolonged wound healing than marginal excision of soft tissue sarcomas.

To compare wound healing following planned marginal excision of cutaneous mast cell tumors (MCTs) with that of soft tissue sarcomas (STSs) and to identify risk factors for wound healing complications and delay in healing. 126 dogs that underwent intentional marginal excision of cutaneous MCTs (n = 77) or subcutaneous STSs (49). Medical records of included dogs were reviewed and signalment, tumor size, tumor location, skin closure type, time to healing, reported complications, histopathological grade, and surgical margins were recorded. These variables and outcomes (complication rate and time to complete healing) were compared between dogs in the MCT and STS groups. Potential risk factors for complications and delayed healing were analyzed. No significant difference between the groups was found in any of the variables. Wound healing complication rates were 29% (22/77) for the MCT group and 31% (15/49) for the STS group. The mean ± SD time to complete healing was 16.5 ± 7.5 days for the MCT group and 17.7 ± 9.3 days for the STS group. These outcomes did not differ significantly between groups. For both groups, the use of subdermal plexus flap reconstruction was associated with the development of complications and increased time to complete healing. Marginal excision of cutaneous MCTs was not associated with a higher rate of complication or prolonged wound healing, compared with marginal excision of STSs. The use of flap reconstruction in skin closure may delay healing and planned adjuvant therapy. Owners should be counseled regarding these risks and where appropriate and feasible, surgery without reconstruction should be considered.

Quantifying Angiogenesis in Feline Cutaneous and Subcutaneous Soft Tissue Sarcomas via Semi-automated Endothelial Cell Detection and Digital Chalkley Counting

Quantifying Angiogenesis in Feline Cutaneous and Subcutaneous Soft Tissue Sarcomas via Semi-automated Endothelial Cell Detection and Digital Chalkley Counting

Correlation between cytologic features and histologic grades in cutaneous and subcutaneous soft tissue sarcomas in dogs-A pilot study.

Currently, canine soft tissue sarcoma (STS) grading is based on histopathology. In humans, several studies have demonstrated concordance between cytologic grading systems for STS and histologic grade. The aim of this study was to correlate several cytologic parameters (smear cellularity, anisokaryosis, nucleolar malignancy score, multinucleation, and the number of mitotic figures per 200 cells) that form part of a human STS cytologic grading system, with histologic grades of canine cutaneous and subcutaneous STS. Three observers (blinded) reviewed the cytologic preparations independently from cases with confirmed histologic diagnoses of STS. A cytologic grading score was assigned for each parameter. Correlations between cytologic grading scores (averaged between observers) and histologic grades were assessed using Spearman's correlation coefficient, with statistical significance defined as P<.05. Twenty-one cases were included in the study (10 Grade I STS, nine Grade II STS, and two Grade III STS). The number of mitotic figures (≥3) per 200 cells was the only parameter that showed a significant but weak, positive correlation with histologic grade (rs =.469; P=.032). No Grade I tumors had ≥3 mitotic figures per 200 cells; however, ≥3 mitotic figures per 200 cells were only observed in 33% of Grade II tumors and 50% (one out of two) of the Grade III tumors. This pilot study suggests that an increased number of mitotic figures seen on cytology might correlate with higher grade STS; however, the sensitivity of this parameter for grading STS appears to be low.

Evaluation of the neoplastic infiltration of the skin overlying canine subcutaneous soft tissue sarcomas: An explorative study.

Studies regarding the neoplastic infiltration of the skin overlying canine subcutaneous soft tissue sarcoma (sSTS) are lacking. In case of the absence of tumor infiltration, there would be the possibility of leaving this unaffected skin in place, thus simplifying surgery. The aim of the study was to investigate whether the skin overlying sSTSs is infiltrated by neoplastic cells. Dogs with sSTSs treated surgically were prospectively enrolled. After excision, the skin was dissected from the tumor along the natural surgical plane of cleavage and histologically evaluated. Twenty-nine dogs with an sSTS were included (22 grade I, 6 grade II, and 1 grade III). The sSTS-overlying skin was not tumor-infiltrated in 14/29 cases (48.3%). A higher frequency of infiltration was observed in higher grade sSTSs (grades II and III, 100%; P=.006); nevertheless, 8/22 grade I sSTSs (36%) also showed cutaneous infiltration. This infiltration involved the dermis of the skin directly in contact with the tumor (multifocal in 11 and diffuse in four cases). Although the cutaneous tumor infiltration is less frequent in grade I sSTSs and a wide excision may still be the safest treatment for any sSTS for a greater possibility of local control, this study opens the possibility to a less aggressive cutaneous excision, but still with a local curative intent, as only the skin directly in contact with the sSTS has been proven to be tumor-infiltrated. Additional studies are warranted to confirm that excision of only this skin may guarantee a complete local control, especially in lower-grade sSTSs.

Prevalence of pulmonary nodules suggestive of metastasis at presentation in dogs with cutaneous or subcutaneous soft tissue sarcoma.

To investigate the prevalence of pulmonary nodules suggestive of metastasis at the time of initial presentation in dogs with cutaneous or subcutaneous soft tissue sarcomas (STSs) and no previous related thoracic diagnostic imaging. 146 client-owned dogs with a cutaneous or subcutaneous STS. Medical records were retrospectively searched to identify dogs with STSs that underwent initial thoracic diagnostic imaging when presented for referral examination between September 2014 and March 2018. Data collected included patient and tumor characteristics. Results were evaluated for dogs grouped on the basis of variables of interest (eg, STS grade, duration, or history). Initial thoracic imaging was performed with CT (131/146 [89.7%]) or radiography (15 [10.3%]). Although the presence or absence of pulmonary nodules suggestive of metastasis on thoracic imaging was uncertain in 9 dogs, it was certain in the remaining 137 dogs, with nodules present in 16 (11.7%) dogs (5/77 [6%] with grade 1 STSs, 2/36 [6%] with grade 2 STSs, and 9/24 [38%] with grade 3 STSs). The odds of such pulmonary nodules being present on initial examination were higher (OR, 10.8 and 3.14, respectively) for dogs with grade 3 STSs (vs grade 1 or 2 STSs) and for dogs with an STS duration > 3 months (versus ≤ 3 months). Results indicated that pulmonary staging was a low-yield diagnostic procedure for dogs with grade 1 or 2 cutaneous or subcutaneous STSs, especially when tumors had been present for ≤ 3 months.

Prognostic factors and proposed grading system for cutaneous and subcutaneous soft tissue sarcomas in cats, based on a retrospective study.

The objectives of this study included utilising a large database from a diagnostic laboratory to identify any breed, sex or age predilections for cutaneous and subcutaneous soft tissue sarcomas (STSs), and the most common anatomical locations. The second aim was to obtain clinical outcomes and to assess histological features of those tumours to identify any potentially useful prognostic indicators and propose a grading system. Records from the laboratory were searched for feline submissions received from January 2012 to December 2013 diagnosed with STSs; the breed, age, sex and neuter status of the cat and anatomical location of the tumour were recorded. Clinical outcomes were acquired using a questionnaire to submitting practices, and histological features of tumours from patients with known outcomes were assessed. No sex, neuter status or breed predispositions were found. Most STSs arise in middle-aged and older cats, and the most common anatomical location was the trunk. Forty-seven cases had a known clinical outcome and archived tissues allowing for histological assessment of the tumour. Significant differences in median survival time (MST), mitotic index and histological score were detected between those cats that died of tumour-related disease and those that did not. A novel grading system applied to these tumours produced significant differences in MST between cats with low (MST = 900.5 days), intermediate (MST = 514 days) and high grade tumours (MST = 283 days). This is the first study applying a histological grading system to these common tumours. Local recurrence is often the cause of a poor outcome, with metastatic disease apparently rare. The proposed grading system incorporates features that can be assessed on routine haematoxylin and eosin-stained sections; in this small study, the histological grade of the tumour appears to be associated with survival time.

Direct Interstitial Treatment of Solid Tumors Using an Injectable Yttrium-90-Polymer Composite.

Purpose: Yttrium-90 (90Y)-polymer composite (radiogel) may be administered directly into cancerous tissues to deliver highly localized beta radiation for therapy. In a dose-escalation study, the authors investigated the feasibility of treating feline and canine soft-tissue sarcomas as a model for nonresectable solid tumors in humans to gain clinical experience and to identify optimal methods for placing the composite uniformly within target tumor tissue.Materials and Methods: Five cats (Washington State University) and three dogs (University of Missouri) were selected for treatment from among veterinary clinic patients presenting with subcutaneous soft-tissue sarcomas. The therapeutic radiogel composite comprised two parts that were combined before therapy: (1) a calibrated activity of highly insoluble 90Y(YPO4) particles in a sterile, phosphate-buffered saline solution and (2) a resorbable hydrogel delivery vehicle containing a dissolved copolymer of poly-(DL-lactic acid-co-glycolic acid) and poly-(ethylene glycol). Sarcomas of anesthetized animals (five cats and three dogs) were injected with the 90Y-radiogel (10%–15% by tumor volume) using a parallel-needle grid pattern with ∼4–5-mm spacings with or without ultrasound guidance. After injection, the composite solution gelled within tumor interstitial spaces to solid phase upon reaching body temperatures to constrain the 90Y activity intratumorally. The animals were then imaged with computed tomography (CT) or positron emission tomography (PET)/CT and placed in radiation isolation for overnight monitoring and follow-up.Results: Gelation of the composite within tumor extracellular spaces confined the 90Y(YPO4) particles in place to deliver a planned radiation absorbed dose (100–320 Gy) to target tissue through complete decay. Response of the tumor tissue to 90Y-radiation therapy postexcision was evaluated by imaging, tumor resection, and histology. Correlation was observed on histopathology between tumor destruction and radiation dose. With uniform placement at high dose, the authors achieved complete remission or stable disease (at 1–2 months posttreatment).Conclusions: This study demonstrated successful injection of 90Y-polymer composite (radiogel) without discernable radiation dose to normal organs or other detrimental side effects. Animal patients recovered quickly from the injection procedure. The better therapeutic responses were observed at mean doses at or above 300 Gy.

Influence of surgical margin completeness on risk of local tumour recurrence in canine cutaneous and subcutaneous soft tissue sarcoma: A systematic review and meta-analysis.

The present peer-reviewed veterinary literature contains conflicting information regarding the impact of surgical margin completeness on risk of local tumour recurrence in canine soft tissue sarcoma (STS). This systematic review and meta-analysis was designed to answer the clinical question: "Does obtaining microscopically tumour-free surgical margins reduce risk for local tumour recurrence in canine cutaneous and subcutaneous STS?" A total of 486 citations were screened, 66 of which underwent full-text evaluation, with 10 studies representing 278 STS excisions ultimately included. Cumulatively, 16/164 (9.8%) of completely excised and 38/114 (33.3%) of incompletely excised STS recurred. Overall relative risk of 0.396 (95% confidence interval = 0.248-0.632) was calculated for local recurrence in STS excised with complete margins as compared to STS excised with incomplete margins. Risk of bias was judged to be low for all studies in terms of selection bias and detection bias but high for all studies in terms of performance bias and exclusion bias. The results of the present meta-analysis, coupled with the results of individual previous studies, strongly suggest that microscopically complete surgical margins confer a significantly reduced risk for local tumour recurrence in canine STS. Future studies ideally should adhere to standardized conducting and reporting guidelines to reduce systematic bias.

Diagnosis and Management of Subcutaneous Soft Tissue Sarcoma.

The proper diagnosis and treatment planning for subcutaneous soft tissue sarcoma is very important. Soft tissue tumors can occur anywhere in the body, but if they occur subcutaneously, patients can easily notice a subcutaneous soft tissue mass. Therefore, it is possible to determine through recording, the growth speed of the mass, which is often difficult to obtain with deep-situated soft tissue masses. Palpation can also provide information about the firmness and mobility of the mass. Thus, history taking and physical examinations are informative for subcutaneous soft tissue tumors, compared to tumors that occur deeply. Because subcutaneous soft tissue tumors are easily recognized, they are often resected, without sufficient imaging analyses or thorough treatment planning. An operation performed based on such an inadequate preoperative plan is called a "whoops surgery." In the case of "whoops surgeries," subsequent radical surgery is required to remove additional areas, including hematomas that result from the initial surgery, that require a wider range of resection and soft tissue reconstruction. Therefore, as with deep-seated soft tissue tumors, it is important to conduct careful imaging examinations and make appropriate preoperative plans for subcutaneous soft tissue tumors. Subcutaneous soft tissue sarcomas often show an invasive pattern, and such tumors require a more careful assessment to prevent local recurrence after surgery. During surgery, it is necessary to remove the entire infiltration area along the fascia. Sometimes, an adequately wide excision is necessary, which is considered the minimum necessary procedure to eradicate the lesion. As noted above, clinicians who see patients with subcutaneous soft tissue tumors are encouraged to have sufficient knowledge and experience regarding the diagnosis and treatment. This article is intended for all doctors who deal with subcutaneous soft tissue tumors and focuses on essential points regarding their diagnosis and management.

Evaluation of local toxic effects and outcomes for dogs undergoing marginal tumor excision with intralesional cisplatin-impregnated bead placement for treatment of soft tissue sarcomas: 62 cases (2009-2012).

OBJECTIVE To evaluate outcomes for dogs following marginal tumor excision and intralesional placement of cisplatin-impregnated beads for the treatment of cutaneous or subcutaneous soft tissue sarcomas (STSs) and assess local toxic effects of cisplatin-impregnated beads in these patients. DESIGN Retrospective case series. ANIMALS 62 client-owned dogs. PROCEDURES Medical records were reviewed to identify dogs with STSs treated with marginal excision and intralesional placement of cisplatin-impregnated beads. Patient signalment; tumor location, type, and grade; dates of tumor resection and bead placement; number of beads placed; and concurrent treatments were recorded. Data regarding toxicosis at the bead site (up to the time of suture removal) and tumor recurrence were collected; variables of interest were evaluated for associations with these outcomes, and systemic adverse effects (if any) were recorded. RESULTS 24 of 51 (47%) evaluated dogs had toxicosis at bead placement sites (classified as mild [n = 12] or moderate [10] in most). Fifteen of 51 (29%) tumors recurred. Median disease-free interval was not reached for dogs with grade 1 and 2 STSs, whereas that for dogs with grade 3 STSs was 148 days. Disease-free survival rates of dogs with grade 1 and 2 tumors at 1, 2, and 3 years were 88%, 75%, and 64%, respectively. One dog was treated for presumptive systemic toxicosis but recovered with medical treatment. CONCLUSIONS AND CLINICAL RELEVANCE Cisplatin-impregnated beads were generally well tolerated; good results were achieved for dogs with grade 1 or 2 STSs. Prospective, controlled studies are needed to determine efficacy of this treatment for preventing recurrence of marginally excised STSs in dogs.

Canine Cutaneous and Subcutaneous Soft Tissue Sarcoma: An Evidence-Based Review of Case Management.

Canine cutaneous and subcutaneous soft tissue sarcomas (STS) account for 20.3% of malignant neoplasms of the skin. This article makes recommendations for the diagnosis, treatment, and follow-up in dogs with STS, using evidence-based medicine concepts. Although our review of the literature on the management of canine STS found many of the studies to be less than rigorous, board-certified specialists in internal medicine, surgery, pathology, oncology, and radiation oncology were able to make several recommendations based on the literature review: cytology and biopsy are important for presurgical planning; wide (>3 cm margins) surgical excision decreases the likelihood of tumor recurrence; the use of a histologic grading scale is useful in predicting biologic behavior; and, in select cases, chemotherapy and radiation therapy may be beneficial adjunct treatments to surgical excision. More research is necessary to determine minimum size of surgical margins, the impact of radiation therapy on incompletely resected tumors, the ideal chemotherapy protocol for high grade STS, and the optimal methods of monitoring dogs for tumor recurrence and metastasis.

Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors.

There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors, and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need.

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors.

Canine perivascular wall tumors (PWTs) are a group of subcutaneous soft tissue sarcomas developing from vascular mural cells. Mural cells are involved in angiogenesis through a complex crosstalk with endothelial cells mediated by several growth factors and their receptors. The evaluation of their expression may have relevance since they may represent a therapeutic target in the control of canine PWTs. The expression of vascular endothelial growth factor (VEGF) and receptors VEGFR-I/II, basic fibroblast growth factor (bFGF) and receptor Flg, platelet-derived growth factor B (PDGFB) and receptor PDGFRβ, transforming growth factor β1 (TGFβ1) and receptors TGFβR-I/II, and cyclooxygenase 2 (COX2) was evaluated on frozen sections of 40 PWTs by immunohistochemistry and semiquantitatively scored to identify their potential role in PWT development. Statistical analysis was performed to analyze possible correlations between Ki67 labeling index and the expression of each molecule. Proteins of the VEGF-, PDGFB-, and bFGF-mediated pathways were highly expressed in 27 (67.5%), 30 (75%), and 19 (47.5%) of 40 PWTs, respectively. Proteins of the TGFβ1- and COX2-mediated pathways were highly expressed in 4 (10%) and 14 (35%) of 40 cases. Statistical analysis identified an association between VEGF and VEGFR-I/II (P = .015 and .003, respectively), bFGF and Flg (P = .038), bFGF and PDGFRβ (P = .003), and between TGFβ1 and COX2 (P = .006). These findings were consistent with the mechanisms that have been reported to play a role in angiogenesis and in tumor development. No association with Ki67 labeling index was found. VEGF-, PDGFB-, and bFGF-mediated pathways seem to have a key role in PWT development and growth. Blockade of tyrosine kinase receptors after surgery could represent a promising therapy with the aim to reduce the PWT relapse rate and prolong the time to relapse.

Prognostic Factors for Cutaneous and Subcutaneous Soft Tissue Sarcomas in Dogs

Soft tissue sarcomas (STSs) develop from mesenchymal cells of soft tissues, and they commonly occur in the skin and subcutis of the dog. Although phenotypically diverse with frequently controversial histogenesis, STSs are considered as a group because they have similar features microscopically and clinically. Following resection, local recurrence rates are low in general but vary according to histologic grade and completeness of surgical margins. Complete margins predict nonrecurrence. Even most grade I STSs with "close" margins will not recur, but propensity for recurrence increases with grade. The frequency of metastasis has not been accurately estimated, but it is believed to be rare for grade I STSs and most likely to occur with grade III STSs. However, metastasis does not necessarily equate with poor survival. High mitotic index is prognostic for reduced survival time. Further research is needed to determine more precise estimates for recurrence rates and survival as related to completeness of surgical margins and to delineate potential differences in metastatic rate and median survival time between grades. Other potential indicators of prognosis that presently require further investigation include histologic type, tumor dimension, location, invasiveness, stage, markers of cellular proliferation, and cytogenetic profiles. Common issues limiting prognostic factor evaluation include biases from retrospective studies, small sample sizes, poor verification of metastasis, inconsistent STS classification and use of nomenclature, difficulties in differentiating STS phenotype, and diversity of the study population (stage of disease and treatment status).

Histologic Grade Predicts Recurrence for Marginally Excised Canine Subcutaneous Soft Tissue Sarcomas

Local recurrence of marginally excised subcutaneous soft tissue sarcomas is variable and difficult to predict. This study aimed to identify predictors of local recurrence after excisional biopsy. Medical records of 236 dogs from which tumors had been received between 2004 and 2007 were analyzed. Medium- to large-breed dogs, median age 10 years, were most commonly affected. A total of 139 tumors were graded histologically: 71 were grade 1 (51%); 59, grade 2 (42%); and 9, grade 3 (7%). Of these, 34 tumors (25%) were completely excised, and 104 (75%) were marginally excised. None of 30 completely excised tumors with follow-up information recurred. Three of 41 grade 1 tumors (7%), 14 of 41 grade 2 tumors (34%), and 3 out of 4 grade 3 tumors recurred after marginal excision. Kaplan-Meier survival curves were generated to evaluate survival and the tumor-free interval. The log-rank test and log-rank test for trend were used for comparisons. Tumor recurrence-free intervals for dogs with grade 1 and 2 tumors and for those with grade 1 and 3 tumors differed significantly (P = .0027 and .0001, respectively) and overall were inversely related to tumor grade (P = .0007). Kaplan-Meier survival curves, regardless of recurrence, for patients with grade 1, 2, or 3 tumors treated by marginal excision did not differ significantly, and none differed from the survival curves of patients treated by complete excision. In conclusion, histologic grade is a strong predictor for recurrence of marginally excised subcutaneous soft tissue sarcomas. Clean margins predict nonrecurrence. Tumor recurrence did not significantly reduce survival time.

Size Matters for Sarcomas!

By the time of diagnosis, sarcomas have frequently reached a large size and many patients have a long history of symptoms prior to diagnosis. The aim of this study was to assess whether size of tumour at presentation or duration of symptoms was a significant factor affecting outcome. A prospective database recording patient, tumour, treatment and outcome factors was reviewed. A total of 1460 patients with newly diagnosed sarcomas and with > 3 years of follow-up were included for analysis. The mean size of sarcomas presenting to our unit was 10.7 cm at the time of diagnosis. Bone sarcomas averaged 11.3 cm with little variation by age or diagnosis, whilst subcutaneous soft tissue sarcomas averaged 10 cm. The incidence of metastases at diagnosis increased almost linearly with increasing size and the prognosis, even for patients without metastases at diagnosis became steadily worse with increasing size for all tumours, independent of other factors. Duration of symptoms did not correlate with size but patients with symptoms > 1 year had a slightly better prognosis than those with a shorter duration. The author makes a plea for greater awareness of potential malignancy in lumps and bumps, particularly those over the size of a golf ball (4.27 cm), making the point that the smaller the tumour at diagnosis the better the prognosis.

The Impact of Previous Surgical Manipulation of Subcutaneous Sarcoma on Oncologic Outcome

We prospectively followed 106 consecutive patients referred for surgical treatment of nonmetastatic subcutaneous soft tissue sarcoma to assess whether prior surgical manipulation had an impact on local control and/or disease-free survival. 10 patients had no previous surgical treatment; 11 had only a previous biopsy, 75 had a previous attempted excision, and 10 were referred after the tumor had recurred locally. Histologic grade was inversely associated with overall survival and disease-free survival. Of the 75 patients with previous attempted excision, 22 (29%) had gross residual disease, 27 (36%) had microscopic residual disease, and 26 (35%) had no identifiable residual disease. The 5-year metastasis-free survival was 88%. Local control was obtained in 100% of patients without previous surgical manipulation, 89% of those with previous surgery, and 60% of those who were referred after a local relapse had been recognized. Cox proportional hazards analysis revealed that larger tumor size negatively impacted disease-free survival in those patients who were treated with previous attempted excision. Of those patients with tumors 4 cm or larger and a previous unplanned sarcoma excision, disease-free survival was lower than in those patients referred without previous attempted excision. Prognostic study, Level I-2 (prospective study). See the Guidelines for Authors for a complete description of levels of evidence.

Oncological outcomes of operative treatment of subcutaneous soft-tissue sarcomas of the extremities.

We reviewed the cases of sixty-two patients who had had a subcutaneous sarcoma to determine the effect of tumor and treatment-related variables on the rates of survival and local recurrence. Fifty-nine (95 per cent) of the patients had had an operation at another hospital before being referred to us. Twenty-nine (47 per cent) of the sixty-two tumors were high-grade, forty-two (68 per cent) were small (five centimeters or less), and thirty (48 per cent) were malignant fibrous histiocytomas. We followed a treatment strategy that consisted of repeat excision with the goal of obtaining wide margins. Excluding thirteen patients who had had a palpable local recurrence at the time of presentation, twenty (49 per cent) of forty-one patients who had had a marginal excision at another hospital had microscopic residual tumor on repeat excision. At a median of fifty-six months after the repeat excision, fifty (81 per cent) of the sixty-two patients had been continuously disease-free, one had no evidence of disease, eight had died of the disease, and three had died of other causes. The five-year rate of disease-free survival was 85 per cent (fifty-three of sixty-two patients). There were three local recurrences, all in patients who had had a marginal resection. No recurrences were noted in patients who had had a wide local excision of the tumor or of the previous operative field. Multivariate analysis revealed that a large tumor (greater than five centimeters), a marginal excision, and adjuvant radiation therapy were associated with a worse prognosis. Excellent rates of survival for patients who have a subcutaneous sarcoma, including those who have a large or high-grade tumor and those who have residual tumor following a previous operation, can be obtained with carefully planned operative treatment alone. We recommend operative excision or repeat excision with wide margins because of the high prevalence of residual tumor. Size is the most important tumor-related factor, and the operative margin is the most important treatment-related factor. The additional value of adjuvant radiation therapy remains unproved.