The Rare Phenomenon of Loss of INI1 Expression at Recurrence/Progression of Primary Central Nervous System Tumors: Report of 3 Cases

Sali, Akash; Chaubey, Vishal; Kodare, Duhita; Sahay, Ayushi; Epari, Sridhar

doi:10.1177/1066896919883942

Cited by 3 publications

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References 28 publications

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“…25 To date, loss of INI1 protein by IHC is considered as the diagnostic feature of AT/RT, as none of the other brain tumors show similar IHC finding except cribriform neuroepithelial tumor, pediatric chordomas, and few case reports of primary CNS tumor with loss of INI1 at progression/recurrence. 4,26 Nonetheless, IHC for INI1 is used consistently to differentiate it from the rest of the brain tumors including medulloblastoma, primitive neuroectodermal tumor, gliomas, and germ cell tumor. 4 In this study, loss of INI1 on IHC was an essential inclusion criterion; hence, all tumors were INI1 negative.…”

Section: Discussionmentioning

confidence: 99%

Atypical Teratoid/Rhabdoid Tumor: Revisiting Histomorphology and Immunohistochemistry With Analysis of Cyclin D1 Overexpression and MYC Amplification

et al. 2020

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Objectives. Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignant pediatric brain tumor, characterized by inactivation of INI1/hSNF5 gene and loss of its protein. We studied the histomorphological and immunohistochemical spectrum of this tumor including cyclin D1 expression and MYC gene amplification. Methods. Cases with INI1 loss by immunohistochemistry (IHC; from 2005 to 2018) were retrieved, reviewed, and evaluated for cyclin D1 expression by additional IHC and fluorescence in situ hybridization for MYC genes. Results. A total of 66 cases were identified. Age ranged from 1 to 20 years (≤3 years, 44 cases; >3 years, 22). Male to female ratio was 1.7:1. Tumor locations were as follows: posterior fossa: 30; supratentorial: 31; spinal: 5. AT/RT in patient ≤3 years was frequently located in the posterior fossa, composed of primitive embryonal morphology ( P = .02), rarely had ample rhabdoid cells ( P = .05), and had a negative impact on overall survival ( P = .04). The rhabdoid cells was a conspicuous component of posterior fossa tumors compared with the supratentorial ones ( P = .06). The supratentorial tumors ( P = .06), absence of rhabdoid cells ( P = .06), and the presence of immunological divergent differentiation ( P = .11) had a comparatively better outcome. Cyclin D1 overexpression (n = 46) was noted in 32 cases and was frequently seen in the posterior fossa tumors ( P = .02). CMYC (n = 42) amplification was seen in 1 case and the NMYC (n = 42) amplification in none. Conclusion. AT/RT can occur in the noninfantile age group, at nonconventional sites and frequently overexpress cyclin D1. The MYC alterations are almost nonexistent in AT/RT.

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Section: Discussionmentioning

confidence: 99%

Atypical Teratoid/Rhabdoid Tumor: Revisiting Histomorphology and Immunohistochemistry With Analysis of Cyclin D1 Overexpression and MYC Amplification

et al. 2020

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“…Traditionally, the ATRTs are identified by a triad of clinical manifestations (less than two years old), histological features including presence of the rhabdoid cells (3,20) defined by eccentric vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasmic inclusions (3,5,21), and IHC results showing the expression of vimentin, smooth muscle actin (SMA), epithelial membrane antigen (EMA), and some other markers such as glial fibrillary acidic protein (GFAP), neuronal markers (neurofilament protein and synaptophysin), and cytokeratin (CK) (21,22). The differential diagnosis of ATRTs includes meduloblastoma, especially large cell/anaplastic variants, poorly differentiated CPC, ependymoma, and other high-grade embryonal tumors, all of which are immunopositive for the INI1 that differentiates them Vol.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of INI1 Protein Expression Through IHC Study in Pediatric High-Grade Brain Tumors in South of Iran in 2008-2021

Mohebbi,

Shokripour,

Mokhtari

2023

Iran J Pathol

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Scan to discover online Background & Objective: Brain tumors are the most frequent solid tumors in children. High-grade tumors are more challenging in diagnosis. Atypical teratoid rhabdoid tumor (ATRT) may be mistaken for other high-grade brain tumors. Molecular genetic analysis of ATRT has shown deletion and mutation in the hSNF5/INI1 gene in most of the cases. The INI1 protein expression can be helpful for the accurate diagnosis. Methods: In this study, immunohistochemical staining (IHC) using INI1 antibody was performed to determine the possibility of ATRT misdiagnosis. Totally, 147 tumors including 6 ATRTs, 81 medulloblastomas, and 60 other CNS tumors were examined in children between 0 and 17 years old.Results: No nuclear staining was found in the six ATRT cases, while most of other CNS tumors demonstrated nuclear staining. Five cases were previously diagnosed with medulloblastoma, primitive neuroectodermal tumor (PNET), and anaplastic oligodendroglioma, while the diagnoses were changed to ATRT based on the reevaluation of the H&E slides and INI1 study. Additionally, two cases were recurrent tumors whose features were consistent with those of ATRT. The INI1 immunostaining was negative in these cases. Conclusion:INI1 was very helpful in distinguishing ATRT from its mimickers in challenging cases. All known ATRT cases in this study were immunonegative for INI1. Thus, INI1 is recommended to be used in the initial IHC panel for the high-grade brain tumors, especially in children under the age of three years, so that they can benefit from intensified therapeutic regimens.

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CNS Low-grade Diffusely Infiltrative Tumors With INI1 Deficiency, Possessing a High Propensity to Progress to Secondary INI1-deficient Rhabdoid Tumors

Nobusawa

Nakata

Nakano

et al. 2020

American Journal of Surgical Pathology

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Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant tumors of the central nervous system that predominantly occur in infants, and are characterized by the presence of rhabdoid cells and inactivation of INI1 or (rarely) BRG1. Most AT/RT are identified as primary tumors; however, rare AT/RT or INI1-deficient RTs arising from other primary tumors have been reported. Here, we report 3 cases of hitherto unclassifiable low-grade tumors with loss of INI1 nuclear expression, for which we propose the designation of central nervous system low-grade diffusely infiltrative tumors with INI1 deficiency (CNS LGDIT-INI1), 2 of which progressed to secondary RT. All 3 CNS LGDIT-INI1 exhibited a similar histology: diffusely distributed small tumor cells with round to oval or irregular nuclei and scant cytoplasm were admixed with degenerative neurons and large reactive astrocytes in an edematous, myxoid, or collagenous background. Mitotic figures were absent. Immunohistochemistry revealed that the tumor cells in all 3 CNS LGDIT-INI1 and 2 RT were negative for INI1. Genetically, total or partial homozygous deletions of the INI1 gene were detected in all CNS LGDIT-INI1 and RT excluding 1 CNS LGDIT-INI1 without sufficient DNA quality and quantity. Despite the loss of INI1 expression, these low-grade lesions were clearly distinguishable from AT/RT by their low proliferative activity, diffusely infiltrative growth pattern, and lack of rhabdoid cells and polyphenotypic immunoreactivity. In conclusion, CNS LGDIT-INI1 may represent a rare group of tumors that are clinically indolent but have a high propensity to progress to RT.

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The Rare Phenomenon of Loss of INI1 Expression at Recurrence/Progression of Primary Central Nervous System Tumors: Report of 3 Cases

Cited by 3 publications

References 28 publications

Atypical Teratoid/Rhabdoid Tumor: Revisiting Histomorphology and Immunohistochemistry With Analysis of Cyclin D1 Overexpression and MYC Amplification

Atypical Teratoid/Rhabdoid Tumor: Revisiting Histomorphology and Immunohistochemistry With Analysis of Cyclin D1 Overexpression and MYC Amplification

Evaluation of INI1 Protein Expression Through IHC Study in Pediatric High-Grade Brain Tumors in South of Iran in 2008-2021

CNS Low-grade Diffusely Infiltrative Tumors With INI1 Deficiency, Possessing a High Propensity to Progress to Secondary INI1-deficient Rhabdoid Tumors

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