ORTHOPAEDIC PATHOLOGICAL SPECIMEN AND HISTOLOGY DESCRIBING GROSS SPECIMEN

ORTHOPAEDIC PATHOLOGICAL SPECIMEN AND HISTOLOGY

DESCRIBING GROSS SPECIMEN A: Identify the part: Knee / prox. femur/ prox. tibia/ pelvis /scapula. Epiphyseal / Metaphyseal / Diaphyseal. Physeal plate visible? – Immature pt.

B: Describe the abnormality: Nature: solid / soft & friable /cystic / varigated Matrix: bony / cartilaginous / fibrous Secondary changes: central necrosis/ hemorrhage / cystic change Cortical destruction, periosteal elevation Intramedullary spread Tumor margin / capsule: well defined / illdefined Extension: into soft tissue / joint; invasion / infiltration to surrounding tissue

C: Give provisional diagnosis.

t Ewing’s sarcoma Myeloma Osteoid osteoma Epiphyseal – Chondroblastoma – Giant cell tumor t Diaphyseal – Ewing’s sarcoma – Myeloma Fibrous dysplasia – – – Majority – Chondroblastoma– Giant cell tumor t Ewing’s sarcoma Myeloma, Fibro sarcoma, Reticulum cell sarcoma Adamantinoma Fibrous dysplasia Osteoid Osteoma Metaphyseal – Most others

t Enchondroma Unicameral bone cyst Round cell tumors Central – Enchondroma – Unicameral bone cyst – Round cell tumors t Cortical – Osteoid osteoma t Eccentric – Most other tumors Majority

GIANT CELL TUMOR Age: 20 -40. Epiphyseal location (After epiphyseal closure) Common location: around knee (50%), distal radius Xray: Geographic lytic lesion, thinned & ballooned out cortex. Gross pathology: Large red - grey - brown tumor Soft & friable Areas of cystic degeneration / necrosis & blood filled cavities

HISTOPATHOLOGY: • Uniform oval mononuclear stromal cells : mesenchymal origin • Appear to grow in a syncytium • Numerous osteoclast-type giant cells: reactive with centrally placed uniform size nuclei (40 -100) • Necrosis, hemorrhage, hemosiderin deposition and reactive bone formation • Relatively few mitotic figures in relation to the dense cellularity of the tumor

GIANT CELL VARIANTS Includes the tumors which show giant cells in histology A. ABC B. Brown tumor C. Chondromyxoid fibroma, chondroblastoma D. Desmoplastic fibroma E. Epulis – Giant cell reparative granuloma F. Fibrous dysplasia, non ossifying fibroma G. Giant cell rich osteosarcoma H. Benign fibrous histiocytoma

Giant cell…… Physiological: Megakaryocyte Pathological Langhans : fused epitheliod cells. Peripherally arranged 7 -21 nuclei. TB, histoplasmosis, sarcoidosis, other mycobacteria Foreign body: fused macrophages. Numerous nuclei scattered in cytoplasm Aschoff : Rheumatic heart disease Reed Sternberg: Hodgkin’s lymphoma Touton : xanthoma, xanthogranuloma, dematofibroma Viral: Warthin Finkeldy (measles), resp syncitial virus, parainfluenza Tumor

Features of malignant changes : (1) Size and number of giant cells decrease (2) Stroma shows : Heterogenicity as : Crowding, Plumping up, Increased chromatin, Increased mitotic figures. (3) Vascularity increases Grading of GCT (Jaffe): Stromal cells Giant cells Stroma less Large number Grade-II or Borderline GCT Prominent cellular atypia Decrease in number Grade-III or fully malignant Sarcomatous stroma Sparse Grade-1 or conventional GCT

Campanacci’s Radiological Grading Grade I – Cystic lesion Grade II – Cortex thin but not perforated Grade III – Tumour extended into surrounding soft tissue Enneking’s Staging of Benign GCT Stage I (Latent) n 10 -15% Stage II (Active) n 70% Stage III (Aggressive) n 10 -15% n No symptom, Pathological #s may occur n Benign, symptomatic, Pathological #s may occur n Benign but rapidly growing, cortex perforated

Treatment (Grade-I and Grade-II) (1) Only curettage. (2) Curettage + bone grafting. (3) Curettage + bone grafting + liquid nitrogen (cryosurgery). (4) Extended aggressive curettage + Phenol / argon beam coagulation / bone cementing. Grade-III – Resection + Reconstructions Resection : En Block (Joints lost) * Role of Radiation in GCT- spine/pelvis (1500 -5000 rads for 5 -6 wks)

Giant Cell Tumour

OSTEOSARCOMA Bimodal age distribution: Primary 10 -20, secondary 50 -70. 75% around knee Bone forming tumor arising from bone Several subtypes – By location (Central or Juxtacortical) Degree of differentiation: well to dedifferentiated Histologic variance: osteoblastic/chondroblastic/fibroblastic/telangictatic/small cell Associated with Retinoblastoma (rb gene), Li Fraumeni syndrome (p 53 gene), Rothmund Thomsen syndrome.

GROSS PATHOLOGY: Metaphyseal Tan-white solid tumor fills most of the medullary cavity of the metaphysis and proximal diaphysis Expanding & infiltrating through the cortex, lifts the periosteum (Codman’s triangle) and forms soft tissue masses on the side of the bone Areas of hemorrhage and central necrosis.

HISTOPATHOLOGY: Pleomorphic and anaplastic cell population- large hyperchromatic nuclei, mitotic figures Abundant fibrous/ chondroid matrix Formation of pink homogenous osteoid by neoplastic cell: characteristic. The neoplastic bone has a coarse, lacelike architecture but is also deposited in broad sheets or as primitive trabeculae. Osteoblastic, chondroblastic or fibroblastic types Osteoclast-like giant cells may be present

CHONDROSARCOMA Age: 30 -60 Primary or Secondary ( Enchondromatosis [Ollier 50%, Maffucci 100%], diaphyseal aclasis 20%, osteochondroma 0. 25%) Pelvis (30%), Femur (20%) Types: Conventional, mesenchymal, clear cell, juxtacotical, dedifferentiated Most common malignant bone tumor of hand

GROSS PATHOLOGY: Large bulky tumor Made up of lobules of gray-white /somewhat translucent glistening tissue. Tumor permeating throughout the medullary cavity, growing through the cortex, and forming a relatively wellcircumscribed soft tissue mass. At center – necrotic/liquefied/cystic. Gelatinous appearance secondary to myxoid changes in matrix. May show calcification. The adjacent cortex is thickened or eroded, and the tumor grows with broad pushing fronts into the surrounding soft tissue.

HISTOPATHOLOGY: • Tumor cells produce cartilaginous matrix; well, moderate or poorly differentiated. • May have only minor or focal atypia • Intracytoplasmic hyaline globules common in low grade tumors

EWING’S SARCOMA James Ewing 1921 GROSS PATHOLOGY: Diaphyseal in long bones; also pelvis, rib, scapula White tan grey mass like brain; or red like red currant gelly if hemorrhagic With necrosis & hemorrhage Cortical destruction Invasion to soft tissue, no capsule

HISTOPATHOLOGY: Homogenous & densly packed undifferentiated small round blue cells like lymphocytes; regular nuclei, infrequent mitoses, scant clear cytoplasm. • Abundant glycogen: PAS + diastase digestible • Rare Homer- Wright pseudorosettes (7 -8 tumor cells arranged in a circle about a central fibrillary space) •

D/D : Small Round Cell Tumor Ewing’s: mic 2 overexpression - CD 99/013. t(11; 22)(EWS-FLI-1). NSE + PNET (Primitive neuroectodermal tumor): CD 99/013. S 100, chromogranin, synaptophysin; > 20% Homer Wright rosettes Lymphoma (reticulum cell sarcoma, NHL): CD 45, LCA Small cell carcinoma: keratin, synaptophysin, chromogranin Mesenchymal chondrosarcoma Neuroblastoma: neurofilament. S 100, chromogranin, synaptophysin. Alveolar rhabdomyosarcoma: actin, desmin, vimentin, Myo. D 1, myogenin Leukemia

OSTEOCHONDROMA GROSS PATHOLOGY: Mushroom shaped Cartilage-capped bony outgrowth Cartilage cap usually regular and thin Sessile / Pedunculated : attached to skeleton by bony stalk; medullary cavity of the osteochondroma and bone are in continuity Diaphyseal aclasis: multiple heriditary exostosis Trevor’s disease: Epiphyseal side osteochondroma

Painful osteochondroma: Fracture Bursitis Malignant transformation: fluffy calcification in the cartilage cap, thickness of cartilage cap > 1 cm. Radiology Treatment

CHRONIC OSTEOMYELITIS Sequestrum is the necrotic bone that is embedded in the pus/infected granulation tissue. Involucrum is the new bone laid down by the periosteum that surrounds the sequestra. Cloaca is the opening in the involucrum through which pus & sequestra make their way out.

Types of sequestrum…. . Tubular: long bone Annular: amputation stump Ring: around pin tracts Flake, coke, rice grain: tubercular Button: histiocytosis Feathery: syphilis Match stick: sickle cell Coloured: fungal Black: gun shot Bombay: exposed bone after open fracture

TUBERCULAR SPONDYLITIS (POTT’S) SPINE Paradiscal Loss of height of vertebra Caseating necrotic tissue Bone necrosis sequestra Sclerosis

Acute osteomylitis is most commonly caused by a)staphylococcus aureus b)H. influenzae c)Streptococcus d)Salmonella e) Pseudomonas

Earliest site of bone involvement in hematogenous osteomyelitis a)Metaphysis b)diaphysis c)Epiphysis d) Physis e)Point of entry of nutrient artery

Complications of acute osteomyelitis a)malignancy b)fracture of the affected bone c)sepsis d)chronicity

The most common organism causing osteomyelitis in drug abusers is a)E coli b)pseudomonas c)Klebsiella d)Staph aureus

Giant cell tumour is located in the? a) Epiphysis b) Metaphysis c) diaphysis d) all of the above

Soap bubble appearance is seen in which of the following tumours? a) Osteosarcoma b) Chondrosarcoma c) Osteoclastoma d) Ewings sarcoma

A 15 year old boy is injured while playing cricket. X-rays of the leg rule out of a possible fracture. The radiologist reports the boy has an evidence of aggressive bone tumour with bone destruction and soft tissue mass. The bone biopsy reveals a bone cancer with neural differentiation. Which of the following is the most likely diagnosis? a) Chondroblastoma b) Ewing‘s sarcoma c) Neuroblastoma d) Osteosarcoma

Both Ewing sarcoma and peripheral neuroepithelioma belong to the Ewing family of tumors and are considered neural tumors. Unlike neuroblastoma, these neural tumors are not derived from the sympathetic system, and catecholamine metabolites are not excreted in the urine. In vitro, these tumors show neural differentiation and have neural features. Results with neuron-specific enolase and S-100 protein testing are positive. electron microscopy reveals neural structures such as neurites and dense-core granules. Glycogen granules are present, and alkaline phosphatase is absent.

Neuroblastoma (NB) is the most common extracranial solid cancer in childhood and the most common cancer in infancy It is a neuroendocrine tumor, arising from any neural crest element of the sympathetic nervous system (SNS). It most frequently originates in one of the adrenal glands, but can also develop in nerve tissues in the neck, chest, abdomen, or pelvis.

CHONDROBLASTOMA Although it can affect people of all ages, it most often appears in males younger than 25 years old. Biopsy and hematoxylin and eosin (H&E) staining under high light microscopy magnification show numerous chondroblastic cells embedded in a highly mesenchymal cartilaginous matrix. Chicken-wire calcification in a latticelike pattern surrounding the tumor cells is present in 30% of chondroblastomas.

Malignant tumour of mesenchymal cells characterized by formation of osteoid is description fit for ? a) Osteosarcoma b) Chondrosarcoma c) Osteoclastoma d) Ewings sarcoma

Secondary osteosarcoma can be caused after? a) Pagets disease b) fibrous dysplasia c) multiple enchondromatosis d) All the above

Causes of secondary osteosarcoma: 1 - Radiation 2 - Bone Diseases: a) Pagets disease b)Hereditary multiple osteochondroma c)Enchondromatosis d) Fibrous dysplasia 3 - Inherited Cancer Syndromes: a) Li–Fraumeni syndrome b) Rothmund-Thomson syndrome c) Hereditary retinoblastoma d) Bloom syndrome e) Werner syndrome f) Diamond-Blackfan anemia

Most common site of metastasis in Osteosarcoma is ? a) Lungs b) Heart c) Brain d) Liver

True statement about involucrum and sequestrum: a) Involucrum is a piece of dead bone b) Sequestrum is a sheath of new bone formation c) Sequestrum is surrounded by involucrum d) Involucrum is surrounded by sequestrum

Pulsatile tumor is seen in 1. Osteosarcoma 2. Osteoclastoma 3. Ewings 4. Chondrosarcoma

Pulsating Tumors of the Bone *Primary tumors that may present as pulsating lesions : 1 - Telengiectatic Osteogenic sarcoma 2 - Angioendothelioma/Angiosarcoma of bone 3 - Aneurysmal bone cyst 4 - Giant cell tumor (rarely) *Secondaries/Metastases that may present as pulsating lesions : 1 - Metastasis from Renal cell carcinoma 2 - Metastasis from Thyroid carcinoma

Ewings sarcoma is believed to arise from : a) Aberrant cartilage rests b) Endothelial cells of bone marrow c) Mesothelial cells d) Periosteocytes

Which of the following malignant tumours is radio resistant? A. Ewing’s sarcoma B. Retinoblastoma C. Osteosarcoma D. Neuroblastoma

Most radio resistant tumors are: 1. Malignant melanoma 2. Osteosarcoma 3. Pancreatic carcinoma

All the statements are true about exostosis, except A. It occurs at the growing end of bone B. Growth continues after skeletal maturity C. It is covered by cartilaginous cap D. Malignant transformation may occur

Which of the following conditions is least likely to present as an eccentric osteolytic lesion: A. Aneurysmal bone cyst B. Giant cell tumour C. Fibrous cortical defect D. Simple bone cyst

7 year old child presents with a lesion in upper tibia. X-ray shows radiolucent area with Codman’s triangle and Sunray appearance. Diagnosis is : a) Ewing’s sarcoma b) Osteosarcoma c) Osteoid osteoma d) Chondrosarcoma

Sunray appearance” on x-rays is suggestive of : 1. an osteogenic sarcoma. 2. a chondrosarcoma. 3. a metastatic tumor in the bone. 4. an Ewing’s sarcoma.

The Codman triangle may be seen with aggressive lesions: 1 - osteosarcoma 2 - Ewing sarcoma 3 - osteomyelitis 4 - active aneurysmal bone cyst 5 - giant cell tumour 6 - metastasis 7 - chondrosarcoma (especially juxtacortical chondrosarcoma) 8 - malignant fibrous histiocytoma

Chondroblastomas most commonly occurs in ? a- epiphysis b- diaphysis c- metaphysis d- medullary cavity

Most common benign tumour of the bone ? a- giant cell tumour b- simple bone cyst c- osteochondroma d- enchondroma

Onion peel appearance on x ray is seen in? a- osteosarcoma b- ewings sarcoma c- osteoclastoma d- osteochondroma

Which of the following is not a benign tumour ? a- chondroma b- chordoma c- osteochondroma d- enchondroma

Most common site of osteogenic sarcoma ? a- femur upper end b- femur lower end c- tibia upper end d- tibia lower end

Turn - o - plasty is used in the treatment of which of the following tumours ? a- osteosarcoma b- osteoclastoma c- osteochondroma d- osteoblastoma e- chondrosarcoma

Which of the following is the least commonly affected site for chondrosarcoma? a. Pelvis b. Proximal Femur c. Proximal Humerus d. Hands and Feet

A 30 -year-old man has pain about his left knee that he says has been worsening "for weeks". On physical examination the left knee appears larger than the right, and there is tenderness to palpaption. A radiograph reveals a 7 cm lytic lesion involving the epiphyseal region of the distal femur with a "soap bubble" appearance. The lesion is curretted, and histologically there are numerous multinucleated cells in a stroma with plump to spindle shaped mononuclear cells. Which of the following is the most likely diagnosis? A Osteosarcoma B Chondrosarcoma C Malignant fibrous histiocytoma D Giant cell tumor E Tuberculosis

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