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Tumor Progression02:07

Tumor Progression

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Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
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Poorly differentiated SMARCB1/INI1-negative chordomas.

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    Poorly differentiated chordomas with SMARCB1/INI1 loss in children are a distinct entity with aggressive behavior. Diagnostic clues include physaliphorous cells and specific immunohistochemical markers.

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    Area of Science:

    • Pediatric oncology
    • Skeletal pathology
    • Molecular diagnostics

    Background:

    • Chordomas are rare bone tumors arising from notochordal remnants.
    • Poorly differentiated chordomas (PDCs) represent an aggressive subtype with limited understanding.
    • SMARCB1/INI1 loss is a key molecular event in certain pediatric tumors.

    Observation:

    • This study analyzed four pediatric cases of PDCs exhibiting SMARCB1/INI1 loss.
    • Histological features included atypical fusiform cells and prominent cytoplasmic vacuoles (physaliphorous cells).
    • Immunohistochemistry confirmed loss of SMARCB1/INI1 expression and nuclear brachyury, with positive staining for Glut-1, keratins, EMA, and vimentin.

    Findings:

    • All analyzed PDCs demonstrated loss of SMARCB1/INI1 expression, confirmed by immunohistochemistry and FISH in most cases.
    • These tumors showed distinct histopathological features compared to conventional chordomas.
    • Nuclear brachyury expression was consistently observed in these PDCs.

    Implications:

    • SMARCB1/INI1-negative PDCs constitute a unique and aggressive subset of chordoma in children.
    • Recognizing physaliphorous cells and utilizing a panel of markers (brachyury, Glut-1, keratins, INI1) aids in diagnosis.
    • Accurate classification is crucial for appropriate management and distinguishing from conventional chordomas due to differing prognoses.