Pathology Modified 5 PDF

MUSCULOSKELETAL PATHOLOGY-5 BONE TUMORS-2 Professor Tariq Aladily Department of Pathology The University of Jordan [email protected] EWING SARCOMA It is a highly malignant tumor ▪ Uncommon malignant, undifferentiated tumor The cells don’t form bone or cartilage or any other material ▪ 10% of prima...

MUSCULOSKELETAL PATHOLOGY-5 BONE TUMORS-2 Professor Tariq Aladily Department of Pathology The University of Jordan [email protected] EWING SARCOMA It is a highly malignant tumor ▪ Uncommon malignant, undifferentiated tumor The cells don’t form bone or cartilage or any other material ▪ 10% of primary malignant bone tumors ▪ Second most common bone sarcoma in children ▪ 80% of patients are F ▪ 20% of cases arise extra-skeletal It is arises in soft tissue NOT only in the bone these a difference from osteosarcoma The cell of origin of this tumor still UNKNOWN exactly bcz it is primitive tumor it was thought that this tumor arise from stem cells of mesenchymal in soft tissue Another theory : this tumor build the structure of neuron BUT is NOT complete ▪ Arise from primitive cell (mesenchymal stem cell vs neuroectodermal cell) PATHOGENESIS ▪ >90% have balanced translocation Which mean there is translocation between two chromosome without loos of DNA material ▪ Fusion of EWSR1 gene (chr 22) and FLI1 gene (chr 11). ▪ The resultant protein binds DNA, dysregulate transcription and lead to uncontrolled growth and abnormal differentiation In long bone in the ▪ Tumor arise in the medulla , middle part & diaphysis - ▪ Severe necrosis and destruction, periosteal reaction of multiple layers, appear in X-ray as “onion skin” And it can activation of new bone synthesis BUT multi layers ‫اكثر من‬ ‫تحفيز نمو العظام إذا تم تصويرها رح تظهر مثل البصلة نتيجة طبقة من العظام بالتالي‬ After this fusion there is transcription of DNA and new protein is formed which is oncogene This protein dysregulate transcription MORPHOLOGY In the left side we see under the LM very primitive cells ( small / round ) and it is mainly a nucleus it DOSE NOT take any shape bcz abnormal differentiated so it looks like a lymphocyte ‫النو انويتها صغيرة‬ ▪ Left: Ewing sarcoma composed of sheets of small round cells with minimal clear cytoplasm ▪ Right: Homer-Wright rosettes: circular arrangement of cells with a central fibrillary material In the right side sometimes they can take the form of primitive neuron called Homer-Wright rosettes ‫و شكلها دائري النهم مثل الوردة‬ ‫اللون الوردي بالصورة عبارة‬ ‫ عن‬fibrillary part of neuron GIANT CELL TUMOR These tumor in the middle between completely benign and malignant SO it is more benign ‫صح انو حميد لكنه شوي عنيف اكثر من المعتاد‬ It can make more damage BUT still it can be controlled by surgery. ▪ Mostly benign tumor, but locally aggressive (may recur) This is the first tumor arise from Epiphyseal of long bone at the end ▪ Epiphyseal tumor, causes destruction of overlying cortex and of long bone bulge into soft tissue (arthritis-like symptoms) It can affect joint ▪ Most common site: distal femur and proximal tibia ▪ Third decade of life ▪ 4% develop lung metastasis, but controlled by surgical removal ▪ Tumor is composed of two population of cells: primitive They can take form of mononuclear cells osteoblast precursors (neoplastic) that secrete RANKL, and reactive osteoclasts (non-neoplastic) ▪ Radiographically, giant cell tumor of the proximal fibula is predominantly lytic and expansile with destruction of the cortex. A pathologic fracture is also present. This is X-ray of GIANT CELL TUMOR in the fibula you can see there is a large tumor in the Epiphysial at the end of the bone. MORPHOLOGY ↳ ▪ Giant cell tumor illustrating an abundance of multinucleate giant cells with background mononuclear stromal cells. There is a lot of multinucleated giant cells which is osteoclast. In the background you can see small cells contain single nuclei (neoplastic cell) ANEURYSMAL BONE CYST (ABC) ▪ Multiloculated blood-filled spaces ▪ Affects all age groups, but most commonly in adolescents ▪ Affects femur, tibia MOST common site or vertebra ▪ Arise in metaphysis ▪ Appear well-defined lesion with internal septa and filled with blood ▪ Septa are composed of plump uniform fibroblasts, multinucleated giant cells and woven bone ▪ Causes pain, swelling, pathologic fracture ▪ Locally aggressive (may recur) It can remove by surgery. You can not see a sold bone SO no neoplastic cell. ANEURYSMAL mean balloon like cavity in the tisse. ‫بمعنى منفوخ و فاضي‬ It is a tumor cases a mass and bone damage BUT it forms a cavity CYST means cavity The number of cells is little The bone has cavity filled with blood. ‫العظام بصير فيه تجاويف مليئة في‬ ‫الدم‬ PATHOGENESIS ▪ Neoplastic cells are spindle, unknown origin ▪ Rearrangement of chromosome 17p13 ▪ Fusion of USP6 with COL1A1 genes ▪ Results in overexpression of USP6 ▪ Activation of NF-kB pathway ▪ Increase in matrix metalloproteases, leading to cystic bone resorption MORPHOLOGY ▪ Aneurysmal bone cyst. (A) Axial magnetic resonance image demonstrating characteristic fluid-fluid levels (arrow). (B) Gross appearance of aneurysmal bone cyst. The lesion appears hemorrhagic and spongelike in this bisected portion of proximal fibula MORPHOLOGY ▪ Aneurysmal bone cyst with blood-filled cystic space surrounded by a fibrous wall containing proliferating fibroblasts, reactive woven bone (yellow arrow), and osteoclast-type giant cells (red arrows). Developmental defects: Occur when there is a disturbance in the development of the body FIBROUS CORTICAL DEFECT AND NONOSSIFYING FIBROMA This is not a true tumor ▪ Developmental defects, where fibrous tissue replaces bone. ( part of the bone is fibrous tissue) ▪ Present in 50% of children >2 years(it's a very common condition, but it's generally very small and not important), incidental finding ( it's not symptomatic, and it's discovered by Remember: chance when they take an X-ray for another region) ▪ Most commonly in metaphysis of distal femur or proximal tibia ▪ 50% multiple and bilateral ( more than one lesion) the Metaphysis Of bone ▪ Fibrous cortical defect: small ( acquired, single bone Syndromic --> appears early in life, multiple bones Sometimes we have polyostotic fibrous dysplasia with other diseases in the body = forms syndromes It's a rare syndrome, but it's commonly asked in medicine. Additional: McCune Albright syndrome -Notice the brown lesion Notice the disfigurement ‫( التشوه‬as we said it's more common in the face or the skull) PATHOGENESIS The most important mutation in this disease is GNAS1 gene mutation, it makes gain of function ▪ Gain of function mutation in GNAS1 gene ▪ Constitutively active Gs-protein ( will not be suppressed ) A mitogen: is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division ▪ Increase level of cAMP ( cAMP is a potent mitogen) ▪ Promotes cell proliferation and disrupts osteoblast differentiation ( so we will have tumor with little osteoblast without full maturation) GNAS1 gene mutation --> Gs-protein is permanently active without suppression --> increase cAMP in the cytoplasm -> Proliferation of the cells and distruption of OB​ ▪ Tumor arise in medulla, causes cortical thinning and bowing Additional: Notice the bowing !! Remember: there is bone formation, but it's incomplete ( not mature) MORPHOLOGY fibroblasts Those are the woven bone, (the pink material) they are curved, separated from each other. ‫بشبهوها بالحروف الصينية‬ Normally, it should rimmed by OB. So here I don't see them. ▪ Small curved woven bone trabeculae (Chinese letters), not rimmed by osteoblasts ▪ Abundant fibroblasts in between NOTE: Early bone (woven bone ): - Small - Separated from each other - Doesn't show the lamellae of lamellar bone Lamellar bone: is characterized by the organized arrangement of collagen fibers into layers or lamellae Woven bone: is characterized by the irregular arrangement of collagen fibers, large cell number, and reduced mineral content BONE METASTASIS -Any cancer can spread to bone, because bone is very vascular organ, so we have high chance for metastatic cells to reach bone. -Direct invasion = from other organ (eg. Lung) ▪ More common than primary bone tumors ▪ Any cancer can spread to bone (hematogenous, lymphatic or direct invasion) -mixed pattern: destruction and at the same time it synthesises new bone ▪ Commonly multifocal (multiple bones) ▪ Can be bone destroying (lytic lesion), pure blastic (bone forming) or mixed ▪ Prostate cancer commonly cause osteoblastic lesion ▪ Malignant cells secreted prostaglandins, cytokines and PTH- like peptide, activating osteoclasts ▪ WNT proteins are secreted in osteoblastic metastasis Wnt proteins comprise a major family of signaling molecules that orchestrate and influence a myriad of cell biological and developmental processes When we take a radiograph for the spine of the patient with prostate cancer, and if we see a very thick bone, we will know that he has metastasis. Additional: lytic Resorb the bone mixed Lytic + blastic Blastic Forming bones Prostate cancer