Notochordal Tumor Research Articles

Diagnostic Utility of Squash Smear Cytology in Chordoma: A Tertiary Care Center Experience

Abstract Background and Aims: Chordomas are rare notochordal tumors. They are suitable candidates for squash smear cytology (SSC) owing to their gelatinous consistency and destructive nature. SSC is an important tool for making a quick intra-operative preliminary diagnosis and taking real-time surgical and further management decisions. This study aimed to evaluate the diagnostic accuracy of SSC for chordoma cases. Materials and Methods: This retrospective study conducted in a North Indian tertiary care center enrolled chordoma cases histopathologically diagnosed between 01.01.2013 and 31.07.2023, for which SSC was also performed. SSC smears and their corresponding histopathology slides (±immunohistochemistry [IHC] slides) were retrieved. Histo-cytological correlation was performed. Results: In total, 13 such cases were retrieved. The mean age was 34.4 + 5.6 years. The male–female ratio was 1:1.6. The most common location was the spheno-occipital region (10 cases), followed by sacro-coccygeal (two cases) and vertebral regions (1 case). The SSC was positive for chordoma in 10/13 cases. Thus, the calculated accuracy of SSC in chordoma diagnosis was 76.9%. A total of 3/13 (23.1%) cases where SSC was inconclusive for chordoma were difficult to diagnose cases, requiring IHC for ultimate diagnosis. Cytological features such as abundant myxoid matrix and physaliphorous cells help in correct diagnosis of chordoma on SSC. Conclusions: We found the diagnostic accuracy of SSC in chordoma diagnosis to be 76.9%. Features such as abundant myxoid matrix and physaliphorous cells are helpful in correct diagnosis on SSC. Thus, even though chordomas are rare, one should consider them among the differential diagnoses in cases presenting with appropriate clinico-radiological features and characteristic cytological findings.

Mesenchymal and Non-meningothelial Tumors Involving the Central Nervous System

In the World Health Organization Classification of Brain Tumors Fifth Edition, mesenchymal non-meningothelial tumors involving the central nervous system are divided into three major categories: soft tissue tumors, chondro-osseous tumors, and notochordal tumors. Soft tissue tumors are classified into four groups: fibroblastic and myofibroblastic tumors, vascular tumors, skeletal muscle tumors, and tumors of uncertain differentiation. This article will focus on solitary fibrous tumors(SFTs), which are frequently encountered clinically and continue to undergo classification revisions in the 5th edition, and outline the three newly added histological diagnoses. Although SFTs and hemangiopericytomas occur throughout the body, including the central nervous system, nomenclatures have been different between the classifications of "Tumours of Soft Tissue and Bone" and "Tumours of the Central Nervous System." The latest nomenclature is "SFT" in accordance with the nomenclature of bone and soft-tissue tumors. In addition, three new diagnoses, which are intracranial mesenchymal tumor FET-CREB fusion-positive, CIC-rearranged sarcoma, and primary intracranial sarcoma DICER1-mutant, have been defined based on genetic abnormalities in tumors of uncertain differentiation.

Some CNS sarcomas seen: A 22-year series.

Central nervous system (CNS) and spine are seldom impacted by primary or metastatic sarcomas. We reviewed our 22-year experience with metastatic versus primary mesenchymal sarcomas in adults versus pediatric patients, additionally asking how many might today undergo nomenclature changes using CNS World Health Organization, 5th edition criteria. Case identification via text word search of pathology databases from our adult and pediatric referral hospitals, 2000 to August 2022, with exclusion of peripheral nervous system and primary chondro-osseous and notochordal tumors. Demographic, immunohistochemical, fluorescence in situ hybridization (FISH), and fusion results performed at the time of original diagnosis were acquired from reports. 57 cases were identified, with a 16 : 15 primary and 19 : 7 metastatic ratio in adult versus pediatric patients. Ewing sarcoma was the most frequent type (n = 18, 7 adult, 11 pediatric), with a rare primary PEComa, 2 alveolar soft part sarcomas, and metastatic angiosarcoma in the cohort. Only 3 cases, an intracranial sarcoma, DICER-1 mutant formerly diagnosed as rhabdomyosarcoma, an intracranial mesenchymal tumor, FET::CREB fusion-positive formerly diagnosed as angiomatoid fibrous histiocytoma, and a CIC-rearranged sarcoma required nomenclature updating by CNS WHO5 criteria. Few primary or metastatic, adult or pediatric, CNS/spinal sarcomas required nomenclature updates; almost all had been satisfactorily classified at the time of diagnosis, using immunohistochemistry, FISH, or fusion results.

Update of pediatric bone tumors-other mesenchymal tumors of bone, hematopoietic neoplasms of bone, and WHO classification of undifferentiated small round cell sarcomas of bone.

There are numerous bone tumors in the pediatric population, with imaging playing an essential role in diagnosis and management. Our understanding of certain bone tumors has rapidly evolved over the past decade with advancements in next-generation genetic sequencing techniques. This increased level of understanding has altered the nomenclature, management approach, and prognosis of certain lesions. We provide a detailed update of bone tumors that occur in the pediatric population with emphasis on the recently released nomenclature provided in the 5th edition of the World Health Organization Classification of Soft Tissue and Bone Tumours. We discuss other mesenchymal tumors of bone, hematopoietic neoplasms of bone, and WHO classification of undifferentiated small round cell sarcomas of bone. We have detailed osteogenic tumors and osteoclastic giant cell-rich tumors, as well as notochordal tumors, chondrogenic tumors, and vascular tumors of the bone in separate manuscripts.

Chordoma: Retrospective analysis of patients treated with radiotherapy at a single institution

Introduction: Chordoma is a low-grade notochordal tumor of the skull base, mobile spine, and sacrum, which is locally invasive and tends to present late in the disease course and confers a poor prognosis. They usually recur locally and surgery is the mainstay of treatment. Radiotherapy (RT) is often given postoperatively to reduce local recurrence. The purpose of this study is to assess RT treatment given at our center for chordoma patients. Materials and Methods: In this retrospective analysis, 25 patients with chordoma treated with RT between 2013 and 2020 at a single institution were reviewed. Eleven patients had sacrococcygeal tumors, three had clival tumors, two had lumbar, one had sphenoid tumors, one had nasal cavity tumors, two had cervical spine tumors, and two had sellar/suprasellar tumors. Out of 25 patients, 19 patients underwent surgical excision (partial/complete) and in 6 patients only a biopsy was done. Two patients underwent recurrent surgical excision. All patients received RT either postoperative or in recurrent settings or after biopsy only. The median RT dose was 30 Grey (Gy) (range, 16–60 Gy). Results: On analysis, seven patients were lost to follow-up. Three patients were on follow-up till 56, 53, and 41 months and were included in a 4-year survival analysis. Eighteen patients follow-up were available. Out of 18 patients, 8 patients had died and 10 patients were alive. With the median follow-up of 37.5 months, the 4-year overall survival rate was 61.9% in 21 patients. With the median follow-up of 39 months, the 5-year overall survival rate was 55.6% in 18 patients. Conclusions: RT in the postoperative setup may improve the overall survival in chordoma patients. Further detailed analysis is necessary for RT dose and/or higher techniques need to be used for local control of the disease.

Chordoma: analysis of 47 fine-needle aspiration biopsy, cytologic imprint, and small biopsy specimens.

Fine-needle aspiration (FNA) and small tissue biopsy of chordoma have been reported in several small series, but no large series exists. We undertook an examination of 47 cases (with concurrent core needle biopsy in a subset) to analyze diagnostic accuracy, cytomorphology, and immunohistochemistry. Our cytopathology files were searched for examples of chordoma with histopathologic verification. FNA biopsy smears and core needle were performed using standard techniques. Forty-seven cases of chordoma were retrieved from 44 patients [M:F; 1.8:1; age range 5-81 years; mean age 55 years]. Twenty-seven presented with primary, 10 with locally recurrent, and 7 with metastatic tumors. Two aspirates were from the appendicular skeleton, 2 from the trunk, 1 from neck lymph node, and 42 aspirates (89%) from axial and peri-axial skeleton and surrounding soft tissues. Four were cytologic touch imprints while the remainder were FNA biopsy specimens. Specific cytologic diagnoses were chordoma/consistent with chordoma (44 cases, 94%), suspicious for chordoma (2), and malignant neoplasm (1). Along with a single case of benign notochordal tumor misdiagnosed as chordoma, our diagnostic accuracy was 91%. Concurrent tissue biopsy was performed in 51% of cases. Immunohistochemical staining of tumor in 29 (62%) cases showed expression of brachyury in 23 of 24 (96%) instances. Cytopathology consisted of cellular smears populated by large cells possessing enormous amounts of vacuolated and non-vacuolated cytoplasm with an abundant background myxoid/chondromyxoid stroma. FNA and small tissue biopsy specimens show a very high degree of diagnostic accuracy in recognition of chordoma.

Update of pediatric bone tumors-notochordal tumors, chondrogenic tumors, and vascular tumors of the bone.

There are numerous bone tumors in the pediatric population, with imaging playing an essential role in diagnosis and management. Our understanding of certain bone tumors has rapidly evolved over the past decade with advancements in next-generation genetic sequencing techniques. This increased level of understanding has altered the nomenclature, management approach, and prognosis of certain lesions. We provide a detailed update of bone tumors that occur in the pediatric population with emphasis on the recently released nomenclature provided in the 5th edition of the World Health Organization Classification of Soft Tissue and Bone Tumours. In the current manuscript, we address notochordal tumors, chondrogenic tumors, and vascular tumors of the bone.

Chordoma-An update

Chordomas are rare malignant tumors of the axial skeleton with notochordal differentiation. From amorphological point of view, chordomas display abroad spectrum ranging from the classical, conventional form not otherwise specified (NOS) to forms with hepatoid or renal carcinoma-like differentiation or even poorly or dedifferentiated variants. The detection of brachyury is highly characteristic, though not exclusive. The morphological differential diagnosis from abenign notochordal tumor (BNCT) requires integration of imaging since BNCT is limited to the vertebral bodies and is not osteolytic. Targeted therapy is a current research focus and cell lines as in vitro models are aprecondition for the establishment and validation of this approach.

Les tumeurs notochordales : de la notochorde au chordome

The group of notochordal tumors consists of the benign notochordal cell tumor and the conventional, dedifferentiated and poorly differentiated chordomas in the fifth edition of the WHO classification of bone and soft tissue tumors. This update covers recent advances in the knowledge of the histogenesis and biology of these tumors and their implications in terms of diagnosis, prognosis assessment and therapeutic management.

Multicentric Chordoma With Initial Resection by Bilateral Transcondylar Approach: 2-Dimensional Operative Video.

Chordoma is a rare skull base tumor with malignant behavior.1-3 It invades locally with high recurrences, metastasizes distally, and seeds after interventions.1-4 Chordoma exemplifies the malignant progression doctrine as it accumulated genetic mutations. The natural history of untreated disease is 2.4 yr on average survival.5 Best tumor control is achieved by radical resection, followed by high doses radiation. Multicentric chordoma is an ill-defined challenging entity extremely rare in the literature. However, chordoma is known for distal metastasis, particularly to the lungs, iatrogenic cerebrospinal fluid (CSF) dissemination with drop metastasis, or surgical implantation. A subset of patients present with synchronous or metachronous regional or distal neuraxial lesions associated with the initial chordoma. Patients presenting with multicentric bony axial lesions and no extra-axial metastases point toward the multicentric chordoma concept rather than local, hematogenous, or CSF spread.6-12 Biopsy of these multicentric lesions can show a spectrum of abnormalities ranging from benign notochordal tumor to chordomas confirming the multicentric hypothesis.9 We present a patient who underwent a bilateral transcondylar approach for giant craniovertebral junction chordoma and then treated with radiation and a second lesion at the C6 transverse foramen. Six years later, she presented with a chordoma at the petrous apex. The patient consented to surgery and to the publications of her image. The participants and any identifiable individuals consented to publication of his/her image. Image at 1:39 reprinted with permission from Al-Mefty O, Operative Atlas of Meningiomas. Vol 1, © LWW, 1998.

Clinicopathological features of notochordal tumors: a study of 48 cases

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of notochordal tumors. Methods: The clinical, radiologic and pathologic data of 48 notochordal tumors were collected from 2008 to 2019 at Shanghai Jiaotong University Sixth People's Hospital. Expression of cytokertin, S-100 protein, vimentin, brachyury and INI1 was detected by immunohistochemistry. The pathologic differential diagnoses and biologic behavior of various types of notochordal tumors were analyzed using the new standard in the 5th edition of WHO tumor classification. Results: Four cases of benign notochordal cell tumor were confined to vertebral body. Histopathologically, they lacked lobular architecture and extracellular myxoid matrix. The tumor cells were vacuolated and had centrally or peripherally located round to oval nuclei, with small nucleoli, without atypia, mimicking mature adipocytes. No mitotic figures were seen. Two cases of poorly differentiated chordoma, from patients aged 12 years and 21 years respectively, were located in cervical vertebra, and were composed of cohesive sheets or nests of epithelioid cells, with focal rhabdoid morphology. There was relatively abundant eosinophilic cytoplasm and scattered cytoplasmic vacuoles. The moderately pleomorphic nuclei were round to ovoid with vesicular chromatin and mitotic figures could be seen. Extracellular myxoid stroma was observed focally. Forty cases of conventional chordoma and two cases of extra-axis chordoma had similar histologic features. All 48 cases expressed cytokeretin, 45 cases expressed brachyury, and two poorly differentiated tumors showed loss of INI1/SMARCB1. Conclusions: There are four subtypes of chordomas: conventional, dedifferentiated, poorly differentiated and extra-axis. Chondroid chordoma is no longer thought to be a distinct entity. Each type has its unique clinicopathological characteristics. Brachyury is highly specific and sensitive for the diagnosis of various notochordal tumors. Poorly differentiated chordoma shows distinct clinicopathological features, including young age and loss of immunohistochemical expression of INI1/SMARCB1, and its diagnosis requires the combined detection of brachyury and INI1/SMARCB1.

Chordoma-Current Understanding and Modern Treatment Paradigms.

Chordoma is a low-grade notochordal tumor of the skull base, mobile spine and sacrum which behaves malignantly and confers a poor prognosis despite indolent growth patterns. These tumors often present late in the disease course, tend to encapsulate adjacent neurovascular anatomy, seed resection cavities, recur locally and respond poorly to radiotherapy and conventional chemotherapy, all of which make chordomas challenging to treat. Extent of surgical resection and adequacy of surgical margins are the most important prognostic factors and thus patients with chordoma should be cared for by a highly experienced, multi-disciplinary surgical team in a quaternary center. Ongoing research into the molecular pathophysiology of chordoma has led to the discovery of several pathways that may serve as potential targets for molecular therapy, including a multitude of receptor tyrosine kinases (e.g., platelet-derived growth factor receptor [PDGFR], epidermal growth factor receptor [EGFR]), downstream cascades (e.g., phosphoinositide 3-kinase [PI3K]/protein kinase B [Akt]/mechanistic target of rapamycin [mTOR]), brachyury—a transcription factor expressed ubiquitously in chordoma but not in other tissues—and the fibroblast growth factor [FGF]/mitogen-activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK] pathway. In this review article, the pathophysiology, diagnosis and modern treatment paradigms of chordoma will be discussed with an emphasis on the ongoing research and advances in the field that may lead to improved outcomes for patients with this challenging disease.

Spontaneous tension pneumocephalus and pneumoventricle in ecchordosis physaliphora: case report of a rare presentation and review of the literature

We describe the case of a 65-year-old lady who presented with mutism and a right hemiparesis. Imaging showed a severe spontaneous tension pneumocephalus. The cause was diagnosed as Ecchordosis physaliphora (EP). EP is a rare cystic congenital hamartomatous benign notochordal tumor (BNCT) arising from an ectopic notochordal remnant. To the authors’ knowledge, this is the first case of EP to be described in the literature which presented with a life-threatening but treatable condition of severe tension pneumocephalus.

Notochordal tumors : Benign notochordal tumors and chordomas

Benign notochordal tumors (BNCT) and chordomas are primary bone tumors of the spine with apredominant 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 aloss 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.

Proximal tibial extra-axial chordoma masquerading as renal cell carcinoma metastasis

Chordomas are rare, locally aggressive notochordal tumors, which most frequently occur in the neuraxis. We describe the case of a 74-year-old male with a history of renal cell carcinoma, who presented with a slowly enlarging mass in his left leg. While the clinical history and imaging suggested metastatic renal cell carcinoma, immunohistochemical staining with brachyury ultimately made the diagnosis of extra-axial chordoma. At 74 years of age, our patient is the oldest ever reported with bony extra-axial chordoma objectively confirmed by brachyury staining. A detailed case discussion and a review of the available literature on this rare clinicopathologic entity are provided.

Diagnosis and Treatment of Benign Notochordal Cell Tumors of the Spine

Clinical case series. To describe the clinical, radiological, and histological presentation of a series of patients presenting with benign notochordal tumors, and review the existing literature on the topic. During the past decade, several authors have reported a spine tumor with benign clinical characteristics and histological resemblance to notochordal tissue. The prognosis and appropriate management remain controversial. Description of clinical, radiological, and histological findings in 3 patients with benign notochordal tumors of the spine. All cases presented with subacute mild pain, without neurological deficit. Tumors developed at L3, S1, and S4, without canal involvement or apparent instability. The first 2 patients presented with classic imagenological findings were treated conservatively, showing no progression on follow-up. The last patient presented an atypical lytic pattern and contrast enhancement on magnetic resonance imaging, and underwent en bloc resection, with significant associated morbidity. Histopathology of the specimen revealed coexistent foci of incipient chordoma. Benign notochordal cell tumors represent a clinical entity derived from notochordal tissue, with characteristics distinct but closely related to the classic chordoma. Some radiological features may suggest the presence of chordoma precursors. Because its true potential for aggressiveness is still undetermined, a careful decision making must weigh the morbidity of en bloc procedures in the spine with uncertain natural history.

Role of Diffusion-Weighted MRI in Clival Chordoma

Purpose: Chordoma is a rare notochordal tumor with a proclivity for the skull base and sacrococcygeal region. Poorly differentiated chordoma (PDC), as reported in the pediatric literature, displays more aggressive behavior compared with classic chordoma (CC). We investigated the role of diffusion-weighted imaging (DWI) MRI in evaluating these chordoma types.

Multicentric Chordoma

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.

Revisiting chordoma with brachyury, a "new age" marker: analysis of a validation study on 51 cases.

Abstract Context.—Chordoma is a rare, notochordal tumor with a characteristic histomorphology and immunohistochemical profile. At times, it presents a diagnostic challenge, especially in small biopsies. Brachyury, a nuclear transcription factor, is a recently described immunohistochemical marker for diagnosing chordomas. Objective.—To study the sensitivity and specificity of brachyury in diagnosing chordomas by comparing its expression in axial chordomas with nonchordomatous tumors. Design.—Fifty-one axial chordomas, accessioned during a 10-year period, and 58 nonchordomatous tumors were subjected to brachyury staining by immunohistochemistry. Results.—The 51 chordomas occurred in 36 men and 15 women. Sitewise, 34 cases (66.7%) occurred in the sacrococcyx, 9 (17.6%) in the spine, and 8 (15.7%) in the skull base. Histologically, 34 cases (66.7%) were classical chordomas, 13 cases (25.5%) had a dominant chondroid component, and 2 cases each (3.9%) were chondroid chordomas and dedifferentiated chordomas, res...

Revisiting Chordoma With Brachyury, a “New Age” Marker: Analysis of a Validation Study on 51 Cases

Chordoma is a rare, notochordal tumor with a characteristic histomorphology and immunohistochemical profile. At times, it presents a diagnostic challenge, especially in small biopsies. Brachyury, a nuclear transcription factor, is a recently described immunohistochemical marker for diagnosing chordomas. To study the sensitivity and specificity of brachyury in diagnosing chordomas by comparing its expression in axial chordomas with nonchordomatous tumors. Fifty-one axial chordomas, accessioned during a 10-year period, and 58 nonchordomatous tumors were subjected to brachyury staining by immunohistochemistry. The 51 chordomas occurred in 36 men and 15 women. Sitewise, 34 cases (66.7%) occurred in the sacrococcyx, 9 (17.6%) in the spine, and 8 (15.7%) in the skull base. Histologically, 34 cases (66.7%) were classical chordomas, 13 cases (25.5%) had a dominant chondroid component, and 2 cases each (3.9%) were chondroid chordomas and dedifferentiated chordomas, respectively. Brachyury staining was positive in 46 of the 51 chordomas (90.2%) and negative in all 58 nonchordomatous tumors. The dedifferentiated area in 2 chordomas was negative for brachyury staining. Fourteen of 15 chordomas with chondroid component showed positive brachyury staining. Immunohistochemical expression of other markers, included cytokeratin (positive in 23 of 23 cases; 100%), epithelial membrane antigen (positive in 22 of 22 cases; 100%) and S100 protein (positive in 18 of 21 cases; 85.7%). Exclusive brachyury expression in more than 90% of chordomas indicates its value as a unique, specific marker with other sensitive markers like cytokeratin, epithelial membrane antigen, and/or S100 protein in substantiating a diagnosis of chordoma, including on small biopsies.