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Pathology Answers
Q1. Difference between Leiomyoma & Leiomyosarcoma
(Robbins & Kumar Basic Pathology)
| Feature | Leiomyoma (Benign) | Leiomyosarcoma (Malignant) |
|---|---|---|
| Nature | Benign smooth muscle tumor | Malignant smooth muscle tumor |
| Common site | Uterus (fibroids), skin (pilar leiomyoma), GI tract | Deep soft tissues of extremities, retroperitoneum, uterus, great vessels (IVC) |
| Age/Sex | Common in reproductive age women | Primarily older adults; more common in women |
| Size | Usually 1-2 cm | Can grow very large (retroperitoneal) |
| Gross | Well-circumscribed, firm mass | Painless, firm mass; retroperitoneal tumors may be huge |
| Microscopy | Fascicles of densely eosinophilic spindle cells with minimal atypia and extremely rare mitotic figures | Interweaving fascicles of eosinophilic spindle cells to sheets of pleomorphic cells; mitotic activity and necrosis are common |
| Nuclear atypia | Absent / minimal | Present (pleomorphic, hyperchromatic nuclei) |
| Mitoses | Extremely rare | Frequent (key criterion) |
| Necrosis | Absent | Common |
| Karyotype | Simple / normal | Complex karyotype with multiple chromosomal gains and losses (genomic instability) |
| Genetics | Germline FH (fumarate hydratase) mutations in hereditary multiple leiomyoma syndrome | Complex karyotypic abnormalities; underlying genomic instability |
| IHC | Smooth muscle actin (+) | Smooth muscle proteins (+) on IHC (aids diagnosis) |
| Prognosis | Cured surgically (solitary lesions) | Superficial: good prognosis. Retroperitoneal: difficult to control; metastasizes to lungs; often fatal |
| Metastasis | Never | Yes - especially to lungs |
Key distinguishing criteria (pathological): number of mitoses per HPF, degree of nuclear atypia, and presence of necrosis.
Q2. Short Note on Retinoblastoma
(Robbins & Kumar Basic Pathology)
Definition: The most common primary intraocular malignancy of children. A "small round blue cell" tumor of the retina.
Genetics (Two-hit hypothesis - Knudson)
- Hereditary (40%): Germline mutation in the RB tumor suppressor gene (chromosome 13q14). Typically bilateral and multifocal. Autosomal dominant pattern of inheritance. Also increased risk of osteosarcoma and other soft tissue tumors.
- Sporadic (60%): Somatic mutations in RB gene. Typically unilateral and unifocal.
- Both alleles of RB must be inactivated ("two hits") for tumor to develop.
Morphology
- Gross: Nodular masses, usually in the posterior retina, sometimes with satellite seedlings.
- Microscopy:
- Undifferentiated elements: small round cells with hyperchromatic nuclei (resembling retinoblasts) - "small round blue cells"
- Differentiated elements: Flexner-Wintersteiner rosettes (single layer of cuboidal/columnar cells around a central lumen - reflecting photoreceptor differentiation) and fleurettes
- Viable tumor cells cluster around blood vessels; necrosis in avascular areas
- Focal dystrophic calcification is characteristic
Spread
- To brain, skull, bone marrow
- Seldom to lungs (unlike most sarcomas)
- Prognosis worsened by: extraocular extension, invasion along optic nerve, choroidal invasion
Treatment
- Chemoreduction (including selective intra-ophthalmic artery delivery) followed by laser/cryopexy
- Goal: preserve vision + eradicate tumor
Q3. Short Note on Rhabdomyosarcoma (RMS)
(Robbins & Kumar Basic Pathology)
Definition: A malignant mesenchymal tumor with skeletal muscle differentiation. The most common soft tissue sarcoma of childhood and adolescence.
Subtypes (4)
| Subtype | Frequency | Age | Site | Morphology | Genetics | Prognosis |
|---|---|---|---|---|---|---|
| Embryonal | 50% | 1-5 years | Head/neck, genitourinary | Primitive round and spindle cells in myxoid stroma; strap cells with cross-striations ("rhabdomyoblasts") | LOH 11p15 | Better |
| Alveolar | 20% | 5-15 years | Extremities | Round cells divided by fibrous septa into alveolar-like spaces | t(2;13) → PAX3-FOXO1 fusion; t(1;13) → PAX7-FOXO1 | Worse |
| Pleomorphic | 20% | Adults | Deep extremities | Large, bizarre, multinucleate eosinophilic cells | Complex karyotype | Often fatal |
| Spindle cell/Sclerosing | 10% | All ages | Variable | Fusiform cells in fascicles/storiform pattern; dense sclerotic stroma | - | Variable |
Key Points
- Sarcoma botryoides: grape-like variant of embryonal RMS; develops in hollow viscera (urinary bladder, vagina) - best prognosis
- Arises from undifferentiated mesenchymal stem cells (not from pre-existing skeletal muscle)
- IHC: positive for myogenin, MyoD1, desmin, muscle-specific actin
- Head and neck is the second most common site (orbit is most common within H&N)
- Treatment: surgery + chemotherapy ± radiation; COG protocols
Q4. Classification of Soft Tissue Tumours
(Robbins & Kumar Basic Pathology, Table 19.3)
By convention, soft tissue = nonepithelial tissue exclusive of skeleton, joints, CNS, and hematopoietic/lymphoid tissues. Benign soft tissue tumors are 100 times more frequent than sarcomas.
Classification by Tissue of Origin
| Category | Benign | Malignant |
|---|---|---|
| Adipose tissue | Lipoma | Liposarcoma (well-differentiated, myxoid, pleomorphic) |
| Fibrous / myofibroblastic | Nodular fasciitis, Deep fibromatosis (desmoid) | Fibrosarcoma |
| Skeletal muscle | Rhabdomyoma | Rhabdomyosarcoma (embryonal, alveolar, pleomorphic, spindle cell/sclerosing) |
| Smooth muscle | Leiomyoma | Leiomyosarcoma |
| Vascular | Hemangioma | Angiosarcoma, Kaposi sarcoma |
| Peripheral nerve | Schwannoma, Neurofibroma | Malignant peripheral nerve sheath tumor (MPNST) |
| Cartilage | - | Extraskeletal chondrosarcoma |
| Bone | - | Extraskeletal osteosarcoma |
| Uncertain origin | - | Synovial sarcoma, Undifferentiated pleomorphic sarcoma (UPS), Ewing sarcoma |
| Uncertain/other | Tenosynovial giant cell tumor | - |
Classification by Karyotypic Pattern
- Simple karyotype (15-20%): Single or few chromosomal changes (e.g., Ewing sarcoma, synovial sarcoma). Young patients, monomorphic appearance.
- Complex karyotype (80-85%): Aneuploid/polyploid with multiple gains and losses (e.g., leiomyosarcoma, undifferentiated pleomorphic sarcoma). Older adults, pleomorphic cells.
Classification by Clinical Behavior
- Benign - self-limited, minimal treatment needed
- Intermediate grade - locally aggressive, minimal metastatic risk
- Malignant (sarcomas) - high risk of metastasis and mortality; cause 2% of cancer deaths despite being <1% of all cancers
Sources: Robbins & Kumar Basic Pathology, Cummings Otolaryngology
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