Perioperative Care: Sarcoma and Melanoma

Introduction

Sarcoma is an umbrella term for malignant neoplasms of mesenchymal origin. A wide variety of underlying cell types can become neoplastic, and so these cancers are best understood by division into histologic subtype and anatomic location.

Sarcomas are rare cancers in adulthood, making up less than 1% of all adult malignancies. Approximately 10% are of bony origin and the remainder originate in soft tissues. The occurrence of soft tissue sarcomas is lowest amongst young adults and slowly increases as patients get older, with a dramatic increase in incidence over the age of 50 years. Incidence of bony sarcomas has a bimodal distribution, with a peak in adolescents and young teens, and a second smaller peak in incidence in the elderly. ^,

Risk factors for sarcomas are not well understood. There are certain genetic syndromes that predispose to the development of soft tissue and bone sarcomas. Germline mutation in TP53 causing Li–Fraumeni syndrome, loss of function of the NF1 gene causing neurofibromatosis, and RB1 gene-causing retinoblastoma and secondary malignancies are some of the more well-known syndromes. Geographic and race distribution of certain sarcomas, for example, Ewing sarcoma, being more common in Caucasian populations indicate further unidentified genetic links.

Environmental exposures have also been implicated in the development of sarcomas, but studies are small and results conflicting. Radiation exposure is clearly understood to increase the risk of sarcoma, and certain chemicals. However, there is currently insufficient evidence to generate guidelines on limiting exposure.

General Principles

Presentation of the sarcoma patient is determined both by the anatomic location of the tumor and the histologic subtype.

Extremity soft tissue tumors can present with a self-identified mass and symptoms due to invasion or compression of surrounding structures. Patients can complain of worsening pain or pain in a specific neurologic distribution. Persistent unexplained bone pain, recurrent limp, and pathologic fractures are all features of bony sarcomas.

Retroperitoneal tumors tend to present later, with larger tumors, due to the large area for the tumor to expand into before beginning to compress structures and cause symptoms. These patients often describe a prolonged course of vague abdominal symptoms, which are difficult to classify or correlate, prior to undergoing diagnostic scanning.

Diagnosis is usually confirmed by image-guided core biopsy, which permits targeting specific areas of the lesion that are most likely to provide diagnostic tissue. Core needle biopsy is used to reduce the risk of tumor seeding. However, should open incisional biopsy be required, it is advisable that this be done by the team who will perform the definitive resection, as open biopsies have a higher risk of tumor seeding. This incision must be carefully placed to allow later excision.

Retroperitoneal sarcomas provide their own challenges in terms of diagnosis and provision of tissue. The biopsy should be performed by a unit that regularly undertakes such biopsies, as sampling of tissue that is more likely to yield a diagnosis is important (for example, areas of increased density or metabolic activity on scanning). Peritoneal breaches and intraabdominal tumor seeding should be avoided wherever possible. Therefore all core biopsies should be performed via a retroperitoneal approach. Advice should be requested from a high-volume team as to the best method of proceeding. Core biopsy under direct vision can be considered but is at risk of being nondiagnostic and causing vascular injury.

When planning definitive treatment, cross-sectional imaging to assess the relationship of the primary tumor to adjacent organs, as well as to assess for the presence of metastatic disease, is required. Good quality imaging is useful for diagnosis and planning resection. Choice of imaging modality is based on surgeon preference, but CT for central tumors and MRI for skeletal and extremity masses are widely used as the starting point. Functional imaging such as fluorine-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) provides added information about tumor activity and distant disease. ^{, , ,}

Histology

The WHO classification of soft tissue tumors includes more than 100 histologic subtypes. Tumor diagnostics are dependent on histologic appearance, patterns of immunohistochemistry (IHC) staining, and molecular pathology. Specific mutations in genes, for example, EWSR1 in Ewing sarcoma, are commonly used to definitively diagnose certain tumors.

In general, sarcomas are named based on the presumed tissue of origin, for example, liposarcomas, leiomyosarcomas, angiosarcoma. This does not apply to all sarcomas and this can cause diagnostic dilemmas. Synovial sarcoma does not originate in synovium but was named because those were the cells that the tumor most closely resembled. IHC patterns are not always definitive. Histologic diagnosis is essential to allow for accurate prognostication and tailored therapy, both surgical and adjuvant. Tumor histology can predict both risk of local recurrence and distant metastasis, and this varies widely across different subtypes. Diagnosis also allows for consideration of added adjuvant or neoadjuvant therapy if benefit has been demonstrated. For example, different treatment strategies will be used when considering a patient with an undifferentiated pleomorphic sarcoma of the extremity, a tumor with a high risk of distant metastases compared to a myxofibrosarcoma, a locally aggressive tumor that has a high rate of local recurrence.

Natural History and Prognosis

The natural history of sarcoma depends on the histologic subtype, with a variety of disease trajectories. In general, the natural history of sarcoma is as a locally aggressive tumor with risk of hematogenous metastasis. Approximately 50% of soft tissue sarcomas (STS) will develop metastatic disease, most commonly in the lungs. Important prognostic factors include histologic grade, subtype, tumor size, pathologic stage, anatomic site, and age. Current American Joint Committee on Cancer (AJCC) staging (8 ^th edition) also separates extremity and retroperitoneal tumours.

Management

Once histology has been confirmed and the intent of treatment has been assessed as curative or palliative, a management plan can be determined. As with other solid malignancies, the aim of treatment is to minimize the risk of local recurrence and distant metastasis while maximizing the functional outcome. Choice of treatment varies according to histology and lesion location, but many types of sarcoma will receive neoadjuvant chemotherapy or radiotherapy prior to definitive surgical resection.