Pathology/oncology Flashcards
1
Q
Describe Bone lesions by patient age:
Table 9.1
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2
Q
Types of tumor bone interactions:
Tabie 9.2
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3
Q
Figure 9.4:
Distributions of varius lesions in patients less than 30
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4
Q
Figure 9.4B
Distribution of varius bone lesions in patients older than 30
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5
Q
Classification of Primary Tumors of Bone and Bone Matrix:
Table 9.3
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6
Q
Tumors by Location:
Table 9.4
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7
Q
Principles of Biopsy:
Table 9.5
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8
Q
Immunohistochemistry and molecular testing for bone and Soft tissue Tumors:
Table 9.6
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9
Q
Common Chomosomal translocations in Bone and Soft Tissue Tumors:
Table 9.7
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10
Q
Musculoskeletal Syndromes, Genes, and Neoplasms:
Table 9.8
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11
Q
Histologic grading of soft tissue tumors:
Table 9.9
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12
Q
Staging System; Enneking System
Table 9.10
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13
Q
American Joint Committee on Cancer Staging System for primary malignant tumors of bone for those tumors diagnosed on or after Jan 1 2010:
Table 9.11
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14
Q
American Joint Committee on Cancer staging system for primary malignant tumors of soft tissue for those tumors diagnosed on or after Jan 1,2010:
Table 9.12
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15
Q
Treatment regimens for malignant bone tumors:
Table 9:13
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16
Q
Chemotherapy for bone sarcomas:
Table 9.14
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17
Q
Radiation Therapy for soft tissue sarcoma:
Table 9.15
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18
Q
Most Common MSK tumors:
table 9.16
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19
Q
Key points about soft tissue sarcomas:
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A mass that is more than 5cm, growing and deep to the fascia should be presumed to be a soft tissue sarcoma.–image with MRI.
MRI is the best imaging modality
CT of the chest is performed to evaluate for mets
ESARC–STS with mets to lymph nodes—5% of STS
Epitheloid, Synovial, Angiosarcoma, Rhabdomyosarcoma, Clear cell
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Q
Table 9.22
Cartilage tumors
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21
Q
why do I have to learn about Ollier and Mafucci Syndrome?
A
Ollier disease/Maffucci syndrome
When there are many lesions, the involved bones are dysplastic, and the lesions tend toward unilaterality, the diagnosis is multiple enchondromatosis, or Ollier disease.
Inheritance pattern is sporadic.
If soft tissue angiomas are also present, the diagnosis is Maffucci syndrome.
Patients with multiple enchondromatosis are at increased risk of malignancy (in Ollier disease, 30%; in Maffucci syndrome, 100%).
Patients with Maffucci syndrome also have a markedly increased risk of visceral malignancies, such as astrocytomas and gastrointestinal malignancies.
22
Q
why do I have to learn about MHE or multiple Heridetary Exostoses?
A
Multiple hereditary exostoses
The osteochondromas in MHE are often sessile and large. This is an autosomal dominant condition with mutations in the EXT1 and EXT2 gene loci. In approximately 10% of patients with multiple exostoses, a secondary chondrosarcoma develops. The EXT1 mutation is associated with a greater burden of disease and higher risk of malignancy.
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Q
Describe a chondroblastoma:
A
Centered in the epiphysis in young patients, usually with open physes; it may also occur in an apophysis
Pain referable to the involved joint
The most common locations are the distal femur, proximal tibia, and proximal humerus.
Imaging Shows a central region of bone destruction that is usually sharply demarcated from the normal medullary cavity by a thin rim of sclerotic bone
Histology
The basic proliferating cells are thought to be chondroblasts.
Scattered multinucleated giant cells are found throughout the lesion.Zones of chondroid are present.Mitotic figures may be found.
Treatment: Intralesional resection with curettage and reconstruction
Differential diagnosis: Brodie’s abscess and giant cell tumor of bone
Less than 5% mets to the lungs
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Q
Epiphyseal Lesions:
Table 9.23
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25
Describe a chondromyxoid fibroma
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Describe a chondrosarcoma
Presentation
Pain or a mass in adults over 50 years old
Most common locations include flat bones (e.g., the scapula), pelvis, and spine.
Imaging
Radiographs usually yield diagnostic findings, with bone destruction, thickening of the cortex, and mineralization consistent with cartilage within the lesion (see Fig. 9.16).
Prominent cortical changes (endosteal scalloping and erosion) are present in 85% of affected patients.
Histology-Differentiating malignant cartilage may be extremely difficult on the basis of histologic features alone.
The clinical, radiographic, and histologic features must be considered in combination for an accurate diagnosis. Criteria for the diagnosis of malignancy include the following:
Many binucleate cells with plump nuclei
Particularly large cartilage cells with large single or multiple nuclei containing clumps of chromatin-Infiltration of the bone trabeculae
Chondromas of the hand (enchondromas)—the lesions in patients with Ollier disease and Maffucci syndrome—and periosteal chondromas may have atypical histopathologic features.
Treatment: Wide surgical resection
Chemotherapy has not been shown to improve survival.
Dedifferentiated chondrosarcoma: The most malignant cartilage tumor
Presentation
Pain and decreased motion.
Most common locations include the distal and proximal femur and the proximal humerus.
Imaging: Biomorphic appearance with that of a typical chondrosarcoma with a superimposed, highly destructive area
Histology: Low-grade cartilage component that is intimately associated with a high-grade spindle cell sarcoma (osteosarcoma, fibrosarcoma, MFH)
Treatment: Wide-margin surgical resection and multiagent chemotherapy
Other features: Prognosis is poor, and rate of long-term survival is less than 10%.
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Blue Cells-
Learn em
Table 9.24
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Key considerations for lymphoma of bone
Non-Hodgkins Lymphoma
Presentation:
Pain in patients of all ages.
The most common locations include the distal femur, proximal tibia, pelvis, proximal femur, vertebra, and shoulder girdle.
Imaging:
Images often show a lesion that involves a large portion of the bone
•Bone destruction is common and often has a mottled appearance.
A large soft tissue mass out of proportion to the amount of bone destruction is characteristic of lymphoma of bone.
Histology: A mixed cellular infiltrate is usually present. Most lymphomas of bone are diffuse, large B-cell lymphomas.
Immunohistochemistry: **CD45 and leukocyte common antigen (LCA) positive.**
Treatment: **Multiagent chemotherapy ( [CHOP]) is curative.**
Surgery is used only to stabilize fractures.
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multiple Myeloma
Plasma cell dyscrasias represent a wide range of conditions from monoclonal gammopathy of undetermined significance (MGUS; Kyle disease) to multiple myeloma.
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Three plasma cell dyscrasias pertain to orthopaedic surgery: multiple myeloma, solitary plasmacytoma of bone, and osteosclerotic myeloma.
Multiple myeloma:
Malignant plasma cell disorder that commonly occurs in patients between 50 and 80 years of age
Presentation: Manifests with bone pain, usually in the spine and ribs, or as a pathologic fracture
Fatigue is a common complaint secondary to the associated anemia.
Symptoms may be related to complications such as renal insufficiency, hypercalcemia, and the deposition of amyloid.
Serum creatinine values are elevated in about 50% of affected patients.
Hypercalcemia is present in about 33% of affected patients.
Imaging: Radiographic appearance is of punched-out, lytic lesions which may show expansion and a “ballooned” appearance.
Histology:
Sheets of plasma cells that appear monoclonal with immunostaining
**Well-differentiated plasma cells have eccentric nuclei that have peripherally clumped, chromatic “clock faces.”**
Treatment
**Systemic therapy and bisphosphonates**
**Surgical stabilization with irradiation is used for pathologic fractures.**
Radiotherapy is also used for palliation of pain and treatment of neurologic symptoms.
The prognosis is related to the stage of disease; the overall median survival time is 18–24 months.
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Solitary Plasmocytoma of bone
It is important to differentiate solitary myeloma from multiple myeloma because of the more favorable prognosis in patients with the solitary form. Diagnostic criteria include the following:
A solitary lesion on skeletal survey
Histologic confirmation of plasmacytoma
Bone marrow plasmacyte count of 10% or less
Patients with serum protein abnormalities and Bence Jones proteinuria (protein levels \<1 g/24 hr) at presentation are not excluded if they meet the aforementioned criteria.
Treatment
**External beam irradiation of the lesion (4500–5000 cGy)**
**When necessary, prophylactic internal fixation**
In approximately 50%–75% of affected patients, solitary myeloma progresses to multiple myeloma.
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Giant Cell Tumor
Presentation
Pain and pathologic fracture
Patients over 30 years old with closed physes
Most common in the epiphysis and metaphysis of long bones, and about 50% of lesions occur about the knee; the vertebra, sacrum, and distal radius are involved in about 10% of cases.
The sacrum is the most common axial location of giant cell tumors of bone.
Imaging: A purely lytic destructive lesion in the metaphysis that extends into the epiphysis and often borders the subchondral bone
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Histology
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Basic proliferating cell has a round to oval or even spindle-shaped nucleus, and **the multinucleated giant cells appear to have the same nuclei as the proliferating mononuclear cells.** The stromal cell directs the multinucleated giant cell.
**Stromal malignant cells produce RANKL (receptor activator for nuclear factorκB ligand).**Multinucleated giant cells express RANK and are responsible for the osteolytic aspect of GCT.
Treatment:Aimed at removing the lesion, with preservation of the involved joint
**Denosumab (Prolia), a human monoclonal antibody that binds RANKL, thereby inhibiting the maturation of osteoclasts.**
**Extensive intralesional resection (removal of a large cortical window over the lesion) is performed using curettage with manual and power instruments.**
**Chemical cauterization may be used (phenol, peroxide).**
**Area of defect is usually reconstructed with subchondral bone grafts, methylmethacrylate, or both.**
**Local control with this treatment regimen has a success rate of 85%–90%.**
Other features: **GCT is described as benign but is aggressive, because in rare cases (\<5%) it metastasizes to the lungs.**
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Ewings Sarcoma
Presentation
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Patient age less than 30 years
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Pain and fever may be present; the presentation can be similar to that in an infection.
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Patients may exhibit elevated ESR, leukocytosis, anemia, and elevated WBC count.
Most common locations include the pelvis, distal femur, proximal tibia, femoral diaphysis, and proximal humerus.
Imaging
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Radiographs often show a large, destructive lesion that involves the metaphysis and diaphysis.
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The lesion may be purely lytic or may have variable amounts of reactive new bone formation (Fig. 9.24).
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The periosteum may be lifted off in multiple layers, producing a Codman triangle and an onion-skin appearance.
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The soft tissue component is distinctively large.
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Histology
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Small round blue cells with minimal cytoplasm, pseudorosettes (attempted formation of vascular channels)
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Immunohistochemistry: **CD99 positivity.**
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A classic 11:22 chromosomal translocation produces the EWS-FLI1 fusion gene.
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Bone marrow biopsy is performed for staging purposes.
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Treatment: **A multimodality approach with multiagent chemotherapy, irradiation, and surgical resection**
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Standard treatment includes chemotherapy.
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Standard for local tumor control is surgery.
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Radiation therapy may be used primarily for pelvic and spine disease, where resection would be morbid, or as an adjunct to surgery to maintain function while sparing critical structures.
Differential diagnosis: When a small blue cell tumor is found in a child younger than 5 years, metastatic neuroblastoma and leukemia should be considered.
Other features
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Survival
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The rate of long-term survival with multimodality treatment may be as high as 60%–70%.
**There is a consistent chromosomal translocation (11;22) with the formation of a fusion protein (EWS-FLI1).**
Metastatic disease involves the lungs (50%), bone (25%), and bone marrow (20%).
Poor prognostic factors include the following:
Spine and pelvic tumors
Tumors greater than 100 cm3 in diameter
A poor response to chemotherapy (\<90% tumor cell necrosis)
Elevated serum LDH (Temple)
The p53 mutation and gene fusion products other than EWS-FLI1
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Adamantinoma
Rare low-grade, malignant tumor of long bones that contains epithelium-like islands of cells
Presentation
Patient less than 30 years old with prolonged periods of pain
The tibia is the most common site; other long bones can be but rarely are involved (fibula, femur, ulna, radius).
Imaging: Radiographic appearance: multiple, sharply circumscribed, “soap bubble”–looking lucent defects of different sizes, with sclerotic bone interspersed between the zones and extending above and below the lucent zones one of the lesions in the midshaft is the largest and is associated with cortical bone destruction.
Histology: Cells have an epithelial quality and are arranged in a palisading or glandular pattern; the epithelial cells occur in a fibrous stroma.
Treatment: Wide-margin surgical resection
Other features: Tumor may metastasize either early or after multiple failed attempts at local control.
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ABC vs UBC
Figure 9.25
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ABC
Nonneoplastic reactive condition that may be aggressive in its ability to destroy normal bone and expand into the soft tissues
Presentation: Patients are less than 30 years old and present with pain and swelling.
Imaging
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Characteristic radiographic finding: an eccentric, lytic, expansile area of bone in the metaphysis with a thin rim of periosteal new bone surrounding the lesion. The lesion is wider than the physis of the bone it is closest to (Fig. 9.25 inTable 9.25).
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MRI usually shows the periosteal layer surrounding the lesion.
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Fluid-fluid levels visible on T2-weighted MRI are characteristic of, but not exclusive to, ABC.
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Histology
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Cavernous blood-filled spaces without an endothelial lining.
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Thin strands of bone are present in the fibrous tissue of the septa.
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Benign giant cells may be numerous.
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Treatment: Curettage and reconstruction, which may include bone grafting or fixation in the setting of a fracture.
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Differential diagnosis: Unicameral bone cyst, telangiectatic osteosarcoma
Other features
Local recurrence is common in children with open physes.
ABC may arise primarily in bone or may be found in association with other tumors, such as giant cell tumor, chondroblastoma, chondromyxoid fibroma, and fibrous dysplasia.
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UBC
Presentation
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Patient less than 30 years old presents with pain, usually after a fracture caused by minor trauma (e.g., sporting event, throwing a baseball, wrestling).
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Occurs most often in the proximal humerus; other sites are the proximal femur and distal tibia.
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Imaging
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Symmetric cystic expansion with thinning of the involved cortices
Affected bone is often expanded; however, **the bone is generally no wider than the physis.**
Often appears trabeculated
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When the cyst abuts the **physeal plate**, the process is called active; when normal bone intervenes, the cyst is termed **latent.**
Histology: Thin, fibrous lining contains fibrous tissue, giant cells, hemosiderin pigment, and a few chronic inflammatory cells.
Treatment
Asymptomatic: Observation
Symptomatic: **Aspiration and injection (bone aspirate, bone graft substitute, or methylprednisolone acetate may be used)**
**Unicameral bone cysts in high-stress areas (e.g., proximal femur) are often treated with curettage, grafting, and internal fixation to avoid fracture and osteonecrosis.**
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Fibrous Dysplasia:
Developmental abnormality of bone that is characterized by monostotic or polyostotic involvement and is the failure of the production of normal lamellar bone.
Presentation
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Pain from a fracture or stress fracture; or an incidental finding if asymptomatic; café au lait spots with irregular borders (**resembling the coast of Maine)** may accompany the bone lesions.
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Any bone may be involved; the proximal femur is the most commonly affected.
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Imaging: Variable appearance that can look highly lytic or like ground glass
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Histology
Well-defined rim of sclerotic bone
Proliferation of fibroblasts (produces a dense collagenous matrix)
Trabeculae of osteoid and bone within the fibrous stroma are present in a disorganized manner, and their appearance has been likened to **“alphabet soup” and “Chinese letters.”**
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Treatment
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Predicated on the presence of symptoms and the risk of fracture
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Internal fixation and bone grafting are used in areas of high stress in which nonoperative treatment would not be effective.
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Most affected patients do not need surgical treatment.
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Autogenous cancellous bone grafting is never used because the transplanted bone is quickly transformed into the woven bone of fibrous dysplasia. Cortical or cancellous allografts are usually used.
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**Bisphosphonate therapy has been shown to be effective in decreasing pain and reducing bone turnover in patients with polyostotic fibrous dysplasia**.
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Other features
**Genetic mutation is an activating mutation of the GSα surface protein (GNAS)**
**Increased production of cAMP**
When endocrine abnormalities (especially precocious puberty) accompany multiple bone lesions and skin abnormalities, the condition is called **McCune-Albright syndrome.**
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Lahngerhans Histocytosis
Occurs as three entities:
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LCH monostotic, also known as eosinophilic granuloma. Only a single bone or, on occasion, multiple bones involved. Most common.
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LCH polyostotic plus visceral disease, or Hand-Schüller-Christian disease
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LCH polyostotic plus visceral disease in an infant, or Letterer-Siwe disease
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The cellular abnormality is a proliferation of the Langerhans cells of the dendritic system.
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LCH monostotic
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Presentation: Pain and swelling
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Imaging
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The lesion is lytic and has well-defined margins, described as “punched out” (Fig. 9.27).
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Cortex may be destroyed, and a periosteal reaction with a soft tissue mass simulating a malignant bone tumor may be present.
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Often there are different amounts of bone destruction of the involved cortices, resulting in the appearance of a bone within a bone.
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There may be expansion of the involved bone.
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Any bone may be involved.
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Histology
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The proliferating Langerhans cell, with an indented or grooved nucleus, is the characteristic cell.
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Cytoplasm is eosinophilic.
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Nuclear membrane has a crisp border.
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Mitotic figures may be common.
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**Bilobed eosinophils with bright, granular, eosinophilic cytoplasm are present in large numbers.**
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**Electron microscopy shows a tennis racquet–shaped Birbeck granule.**
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Treatment: **LCH is a self-limiting process that often resolves after biopsy and/or curettage.**
**LCH polyostotic plus visceral disease: Hand-Schüller-Christian disease**
Bone lesions and visceral involvement
Classic triad, which occurs in fewer than one fourth of patients, **consists of exophthalmos, diabetes insipidus, and lytic skull lesions.**
Multifocal disease is usually treated with chemotherapy.
Letterer-Siwe disease occurs in young children and is usually fatal.
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