Myles Smith

Management of Recurrent Retroperitoneal Sarcoma (RPS) in the Adult: A Consensus Approach from the Trans-Atlantic RPS Working Group

IntroductionRetroperitoneal soft tissue sarcomas (RPS) are rare tumors. Surgery is the mainstay of curative therapy, but local recurrence is common. No recommendations concerning the best management of recurring disease have been developed so far. Although every effort should be made to optimize the initial approach, recommendations to treat recurring RPS will be helpful to maximize disease control at recurrence.MethodsAn RPS transatlantic working group was established in 2013. The goals of the group were to share institutional experiences, build large multi-institutional case series, and develop consensus documents on the approach to this difficult disease. The outcome of this document applies to recurrent RPS that is nonvisceral in origin. Included are sarcomas of major veins, undifferentiated pleomorphic sarcoma of psoas, ureteric leiomyosarcoma (LMS). Excluded are desmoids-type fibromatosis, angiomyolipoma, gastrointestinal stromal tumors, sarcomas arising from the gut or its mesentery, uterine LMS, prostatic sarcoma, paratesticular/spermatic cord sarcoma, Ewing sarcoma, alveolar/embryonal rhabdomyosarcoma, sarcoma arising from teratoma, carcinosarcoma, sarcomatoid carcinoma, clear cell sarcoma, radiation-induced sarcoma, paraganglioma, and malignant pheochromocytoma.ResultsRecurrent RPS management was evaluated from diagnosis to follow-up. It is a rare and complex malignancy that is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, but some patients may experience prolonged disease control also at recurrence, when the approach is optimized and follows the recommendations contained herein.ConclusionsInternational collaboration is critical for adding to the present knowledge. A transatlantic prospective registry has been established.

Outcome following resection of retroperitoneal sarcoma.

Retroperitoneal sarcoma comprises a range of different histological subtypes with dissimilar behaviour and biology. This study sought to characterize the morbidity and mortality associated with multivisceral resection and oncological outcomes according to subtype.

Patterns of disease relapse in primary extremity soft-tissue sarcoma

Extremity soft‐tissue sarcomas comprise a range of distinct histological subtypes. This study aimed to characterize the patterns of disease relapse in patients undergoing resection of primary extremity soft‐tissue sarcoma.

p16 Expression in Fat Necrosis: A Potential Diagnostic Pitfall in the Evaluation of Differentiated Adipocytic Neoplasms.

Distinguishing well-differentiated liposarcoma (WDL) from lipoma is of clinical and prognostic importance, but can be difficult on imaging and histology alone. WDL characteristically harbor amplifications of the MDM2 and CDK4 cell cycle oncogenes and overexpress the cell cycle regulator p16. Fluorescence in situ hybridization (FISH) to assess for MDM2 and CDK4 gene amplification is the diagnostic gold standard, and immunohistochemistry for the overexpressed MDM2 and CDK4 proteins is also useful but may not be routinely offered by pathology laboratories. p16 immunohistochemistry is a sensitive marker for WDL and is in the repertoire of most laboratories, and it has been suggested as a useful method of distinguishing WDL from lipomas when other ancillary modalities are not readily available. We describe a case of a large retroperitoneal adipocytic mass occurring in a 27-year-old male, which was clinically and radiologically in keeping with WDL. Histologically this was a differentiated adipocytic neoplasm with prominent fibrous septa and fat necrosis, more suggestive of retroperitoneal lipoma. Immunohistochemistry showed diffuse, strong nuclear expression of p16 in the areas of fat necrosis. However, CDK4 was negative and the lesion lacked evidence of MDM2 amplification with FISH. Diffuse expression of p16 in areas of fat necrosis in large or deep lipomas highlights the potential for diagnostic misinterpretation as well differentiated liposarcoma, and we therefore emphasize that p16 immunohistochemistry should always be interpreted as part of a panel with CDK4 +/− MDM2 in the differential diagnosis of WDL and lipoma.

The Adequacy of Core Biopsy in the Assessment of Smooth Muscle Neoplasms of Soft Tissues: Implications for Treatment and Prognosis

The grading of soft tissue sarcomas is one of the most important prognostic factors and determines patient management. Although grading of most adult-type soft tissue sarcomas on biopsies correlates highly with the final grading on the excision specimen, it appears less reliable for tumors of smooth muscle. We assessed the pathologic findings for smooth muscle neoplasms diagnosed by core biopsy at our tertiary sarcoma center, and compared them with those in the subsequent excision specimens. A total of 100 patients with leiomyosarcoma first diagnosed on core biopsy and with a subsequent excision were identified and the accuracy of the biopsy grade determined by comparison with the excision grade. Differences in other salient histologic parameters were also noted. A grade difference between biopsy and excision specimens of leiomyosarcomas was found in 68% of cases, with all these cases showing an increase in grade from biopsy to excision specimen. Of the 3 parameters used for grading using the French Federation of Cancer Centers Sarcoma Group Grading System (FNCLCC), necrosis was the score that most commonly differed between biopsy and excision specimen (55%), closely followed by the mitotic count (51%). The grading of soft tissue smooth muscle tumor biopsies has a lower accuracy compared with other adult soft tissue sarcomas and should therefore be taken with caution, particularly as this may be an underrepresentation of the true tumor grade.

Selective marginal resections in the management of aggressive angiomyxomas

Aggressive angiomyxomas (AA) are rare tumors, most commonly presenting in the pelvis of women of childbearing age. This study presents the results of selective marginal resection of this disease in patients managed at a single institution.

The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors

A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox‐proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5‐year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05–2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies.

Elastofibroma dorsi: The clunking tumour that need not cause alarm

INTRODUCTION Elastofibromas are rare, pseudo-tumours arising at the inferior pole of the scapula that have a characteristic presentation. Due to their tissue of origin and size, they may often be mistaken for soft tissue sarcomas. We present the management of patients diagnosed with elastofibroma at a single institution. METHODS Patients diagnosed with elastofibroma between January 1995 and January 2015 were identified from a prospectively maintained histopathology database. Electronic patient records, imaging and pathology reports were retrieved and reviewed. RESULTS Thirty seven patients were identified, with a median age of 66 years and a male-to-female ratio of 1:1.6. All tumours occurred in the characteristic subscapular location. The median maximum tumour diameter was 8.2 cm. A synchronous contralateral lesion (15.8%) was found in six patients. Cross-sectional imaging was performed in 29 patients, with magnetic resonance imaging the most common modality (59.5%). Diagnosis was confirmed with percutaneous biopsy in all but one patient, who proceeded directly to surgery. Eighteen patients were managed non-operatively; 19 opted for surgical excision due to significant symptoms. Excision was performed in a marginal fashion and, at a median follow-up of 5 months, no functional impairment or local recurrences were observed. CONCLUSIONS Soft tissue masses greater than 5 cm in diameter should prompt the clinician to exclude soft tissue sarcoma. The diagnosis of elastofibroma may be alluded to by its typical presentation and can be confirmed by percutaneous biopsy. After excluding malignancy, these lesions can be safely managed non-operatively, with surgery reserved for symptomatic patients.

The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma

The characterisation and clinical relevance of tumour-infiltrating lymphocytes (TILs) in leiomyosarcoma (LMS), a subtype of soft tissue sarcoma that exhibits histological heterogeneity, is not established. The use of tissue microarrays (TMA) in studies that profile TIL burden is attractive but given the potential for intra-tumoural heterogeneity to introduce sampling errors, the adequacy of this approach is undetermined. In this study, we assessed the histological inter-and intra-tumoural heterogeneity in TIL burden within a retrospective cohort of primary LMS specimens. Using a virtual TMA approach, we also analysed the optimal number of TMA cores required to provide an accurate representation of TIL burden in a full tissue section. We establish that LMS have generally low and spatially homogenous TIL burdens, although a small proportion exhibit higher levels and more heterogeneous distribution of TILs. We show that a conventional and practical number (1-3) of TMA cores is adequate for correct ordinal categorisation of tumours with high or low TIL burden, but that many more cores (≥ 11) is required to accurately estimate absolute TIL numbers. Our findings provide a benchmark for the design of future studies aiming to define the clinical relevance of the immune microenvironments of LMS and other sarcoma subtypes.

The effect of age on outcomes after isolated limb perfusion for advanced extremity malignancies

BACKGROUND Isolated limb perfusion (ILP) is a well-established treatment for patients with advanced extremity malignancies unsuitable for limb-conserving surgery. However, little is known about the outcomes of this treatment in elderly patients. We sought to determine the effects of age on the tolerability and efficacy of ILP for advanced extremity malignancy. PATIENTS AND METHODS Patients undergoing ILP at our institution between January 2005 and January 2018 were identified from a prospectively maintained database. Patients were stratified by pathology (melanoma, soft-tissue sarcoma, other) and age (<75 years and ≥75 years). Outcomes of interest were perioperative morbidity and mortality, locoregional toxicities, response rates and oncological outcomes. RESULTS During the study period, a total of 189 perfusions were attempted. Successful perfusions were performed in 179 patients, giving a technical success rate of 94.7%. No difference in perfusion success rates, severe locoregional toxicity and perioperative morbidity or mortality was noted between those aged <75 years and ≥75 years. The overall response rate in melanoma was 82.4%, and no difference in response rates or oncological outcomes between age groups was noted in these patients. The overall response rate in soft-tissue sarcoma was 63.5%, with no difference in response rates noted between age groups. However, patients aged <75 years with soft-tissue sarcoma had prolonged local recurrence-free survival compared with older patients (13 versus 6 months), possibly due to the prevalence of chemosensitive subtypes in the younger age group. CONCLUSION ILP is an effective treatment for advanced extremity malignancies in the elderly, with comparable response rates and toxicities to younger patients.