Bone & Soft Tissue Tumour Pathology: OmpathStudy

Bone & Soft Tissue Pathology — Must-Knows --- Soft Tissue Tumours — Fat, Fibrous, Muscle Lipoma vs liposarcoma Lipoma: mature fat cells, thin capsule, benign — the most common soft tissue tumour overall Well-differentiated liposarcoma: looks almost identical to lipoma under the microscope, but is malignant — the only way to tell them apart is a genetic test showing MDM2/CDK4 gene amplification (region 12q13-15) Myxoid liposarcoma: has a jelly-like (myxoid) background plus immature fat cells called lipoblasts; caused by a specific gene fusion, t(12;16) FUS-DDIT3 Pleomorphic liposarcoma: the most aggressive type, cells look wildly different from each other (pleomorphic) Nodular fasciitis — the great impersonator Grows fast, has lots of dividing cells (mitoses) — looks alarming, like cancer But it's actually benign and self-limiting (goes away on its own) Caused by a gene fusion: t(17;22) MYH9-USP6 Exam trap: don't call this a sarcoma just because it grows fast and has mitoses Desmoid tumour (deep fibromatosis) Grows into surrounding tissue (locally invasive) but never spreads to distant organs (no metastasis) Linked to a faulty APC gene — same gene that's faulty in familial adenomatous polyposis (FAP), a condition causing hundreds of colon polyps On biopsy: bland-looking fibroblasts, but with abnormal build-up of a protein called beta-catenin inside the nucleus (because APC normally breaks beta-catenin down, and when APC is broken, beta-catenin piles up) Rhabdomyosarcoma (skeletal muscle cancer) Embryonal type — most common type in children; the "botryoid" (grape-like) variant grows as clusters in the vagina or bladder of young children Look for cross-striations on histology — proof the cells are trying to become muscle Leiomyoma vs leiomyosarcoma Leiomyoma: benign smooth muscle tumour, very common in the uterus (fibroids); cells have blunt-ended nuclei and minimal atypia Leiomyosarcoma: malignant version, seen in deep sites like the retroperitoneum; markers SMA and desmin (both smooth muscle markers) are positive, but the cells look atypical and hyperchromatic Synovial sarcoma Confusing name — it does NOT come from the joint synovium Occurs near joints in young adults, grows slowly over years Defining feature: a translocation, t(X;18) SS18-SSX Undifferentiated pleomorphic sarcoma (UPS) This is a "leftover" diagnosis — given only when a high-grade sarcoma doesn't show any specific line of differentiation on special stains (not fat, not muscle, not anything specific) --- Nerve Sheath Tumours Schwannoma Comes from Schwann cells (which make the myelin sheath around peripheral nerves) Encapsulated (has a clear boundary), painless Classic histology: Antoni A areas (densely packed cells) and Antoni B areas (loose, myxoid) — plus Verocay bodies (rows of nuclei lined up around a pale zone) Positive for S100 stain Neurofibroma types — and how they link to NF1 vs NF2 Localised cutaneous neurofibroma: a single small nodule in the skin Diffuse neurofibroma: spreads more broadly through the dermis Plexiform neurofibroma: grows along the length of a nerve, looks like a "bag of worms" — this type is specifically linked to NF1, and carries a 15-20% lifetime risk of turning into a malignant peripheral nerve sheath tumour (MPNST) NF1 (neurofibromatosis type 1) → neurofibromas are the hallmark NF2 (neurofibromatosis type 2) → bilateral schwannomas (especially in the internal auditory canal, causing hearing loss) are the hallmark instead — don't mix these two up --- Bone Tumours Osteosarcoma Most common in teenagers, at the distal femur (metaphysis, near the knee) Look for: a Codman triangle on X-ray (a triangular shadow where the tumour lifts the periosteum off the bone) and a mixed lytic (bone-destroying) and sclerotic (bone-forming) pattern Osteoid osteoma vs osteoblastoma — same family, different size Osteoid osteoma: small (under 2cm), causes severe night pain that is dramatically relieved by aspirin (because the tumour produces prostaglandins, which aspirin blocks) — commonly in the proximal tibia Osteoblastoma: essentially a bigger version (over 2cm), often in the posterior elements of the spine, but does NOT respond dramatically to aspirin the way osteoid osteoma does Osteochondroma A painless bony bump that grows outward from the metaphysis Key finding: the medullary cavity (the hollow center of the bone) is continuous with the tumour's own cavity — proving it's really just an outgrowth of normal bone with a cartilage cap on top Chondrosarcoma A malignant tumour made of cartilage-producing cells Classic site: pelvis or axial skeleton (unlike osteosarcoma, which favours long bone metaphyses) Ewing sarcoma Occurs in adolescents, made of small round blue cells (very immature-looking cells with little cytoplasm) Defining translocation: t(11;22) EWS-FLI1 Positive for CD99 marker Fibrous dysplasia Caused by a GNAS gene mutation On X-ray/histology, the bone trabeculae look like "Chinese letters" — an odd, curved shape --- Bone