Dedifferentiated Chordoma: Clinicopathologic and Molecular Characteristics With Integrative Analysis.

Dedifferentiated chordoma is a rare chordoma subtype characterized by a high-grade sarcoma juxtaposed to conventional chordoma. We identified a series of dedifferentiated chordomas, reviewed clinicopathologic features, performed next-generation sequencing in select cases, and analyzed all related English-language publications. Our series included 7 men and 3 women (age 15 to 80 y [median: 54 y]; <1% of >1000 chordomas surveyed). The tumor (2.8 to 24.5 cm [median: 5.8 cm] in size) presented de novo or as recurrence (including postradiotherapy) in sacrum (n=5), skull base (n=2), lumbar spine (n=1), thoracic/mediastinum (n=1), and lung (n=1; as metastasis). Histologically, the dedifferentiated component (3% to 95% [median: 60%]) was pleomorphic-to-fibrosarcomatous, juxtaposed to conventional (n=8) or chondroid (n=2) component. By immunohistochemistry, the conventional/chondroid component consistently expressed cytokeratin and brachyury, whereas the dedifferentiated component showed loss of both. We identified a sacral conventional chordoma with INI1 loss, with one of the lung metastases showing biphasic histology with loss of cytokeratin and brachyury in the dedifferentiated component. Sequencing identified tumor suppressor mutations in 4 tumors, including TP53 mutations in the dedifferentiated component in 3 tumors. Of 7 patients with follow-up, 6 developed metastases; 4 died at 15 to 99 months (median: 24 mo) after dedifferentiated chordoma diagnosis. Collectively, of 87 dedifferentiated chordoma patients described in 1913-2020 (including 10 herein), the median overall survival was 20 months. In summary, dedifferentiated chordoma involves diverse sites and presents de novo, postradiotherapy, or as recurrence/metastasis months-to-years after initial diagnosis. The dedifferentiated component shows loss of brachyury and cytokeratin staining and harbors recurrent TP53 mutations, implicating tumor suppressor dysregulation in chordoma dedifferentiation.

High expression of survivin independently correlates with tumor progression and mortality in patients with skull base chordomas.

OBJECTIVE: The object of this study was to clarify the expression characteristics and prognostic value of survivin in skull base chordomas. METHODS: In this retrospective study, the authors measured the expression of survivin at the mRNA level in 81 samples from 71 patients diagnosed with skull base chordomas at their hospital in the period from July 2005 to January 2015. Clinical data collection, follow-up, and survival analyses were performed, and correlations were analyzed. RESULTS: Of the 71 patients, 50 had primary chordomas with a mean survivin expression level of 1.09; the other 21 patients had recurrent chordomas with a mean survivin expression level of 2.57, which was 2.36 times higher than the level in the primary chordoma patients (p < 0.001, Mann-Whitney U-test). In addition, an analysis of 18 paired samples derived from 9 patients showed that the expression level of survivin was 2.62 times higher in recurrent tumors than in primary tumors (p = 0.002, paired t-test). The Spearman rank correlation coefficient method showed that the expression level of survivin was positively correlated with the mean ratio of tumor signal intensity to the signal intensity of surrounding brainstem on T1-weighted sequences (RT1; rs = 0.274, p = 0.021) and was negatively correlated with the mean ratio of tumor signal intensity to the signal intensity of surrounding brainstem on T2-weighted sequences (RT2; rs = -0.389, p = 0.001). A multivariate Cox proportional-hazards model suggested that pathology (p = 0.041), survivin expression level (p = 0.018), preoperative Karnofsky Performance Status (KPS; p = 0.012), and treatment history (p = 0.009) were independent prognostic factors for tumor progression. Survivin expression level (p = 0.008), preoperative KPS (p = 0.019), tumor diameter (p = 0.027), and intraoperative blood loss (p = 0.015) were independent prognostic factors for death. CONCLUSIONS: Survivin expression level and preoperative KPS were independent significant prognostic factors for tumor progression and death in skull base chordoma patients. Recurrent skull base chordomas and chordomas with high RT1 and low RT2 were likely to have high survivin expression. Other independent risk factors related to tumor progression included conventional pathology and treatment history, whereas additional mortality-related risk factors included larger tumor diameter and greater intraoperative blood loss.

Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue.

Axial chordoma represents approximately 1% of malignant bone tumors. This tumor expresses cytokeratins, specifically cytokeratin 19, and commonly S100. More recently brachyury, a transcription factor important in mesodermal differentiation, including notochord development, has been detected by immunohistochemistry in axial chordomas and hemangioblastomas but not chondrosarcomas or other neoplasms. In this report, we describe 10 cases (6 men, 4 women: age 18 to 68 y; mean 44.6) of extra-axial tumors, 8 in bone and 2 in soft tissue, with morphologic and immunohistochemical features identical to those of axial chordoma. Imaging excluded metastases from axial chordoma. Three tumors occurred in the tibia, the others in the rib, metatarsal, ulna, femur, pubis: 2 intracortical, 6 intramedullary. Both soft tissue brachyury-positive tumors, one involving the thumb the other the wrist, were sited in the juxta-articular region. Seven of the tumors were widely excised and these patients are disease-free but of the 3 tumors that recurred, 1 was curetted, 1 was marginally excised, and 1 had a pathologic fracture on presentation. Metastases have not occurred in any of the patients. We also confirm the expression of brachyury in hemangioblastomas, and for the first time demonstrates its expression in spermatogonia and testicular germ cell tumors by immunohistochemistry. Brachyury was not detected in a wide range of tumors including carcinomas, lymphomas, and sarcomas. In conclusion, we describe the first series of extra-axial skeletal chordomas bringing the total number of such cases reported in the literature to 11, and present the first report of 2 soft tissue chordomas as defined by brachyury expression.

CDK4 expression in chordoma: A potential therapeutic target.

Chordomas are rare bone tumors and treatment is commonly based on a combination of surgery and radiotherapy. There is no standard chemotherapy treatment for chordoma. The aim of this study was to determine the expression of cyclin-dependent kinase 4 (CDK4) in chordoma and its therapeutic implications. We evaluated CDK4 expression both in chordoma cell lines and in chordoma tissues. Also, we investigated the functional roles of CDK4 in chordoma cell growth and proliferation. Furthermore, the therapeutic implications of targeting CDK4 in chordoma were evaluated. We found CDK4 highly expressed in chordoma cell lines and in a majority (97.7%) of chordoma tissues. Higher CDK4 expression correlated with metastasis and recurrence of chordoma. Treatment of chordoma cells using CDK4 inhibitor palbociclib could efficiently inhibit chordoma cells growth and proliferation. These data demonstrate that targeting CDK4 may be useful as a novel strategy in the treatment of chordoma. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1581-1589, 2018.

Chordoma arising in a mature cystic teratoma of the ovary: a case report.

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.

Preferential expression of alternatively spliced transcript of type II procollagen in the rabbit notochordal remnant and developing fibrocartilages.

Expression patterns for the two isoforms of alpha 1(II) mRNA in various cartilaginous tissues were examined using newly isolated cDNA clones encoding rabbit type II procollagen amino- and carboxy-terminal propeptide regions. In nonchondrogenic nucleus pulposus, the switching of the mRNA from the long form to the short form was accompanied by disc maturation after birth. Interestingly, the short transcript was also expressed preferentially in human chordoma tissues as aberrant chordal vestiges. These results suggest an abundance of the differentiated chondrocyte-like phenotype in the heterogeneous notochordal remnants.

Soft tissue sacrococcygeal chordoma with intracytoplasmic filamentous inclusions.

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.

Overexpression of the BMP4/SMAD signaling pathway in skull base chordomas is associated with poor prognosis.

Chordomas are rare, locally invasive tumors with characteristic expression of the T-box transcription factor Brachyury. Little is yet known of the molecular events involved in the development of these tumors. Bone morphogenesis protein 4 (BMP4) signaling, which acts upstream of Brachyury in embryonic development, has been implicated in carcinogenesis in multiple malignancies. To explore the role of the canonical BMP4/SMAD signaling pathway in the pathogenesis of chordoma, we investigated, in 40 skull base chordomas, the expression of three major components of the signaling axis: BMP4, phospho-SMAD5 and SMAD4. Immunostaining revealed positive expression in 70%, 52.5% and 90% of cases, respectively. Eighteen (45%) of patients exhibited concurrent positive expression of these markers, which we defined as "high" expression of the BMP4/SMAD signaling pathway. Interestingly, when we compared the pattern of expression with clinicopathological parameters, we found that high expression of the pathway was more often observed in larger tumors (≥ 4 cm) than smaller ones (P = 0.010), and correlated significantly with dural invasion (P = 0.024). The Kaplan-Meier log-rank test showed that the 5-year overall survival rate for patients with high expression of the pathway was significantly lower than those with low expression (71.4% vs. 90.2%, P = 0.010). In conclusion, our results demonstrate for the first time that overexpression of the BMP4/SMAD signaling pathway could predict poor clinical outcome in skull base chordomas, suggesting activation of this pathway is involved in chordoma pathogenesis.

Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases.

Brachyury is a transcription factor of the T-box family typically expressed in notochord and chordoma. Some studies report brachyury as highly specific for chordoma, whereas others have concluded that brachyury is expressed in many types of common carcinomas by reverse transcription polymerase chain reaction and immunohistochemistry and could be involved in the epithelial-mesenchymal transition and metastatic process. In this study, we immunohistochemically evaluated 5229 different tumors for nuclear brachyury expression using a new rabbit monoclonal antibody and automated immunostaining (Leica Bond Max). Only nuclear labeling was scored, and antibody dilution of 1:2000 was used. In normal tissues, only rare cells in seminiferous tubules were labeled; all other organs were negative. All chordomas (75/76), except a sarcomatous one, were positive, whereas chondrosarcomas were negative. Among epithelial tumors, positivity was often detected in embryonal carcinoma (74%) and seminoma (45%). Pulmonary small cell carcinoma was often positive (41%), whereas pulmonary and pancreatic adenocarcinomas only rarely showed nuclear brachyury positivity (3% to 4%). Common carcinomas such as ductal carcinomas of the breast or adenocarcinomas of the prostate only exceptionally showed nuclear positivity (<1%). No colorectal, hepatocellular, renal cell, squamous cell, thyroid or urothelial carcinoma, or mesothelioma showed nuclear brachyury positivity. Among mesenchymal and neuroectodermal tumors, only isolated cases of melanoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, synovial sarcoma, and follicular lymphoma showed nuclear expression. However, as shown previously with lung carcinoma, experiments with lower antibody dilutions (1:200 to 1:500) showed weak cytoplasmic and nuclear labeling in breast cancers. In addition to chordoma, we show here for the first time that nuclear brachyury expression is prevalent in embryonal carcinoma, seminoma, and small cell carcinoma of the lung but very rare in common carcinomas, sarcomas, and melanoma. With these reservations, we have demonstrated the presence of nuclear brachyury immunoreactivity to be a sensitive and fairly specific marker for chordoma.

Chordoma periphericum: a case report.

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.

Chordomas of the mediastinum: clinicopathologic, immunohistochemical, and ultrastructural study of six cases presenting as posterior mediastinal masses.

Six cases of chordomas presenting as primary posterior mediastinal tumors are described. Three patients were female, and three were male between the ages of 8 and 65 years (mean, 40.6 years). In all cases, the tumors presented radiographically as relatively well-circumscribed, encapsulated soft tissue masses that did not seem to be related to the thoracic or dorsal spine. Only in one case, focal infiltration of bone at the level of T6-T7 was observed at the time of surgery. Histologically, the lesions showed a spectrum of features that ranged from sheets and cords of large cells with abundant vacuolated cytoplasm to small, stellate cells embedded within an abundant mucoid matrix. In one case, the cell population showed more pronounced nuclear atypia with loss of cytoplasmic vacuolization, frequent mitotic figures, necrosis, and solid areas characterized by a perivascular distribution of atypical spindle cells set against a myxoid stroma. Another case showed features of chondroid chordoma, with an immature chondroid-appearing matrix surrounding the atypical tumor cells. Immunohistochemical studies in all cases showed positive staining of the tumor cells with CAM 5.2 and broad-spectrum keratin, epithelial membrane antigen (EMA) and vimentin, and, to a lesser extent, with S-100 protein. Stains for muscle actin, carcinoembryonic antigen (CEA), and desmin were negative. Ultrastructural examination in two cases showed a spectrum of features that varied from large cells with abundant cytoplasm containing scattered ribosomes, glycogen granules, Golgi apparatti, abundant intermediate filaments, and small lumen formation with immature microvilli to smaller cells with elongated cytoplasmic processes, fewer intermediate filaments, rare desmosome type intercellular junctions, and complexes of mitochondria/rough endoplasmic reticulum. On clinical follow-up, two patients died with metastases to the lungs, chest wall, and liver from 1 to 3 years after diagnosis, and two patients are alive and well without evidence of disease after 3 and 16 years. Chordoma should be entertained in the differential diagnosis of posterior mediastinal tumors. Application of immunohistochemical stains or electron microscopy will be of aid in separating them from other conditions that may histologically closely resemble these lesions.

Fine-needle aspiration biopsy in the preoperative diagnosis of chordoma: a study of 17 cases with application of electron microscopic, histochemical, and immunocytochemical examination.

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.

Myasthenia gravis in a man with a history of chordoma: Observations of muscle-like antigens in chordoma

A 67-year-old white man with a remote history of a chordoma of the clivus presented with myasthenia gravis. We investigated the possibility that these conditions were related immunologically. Tissue sections of various chordoma specimens were reacted with dilutions of patient serum and control serum by an indirect immunoperoxidase method. In addition, sections were reacted with antibodies to muscle antigens. Of six chordomas, five reacted positively to patient serum. None reacted to control serum. One chordoma reacted positively to desmin, and all six reacted positively to myoglobin. We propose that the patient may have produced antibody to muscle-like antigens of the chordoma that subsequently cross-reacted with acetylcholine receptor and led to clinical myasthenia gravis.

Chondroid chordoma. A hyalinized chordoma without cartilaginous differentiation.

"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.

Expression of tau proteins and tubulin in extraskeletal myxoid chondrosarcoma, chordoma, and other chondroid tumors.

Tau proteins are microtubule-associated proteins required for the polymerization of tubulin. The abnormal accumulation of tau proteins in neurofibrillary tangles is a well-known phenomenon and has been studied extensively. However, the role of tau protein in chondroid tissue and its neoplasia is unknown. In the present study, 2 extraskeletal myxoid chondrosarcomas (EMCs), 6 chordomas, 6 chondrosarcomas, 3 myxoid chondrosarcomas of bone, 2 osteochondromas, 6 chondroblastomas, and 2 nonneoplastic adult articular cartilages were immunostained with monoclonal antibodies against tau proteins and tubulin. The results showed that the coexpression of tau proteins and tubulin was present only in EMCs (2/2) and chordomas (4/6). Although tubulin was detected in chondroblastomas (5/6), osteochondromas (2/2), chondrosarcomas (5/6), and myxoid-chondrosarcomas of bone (3/3), tau expression was absent in these tumors. The perichondrial chondroblasts but not chondrocytes from nonneoplastic articular cartilage also localize tau and tubulin with a much weaker staining intensity. The results mainly demonstrate that there is frequent expression of tau proteins in some microtubule-rich neoplasms, such as EMC and chordoma. The different immunostaining pattern of tau proteins between chordoma and myxoid chondrosarcoma of bone may be useful in the differential diagnosis, especially when both neoplasms occur in the base of skull.

Immunohistochemical analysis of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin, and neural cell adhesion molecule (NCAM) in chordoma.

AIMS: The epithelioid features seen in chordoma are unique among mesenchymal tumours. However, no detailed analysis regarding cell-cell communication has been conducted in this epithelioid tumour. The aims of this study were to investigate cell-cell communication in chordoma. METHODS: By means of immunohistochemical techniques that incorporated a panel of monoclonal antibodies against cell adhesion molecules (CAMs), including E-cadherin, alpha-catenin, beta-catenin, gamma-catenin, and neural cell adhesion molecule (NCAM), the expression of CAMs was studied in 15 specimens of chordoma and eight specimens of chondrosarcoma. RESULTS: Most chordoma specimens showed some positive immunoreactivity for all the CAMs examined. For the various CAMs investigated, between two and five cases showed diffuse immunoreactions, indicating well preserved expression. Well preserved expression of all the CAMs examined was limited to only one case, thus indicating that the expression of CAMs was decreased in most of the chordoma specimens; however, no significant correlation was found between the decreased expression of CAMs and the histological grade of malignancy, cellular growth pattern, or clinical parameters in chordoma. In chondrosarcoma, only a few specimens showed positive immunoreactivity for CAMs and the expression of E-cadherin, beta-catenin, gamma-catenin, and NCAM was seen more frequently in the chordoma specimens than in the chondrosarcoma specimens. CONCLUSIONS: These results suggest that the expression of CAMs is associated with the formation and maintenance of chordoma tissue architecture, just as it is in other epithelial tumours or normal tissue. Immunohistochemistry for CAMs was found to be of diagnostic value for discriminating chordoma from chondrosarcoma, and these markers could be used along with the cytokeratins, which are already used for this purpose.

New developments in the pathology of skull base tumors.

As an anatomical interface between various tissues, the skull base harbors an exceptionally broad variety of neoplasms, some of which pose a major challenge for surgical pathology. The characterization of distinct immunohistochemical expression profiles and the identification of molecular genetic alterations associated with different tumor entities have significantly advanced this field. The new World Health Organization (WHO) classification of tumors of the nervous system lists 15 histopathological variants of meningioma. Of clinical importance are those entities that carry an increased risk of recurrence and a poor prognosis, i.e., the atypical meningioma (WHO grade II), clear-cell meningioma (WHO grade II), chordoid meningioma (WHO grade II), rhabdoid meningioma (WHO grade III), papillary meningioma (WHO grade III), and anaplastic meningioma (WHO grade III). Diagnostic criteria for atypical and anaplastic meningioma variants have now been stringently defined. The differential diagnosis of meningiomas includes hemangiopericytoma, hemangioblastoma, solitary fibrous tumor, sarcomas, and chordoid neoplasms. Recent data highlight the importance of distinguishing chordoma and chondrosarcoma of the skull base since chondrosarcomas show a significantly better clinical outcome. Among the less common, aggressive tumor entities in this anatomical region, infiltrating pituitary adenoma/pituitary carcinoma, superficial malignant gliomas, rhabdomyosarcoma, olfactory neuroblastoma, various sarcomas, and malignant lymphoma must be considered. Profiles of molecular genetic alterations have been established for several of these neoplasms and may facilitate the differential diagnosis. This review summarizes recent developments in the histopathological characterization, classification, and molecular pathology of neoplasms arising at the skull base.

Ectopic chordoma with orbital invasion.

PURPOSE: To report a rare ectopic chordoma within the orbital wall. METHODS: Case report. RESULTS: 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. CONCLUSION: Orbital wall ectopic localization of a chordoma distant from the clivus is a rare occurrence.

Chordoma cutis.

We report a case of an 85-year-old white man with a diffuse form of psoriasis, who showed a large asymptomatic subcutaneous tumour in the sacrococcygeal region. On cut section there was a subcutaneous neoplasia with a glistening, friable surface. Histologically, the deep dermis was infiltrated by cords and nests of pleomorphic cells embedded in an abundant mucinous stroma, and characteristic physaliphorous (multivacuolated) cells were observed. The neoplastic cells were immunohistochemically positive for cytokeratins (using CAM 5.2 and AE1/AE3), vimentin, S100 protein, and epithelial membrane antigen (EMA), but negative for carcinoembryonic antigen (CEA). Histological and immunohistochemical findings led us to the diagnosis of classic chordoma. Chordomas are rare, slow growing malignant tumours of the spinal axis originating from remnants of the notochord. Occasionally, a skin lesion is the first sign of a primitive or metastatic chordoma.