Scientists report first case of immunohistochemical marker confirming diagnosis of extra-axial dedifferentiated chordoma

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n exceptionally rare and aggressive malignant bone tumor was positively confirmed via the expressions of a DNA protein transcription factor, according to a recent study by American researchers.

ai???We herein report an exceptional case of extra-axial dedifferentiated chordoma confirmed by the expression of brachyury, the first case report of this kind,ai??? reported surgical pathologist Dr. Evita Bonita Henderson-Jackson and her research colleagues from Moffitt Cancer Center in Tampa, Florida, United States, in a case report offering literature review and pathologistsai??i?? perspective, published by the free access peer-reviewed journal Advances in Modern Oncology Research (AMOR).

Chordoma, or bone tumor of the skull and spine, is a very uncommon type of cancer with low prognosis (55% for a five-year survival), and accounts for about 3% of all bone tumors. Every year in the United States, according to the Chordoma Foundation, only one new case per million people is diagnosed. In the entire population of 321 million people in the United States, there are scarcely 2,400 chordoma patients.

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Chordoma of the cervical spine: T2 weighted images with and without fat suppression. Notice the involvement of more than one vertebral level, extensive soft tissue mass and very high signal intensity. (Source: radiologyassistant.nl)

The tumor primarily occurs within the axial skeleton, along a human bodyai??i??s spinal axis from the skull to the tailbone. When identified outside of the axial skeleton, these subsets are known as extra-axial chordomas. Chordoma has no known environmental, dietary or lifestyle risk factors, and is believed to emerge from the remnants of embryonic notochord ai??i?? a rod-shaped, cartilage-like scaffolding structure during the early formation of the spinal column. Notochord cells normally persist after birth, lodged inside the spine and skull, until becoming malignant to form chordoma.

Diagnostic challenge

Dedifferentiated chordoma, meanwhile, is a fatal variant of conventional chordoma that is even rarer, occurring in only 2%ai??i??8% of all chordomas. It is typically identified following radiation therapy of primary tumors or as recurrences, and with its additional high-grade sarcomatous elements, i.e. malignancies affecting connective tissues, dedifferentiated chordoma is known to be very aggressive and likely to culminate in distant metastases, thus accelerating the patientai??i??s demise to within one year of diagnosis.

It is difficult to identify chordoma ai??i?? let alone dedifferentiated chordoma ai??i?? at extra-axial sites, according to the researchers. ai???There have been only a few reports of primary dedifferentiated chordoma,ai??? they noted. ai???Owing to its rarity, especially when it is in an unusual extra-axial location, primary dedifferentiated chordoma presents a diagnostic challenge.ai???

The ability to accurately identify the extra-axial skeletal and soft tissue chordomas is of paramount importance, according to the researchers, as the treatment and prognosis of this neoplasm is vastly different than that of other neoplasms, which it could be misdiagnosed as.

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In addition to displaying features of conventional chordoma, dedifferentiated chordoma harbors sarcomatous areas similarly ravaged by other tumors. ai???The sarcomatous areas commonly appear as high-grade undifferentiated spindle cell sarcoma; however, other histomorphologies have also been reported, such as fibrosarcoma, osteosarcoma, or rhabdomyosarcoma,ai??? the study reported.

Clinicians examining a neoplasm would still need to review clinical and radiological findings to determine elements of a metastatic carcinoma, according to the study; however, ai???[i]f history does not indicate metastasis and tumor of unknown origin is raised, a panel of immunostains including brachyury would be of value,ai??? it proposed.

Sensitive marker

Brachyury, a member of the T-box protein family bounded to specific DNA sequences, is a transcription factor which initiates and regulates the rate of transcription of genetic information, and it is highly expressed in nearly every chordoma tumor.

ai???[B]rachyury was identified as a sensitive and specific marker for chordoma with the ability to discern between extra-axial chordoma and other chordoma-like lesions such as parachordoma/myoepithelioma,ai??? explained Dr. Henderson-Jackson and her research colleagues

ai???Given that extra-axial chordomas are rare and our case of extra-axial dedifferentiated chordoma is even rarer, brachyury is extremely useful in confirming the diagnosis,ai??? they said, adding that brachyury nuclear expression has been observed in most axial and skull-based chordomas, ranging between 89.7% and 100%, including dedifferentiated and metastatic ones.

For their study, the researchers examined the case of a 68-year-old female suffering from pain and swelling with purple discoloration on her right foot, who was originally diagnosed with plantar fasciitis at a different facility but a post-surgery MRI later reported the presence of a multilobulated and erosive mass.

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Noted the study, ai???A core needle biopsy of the right plantar foot mass was performed at an external hospitalai??i??and the pathology results showed the possibility of dedifferentiated chondrosarcoma.ai??? However, the case referred for consultation at yet another facility, which instead diagnosed the lesion as an epithelioid malignant neoplasm, favoring carcinoma over epithelioid sarcoma, according to the study.

When the patient sought a secondary suggestion from Moffitt Cancer Center, her core biopsy was reviewed, and ai???the histological sections revealed poorly differentiated malignant neoplasm,ai??? reported the authors, while noting that carcinoma, melanoma, and sarcoma were all fair diagnoses at that point.

Upon immunohistochemical staining, however, the ai???immunostain panel does not support epithelioid sarcoma, melanoma, angiosarcoma, malignant peripheral nerve sheath tumor, renal cell carcinoma, or leiomyosarcoma,ai??? said the researchers.

Additionally, closer examination of the core biopsy revealed ai???small groups of cells that had clear and vacuolated cytoplasm with myxoid matrixai??? suggestive of a chordoma, according to the study. A brachyury immunostain was performed for confirmation, and it showed uniform and diffuse nuclear positivity.

ai???Specifically, the recognizable chordoma-like areas were brachyury-positive while the dedifferentiated areas were negative,ai??? the authors reported. Given the morphology and immunophenotype, a diagnosis of dedifferentiated chordoma with extra-axial type was rendered.

Additional immunohistochemical stains were performed in order to compare the pattern of staining in the resection to the prior biopsy: ai???The histomorphology and immunohistochemical staining pattern, including the positive brachyury nuclear expression, were identical to the findings in the core biopsy supporting the diagnosis of dedifferentiated chordoma, extra-axial type,ai??? the study concluded.

There are only 10 reported cases of brachyury-positive skeletal extra-axial chordoma in entire English-language scientific literature, according to the researchers. ai???Based on our knowledge and findings, this report is the first to report an extra-axial dedifferentiated brachyury-positive chordoma,ai??? they said.

The team of researchers also included Marilyn Bui from Moffitt Cancer Centerai??i??s Department of Anatomic Pathology, Jaime Caracciolo from the Department of Radiology and Douglas Letson from the Department of Sarcoma.

The case report is available AMOR website at http://www.advmodoncolres.com.

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Foot mass surgical resection. (a) On the right side of the image, neoplastic cells with abundant, clear, vacuolated cytoplasm is present and on the left side of the image, neoplastic cells with sarcomatoid morphology with moderate to marked nuclear atypia and eosinophilic cytoplasm is seen (hematoxylin and eosin, x200). (b) Strong nuclear positivity with brachyury (x200) on the right side of image; dedifferentiated area shows negative staining on the left side of image.