Miller Oncology Lectures Flashcards
Malignant bone lesions seen in age < 5
LCH (Letter-Siwe), LCH (Hand-Schuller-Christian), metastatic rhabdomyosarcom, metastatic neuroblastoma
Malignant bone lesions seen age 5-30
Ewing’s, osteosarcoma
Malignant bone lesions seen age >30
Chondrosarcoma, (BPKLT) metastases, lymphoma, myeloma, chordoma, adamantinoma
Benign bone lesions seen in age <5
Osteomyelitis, osteofibrous dysplasia
Benign bone lesions seen in age 5-30
Osteoid osteoma, osteoblastoma, chondroblastoma, ABC, LCH, osteofibrous dysplasia, NOF
Benign bone lesions seen in age >30
Giant cell, Pagets
t(11;22)
Ewing’s
t(X;18), SSX1-SYT
Synovial sarcoma
Rb and p53
Osteosarcoma
Soft tissue sarcomas that are treated with chemotherapy
Synovial sarcoma and rhabdomyosarcoma. Otherwise, other soft tissue sarcomas are treated with XRT and surgery only.
Sarcomas treated with chemo, surgery, chemo
Ewing’s sarcoma, intramedullary and periosteal osteosarcoma
Tumors treated with ORIF and XRT
Mets (BPKLT), myeloma and lymphoma
Tumors treated with intralesional resection
GCT, ABC, NOF, LCH, osteoblastoma, chondroblastoma
Tumor treated with RFA
osteoid osteoma that has failed NSAIDs
Tumors treated with wide excision and limb salvage
Chondrosarcoma, adamantinoma, chordoma, parosteal osteosarcoma and soft tissue sarcoma
Cardiotoxic chemo drug used for osteosarcoma and Ewing’s sarcoma
Doxorubicin
35 year old patient with history of Ewing’s treated with chemotherapy presents with fatigue, gum bleeding and bruising. What’s his diagnosis?
Post-chemotherapy leukemia, confirm with CBC with peripheral blood smear
Palliative XRT dose for mets
25-30 Gy
Pre-op XRT dose for soft tissue sarcoma, associated complications
50 Gy, perioperative wound healing complications
Post-op XRT dose for soft tissue sarcoma, associated complications
60 Gy, fibrosis, bone necrosis and fracture complications
HO prophylaxis XRT dose
5 Gy
Diaphyseal bone lesions
AEIOUY - Adamantinoma, eosinophilic granuloma, infection, osteoid osteoma/osteoblastoma, “U”-wings sarcoma, fYbrous dysplasia, lYmphoma, mYeloma
Top 2 locations for bony metastases
1) Spine via Batson’s plexus 2) Proximal femur
Enneking’s 4 questions
Location, what’s the tumor doing to the bone, what’s the bone doing to the tumor, what is the matrix of the lesion
Common epiphyseal tumors
Chondroblastoma (skeletally immature), giant cell and clear cell chondrosarcoma (femoral head)
Common epiphyseal tumors
Chondroblastoma (skeletally immature), giant cell, clear cell (femoral head)
Common metaphyseal tumors
Osteosarcoma, chondrosarcoma and metastases (BPKTL)
Common anterior spine tumors? Posterior?
Anterior = giant cell and mets. Posterior = osteoid osteoma, osteoblastoma and ABC
Common sacral lesions
ABC, giant cell, chordoma (shown), mets
Common flat bone lesions
Hemangioma, fibrous dysplasia, chondrosarcoma, Paget’s, Ewing’s, mets
Common tibial lesions
Chondromyxoid fibroma (shark bite in proximal medial tibia), non-ossifying fibroma (soap bubbles) and adamantinoma (cortical lesions up and down diaphysis)
Chondromyxoid fibroma histology
Chondroid matrix, myxoid matrix and fibrous matrix
Non-ossifying fibroma histology
Mostly fibrous tissue
Adamantinoma histology
Nests and glands in the bone
Common intracortical lesions
Osteomyelitis, osteoid osteoma, osteoblastoma, osteofibrous dysplasia and adamantinoma
Brown tumor
Multiple lytic bone lesions from hyperparathyroidism
Systemic staging
CT C/A/P (only chest if sarcoma), whole body bone scan (skeletal survey if Myeloma) +/- PET, bone marrow bx in Ewing’s and Myeloma
Note that SPEP/UPEP are used for diagnosis of myeloma, not staging
Cold bone scan lesions
Myeloma, renal cell and thyroid, these turn over too quickly to be caught on bone scan
SUV that identifies malignancy
2.0
Biopsy principles
Longitudinal incision in line with future resection, avoid critical neurovascular structures, preferentially biopsy soft tissue over bone to not weaken the bone, strict hemostasis
Indications for incisional vs excisional biopsy
Mass >3cm (1.5 in hand/foot) and unsure of diagnosis = incisional, any smaller = excisional
3 cell lineage tumor origins
Parenchymal = organs = carcinoma
Hematopoietic = lymphatic/bone = myeloma, leukemia
Mesenchymal = connective tissue = sarcoma
Synovial chondromatosis is an example of ___
Metaplasia, the irritated synovial tissue has changed to produce small cartilagenous bodies
What is this?
Normal bone. Note the flat blue osteoblasts making woven bone that matures into lamellar bone and intervening fat.
What is this?
Normal cartilage. Note the plump chondrocytes with double lacuna and bluish color.
Small round blue cell tumors
“LERNM” - Lymphoma, Ewing’s, Rhabdomyosarcoma, Neuroblastoma, Myeloma
Lymphoma lab markers
CD45+, leukocyte common antigen (LCA+)
Ewing’s lab markers
t(11;22), EWS-FLI-1, Vimentin+, Keratin+, CD99+, pseudorosettes on path
Rhabdomyosarcoma lab marker
Desmin+ (shown), t(2;13), PAX-FKHR
Neuroblastoma lab marker
Neuron specific enolase (NSE+), NB84
Myeloma lab markers
Monoclonal spike on SPEP/UPEP, monoclonal immunoreactivity for kappa or lambda light chain, CD 20+, plasma cells with clock faced nuclei
Tumors with giant cells
Giant cells are large osteoclasts seen in many tumors.
ABC, chondroblastoma, chondromyxoid fibroma, giant cell tumor of tendon sheath, giant cell tumor and giant cell rich osteosarcoma.
In giant cell tumor of bone, the stroma cells look the same as the cells within the giant cell (shown).
Diagnosis?
Giant cells in chondroblastoma, notice the fried egg, cobblestone, chicken wire calcifications next to the giant cells, indicating chondroblastoma
Leiomyosarcoma immunohistochemistry
Smooth muscle actin (SMA)
MPNST and Schwannoma immunohistochemistry
S-100, neural origin
Hemangioma, hemangioendothelioma and angiosarcoma immunohistochemistry
CD31 and CD34, endothelial origin
Fibromatosis (extra-abdominal desmoid) immunohistochemistry
Beta-catenin
Ewing’s/PNET immunohistochemistry
CD 99
Epithelioid sarcoma immunohistochemistry
Loss of INI 1
Epithelioid sarcoma, synovial sarcoma and carcinoma immunohistochemistry
Keratin +
Epithelioid and synovial sarcoma immunohistochemistry
Epithelial membrane antigen (EMA)
Rhabdomyosarcoma immunohistochemistry
MyoD1, myogenin (Myf-4)
Soft tissue sarcoma immunohistochemistry
Vimentin+
Chromosomal translocation for:
Ewing’s/PNET
Myxoid liposarcoma
Alveolar rhabodomyosarcoma
Clear cell sarcoma
Synovial sarcoma
Myxoid chondrosarcoma
Maffucci’s syndrome
PTHR1 mutation -> enchondromas, hemangiomas, CNS, pancreatic and ovarian malignancy.
May see calcified phleboliths on x-ray and higher grade histology.
May develop angiosarcoma and chondrosarcoma.
Enneking staging system
Grade 0, 1 or 2 based on histology
Site: T1 (intracompartmental, within limits of periosteum), T2 (extracompartmental, breach into adjacent joint, cartilage, bone cortex or periosteum)
Mets: M0 (no mets), M1 (any skip lesions, regional lymph nodes or distant mets)
What is the key size in the AJCC bone staging system? Soft tissue sarcoma size?
>8cm. In the soft tissue sarcoma staging, the key size if >5cm
Identify this soft tissue sarcoma.
Undifferentiated pleomorphic sarcoma.
Note the giant cells, pyknotic cells, mitosis and pleomorphic spindle cells.
Identify this soft tissue sarcoma
Synovial sarcoma.
Note the cigar shaped cells in some planes, then circular cells in the other plane. Can have only spindle cells (monophasic, as shown in question stem) or spindle cells and epithelial glands (biphasic as shown below).
Identify this soft tissue sarcoma
Liposarcoma
Note the fat cells with cellular stranding in between with large pyknotic, bizarre mononucleated cells and immature lipoblasts.
Identify this soft tissue sarcoma
Leiomyosarcoma
Note the striated pattern similar to muscle and spindle cells intersecting at 90 degree angles.
How to distinguish liposarcoma from lipoma (shown below)
Lipoma is isointense to fat on T1 sequence, liposarcomas are dark on T1.
MDM2 = well differentiated liposarcoma
Myxoid liposarcoma has 12;16 translocation
Signet ring cells with atypia on histology
Identify this soft tissue sarcoma
Fibrosarcoma, note the herringbone pattern
Identify this soft tissue sarcoma
Angiosarcoma
Note nests of epithelioid cells, spindle cells and rudimentary vascular channels.
Identify this soft tissue sarcoma.
Rhabdomyosarcoma, Desmin+, t(2;13), PAX-FKHR gene
Treated with chemo, surgery, then XRT
Identify this soft tissue sarcoma. What would molecular testing show?
Epithelioid sarcoma. Note the nodular growth pattern, polygonal cells, eosinophilic cytoplasm with spindle and epithelioid cells.
Seen mostly in hand/forearm, may ulcerate, metastasizes to lymph nodes, pathology shows loss of INI1.
28 year old female presents with slowly growing soft tissue mass. Family history is notable for colon polyps. Imaging and biopsy are shown. What other labs to confirm? What is diagnosis and treatment?
Immunohistochemistry +beta-catenin and estrogen receptor.
Fibromatosis (extra-abdominal desmoid)
These grow in adolescents and young adults, estrogen increases tumor size during pregnancy, very high local recurrence rate so need wide margins, XRT and tomoxifen to block the estrogen receptor.
What would you expect to see on histology? Treatment?
Schwannoma. Swirly nuclear palisading with verocay bodies (Antoni A = black arrow) and loose collagen matrix (Antoni B).
Treatment is resection.
Difference between neurofibroma and schwannoma
Neurofibroma is confluent with the nerve, Schwannoma sits adjacent to the nerve.
This patient has a waxing and waning leg mass that shrinks at night and grows during the day. What would histology show? Treatment?
Hemangioma, note the calcified phlebolith on x-ray.
Pathology shows mature thick walled veins and cavernous vascular spaces.
Treatment is initally non-op with compression, then sclerotherapy with alcohol, then surgery only if refractory.
Two types of PVNS, histology and treatment.
Histology shown with synovial cells, giant cells and hemosiderin.
Nodular, treated with complete excision.
Diffuse, treated with complete synovectomy +/- arthroplasty and XRT.
The neoplastic cell is a mononuclear phagocyte involving 1p13 rearrangment in the CSF1 gene. This gene has a pharmacologic CSF1-inhibitor (plexicon).
What histology would you expect to see in this lesion?
This is synovial chondromatosis, note the rice body appearance in the suprapatellar pouch.
Histology shows cartilage clumps covered in synovium
Infectious mimicker of sarcoma
Cat scratch disease from bartonella, imaging shows a mass dark on T1, bright on T2
Biopsy shows mass is a lymph node with lymphocytes, treated with doxycycline
Diagnosis and treatment?
Likely osteoid osteoma. These are <2cm. If larger it is osteoblastoma. Start treatment with NSAIDs, then RFA.
No RFA if close to skin/nerves or >2cm (needs curettage).
Note the histology and woven bone with rimming osteoblasts, the histology looks the same for osteoblastoma, it is just >2cm in size.
Diagnosis and treatment?
Conventional osteosarcoma. Treat with chemo, surgery, chemo with 65% 5 year survival.
Note the immature osteoid and malignant rimming osteoblasts and atypical spindle cells.
<45 year old with knee pain. Diagnosis and treatment?
Parosteal osteosarcoma. These are very low grade tumors and are treated with excision only. 95% 5 year survival.
<30 year old with knee pain. What would you expect to see on pathology? What is the treatment?
Periosteal osteosarcoma, note the bone forming lesion on the surface expanding from the periosteum.
Pathology has a chondroblastic componenent and formation of malignant bone.
Treated with chemo, surgery, chemo with 80% 5 year survival.
15-year-old female with left knee pain. What would you expect on histology?Diagnosis and treatment?
This is either ABC or telangiectatic osteosarcoma.
For telangiectatic osteosarcoma, histology shows malignant osteoid in vascular lakes and channels with giant cells. ABC has the lakes and channels with lack of malignant cellularity.
Treatment is chemo surgery chemo.
60-year-old has malignant intramedullary distal femr mass dark on T1, bright on T2. Biopsy is shown. What is your diagnosis and treatment?
This is malignant fibrous histiocytosis (MFH).
Note the mixed spindle cells with high mitoses, pleomorphic nuclei and giant cells.
Treatment is chemo surgery chemo
70-year-old male with left hip pain and hats that no longer fit. What would you expect to see on histology. Treatment?
Histology shows malignant osteoblasts within pagetoid bone (cement lines), indicating osteosarcoma.
Treatment is difficult because they don’t do well with chemo, so just surgery +/- chemo.
Enchondroma histology
Acellular with lots of matrix
Osteochondromas concerning for malignant transformation to chondrosarcoma
Cartilage cap >2cm (shown below), painful, associated with MHE (mutation in tumor suppressor genes EXT 1/2/3)
Histology of chondromyxoid fibroma? Treatment?
Both cartilage and fibrous tissue.
This is a benign aggressive lesion that needs to be treated with intralesional curettage.
17-year-old with knee pain, a lytic lesion and epiphyseal calcifications on x-ray. MRI is shown with significant edema around the lesion. What would you expect to see on histology and how would you treat?
Chondroblastoma has chichen wire calcifications and cobblestone appearance.
Treatment is curettage and grafting.
60-year-old male with right thigh pain and this x-ray. What would expect to see on histology? What is the treatment?
Chondrosarcoma.
Note the bone expansion, endosteal scalloping, arcs, rings and punctate calcifications on x-ray.
Histology is shown with increased cellularity, binucleate cells, mitoses, atypia.
Treatment is surgery and reconstruction alone.
What is your diagnosis? What do you see on histology? What is it called when there are multiple?
Non-ossifying fibroma. This is thought to occur where tendons insert.
Histology shows spindle shaped fibroblasts in a whorled pattern with giant cells and hemosiderin.
Multiple lesions is Jaffe-Campanacci syndrome. Lesions can be observed or curettage and bone grafting if they become symptomatic.
<20 year old presents with this benign lesion. What’s your diagnosis and treatment?
Osteofibrous dysplasia is an anterior tibial cortically based lesion.
Histology confirms this is benign and not adamantinoma. You’ll see spindle cells in scattered trabeculae of bone (Chinese letters) WITH RIMMING OSTEOBLASTS (as opposed to fibrous displasia that does not have rimming osteoblasts)
Treatment is observation until skeletal maturity, then excise if symptomatic or progressive.
18 year old with painful hip and ground glass lesion on x-ray with healing fracture. Histology is shown. What are other findings, diagnosis and treatment.
Note the chinese character like lamellar bone with NO RIMMING OSTEOBLASTS. This is fibrous dysplasia.
Other findings may be cafe au lait spots and precocious puberty (McCune Albright syndrome). They’ll have the GNAS1 mutation.
Treatment is ORIF/IMN with allograft if there is a fracture (don’t use autograft)
Diagnosis? Histology?
Left is osteofibrous dysplasia (cortically based, soap bubble appearance, tibial lesion, bowing, rimming osteoblasts on histology)
Right is fibrous dysplasia, medullary ground glass lesion with no rimming osteoblasts
Asymptomatic lesion found incidentally. Diagnosis and histology?
This is likely an intra-osseous hemangioma. These are seen in the spine 20% of the time. Pulsations in the blood may create jail bar like calcifications. Histology shows well developed large vascular channels.
60 year old male presents with thigh mass. Biopsy is shown, it is CD45+ and LCA+. What is diagnosis and treatment?
Lymphoma. Treatment is chemo +/- XRT. Surgery is only necessary for fracture management.
60-year-old male with proximal femur mass. Biopsy is shown which is CD45- and CD56+. What are further tests, diagnosis and treatment?
Myeloma. Note the atypical plasma cells, eccentric and eosinophilic nuclei.
Check for monocolonal kappa or lambda light chains and monoclonal spike on SPEP/UPEP. Advanced imaging with skeletal survey (bone scan cold).
Treatment is chemo, radiation +/- bone marrow transplant. Surgery reserved for fracture stabilization
45-year-old male with midline low back pain. Imaging shown below. What does the histology look like? What is diagnosis and treatment?
Chordoma. Note the midline expansile mass of notochord origin.
Histology shows physaliferous cells with bubbly cytoplasm, sheets and cords of cells in a myxoid stroma, vacuolation of cells.
Treat with intralesional vs wide resection and XRT
25-year-old with thigh pain. iopsy of the lesion shows tennis racket appearing granules on electronmicroscopy. What might spine x-rays show? What is the diagnosis and treatment?
Langerhans Cell Histiocytosis. Note the histiocytes with grooved nucleus (coffee bean), these are the Langerhans cells.
Spine films would show vertebra plana
Treatment is curettage if symptomatic and unifocal. In disseminated type, treatment is corticosteroids, chemo and XRT.
3-year-old with diabetes insipidus, exopthalmos, lytic bone and skull lesions. What is your diagnosis? What is the most severe form of disease?
Hand-Schuller-Christian LCH. Most fatal form is seen in infacnts as Letterer Siwe disease.
40-year-old with epiphyseal lytic lesion in distal femur. Biopsy is shown below. What is diagnosis and treatment?
Giant cell tumor of bone, note the giant cells with matching smaller stromal cells.
Treatment is intralesional resection and reconstruction.
Can use denosumab to limit RANK-L induced osteoclast differentiation and reduce bony destruction.
16-year-old with fevers, weight loss, elevated ESR/CRP and this scapular mass. There is evidence of onion skinning and periosteal reaction on x-rays. Biopsy is CD99+ and shows small round blue cells in pseudorosettes. What is the diagnosis and treatment?
Ewing’s sarcoma. Confirm 11:22, EWS-FLI-1 translocation.
Treat with chemo, surgery, chemo.
Prognosis of axial and more proximal lesions are worse.
30 year old with right leg pain. Radiographs are shown. What other studies do you want, what will you see on histology and what is your treatment?
Adamantinoma, note the mixed lytic and sclerotic lesions along the length of the bone. He needs a CT chest because 25% metastasize to the lungs.
Pathology shows nests of epithelial cells in a fibrous stroma, these cells will be keratin positive. Biopsy is usually needed to discern admantinoma from osteofibrous dysplasia (rimming osteoblasts around Chinese characters).
Treatment is wide excision.
Mirel’s criteria
9+ = surgery, 8 = borderline, 7 or less = no surgery
How do tumors cause bone lysis? How can medications fight this?
Tumors activate osteoblasts, which make more RANK-L and stimulate osteoclast function and monocyte precursor cell differentiation into osteoclasts.
Denosumab and bisphosphonates disrupt this cycle
14-year-old with this expansile lytic lesion. Biopsy is performed and immunhistochemistry positive for USP6 rearrangement. What is your diagnosis and treatment?
ABC. Note blood filled cystic spaces, giant cells, reactive woven bone and fibrous septa. USP6 marks the 17p13 gene rearrangement.
Treat with open curettage and bone grafting.
What would you see on histology? What’s your diagnosis and treatment?
Note the fallen leaf sign and central lesion. This is an active UBC. They become latent when they are further away from the physis.
Histology would show a thin fibrous lining with fibrous tissue, giant cells and hemosiderin. There is only one cyst channel as opposed to ABC (numerous).
Treatment is observation, aspiration/injection or currettage and grafting for those at risk for pathologic fracture.
60-year-old with bilateral leg pain. Bone scan is shown. He has a history of paramyxovirus infection. What would x-rays show?
Polyostotic Paget’s disease. Note how it travels from proximal to distal.
X-rays show cotton wool exudate, osteoporosis, mixed lytic/blastic lesions, thickened and enlarge cortices
Diagnosis? Treatment?
Paget’s disease. Note the mosaic pattern and cement lines. Check alk phos, urine hydroxyproline and N-telopeptides to confirm diagnosis.
Treat with bisphosphonates, surgery only for deformity and fracture.
Diagnosis?
Osteomyelitis. There isn’t a single replicated cell, it’s a mix of lymphocytes and plasma cells.
Chronic draining osteomyelitis turned squamous cell carcinoma. What would you see on biopsy?
Keratin pearls
