Primary iliocaval leiomyosarcomas: The path beyond surgery

IntroductionIliocaval leiomyosarcoma (ICLM) is a rare and aggressive form of sarcoma within the retroperitoneum. Surgery is the mainstay of treatment, with no consensus on the benefit of chemoradiotherapy in the neo/adjuvant setting. This study aims to describe the natural history of a chemotherapy-naïve ICLM treated in a tertiary cancer centre and to explore potential directions to improve oncological outcome.Materials and methodsA prospective database was used to identify patient demographics, clinicopathological variables and oncological outcomes in 30 patients who underwent surgical resection in our institution for primary non-metastatic ICLM between 2003 and 2018.ResultsThere was no 90-day mortality. With a median follow-up time of 70.0 months (95% CI 52.6–87.4), 5/30 patients (16.7%) developed local recurrence while 11/30 (36.7%) developed distant metastatic disease. 1 patient (3.3%) developed both local and distant recurrence. Median overall survival of our cohort was 41.0 months (95% CI 33.6–48.4) and 5-year overall survival rate was 32.1%. Multivariate survival analysis using the Cox proportional hazard model identified tumour grade and blood loss of more than 600 mL as key prognostic factors in our model.ConclusionManagement of ICLM should be centralised in high-volume sarcoma centres with expertise in the management of retroperitoneal sarcomas. Integration of tumour biology with a concerted effort to conduct conclusive multi-centre phase III in histological and molecularly defined sarcoma subgroups is necessary to improve patient outcome. We eagerly await the results of STRASS 2 study to gain more insights to the efficacy of neoadjuvant chemotherapy on patient prognosis.     

Uterine mesenchymal tumours: recent advances

Almost all uterine mesenchymal tumours have been historically classified as either smooth muscle or endometrial stromal neoplasms. Recent application of molecular techniques has identified numerous lesions with distinctive genetic abnormalities and clinicopathological characteristics. Newly discovered uterine sarcoma subtypes include high-grade endometrial stromal sarcomas with BCOR genetic abnormalities, fibrosarcoma-like uterine sarcomas with NTRK rearrangements and COL1A–PDGFRB fusions, as well as undifferentiated uterine sarcomas with SMARCA4 mutations. Novel PLAG1 and PGR fusions have been identified in subsets of myxoid and epithelioid leiomyosarcomas. Some uterine tumours resembling ovarian sex-cord tumour harbour GREB1 and ESR1 rearrangements. Histological and immunophenotypical features as well as underlying genetic abnormalities defining these lesions are discussed.     

Cardiac metastasis of great saphenous vein leiomyosarcoma

We present a case with cardiac metastasis of the great saphenous vein leiomyosarcoma (LMS) that presented to the emergency department with dyspnea and palpitations 2 months ago. In this patient, hemodynamic instability was caused by an extensive right ventricular cavity and outflow tract invasion of the LMS. Treatment of the patient included incomplete mass resection, adjuvant chemotherapy, and permanent pacemaker implantation (due to postoperative complete atrio-ventricular block).     

Retroperitoneal tumors: Review of diagnosis and management

Retroperitoneal tumors are extremely rare tumors occurring in the retroperitoneum. Retroperitoneal tumors are divided into benign tumors and malignant tumors, including retroperitoneal sarcoma. Approximately 70–80% of primary retroperitoneal soft-tissue tumors are malignant; however, these only account for 0.1–0.2% of all malignancies. Retroperitoneal sarcoma is an orphan malignant disease with a low incidence. The information on benign retroperitoneal tumors is limited. The American Joint Committee on Cancer/TNM classification updated to the 8th edition in 2017. In 2010, three new drugs for soft tissue sarcoma were approved based on the results of phase III trials, but the histological subtypes of the patients enrolled in the trials of each drug differed. Recently, in addition to surgery for retroperitoneal sarcoma, the effectiveness of perioperative radiation therapy has become interesting. For malignant retroperitoneal tumors and retroperitoneal sarcoma, survival improvement and locoregional recurrence prevention can be undertaken by carrying out surgery to secure negative margins with wide and combined resection of some adjacent organs, and cooperation with a trained medical team comprising of radiologists, pathologists and medical oncologists in centralized hospitals. Some clinical trials aimed at further improving treatment results by adding preoperative chemotherapy and radiation therapy based on histological confirmation using a correct needle biopsy are in progress. In recent years, molecular profiling has been used to select eligible patients for chemotherapy. In the future, precision medicine with next-generation sequencing technology will be expected among the diverse and potential future treatments for retroperitoneal sarcoma. In this review, we summarized the current state of retroperitoneal tumors and retroperitoneal sarcoma.     

A randomised phase II trial of selumetinib vs selumetinib plus temsirolimus for soft-tissue sarcomas

Background:

The MEK inhibitor, selumetinib, suppresses soft-tissue sarcoma (STS) cell proliferation in vitro. Mammalian target of rapamycin inhibitors possess modest activity against STS; however, resistance develops via MAPK pathway feedback activation. The combination of selumetinib and temsirolimus synergistically inhibits STS cell line growth. Therefore, a randomized phase II trial of selumetinib vs selumetinib plus temsirolimus was conducted.

Methods:

Seventy-one adults with advanced STS who received ⩽2 prior chemotherapeutics were randomized to selumetinib 75 mg p.o. bid and allowed to crossover upon progression, or to selumetinib 50 mg p.o. bid plus temsirolimus 20 mg i.v. weekly, with primary endpoint of progression-free survival (PFS).

Results:

There was no difference in PFS between the two arms for the overall cohort (median 1.9 vs 2.1 months); an improved median PFS was observed in the combination arm (N=11) over single agent (N=10) in the prespecified leiomyosarcoma stratum (median 3.7 vs 1.8 months; P=0.01). Four-month PFS rate was 50% (95% confidence interval 0.19–0.81) with the combination vs 0% with selumetinib alone in the leiomyosarcoma cohort. Most common grade 3/4 adverse events with the combination were mucositis (29%), lymphopenia (26%), neutropenia and anaemia (20% each).

Conclusions:

While single-agent selumetinib has no significant activity in STS, the combination may be active for leiomyosarcomas.     

S100A6 expression in cutaneous smooth muscle neoplasms

The S100A6 protein is expressed in a variety of tissues and distinct staining patterns in S100A6 immunohistochemistry may be useful in the differential diagnosis of difficult lesions. We evaluated the staining pattern of the S100A6 antibody in 22 cases each of pilar leiomyoma (LM), angioleiomyoma (ALM), and cutaneous leiomyosarcoma (LMS). S100A6 labeled both the nucleus and cytoplasm of myocytes in positive cases. About 64% of LM and 86% ALM had positive staining to the S100A6 antibody but predominantly in a weak staining pattern. In contrast, 95% of the LMS exhibited moderate to strong staining with the S100A6 antibody. The difference in the frequency of positive cases was statistically significant in the LM vs LMS comparison (p = 0.025), but we found intensity of staining to be of greatest practical utility. Analysis between the groups taking in to consideration differences in intensity of staining using the nonparametric rank sum (Mann–Whitney U test) demonstrated that there was a statistically significant difference between LM and LMS and between ALM and LMS. Weak or absent S100A6 staining supports a diagnosis of LM, whereas strong positive staining supports a diagnosis of LMS.     

Complete remission of leiomyosarcoma with lung and brain metastasis by chemoradiotherapy after surgery

Nowadays, leiomyosarcoma is stil dif icult to early diagnosis, has no standard treatment to fol ow, and the thera-peutic value of surgery, chemotherapy and radiotherapy haven’t been evaluated ef ective...     

A case of Epstein–Barr virus–associated pulmonary leiomyosarcoma arising five yr after a pediatric renal transplant

Suzuki K, Urushihara N, Fukumoto K, Watanabe K, Wada N, Takaba E. A case of Epstein–Barr virus–associated pulmonary leiomyosarcoma arising five yr after a pediatric renal transplant. Pediatr Transplantation 2011: 15: E145–E148. © 2010 John Wiley & Sons A/S. Abstract: EBV‐associated SMTs in immuno‐compromised patients have recently been reported. We report on a case of EBV‐associated pulmonary leiomyosarcoma arising five yr after renal transplantation. The patient was an eight‐yr‐old girl, who received a living related kidney transplant from her mother. She had had bilateral giant Wilm’s tumors as an infant and underwent bilateral nephrectomy at one and two yr of age. At the age of seven, she suffered from bronchitis several times, and a year later, two nodules were detected in her left lung by X‐ray and computed tomography. We suspected a recurrence of Wilm’s tumor and performed surgical resection. The pathological finding was SMT with moderate mitosis and no evidence of Wilm’s tumor. The fact that the tumors were positive for EBER suggested an association with the EBV. Six months later, there was a recurrence in her left lung. Surgical resection was performed, and immunosuppressive agents were reduced. Two yr after the second operation, she is well with no recurrence. We report the first case of EBV‐associated pulmonary leiomyosarcoma in a pediatric patient after renal transplantation owing to a malignant tumor.     

Laparoscopic pancreaticoduodenectomy for remnant pancreatic recurrence after laparoscopic distal pancreatectomy and hepatectomy for greater omentum leiomyosarcoma

Laparoscopic pancreatic surgery is one of the most difficult procedures, and the adoption of laparoscopic pancreaticoduodenectomy has been limited. The application of laparoscopic surgery has extended to advance cancer, but there have been no reports of laparoscopic pancreaticoduodenectomy after laparoscopic liver resection and distal pancreatectomy. In the present case, a 67‐year‐old woman was diagnosed with remnant pancreatic recurrence of metastatic greater omentum leiomyosarcoma. She had previously undergone laparoscopic distal pancreatectomy and left lateral liver sectionectomy in 2016. We performed laparoscopic subtotal stomach‐preserving pancreaticoduodenectomy in June 2017. The operation time was 274 minutes, and the estimated blood loss was 50 mL. There were no postoperative complications. In summary, laparoscopic pancreaticoduodenectomy is a safe and feasible procedure for a patient who had previously undergone pancreas and liver surgery.