Dr. Nielsen's Study Set 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.
