Primary Malignant Rhabdoid Tumor Research Articles

Isolated Pure Malignant Rhabdoid Tumor (MRT) of the Bladder: Case Report and Lessons Learned

Pediatric extrarenal malignant rhabdoid tumors (MRTs) are rare, aggressive tumors with a poor prognosis (20% 5-year survival). There are currently fewer than 10 published case reports of primary MRT of the bladder. We report the case of an 18-month-old female with an isolated MRT of the bladder which was initially misdiagnosed as an inflammatory myofibroblastic tumor on biopsy. We review the history, tumor biology, histology, and current management of extrarenal MRT, along with lessons learned from the difficulty with the patient's initial diagnosis.

Primary Intraocular Malignant Rhabdoid Tumor Without Extrascleral Compromise.

Primary intraocular malignant rhabdoid tumor is classified as a malignant extrarenal rhabdoid tumor. It is extremely rare, highly aggressive, and, so far, only one case (in a newborn) has been described in the medical literature. The authors report a second case of primary intraocular malignant rhabdoid tumor, this time without extrascleral involvement and in a teenager, and describe its histological, immunohistochemical, and radiological characteristics along with clinical correlations. [J Pediatr Ophthalmol. 2018;55:e7-e9.].

Abstract 4875: Identification of the cellular origin and "stemness" phenotype of Malignant Rhabdoid Tumors (MRT) may represent a new therapeutic approach in paediatric oncology

Abstract Malignant Rhabdoid Tumors (MRT) are highly aggressive childhood malignancies characterized by a single mutation; biallelic inactivation of SMARCB1, a component of the SWI/SNF chromatin remodeling complex. These tumors may occur anywhere, most frequently in the brain (Atypical Teratoid/Rhabdoid Tumor, ATRT) and in the kidneys and soft tissues (Extra Cranial Rhabdoid tumor, ECRT). MRT presents immune markers from multiple lineages exhibiting a teratoid phenotype, characterized by cells with heterogeneous morphology within the same tumor leading to speculation that the MRT cell of origin is a type of multipotent stem cell. Despite recent advances in treating other solid tumors, treatment for MRT still remains ineffective and we hypothesized that MRT “stemness” characteristics are key to its aggressive clinical course and resistance to treatment. Here we analyze the expression profiles of primary MRT (n= 134) and catalog the expression of a program of “stemness” genes capable of driving aberrant self-renewal. Further, we show by re-expression of SMARCB1 in MRT cells that several of these key “stemness” genes are aberrantly activated by SMARCB1 mutation. One such gene, BMI1 was further demonstrated to be critical to MRT tumorigenesis by shRNA knockout, and a novel anti-BMI1 drug, PTC209 was tested to show efficacy in MRT. Knockdown of BMI1 in MRT cells reduced the self-renewal capability of cells as seen from the number of tumorspheres formed in limiting dilution assay (LDA). Interestingly, BMI1 loss triggers upregulation of p16(INK4a) expression and this mimics the expression profile when SMARCB1 was re-expressed into MRT cells. To identify a putative MRT cell of origin we performed a meta-analysis cross-referencing expression profiles from primary MRT (n= 20), and functional models in which SMARCB1 was re-expressed (n=5 lines) with expression profiles from multiple stem cell types including epithelial, embryonic, neural mesenchymal and neural crest (n= 446). Analysis by t-SNE and NMF consensus clustering suggested that MRT bore the closest resemblance to either early neural progenitors (ATRT) or early neural crest cells (ECRT). In MRT cells in which SMARCB1 was forcibly re-expressed, cells became gradually more differentiated and their expression profile altered from that of an early neural crest to a more differentiated mesenchymal pattern. For the first time, we show evidence that ECRTs and ATRTs appear to have different cells of origin, despite having the same mutation and tumor appearance. We further demonstrate that SMARCB1 expression is necessary for MRT cells to maintain a de-differentiated “stem-like” state and finally that the SMARCB1-dependent stemness gene BMI1 shows potential as a novel therapeutic target in MRT. Citation Format: Ras A. Ramli, Martina A. Finetti, Matthew P. Selby, Yura Grabovska, Stephen Crosier, Amanda J. Smith, Steven C. Clifford, Daniel Williamson. Identification of the cellular origin and "stemness" phenotype of Malignant Rhabdoid Tumors (MRT) may represent a new therapeutic approach in paediatric oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4875. doi:10.1158/1538-7445.AM2017-4875

Primary malignant rhabdoid tumors of the central nervous system: Clinicoradiological study of three cases and their outcome

Malignant rhabdoid tumors of the brain are extremely malignant, highly aggressive neoplasms found in infants and young children. These are rare and not associated with renal neoplasm as believed earlier. We report three cases of malignant rhabdoid tumors with reference to their clinicoradiological aspect and fatal outcome despite a multimodality approach of management (aggressive surgical resection and chemoradiotherapy). The first case was a two and one half-year-old girl who presented with seizures, raised intracranial pressure and right hemiparesis. Contrast magnetic resonance imaging showed a huge heterointense tumor of the left hemisphere, which was a soft, suckable, and very vascular, infiltrative mass with areas of necrosis. Postoperatively, the girl had a difficult course with multiple metastases detected on the 45th day and death on the 52nd day post diagnosis. The second patient was admitted with large and infiltrative posterior fossa mass that required ventilatory support in postoperative period for 3 weeks until his death. The third patient was operated for a large, vascular and friable mass of the temporal lobe, which recurred in 5 weeks. He was offered chemoradiotherapy but the length of his life was only 8 months.

A Rapid Progression of Disease After Surgical Excision of a Malignant Rhabdoid Tumor of the Bladder

Extrarenal malignant rhabdoid tumors (MRTs) are rare tumors with a poor prognosis. Five-year overall survival for patients with MRTs is poor at approximately 20%.(1) There are 5 case reports of histologically confirmed primary MRT of the bladder in pediatric patients. Herein, we report a case of an MRT of the bladder in a 14-year-old boy and discuss the preoperative evaluation, treatment options, and possible etiologies of metastasis after radical surgery.

Malignant rhabdoid tumor of liver

Malignant rhabdoid tumor (MRT) is a rare, but aggressive tumor commonly arising from the kidney in young children. Extrarenal MRT has been reported in the literature in various other sites including the liver, pelvis, CNS, abdomen, heart and other soft-tissues. Reported herein are the presentation, radiology, histopathology, immunohistochemistry, treatment and outcome of a 6 month infant with primary MRT of liver.

Primary Intraocular Malignant Extrarenal Rhabdoid Tumor: A Clinicopathological Correlation

Malignant extrarenal rhabdoid tumor is a rare and highly aggressive tumor of childhood. Intraocular involvement by malignant extrarenal rhabdoid tumor has only been described once as a metastasis. No report exists in published literature describing a primary intraocular malignant extrarenal rhabdoid tumor. The authors report the first such case along with its clinico-radiological features and histopathologic and electron microscopic characteristics. [J Pediatr Ophthalmology Strabismus 2013;50:e18–e20.]

A Primary Malignant Rhabdoid Tumor in Adult Liver

Malignant rhabdoid tumors (MRTs) are rare high-grade malignancies in the renal or extrarenal organs. MRTs of the extrarenal organs mostly affect the liver, central nervous system, pelvis, soft tissue,1 and intra-abdominal cavity.2 Most MRTs occur in infants and young children,3-8 although adult onset MRTs do occur.9 Here, we report a case of primary MRT arising in the liver of a 50-year-old male.

Malignant rhabdoid tumour of the liver in a seven-month-old female infant: A case report and literature review

Malignant rhabdoid tumours in children are rare and aggressive neoplasms that occur most commonly in the kidney. Extra-renal malignant rhabdoid tumours are even rarer and have been reported in the central nervous system (atypical teratoid/rhabdoid tumour) and other sites including the liver. To date fewer than 40 cases have been reported in the literature. Here we present a case of a 7-month-old female infant with a primary malignant rhabdoid tumour of the liver and review this entity as it compares to other cases reported in the literature.

Molecularly confirmed primary malignant rhabdoid tumor of the urinary bladder: implications of accurate diagnosis

Malignant rhabdoid tumors (MRTs) are well recognized in the kidney and extrarenal sites such as soft tissues, retroperitoneum, and bladder but are classified as atypical teratoid/rhabdoid tumors in the central nervous system. The unifying features of both extracranial MRT and atypical teratoid/rhabdoid tumors are the exon deletions/mutations of the SMARCB1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) gene in 22q11.23 and resulting loss of SMARCB1/INI1 (integrase interactor 1) protein expression by immunohistochemistry. We herein report a case of extrarenal rhabdoid tumor confined to the bladder in a 3-year-old child, diagnosed by histopathology and confirmed by immunohistochemical and molecular studies. This is only the fourth molecularly proven primary MRT of the bladder to be reported. The patient's peripheral blood was negative for the deletions observed in the tumor, thereby confirming a sporadic origin for the tumor. Given the possible dismal outcome, urgency for definitive diagnosis to institute intensive multimodality therapy, histopathologic differential diagnosis with rhabdomyosarcoma and urothelial carcinoma with rhabdoid features, and lack of consensus management guidelines, oncologists, urologists, and pathologists must be aware of this entity. Evaluation for a germ line SMARCB1 alteration may greatly aid risk stratification and family planning.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway

Aberrant activation of the Hedgehog (Hh) pathway can drive tumorigenesis. To investigate the mechanism by which glioma-associated oncogene family zinc finger-1 (GLI1), a crucial effector of Hh signaling, regulates Hh pathway activation, we searched for GLI1-interacting proteins. We report that the chromatin remodeling protein SNF5 (encoded by SMARCB1, hereafter called SNF5), which is inactivated in human malignant rhabdoid tumors (MRTs), interacts with GLI1. We show that Snf5 localizes to Gli1-regulated promoters and that loss of Snf5 leads to activation of the Hh-Gli pathway. Conversely, re-expression of SNF5 in MRT cells represses GLI1. Consistent with this, we show the presence of a Hh-Gli-activated gene expression profile in primary MRTs and show that GLI1 drives the growth of SNF5-deficient MRT cells in vitro and in vivo. Therefore, our studies reveal that SNF5 is a key mediator of Hh signaling and that aberrant activation of GLI1 is a previously undescribed targetable mechanism contributing to the growth of MRT cells.

Primary Malignant Rhabdoid Tumor of the Stomach, a Rare Case Report and Review of Literature

Rhabdoid tumor is a distinct entity reported in renal and extrarenal sites. There have been very rare reported cases in the stomach, all of which have shown an aggressive clinical course. Herein, we report a primary gastric neoplasm in an old man who presented with profuse intractable GI bleeding and undergone emergency surgery. Resected specimen showed primary malignant rhabdoid tumor. The patient died 24 h after surgery with no additional therapy. Our case emphasizes on this very rare subtype of gastric tumor, with extremely aggressive behavior.

Primary malignant rhabdoid tumor of rectum:report of a case

患者女,23岁.因大便性状改变及便血1个月余入院.1个月前无明显诱因出现便秘,呈羊粪状,外附血迹,色红,量少,偶阵发性腹痛,并逐渐加重,出现水样便.体检肛诊:距肛门5 cm左右直肠前壁可扪及一肿块,质硬,表面凹凸不平。

Primary malignant rhabdoid tumour of the brain in adults

Malignant rhabdoid tumour (MRT) was described for the first time in the kidney, and is rarely reported in the brain. Most rhabdoid tumours affect infants and young children and there have been only isolated adult patients reported. The optimal treatment for this very aggressive tumour has not yet been established. We describe the clinical and pathological features of a rare primary malignant rhabdoid tumour of the brain in a 27-year-old pregnant female. The literature is reviewed briefly and the role of the INI1 gene in adult MRTs and the also possible interactions between MRTs and pregnancy are discussed.

Malignant Rhabdoid Tumor Mimicking Hepatoblastoma: A Case Report and Literature Review

Hepatoblastoma accounts for the vast majority of malignant primary liver tumors in infancy. In contrast, rhabdoid tumors arising in the liver are extremely rare, but they can share clinical and histologic features with hepatoblastoma and can create diagnostic confusion, especially when one is dealing with small biopsies. In this case report we demonstrate that immunohistochemical and molecular techniques can identify the characteristic loss of INI1 and facilitate making the correct diagnosis of primary hepatic malignant rhabdoid tumor. Important similarities and differences between hepatoblastoma and rhabdoid tumors are reviewed, and suggestions are offered to help distinguish these 2 tumor types.

Metachronus malignant rhabdoid tumor of the ileum and adenocarcinoma of lung: a unique case report

Malignant extrarenal rhabdoid tumors had been described in a variety of anatomic locations including gastrointestinal tract. Carcinomas of small intestine are quite uncommon neoplasms, and those with rhabdoid differentiation are exceedingly rare. These poorly differentiated tumors pose a great deal of difficulty in diagnosis as well as in deciding whether they are primary or metastatic in origin because malignant rhabdoid tumors or carcinomas with rhabdoid differentiation of other sites can metastasize to the small intestine. They behave more aggressively than the typical adenocarcinomas of the same location. Herein, we report a 52-year-old patient with primary small bowel malignant rhabdoid tumor, who was completely disease-free after the initial presentation and management. Five years later, he was found to have a lung mass proved to be adenocarcinoma, exhibiting focal giant cell differentiation without rhabdoid features.

Advanced malignant rhabdoid tumor of the ovary effectively responding to chemotherapy: A case report and review of the literature

Malignant rhabdoid tumors (MRTs) are highly malignant neoplasms that consist of both renal and extrarenal subtypes. Primary ovarian cases are extremely rare. We herein describe the third known case of ovarian origin, which effectively responded to combination chemotherapy with ifosfamide, epirubicin, and cisplatin (IEP chemotherapy). A 19-year-old woman was diagnosed to have stage IIIc primary MRT of the ovary following the resection of tumors. Two months after surgery, an 8 cm-sized pelvic mass and enlarged retroperitoneal lymphnodes were detected. The patient received intravenous tri-weekly IEP chemotherapy. After the second course of chemotherapy, she demonstrated a complete clinical response. Although this type of tumor is quite aggressive and chemotherapy is generally not considered to be effective, IEP chemotherapy may be useful in the treatment of MRT of the ovary.

Treatment of unresectable malignant rhabdoid tumor of the orbit with tandem high‐dose chemotherapy and gamma‐knife radiosurgery

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that primarily occurs in very young children. We report here a patient with a primary MRT of the orbit who received tandem high-dose chemotherapy and gamma-knife radiosurgery. Although the tumor was not completely removed, and the initial chemotherapy failed, the patient achieved long-term survival after this modality of treatment. This approach may be one to be further considered in patients with MRT.

Malignant Rhabdoid Tumor in a Pregnant Adult Female: Literature Review of Central Nervous System Rhabdoid Tumors

Rhabdoid tumors of the central nervous system are uncommon, aggressive childhood malignancies. The 13 described adult cases comprise both primary CNS tumors and malignant transformation of previously existing gliomas, meningiomas, and astrocytomas. Central nervous system rhabdoid lesions of adults have been diagnosed as primary malignant rhabdoid tumors, atypical teratoid/rhabdoid tumors, and more recently, rhabdoid glioblastomas. We report a case of a 20-year-old woman in her 30th week of pregnancy who presented with headache, nausea and blurry vision. MRI revealed a large rim-enhancing mass of the right occipital lobe. Gross total resection was achieved via a right parietal-occipital craniotomy. Pathologic evaluation revealed histology, electron microscopy and immunohistochemistry consistent with the diagnosis of malignant rhabdoid tumor. FISH studies were negative for the INI-1 genetic mutations and chromosome 22q deletion associated with childhood atypical rhabdoid/rhabdoid tumor in 75% of cases. The patient delivered her infant via caesarian section prior to initiating further therapy. We briefly describe the characteristics and current understanding of rhabdoid tumors, and review the literature comparing the 12 other cases of central nervous system rhabdoid tumors in adults. Furthermore, we consider and discuss the implications of this case being the second presentation of MRT during pregnancy in only six adult female patients.