Lipomas

Lipomas consist almost entirely of mature fat and are uncommonly found in the retroperitoneum. They are probably the most common soft tissue tumor in humans. Most of these lesions occur superficially, but they may occur in other areas, such as the retroperitoneum. Deep lipomas within the retroperitoneum are usually not as well circumscribed as their superficial counterparts and can conform to irregular spaces in this body space (DeWeerd and Dockerty, 1952; Mowat and Clark, 1961). The adipocytes are normal or slightly larger in appearance and have a well-developed vascular network. There is very little in the way of nuclear irregularity. Differing levels of fibrous connective tissue can be found in these lesions. The rim of the lipocyte is reactive for S-100 protein. Although the majority of these masses are idiopathic, they can occasionally be a manifestation of steroid lipomatosis.

Pelvic lipomatosis, although not a distinct tumor per se, was first described in 1959 as an overgrowth of fat in the perivesical and perirectal area. It is a hyperplastic rather a neoplastic entity that can create a space-occupying lesion. Approximately two thirds of patients are African-American, and women are rarely affected (Heyns, 1991). The growth is diffuse rather than nodular, and often it is difficult to distinguish it from normal adipose tissue. The condition may be associated with cystitis glandularis (Yalla et al, 1975). The general clinical course is slowly progressive and may result in the need for urinary diversion (Klein et al, 1988). Occasionally, fat necrosis in these lesions can be mistaken for sarcomatous degeneration (Andac et al, 2003).

Myelolipoma

Myelolipoma is a tumor-like growth of mature fat and bone marrow elements. Although it usually occurs in the adrenal gland it can be seen as an isolated pelvic lesion (Chen et al, 1982; Sanders et al, 1995). It is distinct from extramedullary hematopoietic tumors, which are usually multiple and generally associated with mild proliferative diseases and skeletal disorders. These generally occur in patients older than age 40 years and are rarely greater than 5 cm (Fowler et al, 1992; Mukherjee et al, 2010). They are usually noted as incidental findings on imaging. The adrenal gland can create inferior renal displacement due to a radiolucent mass. Pathologically it may display the features of a lipoma or have a darker appearance if myeloid elements predominate. Adrenal myolipoma development may be secondary to prolonged stress and excessive stimulation with adrenocorticotropic hormone.

Leiomyoma

These generally rare lesions are seen in a distribution that represents smooth muscle tissue in the body. They are overwhelmingly found in the female genital tract but have also been reported in the urinary bladder. There are occasional reports of these tumors in the retroperitoneum, where they can grow asymptomatically to a considerable size. Leiomyomas stain positive for desmin, which separates them from their malignant counterpart. Extension of these lesions from the uterus into the vascular system can create tumor thrombi not unlike those seen with renal lesions (Clement, 1988).

Liposarcoma

Liposarcomas are among the most common of primary retroperitoneal tumors and are distinguished by their often large dimensions and range of subtypes. These lesions have their peak incidence between ages 40 and 60 (Kindblom et al, 1975). They account for 10% to 15% of sarcomas, and approximately 20% of these lesions arise in the retroperitoneum. One unfortunate clinical feature of these lesions is their usual tendency to recur, often within the first 6 months after surgery. The principal tissue type is usually recapitulated at the time of recurrence. The rate of metastasis depends on the degree of tumor differentiation, with nearly 90% of poorly differentiated tumors metastasizing (Enterline et al, 1960; Spittle et al, 1971; Weiss and Rao, 1992).

Significant advances in cytogenetics have allowed the reclassification of these lesions on a molecular basis. Well-differentiated and dedifferentiated lesions are a continuum of lesions based on the genetic abnormality of giant and ring chromosomes usually involving chromosome 12. Gene amplification, particularly of MDM2, drives their pathology (Pilotti et al, 1998; Forus et al, 2001). Myxoid and round cell lesions (poorly differentiated myxoid) are another continuum that have fusion transcripts caused by translocations in chromosomes 16 and 12 as their principal pathologic feature. Pleomorphic liposarcomas are rare and poorly understood (Dal Cin et al, 1997).

Unlike benign lipomas, liposarcomas may bear little resemblance to classic fat-filled structures. The gross lesion is usually described as having a “fish flesh” appearance and, although generally encapsulated, it can often display invasive characteristics. Besides the retroperitoneum, these lesions arise in the deep soft tissues of the proximal extremities. They generally present as very large lesions when originating from the retroperitoneum.

Myxoid liposarcomas are the most common type and usually occur in the lower extremity. They account for 50% of sarcomas and represent a large proportion of retroperitoneal lesions. The peak presentation is in the fifth decade. These tumors display a background of stellate mesenchymal cells and a prominent capillary pattern often described as a “chicken wire” appearance. The distinct cell is the lipoblast, which is similar to the fetal adipocyte. These cells are noted by a lipid vacuole that scallops the nucleus. This creates the lipoma-like appearance of these lesions, which can demonstrate fusion proteins (TLS-CHOP) on molecular analysis. Higher-grade lesions tend to demonstrate a higher number of TP53 mutations (Deitos et al, 1997). The round cell subtype is also referred to as a lipoblastic variant and is distinguished by sheets of round cells with lipoblastic differentiation. These lesions are considered the most aggressive part of the spectrum of myxoid lesions.

Well-differentiated liposarcomas most resemble lipomas and are usually designated as low grade. They are a common sarcoma of later life. Subvariants include the lipoma-like, inflammatory, sclerosing, and differentiated types. The first three variants are often confused with benign processes such as scarring or inflammation, whereas the differentiated subtype is often noted in long-standing retroperitoneal lesions and considered higher grade. Generally these lesions are now considered as a group with dedifferentiated lesions because they share genetic similarities.

Pleomorphic liposarcomas comprise 10% to 15% of liposarcomas and are defined as high-grade malignant variants with very bizarre nuclei and huge lipoblasts.

Leiomyosarcoma

Leiomyosarcomas account for less than 10% of all soft tissue sarcomas yet a significant percentage of retroperitoneal sarcomas because almost half of them appear in this region. They have a 2 : 1 female-to-male presentation and generally occur in middle age (mean age 60 years). The molecular pathology of these lesions has not been reduced to any common pathway and demonstrates a tremendous amount of variation on cytogenetic and molecular analysis. The tumors are usually categorized by site of origin (soft tissue, vascular, or superficial), although many of the soft tissue lesions are believed to originate from smaller blood vessels. On imaging examinations, however, they appear to have moderate to low vascularization.

Grossly, low-grade leiomyosarcomas can be difficult to distinguish from leiomyomas but higher-grade lesions display a more infiltrative fleshlike appearance (Shmookler and Lauer, 1983). Low-grade lesions are often distinguished from leiomyomas by their chromatin pattern and the number of mitoses (more than five mitoses per high-power field) present in the specimen.

Again, a continuum exists in the pathologic progression of these smooth muscle lesions; therefore the cut point between benign, moderate, and high grade may sometimes be arbitrary. There is little evidence of sarcomatous degeneration from benign leiomyomas. The characteristic pathologic finding of a leiomyosarcoma is malignant spindle cells with “cigar”-shaped nuclei. The muscle fascicles interweave. These tumors immunohistochemically stain for smooth muscle myosin, vimentin, and actin and less often for desmin. They stain negative for S-100. Ultrastructural features include bundles of thin cytofilaments, which can help distinguish leiomyosarcomas from other lesions.

A rare retroperitoneal variant of these tumors are leiomyosarcomas that originate from the great vessels (Demers et al, 1992). These occur predominantly in women. Tumors of the iliac vessels usually present as lower extremity edema, whereas those of the inferior vena cava can display findings consistent with Budd-Chiari syndrome (Cardell et al, 1971). Resection of these lesions is recommended when anatomically feasible. Survival, however, is usually less than 2 years, and many inferior vena caval tumors are unresectable because of the intrahepatic location of many of these lesions.

Malignant Fibrous Histiocytoma

Malignant fibrous histiocytoma was originally described in 1963 and has come to be the predominant histologic diagnosis for currently reported soft tissue sarcomas (Ozello et al, 1963). It was first defined as a sarcoma of primary histiocytic origin, but it is now believed that it is a lesion derived from fibroblast differentiation. Many pleomorphic variants of fibrosarcoma, liposarcoma, and rhabdomyosarcoma have been reclassified into this category. With the thorough evaluation of a tumor specimen, distinct regions of leiomyosarcoma, liposarcoma, and other soft tissue sarcomas may be identified. In such cases the tumor may be defined by those findings and the mention of an associated malignant fibrous histiocytoma pattern (Weiss, 1982). These lesions are most often seen on the extremities and are less common in the retroperitoneum. Their molecular pathology is unclear. An analysis of these lesions in the retroperitoneum suggests that many of these could be reclassified as a dedifferentiated liposarcoma and that they may represent a common end point for several tissue types (Coindre et al, 2003; Tschoep et al, 2007). Storiform-pleomorphic, myxoid, giant cell, and inflammatory subtypes of malignant fibrous histiocytoma may coexist in a particular lesion.

The storiform-pleomorphic variant has a distinct but not pathognomonic pinwheel pattern caused by the collagen pattern of curling fascicles of cells. It is the most common variant, usually comprising 40% to 60% of most series. Although this pattern may predominate, it may not be present throughout the lesion in question. Areas of collagen or foamy cells may also be encountered. The nuclei tend to be irregular and large with discernible mitosis. The constellation of tissue histology and nuclear irregularities in addition to the inflammatory components differentiate this lesion from benign entities.

Myxoid malignant fibrous histiocytoma comprises 25% of this overall tumor type. It is often difficult to distinguish it from liposarcoma; however, the myxoid subtype has little neutral fat but is rich in mucopolysaccharide residing in intracytoplasmic vacuoles.

Malignant fibrous histiocytoma, giant cell type, is distinguished by large benign-appearing osteoclasts. Multinucleated giant cells and the stroma comprise the malignant components of this lesion. If cartilage or osteoid is detected, these lesions are classified as a soft tissue osteosarcoma, which usually has a poorer prognosis than malignant fibrous histiocytoma.

Fibrosarcoma

Fibrosarcomas are malignant tumors of fibroblast origin. They have a range of gradation and grossly display a classic “fish flesh” pattern with hemorrhage and necrosis. Low-grade lesions can display a herringbone/spindle-shaped histologic pattern. On retrospective review these lesions are often reclassified as malignant fibrous histiocytoma or as a desmoid lesion (aggressive fibromatosis). Therefore these lesions represent a smaller proportion of primary retroperitoneal tumors than previously reported. There is a greater incidence of blood-borne metastases from this tumor to the lung and bones (Bizer, 1971).

Rhabdomyosarcoma

Rhabdomyosarcoma comprises a minor percentage of reported retroperitoneal sarcomas yet is a significant lesion in pediatric oncology as well as pediatric tumors associated with the genitourinary system. These lesions are generally classified as embryonal, botryoid, alveolar, or pleomorphic, with a spindle cell subtype more recently described within the embryonal type (Horn and Enterline, 1958; Cavazzana et al, 1992). The pathology of these lesions is associated with chromosomal abnormalities and the fusion transcripts associated with these translocations.

Embryonal rhabdomyosarcoma comprises more than half of all rhabdomyosarcomas and has a large array of anatomic locations, including the genitourinary tract and retroperitoneum. It can range from very well to poorly differentiated lesions and can express the multiple stages of muscle development. Botryoid lesions are an anatomic variant of the embryonal type and generally found in hollow viscera. The spindle cell subtype is noted for its favorable clinical behavior.

Alveolar rhabdomyosarcoma accounts for approximately 20% of all rhabdomyosarcomas and tends to occur more frequently in the extremities. The tumor is arranged in aggregates of round or oval cells that create irregular spaces reminiscent of alveoli. They can be classified into subtypes based on fusion gene transcripts (PAX-FKHR). These tissues may be surrounded by fibrous septa, and areas of necrosis are not uncommon.

Pleomorphic rhabdomyosarcoma comprises 5% of adult rhabdomyosarcomas and generally occurs in older patients. It usually is found in the extremities and is not unlike malignant fibrous histiocytoma in its appearance. The absence of cross striations makes diagnosis difficult. With all rhabdomyosarcomas, immunostaining for desmin, myoglobin, and muscle-specific actin is useful.

Malignant Hemangiopericytoma

These rare lesions originate from pericytes, which are unique cells that arborize about small vessels and capillaries. Their contractile properties allow them to control microvascular flow and permeability. Fewer than 200 of these lesions have been described, yet 25% of them have occurred in the retroperitoneum or pelvis. They are usually well circumscribed and, if possible, complete surgical excision is warranted. Hemangiopericytomas display a rich vascular pattern and stain positive for factor VIIIa. They are negative for desmin and actin. The clinical behavior of these lesions is difficult to predict, but metastases may develop in 20% to 50% of cases. Those lesions with more than four mitoses per 10 high-power field have a worse prognosis (Enzinger and Smith, 1976; Zirkin 1977).