Well-differentiated liposarcomas (WDLPS) or atypical lipomatous tumours (ALT) are locally aggressive adipocytic soft tissue neoplasms and are the most common form of liposarcomas.

Terminology

The terminology well-differentiated liposarcoma and atypical lipomatous tumour depend on the localisation of the tumour and its resectability. Atypical lipomatous tumours/well-differentiated liposarcomas (ALT/WDLPS) are also termed ‘atypical lipomas’, but this term has been discouraged ¹.

Epidemiology

Atypical lipomatous tumours or well-differentiated liposarcomas account for 40-45% of liposarcomas and constitute the largest subgroup of adipocyte malignancies. They occur mostly in adults with a peak incidence in the 30s and 40s. In childhood, they are extremely rare. Inguinal lesions are more common in men otherwise there is no gender predominance however ^1-3.

Associations

Atypical lipomatous tumours/well-differentiated liposarcomas may be associated with Li-Fraumeni syndrome ¹.

Diagnosis

The diagnosis of well-differentiated liposarcoma is based on typical pathological features.

Diagnostic criteria

Diagnostic criteria according to the WHO classification of soft tissue and bone tumours (blue book(5^th edition) differ with subtype ¹:

• lipoma-like subtype:
  • varying sizes of adipose cells
  • nuclear atypia in adipose or stromal cells
• sclerosing subtype: bizarre hyperchromatic stromal cells in a fibrillary collagenous stroma
• inflammatory subtype: atypical stromal cells in a chronic inflammatory infiltrate

The following criteria are described as desirable in challenging cases ¹:

• MDM2 and/or CDK4 nuclear expression
• MDM2 and/or CDK4 gene amplification

Clinical presentation

The most common presentation is that of a painless mass. Deep-seated atypical lipomatous tumours/well-differentiated liposarcomas are most often found incidentally ¹.

Complications

If left untreated atypical lipomatous tumours/well-differentiated liposarcomas can dedifferentiate into higher-grade malignancies such as dedifferentiated liposarcoma or undifferentiated pleomorphic sarcoma ^1-4.

Pathology

Atypical lipomatous tumours/well-differentiated liposarcomas are adipocytic neoplasms characterised by a proliferation of pleomorphic mature adipocytes of different patterns featuring atypical hyperchromatic stromal cells. They are intersected by fibrous septa and might have myxoid or fibrous components and areas of fat necrosis ^1-4.

Location

Atypical lipomatous tumours/well-differentiated liposarcomas commonly involve the deep soft tissues in particular of the proximal extremities and the trunk ^1-5.

Common locations include the following ¹:

• thigh and buttocks
• shoulder and back
• retroperitoneum
• paratesticular area

Rarer locations of involvement include the following ¹:

• head and neck
• mediastinum
• distal extremities
• skin

Classification

Atypical lipomatous tumours/well-differentiated liposarcomas include the following subtypes ^1-4,6:

• lipoma-like liposarcoma
• sclerosing liposarcoma
• inflammatory liposarcoma

Macroscopic appearance

Macroscopically atypical lipomatous tumours/well-differentiated liposarcomas usually present as well-circumscribed, large lobulated masses of variable consistency and white to yellowish colour. They might display foci of necrosis or small punctate haemorrhages ¹.

Microscopic appearance

The microscopic appearance of atypical lipomatous tumours/well-differentiated liposarcomas includes the following features. Larger tumours and especially retroperitoneal tumours commonly show more than one morphologic pattern within the same lesion^1,4:

• presence of atypical hyperchromatic stromal cells
• variable number of lipoblasts
• possibly variations in adipocyte size with nuclear atypia (lipoma-like subtype)
• possibly copious inflammatory infiltrates (inflammatory subtype)
• possibly bizarre stromal cells within a fibrillary sclerotic, collagenous background (sclerosing subtype)

Immunophenotype

Immunohistochemistry stains are usually positive for MDM2 and/or CDK4 ¹.

Genetics

The pathogenesis of atypical lipomatous tumours/well-differentiated liposarcomas involves MDM2 and/or CDK4 nuclear gene amplification ^1,2.

Radiographic features

Imaging features of atypical lipomatous tumours/well-differentiated liposarcomas resemble that of benign lipomas as discussed in the article lipoma vs well-differentiated liposarcoma and include ^3-5,7:

• size >5 cm or >13 cm ⁷
• thick or nodular septa (>2 mm) with possible enhancement
• multinodular tumour margins
• focal nodular patchy non-fatty tissue components
• more than 3/4 of fatty tissue

They might displace other organs or tissue.

Ultrasound

Usually appears as multilobulated well-defined mass sometimes with hyperechoic foci ³.

CT

CT usually shows a fat tissue density mass with thick or nodular enhancing septae. Calcifications might be rarely found ⁴.   

MRI

On MRI atypical lipomatous tumours/well-differentiated liposarcomas will display a mass of fat isointense signal in all sequences. In addition, atypical lipomatous tumours/well-differentiated liposarcomas will show thick septa or nodular non-lipomatous areas with contrast enhancement ^3-5.

• T1: hyperintense
• T2: hyperintense possibly with prominent high signal foci
• T2FS/PDFS: hypointense
• T1 C+ (Gd): moderate to a markedenhancement of septa

Radiology report

The radiological report should include a description of the following ^5,7:

• form, location and size
• tumour margins
• thick septa and septal enhancement
• amount of non-adipose tissue
• distance from the muscular fascia
• relationship to local nerves and vessels 

Treatment and prognosis

The management of choice in atypical lipomatous tumours/well-differentiated liposarcomas is resection, which is curative if complete ¹. TheThese tumours are not sensitive to radiotherapy or chemotherapy ². Tumour prognosis is therefore mostly dependentand the likelihood of distant metastases depend on the risk of dedifferentiation and on how amenable the location is to surgical excision. TheIt varies with the location of the tumour doesranging from >20% in the retroperitoneum to <2% in the extremities. The tumours do not cause distant metastasis unless there is dedifferentiation. Therefore tumours

Tumours of the mediastinum retroperitoneum or spermatic cord have a worse prognosis, due to their location they are also more prone to local recurrence ^1,2. On the other hand patients with tumours affecting the extremities have a very good prognosis with >90% survival after 10 years of follow-up and thus the name atypical lipomatous tumour ⁸. For selected patients with atypical lipomatous tumours of the extremities, active surveillance has been suggested as a viable option to prevent overtreatment ⁸. 

Differential diagnosis

Conditions or tumours which can mimic the presentation and/or the appearance of atypical lipomatous tumours/well-differentiated liposarcomas include ^1-5:

• lipoma e.g. intermuscular/intramuscular lipoma
• lipomatosis
• myxoid liposarcoma
• dedifferentiated liposarcoma
• myolipoma
• angiomyolipoma
• fibrolipomatosis
• spindle cell/pleomorphic lipoma
• hibernoma
• fat necrosis

See also

• lipoma vs well-differentiated liposarcoma
• liposarcoma