Bone Forming Tumours Flashcards
Osteoid osteoma
- Benign, bone forming tumor
- M:F = 2:1
- More common in children and adolescents
- Broad skeletal distribution
- 50% occur in the long bones of the lower extremities
- Femoral neck is the single most frequent anatomic site
- Usually near the end of the diaphysis of long bones
- Less common in the long bones of upper extremities
- Bones of elbow are the most common site in upper extremity
- Small bones of hands and feet and posterior elements of vertebral body
- Nocturnal pain, relieved by aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
Radiology:
Xray:
* Intracortical lesions have a nidus with a variable degree of mineralization and surrounding reactive osteosclerosis
Macro:
* Oval red nidus is easily distinguishable from surrounding tissue
* Soft and friable to sclerotic nidus
* Surrounded by densely sclerotic reactive bone
Micro:
* Nidus: Haphazard trabeculae of woven bone with prominent osteoblastic rimming
* Different thickness and mineralization level
* Disordered (Pagetic) cement lines in some cases
* Sheet-like osteoid deposition in some cases
* Densely sclerotic woven bone in some cases
* Surrounding bone: Thickened trabeculae of bone with adjacent loose fibrovascular stroma
Molecular:
* Rearrangement of AP1 transcription factor
* FOS (more common) gene on chromosome 14
* FOSB (less common) gene on chromosome 19
–
Other tumors with FOSB gene rearrangement:
* Osteoblastoma
* Epithelioid hemangioma
* Pseudomyogenic hemangioendothelioma
Osteoblastoma
- Osteoblastoma is a locally aggressive bone forming tumor
- morphologically similar to osteoid osteoma but with growth potential and generally > 2 cm in dimension
- Predilection for the spine and sacrum (40 - 55%), most commonly involving the posterior elements of the spine
- Expresses Runx2 and Osterix, transcription factors involved in osteoblastic differentiation
Radiology:
* Characteristic appearance on radiographs
* Dense shell of bone surrounding the lesion,
* Some tumors resembling osteoid osteoma with a radiolucent nidus and surrounding sclerotic changes
Micro:
* Expansile, surrounded by a sclerotic rim, may or may not have a central sclerotic nidus
* Composed of interanastomosing trabeculae of woven bone, set within loose edematous fibrovascular stroma, often with extravasated erythrocytes
* Tumors show a spectrum of bony maturational changes ranging from cords and clusters of activated osteoblasts associated with minimal osteoid to lace-like wispy osteoid to broad anastomosing trabeculae of woven bone to sclerotic sheets of woven bone
* Osseous trabeculae are lined by a single layer of osteoblasts
* Diffusely scattered osteoclast type, multinucleated giant cells are often present
* Mitotic rate may be high but atypical mitoses are not present
Molecular:
* Homo or hemizygous deletions in chromosome 22
* Losses of ZNRF3, KREMEN1 and NF2 (inhibitors of the Wnt / beta catenin pathway)
IHC:
* Nuclear beta catenin staining
* FOS
* SATB2
Osteoid osteoma vs osteoblastoma
Osteoid osteoma and osteoblastoma are both benign bone tumors, but they differ in several important aspects such as size, location, clinical presentation, and imaging characteristics. Here’s a breakdown of their key differences:
- Size
Osteoid Osteoma: Typically smaller, usually less than 2 cm in diameter.
Osteoblastoma: Larger than osteoid osteomas, usually greater than 2 cm in diameter. In fact, they can sometimes exceed 4 cm. - Location
Osteoid Osteoma: Commonly found in the long bones (especially the femur, tibia) and the spine. They are more likely to affect the cortex of the bone.
Osteoblastoma: Also seen in the long bones and spine, but more frequently in the vertebrae and pelvis. They tend to involve the medullary (inner) part of the bone more than osteoid osteomas. - Age of Onset
Osteoid Osteoma: Most common in younger individuals, typically affecting children and adolescents (ages 10-25).
Osteoblastoma: Also affects younger people but can be seen in adults (ages 20-40). It is less common in children compared to osteoid osteoma. - Clinical Presentation
Osteoid Osteoma: Characterized by severe night pain, which is often relieved by nonsteroidal anti-inflammatory drugs (NSAIDs). The pain is often localized to the area of the tumor and is typically dull and aching.
Osteoblastoma: Pain in osteoblastoma is often less responsive to NSAIDs and may be more persistent or progressive. The pain can also be associated with swelling or deformity, especially when the tumor is large. - Radiographic Appearance
Osteoid Osteoma: On radiographs, it often presents as a small, round or oval radiolucent nidus with a surrounding sclerotic bone reaction. The nidus is usually well-defined.
Osteoblastoma: Appears as a larger, lytic lesion with a less defined border. It may be surrounded by more significant reactive sclerosis, and it can have a more heterogeneous appearance compared to the osteoid osteoma. In some cases, there may also be cortical destruction or bone expansion. - Histopathology
Osteoid Osteoma: Characterized by nidus of osteoid and woven bone with a surrounding rim of reactive bone sclerosis. The cells in the nidus are usually relatively small.
Osteoblastoma: Typically has a more abundant osteoid tissue and is generally composed of a mix of osteoblasts (bone-forming cells), woven bone, and sometimes more prominent fibrous tissue. There is usually more cellularity compared to osteoid osteoma. - Treatment
Osteoid Osteoma: Can often be treated successfully with NSAIDs for pain relief. In cases where the tumor is symptomatic or difficult to manage, surgical excision or radiofrequency ablation (RFA) is common.
Osteoblastoma: Due to its larger size and less favorable response to NSAIDs, surgical excision is typically required. In some cases, especially in spinal osteoblastomas, more complex surgical management may be necessary. - Prognosis
Both tumors are benign, but osteoblastomas have a slightly higher potential for local recurrence compared to osteoid osteomas. While they do not metastasize, they can be locally aggressive, especially if located in the spine or pelvis.
Osteosarcoma
- Malignant tumor of connective tissue (mesodermal) origin
- The tumor cells produce bone or osteoid (tumor bone or tumor osteoid)
- Permeative and destructive growth pattern
- Intramedullary sarcoma
Primary osteosarcoma:
* Li-Fraumeni syndrome (TP53)
* Hereditary retinoblastoma syndrome (RB1)
* Bloom syndrome (RECQL3)
* Rothmund-Thompson syndrome (RECQL4)
* Werner syndrome (RECQL4)
Secondary osteosarcoma:
* Known history of Paget disease of bone
* Previous radiation therapy
* bone infarction
* osteomyelitis
* orthopedic implants
- Incidence: most common high grade sarcoma of skeleton
- Age (bimodal age distribution)
- Most cases: 10 - 14 years old
- Second smaller peak: adults (> 40 year old); usually secondary osteosarcoma
Subtypes:
* Conventional (high grade intramedullary) osteosarcoma: Osteoblastic, chondroblastic and fibroblastic are based on the prominent matrix they secrete (often admixed in 1 tumor)
* Small cell
* Telangiectatic
* Parosteal
* Periosteal
Radiology:
* Medullary and cortical bone destruction
* Wide zone of transition, permeative appearance
* Aggressive periosteal reaction
* Sunburst type
* Codman triangle
* Lamellated (onion skin) reaction
* Tumor matrix ossification / calcification
* Soft tissue involvement
Micro:
* Permeative growth: intramedullary permeative growth (replacement of medullary space, surrounds and erodes native trabeculae, fills Haversian systems) and cortical destruction with soft tissue invasion
* Neoplastic cells: marked atypia (pleomorphic, hyperchromatic)
* Multiple cell morphologies often present in 1 tumor (epithelioid, plasmacytoid, spindled, small round cells, clear cells, giant tumor cells)
* Mitotic figures are easily demonstrable and atypical mitotic figures may also be identified
* Neoplastic bone (necessary for diagnosis): no minimum quantity necessary
* Nonneoplastic giant cells: ~25% of cases
Molecular:
* TP53 inactivation: ~40% (Li-Fraumeni syndrome increases risk of osteosarcoma)
* Rb inactivation
IHC:
* Often positive: SATB2, SMA, CD99, osteocalcin
* SOX9 (not reliable distinguisher with chondrosarcoma)
Fibrous dysplasia
- Benign fibro-osseous lesion that may involve one (monostotic) or multiple (polyostotic) bones
- Developmental disorder of bone resulting in the failure to form mature lamellar bone
- Mass forming developmental defect composed of woven bone and fibroblast-like spindle cells
- Slow growing expansion of bone
- Intramedullary lesions without cortical destruction
- May be congenital or hereditary
- 2 basic clinical forms: monostotic and polyostotic
- Usually manifests during the first 3 decades of life
- Polyostotic can be sporadic or occur in patients with germline GNAS1 mutations, which can lead to distinct clinical syndromes; McCune-Albright syndrome (endocrine abnormalities, café au lait spots) and Mazabraud syndrome (with soft tissue myxomas)
- Alkaline phosphatase can be elevated in certain cases, especially when tumor is growing
Radiology:
* Ill defined margins; diffusely radiopaque with ground glass image
* Single or multiple well circumscribed intramedullary lesions with a sclerotic rim
* May see cortical thinning as lesion expands
Micro:
* Branching and anastomosing irregular trabeculae of woven bone (“C” and “S” shapes) with no conspicuous osteoblastic rimming
* No / rare osteoclasts
* Intervening fibrous stroma containing cytologically bland spindle cells, without prominent cytologic atypia
* Mitotic figures rare
Molecular:
* Postzygotic somatic mutations in GNAS; typically gain of function single nucleotide substitutions
IHC:
* SATB2, expressed in bone forming lesions, may be expressed in up to 89% of cases
Giant cell tumor of bone
- Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastasizing neoplasm composed of neoplastic mononuclear stromal cells admixed with macrophages and osteoclast-like giant cells
- A small subset of cases are malignant
- Median age of 35 years
- Tumor typically involves the metaphysis and the epiphysis of long bones
- Distal femur and proximal tibia are the most common sites but the distal radius and proximal humerus are not uncommonly affected
- GCTB present with pain, swelling and occasionally restricted joint movement
Micro:
* Highly cellular lesion composed of large number nonneoplastic osteoclast-like giant cells, between which mononuclear neoplastic cells are embedded
* Mononuclear neoplastic cells exhibit a variety of morphological appearances, including round to oval cells and spindled cells with pale eosinophilic cytoplasm and nuclei with dispersed chromatin and small nucleoli
* Mitoses are commonly present and can be numerous
* Presence of atypical mitoses should raise suspicion for malignancy
* Necrosis is usually seen in the setting of pathological fracture
* Hemorrhage, aneurysmal change, hemosiderin deposition, foamy microphages and fibrosis are common
* Tumor may contain woven bone and foci of cartilage matrix
* Vascular invasion may be present
Molecular:
* Pheochromocytoma paraganglioma and GCTB syndrome is caused by postzygotic G34W mutation of the histone 3.3 gene, H3F3A
* Patients with Paget bone disease have an increased risk of developing multifocal GCTB
* Gorlin-Goltz syndrome has occasionally been associated with GCTB
IHC:
* H3G34W
* p63
* SALL4
* SATB2
* CD68
Aneurysmal bone cyst
- Benign, locally destructive multiloculated blood filled cystic lesion of bone
- Classified as an osteoclastic giant cell rich tumor (WHO 2020)
- Primary and secondary forms
- High rate of local recurrence
- More common in skeletally immature patients
- Pain and swelling
- Pathologic fracture
- Nerve compression symptoms in cases of vertebral column involvement
- May massively expand the mandible
Radiology:
Xray:
* Eccentric radiolucent lesion with expansile remodeling, involving the metaphysis of long bones
* Finger in the balloon sign possible
Micro:
* Multiloculated cystic lesion
* Blood filled cystic spaces separated by cellular septa containing fibroblasts, giant cells and woven bone
* Calcified, basophilic material (blue reticulated chondroid-like material)
* Necrosis not common but mitotic activity is easily identified
* No cytologic atypia
* Numerous giant cells in connective tissue that line large sinusoidal spaces
Molecular:
* Abnormalities of 17p13.2 locus in 63%
* Fusion of USP6 with:
CDH11 (most frequent, approximately 30%), TRAP150 (THRAP3), ZNF9 (CNBP), OMD, COL1A1, RUNX2, PAFAH1B1, CTNNB1, SEC31A, E1F1, FOSL2, STAT3, USP9X, ASAP1, FAT1, SAR1A, TNC
Giant Cell Tumour of Tendon Sheath
- Tenosynovial giant cell tumor encompasses a group of lesions that most often arise from the synovium of joints, bursae and tendon sheaths and show synovial differentiation
- Second most common tumor of the hand (after ganglion cyst)
- Malignant tenosynovial giant cell tumor is very uncommon and is defined by the coexistence of a benign tenosynovial giant cell tumor with overtly malignant areas or by recurrence of a typical giant cell tumor as a sarcoma
Localized type:
* Predominantly occurs in the digits (85%), especially fingers (75%)
* Uncommon around large joints (10%)
Diffuse type:
Intra-articular
* Knee (65%)
* Hip and ankle (25%)
* Elbow, shoulder, temporomandibular joint, spine
Extra-articular extension:
* Knee
* Foot, wrist, inguinal, elbow region, digits
Micro:
* Composed of mononuclear cells, multinucleated giant cells, foamy macrophages, inflammatory cells and hemosiderin
2 principal cell types of the mononuclear components:
* Small histiocyte-like cells: pale cytoplasm and round or reniform nuclei
* Large epithelioid cells: amphophilic cytoplasm and rounded vesicular nuclei, often containing a peripheral rim of hemosiderin granules
- Mitotic activity may be brisk
- Necrosis can be present
Molecular:
* Translocations involving CSF1 gene at 1p13 are most common
* Malignant: Loss of the CDKN2A/B gene
IHC:
* Epithelioid cells: clusterin, patchy desmin
* Histiocytes: CD68, CD163
* Osteoclast-like giant cells: CD68, CD45, TRAP
Chordoma
- Malignant tumor with notochordal differentiation
- Expansile lobulated intraosseous mass that usually permeates the cortex and invades adjacent soft tissue
- Most commonly arises in the 40 - 60 year old age group
- Intraosseous: > 95% of cases (usually axial skeleton)
- Base of skull / clivus of occipital bone
- Vertebral bodies
- Sacrococcygeal bones
- Extra-axial skeleton (rare)
Micro:
* Infiltrative border
* Low power architecture is lobular, with fibrous bands separating lobules
* Cytoarchitecture (within the lobules) consists of cells forming short chords, dense epithelioid sheets / nests and single cells within the matrix
* Extracellular myxoid matrix
* Cells are epithelioid with abundant clear (glycogen) to eosinophilic cytoplasm that may be have a bubbly / vacuolated appearance (physaliphorous cells)
* Nuclear pleomorphism is heterogenous throughout the neoplasm, with low grade and higher grade areas; vesicular nucleus is common; nuclear pseudoinclusions may be seen
* Mitoses usually identifiable (high grade areas)
* Necrosis may be present
* Occasionally, mitotically active spindle cells
Molecular:
* T gene (brachyury) duplication (6q27) occurs in ~27% of sporadic chordomas; however, nearly all notochordal tumors over express brachyury (epigenetic mechanisms)
IHC:
* Cytokeratin cocktail (CK8, CK18, CK19), EMA, S100 protein (expressed in conventional chordoma; usually negative in poorly differentiated chordoma), brachyury (a nuclear stain, highly specific, positive in poorly differentiated chordoma)
* Decalcification may result in a loss / decrease in brachyury immunoreactivity
Ewing sarcoma
- Second most common malignant bone tumor in children / young adults after osteosarcoma
- 5-20 years
- Localized pain and swelling
- Painful enlarging mass
- Associated pathologic fracture sometimes present
- Systemic findings (fever, weight loss, anemia, leukocytosis and increased sedimentation rate) can occur
Micro:
* Uniform small round cells
* Tumor cells 1 - 2x size of lymphocytes
* Round nuclei
* Finely stippled chromatin
* Inconspicuous nucleoli
* Scant clear to eosinophilic cytoplasm
* Indistinct cytoplasmic membranes
* Sheet-like growth pattern
* Islands separated by dense fibrous tissue
* Subset with neuroectodermal differentiation (Homer-Wright pseudorosettes)
Molecular:
* Most common translocation is t(11;22)(q24;q12), resulting in EWSR1-FLI1 fusion (~85 - 90%)
* Second most common is t(21;22)(q22;q12), resulting in EWSR1-ERG fusion (~5 - 10%)
IHC:
* CD99 (strong, diffuse membranous expression in ~90 - 95%)
* NKX2.2 (high specificity)
* Vimentin (80-90%)
* FLI1 (nuclear staining)
