Cancer, Liposarcoma

Article Author:
Rabia Zafar
Article Editor:
Yurong Wheeler
Updated:
6/4/2019 4:01:16 PM
PubMed Link:
Cancer, Liposarcoma

Introduction

Liposarcoma, a tumor of lipoblasts, is a rare mesenchymal neoplasm and involves deep soft tissues including retroperitoneum and popliteal fossa [1]. The relative frequency of liposarcoma at various body sites is much dependent on the tumor subtypes.  For example, dedifferentiated liposarcoma is much more common in retroperitoneal location, while myxoid liposarcoma occurs in the lower extremities [2]. Liposarcoma is exceedingly rare in the esophagus [1][3].  Esophageal liposarcoma typically behaves as a slow-growing tumor and involves the upper part of the throat. Most of them are of a well-differentiated type, confined to the esophagus with a low risk of metastasis [[4], and have a high rate of local recurrence (10%), even up to 25 years after the resection [5].    

Etiology

The cause of liposarcoma is still unknown, although trauma has been implicated.

Epidemiology

Although liposarcoma is the most common soft tissue sarcoma of adults, it is rare in the esophagus. The most common esophageal cancer in the United States is adenocarcinoma and worldwide is squamous cell carcinoma. Overall, sarcoma only accounts for 0.5% of all esophageal neoplasms [6]. Among those, only 40 cases of esophageal liposarcoma have been reported [5]. According to these published cases, esophageal liposarcoma tends to occur in the middle to elderly male patients (age range 38-83 years, with an average of 62 years; male to female ratio = 4:1) [5].

Pathophysiology

Liposarcoma is a complex tumor, and its pathophysiology can be best explained by dividing it into three subtypes (per WHO 2002), well-differentiated and dedifferentiated liposarcoma (WDLPS/DDLPS), myxoid and round cell liposarcoma (MLS and RCL), and pleomorphic liposarcoma (PLS).  WDLPS/DDLPS will have a diagnostic giant marker and ring chromosome, which have an overall effect of uncontrolled cell proliferation [7].  For MCL and RCL, reciprocal translocation occurs between chromosomes 12 and 16, leading to the fusion of genes DDIT3 and FUS, and subsequently, activating some downstream targets such as PPARgamma2 and C/EBPalpha which promotes cell cycle proliferation [7].  Pleomorphic liposarcoma is the most complex and least understood type of these three. Mutations in various tumor suppressor pathways like p53, NF1, RB1 lead to many gains and hence account for the aggressive nature of this tumor [8].

Histopathology

The most common type of esophageal liposarcoma is the well-differentiated type, which is characterized histologically by mature adipocytes with a variable amount of fibrous stroma containing atypical nuclei. It has three main subtypes, the lipoma-like subtype, the sclerosing subtype, and the inflammatory subtype.  The lipoma-like subtype frequently has lipoblasts and scattered atypical cells. This type closely mimics benign lipoma.  The sclerosing subtype has abundant fibrous areas with scant lipogenic components.  The inflammatory subtype has chronic inflammatory infiltrate, with a predominance of B cells. These cells can pose a diagnostic challenge as inflammatory infiltrate can obscure the adipocytes.

The second most common type of esophageal liposarcoma is the myxoid liposarcoma (MLS), which is subdivided into low grade and high-grade tumors. Low-grade MLS have low cellularity with bland nuclei and a rich, prominent network of curving capillaries, resembling a chicken wire pattern.  High-grade MLS are markedly hypercellular with solid sheets of round cells comprising at least 5% of the tumor.

The least common type of esophageal liposarcoma is the pleomorphic type, which has marked pleomorphic cells occupying at least 65% of the tumor and at least focal areas of typical liposarcoma.

History and Physical

The most common site of esophageal liposarcoma is the upper esophagus, which explains most of the symptoms associated with this neoplasm. Patients usually present with progressive dysphagia with weight loss[5].  In some cases, when the size of the tumor is large, patients also present with polyp/mass protruding from mouth [9].  Regurgitation of food can occur. Shortness of breath and cough are less common symptoms due to the compression of the trachea [[6].

Evaluation

Different radiology diagnostic modalities such as barium swallow, CT scan, magnetic resonance imaging (MRI) and esophagogastroduodenoscopy, can be used to diagnose esophageal liposarcoma.  Although none of these techniques is specific, CT scan and MRI can be more helpful in narrowing down the differential diagnosis as both modalities can detect the percentage of a lipomatous component of the tumor. Higher fat content is associated with benign lipoma, while less fat is consistent with atypical lipoma or sarcoma. A definitive diagnosis can only be achieved by tissue examination.  And in the majority of the cases, complete resection of the tumor is needed for a correct diagnosis [5].

Treatment / Management

Surgical excision is the mainstay of treatment [1].  Depending on the size of the tumor, the surgery can be either a minimally invasive endoscopic submucosal resection [10], or an aggressive partial or total esophagectomy. There are some case reports of using adjuvant radiation therapy to decrease the rate of recurrence. However, the role of adjuvant chemo and radiation therapy is controversial, and long-term follow-up is recommended due to the high rate of recurrence [[5].   

Differential Diagnosis

There are some other benign or neoplastic lesions in the esophagus clinically and microscopically mimicking liposarcoma.   First is the typical lipoma, which is composed of benign mature adipose tissue and lacks lipoblasts or any atypical nuclei. Second is the fibroepithelial polyp, which is usually characterized histologically by fibrovascular cores with overlying non-keratinizing squamous epithelium.  Although large polyps may have adipose tissue with myxoid areas, closely mimicking myxoid or well-differentiated liposarcoma, they can be ruled out by immunohistochemical stains (fibroepithelial polyp stains negative for either CDK4 or MDM2).  Leiomyoma/leiomyosarcoma and gastrointestinal stromal tumor are two other entities that can mimic liposarcoma.  Leiomyoma/leiomyosarcoma are composed of intersecting bundles of smooth muscle cells that have characteristic nuclei with blunt ends and are immunohistochemically positive for actin and desmin.  Gastrointestinal stromal tumor cells are also spindle-shaped but show immunoreactivity to CD34 and c-Kit (CD117) [8].

Prognosis

The prognosis of the esophageal liposarcoma depends on several factors. The most important ones are the histological type and grade of the tumor, location of cancer, and the status of surgical margins. [4].  A well-differentiated liposarcoma has been reported to have a 50% rate of recurrence with no risk of distant metastasis and an excellent five-year survival rate (75-100%), while myxoid and pleomorphic liposarcomas have a higher percentage of recurrence (up to 80%) and a poor to intermediate survival rate (ranging from 4 -107 months).   De-differentiated liposarcoma has a risk of distal metastasis.  Positive surgical resection margin is associated with local recurrence.  Although there are some case reports of using adjuvant radiation therapy to decrease the rate of recidivism, the role of adjuvant chemo and radiation therapy is controversial as there are significant comorbidities associated with the radiation of mediastinum.

Complications

Long-standing esophageal liposarcoma can have serious complications, such as dysphagia and consequent anemia and weight loss, and regurgitation associated aspiration, asphyxiation and respiratory failure [11].

Enhancing Healthcare Team Outcomes

Esophageal liposarcoma is a rare entity with a high rate of recurrence. The clinical presentation and symptoms are not very specific.  Radiological examination modalities such as barium swallow, esophagomanometry, chest CT/MRI, are not very sensitive to make this diagnosis.  A definitive diagnosis can only be made by tissue biopsy/excision, and in most cases, an entire tumor excision with microscopic examination is required as the small biopsy material can be misleading.

A multidisciplinary approach is needed for better patient outcome. Surgical resection is the mainstay of the treatment.  Depending on the size of the tumor, this can be performed either as a minimally invasive endoscopic submucosal excision (for small tumors with narrow stalk), or partial/total esophagectomy (for large tumor) [10].  The role of oncology is not clear at this moment. Adjuvant radiotherapy is used in some cases to decrease the rate of recurrence; however, this is controversial, and there are currently no established guidelines [5].   


References

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