Cells of Origin for Soft Tissue Tumors
Lipoma and Liposarcoma
Lipomas are benign tumors composed of mature adipocytes (fat cells), while liposarcomas are malignant tumors that contain lipoblasts—immature fat cells with hyperchromatic, indented nuclei. 1, 2
- Lipoma: Consists of mature, well-differentiated adipocytes that are uniform in size and lack cytologic atypia, encapsulated in fibrous tissue 1, 3
- Liposarcoma: The hallmark cell is the lipoblast, defined as a lipid-containing cell with an eccentric, hyperchromatic nucleus that is indented or scalloped by one or more fat vacuoles 4, 2
- Lipoblasts represent immature or precursor forms of adipocytes and recapitulate the differentiation process of normal fat (adipogenesis) 2
- Well-differentiated liposarcomas contain relatively mature adipocytes with nuclear atypia and varying numbers of lipoblasts 5
Leiomyoma and Leiomyosarcoma
Leiomyomas and leiomyosarcomas originate from smooth muscle cells, with leiomyomas being benign tumors of well-differentiated smooth muscle and leiomyosarcomas being their malignant counterparts. 4, 6
- Leiomyoma: Composed of well-differentiated smooth muscle cells arranged in fascicles, arising from either the muscularis mucosae or muscularis propria 4
- Microscopically characterized by spindle-shaped cells in a whorled pattern typical of smooth muscle, with no nuclear atypia 4
- Immunohistochemically positive for smooth muscle actin and desmin, and negative for CD117, CD34, and S100 protein 4, 6, 7
- Leiomyosarcoma: Malignant smooth muscle tumors with intersecting fascicles of spindle cells displaying nuclear atypicality and mitotic figures 8
- Requires positivity for at least 2-3 smooth muscle markers (smooth muscle actin, desmin, caldesmon) with negative CD117 and CD34 to distinguish from GIST 6
Rhabdomyoma and Rhabdomyosarcoma
Rhabdomyomas and rhabdomyosarcomas arise from skeletal muscle cells, with rhabdomyomas being benign and rhabdomyosarcomas being malignant tumors showing skeletal muscle differentiation. 4
- Rhabdomyosarcoma: The most common soft tissue sarcoma of childhood, showing skeletal muscle differentiation 4
- Alveolar rhabdomyosarcoma is characterized by specific chromosomal translocations: t(2;13)(q35;q14) producing PAX3-FKHR fusion or t(1;13)(p36;q14) producing PAX7-FKHR fusion 4
- Embryonal rhabdomyosarcoma shows complex genetic alterations 4
- These tumors recapitulate various stages of skeletal muscle development 4
Solitary Fibrous Tumor
Solitary fibrous tumors originate from mesenchymal cells, likely of fibroblastic or myofibroblastic lineage, and are characterized by a specific genetic fusion. 4
- Characterized by NAB2-STAT6 gene fusion, which is diagnostic for this entity 4
- Composed of spindle cells in a patternless architecture with variable collagen deposition 4
- The cell of origin is believed to be a primitive mesenchymal cell with fibroblastic differentiation 4
Key Diagnostic Pitfalls
- Lipoblast identification: Lipoblasts must occur in the appropriate histologic background, as similar cells can be seen in non-lipomatous lesions (silicone reaction, brown fat cells, Lochkern cells) 4, 2
- Smooth muscle vs. GIST: True leiomyomas are rare in the stomach; most tumors previously classified as leiomyomas were actually GISTs 4
- Desmin variability: Skull base leiomyomas may show negative or variable desmin staining despite being smooth muscle tumors, though they typically stain positive for smooth muscle actin 7
- Dual differentiation: Rare sarcomas can show combined features of liposarcoma and leiomyosarcoma, requiring immunohistochemical markers for proper identification 8