Path - MSK 3 MCQ (MD2)

Musculoskeletal Pathology: Neoplasms

• Musculoskeletal pathology includes neoplasms, fractures and other traumatic injuries, and metastatic disease.
• Plasma cell myeloma, osteosarcoma, osteoid osteoma, enchondroma, osteochondroma, fibrous dysplasia, and Ewing sarcoma are included in musculoskeletal pathology.
• Dr. Marcus Dabner is associated with musculoskeletal pathology, his email is [email protected]

Bone Tumors and Soft Tissue Tumors

• Bone tumors and soft tissue tumors originate from the mesoderm
• Soft tissue tumors are from mesenchymal tissue, fat, fibrous tissue, muscle, blood vessels, etc.
• Metastatic disease and plasma cell myeloma are more common than primary bone tumors

Bone Terminology

• Compact bone is also known as cortical bone and forms the cortex.
• Spongy bone is also known as trabecular or cancellous bone
• Spongy bone plus bone marrow make up the medullary cavity
• Lamellar bone is mature bone
• Woven bone is immature/new bone and is osteoid
• Long bones include the femur, tibia, and humerus.

Bone Tumors

• Metastatic disease, haematolymphoid malignancies and primary bone tumors affect bones
• Plasma cell myeloma and primary bone lymphoma are types of haematolymphoid malignancies
• Haematolymphoid malignancies are the most common type of bone tumor
• Primary bone tumors are rare compared to metastases and haematolymphoid malignancies

Metastases to Bone

• Metastases to bone is an active process
• Primary sites for metastases include lung, breast, prostate, colorectal adenocarcinoma, malignant melanoma, thyroid (follicular) adenocarcinoma, and renal cell carcinoma.
• Any bone can be affected, but common sites are vertebrae, ribs, skull, pelvis, and long bones (typically the axial skeleton).
• Metastases can be osteolytic or osteoblastic
• Osteolytic metastases are most common and involve bone destruction by tumor cells, leading to radiolucency on imaging.
• Cytokines stimulate osteoclastic bone resorption
• Osteoblastic metastases involve cytokines stimulating osteoblastic activity and new bone formation, leading to increased density on X-ray
• They are typical in prostate and breast carcinoma, occurring > 99% of the time.

Plasma Cell Myeloma

• Plasma cell myeloma involves multiple tumors throughout the skeletal system, and presents bone pain and pathological fractures
• Pathologic mechanisms include multiple tumors in bone, osteoclastic bone destruction, and clonal proliferation of plasma cells
• Clinical manifestations include bone pain, pathological fracture, hypercalcemia, monoclonal immunoglobulin, renal failure, susceptibility to infection, and anaemia due to deposits which cause amyloid or cast nephropathy
• Hypercalcemia is when osteoclastic bone destruction releases calcium into the blood
• It is a bone marrow-based malignant neoplasm of plasma cells
• Plasma cell myeloma is the most common primary malignancy of bone
• It usually affects individuals over 50 years old, with a male predominance (M=F)
• It manifests as monoclonal immunoglobulin in serum and urine (Paraprotein/M protein) and is previously called multiple myeloma where multiple tumors throughout skeletal system especially axial skeleton
• There is malignant proliferation of plasma cells forming tumourous masses within bone. Consisting of sheet-like atypical proliferations

Primary Bone Tumors

• Clinicopathological, the age of patient (skeletal maturity), the bone and area affected (eg tibial metaphysis), radiological features and pathological features are constant among primary bone tumors
• Clinical, radiological, and pathological features must correlate, its essential to correct diagnosis
• Multidisciplinary bone tumor meetings are essential for diagnosis

Pathological Classification

• Bone-forming tumors can be osteoid osteoma, osteoblastoma, or osteoma, which are benign, or osteosarcoma, which is malignant
• Cartilaginous tumors can be enchondroma, osteochondroma, chondroblastoma, or chondromyxoid fibroma, which are benign, or chondrosarcoma, which is malignant.
• Fibro-osseous tumors can be fibrous dysplasia or osteofibrous dysplasia, which are benign, or adamantinoma, which is malignant
• Fibrous/fibrohistiocytic tumors can be non-ossifying fibroma/fibrous cortical defect or benign fibrous histiocytoma, which are benign, or malignant fibrous histiocytoma, which is malignant
• Giant cell-rich tumors can be giant cell tumor, giant cell reparative granuloma, or brown tumor, which are benign, or giant cell osteosarcoma, which is malignant.
• Cystic lesions can be unicameral bone cyst or aneurysmal bone cyst, which are benign, or telangiectatic osteosarcoma, which is malignant
• Miscellaneous tumors can be haemangioma, which is benign, or angiosarcoma, chordoma, or Ewing sarcoma, which are malignant
• Tumours covered in this lecture are common, critical and classical

Osteosarcoma

• Osteosarcoma is a critical, malignant mesenchymal neoplasm (sarcoma) that produces bone matrix (osteoid)
• It has connective tissue differentiation
• It is known as a primary malignant tumor of bone, excluding haematolymphoid tumors
• Rare in adults, accounting for the top 10 pediatric cancers
• Males are slightly more commonly affected
• It has a Bimodal age distribution occurring throughout the 10-20s to > 50 years old
• Primary risk factors include Adolescents, Majority idiopathic, Hereditary retinoblastoma, Li-Fraumeni syndrome (p53 mutation) and Ionising radiation
• Secondary risk factors include Older adults, Underlying benign bone disease (Paget's disease), Benign bone tumors and Chronic osteomyelitis
• Paget's disease is the most common secondary risk factor
• Clinical presentation includes localized nocturnal pain that is a deep boring pain, typically near the knees in Palpable mass
• Pathological fracture and Constitutional symptoms like fever, anorexia and weight loss
• Metastatic disease can also be a clinical presentation
• Prognosis includes 80% five year survival for localized disease and 30% five year survival for metastatic disease
• Radiological clues include Codman’s triangle when the lifted periosteum at the edge of the tumors
• Includes Sunburst pattern where the periosteum becomes irritated it starts to produce new bone and is deposited in parallel rays at 90° to the long bones
• The destructive mass in medullary cavity, has a heterogeneous appearance in medullary cavity. Showing Areas of haemorrhage and Possible areas of necrosis
• Osteosarcoma is composed of malignant tumour cells producing osteoid matrix, often in delicate pericellular lacelike pattern (prominent in osteoblastic variant)
• Chondroblastic variant consist still of osteoid production
• Fibroblastic variant allows to deposition of fibrous tissue

Osteoid Osteoma

• Osteoid osteoma is a classical, benign bone-forming tumour and a disease of kids
• Fifteen percent of all primary benign bone tumors consist of osteoid osteoma
• Highest in the 5 to 20s range, where Males are affected more than Females in a 2:1 ratio
• Long bones that are affected, notably the tibia/femur, are affected in the cortex
• Clinical Presentation for Osteoid Osteoma: Nocturnal pain with a very pinpoint local pain that is responsive to NSAIDs because the tumor produces prostaglandins
• Can be seen circumscribed lucency within the cortex which has expanded around it
• It is a Small circumscribed cortical based lesion with Trabeculae of woven bone and Plump osteoblastic rimming

Enchondroma

• Enchondroma is a common, benign intramedullary cartilaginous neoplasm of cartilaginous tumor
• Up to 25% of primary benign bone tumors, is in the 20–30s age range, with males and females equally affected
• Small tubular bones of hands and feet (phalanges) are affected, almost always.
• Risk factors include multiple lesions in Ollier’s syndrome, which is non-inherited
• Clinical presentation: Asymptomatic; incidental radiological finding, pain when pathological fracture
• Prognosis includes Benign; treated with local curettage
• Presents Nodules of hyaline cartilage that form sharply with the interface with trabecular bone. While expanding medullary cavity of tubular bone

Osteochondroma

• Osteochondroma is common benign pedunculated tumor of bone with cartilage cap overlying bony stalk
• It is commonly called “exostosis” and can be classified as a form of cartilaginous tumor
• Most common benign bone tumor at 50% of cases are diagnosed at 10 – 20 years of age, and it occurs more in males
• Located on the Metaphyseal surface of long bones
• Multiple hereditary exostosis is risk factors (autosomal dominant)
• Clinical presentation: Asymptomatic; usually incidental radiological finding, Pain if impinging on nerve or fracture of stalk
• Prognosis: Benign; conservative management and Symptomatic cases cured with simple excision
• Cartilage cap is neoplastic
• Arises from metaphysis and points away from joints with merges with underlying bony stalk through enchondral ossification
• The Stalk is continuous with medullary cavity

Fibrous Dysplasia

• Fibrous dysplasia is a classic, benign fibro-osseous tumor of bone and
• Seven percent of primary benign bone tumors in the Early-Mid adulthood range, M=F is affected
• Found on the Axial skeleton affecting longer bones
• Risk factors include Polyostotic disease (McCune-Albright syndrome)
• Clinical presentation is Most of the time there are incidental radiological findings
• Prognosis: Benign (although low risk of malignant change)
• Exhibits Well-defined ground glass opacity within medullary cavity: Varus deformity in femur – “Shepherd’s crook” and consists of Curvilinear arrays of woven bone & with bland spindle cells.

Ewing Sarcoma

• Ewing sarcoma is a critical highly malignant neoplasm that is a small round blue cell tumour
• It consists of Primitive neuroectodermal tumor (PNET)
• It consists of 10% of primary malignant bone tumors and a Paediatric disease found at 10 – 15 years of age, M>F
• The Site is on the Long bones, causing Pelvis
• The Clinical presentation is a Painful enlarging mass and Systemic symptoms with metastatic disease
• Prognosis of Ewing Sarcoma: 5 yr survival 75% with a long term cure at to 50%
• Prototypical of “small round blue cell tumour” with rosettes, Two genes are abnormally fused together

Soft Tissue Tumors

• Malignant soft tissue tumors are sarcomas
• Paediatric Soft tissue tumours includes Brain Other CNS and Intracranial Tumours for both buys and girls
• Red flags raising suspicion for sarcomas include Tumor size >5cm with deep-seated intramuscular pain occurring in multiple lesions
• Classification of soft tissue tumors: World Health Organisation (WHO) classification, Subtypes and Histological classification by differentiation which most closely resembles Mature mesenchymal tissue classification
• FAT and LIPOMA: Uniform Adipocytes in 1 sheet
• SMOOTH MUSCLE: Exhibit Cigar shaped nuclei of Eosinophilic cytoplasm
• SKELETAL MUSCLE: exhibit Spindle cells with atypical cells
• NERVE: Exhibit Uniform fibrous and Collagenous cells with Atypical
• BLOOD VESSELS and Uniform endothelial cells where Invasive proliferation happens

Integrated Diagnosis

• Clinical/radiology, Immunohistochemistry,Histology , Electron Microscopy, and Molecular tools allows to integrate for diagnosis

Summary

• Primary bone and soft tissue tumors rare
• Metastatic disease and plasma cell myeloma far more common in comparison
• Common (relative) are Osteochondroma, enchondroma.
• Classical cases can be Osteoid osteoma, fibrous dysplasia.
• Critical cases are Osteosarcoma, Ewing sarcoma
• Nomenclature for soft tissue tumours