pathology Flashcards
<5 Malignant bone lesion
Metastatic rhabdomyosarcoma Metastatic neuroblastoma
LCH
<5 Benign bone lesion
Osteomyelitis
Osteofibrious dysplasia
< 30 Malignant bone lesion
Ewing Sarcoma
Osteosarcoma
<30 benign bone lesion
osteoid osteoma osteoblastoma chondroblastoma ABC LCH osteofibrous dysplasia NOF
> 30 malignant bone lesion
chondrosarcoma metastases lyphoma myeloma chordoma adamantinoma
> 30 benign bone lesion
GCT
paget disease
If there are multiple destructive lesions in middle-aged and older patients (age >40), the most likely diagnosis is
metastatic bone disease, multiple myeloma, or lymphoma
EPIPHYSEAL bone lesion
Chondroblastoma
Giant cell tumor
Clear cell chondrosarcoma (femoral head)
METAPHYSEAL bone lesion
Osteosarcoma
Chondrosarcoma
Metastatic disease
DIAPHYSEAL bone lesion
A = adamantinoma E = eosinophilic granuloma I = infection O = osteoid osteoma/osteoblastoma U = Ewing sarcoma Y = myeloma, lymphoma, fibrous dysplasia Metastatic disease
SPINE bone lesion
Anterior column Giant cell tumor Metastatic disease Posterior column Osteoid osteoma/osteoblastoma Aneurysmal bone cyst
SACRUM bone lesion
Midline
Chordoma
Eccentric
Aneurysmal bone cyst/giant cell tumor/metastatic disease
Principles of Musculoskeletal Biopsy
Make longitudinal incision in line with future resection.
Biopsy through a single compartment.
Avoid critical structures (i.e., neurovascular bundles).
Biopsy the soft tissue component when present.
(Avoids weakening bone, decalcification)
Maintain strict hemostasis. Use a drain in line with the incision when needed.
Immunohistochemistry markers
SMA (smooth muscle actin)
smooth muscle
leiomyosarcoma
Immunohistochemistry markers
Desmin
skeletal muscle
rhabdomyosarcoma
Immunohistochemistry markers
MyoD1/myogenin (myf-4)
skeletal muscle
rhadomyosarcoma
Immunohistochemistry markers
S100
neural
schwannoma
MPNST
Immunohistochemistry markers
CD34/CD31`
Endothelial cells/vascularity
hemangioma, hemangioendothelioma, angiosarcoma
Immunohistochemistry markers
B-catenin
membrane marker, Wnt signaling pathway
Fibromatosis
Immunohistochemistry markers
CD99
Ewing Sarcoma
PNET
Immunohistochemistry markers
Keratin
Epitheloid sarcoma
synovial sarcoma
carcinoma
adamantinoma
Immunohistochemistry markers
EMA (epithelial membrance antigen)
epithelioid sarcomas
synovial sarcoma
Immunohistochemistry markers
vimentin
soft tissue sarcoma
Immunohistochemistry markers
CD20, CD45
lymphoma
Immunohistochemistry markers
CD138
Myeloma
Ewing sarcoma translocation and gene fusion product
11:22 (balanced)
EWS-FLI1 oncogene
Tumor suppressor gene mutations in oseosarcomas
Rb (35%)
p53 (50%)
Common Chromosomal Translocations and Gene
Ewings/PNET
11;22
EWS-FLI1
Common Chromosomal Translocations and Gene
myxoid liposarcoma
12;16
TLS-CHOP
Common Chromosomal Translocations and Gene
alveolar rhadomyosarcoma
2;13
PAX3-FKHR
Common Chromosomal Translocations and Gene
clear cell sarcoma
12;22
EWS-ATF1
Common Chromosomal Translocations and Gene
synovial sarcoma
x;19
SSX1-SYT
Common Chromosomal Translocations and Gene myxoid chondrosarcoma (extrasekelteal)
9;22
EWS-CHN
Common Chromosomal Translocations and Gene
osteosarcoma
none
Musculoskeletal Syndromes, Genes, and Neoplasms
Li-Fraumeni
SBLA syndrome Osteosarcoma P53
Musculoskeletal Syndromes, Genes, and Neoplasms
Retinoblastoma
Bilateral malignant tumor of the eye in children Osteosarcoma RB1
Musculoskeletal Syndromes, Genes, and Neoplasms
Rothmund-Thomson
Sun-sensitive rash with prominent poikiloderma and telangiectasias
Osteosarcoma RECQL4
Musculoskeletal Syndromes, Genes, and Neoplasms
Multiple hereditary exostoses
Multiple osteochondromas Chondrosarcoma EXT1, EXT2
Musculoskeletal Syndromes, Genes, and Neoplasms
Ollier disease
Enchondromas Chondrosarcoma PTHR1
Musculoskeletal Syndromes, Genes, and Neoplasms
Maffucci syndrome
Enchondromas + angiomas and CNS, pancreatic, and ovarian malignancies
Chondrosarcoma and/or angiosarcomas
PTHR1
Musculoskeletal Syndromes, Genes, and Neoplasms
McCune-Albright
Polyostotic fibrous dysplasia, precocious puberty, and café au lait spots
GNAS1
Musculoskeletal Syndromes, Genes, and Neoplasms
Mazabraud
Fibrous dysplasia + soft tissue myxomas GNAS1
Musculoskeletal Syndromes, Genes, and Neoplasms
Jaffe-Campanacci
Multiple nonossifying fibromas with café au lait skin patches
Musculoskeletal Syndromes, Genes, and Neoplasms
POEMS
Polyneuropathy (peripheral nerve damage)
Organomegaly (abnormal enlargement of organs)
Endocrinopathy (damage to hormone-producing glands)
M protein (an abnormal immunoglobulin)
Skin abnormalities (hyperpigmentation)
Myloma
Musculoskeletal Syndromes, Genes, and Neoplasms
Hand-Schüller-Christian disease (<5 years old)
Multifocal LCH and exophthalmos, diabetes insipidus, and lytic skull lesions
LCH
Musculoskeletal Syndromes, Genes, and Neoplasms
Letterer-Siwe disease (infants)
Multifocal LCH, visceral and bone disease, and is fatal LCH
Musculoskeletal Syndromes, Genes, and Neoplasms
Stuart-Treves
Chronic lymphedema Angiosarcoma
Musculoskeletal Syndromes, Genes, and Neoplasms
Neurofibromatosis type 1
Multiple neurofibromas MPNST NF1
Musculoskeletal Syndromes, Genes, and Neoplasms
Familial adenomatous polyposis
Multiple intestinal polyps, colon cancer, hepatoblastomas Desmoid tumors APC
Grading of bone/soft tissue tumors
Based on histology (I–> III, well to poorly differentiated, <10% to >50% of metastatic potential)
Most malignant bone lesions are G2 (G1 are rare) while soft tissue tumors have a greater range)
Treatment - Chemotherapy + surgery
rhadomyosarcoma osteosarcoma nonosteogenic osteosarcoma (malignant fibrous histiocytoma [MFH] of bone, fibrosarcoma, etc.) periosteal osteosarcoma Ewing sarcoma dedifferentiated chondrosarcoma mesenchymal chondrosarcoma.
Treatment - Radiation + surgery
Soft tissue sarcoma (except rhadomyosarcoma - chemo)
Treatment - Limb salvage surgery/wide excision
Chondrosarcoma, adamantinoma, chordoma, parosteal osteosarcoma
Treatment - ORIF (+ radiation/chemotherapy)
Metastases, lymphoma, myeloma
Treatment - Intralesional resection
GCT, ABC, NOF, LCH, osteoblastoma, chondroblastoma
Treatment - Radiofrequency ablation
Osteoid osteoma
Most Common Musculoskeletal Tumors - Soft tissue tumor (children)
Hemangioma
Most Common Musculoskeletal Tumors - Soft tissue tumor (adults)
Lipoma
Most Common Musculoskeletal Tumors - Malignant soft tissue tumor (children)
Rhabdomyosarcoma
Most Common Musculoskeletal Tumors - Malignant soft tissue tumor (adults)
Undifferentiated pleomorphic sarcoma (UPS)
Most Common Musculoskeletal Tumors - Primary benign bone tumor
Osteochondroma
Most Common Musculoskeletal Tumors - Primary malignant bone tumor
Osteosarcoma
Most Common Musculoskeletal Tumors - Secondary benign lesion
Aneurysmal bone cyst
Most Common Musculoskeletal Tumors - Malignant fibrous histiocytoma
Osteosarcoma
Fibrosarcoma
Malignant fibrous histiocytoma
Osteosarcoma
Fibrosarcoma
Most Common Musculoskeletal Tumors - Phalangeal tumor
Enchondroma
Most Common Musculoskeletal Tumors - Soft tissue sarcoma of the hand and wrist
Epithelioid sarcoma
Most Common Musculoskeletal Tumors - Soft tissue sarcoma of the foot and ankle
Synovial sarcoma
Soft tissue should be presumed to be a sarcoma if…
> 5 cm
growing
deep to fascia
firm
get 3D imaging
what imaging is needed for soft tissue sarcomas
MRI of lesion
CT of chest for mets
CT a/p if liposarcoma b/c of synchronous retroperitoneal liposarcoma
What should you do if unplanned excision of a sarcoma occurs?
repeat excision
where do most soft issue tumors metastasize?
lungs
lymph nodes 5%
soft tissue sarcomas that metastasize to lymph nodes?
ESARC
Epithelioid sarcoma (hand, young adults)
Synovial sarcoma (x;18, SYT-SSX)
Angiosarcoma (Stewart-Treves syndrome, cutaneous spread)
Rhadomyosarcoma (peds)
Clear cell sarcoma (lower extremity/foot, young adults)
Extraabdominal desmoid tumor
Most locally invasive of all benign soft tissue tumors
Patients with Gardner syndrome (familial adenomatous polyposis) have colonic polyps and a 10,000-fold increased risk of developing desmoid tumors.
distinctive “rock-hard” character
estrogen receptor positive
wide resection, but recurrence is common often years later
malignant fibrous lesions - types, presentation, MRI, treatment
UPS (previously MFH)
fibrosarcoma
**30-80 years, enlargeing, painless mass
**MRI w/ deep inhomogeneous mass w/ low T1 and high T2
**treatment: wide excision, RT if >5 cm
Liposarcomas metastasize according to…
the grade of the lesion:
•
Well-differentiated liposarcomas have a very low rate of metastasis (<10%).
•
The metastasis rate of intermediate-grade liposarcomas is 10% to 30%.
•
The metastasis rate of high-grade liposarcomas is more than 50%.
Rhabdomyosarcoma -
most common sarcoma in young patients; may grow rapidly
spindle cells in parallel bundles, multinucleated giant cells, and racquet-shaped cells
sensitive to multiagent chemotherapy and wide-margin surgical resection after induction of chemotherapy. External beam irradiation plays a prominent role in treatment.
Ganglia
Outpouching of the synovial lining of an adjacent joint
Filled with gelatinous mucoid material
Paucicellular connective tissue without a true epithelial lining
MRI low T1, high T2, do not enhance
PVNS
proliferation of synovium
Knee>hip>shoulder
local = partial synovectomy
diffuse=arthroscopic for intraarticular and open posterior for extraarticular extension
high recurrence, may use RT to reduce risks
Synovial sarcoma
it rarely arises from an intraarticular location.
ages of 15 and 40 years
Lymph nodes may be involved.
most common sarcoma in the foot.
t(X;18); SYT-SSX1 and SYT-SSX2.; staining of tumor cells yields positive results for keratin and epithelial membrane antigen.
Radiographs or CT scans may show mineralization within the lesion in up to 25% of cases (spotty mineralization may even resemble the peripheral mineralization seen in heterotopic ossification).
Epithelioid sarcoma
Most common sarcoma of the hand
May ulcerate and mimic a granuloma or rheumatoid nodule
Lymph node metastases are common.
night pain relieved by NSAIDs
Osteoid osteoma has a characteristic night pain or diurnal pain pattern relieved with aspirin or NSAIDS.
bone sarcoma vs soft tissue sarcoma presentation
Malignant bone tumors manifest most commonly with pain. This is in contrast to soft tissue tumors, which most commonly manifest as a painless mass.
bone sarcoma metastasize route…
Bone sarcomas metastasize primarily via the hematogenous route; lungs are the most common site.
Osteosarcoma and Ewing sarcoma may also metastasize to other bone sites either at initial manifestation or later in the disease.
three lesions in which tumor cells produce osteoid
osteoid osteoma, osteoblastoma, and osteosarcoma.
Osteoid osteoma
self limited, young patient, night pain better w/ NSAIDs
nonstructural scoliosis from muscle spams
imaging: radiolucent nidus (<1cm) w/ intense bone sclerosis around
treatment: 50% burn out w/ NSAIDs, RFA unless close to NV bundle or spine then surgery
osteoblastoma
~osteoid osteoma but random pain not better w/ NSAIDs, nidus >2 cm w/ less reactive bone, not self limited so requires intralesional excision
High-grade intramedullary osteosarcoma
Rb and P53 (Li-Fraumeni syndrome)
occurs about the knee in children and young adults
90% high grade and penetrate cortex to form soft tissue mass (stage IIB)
imaging: mixed bone destruction and formation
two histologic criteria: (1) tumor cells produce osteoid and (2) stromal cells are frankly malignant.
Treatment: neoadjuvant chemotherapy (i.e., before surgery), followed by wide-margin surgical resection and adjuvant chemotherapy (i.e., after surgery)
Parosteal osteosarcoma (low-grade surface)
surface of the metaphysis of long bones - usually around knee posteriorly
painless mass
Treatment: resection with a wide margin, which is usually curative; no chemo
Periosteal osteosarcoma (intermediate grade surface)
Rare surface form of osteosarcoma occurs most often in the diaphysis of long bones (typically femur or tibia).
Radiographic appearance is fairly constant: a sunburst-type lesion rests on a saucerized cortical depression
Treatment: Preoperative chemotherapy, resection, and maintenance chemotherapy constitute the preferred treatment. The risk of pulmonary metastasis is 10% to 15%.
chondrosarcoma treatment
wide resection
Chemotherapy is added with dedifferentiated and mesenchymal chondrosarcoma.
enchondroma vs low grade chondrosarcoma
In low-grade chondrosarcomas, cortical bone changes (large erosions [>50%] of the cortex, cortical thickening, and destruction) or lysis of the previously mineralized cartilage is visible.
Radiographs are obtained every 3 to 6 months for 1 to 2 years and then annually as necessary.
Ollier disease/Maffucci syndrome
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% usually visceral).
surgical treatment is necessary, enchondromas are treated by curettage and bone grafting. Periosteal chondromas are usually excised with a marginal margin.
MHE
osteochondromas are often sessile and large.
autosomal dominant condition with mutations in the EXT1 and EXT2 gene loci.
Approximately 10% of patients with multiple exostoses develop a secondary chondrosarcoma.
The EXT1 mutation is associated with a greater burden of disease and higher risk of malignancy.
Chondroblastoma
Centered in the epiphysis in young patients, usually with open physes; may also occur in an apophysis (vs. GCT)
histo: Chondroblasts
“Chicken-wire” calcifications in a lacelike pattern
Treatment: curettage (intralesional margin) and bone grafting
Intramedullary chondrosarcoma
older adults
Radiographs usually show diagnostic findings, with bone destruction, thickening of the cortex, and mineralization consistent with cartilage within the lesion
Differentiating malignant cartilage may be extremely difficult on the basis of histologic features alone.
Treatment: wide-margin surgical resection
Chemotherapy has not been shown to improve survival.
Dedifferentiated chondrosarcoma
More than 80% of the lesions are typical chondrosarcomas with a superimposed highly destructive area
Prognosis is poor; rate of long-term survival is less than 10%.
Treatment: wide-margin surgical resection and multiagent chemotherapy
Metaphyseal fibrous defect (also known as nonossifying fibroma, nonosteogenic fibroma, and xanthoma)
- natural hx
- appearance
- histo
- treatment
Most such lesions resolve spontaneously and are probably not true neoplasms.
Characteristic radiographic appearance: a lucent lesion that is metaphyseal, eccentric, and surrounded by a sclerotic rim. The overlying cortex may be slightly expanded and thinned.
histo: Cellular fibroblastic connective tissue background, with cells arranged in whorled bundles
treatment: observe unless If more than 50% to 75% of the cortex is involved and the patient has symptoms, curettage and fixation are performed.
Malignant Fibrous Histiocytoma
- origin
- treatment
Also known as nonosteogenic osteosarcoma. This is a primary bone osteosarcoma with a mesenchymal origin and cellular pattern, but no osteoid is produced or seen in histology.
Treatment: same as osteogenic sarcoma—chemotherapy and surgery
chordoma
primitive notochordal tissue
Occurs predominantly at the ends of the vertebral column clivus of the skull or sacrum (sacrococcygeal)
CT scans show midline bone destruction and a soft tissue mass
Treatment: wide-margin surgical resection
Radiation therapy may be added if a wide margin is not achieved.
blue cell tumors
LERNM (learn ‘em)
lymphoma
ewing sarcoma
rhadomyosarcoma
neuroblastoma
myeloma
Giant cell tumor
Most common in the epiphysis and metaphysis of long bones; about 50% of lesions occur about the knee. 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.
A purely lytic destructive lesion in the metaphysis that extends into the epiphysis and often borders the subchondral bone
Treatment is aimed at removing the lesion, with preservation of the involved joint. may use phenol, peroxide too
Ewing tumor
small round cell sarcoma that occurs most often in children and young adults
When a small blue cell tumor is found in a child younger than 5 years, metastatic neuroblastoma and leukemia should be confirmed or ruled out. In patients older than 30 years, metastatic carcinoma must be confirmed or ruled out
Periosteum may be lifted off in multiple layers, which produces a Codman triangle and an onionskin appearance.
CD99 positivity. 11 : 22. EWS/FLI1
Standard treatment includes chemotherapy
Local tumor control may be irradiation or surgery.
Adamantinoma
Rare low-grade malignant tumor of long bones that contains epithelium-like islands of cells
Radiographic appearance: multiple sharply circumscribed, lucent defects of different sizes, with sclerotic bone interspersed between the zones and extending above and below the lucent zones
Treatment: wide-margin surgical resection
ABC vs UBC radiograpahs
ABC - eccentric, no fallen leaf sign, curettage instead of aspirate, eccentric
Width of the tumor is greater than the width of the physis
ABC
May arise primarily in bone or be found in association with other tumors (e.g., giant cell tumor, chondroblastoma, chondromyxoid fibroma, fibrous dysplasia)
May arise primarily in bone or be found in association with other tumors (e.g., giant cell tumor, chondroblastoma, chondromyxoid fibroma, fibrous dysplasia)
Essential histologic feature: cavernous blood-filled spaces without an endothelial lining
Treatment: careful curettage and bone grafting
Local recurrence is common in children with open physes.
Unicameral bone cyst (simple bone cyst)
proximal humerus
Symmetric cystic expansion with thinning of the involved cortices
Treatment: aspiration to confirm the diagnosis, followed by methylprednisolone acetate injection
Five carcinomas most likely to metastasize to bone
“BLT and a Kosher Pickle”
breast, lung, prostate, kidney, and thyroid
Bone destruction is caused not by the tumor cells themselves but by activation of osteoclasts
bone destruction in metastatic bone disease
Tumor cells secrete parathyroid hormone–related peptide (PTHrP), which stimulates release of the receptor activator for nuclear factor κB ligand (RANKL) from osteoblasts and marrow stromal cells.
RANKL attaches to the receptor activator for nuclear factor κ (RANK) receptor on osteoclast precursor cells.
Paget disease
abnormal bone remodeling. Affected patients may present with degenerative joint disease, fracture, or neurologic encroachment; joint degeneration is common in the hip and knee.
Radiographs demonstrate coarsened trabeculae and remodeled cortices
Medical treatment: aimed at retarding activity of osteoclasts
Agents used include diphosphonates and calcitonin (pamidronate and Zometa).
Paget sarcoma (<1% of patients) is a deadly tumor with a poor prognosis (rate of long-term survival <20%).
Osteofibrous dysplasia (also called ossifying fibroma or Jaffe-Campanacci lesion)
anterior tibial cortex: Multilocular, eccentric, lytic defects of cortex with a well-defined sclerotic border
Fibroosseous lesion WITH rimming osteoblasts (vs fibrous dysplasia which doesn’t have)
Bowing is very common
children < 10 years
These lesions usually regress and do not cause problems in adults
