Pleomorphic liposarcomas are high-grade malignant neoplasms arising from adipocytic tissues characterized by a variable number of pleomorphic lipoblasts and the absence of areas of well-differentiated liposarcoma and other lines of differentiation.

Epidemiology

Pleomorphic sarcomas are rare and make up for less than 5% of all liposarcomas and about 20% of pleomorphic sarcomas. Most commonly they occur in the 7th decade of life with men slightly more frequently affected ^1-5. In children, they are extremely rare ¹.

Diagnosis

The diagnosis of pleomorphic liposarcoma is established histologically.

Diagnostic criteria

Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5^th edition) ¹:

• variable number of pleomorphic lipoblasts in one of the following tumor morphologies

  • pleomorphic spindle cell sarcoma

  • tumor with myxofibrosarcoma-like morphology

  • epithelioid cell morphology with carcinoma-like epithelioid cells 

• only pleomorphic lipoblasts

Clinical presentation

The most frequent symptom is that of a fast-growing painless tumor, pain and/or symptoms related to organ displacement are less common complaints ^1,2.

Pathology

Pleomorphic liposarcomas are highly malignant neoplasms characterized by pleomorphic lipoblasts with features of pleomorphic spindle cell sarcoma or myxofibrosarcoma and in the case of the epithelioid subtype with sheets of carcinoma-like epithelioid cells ^1,3,5. They commonly have necrotic and myxoid changes ².

Location

The most frequent sites of involvement by pleomorphic liposarcomas are the extremities in about 2/3 of the cases. The lower limbs are more commonly affected. Less frequent locations include the following ^1-5:

• trunk: thoracic and abdominal wall

• retroperitoneum

• spermatic cord

Rare sites of involvement are ¹:

• mediastinum

• heart

• pleura

• breast

• scalp

• colon

• orbit

Subtypes

There is a single subtype, the epithelioid liposarcoma ^1,3,4.

Macroscopic appearance

Macroscopically pleomorphic liposarcomas are usually large when detected, not encapsulated, sometimes well-demarcated or multinodular other times ill-defined and infiltrative and of yellowish-white color. They often feature areas of necrosis or myxoid change ¹.

Microscopic appearance

The microscopic appearance of pleomorphic liposarcomas includes the following features ^1,3-5:

• infiltrative margins

• varying proportions of pleomorphic lipoblasts

• non-lipogenic background of undifferentiated pleomorphic sarcoma with spindle cells and multinucleated giant cells

• possibly myxofibroma-like areas (≈50%)

• areas of necrosis (≈50%)

• epithelioid morphology (≈25%)

Immunophenotype

Pleomorphic liposarcomas in contrast to well-differentiated or dedifferentiated liposarcomas usually demonstrate negative immunohistochemistry stains for MDM2 and/or CDK4. The epithelioid subtype might show positive stains for melan-A and/or keratins ^1,4.

Genetics

Genetically most mutations involve TP53 and/or NF1. No amplification involving the MDM2 nuclear gene is seen ^1,3.

Radiographic features

Pleomorphic liposarcomas look like nonspecific soft tissue masses with heterogeneous areas of necrosis and hemorrhage ². Compared to other liposarcomas they contain less or no fatty tissue. Like other tumors, they displace other organs or tissue.

Ultrasound

Usually appears as multilobulated to irregular with areas of low echogenicity ^2,6.

CT

CT usually shows an unspecific heterogeneous soft-tissue density mass isodense to muscle with streaky enhancing areas ^7.

MRI

On MRI pleomorphic liposarcomas will display a soft tissue mass with fibrous components that enhance ^2,7.

• T1: heterogeneous hypointense

• T2: heterogeneous hyperintense similar to or slightly lower than fat

• T1 C+ (Gd): heterogeneous enhancement

Radiology report

The radiological report should include a description of the following:

• form, location and size

• tumor margins

• amount of solid and lipoid components

• relation to other organs and/or structures

Treatment and prognosis

The management of pleomorphic liposarcomas includes resection and also shows a response to the combination of ifosfamide and doxorubicin, which makes (neo-) adjuvant chemotherapy another option ^{1,2, 5,8}.  Local recurrence happens in about 30-50%, distant metastases occur in up to 50% of the cases and the 5-year survival is in the range of 60% ^1-4.

Increased tumor depth and more central location, as well as a greater size and higher mitotic activity, are associated with worse outcomes ¹.

History and etymology

Liposarcomas in general were first described by the German pathologist Rudolph Virchow in 1857 ⁹ whereas the history and etymology of the pleomorphic type remain elusive in a sense. The Austrian-American pathologist Franz Michael Enzinger and his American colleague Donald J Winslow analyzed pleomorphic liposarcomas and other liposarcoma types in a study in 1962 ^3,10. It is very well possible that this subtype has been already described before the 1960s. The American pathologist Arthur Purdy Stout already describes types with fibrosarcoma-like areas in his works about liposarcoma from 1944 ¹¹. The epithelioid subtype of pleomorphic liposarcoma was described by Markku Miettinen and Franz Michael Enzinger in 1999. ¹².

Differential diagnosis

Conditions that can mimic the clinical or radiological presentation of pleomorphic sarcoma are any fast-growing soft tissue tumors and include ^1-4:

• myxoid pleomorphic liposarcoma

• myxoid liposarcoma

• dedifferentiated liposarcoma

• fibrosarcoma

• myxofibrosarcoma

See also

• liposarcoma