bromochloroacetic-acid and Chordoma

Chordomas are uncommon, bone, axial, or (rarely) extra-axial tumors that are malignant and frequently recur but less commonly metastasize. They usually affect adults, with a very small proportion being pediatric tumors. For children, such tumors present a different biology, since they are more common as scull rather than sacral tumors, with aggressive histological features, including a loss of SMARCB1/INI1 and a dismal prognosis. Histologically, chordomas, believed to derive from notochordal tissue, characteristically show physaliphorous cells in a myxoid or chondroid matrix. Dedifferentiated and poorly differentiated forms can be observed. Moreover, a grading scale for chordomas has been proposed. Cytokeratin, EMA, S100, and brachyury are expressed by most chordomas. These are chemo-resistant tumors, for which surgical resection and/or radiotherapy are the treatments of choice. In this review, the histological, immunohistochemical, molecular, and clinical data of chordomas are discussed.

Topics: Chordoma; Fetal Proteins; Humans; Keratins; Neoplasm Recurrence, Local; Pathology, Molecular; Spinal Neoplasms; T-Box Domain Proteins

Benign notochordal tumors (BNCT) and chordomas are primary bone tumors of the spine with a predominant localization in the sacrum and clival region followed by the vertebral bodies. Besides the most common variant (NOS [not otherwise specified] with hepatoid or renal carcinoma cell-like differentiation) chordomas with chondroid, and polymorphic to anaplastic morphology are described. An unfavorable variant are pediatric chordomas with a loss of INI-1. BNCT and chordomas are characterized by the following immunohistological profile: vimentin+, cytokeratin+/-, epithelial membrane antigen (EMA)+/-, S100 protein+/-, brachyury+. This profile helps to distinguish these tumors from other lesions such as chondrosarcoma, chordoid meningioma, and metastases of carcinoma.

Topics: Bone Neoplasms; Child; Chondrosarcoma; Chordoma; Humans; Keratins; S100 Proteins

Topics: Cell Dedifferentiation; Chordoma; Diagnosis, Differential; Female; Fibrosarcoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Sacrococcygeal Region; Sarcoma; Spinal Neoplasms; Vimentin

Chordomas are relatively rare tumors that arise from the neuraxis. Most often, chordomas are single lesions that metastasize late. There have been very few cases of chordomas arising from multiple foci along the neuraxis. Here, we present a case of a multicentric chordoma.. The patient presented with pain in her right neck and soreness in her right shoulder that she had experienced for about 2.5 years that she attributed to a muscle strain. She experienced worsening of her symptoms, which prompted her to seek medical care. The patient underwent an occiput-to-C6 posterolateral fusion with autograft and an occiput-to-C6 posterior segmental instrumentation, along with decompression of the spinal cord. One month after the initial surgery, the patient underwent a second surgery. The C2 and C3 vertebral bodies were completely resected, and a C1-C4 anterior fusion was then carried out. A C5 vertebrectomy and C4-C6 fusion were also performed at this time. The patient then received proton beam radiation to the entire affected area.. Recent studies have suggested that chordomas arise from benign notochordal tumors. We suggest that our patient suffered from multicentric chordomas with possible benign notochordal tumors. Although benign notochordal tumors do not require surgical resection, the possibility of transformation to a malignant lesion requires close follow-up.

Topics: Adult; Cervical Vertebrae; Chordoma; Female; Fetal Proteins; Follow-Up Studies; Humans; Keratins; Magnetic Resonance Imaging; S100 Proteins; Spinal Neoplasms; T-Box Domain Proteins; Vimentin

Chordoid meningioma, World Health Organization grade II, is an uncommon variant of meningioma with a propensity for aggressive behavior and increased likelihood of recurrence. As such, recognition of this entity is important in cases that show similar morphologic overlap with other chondroid/myxoid neoplasms that can arise within or near the central nervous system. A formal comparison of the immunohistochemical features of chordoid meningioma versus tumors with significant histologic overlap has not been previously reported. In this study, immunohistochemical staining was performed with antibodies against D2-40, S100, pankeratin, epithelial membrane antigen (EMA), brachyury, and glial fibrillary acidic protein (GFAP) in 4 cases of chordoid glioma, 6 skeletal myxoid chondrosarcomas, 10 chordoid meningiomas, 16 extraskeletal myxoid chondrosarcoma, 18 chordomas, 22 low-grade chondrosarcomas, and 27 enchondromas. Staining extent and intensity were evaluated semiquantitatively and mean values for each parameter were calculated. Immunostaining with D2-40 showed positivity in 100% of skeletal myxoid chondrosarcomas, 96% of enchondromas, 95% of low-grade chondrosarcomas, 80% of chordoid meningiomas, and 75% of chordoid gliomas. Staining with S100 demonstrated diffuse, strong positivity in all (100%) chordoid gliomas, skeletal myxoid chondrosarcomas, low-grade chondrosarcomas, and enchondromas, 94% of chordomas, and 81% of extraskeletal myxoid chondrosarcomas, with focal, moderate staining in 40% of chordoid meningiomas. Pankeratin highlighted 100% of chordoid gliomas and chordomas, 38% of extraskeletal myxoid chondrosarcomas, and 20% of chordoid meningiomas. EMA staining was positive in 100% of chordoid gliomas, 94% of chordomas, 90% of chordoid meningiomas, and 25% of extraskeletal myxoid chondrosarcomas. Brachyury was positive only in the chordomas (100%), whereas GFAP was positive only in the chordoid gliomas (100%). EMA was the most effective antibody for differentiating chordoid meningioma from skeletal myxoid chondrosarcoma, low-grade chondrosarcoma, and enchondroma, whereas D2-40 was the most effective antibody for differentiating chordoid meningioma from extraskeletal myxoid chondrosarcoma and chordoma. Our findings demonstrate that in conjunction with clinical and radiographic findings, immunohistochemical evaluation with a panel of D2-40, EMA, brachyury, and GFAP is most useful in distinguishing chordoid meningioma from chordoid glioma, skeletal myxoid

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Biomarkers, Tumor; Child; Chondroma; Chondrosarcoma; Chordoma; Diagnosis, Differential; Female; Fetal Proteins; Glial Fibrillary Acidic Protein; Glioma; Humans; Immunohistochemistry; Keratins; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Mucin-1; Predictive Value of Tests; S100 Proteins; T-Box Domain Proteins; Young Adult

Case report.. We present a giant cervical chordoma without typical vertebral bony destruction in an 11-year-old girl.. Chordomas are rare malignant bone tumors that arise at both the cranial and the caudal ends of the axial skeleton, characteristically destroying the bone. Cervical chordomas comprise only 3% to 7% of all chordomas. To our knowledge, there is no case of cervical chordoma in a child, presenting without vertebral body involvement, in English literature.. Discussion on the patient's clinical, radiologic history, and histopathologic diagnosis of the resected tumor, with a review of the relevant background literature.. We report the first case of cervical chordoma in a child without typical vertebral bony destruction, the diagnosis of which was difficult to confirm before and after operation.. Giant notochordal rest and benign notochordal cell tumors (BNCTs) need to be recognized for differential diagnosis of this atypical chordoma. A long-term follow-up might be necessary for the diagnosis of this nontypical patient.

Topics: Cervical Vertebrae; Child; Chordoma; Female; Humans; Keratins; Radiography; S100 Proteins; Spinal Neoplasms; Treatment Outcome

The authors describe an unusual case of an intradural cerebellar chordoma, the first such case to be reported in a child. A 9-year-old girl presented with headaches and papilloedema, and a discrete cerebellar mass was resected, which was shown histologically to be chordoma. There was no bony or dural association, and after radiologically proven complete resection it was elected that the child be followed expectantly.. The case is compared with the few previously reported intradural chordomas, and insights into the origins and management of such cases are discussed.

Topics: Cerebellar Neoplasms; Child; Chordoma; Female; Headache; Humans; Keratins; Magnetic Resonance Imaging; S100 Proteins; Subarachnoid Space

Parachordomas are rare cutaneous tumors that show virtually identical histologic findings to chordomas. Therefore, the major differential diagnosis in a case of parchordoma is metastatic chordoma. Parachordomas are benign neoplasms and most often develop on the extremities adjacent to tendons, synovium or osseous structures, as opposed to chordomas, which are malignant tumors located along the craniospinal axis. While recurrences may occur in cases of parachordoma, metastases have not been reported. In this report, two cases of parachordomas are reported and the literature reviewed. By light microscopy, parachordomas show eosinophilic bands of fibrous tissue separating lobules of cells with variably vacuolated cytoplasm (physaliphorous cells) admixed with more epithelioid cells in a myxoid stroma. Parachordomas and chordomas share immunohistochemical and ultrastructural features. Both stain with S-100 protein and vimentin, and ultrastructurally both demonstrate cytoplasmic vacuoles, intermediate filaments, pinocytotic vesicles, celljunctions, and cytoplasmic membranes with microvillous processes. Chordomas more frequently express cytokeratin (98% vs. 66% in parachordomas) and epithelial membrane antigen (90% vs. 20% in parachordomas) and chordomas have a larger number of rough endoplasmic reticulum-mitochondrial complexes. Thus, positive staining with epithelial membrane antigen and the identification of a large number of rough endoplasmic reticulum-mitochondrial complexes are suggestive of metastatic chordoma. However, the definitive distinction remains a clinical one after appropriate radiologic studies of the skull and spinal chord.

Topics: Adolescent; Adult; Chordoma; Extremities; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Skin Neoplasms; Vimentin

Malignant fibrous histiocytoma (MFH), arising in combination with a sacral chordoma in a 70-year-old men, is described. Intermediate spindle-shaped cells demonstrating keratin positivity, showed a gradual transition between the areas of conventional chordoma, and the spindle cell areas, lending credence to the theory of a multipotential neoplasm. We chose the descriptive term "chordoma with malignant spindle cell component" in the sense that high malignant sarcomatous components exists in conjunction with chordomas in the primary tumor and the local recurrence. A review of literature is undertaken chronicling the documented associations of chordoma and sarcoma, followed by a discussion of the various causes proposed to explain this phenomenon.

Topics: Aged; Biomarkers, Tumor; Cell Division; Cell Transformation, Neoplastic; Chordoma; Coccyx; Diagnosis, Differential; Histiocytoma, Benign Fibrous; Humans; Keratins; Male; Neoplasms, Multiple Primary; Sacrum; Spinal Neoplasms

"Chondroid chordoma" is a controversial and confusing entity that was originally described by Heffelfinger and colleagues as a biphasic malignant neoplasm possessing elements of both chordoma and cartilaginous tissue. Because the premise for this distinction was based strictly on histomorphologic criteria, the light microscopic, immunohistochemical, and electron microscopic features of the chondroid and chordoid areas of five chondroid chordomas of the skull base were evaluated separately, and compared to five typical chordomas and six low grade chondrosarcomas. Using light microscopy, chondroid chordoma revealed areas that resembled typical chordoma (chordoid areas) and areas that resembled low grade chondrosarcoma (chondroid areas). However, both the chordoid and chondroid areas had an epithelial phenotype and stained strongly for cytokeratin and EMA as well as S-100. 5'-nucleotidase, an enzyme that has been described in chordoma but not in chondrosarcoma, was found in both the chordoid and chondroid areas of one chondroid chordoma. Electron microscopic studies of both the chordoid and chondroid areas in four of the tumors demonstrated both tonofibrils and desmosomes. Chordoma demonstrated immunohistochemical and electron microscopic features that were nearly identical to chondroid chordoma. Chordoma was cytokeratin, EMA, S-100, and 5'-nucleotidase positive. Ultrastructurally, chordoma exhibited variably-sized vacuoles, abundant rough endoplasmic reticulum (RER), and desmosomes with tonofilaments. In contrast to chondroid chordoma, chondrosarcoma consistently stained for only S-100 protein and was cytokeratin, EMA and 5'-nucleotidase negative. Ultrastructurally, chondrosarcoma demonstrated a flocculogranular matrix, glycogen, abundant RER, and scalloped cellular outlines, but lacked desmosomes with tonofilaments. These findings indicate that "chondroid chordoma" is a variant of chordoma with histologic features that may mimic chondrosarcoma. Despite the resemblance of these hyalinized areas to cartilaginous tissue, these tumors retain their epithelial phenotype. Biphasic differentiation is not present. These findings undermine the original premise for distinguishing "chondroid chordoma" from typical chordoma. The authors propose that these tumors be classified as "hyalinized chordomas," rather than "chondroid chordoma," to clarify their histogenesis and avoid confusion with chondrosarcomas of the base of the skull.

Topics: Adult; Child; Chondrosarcoma; Chordoma; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Mucins; S100 Proteins; Skull Neoplasms

We report a case of parachordoma occurring in the buttock of a 43-year-old man, and review 20 cases of parachordoma reported in the English literature. The tumor in our case was grossly 3 cm in dimension, solid, lobulated and grayish-white in color. Microscopically, the tumor consisted of epithelioid and spindle cells, and fibromyxoid stroma. The epithelioid cells were immunohistochemically positive for vimentin, S-100 protein, neuron-specific enolase, keratin, carcinoembryonic antigen and epithelial membrane antigen, and negative for HMB45. These findings are similar to those for chordoma rather than extraskeletal myxoid chrondrosarcoma. Although the etiopathogenesis of parachordoma remains obscure, Schwann cells or some other neuron-related cell origin are suspected.

Topics: Adult; Buttocks; Carcinoembryonic Antigen; Chondrosarcoma; Chordoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; S100 Proteins; Soft Tissue Neoplasms

Topics: Brain Neoplasms; Chondroma; Chondrosarcoma; Chordoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Mucin-1; S100 Proteins

Chordomas are slow-growing tumors derived from notochord remnants. Despite margin-negative excision and postoperative radiation therapy, spinal chordomas (SCs) often progress. The potential of immunohistochemical (IHC) markers, such as epithelial membrane antigen (EMA), combined with machine learning algorithms to predict long-term (≥ 12 months) postoperative tumor progression, has been understudied. The authors aimed to identify IHC markers using trained tree-based algorithms to predict long-term (≥ 12 months) postoperative tumor progression.. The authors reviewed the records of patients who underwent resection of SCs between January 2017 and June 2021 across the Mayo Clinic enterprise. Demographics, type of treatment, histopathology, and other relevant clinical factors were abstracted from each patient's record. Low tumor progression was defined as more than a 94.3-mm3 decrease in the tumor size at the latest radiographic follow-up. Decision trees and random forest classifiers were trained and tested to predict the long-term volumetric progression after an 80/20 data split.. Sixty-two patients diagnosed with and surgically treated for SC were identified, of whom 31 were found to have a more advanced tumor progression based on the tumor volume change cutoff of 94.3 mm3. The mean age was 54.3 ± 13.8 years, and most patients were male (62.9%) and White (98.4%). The most common treatment modality was subtotal resection with radiation therapy (35.5%), with proton beam therapy being the most common (71%). Most SCs were sacrococcygeal (41.9%), followed by cervical (32.3%). EMA-positive SCs had a postoperative progression risk of 67%. Pancytokeratin-positive SCs had a progression rate of 67%; however, patients with S100 protein-positive SCs had a 54% risk of progression. The accuracy of this model in predicting the progression of unseen test data was 66%. Pancytokeratin (mean minimal depth = 1.57), EMA (mean minimal depth = 1.58), cytokeratin A1/A3 (mean minimal depth = 1.59), and S100 protein (mean minimal depth = 1.6) predicted the long-term volumetric progression. Multiway variable importance plots show the relative importance of the top 10 variables based on three measures of varying significance and their predictive role.. These IHC variables with tree-based machine learning tools successfully demonstrate a high capacity to identify a patient's tumor progression pattern with an accuracy of 66%. Pancytokeratin, EMA, cytokeratin A1/A3, and S100 protein were the IHC drivers of a low tumor progression. This shows the power of machine learning algorithms in analyzing and predicting outcomes of rare conditions in a small sample size.

Topics: Adult; Aged; Chordoma; Humans; Keratins; Middle Aged; Neoplasm Recurrence, Local; S100 Proteins; Spinal Neoplasms

Assess the significance of chordoma as a neurosurgical pathology, taking into account the latest edition of the WHO classification of soft tissues and bone tumors (2020).. An analysis of 28 chordomas was carried out. All chordomas were histologically verified, including using immunohistochemical markers of notochordal differentiation (S100, EMA, keratin, brachiuria protein).. Patients with chordomas accounted for 0.25% of the total number of neurosurgical patients. The vast majority (27) of chordomas had a cranio-vertebral localization. Sacral localization (S. Chordoma, due to its axial localization, naturally involves adjacent structures of the nervous system, has clinically significant neuropathological manifestations, and often provides direct indications for a special neurosurgical approach. This requires its consideration not only as a bone, but also as a neurosurgical oncological pathology, along with other non-meningothelial (mesenchymal) tumors of the CNS.. Оценить значение хордомы как нейрохирургической патологии с учетом последней редакции классификации ВОЗ опухолей мягких тканей и костей (2020 г.).. Проведен анализ 28 хордом у больных, прооперированных в РНХИ им. проф. А.Л. Поленова. Все хордомы верифицированы гистологически, в том числе с использованием иммуногистохимических маркеров нотохордальной дифференцировки (S100, EMA, кератина, белка брахиурии).. Пациенты с хордомами составили 0,25% от общего числа нейрохирургических пациентов. Подавляющее большинство (27) хордом имели кранио-вертебральную локализацию. Сакральная локализация (S. Хордома в силу своей осевой локализации закономерно вовлекает прилежащие структуры нервной системы, имеет клинически значимые нейропатологические проявления и часто предъявляет прямые показания для специального нейрохирургического пособия. Это требует ее рассмотрения не только как костной, но и нейрохирургической онкологической патологии, наряду с другими неменинготелиальными (мезенхимальными) опухолями ЦНС.

Topics: Chordoma; Humans; Keratins; Spinal Neoplasms

The Perdido Key beach mouse (Peromyscus polionotus trissyllepsis) is a critically endangered subspecies of the oldfield mouse. The captive population, currently maintained by 3 Florida zoos, is entirely derived from just 3 wild-caught ancestor mice. Necropsy and histopathology revealed chordoma of the vertebral column in 38 of 88 (43%) mice. The tumors were locally expansile and invasive masses of large physaliferous (vacuolated) cells with small, round, hyperchromatic nuclei, similar to the "classic" form of chordomas described in humans. Primary tumors rarely contained small amounts of bone and cartilaginous matrix, characteristic of the "chondroid" form. Neoplastic cells contained abundant granules positive by the periodic acid-Schiff reaction. Brachyury and cytokeratin AE1/AE3 were detected in neoplastic cells by immunohistochemistry, but uncoupling protein 1 was not identified. Primary tumors occurred along the entire vertebral column--cervical, 5 of 38 (13%); thoracic, 16 (42%); lumbar, 13 (34%); and sacral, 10 (26%)--and 10 (26%) mice had multiple primary masses. Metastases to the lungs were noted in 13 of the 38 (34%) mice. Mice diagnosed with chordomas postmortem ranged from 424 to 2170 days old, with a mean of 1399 days. The prevalence of chordoma was not significantly different between males (n = 23 of 50; 46%) and females (n = 15 of 38; 39%).

Topics: Animals; Chordoma; Endangered Species; Female; Fetal Proteins; Immunohistochemistry; Keratins; Male; Mice; Peromyscus; Prevalence; Spine; T-Box Domain Proteins

Chordomas are rare malignant tumors that develop from embryonic remnants of the notochord and arise only in the midline from the clivus to the sacrum. Surgery followed by radiotherapy is the standard treatment. As chordomas are resistant to standard chemotherapy, further treatment options are urgently needed. We describe the establishment of a clivus chordoma cell line, MUG-CC1. The cell line is characterized according to its morphology, immunohistochemistry, and growth kinetics. During establishment, cell culture supernatants were collected, and the growth factors HGF, SDF-1, FGF2, and PDGF analyzed using xMAP(®) technology. A spontaneous lymphoblastoid EBV-positive cell line was also developed and characterized. MUG-CC1 is strongly positive for brachyury, cytokeratin, and S100. The cell line showed gains of the entire chromosomes 7, 8, 12, 13, 16, 18, and 20, and high level gains on chromosomes 1q21-1q24 and 17q21-17q25. During cultivation, there was significant expression of HGF and SDF-1 compared to continuous chordoma cell lines. A new, well-characterized clival chordoma cell line, as well as a non-tumorigenic lymphoblastoid cell line should serve as an in vitro model for the development of potential new treatment strategies for patients suffering from this disease.

Topics: Aged; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Chordoma; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 17; Fetal Proteins; Humans; Intercellular Signaling Peptides and Proteins; Keratins; Lymphocytes; Male; S100 Proteins; Skull Base Neoplasms; T-Box Domain Proteins

Chordoma cells can generate solid-like tumors in xenograft models that express some molecular characteristics of the parent tumor, including positivity for brachyury and cytokeratins. However, there is a dearth of molecular markers that relate to chordoma tumor growth, as well as the cell lines needed to advance treatment. The objective in this study was to isolate a novel primary chordoma cell source and analyze the characteristics of tumor growth in a mouse xenograft model for comparison with the established U-CH1 and U-CH2b cell lines.. Primary cells from a sacral chordoma, called "DVC-4," were cultured alongside U-CH1 and U-CH2b cells for more than 20 passages and characterized for expression of CD24 and brachyury. While brachyury is believed essential for driving tumor formation, CD24 is associated with healthy nucleus pulposus cells. Each cell type was subcutaneously implanted in NOD/SCID/IL2Rγ(null) mice. The percentage of solid tumors formed, time to maximum tumor size, and immunostaining scores for CD24 and brachyury (intensity scores of 0-3, heterogeneity scores of 0-1) were reported and evaluated to test differences across groups.. The DVC-4 cells retained chordoma-like morphology in culture and exhibited CD24 and brachyury expression profiles in vitro that were similar to those for U-CH1 and U-CH2b. Both U-CH1 and DVC-4 cells grew tumors at rates that were faster than those for U-CH2b cells. Gross tumor developed at nearly every site (95%) injected with U-CH1 and at most sites (75%) injected with DVC-4. In contrast, U-CH2b cells produced grossly visible tumors in less than 50% of injected sites. Brachyury staining was similar among tumors derived from all 3 cell types and was intensely positive (scores of 2-3) in a majority of tissue sections. In contrast, differences in the pattern and intensity of staining for CD24 were noted among the 3 types of cell-derived tumors (p < 0.05, chi-square test), with evidence of intense and uniform staining in a majority of U-CH1 tumor sections (score of 3) and more than half of the DVC-4 tumor sections (scores of 2-3). In contrast, a majority of sections from U-CH2b cells stained modestly for CD24 (scores of 1-2) with a predominantly heterogeneous staining pattern.. This is the first report on xenografts generated from U-CH2b cells in which a low tumorigenicity was discovered despite evidence of chordoma-like characteristics in vitro. For tumors derived from a primary chordoma cell and U-CH1 cell line, similarly intense staining for CD24 was observed, which may correspond to their similar potential to grow tumors. In contrast, U-CH2b tumors stained less intensely for CD24. These results emphasize that many markers, including CD24, may be useful in distinguishing among chordoma cell types and their tumorigenicity in vivo.

Topics: Aged; Animals; Biomarkers, Tumor; CD24 Antigen; Cell Line, Tumor; Chordoma; Disease Models, Animal; Fetal Proteins; Flow Cytometry; Heterografts; Humans; Immunohistochemistry; Keratins; Male; Mice; Polymerase Chain Reaction; Sacrum; T-Box Domain Proteins; Tumor Cells, Cultured

Spinal chordomas are more often located on the midline and are associated with marked destruction of the vertebral bodies. We report a rare case of large cervical (C2-C3) right lateral paravertebral chordoma extending into the spinal canal through a very enlarged intervertebral foramen. The tumor was initially diagnosed as a mucous adenocarcinoma on a percutaneous needle biopsy. However, the neuroradiological features, including the well-defined tumor margins, the regular and sclerosing lytic bone changes with regular enlargement of the intervertebral C2-C3 foramen, were in favor of a more slowly growing lesion, such as schwannoma or neurofibroma. At surgery a well-demarcated capsulated tumor involving the nerve root was partially resected. Histology was in favor of a low-grade chordoma (Ki-67/MIB-1<1%). Postoperative proton beam therapy was also performed. The differential neuroradiological diagnosis is discussed.

Topics: Adenocarcinoma; Aged; Cervical Vertebrae; Chordoma; Cone-Beam Computed Tomography; Female; Humans; Keratins; Magnetic Resonance Imaging; Spinal Neoplasms

Chordomas are midline tumors that arise from embryonic remnants of the notochord and are considered to be malignant tumors because of their tendency to invade and destroy the involved bone. Cases of intradural chordomas without bone involvement have been rarely described with a predilection for prepontine location. The absence of bony invasion renders the complete excision of these tumors more feasible and is related to their better prognosis in comparison to conventional chordomas. Herein we report the first intradural chordoma arising in the Meckel's cave. The intradural location of the lesion, outside midline structures, in the absence of bone infiltration, made the differential diagnosis versus other meningeal lesions such as chordoid meningioma challenging. The intense and strong immunohistochemical expression of pan-cytokeratins, S100, cytokeratin-19 and of the notochordal marker brachyury allowed differential diagnosis toward other tumors showing chordoid morphology. The expression of brachyury, which had not been previously analyzed in intradural chordoma, definitely links the histogenesis of this neoplasia to the notochord, similar to that of conventional chordoma. We also show that, different from conventional chordoma, intradural chordoma does not express the metallo-proteinases (MMPs) -2 and -9, which may account for its indolent biological behavior.

Topics: Aged; Antigens, CD; Biomarkers, Tumor; Capillaries; Chordoma; Diagnosis, Differential; Endoglin; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Ki-67 Antigen; Magnetic Resonance Imaging; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neovascularization, Pathologic; Paraffin Embedding; Receptors, Cell Surface; Skull Base Neoplasms; Tissue Fixation; Trigeminal Ganglion

Chordomas constitute about 1% of intracranial tumors. They are generally extradural destroying the bone. Intradural chordomas are very rare. We present one such case of a clival intradural chordoma who presented with a left trigeminal nerve sensory neuropathy. The lesion was totally excised uneventfully via a retromastoid suboccipital approach. There was no recurrence of the lesion at 1-year follow-up. Characteristics of intradural chordoma and its close differential ecchordosis physaliphora are reviewed in this article.

Topics: Adult; Brain Stem Neoplasms; Chordoma; Dura Mater; Humans; Keratins; Ki-67 Antigen; Magnetic Resonance Imaging; Male; S100 Proteins; Tomography Scanners, X-Ray Computed

An experimental study to investigate the characterization of 3 chordoma cell lines.. To characterize chordoma cell lines and generate hypothesis for further chordoma studies.. Three cultured human chordoma cell lines have been successfully generated; however, their characterization is incomplete. Complete characterization of chordoma cell lines is necessary for these reagents to be a useful preclinical model.. Three chordoma cell lines, CH 8, U-CH1, and GP 60, were cultured in different commercially available tissue culture media. They were also cultured in different environments, which included collagen substrate, various concentrations of glucose, and various levels of hypoxic conditions. The rate of cell proliferation was assessed by either MTT or numeration assay. A 3-dimensional (3D) cell culture model of these chordoma cell lines was also studied, and the expression of vimentin and cytokeratin was measured by immunofluorescence and Western blot. Additionally, the sensitivity of the 3 chordoma cell lines to 6 chemotherapeutic drugs was analyzed.. CH 8, GP 60, and U-CH1 cells proliferate more actively in Iscove Modified Dulbecco Medium or Dulbecco modified Eagle Medium and less actively in RPMI medium. All 3 chordoma cell lines universally grow better in collagen substrate and survive in hypoxic conditions, whereas glucose concentration has no significant influence on their growth properties. Chordoma cell lines grew well in 3D culture systems and formed acini-like spheroids and retained the expression of vimentin and cytokeratin. MTT analysis indicates that all 3 chordoma cell lines are sensitive to doxorubicin, yondelis, zalypsis, and cisplatin.. We characterized 3 chordoma cell lines for differential growth properties in a variety of media and response to chemotherapeutic agents.

Topics: Antineoplastic Agents; Biomarkers, Tumor; Blotting, Western; Cell Culture Techniques; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Chordoma; Cisplatin; Collagen; Dioxoles; Doxorubicin; Drug Screening Assays, Antitumor; Fluorescent Antibody Technique; Glucose; Humans; Keratins; Tetrahydroisoquinolines; Trabectedin; Vimentin

Topics: Antibodies, Monoclonal; Biomarkers; Chordoma; Humans; Immunohistochemistry; Keratins; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Molecular Weight; Proto-Oncogene Proteins c-met; Spinal Cord Neoplasms

In skull base chordoma, c-MET expression has been reported to correlate with younger patient age and favourable prognosis; however, it also contributes to tumour invasiveness, especially in recurrent lesions, suggesting variable roles for c-MET according to clinical status. The aim of this study was to investigate the significance of c-MET expression in spinal chordoma, which affects patients who are 10-20 years older than those with skull base chordoma.. Using immunohistochemical techniques, the expression of c-MET and its ligand, hepatocyte growth factor (HGF) was investigated in 34 primary spinal chordomas and compared with other clinicopathological parameters. Expression of c-MET and HGF was observed in 85.3 and 21.7% of lesions, respectively. c-MET expression correlated with the expression of an epithelial marker, low-molecular-weight cytokeratin (CAM5.2). Lesions with higher c-MET expression showed significantly stronger expression of proteinases, including matrix metalloproteinase (MMP)-1 and MMP-2. However, c-MET expression was not associated with patient age, proliferative ability estimated by MIB-1 labelling index, or prognosis.. c-MET expression was observed in most spinal chordomas and correlated with the expression of CAM5.2, suggesting a relationship to an epithelial phenotype.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Biomarkers, Tumor; Chordoma; Female; Hepatocyte Growth Factor; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Middle Aged; Prognosis; Proto-Oncogene Proteins c-met; Spinal Cord Neoplasms

Chordoma originates from embryonic notochordal remnants in the midline along the spinal axis and is characterized by cords and lobules of neoplastic cells arranged within myxoid matrix. Because of histologic similarities with myxoid matrix and overlapping immunohistochemical profile, chondrosarcoma, myxopapillary ependymoma, and chordoid meningioma enter in the histologic differential diagnosis at this site. Therefore, the judicious use of a panel of selected immunostains is unquestionably helpful in diagnostically challenging cases. To find useful immunohistochemical markers for assisting in differential diagnosis between chordoma and other tumors with chordoid morphology, an immunohistochemical study using D2-40, epithelial membrane antigen (EMA), pan-cytokeratin (panCK), glial fibrillary acidic protein (GFAP), S-100 protein, galectin-3, neural cell adhesion molecule (NCAM), beta-catenin, E-cadherin, and carcinoembryonic antigen was performed on 14 chordomas, 7 chondrosarcomas, 9 myxopapillary ependymomas, and 4 chordoid meningiomas. Chordoma typically showed positive for EMA and panCK and negative for D2-40 and GFAP; whereas chondrosarcoma revealed positive for D2-40, and negative for EMA, panCK, and GFAP; myxopapillary ependymoma positive for GFAP and negative for EMA; and chordoid meningioma positive for EMA, and negative for panCK and GFAP. On the basis of our immunohistochemical study, a panel of D2-40, EMA, panCK, and GFAP allowed the correct recognition of all tumors examined. Other immunohistochemical markers including S-100 protein, galectin-3, NCAM, beta-catenin, E-cadherin, and carcinoembryonic antigen were of little value in differential diagnosis. In summary, the best immunohistochemical markers useful for the evaluation of tumors with chordoid morphology were D2-40, EMA, cytokeratin, and GFAP. D2-40 was a true chondroid marker to be useful for the differential diagnosis with chordoma.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Biomarkers, Tumor; Chondrosarcoma; Chordoma; Diagnosis, Differential; Ependymoma; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Meningioma; Mucin-1

Topics: Chordoma; Disease Progression; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Mucin-1; Neoplasm Seeding; S100 Proteins; Sacrococcygeal Region; Spinal Cord Neoplasms

The distinction between chondrosarcoma and chordoma of the skull base/head and neck is prognostically important; however, both have sufficient morphologic overlap to make delineation difficult. As a result of gene expression studies, additional candidate markers have been proposed to help in separating those entities. We sought to evaluate the performance of new markers: brachyury, SOX-9, and podoplanin alongside the more traditional markers glial fibrillary acid protein, carcinoembryonic antigen, CD24, and epithelial membrane antigen. Paraffin blocks from 103 skull base/head and neck chondroid tumors from 70 patients were retrieved (1969-2007). Diagnoses were made based on morphology and/or whole-section immunohistochemistry for cytokeratin and S100 protein yielding 79 chordomas (comprising 45 chondroid chordomas and 34 conventional chordomas), and 24 chondrosarcomas. A tissue microarray containing 0.6 mm cores of each tumor in triplicate was constructed using a manual array (MTA-1; Beecher Instruments). For visualization of staining, the ImmPRESS detection system (Vector Laboratories) with 2-diaminobenzidine substrate was used. Sensitivities and specificities were calculated for each marker. Core loss from the microarray ranged from 25 to 29% yielding 66-78 viable cases per stain. The classic marker, cytokeratin, still has the best performance characteristics. When combined with brachyury, accuracy improves slightly (sensitivity and specificity for detection of chordoma 98 and 100%, respectively). Positivity for both epithelial membrane antigen and AE1/AE3 had a sensitivity of 90% and a specificity of 100% for detecting chordoma in this study. SOX-9 is apparently common to both notochordal and cartilaginous differentiation, and is not useful in the chordoma-chondrosarcoma differential diagnosis. Glial fibrillary acid protein, carcinoembryonic antigen, CD24, and epithelial membrane antigen did not outperform other markers, and are less useful in the diagnosis of chordoma vs chondrosarcoma. Podoplanin still remains the only positive marker for chondrosarcoma, though its accuracy is less than previously reported.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; CD24 Antigen; Child; Child, Preschool; Chondrosarcoma; Chordoma; Diagnosis, Differential; Fetal Proteins; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Membrane Glycoproteins; Middle Aged; Sensitivity and Specificity; Skull Base Neoplasms; SOX9 Transcription Factor; T-Box Domain Proteins; Tissue Array Analysis

Little is known about proteinase expression in skull base chordoma, a rare bone tumor exhibiting local invasiveness. Using immunohistochemical techniques, we investigated the expression of matrix metalloproteinases (MMPs)-1, -2, and -9; tissue inhibitors of matrix metalloproteinases (TIMPs)-1 and -2; cathepsin B (CatB); urokinase plasminogen activator (uPA); and plasminogen activator inhibitor, type I (PAI1), in 45 patients with skull base chordoma (45 primary and 25 autologous recurrent lesions). We compared these data with clinicopathologic parameters and the expression of cell differentiation markers. MMP-1, MMP-2, TIMP-1, CatB, uPA, and PAI1 were frequently expressed, and there was a significant correlation in the expression of some proteinases. Immunoreactivity for MMP-1, MMP-2, CatB, and uPA was significantly higher in lesions exhibiting tumor infiltration of host bone than in those without such components. Expression of MMP-1, TIMP-1, CatB, and uPA was associated with that of low-molecular-weight cytokeratin (CAM5.2). There were no differences in proteinase expression in 25 pairs of primary and their recurrent lesions, and proteinase expression did not predict local recurrences. However, patients with higher expression of both MMP-1 and uPA showed worse prognosis compared with the others. In conclusion, expression of some proteinases correlated with CAM5.2 expression and seemed to play an important role in a synergistic manner in the invasion process in skull base chordoma. The authors believe that elevated expression of MMP-1 and uPA can be used to identify patients with a worse prognosis in skull base chordoma.

Topics: Adolescent; Adult; Aged; Biomarkers; Biomarkers, Tumor; Cathepsin B; Child; Chordoma; Female; Fluorescent Antibody Technique, Direct; Humans; Immunoenzyme Techniques; Keratins; Male; Matrix Metalloproteinases; Middle Aged; Neoplasm Proteins; Neoplasm Recurrence, Local; Plasminogen Activator Inhibitor 1; Prognosis; Skull Base Neoplasms; Survival Rate; Tissue Inhibitor of Metalloproteinases; Urokinase-Type Plasminogen Activator

Mature cystic teratoma of the ovary (MCTO) is the most common type of ovarian teratoma and also the most frequent tumor originating from germ cells. It is usually diagnosed in early adulthood and, by definition, is composed of well-differentiated tissues, which originate from all three germ cell layers. Unusual types of tissues can be found in MCTO, such as kidney, adrenal, and prostatic tissues. Malignant transformation is reported in less than 2% of teratomas. Squamous cell carcinoma is the most common malignancy arising in these otherwise benign tumors. We present the first case of MCTO containing a chordoma. The chordoma differentiation was supported by immunohistochemical staining and interphase fluorescence in situ hybridization (IP-FISH) technique showing 19% of the nuclei of the MCTO displaying polysomy for the chromosome X, while 28% of the chordoma nuclei showed chromosome 7 mosaicism. These results are concordant with previous studies, showing chromosomal anomalies in chromosomes X and 7 in MCTO and chordomas, respectively.

Topics: Adult; Cell Differentiation; Cell Transformation, Neoplastic; Chordoma; Chromosomes, Human, Pair 7; Chromosomes, Human, X; Diagnosis, Differential; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Ki-67 Antigen; Mosaicism; Mucin-1; Ovarian Neoplasms; S100 Proteins; Teratoma; Tumor Suppressor Protein p53; Vimentin

Chordomas are malignant tumours that occur along the spine and are thought to derive from notochordal remnants. There is significant morphological variability between and within chordomas, with some showing prominent areas of chondroid differentiation. Our microarray data from a broad range of connective tissue neoplasms indicate that, at the transcriptional level, chordomas resemble cartilaginous neoplasms. Here we show that chordomas express many genes known to be involved in cartilage development, but they also uniquely express genes distinguishing them from chondroid neoplasms. The brachyury transcription factor, known to be involved in notochordal development, is only expressed by chordomas. Using a polyclonal antibody, we show that brachyury is expressed in the embryonic notochord and in all 53 chordomas analysed, labelling both chondroid and chordoid areas of these tumours. In contrast, the protein was not detected in over 300 neoplasms, including 163 chondroid tumours. Brachyury was not detected in the nucleus pulposus, arguing against the hypothesis that this tissue derives directly from the notochord. These data provide compelling evidence that chordomas derive from notochord and demonstrate that brachyury is a specific marker for the notochord and notochord-derived tumours.

Topics: Biomarkers, Tumor; Cartilage Diseases; Chondrosarcoma; Chordoma; Fetal Proteins; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Notochord; Reverse Transcriptase Polymerase Chain Reaction; Spinal Neoplasms; T-Box Domain Proteins; Tissue Distribution

Extraskeletal chordoma arising within soft tissue is a rare occurrence. We report a case of chordoma that is unusual both for its location within the subcutaneous soft tissue of the sacrococcygeal region without involvement of adjacent bones and for the presence of eosinophilic roundish inclusion bodies within the cytoplasm of tumor cells. These bodies revealed immunoreactivity for cytokeratin and a fibrillar, partly whorled structure on the electron microscopic examination, consistent with an intermediate filament-based composition. To our knowledge, this is the first report of chordoma featuring this cellular change although we do not know the significance of these bodies.

Topics: Biomarkers, Tumor; Chordoma; Humans; Immunohistochemistry; Inclusion Bodies; Intermediate Filaments; Keratins; Male; Middle Aged; Sacrococcygeal Region; Soft Tissue Neoplasms; Treatment Outcome

Intraosseous benign notochordal cell tumors are recently recognized conditions that may undergo malignant transformation to classic chordomas. This study attempts to define the morphologic and immunohistochemical characteristics of 34 benign notochordal cell tumors by contrasting them with classic chordomas and the notochordal vestiges in fetal intervertebral discs. Benign notochordal cell tumors were characterized by well-demarcated though unencapsulated sheets of adipocyte-like vacuolated and less vacuolated eosinophilic cells within axial bones. The round nuclei were mildly polymorphic but bland. The tumor cells often contained cytoplasmic eosinophilic hyaline globules and lack any intercellular myxoid matrix or necrosis. The involved bone trabeculae were often sclerotic without evidence of bone destruction. The histologic features were different from those of both notochordal vestiges in fetal intervertebral discs and classic chordomas. There was overlap in immunohistochemical reactivity of benign notochordal cell tumors and chordomas, but notochordal vestiges failed to demonstrate cytokeratin 18 positivity. A more appropriate term for the lesions is "benign notochordal cell tumor" rather than "notochordal rest" or "notochordal hamartoma" as they are not rests and do not fulfill the definition of hamartoma. Benign notochordal cell tumors do not need any surgical procedure and must be adequately recognized to prevent unnecessary operations.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Chordoma; Female; Humans; Immunohistochemistry; Intervertebral Disc; Keratins; Male; Middle Aged; Notochord

We analyzed the expression of proteases and the clinicopathologic significance in non-skull base chordoma (NSBC). By using immunohistochemical techniques, we studied the expression of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, cathepsin B (CatB), and urokinase plasminogen activator (uPA) in 29 NSBCs and compared these data with clinicopathologic parameters and the expression of cell differentiation markers. Expression of MMP-1 (P = .092), MMP-2 (P = .041), and CatB (P = .058) was associated with nuclear pleomorphism, a previously described adverse prognostic indicator. Expression of cytokeratin 8 correlated with that of MMP-1 (P = .005), MMP-2 (P = .002), and uPA (P = .032). Patients with higher MMP-2 expression had a poorer prognosis than those with lower MMP-2 expression (P = .013). We believe that NSBCs with nuclear pleomorphism or stronger epithelial character have a higher invasive ability than those without. In addition, high MMP-2 expression was an indicator of an unfavorable clinical outcome in NSBC.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Cathepsin B; Chordoma; Humans; Immunohistochemistry; Keratins; Matrix Metalloproteinases; Middle Aged; Prognosis; Survival Analysis; Urokinase-Type Plasminogen Activator

Sarcomatous transformation in chordoma is a very rare condition and has been emphasized as a distinct entity because of its more aggressive clinical course. Here we describe a case of dedifferentiated chordoma arising from the skull base region of an 11-year-old boy, with tumor recurrence within one year. This tumor showed features of pleomorphic cell sarcoma with areas more typical of chordoma. Most of tumor cells expressed cytokeratin, epithelial membrane antigen, vimentin and S-100 protein, thus confirming the diagnosis of dedifferentiated chordoma.

Topics: Biomarkers, Tumor; Cell Differentiation; Cervical Atlas; Child; Chordoma; Combined Modality Therapy; Cranial Irradiation; Disease Progression; Fatal Outcome; Humans; Keratins; Male; Mucin-1; Neoplasm Proteins; Neoplasm Recurrence, Local; Osteolysis; Prognosis; S100 Proteins; Sarcoma; Skull Base Neoplasms; Spinal Neoplasms; Torticollis; Vimentin

A 70-year-old man was admitted to hospital because of oral and cervical masses. Computed tomographic scanning revealed a lobulated mass lesion in the retropharyngeal region, with a protruding extension in the oral cavity and with destruction of the second cervical vertebra. A biopsy was performed under the diagnosis of a retropharyngeal tumor. Histologically, this lesion was composed of vacuolated tumor cells in a solid or cord-like arrangement, with an abundant myxoid matrix. Immunohistochemically, the tumor cells were positive for pancytokeratin, epithelial membrane antigen and S-100 protein. The tumor was diagnosed as chordoma. Chordoma presenting as an intra-oral mass lesion is very rare.

Topics: Aged; Cervical Vertebrae; Chordoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Mouth Neoplasms; Mucin-1; S100 Proteins; Spinal Neoplasms

The authors describe a tumor that had the histologic and ultrastructural features and immunohistochemical profile of an axial chordoma, but arose in the distal ulna. A skeletal survey failed to show any other site of involvement. The tumor was resected, and the patient remains free of disease 2 1/2 years later. Rare tumors with the histologic features of chordoma have been reported in appendicular locations. Chordoma periphericum, a tumor that has the potential to metastasize, needs to be distinguished from parachordoma because no classic parachordoma has been reported to disseminate.

Topics: Adult; Biomarkers, Tumor; Bone Neoplasms; Chordoma; Disease-Free Survival; Humans; Immunoenzyme Techniques; Intercellular Junctions; Keratins; Magnetic Resonance Imaging; Male; Neoplasm Proteins; Organelles; Radiography; S100 Proteins; Ulna

To report a rare ectopic chordoma within the orbital wall.. Case report.. A 63-year-old woman developed swelling of the eyelid, tearing, blurred vision, and progressive proptosis RE of 1 month's duration. Neuroimaging studies revealed an osteolytic mass with epicenter at the sphenozygomatic suture that eroded intracranially, invaded into the orbit, and compressed orbital soft tissues. Surgical debulking was done followed by radiation treatment. The pathologic findings of physaliphorous epithelial cells with multiple vacuoles containing mucin, prominent nuclei, and positive immunohistochemical staining for S-100, Vimentin, epithelial membrane antigen, and pancytokeratin were diagnostic for chordoma.. Orbital wall ectopic localization of a chordoma distant from the clivus is a rare occurrence.

Topics: Biomarkers, Tumor; Chordoma; Female; Humans; Keratins; Magnetic Resonance Imaging; Middle Aged; Mucin-1; Neoplasm Invasiveness; Neoplasm Proteins; Orbital Neoplasms; S100 Proteins; Tomography, X-Ray Computed; Vimentin

Chordoma is the fourth most common malignant primary neoplasm of the skeleton and almost the only one showing a real epithelial phenotype. Besides classic chordoma, so-called chondroid chordoma was described as a specific entity showing cartilage-like tissue within chordomatoid structures. However, since its first description, strongly conflicting results have been reported about the existence of chondroid chordoma and several studies suggested chondroid chordomas being in fact low-grade conventional chondrosarcomas. In the present study, we used cytoprotein expression profiling and molecular in situ localization techniques of marker gene products indicative of developmental phenotypes of chondrocytes to elucidate origin and biology of chondroid chordoma. We were able to demonstrate the chondrogenic potential of chordomas irrespectively of the appearance of overt cartilage formation by identifying the multifocal expression of type II collagen, the main marker of chondrocytic differentiation. Additionally, the cartilage-typical large aggregating proteoglycan aggrecan was present throughout all chordomas and, thus, a very characteristic gene product and marker of these neoplasms. Biochemical matrix composition and cell differentiation pattern analysis showed a high resemblance of classic chordomas and in chordoid areas of chondroid chordomas to the fetal chorda dorsalis, whereas chondroid areas of chondroid chordomas showed features similar to adult nucleus pulposus. This demonstrates on the cell function level the chondrocytic differentiation potential of neoplastic chordoid cells as a characteristic facet of chordomas, mimicking fetal vertebral development, ie, the transition of the chorda dorsalis to the nucleus pulposus. Our study firmly establishes a focal real chondrocytic phenotype of neoplastic cells in chordomas. Chondroid chordoma is neither a low-grade chondrosarcoma nor a misnomer as discussed previously.

Topics: Aggrecans; Cell Differentiation; Chordoma; Collagen; Extracellular Matrix Proteins; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Intervertebral Disc; Keratins; Lectins, C-Type; Lumbar Vertebrae; Mucin-1; Phenotype; Proteoglycans; RNA, Messenger; S100 Proteins; Vimentin

We report on the crush preparation findings of a case of "sarcomatoid" chordoma occurring in the sacral region of a 78-yr-old Chinese male. The smears showed clumps and small cords of polygonal tumor cells containing bubbly cytoplasm and round to oval nuclei. Focally, there were also aggregates of long filamentous spindle cells and stellate bizarre cells with marked nuclear pleomorphism. Occasional tumor cells were seen in association with dense amorphous material. Histologic examination of the excised specimen showed features of the so-called "sarcomatoid" chordoma which consisted of prominent foci of mitotically inactive spindle and pleomorphic cells, in addition to the conventional chordoma areas. An osteosarcoma-like pattern of probably metaplastic nature was also seen within the tumor. Immunohistochemical study showed that most tumor cells expressed cytokeratins. Ultrastructural examination revealed the characteristic rough endoplasmic reticulum-mitochondria complexes. While there are many spindle and pleomorphic cells seen in crush preparations, the distinction from other true high-grade malignancies is important. Recognition of these "pseudoanaplastic" cytologic features also helps to expand the morphologic spectrum of chordoma.

Topics: Aged; Biomarkers, Tumor; Chordoma; Cytodiagnosis; Histological Techniques; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Organelles; Sacrum; Sarcoma; Spinal Neoplasms

We report a case of recurrent parachordoma of the left anterior tibial region in a 64-year-old male patient. The tumor was a periosteal tender mass, and, histologically, displayed vague nodules of spindle to rounded eosinophilic cells embedded in a myxoid matrix. Large vacuolated (physalphorouslike) cells were noted as in sacrococcygeal chordoma. This tumor should be differentiated from myxoid chondrosarcoma, myxoid liposarcoma, chondromyxoid fibroma, and metastatic chordoma. The presence of physaliphorous cells in the tumor with positive immunoreactions caused by cytokeratin rules out the diagnosis of another myxoid tumor. The differential diagnosis from metastatic chordoma is basically made by clinicians. Even though parachordoma is usually regarded as a benign soft tissue neoplasm, two recurrences occurred in our case. Since the reported cases, including ours, have diverse clinical courses, it is essential to follow-up the patient carefully.

Topics: Chondrosarcoma; Chordoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Soft Tissue Neoplasms; Tibia; Vimentin

Thirty-five chordomas and more than 100 other tumors that have to be considered in the differential diagnosis, were immunohistochemically analyzed using a panel of antibodies including those to subsets of keratins (K), HBME-1, a monoclonal antibody recognizing an unknown antigen on mesothelial cells, and neuroendocrine markers. The patterns of immunoreactivities in chordoma were compared with those in renal cell carcinoma, colorectal mucinous adenocarcinoma, pituitary adenoma, skeletal chondrosarcoma, and extraskeletal myxoid chondrosarcoma (ESMC). Chordomas were consistently positive for keratin cocktail AE1/AE3, and for the individual keratins K8 and K19, and nearly always positive for K5, but they showed negative or only sporadic reactivity for K7 and K20. The keratin K8 and K19 reactivity was retained in those chordomas showing solid sheets of epithelioid, spindle cells, or cartilaginous metaplasia, and in one of two cases showing overtly sarcomatous transformation. In comparison, keratins were never present in skeletal chondrosarcoma, although K8 and to a lesser extent K19 were seen in occasional cases of ESMC with chordoid features. HBME-1 reacted strongly with chordoma and skeletal chondrosarcoma but was almost never positive in renal or colorectal carcinoma. These carcinomas lacked K5-reactivity, in contrast to chordoma. Chordomas were also consistently positive for neuron-specific enolase and occasionally focally for synaptophysin, but never for chromogranin. In contrast, pituitary adenomas regularly expressed the full spectrum of neuroendocrine markers and differed from chordoma by having a narrower repertoire of keratins, often showing negative or focal keratin 8- or AE1/AE3 reactivity and being almost always K19-negative. These findings indicate that chordoma can be immunohistochemically separated from tumors that can resemble it. Immunohistochemistry is especially useful in the diagnosis of small biopsy specimens that offer limited material for morphological observation.

Topics: Adenocarcinoma, Mucinous; Adenoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Chondrosarcoma; Chordoma; Colonic Neoplasms; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Pituitary Neoplasms

Topics: Adult; Biopsy; Brain Edema; Chordoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lymphocytes; Meningeal Neoplasms; Meningioma; Notochord; Plasma Cells

Chordoma is a well-known bone tumor that shows epithelioid features and in which the expression of cytokeratins (CKs) has been reported to appear very frequently. Numerous immunohistochemical analyses of CK expression have been conducted using such monoclonal antibodies as CAM5.2, which react with CK8, CK18, and CK19, and AE1/AE3, which react with CKs 1-8, 10, 14-16 and 19 in chordoma. No detailed analysis, however, of the expression of each component of CK has yet been conducted in chordoma; thus, the subsets of CK expressed there have yet to be clarified. With the use of immunohistochemical techniques with a panel of monoclonal antibodies against each subset of CK, the authors studied the expression of CKs in 16 specimens of classic chordoma and 14 specimens of the fetal notochord to clarify the subsets of CK expressed in chordoma and to evaluate the similarities and differences of CK expression between chordoma and the fetal notochord. All of the chordoma specimens showed a strong positive immunoreactivity for CK8 and CK19, whereas nine (56.3%) chordoma specimens showed a positive immunoreaction for CK18. In addition, four chordoma specimens were focally positive for keratin-903, which reacts with high molecular weight CKs such as CK1, CK5, CK10, and CK14; one specimen also showed a strong CK7 expression. All of the notochord specimens were also positive for CK8 and CK19, but none showed a positive immunoreaction for keratin-903, CK7, or CK18. In addition, none of the chordoma or notochord specimens showed immunoreactivity for CK20. The expression of CK8 and CK19, observed in all of the chordoma and notochord specimens, was thus considered to be maintained throughout the neoplastic transformation, although some aberrant CK expressions (CK7, CK18, and keratin-903) also occurred in the chordoma specimens examined in this study.

Topics: Adult; Aged; Bone Neoplasms; Child, Preschool; Chordoma; Female; Fetal Proteins; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Proteins; Notochord

Four soft tissue tumors corresponding with the previously reported parachordoma are described. Three of the patients were men, and one was a woman, and their ages ranged from 14 to 53 years (mean age, 29). The tumors were located either superficially or within muscle, and, in one case, involved a tendon. Histologically, the tumors displayed whorls, nests, and pseudoglandular cords of uniform polygonal cells with eosinophilic, vacuolated cytoplasm, in a focally myxoid stroma. Transitions were seen between fascicles of ovoid-spindled cells, with scanty cytoplasm in a fibrous stroma, and, in one case, whorls of bland spindly cells were also present. Electron microscopy of one case showed cells with short interdigitating microvilli and ill-defined junctions. The principal cells in all cases were positive for S100 protein, Leu-7, keratin (CAM5.2), and epithelial membrane antigen (EMA). All tumors were negative with antibody AE1 and with antibodies to cytokeratins CK7 and CK19. No tumor displayed immunoreactivity for carcinoembryonic antigen (CEA), muscle specific actin (MSA), smooth muscle actin (SMA), desmin, glial fibrillary acid protein (GFAP), CD31, or CD34. Parachordoma appears to be an entity with clinical and pathological differences from chordoma, which has a different cytokeratin profile, behaves in a more aggressive fashion, and can dedifferentiate. The differential diagnosis includes myxoid chondrosarcoma, myoepithelial cell tumor, ossifying fibromyxoid tumor, and chondroid lipoma.

Topics: Adolescent; Adult; CD57 Antigens; Chondrosarcoma; Chordoma; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Mucin-1; S100 Proteins; Soft Tissue Neoplasms

In order to investigate the clinicopathological and immunohistochemical features of chordomas, 34 chordomas, with 5 chondrosarcomas for comparison, were studied by clinicopathological and immunohistochemical methods.. Based on the presence or absence of cartilaginous areas, chordomas are classified into two subtypes: chondroid chordoma (14 cases) and classic chordoma (20 cases). Chondroid chordoma occurred in a younger age group (mean age 40.9 years) than classic chordoma (mean age 51.1 years). 7/14 (50%) of chondroid chordomas occurred in the sacrococcygeal region, 4/ 14 (28.6%) occurred in the spheno-occipital region. Immunohistochemical staining showed that all chordomas were positive for cytokeratin, and 16 (47.1%) chordomas were also positive for EMA. In contrast, 5 chondrosarcomas were immunonegative for both cytokeratin and EMA. Vimentin and S-100 protein were positive in the majority of chordomas (29 & 24 respectively) and in the 5 chondrosarcomas. The present study confirms the dual features of chordoma-epithelial and mesenchymal, and also the utility of immunohistochemical staining in the differential diagnosis of chordoma and chondrosarcoma. The pathologic diagnosis of chondroid chordoma and other issues were also discussed in the study.

Topics: Adolescent; Adult; Child; Child, Preschool; Chondrosarcoma; Chordoma; Female; Humans; Immunohistochemistry; Infant; Keratins; Male; Middle Aged; Mucin-1; Sacrococcygeal Region; Skull Base Neoplasms; Spinal Neoplasms

A 37-year-old man presented with right facial pain and a nonpalpable mass over the malar eminence. An incisional biopsy via the intraoral route was performed and interpreted as a vascular malformation with degenerative changes. His symptoms persisted, and a repeat biopsy was suggestive of an epithelioid nerve sheath tumor. Total resection of the tumor was planned to include the infraorbital and malar regions, the infratemporal fossa, and the pterygopalatine fossa. At surgery, the tumor was removed with tumor-free margins obtained along the course of the maxillary nerve just before its entrance into the cavernous sinus. The pathological findings and the immunohistochemistry demonstrated a typical chordoma with no chondroid or sarcomatous dedifferentiation. We think that with greater use of immunohistochemical markers and electron microscopy, patients with chordoma in this location may be diagnosed promptly and accurately.

Topics: Adult; Biomarkers, Tumor; Biopsy; Chordoma; Diagnosis, Differential; Humans; Keratins; Magnetic Resonance Imaging; Male; Microscopy, Electron; S100 Proteins; Skull Neoplasms; Zygoma

A rare case of cutaneous skin metastasis from an intracranial chordoma is presented. A large nodule developed in the left thigh of a 22-year-old woman who had been previously diagnosed to have a chordoma at the base of her skull. Sections from the biopsied specimens of the nodule showed proliferations of physaliphorous cells and stellate cells in cords and in nests in a myxoid stroma. Immunohistochemically, neoplastic cells were stained positively with antibodies to S-100 protein and cytokeratin. The results of the histopathological and immunohistochemical studies of the nodule were interpreted as pointing to a diagnosis of metastatic chordoma based on their similarity to the results of studies of the primary neoplasm in the cranial region. Based on the number of cases of skin metastasis from chordoma reported in the literature, skin should be kept in mind as one of the target organs, although such metastases are still rare.

Topics: Adult; Brain Neoplasms; Cell Nucleus; Chordoma; Cytoplasm; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Neoplasm Recurrence, Local; S100 Proteins; Skin Neoplasms; Thigh; Vacuoles

A chordoma metastatic to the skin of the nose is reported. The patient (a 40-year-old man) had undergone excision of a sacral chordoma 16 months previously. In patients whose clinical histories are unknown, cutaneous metastases of chordoma can be confused with mixed tumors of sweat glands. Cytological features, including the presence of physaliphorous cells, and immunohistochemical coexpression of low molecular weight keratins and S-100 protein are helpful features that lead to a correct diagnosis.

Topics: Adult; Chordoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Nose Neoplasms; S100 Proteins; Sacrum; Skin Neoplasms; Spinal Neoplasms; Sweat Gland Neoplasms; Vimentin

In 1973, Heffelfinger and coworkers described a variant of chordoma that contained cartilaginous areas indistinguishable from hyaline type chondrosarcoma. They designated these tumors chondroid chordomas and found that they had a better prognosis than classic (nonchondroid) chordomas. Since that time, there has been an ongoing debate over whether chondroid chordoma is best considered a distinct clinicopathologic entity separable from chondrosarcoma or a misdiagnosed chondrosarcoma whose concept developed from the erroneous interpretation of morphology. In an attempt to clarify the issue, the authors used light microscopy and immunohistochemistry to study 12 chondroid chordomas, 38 classic chordomas, and 28 chondrosarcomas that arose in the base of the skull or spine. As a reference, they also analyzed the immunohistochemical profile of fetal notochord, ecchordosis physaliphora, and fetal hyaline cartilage. They found that all chondroid and nonchondroid chordomas were positive for cytokeratin, and the majority were also positive for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). In contrast, none of the chondrosarcomas stained for cytokeratin, EMA or CEA. Vimentin and S-100 were positive in more than 95% of both classic and chondroid chordomas and chondrosarcomas. The immunohistochemical profile of these tumors was similar to the pattern of immunoreactivity of their nonneoplastic counterparts. The authors conclude that chondroid chordomas is a variant of chordoma and should not be confused with chondrosarcoma. Because chondroid chordomas have been reported to have a better prognosis, they felt that this nosologic term should be preserved and that chondroid chordoma should continue to be a focus of clinical and pathologic study.

Topics: Adolescent; Adult; Antigens, Neoplasm; Carcinoembryonic Antigen; Chondrosarcoma; Chordoma; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Skull Neoplasms; Spinal Neoplasms; Vimentin

Immunohistochemical and electron microscopic studies were carried out on 9 cases of intracranial chordomas. Three of them were typical chordomas and 6 were chondroid chordomas. Immunohistochemically, both typical chordomas and chondroid chordomas were positively stained for cytokeratin and epithelial membrane antigen. Chondroid chordomas were stained for vimentin with moderate intensity whereas typical chordomas were only slightly stained. In comparison to typical chordomas, the chondroid chordomas had relatively few desmosomes and intermediate filaments. These findings suggest that intracranial chordomas are of mixed epithelial-mesenchymal nature, and that chondroid chordomas have a predominant mesenchymal character as compared to typical chordomas.

Topics: Adult; Aged; Brain; Brain Neoplasms; Chordoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Vimentin

Eight chordomas were studied by using specific antibodies against cytokeratin, vimentin, desmin, type II collagen, S-100 protein, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). One chondrosarcoma was included as a representative of chondroid tumors. All chordomas were positively stained for epithelial markers (cytokeratin and EMA), whereas the chondrosarcoma was not. All chordomas and the chondrosarcoma expressed vimentin, type II collagen and S-100 protein. Oncofetal antigens (CEA and AFP) and desmin were found in five (63%) chordomas, whereas these antigens were not found in the chondrosarcoma. Ultrastructurally the chordoma cells showed junctional complexes, microvillous projections and basal lamina-like structures alongside the tumor cells, whereas the tumor cells of the chondrosarcoma had neither junctions and microvillous projections, nor basement membrane. The present study demonstrates the utility of these tumor markers and ultrastructural features in the differential diagnosis of chordomas and tumors with similar histologic patterns such as chondrosarcomas.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Chordoma; Collagen; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Skull Neoplasms; Vimentin

Topics: Animals; Cervical Vertebrae; Chordoma; Ferrets; Keratins; Male; Spinal Neoplasms; Vimentin

Chordoma, an uncommon tumor originating from remnants of the notochord, with cutaneous involvement has rarely been reported.. Our purpose was to document clinical manifestations, histopathologic features, immunohistochemical findings, treatment, and course of chordoma with cutaneous involvement.. Pathologically proven cases of chordoma were reviewed retrospectively for cutaneous involvement. Detailed clinical data and histopathologic changes were studied. Skin biopsy specimens were stained for immunohistochemical phenotyping.. Of 207 cases of chordoma, 19 had skin involvement: as local recurrences or metastasis in 12, as direct extension of primary tumor in 6, and as a result of distant metastasis from sacrococcygeal chordoma in 1. Local recurrences were frequent, but distant metastasis to various organs, including skin, occurred.. We propose the term chordoma cutis to describe this condition. In seven patients, cutaneous lesions were detected when the diagnosis of primary chordoma was made.

Topics: Adult; Aged; Cause of Death; Cell Nucleus; Chordoma; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Sacrococcygeal Region; Skin Neoplasms; Survival Rate; Vacuoles; Vimentin

Chordomas are rare neoplasms that show a proclivity for the spheno-occiput and sacral regions. A "chondroid" variant involving the spheno-occiput has been associated with improved survival. "Classic" or nonchondroid chordomas are uniformly immunoreactive for keratins. Chondroid chordomas are said to be immunonegative for epithelial markers, a feature used to support the concept that they represent chondrosarcomas.. The authors performed immunohistochemical studies on 25 patients with chondroid chordoma (mean age, 40.0 years) and on 16 patients with classic chordomas (mean age, 44.2 years) to establish tumor subsets based upon immunophenotype, specifically reactivity for epithelial markers. Kaplan-Meier survival curves were then constructed for each group with age as an added variable.. All classic chordomas reacted for keratins as did 8 (32%) of the 25 chondroid chordomas. Forty-four percent of classic and 85% of chondroid chordomas were positive for S-100 protein. At 5 years, all patients younger than 40 years of age were alive in both the classic and chondroid groups. In contrast, of patients older than 40 years of age, only 22% with classic chordomas and 38% with chondroid chordomas were alive.. Regardless of tumor subtype, age is the single most important variable in determining survival; patients younger than 40 years of age do better than older patients. There are no significant survival differences between patients with cartilage-containing tumors that are keratin immunopositive ("true" chondroid chordoma) or negative (chondrosarcoma). Immunostaining for keratins is of no prognostic value in assessing chondroid lesions of the spheno-occiput.

Topics: Adult; Age Factors; Cartilage; Chordoma; Female; Humans; Immunohistochemistry; Keratins; Male; Occipital Bone; Prognosis; S100 Proteins; Skull Neoplasms; Sphenoid Bone; Survival Rate

An immunocytochemical investigation has been carried out on five cases of chordoma (2 of the sacrum, 2 in the spheno-occipital bone and 1 in the parapharyngeal area) to study the expression of the 5 classes of intermediate filaments (IF): cytokeratin (CK), desmin (DES), GFAP, neurofilaments (NF) and vimentin (VIM). Our results show that constant coexpression of CK, NF and VIM does occur in chordomas, whereas DES and GFAP are not demonstrable in tumor cells. The three detected IF are invariably present in all cell types but not in intracellular vacuoles or in the extracellular mucoid substance. The pattern of immunoreactivity of chordomas appears very unique as very few other neoplasms demonstrate the simultaneous occurrence of 3 distinct IF. Only choroid plexus tumors have been shown to manifest CK-NF-VIM immunoreactivity. The complex immunophenotype of chordomas may be related to their supposed origin from the notochord which normally undergoes conspicuous changes in location and morphology during embryonal development. Such changes might require the contemporary presence of multiple IF; IF expression, in fact, is known to be related to cell function and morphology. Notochordal cells and their neoplastic counterpart may consequently express an IF pattern which reflects unique architectural and morphological variations occurring during embryonal and tumor growth. Together with the speculative value of the detection of CK, NF and VIM in chordomas, the unusual immunocytochemical pattern of these tumors might provide useful diagnostic tool in differential diagnosis.

Topics: Adult; Aged; Bone Neoplasms; Chordoma; Female; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Male; Middle Aged; Retrospective Studies; Vimentin

Six chordomas, ten fetal notochords and eight adult notochords were stained for keratin, vimentin, GFAP, desmin, CEA, EMA and s-100 protein. Coexpression of four kinds of intermediate filaments was common in fetal notochords and chordomas. According to the histologic and immunohistochemical characteristics, chordoma may originate from the ectopic remnants of undegenerated notochord during the embryonic stage. The chordoma consists of two cell types; nonvacuolated and physaliphorous cells, and exhibits the potentiality of multidirectional differentiation. The coexpression of different types of intermediate filaments could explain the morphological transformation of chordoma.

Topics: Adult; Chordoma; Female; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Middle Aged; Notochord; Sacrum; Spinal Neoplasms; Vimentin

Altogether 20 chordomas were reported. The site distribution included 9 cases at the sacrococcygeal region, another 9 cases at the spheno-occipital region, 1 at the cervical vertebra, and another 1 at the lumbar vertebra. Histologic examination revealed that characteristic "physaliphorous cells" were easily identified in all the 19 cases. Tissue for immunohistochemistry study was available in 18 cases. Among them, tumor cells were found strongly positive to EMA, but negative for CEA. 16/18 cases also showed positive for keratin and S-100 protein. Totally, 2 cases were studied ultrastructurally and there were abundant RER and microfilaments seen in the cytoplasm of the tumor cells but only few surface microvilli detected. The epithelial nature of chordoma is strongly supported by the ultrastructural and immunohistochemical findings of these 20 cases.

Topics: Adult; Chordoma; Humans; Immunohistochemistry; Keratins; S100 Proteins; Sacrum; Sella Turcica; Skull Neoplasms; Spinal Neoplasms

The cytologic findings in a series of 17 patients with chordoma (one clivus, three cervical, one lumbar, and 12 sacral tumors), all of whom underwent fine-needle aspiration biopsy (FNAB) in the preoperative investigation, were studied. Cytologically, three main cell types were recognized: large, mononucleated or binucleated physaliferous cells with a vacuolated "bubbly" cytoplasm; small, rounded, uniform cells; and short spindle-shaped cells. The May-Grünwald-Giemsa staining was found superior to Papanicolaou staining in demonstrating the mucoid matrix and the vacuolated cytoplasm of the physaliferous tumor cells. Ultra-structurally, the tumor cells contained prominent bundles of filament of the intermediate type, as well as large vacuoles and lumina often bordered by microvillous projections; the cells were connected to one another by well-developed desmosomes. The resin embedding technique for the light and electron-microscopic examination of FNAB material (eight cases), the histochemical demonstration of sulphated glucosaminoglycans in the matrix (four cases), and the immunocytochemical analysis (four cases) with positivity for cytokeratin, epithelial membrane antigen, vimentin, and S-100 protein and negativity for carcinoembryonic antigen were found to be of value for the cytologic diagnosis of chordoma, and helped in distinguishing it from other chondrogenic tumors and metastatic mucous-producing carcinoma. From this study we conclude that a preoperative diagnosis of chordoma can be reached by FNAB, provided the findings are carefully evaluated in relation to the clinical and roentgenographic findings. Adjunctive histochemical, immunocytochemical, and ultrastructural techniques applied on the FNA material may be helpful in reaching a conclusive diagnosis when differential diagnostic problems occur.

Topics: Adult; Aged; Biopsy, Needle; Carcinoembryonic Antigen; Chordoma; Female; Glycosaminoglycans; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Skull Neoplasms; Spinal Neoplasms

A detailed immunohistochemical characterization of different cytokeratin subclasses was performed on frozen tumour tissue from three classical chordomas. Simple epithelium cytokeratins Nos 8, 18, and 19 were detected in all tumour cells while cytokeratin No. 7 was not found. Cytokeratins characteristic of squamous differentiation, including keratinization, were generally lacking, with the exception of the varying expression of cytokeratin No. 4. Vimentin was found in all the tumours, while they lacked desmin immunoreactivity. The present study indicates the co-expression of vimentin and cytokeratins, predominantly of the simple epithelium type. In addition, chordoma cells have the ability to express cytokeratins characteristic of squamous differentiation. This finding corresponds well to the electron microscopic findings of tonofilament bundles ending in well-developed desmosomes.

Topics: Antibodies, Monoclonal; Chordoma; Fluorescent Antibody Technique; Humans; Keratins; Spinal Neoplasms; Vimentin

Chondroid chordomas are cartilage-rich neoplasms, most often located in the spheno-occipital region, that have a better prognosis than classic chordomas. The immunohistochemical features of 19 classic and chondroid chordomas were studied retrospectively using avidin-biotin-complex (ABC) immunoperoxidase histochemistry on formalin-fixed, paraffin-embedded tissue. Of the 19 tumors, all located in the spheno-occipital region, 5 exhibited predominantly chondroid morphologic features. The 14 classic chordomas showed the following pattern of antigen expression (percent of tumors positive): epithelial membrane antigen (EMA) 100%, AE 1/3 (a "cocktail" of monoclonal antibodies directed against low and high molecular weight epidermal cytokeratins) 100%, DP keratin (DPK) 100%, vimentin 100%, S100 86%, neuron specific enolase (NSE) 100%, carcinoembryonic antigen (CEA) 57%, and HMB-45 (an anti-melanoma-associated antibody) 57%. The five chondroid chordomas exhibited the following pattern: EMA 0%, AE 1/3 0%, DPK 0%, vimentin 100%, S100 100%, NSE 100%, CEA 0%, and HMB-45 0%. The focal, weak HMB-45 positivity (performed on the index case because of a clinical concern of metastatic melanoma) seen in 57% of the classic chordomas is a previously unreported finding. This finding suggests either that classic chordomas are capable of HMB-45 expression or that this antibody has broader reactivity than previously recognized. The lack of cytokeratin, EMA, and CEA expression by the chondroid chordomas is similar to chondrosarcomas as reported in the literature and dissimilar to the classic chordoma group. These immunohistochemical findings suggest that chondroid chordomas may more validly be classified as low grade chondrosarcomas.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Neoplasms; Carcinoembryonic Antigen; Child; Chordoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Prognosis; Retrospective Studies; Vimentin

The histomorphologic and immunohistochemical features of chordoma in 20 ferrets were evaluated. The mean age was 3.4 years, and, in the cases for which sex was known, females (n = 10) outnumbered males (n = 5) two to one. All 20 tumors occurred on the tip of the tail. Nineteen of 20 tumors (95%) were composed of three tissue components, often arranged concentrically with lobules of physaliferous cells at the periphery, trabecular bone in the center, and cartilage in between. The bone often contained marrow and hematopoietic cells. One tumor lacked chondromatous or osseous tissue. Immunohistochemical results were consistent with previous studies of chordoma. All 20 tumors (100%) were positive for keratin and vimentin intermediate filaments; 15 (75%) were positive for S-100 protein; and 17 (85%) were positive for neuron specific enolase. This neoplasm shares morphologic and immunohistochemical features with "classic," as well as chondroid chordoma, of human beings, making it a potential animal model.

Topics: Animals; Chordoma; Disease Models, Animal; Female; Ferrets; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Phosphopyruvate Hydratase; S100 Proteins; Tail; Vimentin

The expression of the embryonal and of the differentiational proteins in 12 cases of chordoma and in the notochord of a 4-month-old and a 5-month-old human embryo have been examined immunohistologically by the ABC method using polyclonal antibodies to CEA, AFP, or S-100, and the monoclonal antibody to cytokeratin. It was found that S-100 was expressed in all cases of chordoma and in the notochords examined. CEA and cytokeratin also were found expressed in some cases of chordoma but not in the notochords. These proteins were found expressed more strongly in chordomas without a metastasis than in those with a metastasis. In the metastatic lesions, these proteins were expressed more strongly than in the primary lesions. The antibody to AFP reacted with neither the chordomas nor the notochords tested. These results suggest a possible link between the gene-expression of the tumor cells and the microenvironment in which they are harbored.

Topics: Adult; Aged; alpha-Fetoproteins; Antigens, Differentiation; Carcinoembryonic Antigen; Chordoma; Embryo, Mammalian; Female; Fetal Proteins; Humans; Keratins; Male; Middle Aged; Neoplasm Metastasis; Notochord; S100 Proteins

The authors studied four chordomas with malignant spindle cell components (SCs) and 12 conventional chordomas (CCs) by DNA flow cytometry using paraffin-embedded tissue. In addition, immunohistochemical stains for a variety of epithelial and mesenchymal markers were performed. The four SCs contained areas histologically identical to conventional chordomas, as well as a high-grade malignant spindle cell component. All four (100%) SCs had an aneuploid-multiploid DNA content. Of interest, the conventional chordoma areas in these tumors had DNA contents different from those containing the high-grade malignant spindle cells. In contrast, only three (27%) of the 11 conventional chordomas with analyzable histograms had an aneuploid-multiploid DNA content. Immunohistochemical studies performed on the four SCs showed the high-grade malignant spindle cells to stain strongly for vimentin and weakly for cytokeratin, S-100 protein, and epithelial membrane antigen (EMA), whereas the areas of conventional chordoma in these same neoplasms stained moderately for vimentin and S-100 protein, and strongly for cytokeratin and EMA. In two cases, the staining for EMA and cytokeratin highlighted a gradual transition between the areas of conventional chordoma and the spindle cell areas. The immunohistochemical staining pattern of the 12 conventional chordomas was similar to that seen in the conventional chordoma components of the four chordomas with malignant spindle cell components. These results suggest that: 1) aneuploidy is more common in SCs than in CCs, and 2) some SCs are multipotential neoplasms in which the neoplastic cells are capable of differentiation along both epithelial and mesenchymal pathways.

Topics: Adult; Aged; Biomarkers, Tumor; Chordoma; DNA, Neoplasm; Female; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Nervous System Neoplasms; Organelles; S100 Proteins; Sacrum; Vimentin

Topics: Chordoma; Histiocytoma, Benign Fibrous; Humans; Keratins; Neoplasms, Radiation-Induced

Twenty chordomas from 20 patients, including 17 nonchondroid and three chondroid types, were studied with a variety of antibodies directed against cytokeratin (AE-1/3), epithelial membrane antigen, carcinoembryonic antigen, S100 protein, vimentin, alpha 1-antichymotrypsin, and lysozyme. All 17 nonchondroid chordomas stained for cytokeratin, and most (16) stained for epithelial membrane antigen. In contrast, two chondroid chordomas failed to stain for either cytokeratin or epithelial membrane antigen, while one of them did stain for both antigens. Sixteen of the 20 chordomas (80%) stained for S100 protein, including all three chondroid chordomas. Vimentin was found in six (30%), and alpha 1-antichymotrypsin in 16 chordomas (80%). Carcinoembryonic antigen and lysozyme were each found in two specimens (10%). While these findings basically agree with the immunohistochemical studies of other investigators, there are a few discrepancies. Most significant is the lack of epithelial markers in two of three chondroid chordomas located at the base of the skull. Possible reasons for the discrepancies are discussed.

Topics: Bone Neoplasms; Chordoma; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; S100 Proteins

The relationship of "chordoid sarcoma" (CS) to chordoma and myxoid chondrosarcoma has been debated for several years. In order to reassess this issue, we studied 5 CS, 5 chordomas, and 3 skeletal myxoid chondrosarcomas ultrastructurally and immunohistochemically. By electron microscopy, CS demonstrated smooth cellular outlines, macular intercellular junctions, and cytoplasmic inclusions of matrix-like material. Chordomas displayed a closely similar fine structural appearance, but in addition contained small, membrane-bound, glycogen-containing inclusions. Skeletal myxoid chondrosarcomas resembled CS, except that the former lesions had spiculated cell membranes and lacked intercellular junctions. Immunohistochemically, all CS cases expressed vimentin and lacked cytokeratin (CK). Leu 7 and S100 protein were seen in four cases each of CS, and three of these tumors demonstrated diffuse or focal reactivity for epithelial membrane antigen (EMA). Similar phenotypic features were seen in chordomas, except that all of them stained diffusely for CK, as well as EMA. Skeletal myxoid chondrosarcomas expressed vimentin, S100, and Leu 7 uniformly, but were devoid of epithelial markers. In aggregate, these data support the classification of "chordoid sarcoma" as a form of chondrosarcoma, but reveal that it may exhibit an "epithelial" antigen in some cases.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Bone Neoplasms; Child, Preschool; Chondrosarcoma; Chordoma; Female; Humans; Immunoenzyme Techniques; Infant; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Soft Tissue Neoplasms; Vimentin

The existence of chondroid chordoma (CC), initially described in 1973, has remained controversial. Since the antigenic profiles of both chordoma (CD) and cartilaginous (chondroid) lesions have been well characterized, we decided to study chondroid chordoma immunohistochemically. Our hypothesis was that chondroid chordoma should display a hybrid or mixed pattern of staining: chordomatous areas with an epithelial phenotype and cartilaginous areas with a mesenchymal (non-epithelial) phenotype. An analysis of CC (seven cases) was performed and compared with results obtained on notochord, cartilage, classic CD (18 cases), peripheral chondromas (two cases), and peripheral chondrosarcomas (CS, eight cases). Four epithelial markers were employed: MKER and AE-1 (both monoclonal antibodies to cytokeratin); PKER (a polyclonal antibody to cytokeratin); and, EMA (epithelial membrane antigen). In addition, selected cases were tested for the presence of neurofilament (NF) and glial fibrillary acidic protein (GFAP). All 18 CD's exhibited the expected epithelial immunophenotype - MKER+, AE-1+, PKER+, and EMA+ - a reaction pattern nearly identical to that found in fetal notochord. This reinforced the importance of the growth pattern in assessing the presence of chordomatous elements. All chondromas and CS's failed to express any of the epithelial markers studied and contained only S-100 immunoreactivity, like cartilage. Chondroid chordoma resembled cartilaginous tumors immunohistochemically; no mixed pattern with even focal epithelial marker reactivity was identified. All CC tested were also NF and GFAP negative. We conclude that CC either does not exist or is extremely rare and that these tumors are cartilaginous in nature.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chondrosarcoma; Chordoma; Glial Fibrillary Acidic Protein; Humans; Immunologic Techniques; Intermediate Filament Proteins; Keratins; Neurofilament Proteins; Skull Neoplasms

Three cases of "dedifferentiated" chordoma arising in the sacrococcygeal region are presented. In all three cases, the "dedifferentiated" component arose de novo in conjunction with conventional chordoma. Two of these patients, whose tumors had a prominent malignant fibrous histiocytoma (MFH) component, died within 6 months of diagnosis. Both patients had lung metastases, one of which was histologically documented to be MFH. The third patient, whose initial tumor contained osteosarcoma, died 76 months after diagnosis and multiple recurrences. Most notable in this case was the absence of the "dedifferentiated" component (in this instance, osteosarcoma) in all of the local recurrences as well as the lung metastases. These were composed exclusively of conventional chordoma. None of the patients had a previous history of radiation therapy. The immunohistochemical staining pattern of conventional chordoma was similar to that of previous reports, where the epithelial-like cells stained for cytokeratin and epithelial membrane antigen. In addition, they stained for alpha-1-anti-chymotrypsin and vimentin. These latter two markers were also identified in the "dedifferentiated" component. As with "dedifferentiated" chondrosarcomas and liposarcomas, "dedifferentiation" in a chordoma usually portends an accelerated clinical course.

Topics: Adult; Aged; Chordoma; Histiocytic Sarcoma; Histocytochemistry; Humans; Keratins; Lung Neoplasms; Male; Membrane Proteins; Mucin-1; Neoplasm Recurrence, Local; Osteosarcoma; Sacrococcygeal Region

A 26-year-old woman was operated on for a bulky tumor in the sacral region; she died of massive local tumor recurrence and pulmonary metastases 3 months later. Most of the original tumor showed a highly cellular spindle-cell sarcoma compatible with a fibrosarcoma of a high grade of malignancy. In a few small areas of the tumor, a chordoma-like pattern surrounded by growth of spindle-cell sarcoma was found. The spindle-cell component exhibited vimentin positivity in all tumor cells, but many cells were also cytokeratin-positive. The chordoma-like areas showed cytokeratin in all tumor cells. The chordoma-like areas, but not the spindle-cell areas also were positive for epithelial membrane antigen and S-100 protein. This case indicates that the sarcomatous change associated with chordoma may contain keratins as a sign of epithelial differentiation, and may thus represent sarcomatous transformation of chordoma cells, rather than a coincidental soft-tissue sarcoma or collision tumor.

Topics: Adult; Chordoma; Female; Fibrosarcoma; Humans; Keratins; Lung Neoplasms; Membrane Proteins; Mucin-1; Pelvic Neoplasms; S100 Proteins; Sacrococcygeal Region; Sarcoma; Vimentin

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Bone and Bones; Bone Neoplasms; Chordoma; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Vimentin

This is a unique case of chondroid chordoma arising in the sacrococcygeal area of an asymptomatic man. S100 protein was detected in both chondroid and chordoid tissues; epithelial membrane antigen (EMA) and cytokeratin were present in abundant amounts in the cytoplasm of chordoma cells but not in chondroid cells. The presence of cytokeratin and EMA in chordoma implies the epithelial nature of the tumor and is extremely helpful as a differential marker for chordoma. I suggest that EMA, cytokeratin, and S100 protein should be used conjunctively to provide a resolution for difficult diagnostic problems when dealing with chordomas, especially with their variants, such as chondroid chordomas, which often cause further confusion.

Topics: Bone Neoplasms; Chordoma; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; S100 Proteins; Sacrococcygeal Region

Chondroid chordomas are shown to possess cytokeratins and to stain with HMFG-2 as do ordinary chordomas. These findings support the concepts that these neoplasms are a variant of chordoma and that they are unrelated to myxoid chondrosarcoma.

Topics: Antigens, Neoplasm; Chordoma; Humans; Keratins; Membrane Glycoproteins; Mucin-1; Nasopharyngeal Neoplasms; Skull Neoplasms; Sphenoid Bone

Fourteen chordomas, five myxoid chondrosarcomas, and 15 chondroid tumors (four mesenchymal and 11 conventional chondrosarcomas) were stained for cytokeratin, S-100 protein, carcinoembryonic antigen (CEA), and vimentin. The epithelial markers stained 93 per cent of the chordomas, whereas none of the tumors of other types showed any staining. Sixty-four per cent of the chordomas, 20 per cent of the myxoid chondrosarcomas, and 87 per cent of the other chondroid tumors were positive for S-100 protein. All of the tumors were positive for vimentin. Three of the 14 chordomas were positive for CEA. The present study confirms the utility of these markers in the differential diagnosis of chordoma and tumors with similar histologic characteristics.

Topics: Carcinoembryonic Antigen; Chondrosarcoma; Chordoma; Humans; Keratins; Membrane Proteins; Mucin-1; S100 Proteins; Staining and Labeling; Vimentin

An immunohistological study of 15 chordomas, six chondrosarcomas, four liposarcomas and seven carcinomas on paraffin embedded samples using anti-cytokeratin, anti-epithelial membrane antigen (EMA), anti-S100 protein, anti-vimentin and anti-neurofilaments showed that chordomas has a characteristic immuno-staining, i.e. positive for cytokeratin, EMA, S100 protein and vimentin; and negative for neurofilaments. This immuno-staining allows a clear distinction of chordomas from other tumours.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Chondrosarcoma; Chordoma; Humans; Immunoenzyme Techniques; Keratins; Liposarcoma; Membrane Proteins; Mucin-1; S100 Proteins; Vimentin

Chordomas are rare slow-growing but locally invasive tumors. They are thought to develop from residues of the notochord. Three chordomas and ten chondroid tumors were investigated by an indirect immunoperoxidase method for expression of the epithelial markers: MAM-6, keratin, tissue polypeptide antigen (TPA) and for carcinoembryonic antigen (CEA). In all the chordomas investigated the antigens MAM-6, keratin and TPA were detected using monoclonal antibodies and conventional antisera, respectively. These data provide further evidence of the epithelial nature and the ectodermal origin of chordomas. Moreover, the findings suggest that immunohistochemical methods may be useful for the differential diagnosis between chordomas and morphologically similar chondroid tumors.

Topics: Antibodies, Monoclonal; Bone Neoplasms; Carcinoembryonic Antigen; Chondrosarcoma; Chordoma; Coccyx; Diagnosis, Differential; Humans; Immune Sera; Immunoenzyme Techniques; Keratins; Lumbar Vertebrae; Membrane Proteins; Mucin-1; Osteosarcoma; Peptides; Sphenoid Bone; Spinal Neoplasms; Tissue Polypeptide Antigen

Five cases of chordoma, diagnosed by fine-needle aspiration (FNA) biopsy, are presented. Four cases were histologically confirmed, and in one, immunocytochemical and ultrastructural studies were performed on both the aspirate and tissue specimen. Four cases presented as sacral masses, while in the fifth case, a destructive lesion of the clivus extended into the soft tissues of the lateral neck. A spectrum of cytomorphologic features was encountered including the presence of abundant microtissue fragments and cells in a dissociate pattern, often with abundant metachromatic extracellular matrix. Stellate and cuboidal cells often contained intracytoplasmic vacuoles of varying sizes. Intranuclear inclusions, mitotic figures, and anisonucleosis were prominent features of several cases. Immunoperoxidase studies on a single case demonstrated cytoplasmic staining for low- and high-molecular-weight cytokeratins, vimentin, and epithelial membrane antigen, while glial fibrillary acidic protein and carcinoembryonic antigen were negative. Ultrastructural features included the presence of mitochondrial endoplasmic reticulum complexes, occasional desmosome-like junctions, and abundant extracellular matrix adherent to the tumor cells. We believe the cytomorphologic findings are characteristic and, when taken in concert with immunocytochemical and ultrastructural studies, allow differentiation of chordoma from other primary or metastatic neoplasms occurring in bone. As demonstrated in our series, chordoma is often an unsuspected diagnosis. We believe that FNA biopsy of these lesions can lead to a correct preoperative diagnosis and may also be utilized to document recurrence and thus facilitate the evaluation and management of patients with these lesions.

Topics: Aged; Biopsy, Needle; Bone Neoplasms; Cervical Vertebrae; Chordoma; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged; Sacrum; Spinal Neoplasms

The application of immunohistochemical staining with anti-epithelial monoclonal antibodies to the differential diagnosis of chordomas is described. Cytokeratins and an epithelial membrane-specific oligosaccharide sequence are found in chordomas but not in chondrosarcomas or normal cartilage. The same cytokeratins and oligosaccharide sequence are demonstrated in human fetal notochord. Immunohistochemical staining with antiepithelial antibodies is therefore of value in distinguishing chordomas from cartilaginous tumours. The staining of notochord with the same monoclonal antibodies adds weight to the proposition that chordomas arise from embryonic rests of notochordal cells.

Topics: Adult; Antibodies, Monoclonal; Antigens; Antigens, Neoplasm; Cell Membrane; Chordoma; Embryo, Mammalian; Epithelium; Fetus; Humans; Immunoenzyme Techniques; Keratins; Notochord

Six chordomas, nine chondrosarcomas, and three myxopapillary ependymomas of the filum terminale were evaluated immunohistochemically for the expression of intermediate filament proteins by the use of monospecific antibodies against intermediate filament proteins of keratin, vimentin, and glial fibrillary acidic protein (GFAP) type. All chordomas were positive for keratin but negative for GFAP, whereas chondrosarcomas and ependymomas were negative for keratin. Chondrosarcomas showed strong vimentin positivity, whereas ependymomas were positive for GFAP. Chordomas showed desmosomelike junctions by electron microscopy, whereas chondrosarcomas of different types showed no junctions or only primitive ones. By electron microscopy chordomas often showed prominent intermediate filaments also associated with desmosomes, and poorly differentiated chondrosarcomas also showed prominent intermediate filaments. Keratin positivity of chordomas suggests their epithelial nature, while vimentin positivity of chondrosarcomas is in line with their mesenchymal derivation. The results also show that antibodies against different intermediate filament proteins can be applied as diagnostic aids in making the distinction between chordomas, chondroid tumors, and ependymal tumors.

Topics: Adolescent; Adult; Aged; Antibodies; Chondrosarcoma; Chordoma; Cytoskeleton; Desmosomes; Diagnosis, Differential; Ependymoma; Glial Fibrillary Acidic Protein; Humans; Intermediate Filament Proteins; Keratins; Middle Aged; Vimentin