Leiomyosarcoma is a malignant smooth muscle neoplasm with a complicated histopathologic classification scheme and marked differences in clinical behavior depending on the anatomic site of origin. Overlapping morphologic features of benign and borderline malignant smooth muscle neoplasms further complicate the diagnostic process. Likewise, deciphering the complex and heterogeneous patterns of genetic changes which occur in this cancer has been challenging. Preliminary studies suggest that reproducible molecular classification may be possible in the near future and new prognostic markers are emerging. Robust recapitulation of leiomyosarcoma in mice with conditional deletion of Pten in smooth muscle and the simultaneous discovery of a novel role for Pten in genomic stability provide a fresh perspective on the mechanism of leiomyosarcomagenesis and promise for therapeutic intervention.

Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22)(q24;q12). This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered.

Despite a heightened appreciation of the many defining molecular aberrations in Ewing sarcoma, the cooperative genetic environment and permissive cell of origin essential for EWS/ETS-mediated oncogenesis remain elusive. Consequently, inducible animal and in vitro models of Ewing sarcoma from a native cellular context are unable to fully recapitulate malignant transformation. Despite these shortcomings, human, and murine mesenchymal stem cells (MSCs) are the closest working in vitro systems available. MSCs are tolerant of ectopic EWS/FLI expression, which is accompanied by a molecular signature most similar to Ewing sarcoma. Whether MSCs are the elusive cell of origin or simply a tolerant platform of the EWS/FLI transcriptome, these cells have become an excellent molecular tool to investigate and manipulate oncogenesis in Ewing sarcoma. Our understanding of the biological complexity and heterogeneity of human MSCs (hMSCs) has increased substantially over time and as such, appreciation and utilization of these salient complexities may greatly enhance the efficient use of these cells as surrogate models for Ewing sarcoma tumorigenesis.

Soft tissue sarcomas are a rare group of mesenchymal malignancies which can range from low to high grade. These tumors have different clinical, radiographic, and histopathological characteristics. Beta human chorionic gonadotropin is a naturally secreted hormone by placental syncytiotrophoblast cells during pregnancy. On very rare occasions, sarcomas can develop the ability to ectopically produce human chorionic gonadotropin. Very few cases exist in the literature of soft tissue sarcomas expressing this hormone. We report the case of a 55-year-old female who presented with a posterior thigh soft tissue sarcoma who on the day of surgical resection was found to have an unusually elevated serum human chorionic gonadotropin. Positive immunohistochemical staining of the resected mass confirmed the sarcoma as the source of the beta human chorionic gonadotropin.

Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis.

Background

There are several options for proximal humerus reconstruction in young children after resection of a malignant tumor and no one technique has been definitively shown to be superior to others, leaving the decision to surgeon and patient choice. Claviculo pro humeri (CPH) is a biologic reconstruction of the proximal humerus using the patient's ipsilateral clavicle as a rotational osseous flap. CPH represents a potential option for this complicated clinical problem in very young children, but little is known about it because the indications for its use are so uncommon.

Questions/purposes

The purposes of this study were to (1) assess the oncologic outcomes of CPH at a minimum of 2 years in a small series of patients; (2) elicit the complications associated with this procedure; and (3) show the Musculoskeletal Tumor Society (MSTS) functional score of these patients.

Methods

Four patients (average age, 5 years 11 months; range, 4 years 5 months to 8 years 9 months at the time of surgery) were treated with CPH for reconstruction after resection of a proximal humerus sarcoma; this represented all of the patients treated with this approach for this problem between January 2008 and April 2011 at one institution. During this period, the general indications for using CPH were the need to reconstruct a proximal humerus defect in a child younger than 10 years of age. During this time, CPH was used for all patients treated for proximal humerus sarcomas meeting these criteria. Patient demographics, diagnosis, tumor size and extent, operative details, radiographs and MRIs, complications, and functional outcomes were assessed.

Results

All are alive with no evidence of disease at a minimum followup of 31 months (average, 43 months; range, 31-58 months). Two patients developed nonunion and underwent revision surgery. Osseous union and a stable neoshoulder articulation were ultimately obtained in all patients. Limited shoulder motion was the only functional deficit noted with forward elevation ranging between 30° and 90°. MSTS functional scores were excellent with a range of 87% to 90%.

Conclusions

This is a rarely used procedure in North America but we achieved functional limb salvage in all four patients. Consistent with prior literature, nonunion was the major complication in this series. The two nonunions were successfully treated without interruption of chemotherapy or significant bone graft donor site morbidity. Based on these results, the authors suggest that this procedure is a reasonable reconstruction option to consider after proximal humerus resection in patients younger than 10 years of age. Further followup will be required to assess long-term results and to determine how this procedure compares with the alternatives.

Level of evidence

Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Background and objectives

While convention defines atypical neurofibroma as benign and low-grade malignant peripheral nerve sheath tumors (MPNSTs) as malignant, sparse outcomes data exist for these tumors. This study reviews clinical outcomes of surgically resected low-grade MPNST and atypical neurofibroma, focusing on the effect of surgical margins on outcome.

Methods

This study is a retrospective review of 23 patients who underwent surgical resection of a low-grade MPNST or atypical neurofibroma. Treatment characteristics of adjuvant therapy and surgical margin were noted. Endpoints of local recurrence, presence of metastatic disease, disease-specific survival, and overall survival were reviewed.

Results

Eighteen of 23 patients (78%) had microscopically positive margins on the resection. Disease-specific survival was 100% for both atypical neurofibroma patients and those with low-grade MPNST, regardless of surgical margin. Local recurrence in terms of recurrence of measureable disease occurred in 2/12 (16.7%) of LGMPNST patients and 1/11 (9.1%) of atypical NF patients, all of whom had microscopically positive surgical margins.

Conclusions

In a study dedicated exclusively to "intermediate" nerve sheath tumors, no patients developed metastatic disease nor died of disease despite a high rate of microscopically positive surgical margins (78%). While positive margins did lead to increased rates of local recurrence, these data suggest that surgeons potentially can temper their zeal for negative surgical margins in the setting of low-grade MPNST and atypical neurofibroma, as surgical morbidity may be more important than a presumed survival benefit of wide resection.

Extra-abdominal desmoid tumors are a significant cause of morbidity in patients with familial adenomatous polyposis syndrome. Understanding of the basic biology and natural history of these tumors has increased substantially over the past decade. Accordingly, medical and surgical management of desmoid tumors has also evolved. This paper analyzes recent evidence pertaining to the epidemiology, molecular biology, histopathology, screening, and treatment of extra-abdominal desmoid tumors associated with familial adenomatous polyposis syndrome.

There is much ambiguity surrounding the diagnosis of nerve sheath tumors, including atypical neurofibroma and low-grade MPNST, and yet, the distinction between these entities designates either benign or malignant behavior and thus carries presumed profound prognostic importance that often guides treatment. This study reviews the diagnostic criteria used to designate atypical neurofibroma from low-grade MPNSTs and reviews existing literature the natural history of each of these tumors to see if the distinction is, in fact, of importance.

Rotationplasty is an alternative reconstructive strategy after sarcoma resection that often gets overlooked due to concerns about cosmesis. "Rotating" a distal segment 180 degrees and fixing it to a proximal segment leaves a highly-functional, durable reconstruction that functionally compares favorably to other limb-salvage techniques. Cosmetic outcomes have no discernible impact of the emotional and social functioning of cancer survivors following rotationplasty. This chapter discusses techniques of rotationplasty, as well as its oncologic, functional and emotional outcomes.