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Clinical presentation and diagnosis of retroperitoneal soft tissue sarcoma

Clinical presentation and diagnosis of retroperitoneal soft tissue sarcoma
Literature review current through: May 2024.
This topic last updated: Feb 26, 2024.

INTRODUCTION — Sarcomas are malignant tumors that arise from skeletal and extraskeletal connective tissues. Most soft tissue sarcomas (STS) present in the extremities, but many other sites can be affected, including the retroperitoneum, chest wall, head and neck, and subcutaneous tissues.

The clinical presentation and diagnosis of retroperitoneal STS are discussed here. The initial management of retroperitoneal STS and the management of locally recurrent retroperitoneal STS are discussed separately.

(See "Initial management of retroperitoneal soft tissue sarcoma".)

(See "Management of locally recurrent retroperitoneal sarcoma".)

ANATOMY OF THE RETROPERITONEUM — The retroperitoneum is the space just posterior to the peritoneal cavity and anterior to the paraspinous musculature. The paraspinous musculature includes the psoas major, psoas minor, quadratus lumborum, obturator internus, and pyriformis. Superiorly, the retroperitoneum is bordered by the diaphragm and, inferiorly, it forms a natural extension to the pelvis (pelvic diaphragm) (figure 1) [1].

The structures of the retroperitoneum (figure 2) include the kidneys, adrenal glands, and perirenal fat bilaterally, the aorta and its branches (eg, renal arteries), the inferior vena cava and its tributaries (eg, renal veins), and the bilateral iliac vessels (common, internal, external iliac arteries/veins), as well as the third portion of the duodenum and pancreas. The ascending and descending colon are considered partially retroperitoneal.

EPIDEMIOLOGY — Retroperitoneal soft tissue sarcomas (STS) are rare cancers that make up approximately 10 to 15 percent of all STS [2]. The average annual incidence is approximately 2.7 cases per million people [3].

CLINICAL PRESENTATION

Age and sex — Retroperitoneal soft tissue sarcomas (STS) usually present in patients in their 50s but can occur at any age [4-6]. Retroperitoneal STS is diagnosed with equal frequency in males and females.

Clinical symptoms — Retroperitoneal STS typically does not cause symptoms until the tumor is large enough to compress or invade surrounding anatomic structures. Most tumors are already large and locally advanced when they are initially detected, with a median size at diagnosis of approximately 15 cm [4].

Some patients may present with an incidental abdominal mass that is asymptomatic or minimally symptomatic. Others may present with abdominal pain and/or symptoms related to mass effect of the tumor on surrounding structures, such as:

Lower extremity edema due to compression of retroperitoneal venous structures. (See "Overview of iliocaval venous obstruction".)

Referred pain to the groin or lower extremities due to compression or local invasion of the retroperitoneal nerves (figure 3) or musculoskeletal structures.

Weight loss, early satiety, and/or bowel obstruction due to compression or local invasion of the gastrointestinal tract.

Serous ascites due to portal venous compression [7,8].

Other clinical symptoms include fevers, night sweats, flu-like symptoms, and weight loss in patients with high-grade, rapidly expanding tumors [7,9]. Rarely, retroperitoneal STS may present with paraneoplastic hypoglycemia, which is usually secondary to tumor production of "big" insulin-like growth factor 2 (IGF-2) [7,8,10]. (See "Nonislet cell tumor hypoglycemia".)

Distant metastases are present at the time of diagnosis in approximately 10 percent of patients [11]. The most common sites of disease include the lung and the liver. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Pattern of spread'.)

Physical exam — The physical examination should include palpation of all lymph node basins and an abdominal exam, which may demonstrate an abdominal mass. Other potential findings may include ascites, hepatic masses or lower extremity edema. (See "Evaluation of the adult with abdominal pain".)

Male patients with a retroperitoneal mass should also undergo a careful testicular examination to assess for a mass (with follow-up testicular ultrasound as indicated), since testicular cancer can metastasize to the retroperitoneal nodes. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'Testicular examination'.)

DIAGNOSTIC EVALUATION

When to suspect the diagnosis — The diagnosis of retroperitoneal soft tissue sarcomas (STS) should be suspected in patients with a retroperitoneal mass that is unifocal and extravisceral on imaging studies and without clinical evidence for an alternative cancer diagnosis (eg, no widespread lymphadenopathy concerning for lymphoma; no clinical or imaging evidence of a testicular mass; no elevated tumor markers specific to a germ cell tumor).

Most neoplasms that arise within the retroperitoneal space are malignant (80 percent). Furthermore, most patients who present with a primary retroperitoneal, extravisceral, unifocal soft tissue mass will be found to have a sarcoma. A careful diagnostic evaluation is necessary to distinguish between retroperitoneal STS and other conditions.

Differential diagnosis — The differential diagnosis for a retroperitoneal mass includes lymphoma, a primary germ cell tumor, or metastatic testicular cancer. Cancers originating in the duodenum, pancreas, adrenal glands, or kidney can be distinguished from retroperitoneal STS using imaging studies, as the former tumors arise from their respective organs whereas retroperitoneal soft tissue masses are extravisceral. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors" and "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum".)

The differential diagnosis also includes schwannomas and paragangliomas, particularly for retroperitoneal masses located in the midline adjacent to the aorta or vena cava. (See "Peripheral nerve tumors", section on 'Schwannoma' and "Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology".)

Two typically benign processes, Castleman disease (angiofollicular lymph node hyperplasia) and retroperitoneal fibrosis, arise within the retroperitoneum and can mimic retroperitoneal STS both clinically and radiographically. (See "Unicentric Castleman disease" and "Clinical manifestations and diagnosis of retroperitoneal fibrosis".)

Imaging studies — All patients with a retroperitoneal mass must undergo imaging studies to further characterize the mass and assess for resectability.

Computed tomography – We obtain a computed tomography (CT) scan of the abdomen and pelvis with both oral and intravenous contrast to evaluate the primary tumor site and a CT scan of the chest to assess for metastatic disease to the lungs. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Pattern of spread'.)

CT is preferred to magnetic resonance imaging (MRI) to evaluate the primary tumor. In most cases, CT is less sensitive to motion artifact than MRI, and it better defines the anatomic relationship of the tumor to other abdominal organs. It can also detect metastases to the liver or peritoneum. The radiographic appearance of the primary tumor on a CT scan can also offer clues as to the histologic subtype and grade, which may guide decisions as to the need for a pretreatment biopsy as well as treatment.

MRI – For patients with an allergy to intravenous CT iodinated contrast agent, MRI of the abdomen and pelvis with gadolinium contrast may be obtained in addition to or as an alternative to a non-contrast enhanced CT abdomen and pelvis. For those with an initial CT that demonstrates equivocal muscle, vessel, bone, or foraminal involvement, and/or for some pelvic tumors, a follow-up MRI of the abdomen and pelvis may better delineate tumor involvement of these structures [12]. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'MRI and CT'.)

Positron emission tomography (PET)-CT imaging is not routinely used for the initial work-up of a retroperitoneal soft tissue mass. Further details are discussed separately. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'PET and PET/CT'.)

Laboratory studies — We obtain a complete blood count with differential and a lactate dehydrogenase (LDH) level. A complete blood count with differential is used to assess for leukocytosis, which can be seen in some patients with rapidly expanding tumors [7,9] (see 'Clinical symptoms' above). An isolated LDH in the context of lymphadenopathy may also be suggestive of lymphoma. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors" and "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults" and "Clinical presentation and initial evaluation of non-Hodgkin lymphoma".)

For patients in whom germ cell tumor is in the differential diagnosis, laboratory studies should include measurement of LDH, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (beta-hCG). If elevated, these tumor markers would raise the suspicion for a germ cell tumor. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors" and "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults" and "Clinical presentation and initial evaluation of non-Hodgkin lymphoma".)

Diagnostic biopsy — The diagnosis of retroperitoneal STS is confirmed through diagnostic biopsy with histopathologic analysis demonstrating sarcoma. (See 'Histopathology' below.)

For most patients with suspected retroperitoneal STS, we strongly prefer to obtain tissue using an image-guided percutaneous core needle biopsy rather than proceeding directly to surgery. Obtaining a core needle biopsy allows confirmation of the diagnosis and specific histology prior to initiating treatment (such as neoadjuvant therapy). This approach is safe and does not increase the risk of local recurrence or decrease overall survival [13,14]. Tumor seeding of the biopsy tract is rare [15].

Initial surgery without biopsy (for both pathologic diagnosis and treatment) is an alternative in very select situations, such as patients suspected to have well-differentiated liposarcoma based on initial imaging studies who will not receive neoadjuvant (preoperative) therapy. Patients who are being evaluated for this approach must receive multidisciplinary evaluation at a high-volume sarcoma center so that the risks and benefits of initial surgery versus other approaches (ie, neoadjuvant therapy) can be discussed by medical oncology, radiation oncology, and surgical oncology. Further details are discussed separately. (See "Surgical resection of retroperitoneal sarcoma", section on 'Imaging and pathology' and "Initial management of retroperitoneal soft tissue sarcoma".)

HISTOPATHOLOGY

Adults — In adults, the most common histologic types of retroperitoneal soft tissue sarcomas (STS) are liposarcoma and leiomyosarcoma, followed by undifferentiated/unclassified STS, a subset of which is differentiated pleomorphic sarcoma. Other histologic types may be observed in the retroperitoneum, but they are less common.

Liposarcomas — Among the different variants of liposarcoma that present in the retroperitoneum, the most common are well-differentiated (low-grade) liposarcomas, followed by dedifferentiated liposarcomas. Myxoid, round cell, and pleomorphic liposarcomas are uncommonly found in the retroperitoneum. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Most common subtypes'.)

Well-differentiated liposarcoma – Microscopically, well-differentiated liposarcomas consist of a background of adipocytes that contain scattered lipoblasts, each with a single atypical nucleus surrounded by large intracytoplasmic vacuoles. There is often an inflammatory cell infiltrate. Hypercellular well-differentiated liposarcomas may be confused with dedifferentiated liposarcomas [16].

Well-differentiated liposarcomas that arise in the body wall/trunk or extremity are referred to as atypical lipomatous tumors since they do not metastasize to distant organs [17]. However, these tumors do have a propensity for local recurrence in the retroperitoneum/mediastinum and spermatic cord [17]. Although not common, well-differentiated liposarcoma can also recur as a dedifferentiated liposarcoma, which is more aggressive in nature. For example, a well-differentiated liposarcoma that contains areas of sclerosis or inflammatory changes may be at higher risk for locoregional recurrence or regrowth as a dedifferentiated liposarcoma than a well-differentiated liposarcoma that is purely lipoma-like [18,19].

Dedifferentiated liposarcoma Dedifferentiated liposarcomas are defined by the presence of sharply demarcated regions of nonlipogenic sarcomatous tissue within a well-differentiated tumor [17]. They may be difficult to distinguish from undifferentiated pleomorphic sarcoma [17,20-22]. Most dedifferentiated liposarcomas are high-grade tumors (grade 2 or 3). Compared with well-differentiated low-grade liposarcomas, they have higher local recurrence rates, the potential to metastasize (distant recurrence rate of 20 to 30 versus 0 percent), and a sixfold higher risk of death [23,24]. It is thought that high-grade dedifferentiated liposarcomas may arise from well-differentiated liposarcomas.

Leiomyosarcomas — Leiomyosarcomas (LMS) of the retroperitoneum generally arise from the inferior vena cava, its tributaries, or any small vessel. LMS often presents as a mass or, occasionally, with unilateral or bilateral lower extremity swelling. These tumors are often large at diagnosis. The histopathology of LMS is discussed separately. (See "Uterine sarcoma: Classification, epidemiology, clinical manifestations, and diagnosis", section on 'Leiomyosarcoma'.)

In patients with retroperitoneal LMS, lung or liver metastases are sometimes observed at the time of presentation or appear relatively quickly after diagnosis. LMS may also arise from the wall of the gastrointestinal tract or from the uterus. In this situation, they are visceral rather than retroperitoneal, and they have a greater risk of peritoneal spread and metastasis to the liver. (See "Uterine sarcoma: Classification, epidemiology, clinical manifestations, and diagnosis".)

For these reasons, surveillance imaging of the lungs and liver is imperative in patients with treated LMS. (See "Initial management of retroperitoneal soft tissue sarcoma", section on 'Posttreatment follow-up'.)

Others — Other less common histologic types that present in the retroperitoneum include undifferentiated/unclassified STS, malignant peripheral nerve sheath tumor, synovial sarcoma, solitary fibrous tumor, and desmoplastic small round cell tumor [25]. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma" and "Solitary fibrous tumor".)

Children — Among children, the most common histologic types of retroperitoneal sarcomas (RPS) are extraskeletal Ewing sarcoma/primitive neuroectodermal tumor (PNET), alveolar rhabdomyosarcoma, and fibrosarcoma [26]. The clinical presentation of these tumors is discussed separately. (See "Clinical presentation, staging, and prognostic factors of Ewing sarcoma" and "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging".)

STAGING — Retroperitoneal soft tissue sarcomas (STS) are staged using the eighth edition of the Tumor, Node, Metastasis (TNM) system as defined by the combined American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC). The AJCC/UICC staging system has separate T stage classification (stratified according to size) and prognostic stage groupings for RPS (table 1) [27]. However, tumor size is not a prognostic factor for retroperitoneal STS [4,5,20,21,28-30].

The eighth edition of the AJCC/UICC staging system for retroperitoneal sarcomas (RPS) also includes a nomogram to predict disease-free and overall survival (figure 4) [31].

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (See "Patient education: Soft tissue sarcoma (The Basics)".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Soft tissue sarcoma".)

SUMMARY AND RECOMMENDATIONS

Common histologies – Retroperitoneal soft tissue sarcomas (STS) are rare cancers that make up approximately 10 to 15 percent of all STS. The most common histologies are liposarcoma (both well-differentiated and dedifferentiated) and leiomyosarcoma. (See 'Epidemiology' above and 'Histopathology' above.)

Clinical presentation – Retroperitoneal STS typically does not cause symptoms until the tumor is large enough to compress or invade surrounding anatomic structures. (See 'Clinical symptoms' above.)

Some patients may present with an incidental abdominal mass that is asymptomatic or minimally symptomatic.

Others may present with abdominal pain and/or symptoms related to mass effect of the tumor on surrounding structures, such as lower extremity edema, referred pain to the groin or lower extremities, weight loss, early satiety, bowel obstruction, and serous ascites, among others.

When to suspect the diagnosis – The diagnosis of retroperitoneal STS should be suspected in patients with a retroperitoneal mass that is unifocal and extravisceral on imaging studies and without clinical evidence for an alternative cancer diagnosis such as lymphoma, metastatic testicular cancer, or primary germ cell tumor. (See 'When to suspect the diagnosis' above and 'Differential diagnosis' above.)

Diagnostic evaluation – The diagnostic workup includes (see 'Diagnostic evaluation' above):

Imaging studies – We obtain a computed tomography (CT) scan of the abdomen and pelvis with intravenous and oral contrast to evaluate the primary site as well as a CT scan of the chest to assess for metastatic disease to the lungs. (See 'Imaging studies' above.)

For patients with an allergy to intravenous CT iodinated contrast agents, magnetic resonance imaging (MRI) of the abdomen and pelvis with gadolinium contrast may be obtained in addition to or as an alternative to a non-contrast CT abdomen and pelvis. MRI of the abdomen and pelvis is also an appropriate follow-up study for those with an initial CT that demonstrates equivocal muscle, vessel, bone, or foraminal involvement and/or for some pelvic tumors.

Laboratory studies – We obtain a complete blood count with differential and a lactate dehydrogenase (LDH) level. For patients where germ cell tumor is in the differential diagnosis, we also obtain alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG) levels. (See 'Laboratory studies' above.)

Diagnostic biopsy – The diagnosis of a retroperitoneal STS is confirmed through diagnostic biopsy with histopathologic analysis demonstrating sarcoma. For most patients with suspected retroperitoneal STS, we strongly prefer to obtain tissue using an image-guided percutaneous core needle biopsy rather than proceeding directly to surgery. (See 'Diagnostic biopsy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thomas F DeLaney, MD, who contributed to earlier versions of this topic review.

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