Adipocytic Tumours: WHO Update
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Direct answer
Adipocytic tumours are the commonest mesenchymal neoplasms, and the WHO 2020 classification resolves them by genetics as much as by fat. Benign lipomas carry HMGA2 rearrangements; their variants are exam staples — angiolipoma (painful, fibrin microthrombi), spindle cell and pleomorphic lipoma (same RB1-pathway spectrum, ropey collagen and floret giant cells), hibernoma and paediatric lipoblastoma (PLAG1). Atypical lipomatous tumour or well-differentiated liposarcoma (ALT/WDL) — the same tumour, named by resectability — amplifies 12q13-15 driving MDM2 and CDK4, identified by immunohistochemistry or FISH; dedifferentiated liposarcoma is its non-lipogenic, usually UPS-like progression, typically retroperitoneal. Myxoid liposarcoma, the DDIT3 (CHOP)-fusion tumour of young adults' legs, shows chicken-wire vasculature and carries prognosis that worsens with any round-cell component, while pleomorphic liposarcoma — line-negative for MDM2 — is the most aggressive of the family.
What you must remember
- ALT/WDL subtypes and naming: adipocytic (lipoma-like), sclerosing and inflammatory; the diagnostic cells are scattered atypical stromal cells with hyperchromatic nuclei plus variably present lipoblasts — named ALT for resectable extremity sites and WDL-sarcoma for retroperitoneum or mediastinum, one biology with two labels.
- The MDM2 rule: any fatty tumour that is deep-seated, retroperitoneal, mediastinal, spermatic-cord located or over roughly 10 cm deserves MDM2 testing (immunohistochemistry or FISH) before being called lipoma — the single highest-yield sentence in adipocytic pathology.
- Dedifferentiation: abrupt transition from WDL to non-lipogenic sarcoma, commonly UPS-like or myxofibrosarcoma-like, occasionally with homologous low-grade areas; homozygous CDKN2A deletion marks the progression step; MDM2 amplification persists and proves the lineage.
- Myxoid liposarcoma: lower extremity of young adults, plexiform chicken-wire capillatures, mucin pools, signet-ring lipoblasts; FUS-DDIT3 from t(12;16) or EWSR1-DDIT3; round-cell component over 5% worsens prognosis; uniquely radiosensitive.
- Pleomorphic liposarcoma: pleomorphic lipoblasts, high-grade mitotic activity, MDM2-negative — the most aggressive liposarcoma, metastasising early.
- Spindle cell and pleomorphic lipoma spectrum: CD34-positive bland spindle cells, ropey collagen, mature fat, floret-type multinucleate giant cells, RB1 loss on 16q — the posterior-neck-shoulder location of older men is the clinical signature.
- Angiolipoma: painful, multiple, forearms of young adults; fibrin microthrombi within small vessels distinguish it from ordinary lipoma.
- Lipoblast definition: a nucleus scalloped by cytoplasmic fat vacuoles — a finding, not a diagnosis, since lipoblasts appear in several benign and malignant entities.
Working through a retroperitoneal fatty mass
A 63-year-old man has a 20 cm retroperitoneal fatty mass on CT. Biopsy shows mature adipocytes with fibrous septa containing scattered atypical cells with enlarged hyperchromatic nuclei. Immunohistochemistry: MDM2 and CDK4 positive in the atypical stromal cells; FISH confirms 12q amplification. Diagnosis: well-differentiated liposarcoma, sclerosing subtype — in this location the "atypical lipomatous tumour" euphemism yields to liposarcoma naming because clear margins are anatomically improbable.
The surgical specimen then teaches the second lesson: a 4 cm solid, non-lipogenic nodule with UPS-like atypia abutting the fatty tumour — dedifferentiated liposarcoma. Pathology now determines prognosis honestly: dedifferentiation converts a tumour that metastasises rarely into one that recurs relentlessly and metastasises in a meaningful fraction of patients; CDKN2A homozygous deletion on the solid component corroborates the progression. Follow-up imaging is lifelong, and the pathological definition of response — percentage necrosis after neoadjuvant therapy — comes from careful sampling of the solid component.
Where students slip
The first slip is benign-label reflex: calling a retroperitoneal or giant deep fatty lesion "lipoma" without MDM2 testing forfeits the entire diagnostic opportunity, since ordinary lipomas barely exist in the retroperitoneum. The second is lipoblast worship: the exam expects candidates to name lipoblasts as a shared finding (present in lipoblastoma, ALT, myxoid and pleomorphic liposarcoma, even hibernoma variants) rather than a liposarcoma-specific one. Third, the myxoid liposarcoma pairing: chicken-wire vessels and t(12;16) belong together, and the round-cell percentage threshold (5%) decides whether the tumour is managed as low or high risk. An Indian viva might add cost pragmatics: MDM2 immunohistochemistry is broadly available and cheap, FISH is centralised — the tiered answer scores.
Frequently asked questions
Which molecular test separates ALT/WDL from lipoma?
MDM2 (with CDK4) amplification on FISH or immunohistochemistry, reflecting the 12q13-15 amplicon — mandatory for deep, large or retroperitoneal fatty tumours.
Why do atypical lipomatous tumour and well-differentiated liposarcoma share a WHO entry?
They are biologically identical; the name varies by location — ALT where complete excision is achievable, WDL-sarcoma where it is not.
Which features define myxoid liposarcoma?
Chicken-wire plexiform vasculature, mucin-rich matrix, lipoblasts, FUS-DDIT3 fusion, young-adult legs, radiosensitivity, and prognostic worsening with over 5% round-cell component.
Which liposarcoma has the worst prognosis?
Pleomorphic liposarcoma — MDM2-negative, high-grade from the outset, with early metastatic potential.
What distinguishes angiolipoma from ordinary lipoma?
Painful, often multiple forearm lesions containing small vessels with fibrin microthrombi — a benign tumour with a characteristic clinical signature.