STEPTRACKERMUSCULOSKELETAL + ONCOLOGY | PATHOLOGY + GENETICS | HIGH-YIELD REVIEW

Soft Tissue Tumors

Lumps of fat, muscle, fibrous tissue and nerve sheath — most are benign; the sarcomas are recognized by depth, size, age and translocation.

FOCUS ON
Lipoma is the most common soft tissue tumor; liposarcoma is deep (thigh, retroperitoneum) with lipoblasts and MDM2. Rhabdomyosarcoma: most common childhood soft tissue sarcoma, desmin/myogenin. Synovial sarcoma: young adult near the knee, t(X;18). Desmoid: locally aggressive, β-catenin, Gardner. Deep or > 5 cm mass → imaging and biopsy.
TUMOR
ORIGIN · GENETICS
FEATURES
CLUE
Lipoma
most common soft tissue tumor
Benign mature adipocytes
Soft, mobile, painless subcutaneous mass (back, shoulders)
Rarely becomes malignant
Liposarcoma
Well-differentiated/dedifferentiated: MDM2 amplification · myxoid: t(12;16)
Adults 50–60; deep thigh or retroperitoneum; lipoblasts with scalloped nuclei
Retroperitoneal fatty mass → liposarcoma
Rhabdomyosarcoma
most common childhood sarcoma
Skeletal muscle differentiation; desmin, myogenin, MyoD1
Embryonal: young children, head/neck, GU (sarcoma botryoides) · alveolar: adolescents, extremities, t(2;13) PAX3-FOXO1
Alveolar has worse prognosis
Leiomyosarcoma
Smooth muscle; complex karyotype
Retroperitoneum, uterus, large veins (IVC); older adults
Desmin, SMA ⁺
Synovial sarcoma
Not from synovium; t(X;18) SS18-SSX
Adults 20–40; deep mass near large joints (knee); biphasic (epithelial + spindle) or monophasic
Keratin, TLE1 ⁺
Undifferentiated pleomorphic sarcoma
No line of differentiation; diagnosis of exclusion
Older adults; deep thigh mass; highly pleomorphic cells
Radiation-associated
Desmoid tumor (aggressive fibromatosis)
Fibroblast clonal proliferation; CTNNB1 (β-catenin) or APC (Gardner)
Abdominal wall in young/postpartum women, mesentery (after surgery in FAP); infiltrative
Recurs locally, doesn't metastasize · nuclear β-catenin
Nodular fasciitis
Self-limited reactive/clonal proliferation; USP6 fusion
Young adults; rapidly growing painful forearm nodule over weeks
Fast growth but benign
Nerve sheath tumors
Schwannoma (encapsulated) · neurofibroma (NF1, plexiform) · MPNST
S100 ⁺; plexiform neurofibroma can turn into MPNST (pain, rapid growth)
NF1 → MPNST risk
Infantile fibrosarcoma
ETV6-NTRK3 fusion
Infants; rapidly growing limb mass
TRK inhibitors (larotrectinib)
Sarcoma spread
Mostly hematogenous
Lungs most common; lymph nodes in a few (synovial, rhabdomyosarcoma, clear cell, epithelioid, angiosarcoma)
Chest CT for staging

Mechanism — sizing up a soft tissue lump

Lump
→
Superficial, < 5 cm, soft, stableLikely benign
Deep, > 5 cm, firm, growing, painfulSuspect sarcoma
→
MRI → core biopsyPlan the incision
→
Molecular testTranslocation, amplification

Sarcoma genetics

TUMOR
ALTERATION
STAIN / CLUE
Ewing sarcoma
t(11;22) EWSR1-FLI1
CD99
Alveolar rhabdomyosarcoma
t(2;13) PAX3-FOXO1
Myogenin
Synovial sarcoma
t(X;18) SS18-SSX
Keratin, TLE1
Myxoid liposarcoma
t(12;16) FUS-DDIT3
Lipoblasts
Well-differentiated liposarcoma
MDM2 amplification
Retroperitoneum
DFSP
COL1A1-PDGFB
CD34 · imatinib

How it's tested

COMMON CONFUSIONSynovial sarcoma sits near joints but doesn't arise from synovium; it is a carcinoma-like (keratin ⁺) sarcoma defined by t(X;18).
THE TRAPA desmoid tumor looks bland and never metastasizes, yet infiltrates and recurs — and in an FAP patient it can be the main cause of death after colectomy.
YOUR APPROACHAge + depth + site → line of differentiation (fat, muscle, fibrous, nerve) → stain (desmin, S100, keratin, β-catenin) → translocation → spread.

If you see… think…

Soft, mobile, painless lump on the back → lipoma
Large retroperitoneal fatty mass with MDM2 amplification → liposarcoma
3-year-old with orbital or bladder mass, desmin⁺ → embryonal rhabdomyosarcoma
Teen with forearm sarcoma, PAX3-FOXO1 → alveolar rhabdomyosarcoma
30-year-old with a deep mass beside the knee, t(X;18) → synovial sarcoma
Postpartum woman with firm abdominal wall mass, nuclear β-catenin → desmoid tumor
FAP patient with mesenteric fibrous mass after colectomy → desmoid (Gardner)
Fast-growing forearm nodule in a young adult that resolves → nodular fasciitis
NF1 patient with a plexiform neurofibroma that becomes painful and grows → MPNST
Most common site of sarcoma metastasis → lungs