Soft Tissue Tumors - Flashcard Topics

GENERAL / OVERVIEW

1. Definition of Soft Tissue - what tissues are included/excluded
2. Benign vs. Malignant ratio - ~100:1; ~12,000 sarcomas/year in U.S.
3. Most common sarcoma site - deep soft tissues, especially thigh
4. Pathogenesis: Sporadic vs. Germline - NF1, Gardner, Li-Fraumeni, Osler-Weber-Rendu syndromes
5. Cell of origin - pluripotent mesenchymal stem cells
6. Simple vs. Complex Karyotype - Ewing/synovial sarcoma (simple) vs. leiomyosarcoma/UPS (complex)
7. Prognostic indicators - grade (differentiation) and stage (size & depth)

TUMORS OF ADIPOSE TISSUE

1. Lipoma - most common adult soft tissue tumor; location; treatment
2. Liposarcoma: 3 subtypes - well-differentiated, myxoid, pleomorphic
3. Well-differentiated Liposarcoma - chromosome 12q13-q15 amplification; MDM2 overexpression; p53 inhibition
4. Myxoid Liposarcoma - t(12;16) translocation; arborizing capillaries; intermediate malignancy
5. Pleomorphic Liposarcoma - lipoblasts; complex karyotype; most aggressive subtype
6. Liposarcoma clinical course - local recurrence; pleomorphic type has high metastasis risk

FIBROUS TUMORS

1. Nodular Fasciitis - fibroblastic proliferation; upper extremities; MYH9-USP6 fusion gene; t(17;22)
2. Nodular Fasciitis morphology - zonation pattern; plump fibroblasts; mitotic figures; <5 cm; spontaneous regression
3. Fibromatoses: definition - infiltrative, locally destructive, no metastasis
4. Superficial Fibromatosis: 3 subtypes - Dupuytren contracture (palmar), plantar, Peyronie disease (penile)
5. Deep Fibromatosis (Desmoid Tumors) - CTNNB1/APC mutations; Wnt signaling; Gardner syndrome association
6. Desmoid Tumor morphology - cytologically bland fibroblasts; sweeping fascicles; dense collagen; resembles scar
7. Desmoid Tumor treatment - difficult excision; medical therapy + radiation as alternatives

SKELETAL MUSCLE TUMORS

1. Rhabdomyosarcoma: 3 subtypes - embryonal (60%), alveolar (20%), pleomorphic (20%)
2. Rhabdomyosarcoma epidemiology - most common soft tissue sarcoma in children/adolescents
3. Alveolar Rhabdomyosarcoma genetics - PAX3-FOXO1 (t2;13) or PAX7-FOXO1 (t1;13) fusion
4. Embryonal Rhabdomyosarcoma morphology - primitive round/spindle cells; rhabdomyoblasts with cross-striations
5. Sarcoma Botryoides - embryonal variant; hollow viscera (bladder, vagina); best prognosis
6. Alveolar RMS morphology - fibrous septae; alveoli-like clusters; uniform round cells
7. Pleomorphic RMS - large bizarre eosinophilic cells; multinucleated; requires IHC (myogenin)
8. Rhabdomyosarcoma treatment & prognosis - surgery + chemo ± radiation; pleomorphic often fatal

SMOOTH MUSCLE TUMORS

1. Leiomyoma - benign; most common in uterus; fumarate hydratase (FH) mutation link; blunt-ended spindle cells
2. Leiomyoma vs. Leiomyosarcoma histology - minimal atypia/mitoses vs. high mitotic activity + necrosis
3. Leiomyosarcoma - 10-20% of soft tissue sarcomas; women > men; retroperitoneum/extremities
4. Leiomyosarcoma IHC - positive for actin, desmin, caldesmon
5. Leiomyosarcoma prognosis - retroperitoneal tumors often fatal (lung metastases)

TUMORS OF UNCERTAIN ORIGIN

1. Synovial Sarcoma - NOT derived from synovium; ages 20-40; ~10% of sarcomas
2. Synovial Sarcoma genetics - t(x;18)(p11;q11); SS18-SSX gene fusion; disrupts cell cycle control
3. Synovial Sarcoma: Monophasic vs. Biphasic - spindle cells only vs. spindle cells + gland-like structures; keratin positive
4. Synovial Sarcoma metastasis - lungs AND regional lymph nodes (unusual for sarcomas); 5-year survival 25-62%
5. Undifferentiated Pleomorphic Sarcoma (UPS) - formerly MFH; unclassifiable by histology/IHC/genetics
6. UPS pathogenesis - aneuploid; significant genomic instability
7. UPS morphology - large gray-white masses (10-20 cm); anaplastic spindle-to-polygonal cells; bizarre hyperchromatic nuclei; atypical mitoses
8. UPS prognosis - metastasis in 30-50% of cases; surgery + chemo ± radiation