Bones and Joints





Osteoid Tumors


Osteoma


Clinical Features





  • Male predominance (2:1 to 3:1)



  • Age ranges from second decade to elderly, with most cases occurring in fourth and fifth decades



  • Occurs most commonly in skull bones, including mandible, maxilla, frontal sinuses, ethmoid sinuses, paranasal sinuses, orbital bones, and calvarium; rarely involves the clavicles and long bones



  • May be asymptomatic or, if in sinuses, may present with signs of obstruction, including sinusitis and nasal discharges



  • Orbital tumors may produce diplopia, exophthalmos, and blindness



Radiographic Findings





  • Radiodense, circumscribed surface, or intramedullary mass usually without destructive features



Gross Pathology





  • Nodular or dome-shaped, dense cortical bone



Histopathology





  • Consists of dense lamellar bone with or without haversian canals and usually without a medullary component ( Figure 16.1 )




    Fig. 16.1


    Osteoma.

    Histologic section shows dense lamellar bone.



  • When a medullary component is present, it is represented by hematopoietic tissue or fibroadipose tissue; the process extends up to uninvolved bone and does not blend in with the adjacent normal bone



Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Osteoblastoma





  • Lamellar bone with prominent osteoblastic rimming



  • Osteoma may have focal areas of reactive bone with similar features



Parosteal Osteosarcoma





  • Tumor osteoid is arranged in parallel arrays and separated by a hypocellular fibroblastic stroma



Pearls





  • Asymptomatic, nodular, radiodense tumor involving craniofacial bones and composed of mature osteoid is typically an osteoma



  • Gardner syndrome (colonic polyposis, fibromatoses, osteomas, and epidermal cysts of skin) should be considered in the presence of multiple osteomas or osteomas of long bones



  • If surgically removed, recurrences rarely develop; no reported cases of malignant transformation





Selected References




  • Larrea-Oyarbide N., Valmaseda-Castellon E., Berini-Aytes L., et. al.: Osteomas of the craniofacial region: review of 106 cases. J Oral Pathol Med 2008; 37: pp. 38-42.



  • Unni K.K.: Dahlin’s Bone Tumors: General Aspects and Data on 11,087 Cases.1996.Lippincott-RavenPhiladelphiapp. 117-120.


Osteoid Osteoma


Clinical Features





  • Male-to-female ratio of 3:1



  • Usually occurs in second or third decade



  • Most commonly occurs in the leg, usually in the proximal femur



  • May involve tibia, vertebra (arch more so than body), and small bones of foot and hand



  • Typically intracortical tumors



  • Classic clinical presentation includes progressive pain that is greater at night and is relieved by aspirin



  • Depending on the site, other symptoms may develop




    • Vertebrae: peripheral nerve compression and painful scoliosis owing to muscle spasms (symptoms of intravertebral disk disease)



    • Upper and lower extremities: peritumoral muscular atrophy



    • Epiphyseal tumors: skeletal asymmetry, arthritis, and joint effusions




Radiographic Findings





  • Routine radiographs reveal a small, round, central area of radiolucency (nidus) surrounded by sclerosis



  • Nidus is usually cortical in location and may exhibit central ossification



  • When plain radiographs fail to reveal the tumor (about 25%), tomograms, bone scans, computed tomography (CT), or magnetic resonance imaging (MRI) may be necessary



Gross Pathology





  • Dense sclerotic bone surrounds a central nidus that is round, red, soft, and friable; nidus may be granular if ossified



  • Typically less than 1 cm



Histopathology





  • Central nidus is composed of interlacing thin bone trabeculae or woven bone with variable degrees of mineralization ( Figure 16.2 )




    Fig. 16.2


    Osteoid osteoma.

    Histologic section shows a central nidus of thin bony trabeculae with prominent benign osteoblastic rimming.



  • Trabeculae may vary in thickness



  • Prominent benign osteoblastic rimming of the trabeculae and multinucleated osteoclast-like giant cells are present within intervening fibrovascular stroma



  • Outside the nidus is an abrupt zone of fibrovascular tissue surrounded by sclerotic compact lamellar bone



  • No cartilage in the tumor unless there has been a fracture at the tumor site



  • No hematopoietic tissue or adipose tissue within the tumor



Special Stains and Immunohistochemistry





  • In short decalcified biopsies, FosB proto-oncogene, AP-1 Transcription Factor Subunit (FOS) immunohis- tochemistry can be used to diagnose osteoid osteoma and osteoblastoma, as overexpression is seen in the majority, while being rare in their mimics



Other Techniques for Diagnosis





  • Osteoid osteoma is shown to harbor FOS (87%) and FosB proto-oncogene, AP-1 Transcription Factor Subunit (FOSB) (3%) rearrangements



  • Preoperative tetracycline allows osteoblastic incorporation in the nidus, which is fluorescent under ultraviolet light



  • Preoperative intravenous technetium-99 m with specimen autoradiography is another technique that may be used to identify a small nidus when curettage is used



  • May express c-fos and c-jun by immunohistochemical analysis; some cases have demonstrated partial deletion of the long arm of chromosome 22 (22q13.1)



Differential Diagnosis


Osteomyelitis and Bone Abscesses





  • Lack a central nidus



  • Prominent acute inflammatory cell infiltrate



Osteoblastoma





  • Pain is usually not as severe



  • Tumor size is usually much greater, and there is evidence of progressive growth



  • Lacks a peripheral rim of fibrovascular tissue



  • Exhibits variable mineralization and thickness of woven osteoid trabeculae, whereas the nidus of an osteoid osteoma shows a pattern of central maturation toward a more calcified and thicker woven osteoid trabecula



Osteosarcoma





  • Lacks the fibrovascular stroma and osteoblastic rimming of osteoid osteoma



  • May exhibit chondroid or fibrous differentiation



Stress Fracture





  • Zonal pattern with central, more mature, denser bone and peripheral woven bone



  • Cartilage with endochondral ossification may be present



Pearls





  • Pain is related to the presence of unmyelinated nerve fibers in the fibrovascular stroma of the nidus, production of prostaglandin E 2 , and production of prostacyclin



  • Clinical pain may precede radiographic evidence of osteoid osteoma



  • When osteoid osteoma is present in the small bones of the hands and feet, patients are typically treated for an inflammatory process (osteomyelitis, arthritis) first



  • Intra-articular tumors may produce chronic villous synovitis similar to rheumatoid arthritis



  • Prostaglandin receptors have been identified within bone, and it has been postulated that prostaglandins may also contribute to the formation of osteoid osteoma



  • Few reports of spontaneous regression of osteoid osteomas



  • Treatment is surgical removal





Selected References




  • Baruffi M.R., Volpon J.B., Neto J.B., et. al.: Osteoid osteomas with chromosome alterations involving 22q. Cancer Genet Cytogenet 2001; 124: pp. 127-131.



  • Franchi A., Calzolari A., Zampi G.: Immunohistochemical detection of c-fos and c-jun expression in osseous and cartilaginous tumors of the skeleton. Virchows Arch [B] 1998; 432: pp. 515-519.



  • Freiberger R.H., Loitman B.S., Helpern M., et. al.: Osteoid osteoma: a report on 80 cases. Am J Roentgenol 1959; 82: pp. 194-205.



  • Lam S.W., Cleven A.H.G., Kroon H.M., et. al.: Utility of FOS as diagnostic marker for osteoid osteoma and osteoblastoma. Virchows Arch 2020; 476: pp. 455-463.



  • Sim F.H., Dahlin D.C., Beabout J.W.: Osteoid-osteoma: diagnostic problems. J Bone Joint Surg 1975; 57A: pp. 154-159.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 119-126.


Osteoblastoma


Clinical Features





  • Male predominance, with a male-to-female ratio of 2:1 to 3:1



  • Occurs in first through fourth decades, with most occurring in second and third decades



  • Predilection for the vertebral column (arch) and sacrum followed by the mandible and craniofacial bones; the next most common sites are the extremities, where it follows a distribution similar to that of osteoid osteoma



  • Typically intramedullary



  • Localized pain may be present, but not with the intensity of an osteoid osteoma



  • Vertebral tumors may produce scoliosis, muscle atrophy, and neurologic deficits



Radiographic Features





  • Round, well-demarcated, expansile, radiolucent zone with a peripheral rim of sclerosis (sclerosis may not be as extensive as in osteoid osteoma)



  • Central radiolucent zone (nidus) is greater than 1.5 cm; central stippled calcifications may be present



  • Tumor may be surrounded by an area of new bone formation



  • About one fourth may exhibit cortical destruction with periosteal new bone formation, suggesting a malignant tumor (osteosarcoma)



  • Secondary aneurysmal cyst formation may be present



Gross Pathology





  • Features similar to osteoid osteoma; however, these tumors are larger (>1.5 cm)



  • Central nidus is red, soft, and friable; if calcified, the nidus may be yellow and gritty



  • Cortical bone may be destroyed or thin, and there may be hemorrhagic cysts within the nidus, representing secondary aneurysmal cyst formation



Histopathology





  • Irregular interlacing network of osteoid with prominent osteoblastic rimming and features of woven bone ( Figure 16.3 )




    Fig. 16.3


    Osteoblastoma.

    Histologic section shows an irregular interlacing network of osteoid with prominent osteoblastic rimming.



  • Osteoid may be fine and lacelike with variable mineralization



  • Osteoblasts have benign cytologic features



  • Osteoblasts may exhibit abundant mitotic activity but no atypical forms



  • Osteoid is separated by fibrovascular stroma containing multinucleated osteoclast-like giant cells



  • Appears well circumscribed, with tumor osteoid merging with adjacent uninvolved bone



  • Large blood lakes representing secondary aneurysmal cystic changes may be seen



  • Cartilage is usually not present in the tumor, although rare cases have been reported



  • Osteoblasts may have epithelioid features represented by large cells with abundant eosinophilic cytoplasm and enlarged nuclei containing large nucleoli




    • When epithelioid cells exceed 75% of the osteoblast population, the diagnosis of aggressive osteoblastoma should be made, which denotes an increased risk for recurrence, although no cases of metastases are reported




  • Rare tumors may contain bizarre, cytologically atypical multinucleated giant cells without mitotic activity (these tumors may be designated bizarre osteoblastoma or pseudomalignant osteoblastoma )



Special Stains and Immunohistochemistry





  • In short decalcified biopsies, FOS immunohistochemistry shows as overexpression in the majority



Other Techniques for Diagnosis





  • Osteoid osteoma and osteoblastoma are shown to harbor FOS (87%) and FOSB (3%) rearrangements



Differential Diagnosis


Osteoid Osteoma





  • Usually smaller than 1 cm; clinically, the pain is of greater intensity



  • Periphery of tumor contains a fibrovascular rim



  • Nidus exhibits a more zonal pattern with central maturation and less variability in the thickness and degree of mineralization of the osteoid



  • No evidence of progressive growth



Giant Cell Tumor





  • Usually involves the epiphyses of long bones



  • Rare in vertebrae, but when they occur in a vertebra, the body and not the arch is usually involved



  • Giant cells in giant cell tumors are larger and contain more nuclei



  • Often composed of sheets of giant cells



  • Giant cell tumors contain mononuclear stromal cells



Aneurysmal Bone Cyst





  • Similar presentation and radiographic findings as osteoblastoma and also tend to involve the vertebra



  • Small foci of reactive osteoid may be present in aneurysmal bone cysts, which should not be confused with osteoblastoma



Osteoblastic Osteosarcoma





  • Radiographically, osteosarcoma is poorly circumscribed with cortical destruction and evidence of periosteal reactive bone



  • Permeative pattern of growth at the periphery



  • Stroma of osteosarcoma is sarcomatoid with cytologic atypia and atypical mitoses



  • Sheets or aggregates of atypical osteoblasts are present in osteosarcoma, in contrast to a single rim of osteoblasts around osteoid in osteoid osteoma



  • In short decalcified biopsies, FOS immunohistochemistry shows no overexpression



Pearls





  • About one fourth of the cases of osteoblastoma exhibit radiographic evidence suggesting a malignant tumor (osteosarcoma); differentiation from an osteoblastic osteosarcoma can be difficult (see “Differential Diagnosis”)



  • In short decalcified biopsies, FOS immunohistochemistry can be used to diagnose osteoid osteoma and osteoblastoma, as overexpression is seen in the majority, while being rare in their mimics





Selected References




  • De Oliveira C.R., Mendonca B.B., de Camargo O.P., et. al.: Classical osteoblastoma, atypical osteoblastoma, and osteosarcoma: a comparative study based on clinical, histological, and biological parameters. Clinics (Sao Paulo) 2007; 62: pp. 167-174.



  • Jones A.C., Prihoda T.J., Kacher J.E., et. al.: Osteoblastoma of the maxilla and mandible: a report of 24 cases, review of the literature, and discussion of its relationship to osteoid osteoma of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102: pp. 639-650.



  • Lam S.W., Cleven A.H.G., Kroon H.M., et. al.: Utility of FOS as diagnostic marker for osteoid osteoma and osteoblastoma. Virchows Arch 2020; 476: pp. 455-463.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 126-135.



  • Vigorita V.J.: Orthopaedic Pathology.1999.Lippincott Williams & WilkinsPhiladelphiapp. 322-325.


Conventional Intramedullary Osteosarcoma


Clinical Features





  • Slight male predominance, with a male-to-female ratio of 1.5:1



  • Bimodal age distribution, with most cases occurring in second decade; a second, smaller peak occurs in patients older than 50 years



  • Represents the fourth most common cause of malignancy in the pediatric age group



  • Patients with hereditary retinoblastoma are at increased risk for developing an osteosarcoma



  • Other conditions that may be associated with the development of osteosarcoma: Li-Fraumeni syndrome, Ollier disease, osteoblastoma, fibrous dysplasia, Paget disease of bone, hereditary multiple exostosis, previous radiation or chemotherapy, hypoplastic or aplasia of thumbs, Werner syndrome, and Rothmund-Thomson syndrome



  • Occurs in parts of the skeleton with the highest growth rates



  • Predilection for the distal femur, proximal tibia, and proximal humerus



  • Approximately 50% of cases occur in the region of the knee



  • Typically presents with a history of short-term (several weeks to several months), mild, intermittent pain



  • Affected area may be swollen and tender to palpation, and the overlying skin may exhibit telangiectasia and be warm



  • Serum alkaline phosphatase may be elevated



Radiographic Features





  • Classically shows a large lytic, sclerotic, or mixed lytic-sclerotic mass arising in medullary bone of the metaphysis that extends through the cortex and creates a soft tissue mass



  • Variable mineralization within the tumor, which causes cloudy opacities



  • Outer cortical surface exhibits prominent periosteal reaction represented by Codman triangle, sunbursts, or onion-skinning



  • CT and MRI are used for staging (intramedullary involvement, presence of skip lesions in marrow, and soft tissue involvement)



Gross Pathology





  • Resected specimens exhibit an intramedullary metaphyseal mass that has usually penetrated through the cortex and invades into soft tissue ( Figure 16.4A )




    Fig. 16.4


    Conventional osteosarcoma.

    A, Gross photograph showing distal femur with destructive tumor mass with medullary and cortical involvement and extension into the surrounding soft tissue. B, Histologic section shows a neoplasm composed of sarcomatous stromal cells embedded in a background of osteoid.



  • Marrow extension of the tumor proximally is usually seen, and there may be skip lesions in which normal marrow separates islands of tumor



  • Gross characteristics of the tumor are heterogeneous and variable, depending on the stromal component




    • Highly ossified areas are yellow to white and hard



    • Chondroid areas are lobulated, translucent, and light gray to white



    • Osteoblastic areas are firm, white to yellow, and sometimes gritty



    • Fibroblastic areas are soft and fleshy



    • Tumor may contain areas of necrosis, hemorrhage, and cystic changes




Histopathology





  • Microscopic features may vary considerably in different areas of a tumor




    • Tumor is basically composed of sarcomatous, spindle-shaped cells exhibiting evidence of tumor osteoid production (see Figure 16.4B )



    • Sarcomatous stroma is hypercellular and may exhibit osteoblastic, chondroblastic, fibroblastic, or malignant fibrous histiocytoma-like differentiation



    • Cells usually have obvious cytologic malignant features, including brisk mitotic activity with atypical forms



    • Some cells may exhibit epithelioid features




  • Tumor osteoid is represented by eosinophilic, amorphous, fibrillary deposits between individual tumor cells or small aggregates of tumor cells



  • Early tumor osteoid forms a lacelike pattern around tumor cells, whereas the more advanced type is mineralized and has the appearance of woven tumor bone



  • As tumor cells become incorporated with tumor osteoid, they tend to become smaller; this feature is regarded as normalization



  • Some tumors exhibit prominent chondroblastic differentiation requiring careful search for tumor osteoid



  • Fibroblastic areas may exhibit a herringbone pattern; diligent search for tumor osteoid is sometimes required



  • Some tumors may have large numbers of osteoclast-like giant cells and are designated as giant cell–rich osteosarcoma



  • Some tumors may contain foci rich in vascular structures with an hemangiopericytoma-like pattern



  • Small cell variant




    • May have features suggestive of Ewing sarcoma/primitive neuroectodermal tumor (PNET), mesenchymal chondrosarcoma, and lymphoma and require immunohistochemistry for differentiation



    • Presence of tumor osteoid



    • Rare cases of small cell variant share genetic features of Ewing sarcoma/PNET




  • Preoperative chemotherapy may result in tumor necrosis represented by acellular tumor osteoid, acellular chondroid tissue, fibrosis, or hyalinized vascular stroma; preoperative chemotherapy is considered effective when greater than 90% of the tumor is necrotic



Special Stains and Immunohistochemistry





  • SATB2: recently discovered osteoblast transcription factor (nuclear stain) critical for osteoblast lineage commitment



  • SATB2 immunohistochemistry can be useful in the diagnosis of osteosarcoma when histologic features of matrix are equivocal (i.e., osteoid vs hyalinized collagen) and when biopsy only samples tumor with undifferentiated appearance



Other Techniques for Diagnosis





  • DNA ploidy analysis usually shows prominent aneuploid clones




    • Conversion from pretreatment aneuploidy to predominant diploidy after chemotherapy correlates with subtotal or total necrosis of the tumor




  • One case of the small cell variant of osteosarcoma reportedly demonstrated chromosome translocation t(11;22)(q24;q12) typical of Ewing sarcoma/PNET; however, subsequent studies have not replicated this result



  • Hereditary form shows a loss of function of the RB gene; in nonhereditary form, there may be mutation of the TP53 gene (about 20% of cases)



Differential Diagnosis


Fracture Callus





  • Callus woven bone or osteoid exhibits a parallel pattern with prominent osteoblastic rimming



  • Absence of nuclear atypia and abnormal mitoses in callus



  • Cartilage with endochondral ossification is present in callus



Osteomyelitis





  • Radiographic findings may mimic osteosarcoma



  • Readily differentiated using histologic features



Osteoblastoma





  • Lacks atypical mitoses, infiltrative pattern, and destructive growth pattern



Giant Cell Tumor





  • Giant cell tumors usually affect skeletally mature patients with closed epiphyses



  • Usually involve the epiphyses and extend toward the articular cartilage



  • Mononuclear stromal cells without atypia or abnormal mitotic activity



  • Radiographic findings can help in differentiating these two entities



Chondrosarcoma





  • Low-grade chondrosarcoma with areas of ossification may mimic osteosarcoma, whereas chondroblastic osteosarcoma usually contains a high-grade cartilaginous component



  • Dedifferentiated chondrosarcoma contains an osteoblastic osteosarcoma component but retains low-grade chondrosarcoma foci



  • Clear cell chondrosarcomas may produce bone, thus imitating osteosarcoma



  • Presence of clear cells and typical epiphyseal location of clear cell chondrosarcoma help differentiate these two entities



Malignant Fibrous Histiocytoma





  • Typically occurs in older patients



  • Lacks tumor osteoid formation



Fibrosarcoma





  • No production of tumor osteoid



Small Cell Tumors (Ewing Sarcoma/Primitive Neuroectodermal Tumor, Lymphoma, Mesenchymal Chondrosarcoma)





  • Small cell variant of osteosarcoma will have tumor osteoid



  • Immunohistochemistry may be helpful in differentiating these tumors (leukocyte common antigen [LCA] is positive in lymphoma, S-100 protein is positive in mesenchymal chondrosarcoma, CD99 is positive in Ewing sarcoma/PNET, SATB2 is positive in osteosarcomas)



Metastatic Carcinoma





  • Prostate and mammary carcinomas can elicit a prominent osteoblastic reaction



  • Epithelial markers and specific tumor markers by immunohistochemistry can help differentiate metastatic carcinoma



Pearls





  • Osteosarcoma is the fourth most common malignant tumor found in adolescents; the three most common ones in descending order are leukemia, brain tumors, and lymphoma



  • If pain has been present for more than 1 year, the diagnosis of osteosarcoma is unlikely



  • About half of cases of primary osteosarcomas of bone occur in the knee region; osteosarcomas of the hands and feet are rare



  • Initial clinical presentation of osteosarcoma as a pathologic fracture is rare



  • Elevated serum alkaline phosphatase levels typically occur in tumors with prominent osteoblastic patterns but may also be elevated in other conditions such as osteoblastoma, osteomyelitis, and callus; a posttherapy increase in serum alkaline phosphatase suggests metastatic disease or recurrence



  • Most osteosarcomas exhibit diagnostic features on routine radiographs, whereas occasionally they may exhibit deceptively benign radiographic features



  • Rare cases of epiphyseal osteosarcoma may exhibit radiographic features of clear cell chondrosarcoma or chondroblastoma



  • A radiologically malignant metaphyseal tumor in 10- to 30-year-olds is most likely osteosarcoma



  • Rare osteosarcomas contain cytologically benign-appearing stromal giant cells that hide the sarcomatous component; careful search is necessary to identify the sarcomatous component and tumor osteoid, which is usually found in a perivascular location



  • Osteosarcomas of craniofacial bones, ribs, and vertebrae are usually related to Paget disease or radiation and typically occur in older individuals





Selected References




  • Benedict W.F., Fung Y.K., Murphree A.L.: The gene responsible for retinoblastoma and osteosarcoma. Cancer 1988; 62: pp. 1691-1694.



  • Conner J.R., Hornick J.L.: SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumors. Histopathology 2013; 63: pp. 36-49.



  • Dorfman H.D., Czerniak B.: Bone Tumors.1998.MosbySt. Louispp. 128-194.



  • Glasser D.B., Lane J.M., Huvos A.G., et. al.: Survival, prognosis, and therapeutic response in osteogenic sarcoma: the Memorial Hospital experience. Cancer 1992; 69: pp. 698-708.



  • Martin J.W., Squire J.A., Zielenska M.: The genetics of osteosarcoma. Sarcoma 2012; 2012: pp. 627254.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 136-170.


Telangiectatic Osteosarcoma


Clinical Features





  • Male-to-female ratio is 2:1



  • Most occur in second decade



  • Accounts for about 4% of all osteosarcomas



  • Similar distribution as conventional intramedullary osteosarcoma



  • Predominantly affects distal femur, proximal tibia, and proximal humerus



  • Similar symptoms to conventional osteosarcoma, except it is more likely to present as a pathologic fracture (25% of cases)



Radiographic Findings





  • Recognizable as a completely lytic lesion involving the metaphysis with infiltrating destructive margins



  • May cause cortical expansion of the bone



  • Periosteal new bone formation may be represented by onion-skinning or Codman triangle



  • Some cases may exhibit benign features and mimic an aneurysmal bone cyst



Gross Pathology





  • Hemorrhagic mass that may be multicystic and necrotic



  • No areas of fleshy, sarcoma-like tissue or sclerotic areas



Histopathology





  • Multiple cystlike spaces resembling an aneurysmal bone cyst, except that the septa of the cysts contain stromal cells (mononuclear and multinucleated) with cytologically malignant features intermixed with benign osteoclast-like giant cells ( Figure 16.5 )




    Fig. 16.5


    Telangiectatic osteosarcoma.

    Histologic section shows cystlike spaces surrounded by atypical stromal cells and osteoid.



  • Mitotic features are present, including atypical forms



  • Sometimes the malignant stromal cells are floating in the center of the hemorrhagic cysts; identification of the stromal cells may be difficult, requiring multiple sections



  • Tumor osteoid can be difficult to identify; it is usually focal and found in a delicate lacelike pattern



Special Stains and Immunohistochemistry





  • SATB2 immunohistochemistry can be useful in the diagnosis when histologic features of matrix are equivocal (i.e., osteoid vs. hyalinized collagen) and when biopsy only samples tumor with undifferentiated appearance



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Aneurysmal Bone Cyst





  • Stroma may be cellular but typically lacks cytologic atypia and atypical mitoses; may contain reactive bone with atypical osteoblasts



  • Definitive cytologic malignant features and atypical mitoses are absent



Conventional Osteosarcoma





  • Radiographically, these tumors are not purely lytic



  • Intramedullary osteosarcoma may contain focal telangiectatic areas, which should not be overinterpreted



Pearls





  • Telangiectatic osteosarcoma is frequently the type of osteosarcoma associated with long-term Paget disease



  • Better prognosis than conventional intramedullary osteosarcoma



  • When a diagnosis of aneurysmal bone cyst is being considered, all tissue should be evaluated histologically for evidence of malignant stroma to rule out telangiectatic osteosarcoma





Selected References




  • Conner J.R., Hornick J.L.: SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumors. Histopathology 2013; 63: pp. 36-49.



  • McCarthy E.F.: Differential Diagnosis in Pathology: Bone and Joint Disorders1996.Igaku-ShoinNew Yorkpp. 82-85.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 155-158.



  • Weiss A., Khoury J.D., Hoffer F.A., et. al.: Telangiectatic osteosarcoma: the St. Jude Children’s Research Hospital’s experience. Cancer 2007; 109: pp. 1627-1637.


Parosteal Osteosarcoma


Clinical Features





  • Also known as “juxtacortical osteosarcoma”



  • Slight female predominance, with a male-to-female ratio of 1:1.5



  • Occurs predominantly in third decade



  • Involves metaphyses of long bones with approximately three fourths of cases involving the distal posterior femur, with the proximal tibia as the second most common site



  • Clinically presents as a painless mass of long duration (slow growing); pain may occur late in the course but is not typical initially



  • May also present as an inability to flex the knee



Radiographic Features





  • Radiodense, bosselated, or mushroom-shaped mass arising on the surface of a bone (outside of periosteum); in long-term lesions, tumor may encircle the bone



  • A separate lucent zone between the tumor and the cortex known as a string sign may be seen



  • No evidence of periosteal bone reaction



  • Peripheral lucent areas may represent a cartilaginous cap



  • Central lucent areas may represent high-grade sarcoma or dedifferentiated tumors



  • CT or MRI may be necessary to visualize lucent areas



Gross Pathology





  • Well-ossified mass that appears attached to the cortical surface of the bone



  • Cartilaginous cap may be present and there may be soft foci, which should be sampled; these foci may represent high-grade sarcomatous regions or dedifferentiated tumor



Histopathology





  • Tumor osteoid is arranged in parallel arrays and separated by a hypocellular fibroblastic stroma that exhibits minimal cytologic atypia and minimal mitotic activity without atypical forms ( Figure 16.6 )




    Fig. 16.6


    Parosteal osteosarcoma.

    Histologic section shows parallel arrangement of tumor osteoid separated by fibroblastic stroma with only minimal atypia.



  • Islands of cartilaginous tissue and a cartilaginous cap may be present




    • Chondrocytes are atypical and do not exhibit orderly arrangement



    • Atypia is mild and reminiscent of chondrocytic atypia seen in enchondromas




  • No evidence of periosteal new bone formation



  • Areas of dedifferentiated high-grade sarcoma may be seen (about 15% of cases)



  • No fatty or hematopoietic marrow is seen in association with the tumor



Special Stains and Immunohistochemistry





  • SATB2 immunohistochemistry can be useful



Other Techniques in Diagnosis





  • Cytogenetic studies: a ring chromosome may be seen



Differential Diagnosis


Osteochondroma





  • Medullary spaces contain adipose tissue or marrow hematopoietic tissue



Myositis Ossificans





  • Maturation toward lamellar bone and marrow adipose tissue begins peripherally and extends centrally in this proliferative process, which is the reverse in parosteal osteosarcoma



High-Grade Surface Osteosarcoma





  • These are cytologically high-grade tumors that lack residual low-grade areas



Periosteal Osteosarcoma





  • Abundant cartilage is present



  • Higher-grade osseous component and evidence of periosteal reaction



Pearls





  • Symptoms may last up to 10 years



  • Typically affects an older age group compared with intramedullary osteosarcoma



  • It is not uncommon for these patients to have a history of recurrence of a previously diagnosed osteochondroma



  • Radiologic and histologic evidence of periosteal new bone formation is absent



  • Central lucent areas identified on CT scan or MRI may represent high-grade sarcomatous areas or regions of dedifferentiation



  • Children may exhibit radiographic lesions that mimic parosteal osteosarcoma of the distal femur; histologically, they have features of fibrous cortical defect





Selected References




  • Conner J.R., Hornick J.L.: SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumors. Histopathology 2013; 63: pp. 36-49.



  • Han I., Oh J.H., Na Y., et. al.: Clinical outcome of parosteal osteosarcoma. J Surg Oncol 2008; 97: pp. 146-149.



  • Sinovic J.K., Bridge J.A., Neff J.R.: Ring chromosome in parosteal osteosarcoma: clinical and diagnostic significance. Cancer Genet Cytogenet 1992; 62: pp. 50-52.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 170-177.


Periosteal Osteosarcoma


Clinical Features





  • Slight male predominance, with a male-to-female ratio of 1.7:1



  • Typically occurs in second to third decades (later than a conventional osteosarcoma appears and sooner than a parosteal osteosarcoma appears)



  • Most occur in the diaphysis and metaphysis of the tibia and femur



  • Patients present with pain, swelling, and tenderness; symptoms often present for less than 1 year



  • Rare (<2% of all osteosarcomas)



Radiographic Findings





  • Represented by a surface radiolucent tumor containing a spiculated pattern of calcifications that are oriented perpendicular to the long axis of the primary bone



  • May see cortical thickening or erosion



  • Periosteal reaction may be present



  • No medullary involvement



Gross Pathology





  • Lobulated surface mass having a cartilaginous appearance



  • Cortical erosion may be seen, but the tumor does not extend into the medullary cavity



Histopathology





  • Malignant osteoid must be present (may only be focal), but the predominant pattern of tumor is represented by lobulated chondromatous tissue with cytologic features of grade 2 or 3 chondrosarcoma



  • Tumor is located on the surface of the bone and may extend into soft tissue



  • High-grade anaplastic sarcomatous spindle cell component may separate lobules of the malignant chondroid component



  • Periosteal bone formation may be present, and there may be cortical erosion, but the tumor does not involve the medullary cavity



Special Stains and Immunohistochemistry





  • SATB2 immunohistochemistry can be useful in the diagnosis of osteosarcoma when histologic features of matrix are equivocal (i.e., osteoid vs. hyalinized collagen) and when biopsy only samples tumor with undifferentiated appearance



Other Techniques for Diagnosis





  • Cytogenetics: usually diploid



Differential Diagnosis


Periosteal Chondroma





  • Usually smaller and better defined



  • Composed of benign chondroid tissue; does not contain malignant tumor osteoid



Periosteal Chondrosarcoma





  • Radiographically, it contains “popcorn” calcifications



  • Histologically, it is a low-grade chondrosarcoma containing no tumor osteoid



Parosteal Osteosarcoma





  • Radiographically, these tumors are more radiodense



  • Histologically, this is a low-grade malignant fibro-osseous tumor without chondroid differentiation



Conventional Intramedullary Osteosarcoma





  • This is a higher-grade osteosarcoma involving the medullary cavity



  • Periosteal osteosarcoma does not involve the medullary cavity



High-Grade Surface Osteosarcoma





  • Lacks cartilaginous differentiation



  • Osteoid component is pleomorphic and high grade



Pearls





  • By definition, periosteal osteosarcoma does not involve the medullary cavity



  • CT scan or MRI may be necessary to rule out medullary involvement





Selected References




  • Conner J.R., Hornick J.L.: SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumors. Histopathology 2013; 63: pp. 36-49.



  • Grimer R.J., Bielack S., Flege S., et. al.: Periosteal osteosarcoma—a European review of outcome. Eur J Cancer 2005; 41: pp. 2806-2811.



  • Rose P.S., Dickey I.D., Wenger D.E., et. al.: Periosteal osteosarcoma: long-term outcome and risk of late recurrence. Clin Orthop 2006; 453: pp. 314-317.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 178-182.


High-Grade Surface Osteosarcoma


Clinical Features





  • Very rare tumor, with male-to-female ratio of about 3:1



  • Occurs predominantly in third and fourth decades



  • Distal and midfemur, proximal humerus, and proximal fibula are most common sites



  • Pain and swelling are most common symptoms, with duration from less than a year to many years



  • Similar prognosis to conventional intramedullary osteosarcoma, but poorer prognosis than parosteal osteosarcoma



Radiographic Features





  • Exhibits a surface mass with features similar to those of periosteal osteosarcoma, except the mineralization pattern is similar to that of conventional osteosarcoma, revealing a fluffy, cumulus cloud appearance



  • May be cortical destruction, periosteal reaction, and focal medullary involvement



Gross Pathology





  • Large, lobulated surface mass with variable consistency ranging from soft to firm



  • Should not significantly involve the medullary region



  • May be hemorrhagic



Histopathology





  • Histologically high-grade osteosarcoma with features similar to those of conventional intramedullary osteosarcoma, but lacks significant medullary involvement



Special Stains and Immunohistochemistry





  • SATB2 immunohistochemistry can be useful in the diagnosis when histologic features of matrix are equivocal (i.e., osteoid vs. hyalinized collagen) and when biopsy only samples tumor with undifferentiated appearance



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Dedifferentiated Parosteal Osteosarcoma





  • Usually has residual low-grade malignant fibroblastic stromal component



Parosteal Osteosarcoma





  • Lacks high-grade anaplastic appearance



Conventional Intramedullary Osteosarcoma





  • Significant medullary component (minimal medullary component in a high-grade surface osteosarcoma)



Pearls





  • Radiographically mimics periosteal osteosarcoma, except it has cumulus cloud–like patterns of mineralization



  • Of all the types of surface osteosarcomas, this has the least favorable prognosis (similar to conventional intramedullary osteosarcoma)





Selected References




  • Conner J.R., Hornick J.L.: SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumors. Histopathology 2013; 63: pp. 36-49.



  • Okada K., Unni K.K., Swee R.G., et. al.: High grade surface osteosarcoma: a clinicopathologic study of 46 cases. Cancer 1999; 85: pp. 1044-1054.



  • Staals E.L., Bacchini P., Bertoni F.: High-grade surface osteosarcoma: a review of 25 cases from the Rizzoli Institute. Cancer 2008; 112: pp. 1592-1599.


Low-Grade Central Osteosarcoma


Clinical Features





  • Male-to-female ratio is about 1:1



  • Most cases occur in third and fourth decades; this variant of osteosarcoma can occur in older age groups



  • Patients present with a history of pain for many months up to several years; usually no complaint of swelling



  • Most common sites include mid- and distal femur and proximal and midtibia



  • Some patients may have been previously diagnosed with fibrous dysplasia



Radiographic Features





  • Large, poorly marginated intramedullary mass that either is sclerotic or exhibits trabeculations



  • Usually no evidence of periosteal reaction



  • Medullary tumor may extend along the length of the bone to the subarticular bone



  • May have cortical destruction with formation of a soft tissue mass



Gross Pathology





  • Tumors are gritty, gray, medullary masses that may have fibrous and fleshy areas



  • Cortical destruction may be seen, and the tumor may extend the length of the bone with poor demarcation between tumor and uninvolved medullary bone



  • Mean size about 9 cm



Histopathology





  • Similar to parosteal osteosarcoma and can also mimic fibrous dysplasia



  • Well-differentiated intramedullary fibro-osseous process represented by irregular bony trabeculae separated by fibrous spindly stroma



  • Spindle cells are fibroblastic-like and have elongated nuclei with nucleoli



  • Nuclei exhibit minimal atypia and infrequent mitoses; atypical mitoses are rare to absent



  • Rare chondroid foci may be seen



Special Stains and Immunohistochemistry





  • SATB2 immunohistochemistry may be useful



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Fibrous Dysplasia





  • Benign nonaggressive radiographic features with no cortical disruption



  • Histologically, the woven bone in fibrous dysplasia is delicate and curved, in contrast to the coarse tumor osteoid in low-grade central osteosarcoma



  • Fibrous dysplasia lacks nuclear atypia and mitotic activity



Desmoplastic Fibroma





  • No radiographic evidence of matrix formation



  • Histologically, the central portion of desmoplastic fibroma will not contain any tumor osteoid



Osteoblastoma





  • Typically has benign radiographic features



  • Prominent osteoblastic rimming of bony trabeculae



Conventional Intramedullary Osteosarcoma, Fibroblastic Variant





  • Nuclear pleomorphism and mitotic activity with atypical forms is greater in this tumor compared with low-grade central osteosarcoma



  • Parosteal osteosarcoma



  • Surface location with no medullary involvement, but similar histology



Pearls





  • This variant affects older patients more often than traditional osteosarcomas



  • Not associated with previous radiation therapy or preexisting Paget disease (typical of osteosarcoma seen in elderly patients)



  • A small number of these tumors may be interpreted as benign radiographically



  • Histologically similar to parosteal osteosarcoma





Selected References




  • Andresen K.J., Sundaram M., Unni K.K., et. al.: Imaging features of low-grade central osteosarcoma of the long bones and pelvis. Skeletal Radiol 2004; 33: pp. 373-379.



  • Choong P.F., Pritchard D.J., Rock M.G., et. al.: Low grade central osteogenic sarcoma: a long-term follow-up on 20 patients. Clin Orthop 1996; 322: pp. 198-206.



  • Conner J.R., Hornick J.L.: SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumors. Histopathology 2013; 63: pp. 36-49.



  • McCarthy E.F.: Differential Diagnosis in Pathology: Bone and Joint Disorders1996.Igaku-ShoinNew Yorkpp. 76-81.


Chondroid Tumors


Osteochondroma


Clinical Features





  • Also known as exostosis



  • Most common benign tumor involving bone



  • Male-to-female ratio is about 2:1



  • Most occur in second and third decades, but can present at any age



  • Majority occur in distal femur, proximal tibia, and humerus; pelvis is also a relatively common site



  • Extremely rare in craniofacial bones, vertebrae, sacrum, and sternum



  • Patients present with a longstanding mass that may be painful or asymptomatic



  • Some lesions are asymptomatic and are identified incidentally on radiographs obtained for other reasons



  • Pain may be secondary to impingement of a bursa, fracture, or infarction of the lesion



  • May develop after radiation treatment (more than 1 year) for other malignant processes



  • Hereditary form (autosomal dominant) is called osteochondromatosis or multiple hereditary exostosis (any bone may be involved except craniofacial bones)



  • Other hereditary forms with multiple osteochondromas include Langer-Giedion syndrome and DEFECT-11 syndrome



  • Fewer than 2% of osteochondromas undergo malignant transformation; clinical features suggestive of malignant transformation include pain, rapid growth, large tumor size (>6 cm), and location (axial skeleton)



Radiographic Findings





  • Radiographs reveal a pedunculated metaphyseal mass projecting from the surface of a bone ( Figure 16.7A )




    Fig. 16.7


    Osteochondroma.

    A, Radiograph of the distal femur shows a pedunculated mass. The cortex and medulla at the base of the stock are continuous with those of the femur. B, Low-power view shows a cartilaginous cap overlying bony trabeculae.



  • Variable smooth or irregular surface and a variable base (narrow to wide); points toward the diaphysis and away from the nearest epiphysis



  • Has appearance of mature bone and is continuous with the cortex of the uninvolved adjacent bone



  • Surface cap represented by cartilage is not identified with routine radiographs unless calcified; MRI is necessary to evaluate the nonmineralized cartilaginous cap



Gross Pathology





  • Pedunculated or broad-based mass containing a smooth, thin (<1 cm) cartilaginous cap



  • In older patients, the cartilaginous cap may be attenuated or absent



  • Central part of the mass is represented by normal-appearing medullary bone



Histopathology





  • Outer surface is covered by a thin layer of periosteal fibrous tissue



  • Cap is represented by hyaline cartilage that contains evenly distributed chondrocytes (see Figure 16.7B )



  • Nuclei may exhibit atypia and pleomorphism



  • Junction of the cap and bone mimics the epiphyseal plate and contains linear rows or columns of chondrocytes




    • Columns undergo endochondral ossification and form bony trabeculae



    • Medullary spaces between the trabeculae of bone contain adipose tissue and sometimes hematopoietic tissue




  • Chondrocytic atypia must be evaluated with clinicoradiographic features to determine their significance




    • Nuclear enlargement, variation in nuclear shape, multinucleation, and formation of chondrocytic clusters that are irregularly shaped may cause some concern but can be found in osteochondromas



    • Chondrocytic atypia along with clinical features of malignancy (pain, rapidly enlarging tumor, size > 6 cm) and radiographic features of malignancy (irregular thickened cartilaginous cap > 2 cm, radiolucent areas of the cartilaginous cap, extension through periosteum into soft tissue, and bone destruction) are more ominous and concerning for a secondary chondrosarcoma



    • High mitotic activity is indicative of malignancy




Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Chromosome rearrangement of 8q24.1 (EXT1) is found in patients with Langer-Giedion syndrome



  • Deletions of chromosomal bands 11p11-12 (EXT2) is seen in patients with DEFECT-11 syndrome



  • The EXT1 and EXT2 gene products add heparan sulfate to proteoglycans and may have tumor suppressor functions



Differential Diagnosis


Parosteal Osteochondromatous Proliferation (Nora Lesion)





  • Usually involves small bones of hands and feet



  • Occurs in third and fourth decades of life



  • Medullary component of lesion is not in continuity with host bone



  • Histologically, the cartilage is hypercellular with atypia and multinucleation



  • Chondroid nodules are separated by a spindle cell proliferation that exhibits mitotic activity (no atypical mitoses or nuclear atypia)



  • Woven bone with deep basophilia may be present



Chondrosarcoma Arising in an Osteochondroma





  • Clinical findings consist of pain and a rapidly enlarging mass



  • Radiographic findings consist of thickened (>2 cm), irregular cartilaginous cap, radiolucent zones in cartilaginous cap, extension through periosteum into soft tissue, and evidence of bone destruction



  • Histologic findings consist of increased cellularity, nuclear atypia represented by enlarged nuclei with open chromatin pattern, multinucleation, and mitotic activity



  • Fibroblastic stroma is present in the medullary spaces instead of fat and hematopoietic tissue



  • If a cartilaginous cap is present, it is composed of cytologically low-grade malignant chondrocytes without endochondral ossification



  • Presence of HEY1-NCOA2 fusion gene



Parosteal Osteosarcoma





  • Continuity with the medullary component of the parent bone is not present



  • Appears to be attached to the surface of the parent bone



Pearls





  • Clinical and radiographic findings are important in the evaluation of chondrocytic atypia



  • Radiographically, the long axis of the stalk points away from the nearest epiphysis



  • Malignant transformation is rare (<2%)



  • Cytogenetic abnormalities suggest that osteochondroma represents a true neoplastic process





Selected References




  • Altay M., Bayrakci K., Yildiz Y., et. al.: Secondary chondrosarcoma in cartilage bone tumors: report of 32 patients. J Orthop Sci 2007; 12: pp. 415-423.



  • Chikhladze R., Nishnianidze T.: Clinical-morphological aspects of osteochondroma of long bones. Georgian Med News 2007; 152: pp. 57-59.



  • Nora F.E., Dahlin D.C., Beabout J.W.: Bizarre parosteal osteochondromatous proliferations of the hands and feet. Am J Surg Pathol 1983; 7: pp. 245-250.



  • Shunichi Toki, Toru Motoi, Mototaka Miyake, et al: Minute mesenchymal chondrosarcoma within osteochondroma: an unexpected diagnosis confirmed by HEY1-NCOA2 fusion. Hum Pathol . 2018 Nov;81:255-260.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 37-46.


Enchondroma


Clinical Features





  • Male-to-female ratio is about equal; affects all age groups (most occur in second to fifth decades)



  • Occurs predominantly in the appendicular skeleton, with most occurring in bones of the hands and feet (hands more often affected than feet)



  • Proximal humerus and femur and distal femur are also affected; rarely found in the pelvis, ribs, sternum, and vertebrae (no reported cases in craniofacial bones)



  • In general, these tumors are asymptomatic and may be identified on routine radiographs or nuclear scans



  • Phalangeal tumor may present as a mass



  • Pain may be a presenting feature in association with a pathologic fracture or trauma to the tumor



Radiographic Features





  • Well-defined, predominantly lucent diaphyseal intramedullary mass ( Figure 16.8A )




    Fig. 16.8


    Enchondroma.

    A, Radiograph of the rib shows an expanding radiolucent area with associated calcifications. Gross section of the tumor mass shows a gray-white lesion extending from cortex to cortex. B, Low-power view shows a well-circumscribed nodule composed of lobules of mature hyaline cartilage.



  • Usually lobulated and sharply demarcated with variable mineralization, stippled, ringlike, or flocculent



  • Cortical expansion and thinning may be seen, but the cortex should be intact; rare evidence of periosteal reaction



Gross Pathology





  • Curettage produces fragments of blue-gray translucent, glistening chondroid tissue intermixed with fragments containing yellow foci representing calcification



  • Resected specimens consist of a well-circumscribed medullary, confluent, lobulated, cartilaginous mass; periphery of the tumor may be irregular



Histopathology





  • Composed of lobulated, mature, hyaline-like cartilage (see Figure 16.8B )



  • Lobules may be separated by marrow hematopoietic tissue or endochondral bone



  • Chondrocytic cellularity is low and usually evenly distributed



  • Bland cytologic features with small, slightly hyperchromatic nuclei without pleomorphism; rare multinucleated forms may be present



  • Nuclei with open chromatin patterns and mitoses are generally absent



  • Cellularity may be higher in tumors of the hands and feet



  • Calcifications and endochondral ossification may be present



  • Myxoid areas should arouse suspicion of malignancy except in tumors of the hands and feet



Special Stains and Immunohistochemistry





  • Mib-1 (Ki-67): in tumors involving bones other than the hands and feet in which malignancy is suspected clinically or radiologically, Mib-1 may be used to demonstrate proliferative activity



  • Proliferative index is low in enchondroma



  • Insulin-growth factor II mRNA binding protein (IMP3) is negative in enchondromas that helps to distinguish from chondrosarcomas (IMP3 is overexpressed in 36% of chondrosarcomas)



Other Techniques for Diagnosis





  • Enchondromas may exhibit abnormalities of chromosomes 6 and 12



  • Molecular studies have shown chromosomal rearrangements involving the HMGA2 gene localized to 12q15 in some patients with enchondromas



Differential Diagnosis


Prominent Costochondral Cartilage





  • May clinically mimic enchondroma



  • Composed of histologically benign chondrocytes with an orderly and regular appearance



Fibrous Dysplasia with Chondroid Differentiation





  • Radiographs reveal a ground-glass diaphyseal lesion



  • Fibro-osseouselementsareseen(absent in enchondroma)



Low-Grade Chondrosarcoma





  • Differentiating this tumor from an enchondroma can be extremely difficult and requires clinical, radiographic, and histologic information



  • Pain is usually present in low-grade chondrosarcoma; pain is typically absent in enchondroma unless traumatized or pathologically fractured



  • Radiographic features of low-grade chondrosarcoma include cortical destruction, cortical thickening due to extension of tumor in haversian canals, and a soft tissue mass



  • Increased cellularity and binucleate chondrocytes are more prominent



  • Marrow permeation represented by cellular cartilage surrounding mature bone trabeculae and lobules of cartilage separated by fibrous tissue is seen in low-grade chondrosarcoma



  • Extension of the tumor into haversian canals (not seen in enchondroma)



  • Prominent myxoid features are not typical of enchondromas



  • Immunoperoxidase stains for proliferative activity (Mib-1) reveal nuclear positivity in low-grade chondrosarcomas (generally minimal or no staining in enchondromas except for hand and foot tumors)



  • Insulin-growth factor II mRNA binding protein (IMP3) is negative in enchondromas that helps to distinguish from chondrosarcomas (IMP3 is overexpressed in 36% of chondrosarcomas)



Pearls





  • Any cartilaginous neoplasm in the pelvis, ribs, sternum, or vertebrae should be considered a potentially aggressive tumor unless exhibiting completely benign clinical features, benign radiographic features, and benign histologic features



  • Presence of pain in the absence of trauma or associated pathologic fracture should arouse suspicion of malignancy in a patient with a low-grade chondroid neoplasm



  • Myxoid features in an enchondroma should raise suspicion of malignancy



  • Significance of atypical cytologic features, atypical cellularity, and myxoid features in an enchondroma increases as the tumor location gets closer to the axial skeleton



  • Ollier disease (enchondromatosis) presents with multiple enchondromas and carries a higher risk for malignant transformation



  • Maffucci syndrome: congenital syndrome consisting of multiple enchondromas and hemangiomas; increased risk for developing chondrosarcomas and malignant vascular tumors (angiosarcoma)





Selected References




  • Dorfman H.D., Czerniak B.: Bone Tumors.1998.MosbySt. Louispp. 253-276.



  • Gajewski D.A., Burnette J.B., Murphy M.D., et. al.: Differentiating clinical and radiographic features of enchondroma and secondary chondrosarcoma in the foot. Foot Ankle Int 2006; 27: pp. 240-244.



  • Mirra J.M., Gold R., Downs J., et. al.: A new histologic approach to the differentiation of enchondroma and chondrosarcoma of the bones: a clinicopathologic analysis of 51 cases. Clin Orthop 1985; 201: pp. 214-237.



  • T Shooshtarizadeh, A Nazeri, A Zare-Mirzaie, S Movahedinia: Expression of insulin-like growth factor II mRNA binding protein 3 (IMP3) in enchondroma and chondrosarcoma. Pathol Res Pract. 2016 Apr;212(4):335-339.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 46-52.


Periosteal Chondroma


Clinical Features





  • Male-to-female ratio is 2:1



  • Most cases occur in second and third decades



  • Proximal humerus, proximal femur, distal femur, and hand bones are most commonly affected



  • Usually asymptomatic and often found incidentally on routine radiographs



  • Occurs near tendon insertions and thus may cause functional abnormalities and discomfort related to movement



  • May occasionally be palpable



Radiographic Features





  • Typically a periosteal mass with variable mineralization



  • May appear lytic or markedly calcified



  • Erodes the outer cortex but does not extend into the medullary cavity



  • Periosteal bone formation creating a peripheral buttress causing the tumor to be cup-shaped or crater-like



Gross Pathology





  • Cortical, subperiosteal, gray-white lobulated chondroid mass with an outer thin layer of periosteum



  • Does not extend into the medullary cavity



  • Yellow calcifications may be present



Histopathology ( Figure 16.9 )





  • Similar features to those of an enchondroma composed of hyaline cartilage



  • May exhibit higher cellularity, increased nuclear atypia, and more multinucleated chondrocytes than enchondromas



  • Myxoid change may be present



  • Tumor may appear to extend or push into the medullary cavity, but there is a rim of lamellar bone at the junction of the tumor and medullary cavity




Fig. 16.9


Periosteal chondroma.

Histologic section shows lobulated cellular hyaline cartilage.


Special Stains and Immunohistochemistry





  • Tumor cells express S-100 protein



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Juxtacortical Chondrosarcoma





  • Exhibits radiographic features of an aggressive process and does not have buttressing periosteal new bone at the peripheral margins



  • May extend into soft tissue and may show variable cytologic atypia



Periosteal Osteosarcoma





  • Radiographically, this tumor exhibits perpendicular feathery calcifications and lacks peripheral buttressing



  • Composed of tumor osteoid and has immature mesenchymal stroma between lobules of cartilage



Pearls





  • Periosteal tumor that creates a cup- or crater-shaped mass extending into the superficial cortex but not into the medullary canal



  • Composed of hyaline cartilage similar to enchondroma





Selected References




  • Bauer T.W., Dorfman H.D., Latham J.T.: Periosteal chondroma: a clinicopathologic study of 23 cases. Am J Surg Pathol 1982; 6: pp. 631-637.



  • Nojima T., Unni K.K., McLeod R.A., et. al.: Periosteal chondroma and periosteal chondrosarcoma. Am J Surg Pathol 1985; 9: pp. 666-667.



  • Robinson P., White L.M., Sundaram M., et. al.: Periosteal chondroid tumors: radiologic evaluation with pathologic correlation. AJR Am J Roentgenol 2001; 177: pp. 1183-1188.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 56-59.


Chondroblastoma


Clinical Features





  • Male-to-female ratio is 1.5:1



  • Most cases occur in second decade; 95% occur between ages 5 and 25 years



  • Predilection for epiphyses of bones



  • Typically involves long bones in skeletally immature patients



  • Common sites include distal femur, proximal tibia, and proximal humerus



  • Other sites include acetabular area, iliac crest of pelvis, ribs, scapulae, spine, tarsal bones, base of skull, and temporal bone



  • Usually presents with pain over months to years; may have muscle wasting, arthralgia of the adjacent joint, and joint effusion



  • Rare (<1% of primary neoplasms involving bone)



Radiographic Findings





  • Circumscribed, well-demarcated epiphyseal lytic mass with a rim of sclerotic bone



  • Calcifications vary from focal stippling to coarse trabecular patterns



  • Periosteal reaction is variable, but never to the degree seen in malignant neoplasms



Gross Pathology





  • Curettage reveals friable and gritty red tissue with yellow foci of calcifications



  • Resected specimens reveal a well-circumscribed, epiphyseal gray mass containing regional calcification, hemorrhage, and cystic changes



  • Usually measure 3 to 6 cm in greatest dimension



  • May have bluish-gray areas representing chondroid matrix



  • Rim of sclerotic bone surrounds the tumor



Histopathology





  • Composed of immature cells with features of fetal chondroblasts (stromal cells), multinucleated giant cells, and chondroid matrix ( Figure 16.10 )




    Fig. 16.10


    Chondroblastoma.

    Histologic section shows a neoplasm composed of immature chondroblasts, multinucleated giant cells, and chondroid matrix.



  • Stromal cells are round and have distinct cell membranes




    • Contain predominantly eosinophilic cytoplasm and a centrally placed round nucleus, which gives a fried-egg appearance to the cell



    • Nuclei contain grooves or clefts, and chromatin patterns are finely granular and evenly distributed



    • Infrequent mitotic figures without atypical forms are seen



    • Regional areas where cells do not have well-demarcated borders and form syncytia may be seen



    • Often have areas in which the cells contain larger atypical nuclei




  • Multinucleated giant cells containing numerous nuclei (more than 20) are scattered throughout the tumor



  • Variable amounts of chondroid matrix, which may contain stromal cells



  • Calcification is an important histologic feature and has two patterns




    • Most common pattern is represented by linear calcifications surrounding stromal cells, imparting a chicken-wire appearance



    • Other pattern includes coarse calcifications of the chondroid matrix




  • May also have areas of spindle-shaped cells, secondary aneurysmal cystic changes, myxoid changes, and cystic changes containing eosinophilic amorphous material



Special Stains and Immunohistochemistry





  • H3F3 K36M mutant antibody is a sensitive and specific marker



  • S-100 protein: stromal cells are positive




    • May be helpful to identify the scant numbers of stromal cells in tumors with prominent secondary aneurysmal cystic changes




Other Techniques for Diagnosis





  • 95% of chondroblastomas harbor a p.K36M mutation in either H3F3A (chromosome 1) or H3F3B (chromosome 17), with the majority involving H3F3B



Differential Diagnosis


Chondromyxoid Fibroma





  • Usually involves the metaphyses



  • Lacks calcifications and has more prominent lobulated myxoid stroma



Giant Cell Tumor





  • Usually occurs in skeletally mature patients



  • Stromal cells with nuclear grooves are absent (negative for S-100 protein)



  • Lacks chondroid matrix and calcification



Langerhans Cell Histiocytosis (Eosinophilic Granuloma)





  • May radiographically and cytologically (nuclear grooves) mimic chondroblastoma



  • Contains eosinophils and lacks chondroid matrix and calcifications



Aneurysmal Bone Cyst





  • Chondroblastoma with prominent secondary aneurysmal bone cyst formation may mimic a primary aneurysmal bone cyst



  • S-100 protein may be useful in identifying stromal cells in chondroblastoma



Clear Cell Chondrosarcoma





  • Usually seen in older patients



  • Composed of cells with clear-staining cytoplasm



  • Contains chondrocytic cells with cytologic malignant features



  • Tends to be more heavily calcified than chondroblastoma



Chondroblastic Osteosarcoma





  • May rarely involve the epiphyses and mimic chondroblastoma



  • Contains tumor osteoid



Pearls





  • Three common epiphyseal tumors are giant cell tumor, clear cell chondrosarcoma, and chondroblastoma



  • Rare cases of metastasizing chondroblastoma have been reported without consistent, definitive, and predictable histopathologic features



  • Aneurysmal lesions of tarsal bones may have minute foci of chondroblastic stroma





Selected References




  • Amary M.F., Berisha F., et. al.: The H3F3 K36M mutant antibody is a sensitive and specific marker for the diagnosis of chondroblastoma. Histopathology 2016; 69: pp. 121-127.



  • Atalar H., Basarir K., Yildiz Y., et. al.: Management of chondroblastoma: retrospective review of 28 patients. J Orthop Sci 2007; 12: pp. 334-340.



  • Dahlin D.C., Ivins J.C.: Benign chondroblastoma: a study of 125 cases. Cancer 1972; 30: pp. 401-413.



  • Kurt A.M., Unni K.K., Sim F.H., et. al.: Chondroblastoma of bone. Hum Pathol 1989; 20: pp. 965-976.



  • Unni KK, Inwards CY, Bridge J, et al. Tumors of the Bones and Joints, 4th Series, Fascicle 2. Washington, DC: Armed Forces Institute of Pathology:61–66.



  • Vigorita V.J.: Orthopaedic Pathology.1999.Lippincott Williams & WilkinsPhiladelphiapp. 363-367.


Chondromyxoid Fibroma


Clinical Features





  • Extremely rare benign tumor



  • Male-to-female ratio is 1.5:1



  • Most cases occur in second and third decades, 80% before the age of 40 years



  • Typically occur in the metaphyses of long bones in the lower extremity; most common sites are the distal femur and proximal tibia; may also involve the pelvis or small bones of the feet



  • Patients usually present with a long-term history of pain



Radiographic Features





  • Eccentric, expansile, lobulated metaphyseal mass that sometimes extends to the epiphysis



  • Long axis of the tumor runs parallel to the long axis of the parent bone



  • Well-demarcated, completely lytic mass with scalloped margins



  • Calcifications on radiographs are rare



  • Pelvic tumors have a multiloculated soap-bubble appearance



  • Secondary aneurysmal bone cystic changes may be present



Gross Pathology





  • Sharply circumscribed, lobulated, soft, gray-white tumor, usually 3 to 8 cm in greatest dimension



  • Hemorrhagic and cystic areas may be present



  • Myxoid areas may be seen, but are usually not prominent



Histopathology ( Figure 16.11 )





  • At low magnification, the tumor has a lobulated appearance




    Fig. 16.11


    Chondromyxoid fibroma.

    A, Histologic section shows a lobulated myxoid neoplasm composed of spindle cells. B, Histologic section from another example of chondromyxoid fibroma shows the stellate cells in the stroma.



  • Lobulated areas are myxoid and composed of spindled or stellate cells



  • The lobules are hypocellular centrally and hypercellular at the periphery



  • In the hypercellular peripheral areas, the cells have features of chondroblasts



  • In about 30% of cases, bizarre cells with pleomorphic hyperchromatic nuclei are present and may suggest malignancy; however, there is no mitotic activity



  • Matrix of the lobules may have chondroid or myxoid characteristics



  • Lobules are separated by fibrous tissue containing vessels, multinucleated giant cells, and occasionally osteoid



  • Secondary aneurysmal bone cyst changes and foci of necrosis may be seen



  • Rare to absent mitotic activity



  • Solid cellular areas with features of chondroblastoma may be present



  • Although not seen on radiographs, calcifications are extensive histologically and interfere with appreciation of a lobular architecture



  • Longstanding tumors may show hyalinization



Special Stains and Immunohistochemistry





  • S-100 protein is helpful in demonstrating the presence of chondroid differentiation



  • Smooth muscle actin (SMA) and CD34 positivity can be seen in nonchondroid areas



Other Techniques for Diagnosis





  • Recurrent anomalies of the long arm of chromosome 6 (6q25), in particular the pericentromeric inversion inv(6)p25q13), have been described



Differential Diagnosis


Chondroblastoma





  • Typically involves the epiphyses



  • Calcifications seen both radiographically and histologically (chicken-wire appearance)



Medullary Chondrosarcoma





  • Most occur in older patients and predominantly in the axial skeleton



  • Radiographically, these tumors are poorly circumscribed and contain calcifications; may demonstrate cortical thickening or cortical destruction if high grade



  • May cause a soft tissue mass



  • Demonstrates marrow extension with chondroid tissue surrounding bony trabeculae



  • High-grade tumors may mimic chondromyxoid fibroma but exhibit abundant mitotic activity not seen in the latter



  • Multinucleated giant cells and aneurysmal bone cyst changes are usually not present in chondrosarcoma



Pearls





  • Use low power to appreciate the lobulated or nodular architecture



  • In curettage, the fibrous septa may be fragmented and go unnoticed histologically



  • Mitotic activity is not prominent, but if present it supports a diagnosis of chondrosarcoma





Selected References




  • Budny A.M., Ismail A., Osher L.: Chondromyxoid fibroma. J Foot Ankle Surg 2008; 47: pp. 153-159.



  • Granter S.R., Renshaw A.A., Kozakewich H.P., et. al.: The pericentromeric inversion, inv(6)(q25q13), is a novel diagnostic marker in chondromyxoid fibroma. Mod Pathol 1998; 11: pp. 1071-1074.



  • Rahima A., Beabout J.W., Ivins J.C., et. al.: Chondromyxoid fibroma: a clinicopathologic study of 76 cases. Cancer 1972; 30: pp. 726-736.



  • Safar A., Nelson M., Neff J.R., et. al.: Recurrent anomalies of 6q25 in chondromyxoid fibroma. Hum Pathol 2000; 31: pp. 306-311.



  • Unni K.K., Inwards C.Y., Bridge J., et. al.: Tumors of the Bones and Joints, 4th Series, Fascicle 2.2005.Armed Forces Institute of PathologyWashington, DCpp. 68-72.


Intramedullary Chondrosarcoma (Conventional)


Clinical Features





  • Male-to-female ratio is 1.5:1



  • Usually seen in older adults; most patients are older than 50 years; rare in patients younger than 45 years



  • Predilection for the trunk, with pelvis, ribs, proximal femur, and proximal humerus also affected



  • Childhood tumors oftentimes involve the extremities



  • Dull pain at rest that is often worse at night; symptom duration is typically several months to years



Radiographic Features





  • Radiolucent mass with variable calcifications ranging from ring-shaped or punctate calcifications to markedly calcified lesions



  • Cortex is thin with endosteal scalloping and erosion through the cortex



  • Prominent cortical thickening, representing extension into haversian canals, may be seen



  • Periosteal reaction is minimal or absent



Gross Pathology



Mar 11, 2021 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Bones and Joints
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