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NUT carcinoma and thoracic SMARCA4‐deficient undifferentiated tumour are unique entities in the 5th edition of the World Health Organisation (WHO) Classification of Thoracic Tumours, whose definitions include molecular genetic abnormalities. These aggressive tumours require rapid work‐ups on biopsies, but a broad list of differential diagnoses poses challenges for practising pathologists. This review provides an update on their key clinicopathological and molecular characteristics, as well as controversies regarding tumour classification and diagnostic strategy. Phenotypical assessment plays a substantial role in diagnosis because recurrent and predictable clinicopathological findings exist, including robust immunohistochemical phenotypes. Accurate diagnosis is crucial for appropriate management and a clearer understanding of the disease. [ABSTRACT FROM AUTHOR]

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare CNS cancer that typically occurs in children younger than 3 years of age. Histologically, AT/RTs are embryonal tumors that contain a rhabdoid component as well as areas with primitive neuroectodermal, mesenchymal, and epithelial features. Compared to other CNS tumors of childhood, AT/RTs are characterized by their rapid growth, short symptomatic prodrome, and large size upon presentation, often leading to brain compression and intracranial hypertension requiring urgent intervention. For decades, the mainstay of care has been a combination of maximal safe surgical resection followed by adjuvant chemotherapy and radiotherapy. Despite advances in each of these modalities, the relative paucity of data on these tumors, their inherently aggressive course, and a lack of molecular data have limited advances in treatment over the past 3 decades. Recent large-scale, multicenter interdisciplinary studies, however, have significantly advanced our understanding of the molecular pathogenesis of these tumors. Multiple clinical trials testing molecularly targeted therapies are underway, offering hope for patients with AT/RT and their families. [ABSTRACT FROM AUTHOR]

Papillary and rhabdoid meningiomas are pathologically World Health Organization (WHO) grade III. Any correlation between clinical prognosis and pathologic component is not clear. We analyzed the prognoses of patients with meningiomas with a rhabdoid or papillary component compared to those of patients with anaplastic meningiomas. From 1994 to June 2013, 14 anaplastic meningiomas, 6 meningiomas with a rhabdoid component, and 5 meningiomas with papillary component were pathologically diagnosed. We analyzed magnetic resonance imaging (MRI) findings, extent of removal, adjuvant treatment, progression-free survival (PFS), overall survival (OS), and pathologic features of 14 anaplastic meningiomas (group A), 5 meningiomas with a predominant (≥50%) papillary or rhabdoid component (group B1), and 6 meningiomas without a predominant (<50%) rhabdoid or papillary component (group B2). Homogeneous enhancement on MRI was associated with improved PFS compared to heterogeneous enhancement (p=0.025). Depending on pathology, the mean PFS was 134.9±31.6 months for group A, 46.6±13.4 months for group B1, and 118.7±19.2 months for group B2. The mean OS was 138.5±24.6 months for group A and 59.7±16.8 months for group B1. All recurrent tumors were of the previously diagnosed pathology, except for one tumor from group B1, which recurred as an atypical meningioma without a papillary component. Group B1 tumors showed a more aggressive behavior than group B2 tumors. In group B2 cases, the pathologic findings of non-rhabdoid/papillary portion could be considered for further adjuvant treatment. [ABSTRACT FROM AUTHOR]

Rhabdoid tumors are a spectrum of neoplasias composed of cells which show rhabdoid morphology but are devoid of skeletal muscle differentiation. These tumors are characterized by inactivation of the INI1/SMARCB1 gene and they have been described in virtually every anatomical site, including the central nervous system (CNS) and sinonasal tract. Rhabdoid tumor of the CNS was named atypical teratoid rhabdoid tumor (ATRT) and it mainly affects children under the age of 3 years with supra- or infra-tentorial location.Herein we report the first case of ATRT infiltrating the nasal cavities and skull base in an adolescent. Due to its unusual location, differential diagnosis was challenging and included several other entities such as sinonasal carcinoma or meningioma. Awareness that ATRT may infiltrate the nasal tract and knowledge of its clinico-pathological, immunohistochemical and biomolecular features are essential for its distinction from other rhabdoid tumors which more frequently involve this anatomical site and for appropriate therapeutic management. [ABSTRACT FROM AUTHOR]

Extrarenal rhabdoid tumors (ERRTs) are extremely rare neoplasms; of these, colorectal ERRTs are the most rare, and only nine cases have been previously described in the English language literature. The current study reports the pathological features of a case of poorly differentiated cecal adenocarcinoma with prominent rhabdoid feature, which was combined with mucinous cystadenoma of the appendix in a 73-year-old male, and additionally reviews the previously reported cases. Microscopically, the majority of tumor cells were non-cohesive or loosely cohesive, with a polygonal morphology and prominent rhabdoid feature, showing eccentric vesicular nuclei, prominent nucleoli and abundant eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) and vimentin, but negative for CK20, CK7, desmin and smooth muscle actin. This indicated a diagnosis of poorly differentiated adenocarcinoma with prominent rhabdoid features, combined with appendiceal mucinous cystadenoma. At two months following surgery the patient succumbed to peritoneal seeding and metastasis of liver and bone The emergence of the rhabdoid phenotype is invariably associated with an aggressive and almost always fatal clinical course. The present case is the 10th example of such a tumor in the colon, and to the best of our knowledge, this is the first case of colonic rhabdoid tumor coinciding with appendiceal benign mucinous neoplasm. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to examine the status of Brahma (BRM), a key SWI/ SNF complex subunit, in clear cell renal cell carcinomas ( RCCs), and to analyse the histopathology, immunophenotype, molecular features and prognosis of the BRM-negative cases. Methods and results We identified 19 cases of grade 4 tumours lacking BRM expression among 625 clear cell RCCs. All 19 cases exhibited features of poor differentiation: 13 showed pure poorly differentiated morphology, while six were composite tumours with an admixed typical low-grade component. Besides negative BRM expression, the immunophenotype of these cases was similar to clear cell RCC. VHL gene mutations were identified in nine of the 19 patients (47%). Chromosome 3p deletion was detected in 11 of 13 poorly differentiated RCCs and both areas of five of five composite tumours. All poorly differentiated tumour areas showed polysomy of chromosome 3. No losses or gains of chromosome 3 were observed in low-grade tumour areas of five of five composite RCCs. Conclusions We have shown that loss of BRM expression is a common feature among poorly differentiated tumours in clear cell RCCs. We hypothesize that loss of BRM expression is involved in tumor de-differentiation in clear cell RCCs and may play an important role during tumour progression. [ABSTRACT FROM AUTHOR]

The discovery of biallelic, inactivating SMARCB1 mutations in rhabdoid tumors (RTs) over a decade ago represented the first recognized link between chromatin remodeling and tumor suppression. SMARCB1 is a core subunit of the SWI/ SNF chromatin remodeling complex, and the recent emergence of frequent mutations in genes that encode subunits of this complex across a wide variety of cancers suggests that perturbation of this chromatin remodeling complex constitutes a key driver of cancer formation. Despite the highly aggressive nature of RTs, they are genetically simple cancers that appear to lack chromosomal instability and contain very few mutations. Indeed, the mutation rate in RTs is among the lowest of all cancers sequenced, with loss of SMARCB1 as essentially the sole recurrent event. Given the genetic simplicity of this disease, understanding the chromatin dysregulation caused by SMARCB1 loss may provide more general insight into how epigenetic alterations can contribute to oncogenic transformation and may reveal opportunities for targeted therapy not only of RT but also the variety of other SWI/ SNF mutant cancers. [ABSTRACT FROM AUTHOR]

Rhabdoid features in gastrointestinal stromal tumors (GISTs) are rare. To the authors’ knowledge, only 51 cases have been reported. Most of these reports consist of case series in which the rhabdoid GISTs comprise a small proportion of the tumors studied. Information regarding site of origin and clinical behavior is sparse. Although the stomach is the only site of origin documented, most reports do not include this data. Malignancy has not been reported, though follow-up is inadequate in most cases to comment on tumor behavior. Exon 11 mutations comprise all previously described KIT mutations, the majority of which are deletions. The authors present the case of a malignant small-intestinal rhabdoid GIST that recurred twice following resection and treatment with tyrosine kinase inhibitors. The tumor harbored a KIT exon 11, 579-580 LY insertion that, to the authors’ knowledge, has not been previously reported. This case is the first rhabdoid GIST described in the small intestine and is the first to show documented evidence of malignancy. [ABSTRACT FROM PUBLISHER]

Extrarenal rhabdoid tumors (ERRTs) are very rare neoplasms and have been reported in a range of organs, including sixteen cases in the stomach. We describe a woman aged 86 years who had an advanced gastric tumor with lymph node metastasis. The tumor mostly showed a diffuse arrangement with a small glandular region. The tumor cells were non-cohesive and had polygonal morphology with eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, i.e. they showed rhabdoid features. Immunohistochemically, the rhabdoid tumor cells were strongly positive for cytokeratins and vimentin. However, a candidate tumor suppressor gene of rhabdoid tumors, the INI1 gene, showed no mutations or loss of expression in the tumor cells. Although ERRTs typically have an aggressive clinical course, the patient was still alive without any evidence of recurrence or metastasis at 26 months after surgery. The rhabdoid features of the present case seemed to be a variant of gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Rhabdoid glioblastoma is a recently described entity in which a glioblastoma is associated with a rhabdoid component. Although rhabdoid glioblastoma has not appeared in the new World Health Organization classification of tumors of the CNS, it has a specific morphological feature and highly aggressive clinic process. Up to now, there have been six cases of rhabdoid glioblastoma reported in the literature. We report rhabdoid glioblastoma in the right front temporal lobe from a 31-year-old Chinese man. This tumor consisted of rhabdoid tumor cells with an eccentric nucleus and an eosinophilic cytoplasm. The tumor had an area appearing to be glioblastoma with microvascular proliferation and necrosis, and lacked a primitive neuroectodermal tumor component, and a mesenchymal component. Vimentin, epithelial membrane antigen, GFAP and integrase interactor (INI-1) expression were found in the tumor cells. Genetic abnormalities which include monosomy or a deletion of chromosome 22 were not found in this tumor. After 3 months post-surgery, the tumor was widespread in leptomeningia and the patient died. In conclusion, rhabdoid glioblastoma is a rare glioblastoma with poor prognosis; the differential diagnosis contained other rhabdoid tumors. This case will contribute to the profile of rhabdoid glioblastoma with typical morphology and immunophenotype, genetic and clinic features. [ABSTRACT FROM AUTHOR]

Reported herein is the case of a 70-year-old man with high grade urothelial carcinoma (UC) with rhabdoid features of the renal pelvis. For the most part, the tumor was composed of pleomorphic, non-cohesive round tumor cells with abundant cytoplasm. In situ high-grade UC composed of cohesive tumor cells was seen only in a small portion. Pleomorphic dyscohesive tumor cells often showed rhabdoid features, containing eosinophilic inclusions. These pleomorphic/rhabdoid tumor cells were immunohistochemically positive for vimentin but negative for cytokeratins, CD45, CD20, CD79a, CD3, CD45RO, CD38, and CD138. Loss of heterozygosity (LOH) analysis demonstrated identical allelic losses as well as additional allelic losses for the dyscohesive and cohesive UC lesion, indicating that these two lesions originated from a single clonal lesion. [ABSTRACT FROM AUTHOR]

Abstract: Rhabdoid meningioma is a rare variant of meningioma, often found in tumour recurrences. We report a 55-year-old woman with a history of intraventricular fibroblastic meningioma, who developed headache and tinnitus 5 years after complete resection of the initial tumour. Imaging confirmed a recurrent tumour in the intraventricular location. Histological analysis revealed rhabdoid meningioma. We reviewed the literature and were unable to find any previously reported cases of intraventricular rhabdoid meningioma. [Copyright &y& Elsevier]

Abstract: Malignant rhabdoid tumours (MRT) are highly aggressive cancers of early childhood that arise in different organs or tissues. The unifying criterion for these tumours is the presence of inactivating mutations of the hSNF5/INI1 tumour suppressor gene which encodes a core subunit of the chromatin remodelling SWI/SNF complex. Using a variety of markers we analysed the phenotypic traits of MON and DEV cell lines derived respectively from an undifferentiated abdominal MRT and from a brain MRT. DEV cells express spontaneously a wide range of neural and glial markers. It can be induced to differentiate into the neural lineage following hSNF5/INI1 expression with appearance of neurite processes, strong increase of neural markers and decrease of glial markers. A less pronounced neural differentiation is also observed with MON cells, which possess more primitive polyphenotypic features with positivity for markers from the three embryonic layers. Finally, we show that the neural differentiation of rat PC12 cells in the presence of nerve growth factor (NGF) is strongly impaired when hSNF5/INI1 expression is inhibited by RNA interference. Altogether these results indicate that hSNF5/INI1 is an essential subunit for SWI/SNF-dependant induction of neural differentiation programs. Further experiments should enable documentation of whether it provides instructive or permissive signals for differentiation. [Copyright &y& Elsevier]

Malignant congenital tumors of fetal origin are rare lesions, the most common type being congenital neuroblastoma. Although prenatal diagnosis is possible in large tumors, occasionally the tumor will be diagnosed first by its metastatic involvement of the placenta. Placental metastases can reflect either maternal or fetal primary sites, and each has relatively specific patterns of placental involvement. We describe the clinical and pathologic features of a widely metastatic congenital renal rhabdoid tumor with its placental and autopsy findings, and include the immunohistochemical, cytogenetic, and ultrastructural features. The pathologic features of the placenta in congenital renal rhabdoid tumor with placental metastasis have not been previously described. The examination of the placenta in this case led to the initial diagnosis and obviated the need for additional diagnostic procedures. [ABSTRACT FROM AUTHOR]

Objective and importance: Rhabdoid meningioma (RM) is a relatively new, Grade III tumor entity according to the latest WHO classification. We report rhabdoid and partly papillary, highly anaplastic, intracerebral meningioma with diffuse leptomeningeal spread and distant SCF metastasis to the cervical cord. Clinical presentation: This 27-year-old female was admitted lo the hospital with radiological findings suggestive of a primary brain tumor or a metastasis. After subtotal resection and during radio-therapy, follow-up MRI revealed recurrence, metastasis to meninges at the high cervical level., and diffuse basal leptomeningeal enhancement indicating infiltrating tumor. She died approximately 3 months after onset of symptoms. Results: Histological examination revealed rhabdoid and papillary meningioma with high proliferation rate (80% of MIB1-positive cells), necrosis and extensive brain invasion, It was positive for vimentin and S-100 protein, showed focal epithelial membrane antigen expression and accumulation of intermediate filaments on ultrastructural examination. The recurrent tumor diffusely infiltrated leptomeninges and subarachnoid space. Conclusion: This is a rare example of mixed, rhabdoid and papillary variant of meningioma., located entirely within the brain parenchyma and accompanied by a fulminant clinical course. The combination of the histo-logical anaplasia with the highest reported proliferation rate, and loss of the cohesion of neoplastic cells led to diffused infiltration of the leptomeninges and metastasis to the spinal cord. [ABSTRACT FROM AUTHOR]

A variety of neoplasms with rhabdoid differentiation have been reported in many sites. The authors describe a case of gastrointestinal stromal tumor (GIST) of the stomach that exhibited prominent rhabdoid features. Immunohistochemically, the tumor cells displayed positive staining for vimentin, c-kit, CD34, and alpha smooth muscle actin. Ultrastructural examination of the rhabdoid tumor cells revealed paranuclear whorls of intermediate filaments, which were immunoreactive for vimentin by both light microscopic immunohistochemical and protein A gold immunoelectron microscopic techniques. On H&E light microscopic examination alone, such a tumor could be mistaken for a variety of epithelial, mesenchymal, or other neoplasms that may show rhabdoid features. One report of GIST with a rhabdoid histologic phenotype has been described. This is the second known report of such a case with immunophenotypic and ultrastructural evaluation, and the first case with immunoelectron microscopic examination. [ABSTRACT FROM AUTHOR]

Rhabdoid tumors of the kidney are highly lethal malignancies of infancy. We report the prenatal detection of a renal rhabdoid tumor with mesoblastic components in a fetus at 27 weeks of gestation. The tumor presented as a large mass in the left renal area and there was concomitant massive polyhydramnios. Though the sonographic features alone did not allow distinction from a benign lesion, the aggressive tumor growth indicated malignancy. Amniotic fluid cytology was performed but failed to confirm the diagnosis. Corticosteroids were administered for lung maturation. Tocolysis, including betamimetics, magnesium and indomethacin, was performed to prevent premature labor. Additionally, serial amniodrainage was performed. At 30 weeks of gestation fetal hydrops developed and a Cesarean section was performed. After delivery, ventilation of the preterm infant was insufficient due to diaphragm elevation by the huge tumor, requiring immediate tumor surgery. However, though ventilation was improved the infant died of cardiac failure 4 h after surgery. [ABSTRACT FROM AUTHOR]

Malignant rhabdoid tumor (MRT) is one of very aggressive neoplasm commonly seen in kidney. An 8 months old boy presented with fever, abdominal distension, multiple vomiting and reduced oral intake. CT Angiography revealed a hyper dense mass involving multiple segments of the liver and associated rupture. He had near normal Sr. AFP (Alpha-Feto protein) levels. An emergent laparotomy revealed a tumour arising from the left lobe of liver which had ruptured already and the surface was bleeding. There was a large haemoperitoneum. A left hemi-hepatectomy was done. Post operative course was turbulent. He never recovered enough to be given chemotherapy. Prognosis was explained, the parents took the child home against medical advice. He died at home a few weeks later. Histopathological examination (HPE) revealed to be malignant rhabdoid tumour of the liver. [ABSTRACT FROM AUTHOR]

Biallelic loss of SMARCB1 /INI1 is associated with highly aggressive malignancies, namely renal and extra-renal malignant rhabdoid tumors, and atypical teratoid/ rhabdoid tumor. Increasing availability of molecular testing and immunohistochemical stains acting as surrogate tools to genetic analysis has led to an increasing recognition of SMARCB1 loss in a variety of neoplasms. Interestingly, many of these lack the typical rhabdoid features ascribed to this group of tumors, making their identification difficult. We describe the cytological, histological, immunohistochemical and molecular features of the first case of primary SMARCB1 (INI1)-deficient carcinoma of the thyroid gland in literature. The tumor was unique in various aspects; apart from never having been documented at this location, it showed extensive glandular differentiation, mimicking metastatic adenocarcinoma. Awareness of this novel entity is essential to avoid misdiagnosis, and for appropriate management, especially in an era of increased feasibility of targeted therapy. [ABSTRACT FROM AUTHOR]