ATRT-04. LATE DEVELOPMENT OF METACHRONOUS ATYPICAL TERATOID/RHABDOID TUMORS (AT/RTS) OR MALIGNANT RHABDOID TUMOR (MRT) IN THREE PATIENTS WITH GERMLINE SMARCB1 MUTATIONS

Rhabdoid tumor predisposition syndrome (RTPS) is defined as the presence of a SMARCB1 or SMARCA4 genetic aberration in a patient with malignant rhabdoid tumor. Patients with RTPS are more likely to present with synchronous or metachronous rhabdoid tumors. Based on the current state of rhabdoid tumor taxonomy, these diagnoses are based largely on patient demographics, anatomic location of disease, and immunohistochemistry, despite their nearly identical histologic and immunohistochemical profiles. Thus, the true distinction between such tumors remains a diagnostic challenge. Central nervous system atypical teratoid/rhabdoid tumor (AT/RT) is a rare, aggressive, primarily pediatric malignancy with variable histologic features and a well documented association with loss of SMARCB1 expression. Epithelioid sarcoma (ES) is a rare soft tissue tumor arising in patients of all ages and characteristically staining for both mesenchymal and epithelial immunohistochemical markers while usually demonstrating loss of SMARCB1 expression. To our knowledge we herein present the first documented case of a patient with RTPS who presented with metachronous AT/RT and ES.

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ATRT-21. RHABDOID PREDISPOSITION SYNDROME: REPORT OF MOLECULAR PROFILES AND TREATMENT APPROACH IN THREE CHILDREN WITH SYNCHRONOUS ATYPICAL TERATOID/RHABDOID TUMOR AND MALIGNANT RHABDOID TUMOR

Neuro-Oncology ◽

10.1093/neuonc/noaa222.020 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii280-iii280

Author(s):

Margaret Shatara ◽

Ajay Gupta ◽

Mohamed H Abu Arja ◽

Suzanne E Conley ◽

Priyal Patel ◽

...

Keyword(s):

Molecular Profiling ◽

Rhabdoid Tumor ◽

The Other ◽

Hematopoietic Progenitor Cell ◽

Induction Phase ◽

Malignant Rhabdoid Tumor ◽

Atypical Teratoid Rhabdoid Tumor ◽

Consolidation Phase ◽

Atypical Teratoid ◽

Rhabdoid Tumors

Abstract BACKGROUND Rhabdoid predisposition syndrome is characterized by germline alterations in SMARCB1 or SMARCA4, leading to synchronous or metachronous central nervous system (CNS) and extra-CNS rhabdoid tumors. Rare survivors have been reported to date. METHODS We describe the molecular profiling and treatment regimen of three patients with synchronous atypical teratoid/rhabdoid tumor (ATRT) and malignant rhabdoid tumor of the kidney (MRT-K). All patients underwent radical nephrectomy of the kidney, and gross total resection of the primary CNS tumor was achieved for two patients. An intensive chemotherapy regimen was administered; an induction phase based on the modified Third Intergroup Rhabdomyosarcoma Study (IRS-III) for ATRT followed by a consolidation phase with three cycles of high-dose chemotherapy and autologous hematopoietic progenitor cell rescue, without irradiation. All three patients were enrolled on an institutional comprehensive genomic profiling protocol. RESULTS A germline focal 22q deletion, including SMARCB1, was detected in two patients, while the third patient had a maternally-inherited heterozygous frameshift variant in SMARCB1. Somatic loss of heterozygosity of 22q was identified in all patients, resulting in biallelic inactivation of SMARCB1. Divergent tumor subgroups were described using DNA methylation. The three MRT-K samples were classified as MYC subtype. One ATRT was classified as SHH while the other as TYR. One patient is currently three years off-therapy without evidence of disease, while the other two patients have completed the consolidation phase without recurrent disease. CONCLUSION Molecular profiling of CNS and extra-CNS rhabdoid tumors revealed different epigenetic subgroups. An intensive multimodal therapeutic approach without irradiation may achieve prolonged survival.

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Case Report: The Emerging Role of Ring Chromosome 22 in Phelan-McDermid Syndrome With Atypical Teratoid/Rhabdoid Tumor: The First Child Treated With Growth Hormone

Frontiers in Neurology ◽

10.3389/fneur.2021.741062 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marco Crocco ◽

Marta Panciroli ◽

Claudia Milanaccio ◽

Cristina Morerio ◽

Antonio Verrico ◽

...

Keyword(s):

Growth Hormone ◽

Ring Chromosome ◽

Suppressor Gene ◽

Rhabdoid Tumor ◽

Chromosome 22 ◽

First Case ◽

Atypical Teratoid ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

Atypical teratoid/rhabdoid tumors (AT/RTs) in the rhabdoid tumor predisposition syndromes are most often caused by germline mutations of the SMARCB1 gene located in chromosome 22q11.2. Although rarely, it can also result from the constitutional ring chromosome 22 (r22): during mitosis the ring chromosome may lead to an increased rate of somatic mutations, resulting in rhabdoid tumor predispositions when the tumor-suppressor gene SMARCB1 is involved. Individuals with r22 may present similar features as those with Phelan-McDermid syndrome (PMDS) due to 22q13.3 deletion, including the SHANK3 gene. Despite several reports on AT/RT in children with r22 and/or PMDS have been published, the role of constitutional r22 as new oncogenic mechanism for AT/RT is still under investigation. There is not a lot of data available on therapeutic and prognostic implications of r22 in AT/RT and PMDS. Herein, we present the first case of a child with constitutional r22, PMDS and AT/RT of the brain, who is a long term survivor and is been treated with growth hormone. We also describe an unexpected adverse reaction to midazolam.

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Atypical teratoid rhabdoid tumor in a 65-year-old man presenting with disseminated leptomeningeal disease: A case report and review of the literature

SAGE Open Medical Case Reports ◽

10.1177/2050313x18775298 ◽

2018 ◽

Vol 6 ◽

pp. 2050313X1877529

Author(s):

Marc-Alain Babi ◽

Peter Fecci ◽

Matthew Luedke ◽

Olinda Pineda ◽

Yasmin Ali O’Keefe

Keyword(s):

Brain Biopsy ◽

Rhabdoid Tumor ◽

Leptomeningeal Disease ◽

Atypical Teratoid Rhabdoid Tumor ◽

Review Of The Literature ◽

Progressive Encephalopathy ◽

Atypical Teratoid ◽

Aggressive Tumor ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

Central nervous system atypical teratoid rhabdoid tumors are very rare aggressive tumor of childhood, primarily occurring at age of less than 3 years old. The prognosis of these tumors is very poor, with a reported median survival of 6–12 months in most cases. Treatment typically consists of aggressive chemotherapy and radiotherapy. We present the case of a 65-year-old man who presented with progressive encephalopathy and change in personality over 3 months period. The patient had further accelerated decline over 3 weeks. The diagnosis of atypical teratoid rhabdoid tumor initially remained elusive despite very extensive workup, but was eventually confirmed via open brain biopsy. To the best of our knowledge, this is the oldest reported case of atypical teratoid rhabdoid tumor in the literature. We further extend the spectrum of this rare disease.

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ATRT-08. A PHASE II STUDY OF CONTINUOUS LOW DOSE PANOBINOSTAT IN PAEDIATRIC PATIENTS WITH MALIGNANT RHABDOID TUMORS/ATYPICAL TERATOID RHABDOID TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.008 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii277-iii277

Author(s):

Paul Wood ◽

Jayesh Desai ◽

Kelly Waldeck ◽

Jason Cain ◽

Nick Gottardo ◽

...

Keyword(s):

Real Time ◽

Phase Ii ◽

Low Dose ◽

Phase Ii Study ◽

Malignant Rhabdoid Tumor ◽

Newly Diagnosed ◽

Acetylation Status ◽

Atypical Teratoid ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

Abstract BACKGROUND Panobinostat treatment has been shown to terminally differentiate malignant rhabdoid tumor (MRT)/atypical teratoid rhabdoid tumors (ATRT) in pre-clinical models. This is an open label, phase II study of panobinostat in patients with newly diagnosed or relapsed MRT/ATRT. AIMS: To assess the anti-tumor activity of low dose, continuous panobinostat, its associated toxicities, the biological activity of low dose panobinostat by measuring histone acetylation status in peripheral mononuclear cells (PMNC), and markers of differentiation in fresh tumor tissue specimens. METHODS Following cycles of induction and consolidation chemotherapy and/or radiation treatment, patients were enrolled and commenced on panobinostat as a continuous daily oral dose starting at 10mg/m2 following a three-week wash out period between therapies. Real-time acetylation status, measuring acetylated H4 on PMNC, was performed to determine the pharmacodynamics of panobinostat. Patients were monitored for drug toxicities with the possibility of dose reductions in decrements of 2mg/m2. RESULTS Six patients with newly diagnosed ATRT/MRT and one patient with relapsed MRT have been enrolled to date. The average age at enrollment was 2.5 years. Currently, six patients (85.7%) remain on study with a mean treatment duration of 170 days (range 44–327 days). One patient was removed from study at day 44 due to disease progression. The main dose-limiting toxicity observed to date has been myelosuppression. Panobinostat, at a dose of 10mg/m2, caused significant acetylation of H4 in PMNC. CONCLUSIONS Treatment with panobinostat appears to be well tolerated in infants with MRT/ATRT, with successful real-time pharmacodynamic assessment of H4 acetylation.

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MON-262 A Case of the Suprasellar Atypical Teratoid Rhabdoid Tumor (ATRT) Presenting in an Adult Treated with Intrathecal Chemotherapy

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1261 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Omar Oraibi ◽

Christine Mau ◽

Lekhaj Daggubati ◽

Yahya Khormi ◽

Andrea Manni ◽

...

Keyword(s):

Internal Control ◽

Intrathecal Chemotherapy ◽

Rhabdoid Tumor ◽

Biological Behavior ◽

Atypical Teratoid Rhabdoid Tumor ◽

First Case ◽

Initial Surgery ◽

Atypical Teratoid ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

Abstract Background: Atypical teratoid rhabdoid tumors (ATRTs) are highly malignant tumors that usually present as a posterior fossa mass in children less than 3 years old. Only 38 cases have been reported in adults. They are also typically located in the supratentorial region. In none of the reported cases of suprasellar ATRT in the adult, intrathecal chemotherapy (via ommaya) has been used. Clinical case: A 70-year-old woman presented with a severe headache and magnetic resonance imaging (MRI) revealed a suprasellar mass measuring 2.9 x 2.1 x 3.0 cm. Shortly after her presentation, she developed an acute 3rd nerve palsy, and repeat MRI found dramatic interval growth. A transsphenoidal approach for biopsy/resection was attempted, but the lesion was not accessible via this corridor. She then underwent a right frontotemporal craniotomy and subsequently developed panhypopituitarism, including diabetes insipidus. Pathology revealed poorly differentiated malignant cells. Immunohistochemistry was positive for synaptophysin, Epithelial Membrane Antigen (EMA), Tumor protein p53, and negative for integrase interactor 1 (INI-1 antibody) with loss of expression in tumor nuclei with positive internal control in endothelial cells. These findings confirmed the diagnosis of ATRT. The Ki-67 index was 60% consistent with a highly proliferative tumor. One month later, she developed acute mental status change. Repeat computed tomography, and MRI showed recurrence of the tumor at the same location with new leptomeningeal enhancement involving the left facial nerve. Multimodal treatment was instituted, consisting of intraventricular/intrathecal chemotherapy with etoposide and topotecan plus fractionated external beam cranial irradiation (30 Gy in 10 fractions). She continued to deteriorate, and following consultation with her family, she was transferred to hospice care and died six months following her initial surgery. Conclusion: This is the first case of adult suprasellar ATRT that has been treated with intrathecal chemotherapy. There is no consensus on the best combination of chemotherapy, and often the St. Jude’s protocol used in the treatment of pediatric ATRT is used. In line with the biological behavior reported for this tumor in children and adults in different locations, the tumor was very aggressive, resulting in the patient’s death only after 6 months from the diagnosis despite aggressive surgical and medical treatment. Reference: 1. Athale, U. H., J. Duckworth, I. Odame, and R. Barr. 2009. Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies. J. Pediatr. Hematol. Oncol. 31:651-663. 2. Shonka N, Armstrong T (2011) Atypical teratoid/rhabdoid tumors in adults: A case report and treatment-focused review. J Clin Med Res 3: 85-92.

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Two molecularly distinct atypical teratoid/rhabdoid tumors (or tumor components) occurring in an infant with rhabdoid tumor predisposition syndrome 1

Acta Neuropathologica ◽

10.1007/s00401-019-02001-3 ◽

2019 ◽

Vol 137 (5) ◽

pp. 847-850

Author(s):

Christian Thomas ◽

Friederike Knerlich-Lukoschus ◽

Harald Reinhard ◽

Pascal D. Johann ◽

Dominik Sturm ◽

...

Keyword(s):

Rhabdoid Tumor ◽

Atypical Teratoid ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

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TLE1 Expression in Malignant Rhabdoid Tumor and Atypical Teratoid/Rhabdoid Tumor

Pediatric and Developmental Pathology ◽

10.1177/1093526618761720 ◽

2018 ◽

Vol 21 (6) ◽

pp. 522-527

Author(s):

Virginia E Duncan ◽

Jason A Wicker ◽

David R Kelly ◽

Rong Li

Keyword(s):

Chromosomal Translocation ◽

Scoring Systems ◽

Staining Intensity ◽

Rhabdoid Tumor ◽

Malignant Rhabdoid Tumor ◽

Atypical Teratoid Rhabdoid Tumor ◽

Tissue Sections ◽

Atypical Teratoid ◽

The Central Nervous System ◽

Rhabdoid Tumors

Malignant rhabdoid tumors (MRT; atypical teratoid/rhabdoid tumor [ATRT] in the central nervous system) are aggressive tumors in infants and children which can overlap with other sarcomas, such as synovial sarcoma (SS). The gold standard for SS diagnosis is characterization of the t(X;18) chromosomal translocation. However, stratification of cases for molecular analysis is not always straightforward or feasible. Recent literature suggests transducer-like enhancer of split 1 (TLE1) protein expression may distinguish SS from certain histologic mimics; however, this has not been investigated in MRT and ATRT. We stained whole-tissue sections of 18 archived cases of MRT and ATRT with TLE1. Nuclear expression was scored using a 4-tiered (0, 1+, 2+, and 3+) scale describing staining intensity, extent, or combination of both. The majority of MRT and ATRT cases showed some TLE1 immunoreactivity (n = 16; 89% for ≥1 + staining); 14 (78%) of total cases showed ≥2 + positivity using any of the 3 scoring systems. Over half (n = 10; 56%) of cases showed ≥2 + staining; 4 (22%) cases showed 3 + strong and diffuse TLE1 staining measured by all scoring systems in agreement. Although still of potential use, we urge caution in the interpretation of TLE1 when the differential diagnosis includes both SS and MRT or ATRT.

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