Ecchordosis Physaliphora

Ecchordosis physaliphora (EP) is a benign congenital lesion derived from ectopic notochord remnants along the midline of the axial skeleton. EP arises intradurally and is not associated with bone erosion. Although EP of the spine is very rare, clival region EP is found in up to 2% of random autopsies. Ecchordosis are often clinically silent and discovered incidentally ; reports of clinically apparent EPs are scarce. In contrast, almost all clival chordomas arise extradurally, erode bone, and present clinically, causing pain, cranial neuropathies, and signs of brainstem compression.

In 1987, Wolfe and Scheithauer described a set of extraosseous chordomas having a better prognosis than classical chordomas. They distinguished these from both EP and osseous chordoma with the term “intradural chordoma.” Other pathologists contend that EP is a precursor, or even a benign form, of chordoma.

In the preoperative clinical settings, the distinction between EP and an intradural chordoma is greatly influenced by the clinical picture, particularly growth suggestive of a chordoma, and other radiologic findings. The distinction between these two lesions solely based on histologic and ultrastructural analysis of small tissue samples can be very difficult (see Chapter 2 ). Infiltrative growth, positive staining for brachyury, and an MIB-1 labeling index (i.e., cellular proliferative potential) > 2% favor chordoma.

Radiologically, EP is hypointense on T1-weighted and hypertintense on T2-weighted MR images. Distinct from an intradural chordoma, which shows considerable contrast enhancement, EP does not enhance after contrast injection. Wang et al. reported that EPs are usually smaller than chordomas, with a maximum diameter of less than 2 cm. However, as others have described EPs with diameters of 3 and 4 cm, agreement regarding the distinguishing features of large symptomatic EPs (>2 cm) and intradural chordomas is lacking. Lastly, CT imaging of a presumed EP revealed a small pedicle-like hypertrophic change in the inner table of clival bone, devoid of erosion, just anterior to the intradural mass. In general, asymptomatic patients can be treated conservatively if radiological follow-up shows a small intradural mass that does not enlarge.

Benign Notochordal Cell Tumor

Benign notochordal cell tumor (BNCT), previously called giant notochord rest or notochordal hamartoma, is an intraosseous lesions believed to be a potential precursor of chordomas. Distinct from ecchordosis physaliphora , which occur far more frequently in the skull base, BNCTs have an anatomic predilection for the spine, mainly the sacrococcygeal region. These tumors, usually microscopic in size, are located centrally within the vertebral body and are most often discovered incidentally during autopsies. In fact, small BNCTs are reported to be present in the spine of up to 20% of the population. Macroscopic BNCTs, on the other hand, are quite rare and proper differentiation of this entity from spinal chordoma is of utmost importance since the prognosis and management is completely different. Clinical observation and radiological surveillance with MR imaging is recommended for patients with a presumed diagnosis of BNCT.

As with ecchordosis, MR imaging of BNCT demonstrates low T1 signal, and high T2 signal with intraosseous lesion lacking contrast enhancement. Absence of a soft-tissue mass is also characteristic. On CT, BNCTs appear sclerotic and lack osteolytic changes. Histologically, these lesions are characterized by intraosseous sheets of adipocyte-like vacuolated chordoid cells mixed with eosinophilic cells and absence of myxoid background. Nuclei may appear atypical but mitotic figures are not identified. BNCTs also stain positively for cytokeratin-18. Nevertheless, the differential diagnosis between BNCTs and chordomas can be very difficult as these lesions share a similar histological and immunohistochemical profile. As for EP, the diagnosis of BNCT is greatly influenced by the clinical picture and radiological findings. Table 6.2 summarizes the main differences between EP/BNCTs and chordomas.

Chondroma

Chondromas, also named as osteochondromas, are benign tumors composed of mature hyaline cartilage that most commonly arise from the cartilaginous growth plates of long bones, pelvis, and scapulae. They may be solitary or multiple, in which case the term multiple exostosis applies. When they arise within the medullary osseous cavity, they are called enchondromas and can be a part of either Ollier’s disease or Maffucci syndrome—two different types of enchondromatosis that consist of multiple endochondral bone cysts and soft tissue/visceral hemangiomas, respectively. Vertebral involvement occurs in approximately 7% of the patients and 60% of these lesions arise in the cervical spine, with a predilection for the craniovertebral junction. Skull base chondromas usually arise from embryonic chondrocytic cells remnants located in sphenopetroclival synchondrosis and are rare.

These tumors may become symptomatic during adolescence as their growth rate tends to increase with age. Once the nearest epiphyseal center closes, the tumor growth stops. Malignant transformation should be considered if tumor growth persists into adulthood. Spinal chondromas usually manifest as a painless, slow-growing lesion, while skull base chondromas present with chronic headache and, eventually, intracranial hypertension. Neurological deficits may occur and depend on tumor location and growth pattern. Surgical resection is the treatment of choice.

CT imaging reveals a well-circumscribed, calcified mass, associated with erosion of the surrounding bone. MR imaging commonly shows a mass that is hypointense on T1-weighted images and heterogeneously hypertintense on T2-weighted images. A characteristic peripheral hypointensity, representing mature hyaline cartilage, is commonly seen on T2 weighted imaging. Contrast enhancement is often mild to moderate. Histologically, chondromas display an expansile, noninfiltrative growth pattern and contain well-differentiated cartilaginous cells, low cellularity, and no mitosis. Nonetheless, the differentiation between chondromas and low-grade chondrosarcomas may be challenging.

Chondroblastoma

Chondroblastomas are rare primary cartilaginous tumors that commonly occur in the epiphyses of long bones during adolescence and early adulthood. Skull base and spine chondroblastomas are very rare, tend to affect older people, and usually arise in the temporal bone and cervical spine, respectively. Clinically, these neoplasms may present with local pain, neurological deficits, or a painless, nontender, firm swelling. Although considered benign, these lesions may be locally aggressive and, exceptionally, become malignant. Therefore, some authors recommend a preoperative work up for metastatic disease. Surgery is the main treatment modality with the aim of total resection to avoid recurrences. Radiation therapy can be considered for recurrent disease.

CT imaging often reveals an osteolytic soft-tissue mass with internal calcification and, in some cases, enhancement following contrast injection. MR imaging shows low to intermediate signal on T1-weighted images, a heterogeneous, high signal on T2-weighted images, and heterogeneous contrast enhancement.

Tissue examination reveals a chondromyxoid stroma surrounding sheets of mononuclear polyhedral cells (chondroblasts) admixed with osteoclastic-like giant cells. Zones of lacy calcification (i.e., “chicken wire”) are a distinctive finding. Moreover, these tumors stain positively for S-100 and vimentin. Table 6.3 summarizes the main characteristics and differences between chondromas and chondroblastomas.

Osteoma and Osteoblastoma

Osteomas are benign osseous neoplasms that commonly occur in patients during the second and third decade of life. They have a propensity to involve the posterior elements of the vertebra in the spine, but occur more frequently in the cranial vault and paranasal sinuses in the skull, especially the frontoethmoidal region. The skull base (i.e., clivus) is rarely affected. These tumors may be also a part of Gardner’s syndrome (multiple cranial osteomas, soft-tissue tumors, and colonic polyposis). Osteoblastomas, although histologically similar to osteomas, tend to occur in slightly older patients, have a greater propensity to involve the spine, may behave more aggressively, and undergo malignant transformation.

Pain, including painful scoliosis, is the most common clinical manifestation of spinal lesions. For osteomas, characteristically, pain is more intense at night and responsive to salicylates. These features are not commonly observed in osteoblastomas. Radiculopathy and neurological deficits may be present and are more common in osteoblastomas (up to 70% of cases). Skull base tumors are often asymptomatic but may present with headaches, visual symptoms, and, rarely, spontaneous rhinorrhea and signs of central nervous system infection (i.e., meningitis and brain abscess).

Radiologically, osteomas present as a well-demarcated, hyperdense intraosseous tumor with a diameter smaller than 2 cm. Osteoblastomas are larger (>2 cm), may be predominantly osteolytic, and extend into the soft tissue thus resembling other malignant tumors. MR imaging often reveals a hypo- to isointense tumor on T1- and T2-weighted images corresponding to foci of calcification. Osteoblastomas enhance avidly following contrast injection. Histologically, these tumors show increased osteoid tissue formation surrounded by a vascular fibrous stroma and perilesional sclerosis. The osteoid production and vascularity are more intense in osteoblastomas.

Asymptomatic tumors should be treated conservatively. Radiological signs of tumor progression, intractable pain, and presence of neurological symptoms warrant surgical intervention. Adjuvant radiotherapy is reserved for recurrent cases. Table 6.4 summarizes the main differences between osteomas and osteoblastomas.

Osteosarcoma

Osteosarcomas are neoplasms of mesodermal origin and represent the most common primary malignant bone tumor (excluding multiple myeloma). They occur most frequently in young adults and the elderly, although patients of all ages may be affected, and may arise as primary lesions (i.e., osteosarcoma de novo) or secondary to fibrous dysplasia, Paget’s disease, retinoblastoma, and prior radiation therapy. The axial skeleton is rarely affected (only 4% of all cases). Spinal osteosarcomas represent up to 14.5% of all spinal cancers and most commonly affect the sacral region, while skull base tumors are exceedingly rare.

The clinical presentation of spinal and skull base osteosarcomas resembles that of other malignant bone tumors, and neurological deficits are frequent at the time of diagnosis. Elevation of the serum alkaline phosphatase may be observed. On CT imaging, osteosarcomas often demonstrate an osteoblastic appearance with regions of osteolysis, periosteal remodeling, and destruction of cortical bone. On the other hand, telangiectatic osteosarcomas are predominantly lytic lesions and may resemble aneurysmal bone cysts. On MR imaging, osteosarcomas are typically hypointense on T1-weighted images and hyperintense on T2-weighted images. Densely mineralized tumors are hypointense on all sequences. Tumor enhancement is evident following contrast administration.

Histologically, osteosarcomas may be classified in several subgroups depending on their appearance. Nevertheless, the vast majority is grouped as “conventional” tumors and characterized by anaplastic spindle-shaped cells with pleomorphic and hyperchromatic nuclei in addition to an extracellular matrix composed of immature bone (osteoblastic-type), cartilage (chondroblastic-type), or fibrous tissue (fibroblastic-type). Treatment options include surgical resection, radiation therapy, and chemoteraphy.

Giant Cell Tumor

Giant cell tumors (GCTs) of bone are rare and locally aggressive lesions that often occur in the epiphyses of long bones during the third and fifth decades of life. They arise from differentiated mesenchymal cells of the bone marrow through endochondral ossification and account for approximately 9% of all bone tumors. In the axial skeleton, GCTs affect predominantly the sacrum (up to 8% of cases) followed by the mobile spine (up to 2% of cases) and skull base, with predilection for the sphenoid and temporal bones (only 1% of cases).

Pain, with or without a palpable mass, is the most common presenting symptom. Pathological fractures may occur in spinal tumors. Since about 1% of all cases of GCTs will develop the so-called “benign lung metastasis,” metastatic workup is recommended. This event seems to be much more frequent, with a reported incidence of approximately 13%, in patients with spinal GCTs. Cases of sarcomatous transformation are also reported, usually following irradiation.

Neuroimaging studies reveal an expansile, osteolytic lesion with no evidence of mineralized matrix. Characteristically, sacral tumors involve both sides of the midline and commonly extend across the sacroiliac joints. Spinal tumors frequently involve the vertebral body, though extension into the posterior elements and paraspinal soft tissue is common. MR imaging demonstrates a low to isosignal intensity on T1-weighted images and a characteristic heterogenenous low to intermediate signal on T2-weighted images. These tumors display a variable pattern of enhancement following contrast injection and cystic changes may be also seen within the mass. A curvilinear area of low signal intensity on T1 and T2 images is also reported in spinal lesions, although this finding had been previously described in plasmacytoma and hemangioma.

Histologically, GCTs consist of osteoclast-like multinucleated giant cells intermixed throughout a spindle-shaped, fibroblast-like cell stroma, and round nuclear cells resembling monocytes. Reactive osteoid production may be seen after pathologic fracture. Occasionally, erythrocyst lakes (aneurysmal bone cyst-like changes), xanthomatous changes within collections of histiocytes, and areas of fibrous tissue are observed. Surgery, with the aim of complete tumor resection, is the treatment of choice. The role of radiotherapy for GCTs is still controversial.

Intraosseous Hemangioma

Intraosseous spinal hemangiomas are benign bone tumors usually found incidentally or in 10% of routine autopsies. Most lesions are located in the thoracic spine. Skull hemangiomas, on the other hand, account for less than 1% of all bone tumors. Skull base lesions are exceedingly rare and most commonly arise from the petrous bone. Their etiopathogenesis remains unknown. Histologically, these tumors are composed of thin-walled vascular channels of variable pattern (e.g., cavernous or capillary) lined by a single layer of mature endothelial cells interspersed among bony trabeculae and reactive spindle cell proliferation. The stroma between the osseous trabeculae may be rich in fat tissue.

Although the vast majority of spinal hemangiomas are clinically silent, some patients may present with a palpable mass, local pain, and neurological deficit. Hormone regulation and hemodynamic factors, such as those observed during pregnancy, are well-documented risk factors for symptomatic conversion. A small subset of symptomatic vertebral lesions displays locally aggressive behavior characterized by bone destruction, pathological fractures, extension to adjacent soft tissue, and disturbance of local blood flow. Proptosis and cranial neuropathies are reported in patients with skull base lesions. Primary clival hemangiomas may cause basilar invagination.

CT imaging reveals an expansile, osteolytic lesion with preservation of the cortex and marginal sclerosis. Imaging of vertebral lesions also shows the characteristic “polka dot” and “jail bar” appearances of the vertebral body on axial and sagittal/coronal images, respectively. On MR imaging, hemangionas are most commonly hypo- to isointense on T1-weighted images, heterogeneously hyperintense on T2-weighted images, and markedly enhanced by contrast. Tumors with a “fatty” stroma may present with a high-intensity signal on T1-weighted images. Treatment is only indicated for symptomatic lesions. Table 6.5 summarizes the main differences between osteosarcomas, GCTs, and hemangiomas.

Schwannoma

Trigeminal schwannomas are extra-axial, slow-growing, benign neoplasms that account for less than 0.5% of all intracranial tumors and up to 8% of all intracranial schwannomas. They may be associated with neurofibromatosis type-2 and schwannomatosis. Malignant transformation is uncommon. They occur most frequently in women during the fourth and fifth decade of life and may arise anywhere along the trigeminal nerve. Most patients complain of trigeminal nerve–related dysfunction, such as hemifacial hypesthesia, as the presenting symptom. Depending on tumor location, size, and growth pattern patients may develop signs of intracranial hypertension, dysfunction of multiple cranial nerves, and long tract signs (i.e., pyramidal and cerebellar signs). These tumors may erode the petrous apex, clivus, sella turca, and middle fossa floor and, therefore, be misdiagnosed as a skull base chondrosarcoma.

Sacral schwannomas are usually solitary lesions; they most commonly arise from the sheath of the sacral nerve roots and very rarely from within the bone as intraosseous tumors. Patients initially complain of lower back pain with or without radiculopathy. Motor weakness and sphyncteric disturbance (i.e., cauda equina syndrome) occur later in the course of the disease. These tumors may also compress the rectum and cause constipation.

Neuroimaging studies reveal a skull base tumor that is usually iso- to slightly hyperdense on CT images, and hypo- to isointense on T1-weighted and hyperintense on T2-weighted MR images. Strong, uniform enhancement is common following contrast injection. Intratumoral cysts may be present. A dumbbell-shaped tumor located within the trigeminal cave and enlargement of skull base foramina (i.e., foramina rotundum and ovale) is highly suggestive of trigeminal schwannoma. Sacral schwannomas may also present with significant bone erosion and should be differentiated from chordomas and other primary bone tumors. Lack of intratumoral calcification and absence of adjacent soft tissue and sacroiliac joint involvement are characteristic of schwannomas.

Histologically, schwannomas demonstrate a biphasic pattern with compact arrays of elongated, spindle-shaped cells organized in fascicles along with palisading nuclei (i.e., Verocay bodies) alternating with less cellular areas of myxoid or loose connective tissue. Nuclear pleomorphism, microcystic changes, rare mitotic figures, and necrosis may be identified. Schwannomas also stain diffusely positive for S-100 on immunohistochemical analysis. Treatment options include surgery and radiation therapy.

Pituitary Macroadenoma

Pituitary tumors account for approximately 15% of all intracranial neoplasms. Among these lesions, giant pituitary adenomas (GPAs) (diameter ≥ 4 cm) represent up to 14% of all adenomas in surgical series. GPAs can extend from the pituitary fossa inferiorly, cause significant bone destruction in the clival region, and occasionally be misdiagnosed as primary osseous tumors. Very rarely, ectopic pituitary adenomas may arise within the clivus.

Clinically, GPAs tend to present with visual impairment due to compression of the optic pathways (i.e., optic chiasm) and hypopituitarism. A thorough endocrinological history may reveal signs and symptoms of hormone hypersecretion (e.g., amenorrhea-galactorrhea, acromegaly and Cushing’s syndrome) strongly suggesting the presence of a pituitary adenoma. Therefore, proper endocrinological evaluation, with a full pituitary panel, is recommended especially for skull base tumors affecting simultaneously the clival region and the pituitary fossa.

Non-functioning adenomas, invasive prolactinomas and GH-secreting adenomas are the types most frequently associated with clival involvement.

Pituitary adenomas are usually hypointense to the normal pituitary gland on MR T1-weighted images, hyperintense on T2-weighted images and may present, not as vividly as the normal gland, a homogenous or heterogeneous contrast enhancement. Identification of the normal gland may not be possible in larger tumors and patients with hypopituitarism. CT imaging is less useful for diagnosis of pituitary adenomas but it may reveal, in greater detail, erosion of the sellar floor and sphenoid bone, including the clival region.

Histologically, pituitary adenomas are easily differentiated from cartilaginous and osseous tumors. They display loss of the normal acinar architecture of the pituitary gland and cellular monomorphism. Delicate septae of connective tissue, small perivascular spaces, multinuclear cells and pleomorphism may be seen. Increased mitotic figures, cellular atypia and anaplasia should raise concerns for more aggressive tumors (i.e., atypical and anaplastic adenoma) and metastatic disease. Pituitary adenomas are positive for synaptophysin and neuron-specific enolase and negative for glial fibrillary acidic protein (GFAP) and cytokeratin on immunohistochemical studies, which will also reveal the hormonal content of the adenoma cells (e.g., prolactin-secreting, ACTH-secreting, GH-secreting). Treatment modalities include surgical excision, medical therapy and radiation therapy.