Bone, Fibro-osseous, and Cartilage Tumors Flashcards
Osteopoikilosis, aka bone island
On high lower, this is composed of lamellar bone, and generally looks quite normal – it is just cortical-like bone within the trabeculae.
Osteoma
Mass of lamellar, cortical-like bone with percolating vessels. A minority are composed of trabecular-like bone (trabecular osteomas).
Benign, most frequently in the craniofacial skeleton. Torus palatinus is a common example. Multiple are associated with Gardner syndrome. Not usually on appendicular skeleton outside of Gardner syndrome, but do rarely appear here.
Should have a pretty uniform, radiodense appearance and sharply-demarcated rounded margins.
Gardner syndrome
Phenotypic variant of FAP. Caused by mutations in APC.
Characteristics:
- FAP phenotype
- Osteomas
- Desmoid tumors
- Epidermal cysts
Desmoid-type fibroma/fibromatosis/tumor
Myofibroblastic neoplasm which is locally aggressive and nonmetastasizing. 90% of cases sporadic, 10% familial (often Gardner syndrome).
Composed of myofibroblasts in long, streaming fascicles. Nuclei are bland with tapering, curved edges and often tiny nucleoli. It may be hard to appreciate the typical “star shaped” myofibroblast cytoplasm since cells are densely packed into fascicles. If viewed in cross section, nuclei may just appear round.
There are often foci of storiform whorls. Blood vessels are conspicuous, often compressed or dilated, sometimes with perivascular clearing from edema. Dilated, staghorn vessels may be present, sometimes with hyalinization. These vessels may look like SFT.
IHC: Nuclear beta catenin (75% of cases), SMA+. CD34 negative, S100 negative.
Note - SFT is CD34 strongly pos, which is imporant for differentiation. Also SFT is STAT6 pos.
Molecular: CTNNB1 mutations (beta catenin) in sporadic cases, APC mutations in failial cases (Gardner syndrome).
Osteoid osteoma
Benign, bone-forming tumor. Often small in size, limited growth potential. Tumor of the young, 75% between ages 5 and 25. Often occurs in long, tubular bones (usually appendicular).
Presentation is usually very focal pain, worse at night, in a limb, with an associated lytic mass on imaging. The pain responds well to NSAIDs, as these tumors overexpress COX2 and produce PGE2 and PGI2/prostacyclin, driving local swelling. The tumor also produces osteocalcin, which may raise blood glucose.
Histology shows haphazard, interconnecting trabeculae of woven bone lined by osteoblasts. Plump, activated osteoblasts with characteristic perinuclear hoff (Golgi apparatus in this case) are present at the rim of the woven bone (shown).
IHC: Neoplastic osteoblasts are SATB2 positive and FOS positive. S100 highlights nerve fibers involved in the tumor.
Molecular: 94% of cases involve rearrangement of the FOS locus.
Usually treated with radiofrequency ablation - excellent prognosis.
Osteoblastoma
Unlike most “blastomas”, this one is benign. It tends to occur in young adults, within tubular bones and the posterior spinal column.
Histologically, composed of haphazardly interconnected trabeculae with sheet-like aggregates of woven bone rimmed by metabolically active osteoblasts. Scattered osteoclasts are also present.
Presents with pain, local swelling, and decreased range of motion if near a joint. If near a spinal joint, may have nerve commpression symptoms. Will be a lytic lesion on radiography.
Marker of notochordal differentiation
Brachyury
Conventional chordoma
Malignant tumor with a phenotype that recapitulates the notochord. Arguably a carcinoma (keratin positive). 4th most common primary tumor of bone.
50% occur in the sacrum, 30% in the skull base, and 20% in the spine.
Always lytic on imaging, and always have extraosseous extension at the time of diagnosis. They are thought to arise from benign notochordal tumors, which are sclerotic on imaging.
Histologically, are present as epithelioid cells in abundant myxoid stroma.
IHC: Bracyury +, keratin +, EMA+, S100+, INI-1 +/-
Molecular: No specific recurrent anomaly, but often have chromosomal gains and losses.
INI-1 loss is sometimes seen incidentally in well-differentiated, conventional-appearing chordomas. In this context, it has no prognostic significance. Only in the setting of a histologically poorly differentiated tumor is this meaningful (changing the diagnosis to poorly differentiated chordoma).
Has a relatively poor prognosis. This is why it is so important to differentiate it from low-grade chondrosarcomas, which have a comparatively much better prognosis.
Dedifferentiated chordoma
Histologically defined by a well-differentiated chordoma with an adjacent high grade sarcoma.
Dedifferentiated chordomas have a worse prognosis (duh) and have lost expression of brachyury.
Usually the sarcomatous component is undifferentiated pleomorphic sarcoma.
Poorly differentiated chordoma
Defined by SMARCB1 deficiency in the setting of high grade morphologic features (often rhabdoid). Have a slightly worse prognosis.
Still express keratin and brachyury (unlike dedifferentiated chordoma) but will be INI-1 negative.
Nucleus pulposus of the intervertebral disc
This is the only physiologic remnant of the notochord in an adult human. These cells maintain the intervertebral disc.
IHC: Brachyury positive, keratin positive
Arising from the clivus
Ecchordosis physaliphora
Hamartomatous extraskeletal lesion derived from notochordal remnants, characteristically arising from the clivus as a polypoid mass.
No lobular architecture, necrosis, conspicuous mitoses or high grade nuclei.
IHC: Brachyury +, keratin + (identical to chordoma)
Chondroid chordoma
Now considered a morphologic variant of convetional chordoma. Previously misdiagnosed as low grade chondrosarcoma, but has a much worse prognosis.
Looks a lot like low-grade chondrosarcoma. . . but you can find some clusters of more epithelioid cells with more ample cytoplasm – conventional chordoma cells.
If you have a cartilagenous tumor of the skull base, your differential is really chondroid chordoma vs chondrosarcoma. Throw on a keratin to distinguish the two.
Benign notochordal cell tumor
Previously overlooked as adipose tissue. Now we know that these are not adipocytes at all, but notochordal cell rests. Can be distinguished by slight rimming of eosinophilic cytoplasm and occasional eosinophilic hyaline globules.
Characteristically surrounded by sclerotic bone – but very rare cases have been reported in other extraosseous tissues, including the lung.
IHC: Brachyury positive, keratin positive.
Chordoma treatment
Combo surgery + radiation is the standard.
The initial resection is the best chance you have at curing a chordoma.
Once they recur once, the prognosis plummets, as they tend to seed the surrounding tissue after the initial resection.
Parosteal osteosarcoma
The most common juxtacortical subtype of osteosarcoma, usually involving the metaphysis of long bones. Presents in early adulthood.
Histologically, composed of lamellar and woven bony trabeculae with intervening low grade spindle cell component; cartilage component is common and dedifferentiation is seen in some cases.
MDM2 and CDK4 amplification are the molecular hallmarks.
“Low grade cartilagenous neoplasm”
Top-line diagnosis when you are given insufficient material to determine if something is enchondroma or grade 1 chondrosarcoma. Location determines if it is atypical cartilagenous tumor.
Note: The differential diagnosis includes enchondroma and grade 1 chondrosarcoma. Defer to clinical scenario and radiologic findings.
In a child, a malignant cartilage tumor is ____ until proven otherwise.
In a child, a malignant cartilage tumor is chondroblastic osteosarcoma until proven otherwise.
Chondrosarcoma in children is vanishingly rare. Double check with your radiologist.
IDH1/IDH2 mutation status is also helpful when positive - this is more likely in cartilagenous neoplasia, but does not distinguish between benign or malignant cartilage.
Giant cell tumor of bone
Typically involves the epiphysis of metaphysis of long bones in skeletally mature individuals (post-pubertal). Osteoclastic giant cells floating in a sea of uniform mononuclear cells. Remember that it is the mononuclear cells that are actually the neoplastic component, the giant cells are just recruited.
Denosumab therapy results in a depletion in giant cells and reduction in the number of neoplastic cells, which are replaced by fibrosis or woven bone.
Like so many soft tissue neoplasms, it may undifferentiated, and if this occurs the malignant component may become UPS, fibrosarcoma, chondrosarcoma, or osteosarcoma.
Hallmark molecular alteration H3F3A p.G34W.
IHC: Mutation specific antibodies exist, but in lower resourced settings p63 should also be expressed. SAT2B will also be positive.
Non-ossifying fibroma
Striking histologic resemblance to GCTOB, but note that the background cells are spindled rather than being the rounded mononuclear cells of GCTOB. May also contain aggregates of foamy histiocytes.
Like GCTOB, these are radiolucent lesions on imaging, and are eccentrically placed in the metaphysis.
These are overwhelmingly benign mesenchymal neoplasms, however exceptionally rare (case report worthy) malignant transformations have been described. Usually, they are diagnosed on imaging and are not even biopsied - just watched. They may be removed in the setting of pathologic fracture or concern for potential future pathologic fracture.
IHC does not play a role in diagnosis, but ensuring that the imaging features are consistent and when necessary sending for KRAS or FGFR1 mutation analysis can assist in diagnosis.
MAPK overactivation is the hallmark molecular feature, usually KRAS or FGFR1 (65-80% of cases) with or without inactivation of NF1.
Benign fibrous histiocytoma. . . which is dermatofibroma by another name.
BFH is the name for DF when it occurs outside of the skin.
Composed of tumor cells are spindled in shape with plump ovoid vesicular nuclei and pale eosinophilic cytoplasm, bland nuclei with vesicular chromatin, and small single nucleoli. Spindled cells coalesce into a storiform pattern. Touton-type giant cells may be present. Collagen trapping is frequently seen, if a collagenous interface is present. May have hemangiopericytoma-like staghorn vessels.
Beware: you can have “atypical” fibrous histiocytomas which possess the potential to progress to pleomorphic dermal sarcoma. Pleomorphism and increased mitosis (4 or more per 10 hpf) may indicate an aggressive lesion.
IHC: D2-40 positive (most sensitive marker), Factor XIIIa positive, SMA positive, CD34 +/- (less often than dermal DF), CD68 positive
Molecular: PRKCB or PRKCD mutations (both protein kinase C family).
Chondroblastoma
Benign neoplasm of bone arising from the epiphysis of long bones, usually between ages 10-30 and with slight male predominance. Peaks during puberty growth spurt. It is thought to arise from chondrocytes in the growth plate.
Composed of sheets of mononuclera chondroblasts admixed with osteoclast-like giant cells and eosinophilic chondroid matrix; pericellular chicken wire type calcification may be present. Genearlly, has a strong resemblance to GCTOB without the giant cells. The chondroid matrix is nice when it is present, but it is often absent.
The main DDx of chondroblastoma is chondroblastoma-like osteosarcoma, which should be negative for H3 p.K36M or other H3 alteration. Also be aware that “atypical chondroblastomas” with a higher degree of malignant potential do exist.
IHC: S100+, DOG1+, SOX9+
Molecular: H3 p.K36M (as opposed to H3 p.G34W).
Note that there are multiple H3 genes in which the mutation may occur, most often H3F3A and H3F3B. Know which ones your in-house molecular assay covers and which it does not.
Fibrous dysplasia of bone
Arises in long and craniofacial bones, diaphyseal or metadiaphyseal intramedullary sharply demarcated lesion with ground glass-like appearance on imaging. Generally asymptomatic until pathologic fracture or incidental discovery on imaging.
Filling of the bone space with fibrous tissue and the presence of thin, curvilinear trabeculae of woven bone. The cytology of the stromal cells should be bland. Transformation to a malignancy is extremely rare, but has been reported. Also beware a low-power look of FDOB but high power malignant features, which may betray a fibrous osteosarcoma.
IHC: SATB2+
Molecular: Somatic GNAS mutations are the most common molecular finding.
May be syndrome associated with McCune Albright syndrome (GNAS1 gain of function, endocrinopathy, café au lait spots, fibrous dysplasia) and Mazabraud syndrome (GNAS1 codon 201, soft tissue myxomas and fibrous dysplasia)
