Extrarenal Malignant Rhabdoid Tumor Research Articles

Rhabdoid tumors in patients conceived following ART: is there an association?

In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART? We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT. Anecdotal evidence suggests an association of ART with RT. This was a multi-institutional retrospective survey. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort. We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age). The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205). RTs are very rare malignancies and our results are based on a small number of children with RT_ART. This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series. M.C.F. is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.10, by the 'Deutsche Forschungsgemeinschaft' DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.05. We declare no competing interests. N/A.

ATRT-14. Malignant rhabdoid tumors of cranial nerves – ATRT or extracranial rhabdoid tumor?

Abstract INTRODUCTION: Malignant rhabdoid tumors (MRT) are highly aggressive neoplasias mostly affecting young children. They are classified as rhabdoid tumors of the central nervous system (ATRT, atypical teratoid rhabdoid tumor), rhabdoid tumors of the kidney (RTK) or extracranial rhabdoid tumors arising from any soft tissue outside the central nervous system (eMRT, extracranial extrarenal MRT). We report a series of four MRTs with cranial nerve involvement. METHODS: Patients were identified from a cohort of 132 patients with MRT (2017 – 2021), as part of the European Rhabdoid Registry (EU-RHAB). Diagnosis of MRT was confirmed immunohistochemically with loss of INI1 expression. Details regarding symptoms at first presentation, diagnostic staging, genetic findings, therapy and the course of disease are reported. REPORT OF CASES/RESULTS: The series contains two MRT affecting the trigeminal nerve and two cases with third cranial nerve involvement. They were two female and two male patients with a median age of 4.7 years (1-159 months) at diagnosis. Location of the main tumor mass differed between being located intra- and extracerebrally. Metastases at diagnosis occurred in one patient, a germ-line mutation in SMARCB1 was present in two patients. Two patients received therapy according to EU-RHAB recommendations with an incomplete resection, conventional chemotherapy enhanced by intraventricular methotrexate and radiotherapy. Both patients are currently alive with no signs of progression, one of them bearing a germ-line mutation. Two patients received palliative treatment after surgery due to rapid progression. Median overall survival was 17.3 (1.4-53.1) months. CONCLUSION: MRT of the cranial nerves affect the peripheral nervous system in close proximity to the brain, thus forming a unique sub-entity between ATRT and eMRT. The selected cases provide insight into the particular challenge regarding clear classification, diagnostics and therapy.

Current and Emerging Therapeutic Approaches for Extracranial Malignant Rhabdoid Tumors.

Extracranial malignant rhabdoid tumors (extracranial MRT) are rare, highly aggressive malignancies affecting mainly infants and children younger than 3 years. Common anatomic sites comprise the kidneys (RTK – rhabdoid tumor of kidney) and other soft tissues (eMRT – extracranial, extrarenal malignant rhabdoid tumor). The genetic origin of these diseases is linked to biallelic pathogenic variants in the genes SMARCB1, or rarely SMARCA4, encoding subunits of the SWI/SNF chromatin-remodeling complex. Even if extracranial MRT seem to be quite homogeneous, recent epigenome analyses reveal a certain degree of epigenetic heterogeneity. Use of intensified therapies has modestly improved survival for extracranial MRT. Patients at standard risk profit from conventional therapies; most high-risk patients still experience a dismal course and often therapy resistance. Discoveries of clinical and molecular hallmarks and the exploration of experimental therapeutic approaches open exciting perspectives for clinical and molecularly stratified experimental treatment approaches. To ultimately improve the outcome of patients with extracranial MRTs, they need to be characterized and stratified clinically and molecularly. High-risk patients need novel therapeutic approaches including selective experimental agents in phase I/II clinical trials.

Complex multidisciplinary resection of a malignant rhabdoid tumor of the neck & mediastinum in a pediatric patient

Extrarenal malignant rhabdoid tumors (MRT) are highly aggressive tumors of childhood with a poor overall prognosis. While most commonly found within the kidney and central nervous system, MRT can also occur in other locations and present highly specific challenges for pediatric surgical providers in an effort to achieve a meaningful resection. Cervical rhabdoid tumors are extremely rare. We report the multidisciplinary management of a patient with a complex cervicothoracic malignant rhabdoid tumor who underwent successful surgical resection with a greater than one year survival.

Malignant Epithelioid Soft Tissue Tumours- A Pathologist's Perspective With Review of Literature.

BackgroundSoft tissue tumours with epithelioid morphology have many differential diagnoses, which include epithelioid sarcoma, malignant extrarenal rhabdoid tumour, epithelioid malignant peripheral nerve sheath tumour, epithelioid leiomyosarcoma, epithelioid angiosarcoma and sclerosing epithelioid fibrosarcoma. There are other rare entities also. They often express characteristic patterns of immunohistochemical markers that can be used to identify these tumours.Materials and methodsThis retrospective study comprises 22 cases of malignant soft tissue tumours with epithelioid differentiation diagnosed over a period of four years. Findings regarding clinical presentation, cytological findings, histopathological findings and immunohistochemical profile of the tumours were noted and analyzed.ResultsA total of 22 cases were included in the study including five cases of epithelioid sarcoma (conventional and proximal), three cases of epithelioid angiosarcoma and epithelioid myxofibrosarcoma, two cases of epithelioid malignant peripheral nerve sheath tumour, epithelioid gastrointestinal stromal tumour and clear cell sarcoma each, one case of epithelioid leiomyosarcoma, sclerosing epithelioid fibrosarcoma, malignant extrarenal rhabdoid tumour, monophasic synovial sarcoma and malignant and malignant perivascular epithelioid cell tumour each.ConclusionPathologists should be aware of the various differential diagnoses of soft tissue tumours with epithelioid morphology. Over and above the clinical findings and morphological features, ancillary methods like immunohistochemistry help to arrive at a definitive diagnosis in most cases.

Malignant Extrarenal Rhabdoid Tumor in a 5-Month-Old Male With Mediastinal and Heart/Great Vessel Involvement

Abstract Introduction/Objective Extrarenal rhabdoid tumor is a high-grade soft-tissue predominately pediatric malignancy with a frequency of 0.15 per million children less than 15 years. It is associated with del(22) (q11.2) with SMARCB1 loss, recognized by loss of INI-1 staining. It has distinct perinuclear hyaline inclusions; however, this feature can be present in other tumors. We describe a malignant extrarenal rhabdoid tumor involving the heart and great vessels to highlight the multiple modalities required for the diagnosis of this tumor in this unusual location. Methods We utilized routine histology, immunohistochemistry, and electron microscopy. Results This 5 -month -old male presented with respiratory distress due to a mass that invaded the heart, surrounding the great vessels. The tumor was composed of sheets of polygonal large cells with light pink to clear cytoplasm, eccentric nuclei with mild anisonucleosis, peripherally marginating chromatin, prominent nucleoli, with 2 mitoses per 10 high power field. Hyaline perinuclear inclusions were inapparent. There were frequent clusters of lymphocytes and eosinophils, with 10 percent necrosis and moderately increased vascularity. The tumor was positive for vimentin, SMA, EMA, MSA, S-100, keratin, and WT1, and negative for INI-1, CD34, ALK, AFP, PLAP, CD30, myogenin, NeuN1, synaptophysin, chromogranin, and NSE. Electron microscopy demonstrated occasional cells with perinuclear collections of intermediate filaments, some with whorls. The strong positivity for vimentin, keratin, SMA, MSA, S-100, negative staining for INA-1 and CD34, and visualization of perinuclear intermediate filament whorls by electron microscopy helped make the diagnosis of extrarenal rhabdoid tumor. Conclusion Malignant extrarenal rhabdomyosarcomas may occur in the middle mediastinum, invade the heart, occur in the first 6 months of life, and not have the typical rhabdoid cells. Diagnoses depend on multiple modalities

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.

Malignant Rhabdoid Tumor of the Adrenal Gland: Case Report and Review of the Literature

Malignant rhabdoid tumor was first thought to be a subtype of wilm’s tumor, which was later disproven by Haas et al. and was categorized as a separate entity. Malignant rhabdoid tumors are mainly present in the kidneys of children, however, cases of extra renal malignant rhabdoid tumor were reported in the literature. In this report we describe a case of extra renal malignant rhabdoid tumor in the adrenal gland. Malignant rhabdoid tumor is a highly aggressive neoplasm with very poor prognosis. Due to the rarity of the disease, no universal treatment regimen has been developed yet, where treatment options include the surgical removal of the tumor, chemotherapy, radiotherapy, or a multimodality approach of management. In this report we present a case of 21-year-old lady with MRT in the adrenal gland, who had neoadjuvant radio-chemotherapy followed by laparoscopic adrenalectomy.

Fine needle aspiration cytology of paediatric soft tissue tumours highlighting challenges in diagnosis of benign lesions and unusual malignant tumours.

The type of soft tissue lesions seen in children differs from that seen in adults. The role of fine needle aspiration (FNA) cytology in their diagnosis is not well documented. To study the cytopathological spectrum of paediatric soft tissue tumours to highlight uncommon benign and malignant lesions and the challenges in their diagnosis. A 3-year retrospective audit of all paediatric soft tissue FNA cytology cases from 2015 to 2017 was performed. Smears were reviewed along with cell block immunocytochemistry and follow-up histopathology of resected specimens wherever available. A total of 127 cases were reviewed, which included 72 benign and 55 malignant soft tissue tumours. Uncommon lesions described herein are myxoid fibrohistiocytic tumour, myxoma, lipoblastoma, Bednar tumour, malignant extra-renal rhabdoid tumour and desmoplastic small round cell tumour. Histopathology confirmation was available in 25 cases, out of which 16 cases were completely concordant. In eight cases, all benign diagnoses, histopathology provided more accurate subtyping than FNA. These included cases of lipoblastoma, myxoma and spindle cell haemangioma. FNA cytology of paediatric soft tissue tumours is accurate in classifying lesions as benign or malignant which helps in treatment planning. Immunocytochemistry performed on cell blocks is useful for subtyping malignant lesions.

Clinical and image analysis of extrarenal non-central nervous system malignant rhabdoid tumors

Objective To demonstrate the clinical and imaging features of extrarenal malignant rhabdoid tumor(MRT) outside the central nervous system(CNS) in children and to raise awareness of the disease. Methods A retrospective database review was made of 15 patients diagnosed with extrarenal MRT outside the CNS in Beijing Children′s Hospital, Capital Medical University from April 2008 to February 2017.The ultrasound, CT and magnetic resonance imaging(MRI) examinations were performed in 12, 10 and 7 cases, respectively, and the clinical and imaging features were analyzed. Results The 15 patients included 8 boys and 7 girls.The age at presentation varied from 11 days to 12 years and 9 months old with a median age of 4 years old.The primary tumors were predominant solid masses, most of which were irregular, with a length of 2.20-11.70 cm [(5.87±2.57) cm]. The primary tumors had variable locations, relatively tended to occur in the head and neck region (6 cases) and the mediastinum (4 cases). On ultrasound, 11 cases of the tumors were heterogeneous, 7 cases of the tumors were accompanied with cystic change, and the solid part was mainly hypoechoic.On CT, density of 6 cases of the tumors was uneven, 3 cases presented cystic change, 4 cases were with calcification, and the solid part had slightly low density, with enhancement of different degrees.On MRI, 7 cases of tumors showed mixed signal, 5 cases with cystic change of different degrees; the solid part mainly showed isointensity or slightly hypointensity on T1 weighted image and hyperintensity or slightly hyperintensity on T2 weighted image, with restricted diffusion and predominantly heterogeneous enhancement.Medical imaging showed definite hemo-rrhage within tumors in 5 patients, and metastases occurred in 6 patients at the time of diagnosis, the adjacent bone destruction occurred in 3 patients, and the tumor tissue of 3 patients extended into the spinal canal. Conclusion Extrarenal MRT outside the CNS is more common in preschool kids, most of which are large and heterogeneous solid masses, often with cystic change, sometimes with hemorrhage and calcification; the solid part with restricted diffusion and inhomogeneous enhancement.Some of the patients had metastasis and local invasion. Key words: Malignant rhabdoid tumor; Computed tomography; Magnetic resonance imaging; Child

Malignant extrarenal rhabdoid tumor of parapharyngeal space: A rare presentation

Malignant extrarenal rhabdoid tumors (ERRTs) are very rare, highly aggressive tumors and are associated with a poor prognosis. They usually occur in young children. Diligent histopathological examination along with the use of judicious immunohistochemistry (IHC) panel is essential to diagnose this rare entity with distinct therapeutic implications. We report a rare case of ERRT with extension up to the skull base involving the right jugular fossa with thrombus in the right internal jugular vein.

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.].

Extraordinary disease-free survival in a rare malignant extrarenal rhabdoid tumor: a case report and review of the literature

BackgroundMalignant extrarenal rhabdoid tumor of the gastrointestinal tract is rarely reported in the literature. It is characterized by poor prognosis and aggressive metastatic features.A literature review evidenced only 19 cases, with poor outcome.Case presentationWe report a case of a colonic “pure” malignant extrarenal rhabdoid tumor with metastatic nodes in a 65-year-old Caucasian man. He was treated surgically with no recurrence, no adjuvant chemotherapy, and with 4-year survival without disease at the time of the submission of this article.ConclusionsWe present an extraordinary case of long-term survival due to the extended surgical treatment.We believe that the absence of organ metastasis at presentation is a positive prognostic factor, although pathology confirmed node involvement (13/38 positive) on microscopy.

Tumor rabdoide extrarrenal maligno de colon: presentación de 3 casos y revisión de la literatura

Malignant extrarenal rhabdoid tumour (MERT) of the colon is rare, with only 12 cases published to date. Clinically, they usually occur in elderly patients and present as large, aggressive tumours; their histopathology is that typical of rhabdoid tumours and their immunohistochemistry shows expression of vimentin and cytokeratines. We present 3 cases of colonic MERTs with features similar to previously published cases. One was possibly a metastasis of a renal cell carcinoma with rhabdoid features. We carried out a extensive immunohistological analysis of all 3 cases as well as testing for KRAS and BRAF mutations. Thus we could not only compare our findings with those of the other known cases but also make a differential diagnosis with primary colonic neoplasmas and metastases of similar appearance.

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.

Extrarenal malignant rhabdoid tumor of childhood: a clinicopathologic analysis of 8 cases

To study the clinicopathologic characteristics of extrarenal malignant rhabdoid tumor (E-MRT) with emphasis on diagnosis and differential diagnosis. The clinical and pathologic data of 8 E-MRT cases were reviewed. The outcome was analyzed. There were four males and four females. The age at presentation ranged from 3 days to 8 years (mean, 2.6 years; median, 3 years). The tumors were located in the extremities (n = 1), head and neck (n = 2), trunk (n = 2), cervical cord (n = 1), liver (n = 1) and retroperitoneum (n = 1). Histologically, the tumors were composed of a diffuse proliferation of rounded or polygonal cells with eccentric nuclei, prominent nucleoli, and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies, arranged in sheets and nests. Cellular atypia was easily observed and mitotic activity was high. Necrotic and hemorrhagic areas were abundant. On immunohistochemistry, the tumor cells expressed vimentin and epithelial marker such as EMA, AE1/AE3, and CAM5.2. The absence of INI1 protein expression was a distinctive feature. Follow-up of all eight cases revealed five deaths in one year and the other three were disease-free at last follow-up of one month, three months and seven months. E-MRT is a rare and highly aggressive tumor of infancy and childhood. Recurrence and distant metastasis was common and the 5-year survival rate is low. Increased awareness of the clinocopathologic features and immunophenotypes of E-MRT is helpful for correct diagnosis and effective treatment.

SMARCB1 deletion by a complex three-way chromosomal translocation in an extrarenal malignant rhabdoid tumor

Rhabdoid tumors (RTs) are highly aggressive malignant neoplasms of early childhood that arise in the kidney, brain, and extrarenal sites. The disease is genetically defined by biallelic disruption of the SMARCB1/INI1/SNF5 tumor suppressor gene, a core component of the ATP-dependent chromatin remodeling SWI/SNF complex. The molecular changes leading to SMARCB1 alterations in RTs are heterogeneous, including germline or constitutional inactivating mutations, partial or total gene deletions, copy number neutral loss of heterozygosity, and, less commonly, reciprocal translocations. We report a novel three-way chromosomal rearrangement, which was identified by conventional cytogenetic and sequential fluorescence in situ hybridization studies as the underlying molecular mechanism of the loss of SMARCB1 in an extrarenal RT. This case highlights the heterogeneity of genetic events that may lead to the loss of SMARCB1 and the development of RTs.

Malignant extrarenal rhabdoid tumour in the oral cavity: Report of a rare malignancy in an unusual location

Malignant rhabdoid tumour (MRT) is a well established aggressive malignant neoplasm occurring in kidney particularly in infants and children. When this type of tumor involves any extrarenal site it is termed malignant extrarenal rhabdoid tumor (MERT). Here we report a case of MERT involving the oral cavity. To the best of our knowledge, apart from us only one oral MERT has been documented. Due to their scarcity, prompt and bold diagnosis is quite challenging for a histopathologist. Confirmed final diagnosis must be given after thorough immunohistochemical workup. Confusions and obscurities regarding a definitive treatment policy further complicate management also. We adopted a multimodality approach comprising of surgery, radiotherapy and chemotherapy for our patient. She is disease free for last 30 months on regular followup and maintaining her normal daily activities.

Malignant extra renal rhabdoid tumour presenting as central airway obstruction.

Rhabdoid tumours are one of the most aggressive childhood neoplasms associated with high mortality. The commonest age group affected is children less than five years of age. Rhabdoid tumour presenting as an endoluminal tracheal mass leading to central airway obstruction has not been previously reported. We describe the case of a 17-year-old male patient where malignant rhabdoid tumour masqueraded as bronchial asthma leading to a delayed diagnosis of upper airway obstruction by tracheal growth. Histopathological examination and immunohistochemistry confirmed the diagnosis of malignant rhabdoid tumour.

Malignant Extrarenal Rhabdoid Tumor in Adults: Three Case Reports Originating from the Ileum, Adrenal Gland and Uterus

Malignant Extrarenal Rhabdoid Tumor in Adults: Three Case Reports Originating from the Ileum, Adrenal Gland and Uterus