Atypical Lipomatous Tumour (ALT)

Atypical lipoma

Well-differentiated liposarcoma

Spindle cell liposarcoma

Epidemiology and Etiology:

• Middle aged adults (6^th decade peak)

Common sites:

• deep soft tissues of the proximal extremities
• esp. thigh
• retroperitoneum
• paratesticular
• mediastinum

Gross features:

• well-circumscribed
• lobulated
• may be multiple discontiguous masses
• yellow to white
• fat necrosis common

Histologic features:

• Significant variation in cell size
• At least focal atypia in both adipocytes and stromal cells
• readily identified lipocytes
• significant variation in cell size (note: may see this in fat necrosis)
• hyperchromatic, often multinucleated stromal cells (scattered)
• especially in fibrous septa
• and around blood vessels
• lipoblasts (many to none) – NOT required for diagnosis, NOT pathognomonic
• mimic fetal fat cells
• enlarged, hyperchromatic nucleus
• scalloped nucleus by clear lipid vacuoles
• monovacuolated or multivacuolated
• sclerosing liposarcoma pattern (retroperitoneal or para-testicular lesions most often):
• extensive fibrillary collagenous stroma
• scattered bizarre stromal cells
• rare multivacuolated lipobasts
• lipogenic areas limited in extent
• inflammatory liposarcoma pattern (rare) (retroperitneum most common):
• chronic inflammatory infiltrate predominates
• difficult to appreciate the adipocytic nature of the neoplasm
• bizarre multinucleate stromal cells is a useful diagnostic clue
• spindle cell liposarcoma
• bland neural-like spindle cell proliferation
• fibrous and /or myxoid background
• atypical lipomatous component that usually includes lipoblasts
• heterologous differentiation (rare)
• osseous elements
• smooth or striated muscle component (well-differentiated)

Immunophenotype:

Marker:	Sensitivity:	Specificity:
S100
MDM2 (nuclear) +/- CDK4 (nuclear)	Most (MDM2 negative in spindle cell liposarcomas)

Molecular features:

• supernumerary circular (“ring”) chromosomes and/or giant rod chromosomes (90% of ~150 cases reported) (sole anomaly in >50%) (not seen in spindle cell liposarcoma)
• number and size vary considerably, even in the same tumour
• amplification of 12q14-15 region (85% of ALT)
• MDM2
• CDK4
• others
• Complex structure
• 12q material (12q14-12q15 region invariably)
• High-level amplification restricted to 12q13-q21 and nearly always including 12q14 (CDK4) and 12q15 (MDM2)
• Always contains co-amplification of at least one other genomic segment
• Chromosome 1 material
1. 1q21 to 1q25
2. Peak at 1q23
• Other chromosomes
• consistently contains a neocentromere (no alpha-satellite sequences
• Near diploid usually
• Near tetraploid occasionally
• Telomeric associations frequently (may give false impression of complexity to karyotype)
• Other changes:
• Numerical
• Balanced and unbalanced structural aberrations
• Duplication or triplication of 12q material (12q15 minimal commonly gained region)
• -13/del(13)(q) (>5%)
• -22/del(22)(q) (>5%)

Other features:

• Locally aggressive
• Do not recur after complete (preferably wide) excision
• relatively indolent (and no potential for metastasis unless undergoes dedifferentiation) but recur locally if not adequately excised
• anatomic site is most important prognostic factor (retroperitoneal are often less surgically amenable)
• often recur multiple times and may cause death as a result of uncontrolled local effects
• may dedifferentiate and metastasize (>20% risk in retroperitneum, < 2% risk in limbs
• 6-11 years median time of death (>80% mortality for retroperitoneal location)
• May be more appropriate to use the term well-differentiated liposarcoma for deep / hard to resect tumours

References:

• Fletcher CDM et al. (eds.) WHO Classification of Tumours of Soft Tissue and Bone. (2013)