Surgery and stereotactic radiosurgery for spinal leiomyosarcoma: a single-institution retrospective series and systematic review.

OBJECTIVE: Leiomyosarcoma (LMS) is a rare, aggressive soft-tissue sarcoma that seldom spreads to the bone. The spine can be either the site of LMS osseous metastases or the primary tumor site. The optimal treatment option for spinal LMS is still unclear. The authors present a cohort of patients with spinal LMS treated with either upfront surgery or upfront CyberKnife stereotactic radiosurgery (SRS). METHODS: The authors retrospectively studied the clinical and radiological outcomes of 17 patients with spinal LMS treated at their institution between 2004 and 2020. Either surgery or SRS was used as the upfront treatment. The clinical and radiological outcomes were assessed. A systematic review of the literature was also conducted. RESULTS: Of the 17 patients (20 spinal lesions), 12 (70.6%) were female. The median patient age was 61 years (range 41-80 years). Ten patients had upfront surgery for their spinal lesions, and 7 had upfront CyberKnife radiosurgery. The median follow-up was 11 months (range 0.3-130 months). The median overall survival (OS) for the entire cohort was 13 months (range 0.3-97 months). In subgroup analysis, the median OS was lower for the surgical group (13 months, range 0.3-50 months), while the median OS for the SRS group was 15 months (range 5-97 months) (p = 0.5). Forty percent (n = 4) of those treated with surgery presented with local recurrence at a median of 6.7 months (range 0.3-36 months), while only 14% (n = 1) of those treated with CyberKnife radiosurgery had local recurrence after 5 months. Local tumor control (LTC) rates at the 6-, 12-, and 18-month follow-ups were 72%, 58%, and 43%, respectively, for the SRS group and 40%, 30%, and 20%, respectively, for the surgery group (p < 0.05). The literature review included 35 papers with 70 patients harboring spinal LMS; only 2 patients were treated with SRS. The literature review confirms the clinical and radiological outcomes of the surgical group, while data on SRS are anecdotal. CONCLUSIONS: The authors present the largest series in the literature of spinal LMS and the first on SRS for spinal LMS. This study shows that LTC is statistically significantly better in patients receiving upfront SRS instead of surgery. The OS does not appear different between the two groups.

A Spatiotemporal and Machine-Learning Platform Accelerates the Manufacturing of hPSC-derived Esophageal Mucosa.

Human pluripotent stem cell-derived tissue engineering offers great promise in designer cell-based personalized therapeutics. To harness such potential, a broader approach requires a deeper understanding of tissue-level interactions. We previously developed a manufacturing system for the ectoderm-derived skin epithelium for cell replacement therapy. However, it remains challenging to manufacture the endoderm-derived esophageal epithelium, despite both possessing similar stratified structure. Here we employ single cell and spatial technologies to generate a spatiotemporal multi-omics cell atlas for human esophageal development. We illuminate the cellular diversity, dynamics and signal communications for the developing esophageal epithelium and stroma. Using the machine-learning based Manatee, we prioritize the combinations of candidate human developmental signals for in vitro derivation of esophageal basal cells. Functional validation of the Manatee predictions leads to a clinically-compatible system for manufacturing human esophageal mucosa. Our approach creates a versatile platform to accelerate human tissue manufacturing for future cell replacement therapies to treat human genetic defects and wounds.

First Recurrence of Synovial Sarcoma Presenting With Solitary Pancreatic Mass.

Synovial sarcoma usually presents in the lower extremities and metastasizes to the lungs; however, unusual patterns of recurrence can occur. For patients with recurrent synovial sarcoma to a proximal peripancreatic lymph node, a pancreaticoduodenectomy or Whipple procedure is the best option for a cure. Lymph node metastasis from synovial sarcoma is exceptionally rare, and data guiding the use of the Whipple procedure for curative resection of metastatic synovial sarcoma are even more sparse. In this report, we describe the management of a patient with metastatic synovial sarcoma to a proximal peripancreatic lymph node with a pancreaticoduodenectomy.

Methylation profiling reveals novel molecular classes of rhabdomyosarcoma.

Rhabdomyosarcomas (RMS) represent a family of aggressive soft tissue sarcomas that present in both children and adults. Pathologic risk stratification for RMS has been based on histologic subtype, with poor outcomes observed in alveolar rhabdomyosarcoma (ARMS) and the adult-type pleomorphic rhabdomyosarcoma (PRMS) compared to embryonal rhabdomyosarcoma (ERMS). Genomic sequencing studies have expanded the spectrum of RMS, with several new molecularly defined entities, including fusion-driven spindle cell/sclerosing rhabdomyosarcoma (SC/SRMS) and MYOD1-mutant SC/SRMS. Comprehensive genomic analysis has previously defined the mutational and copy number spectrum for the more common ERMS and ARMS and revealed corresponding methylation signatures. Comparatively, less is known about epigenetic correlates for the rare SC/SRMS or PRMS histologic subtypes. Herein, we present exome and RNA sequencing, copy number analysis, and methylation profiling of the largest cohort of molecularly characterized RMS samples to date. In addition to ARMS and ERMS, we identify two novel methylation subtypes, one having SC/SRMS histology and defined by MYOD1 p. L122R mutations and the other matching adult-type PRMS. Selected tumors from adolescent patients grouped with the PRMS methylation class, expanding the age range of these rare tumors. Limited follow-up data suggest that pediatric tumors with MYOD1-mutations are associated with an aggressive clinical course.

Surgical resection of leiomyosarcoma of the inferior vena cava: A case series and literature review.

OBJECTIVES: We review our institution's experience in treating leiomyosarcomas involving the inferior vena cava, and we offer guidance on the management. METHODS: A text-based search was performed to identify all patients who underwent surgical resection between January 2002 and October 2020. Clinicopathologic data, intraoperative variables, and outcomes were extracted from chart review. RESULTS: Twelve of 16 patients (75%) had localized disease; the remaining had limited metastatic disease. Seven of 16 patients (44%) received neoadjuvant chemotherapy or radiation; three patients had partial responses, and four patients had stable disease using RECIST 1.1 criteria. IVC reconstruction was performed in 14 of 16 patients (88%); IVC was ligated for the remaining two patients. Half of all patients had R0 resection on final pathology; the remaining had R1 resections. Progression-free survival (PFS) and overall survival (OS) were not statistically different between patients with R0 and R1 resection. Median PFS was 1.8 years (95% CI 0.89 - not reached); median OS was 6.5 years (1.8 - not reached). Only one patient (6%) experienced local disease recurrence; 4 of 16 patients (25%) experienced disease recurrence distally without local recurrence. CONCLUSIONS: Resection of IVC leiomyosarcomas at a sarcoma referral center with experience in vascular reconstruction can lead to many years of recurrence-free survival. Surgical resection should be offered to patients with a low volume of metastatic disease to reduce local complications from the primary tumor, many of which exert significant mass effect on surrounding organs. For patients with metastatic disease or large, high-risk tumors, neoadjuvant chemotherapy can provide a biologic test of disease stability prior to resection.

Evidence for a 'preinvasive' variant of fungal sinusitis: Tissue invasion without angioinvasion.

Clinical experience has suggested the existence of an intermediate form of fungal sinusitis between the categories of non-invasive fungal sinusitis (non-IFS) and invasive fungal sinusitis (IFS). This fungal sinusitis variant demonstrates unhealthy mucosa by endoscopy with fungal invasion, but lacks angioinvasion microscopically, representing what clinically behaves as a 'pre-invasive' subtype of fungal sinusitis. Unlike non-IFS disease, patients with pre-invasive fungal sinusitis were still felt to require anti-fungal medications due to histologic presence of invasive fungus. While sharing some clinical features of IFS, these 'intermediate' patients were successfully spared extended and repeated surgical debridements given the microscopic findings, and have been successfully treated with shorter courses of antifungal therapy. These select patients have had favorable outcomes when managed in a judicious and semi-aggressive manner, in an undefined zone between the treatments for routine fungal ball and aggressive IFS.