Diagnosis Of Malignant Rhabdoid Tumor Research Articles

Fetal Disseminated Malignant Rhabdoid Tumor.

Fetal Disseminated Malignant Rhabdoid Tumor.

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.

Malignant Rhabdoid Tumor, an Aggressive Tumor Often Misclassified as Small Cell Variant of Hepatoblastoma.

The clinical management of pediatric liver tumors involves stratification into risk groups. One previously defined, high-risk group of hepatoblastomas is the small cell undifferentiated variant. In light of molecular studies showing SMARCB1 deletion in these tumors, it is now recognized that most small cell, undifferentiated liver tumors represent an aggressive unrelated tumor—the malignant rhabdoid tumor (MRT). SMARCB1 is a member of the chromatin remodeling SWI/SNF complex and encodes the INI1 protein. The histologic diagnosis of MRT is currently based on INI1 negative immunoreactivity and the presence of rhabdoid morphology. INI1-negative small cell liver tumors lacking classic rhabdoid morphology are often misclassified as small cell undifferentiated hepatoblastomas (SCUD-HB), according to the current classification. Pediatric liver tumors diagnosed between 2003–2017 as SCUD-HB (four cases) or MRT (two cases) were identified from the Columbia University Pathology Department Archives. All tumors were associated with normal or low serum alpha fetoprotein levels, and showed an absence of immunohistochemical staining of hepatocellular markers (Hep-par1, Arginase) and loss of INI1 staining. Two cases were initially diagnosed as MRT, one with prominent rhabdoid morphology, the other with predominant small cell morphology. The remaining four cases with small cell morphology were classified as SCUD-HB. Ancillary molecular studies confirmed the loss of SMARCB1, supporting the diagnosis of MRT in all cases, proving morphology an unreliable criterion. It is critical to eliminate the term INI1-negative hepatoblastoma from the current classification scheme, and classify INI1-negative tumors as MRT, particularly since high-risk HB-chemotherapy regimens are not effective for treating MRT.

A newborn with malignant Rhabdoid tumors: A visual diagnosis case

Malignant rhabdoid tumor (MRT) is a rare tumor and is first thought a variant of Wilms’ tumor in the kidney. It is recognized as presenting at renal, central nervous system (CNS) and other extra-renal primary sites. A full term baby boy with multiple different sizes bluish skin nodules and masses were found on the surface of his body, which was consistent with MRT. Under the emergency skin biopsy, the result showed that the histologic diagnosis of malignant rhabdoid tumor. The presence of metastasis at diagnosis of MRT seems to be the only prognostic factor of outcome. Keywords: Rhobdiod tumor, Newborn, Cutaneous, Treatment.

INI1 negative hepatoblastoma, a vanishing entity representing malignant rhabdoid tumor

Malignant rhabdoid tumors (MRT) represent a distinct group of aggressive tumors usually occurring in infancy involving a variety of anatomic locations including the kidney, brain, soft tissue and liver. The molecular hallmark of these tumors is the presence of deletions and/or mutations of SMARCB1 or rarely SMARCA4 that lead to the absence of INI1 or BRG1 proteins, core components of the SWI/SNF chromatin remodeling complex.MRT of the liver are rare tumors that comprise less than 5% of malignant pediatric liver tumors. They are currently diagnosed on the basis of documenting both INI1 negative immunoreactivity and rhabdoid morphology. In the absence of molecular testing, MRT lacking classic rhabdoid morphology are currently classified as small cell undifferentiated hepatoblastoma (HB). Here we report a case of MRT initially classified as a INI1 negative small cell HB. Whole Exome Sequencing with Transcriptome subsequently showed homozygous deletion of SMARCB1 on chromosome 22q11.23 with evidence of loss of expression of the gene, establishing the diagnosis of MRT. As molecular testing of these tumors is performed on a more routine basis, this case illustrates that the INI negative small cell undifferentiated variant of HB actually represents MRT, a tumor unrelated to HB.

Malignant rhabdoid tumor in the renal allograft of an adult transplant recipient: a unique case of a rare tumor

BackgroundRenal transplant recipients have increased risk for developing malignant diseases because of immunosuppression or donor-to-recipient transmission. Malignant rhabdoid tumor (MRT) is a rare, highly aggressive and lethal tumor primarily affecting the kidney of infants and young children. MRT has not been reported in the renal allograft of an adult recipient after kidney transplantation.Case presentationIn this report, a 47-year-old woman who received a kidney transplantation from an infant donor and developed a mass in the transplanted kidney is presented. Pathological examinations revealed a malignant tumor with rhabdoid cells morphologically and the loss of INI1 expression immunohistochemically. The diagnosis of malignant rhabdoid tumor in the transplanted kidney was made. We confirmed that donor-to-recipient malignancy transmission was the cause of MRT in the transplanted kidney by fluorescence in situ hybridization (FISH) and short tandem repeat (STR) analysis.ConclusionTo our knowledge, this is the first case of MRT in an adult renal allograft recipient. This report highlights the importance of the criteria for selection of donors to screen possible malignant tumors transmission.

Oncogenic roles of SMARCB1/INI1 and its deficient tumors.

SMARCB1/INI1 is one of the core subunit proteins of the ATP‐dependent SWI/SNF chromatin remodeling complex, and is identified as a potent and bona fide tumor suppressor. Interactions have been demonstrated between SMARCB1/INI1 and key proteins in various pathways related to tumor proliferation and progression: the p16‐RB pathway, WNT signaling pathway, sonic hedgehog signaling pathway and Polycomb pathway. Initially, no detectable SMARCB1/INI1 protein expression was found in malignant rhabdoid tumor cells, whereas all other kinds of tumor cells and non‐tumorous tissue showed SMARCB1/INI1 protein expression. Therefore, immunohistochemical testing for the SMARCB1/INI1 antibody has been considered useful in confirming the histologic diagnosis of malignant rhabdoid tumors. However, recently, aberrant expression of SMARCB1/INI1 has been found in various tumors such as epithelioid sarcomas, schwannomatosis, synovial sarcomas, and so on. In addition, it has been reported that aberrant expression can be classified into three patterns: complete loss, mosaic expression and reduced expression. Although the various pathways related to mechanisms of tumorigenesis and tumor proliferation are complexly intertwined, the clarification of these mechanisms may contribute to therapeutic strategies in SMARCB1/INI1‐deficient tumors. In terms of pathological classifications, SMARCB1/INI1‐deficient tumors may be re‐classified by genetic backgrounds.

Malignant Renal Tumors in Childhood: Report of 54 Cases Treated at a Single Institution

Wilms tumor is the most common primary renal malignancy occurring in childhood. Significant improvement has been made in the treatment of children with Wilms tumor. However, the treatment of patients with non-Wilms renal tumors remains challenging. Between 1991 and 2010, 70 children with renal tumors were diagnosed at a single institution. Fifty-four patients were histologically confirmed and divided into three groups, including 42 Wilms tumors, seven clear cell sarcomas of kidney, and five malignant rhabdoid tumors. Most patients underwent unilateral nephrectomy and lymph node sampling followed by adjuvant chemotherapy. Twenty-one of these patients subsequently received radiotherapy. During follow-up, 12 patients died of progressive disease and one died of operative mortality. One patient with unilateral pleural metastases subsequently underwent hematopoietic stem cell transplantation. The median survival time of all patients was 88 months. Children under 2 years of age at diagnosis with Wilms tumor or clear cell sarcoma of kidney had an excellent survival rate of 100% compared to the 0% survival rate of MRT. Younger age at diagnosis bore a better prognosis than did older age, whereas a diagnosis of malignant rhabdoid tumor portended a worse prognosis. Younger patients and appropriate treatment may have contributed to the improved prognosis of clear cell sarcoma of kidney.

Malignant Brain Tumor With Rhabdoid Features in an Adult -Case Report-

Rhabdoid tumor (RT) of the central nervous system is an uncommon and aggressive neoplasm that usually affects pediatric patients. Currently, these tumors are classified as malignant RT or atypical teratoid/RT. Another entity of intraparenchymal brain tumor with a rhabdoid component is the extremely rare rhabdoid glioblastoma. A 23-year-old woman presented with a malignant RT in the right thalamus. The tumor was adjacent to the right lateral ventricle and was partially resected. Histological examination revealed prominent proliferation of rhabdoid cells, which is consistent with a diagnosis of malignant RT; the typical features of glioblastoma were not observed. The tumor cells stained positively for integrase interactor-1 and glial fibrillary acidic protein. Therefore, the tumor may have originated from glial components. Genetic analysis using comparative genomic hybridization showed a deoxyribonucleic acid copy-number gain on chromosome 7 but not on chromosome 22. The tumor did not respond to chemotherapy or radiotherapy, and the patient survived for only 4 months after surgery. The present case of malignant RTs shows certain similarities with those of rhabdoid glioblastoma. Further accumulation and analysis of data, including data from genetic analyses, may lead to the identification of a new type of malignant RT.

Pediatric Non-Wilms Renal Tumors: Subtypes, Survival, and Prognostic Indicators

To determine the outcomes and predictors of survival for pediatric non-Wilms renal tumors (NWRT). The SEER database (1973-2005) was queried for all patients < 20 y of age. Overall, 349 cases of NWRT were identified. The major histologic groups included renal cell carcinoma (RCC) (44%), clear cell sarcoma of the kidney (CCSK) (17%), and malignant rhabdoid tumor (MRT) (12%). A bimodal age distribution was observed, with tumors commonly presenting in patients ≤4 y of age and ≥15 y of age. More than 50% of RCC presented at ≥15 y of age, whereas ≥80% of CCSK or MRT patients were ≤4 y of age. Most RCC (57%) and CCSK (53%) were locally staged while most MRT presented with distant disease (51%, P < 0.001). Overall 10-y survival was 63% with improved survival observed in patients with CCSK (79%) and RCC (70%) versus MRT (29%, P< 0.001). By univariate analysis, surgical resection was associated with improved overall 10-y survival (68% versus 30%, P < 0.001), while no benefit was observed for radiotherapy (60% versus 63%, P = 0.8). By multivariate analysis, worse overall survival was observed for patients ≥ 10 y old (HR 4.01, P = 0.013) and those with advanced disease (HR = 12.78, P < 0.001). Patients with MRT (HR = 11.61, P < 0.001) and CCSK (HR = 3.68, P = 0.038) had significantly worse prognosis compared with those with RCC. Surgical resection improved overall survival (HR = 0.36, P = 0.001). For pediatric NWRT, younger patients and those with RCC have improved survival, while adiagnosis of MRT portends a worse prognosis. Surgical extirpation significantly improves survival for all patients.

Malignant rhabdoid tumor of rectum: report of a case

Dear Editor, Malignant rhabdoid tumor, which first described in kidneys of infants and children, is a rare and highly aggressive neoplasm with very poor prognosis and unresponsiveness to conventional treatment [1–3]. This tumor has been reported at many other sites, such as central nervous system, spine, urinary bladder, thyroid, retroperitoneum, and so forth [1–4]. The gastrointestinal tract is even rarer site of this disease, only 22 cases of gastrointestinal malignant rhabdoid tumor have been previously described in literature, but only one case of rectal malignant rhabdoid tumor has been published to date [3]. We report a case of a 23-year-old woman with malignant rhabdoid tumor of the rectum, she was healthy 17 months later after operation, who was treated by radical resection followed by adjuvant chemoradiotherapy. The aim of this correspondence is to call the clinician’s attention to the differential diagnostic importance of this entity. Although there are isolated reports of long-term survival with intensive, multimodal therapy, the prognosis of malignant rhabdoid tumor is generally poor [4]. A retrospective review of 34 pediatric malignant rhabdoid tumors from Morgenstern et al. [2], only four survived long ([30 months), all of whom received chemotherapy with or without surgical resection or radiotherapy. However, our experience suggests that radical resection is the first choice of treatment for rectal malignant rhabdoid tumor, followed by adjuvant radiotherapy and chemotherapy after operation; this is in agreement with Macak’s opinion [3]. A 23-year-old woman presented with 1 month of abdominal pain and bloody diarrhea. Her medical history was unremarkable except for an appendectomy because of acute purulent appendicitis 2 years previously. The physical examination revealed that a well-developed and wellnourished, the abdomen was protuberant, there was no palpable masses or organomegaly, and there were active bowel sounds, there was no lower abdominal rigidity or rebound tenderness either. The rectal digital examination revealed a cauliflower-like rectal tumor, 5.0 9 5.0 cm in diameter, at 5 cm distance from the anal verge was palpable. Laboratory examination revealed that the initial leukocyte count was 14.9 9 10/L, neutrophil 0.758, red blood cell count 4.36 9 10/L, a platelet count 410 9 10/L, alpha-fetoprotein (AFP) 1.7 ug/L, carcinoembryonic antigen (CEA) 0.4 ug/L, cancer antigen (CA)19–9 6 U/ml, prothrombin time and partial thromboplastin time were normal. Computerized tomography (CT) revealed that thickening of diseased rectum associated with enlargement of afferent bowel. Colonoscopy revealed an ulcerated tumor at anterior wall of rectum 5 cm distance from the anal verge, and biopsy demonstrated a well-differentiated adenocarcinoma of the tumor. At laparotomy, a tumor of 5.0 9 6.0 cm in size located at below the peritoneal reflection, no evidence of invasion to adjacent organ was found, and therefore Miles’ operation was performed. A histological diagnosis of malignant rhabdoid tumor of the rectum was made after operation, and tumor cells invaded fibrous membrane of the rectum. The postoperative histopathological examination revealed that the tumor was arranged diffusely, and histologically S. L. Han (&) J. L. Li Z. Liu J. Cheng S. C. Guo Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical College, 325000 Wenzhou, Zhejiang Province, China e-mail: slhan88@yahoo.com.cn; slhan88@126.com

Immunohistochemical Study as a Tool in Differential Diagnosis of Pediatric Malignant Rhabdoid Tumor

Malignant rhabdoid tumors (MRTs) are aggressive childhood neoplasms, occurring mainly in the kidney and brain. We describe 2 unusual cases of extrarenal and noncranial location (liver and soft tissue with dissemination) mimicking hepatoblastoma, neuroblastoma or Ewing sarcoma. Both cases revealed a polyphenotypic profile, combined with cytokeratin, vimentin, and CD99 expression. INI1/BAF-47 showed negative protein nuclear expression in both cases, suggesting a diagnosis of MRT. An extensive immunohistochemical panel was performed to exclude pediatric tumors reminiscent of MRT. The genetic studies failed to detected MYCN amplification, 11q23 deletion, and EWS break-apart positivity. No alterations of 22q integrity were demonstrated with the probes used for the study (N25 Di George/22q11.2, 22qter, and EWS/22q12). We discuss the differential diagnosis in pediatric polyphenotypic tumors (Wilms tumor, neuroblastoma, desmoplastic small round cell tumor, and Ewing sarcoma). Analysis of INI1/BAF-47 expression can offer important clues in the diagnosis of pediatric tumors with rhabdoid phenotype. The integration of clinical, morphologic, immunohistochemical, and genetic data is required to approach a correct diagnosis of pediatric tumor in unusual location with atypical or undifferentiated morphology.

Malignant rhabdoid tumor of the liver: a case report with US and CT manifestation

A case of malignant rhabdoid tumor (MRT) of the liver in a 4-month-old boy with hepatomegaly was described with the help of US and CT findings. The boy had multiple liver tumors, and the liver parenchyma showed a diffuse heterogeneous appearance. Lymph node swelling was noted, although the alpha-fetoprotein concentration was not elevated. A diagnosis of MRT was confirmed pathologically. Twenty-seven cases of MRT of the liver with solitary tumors, multiple tumors, or diffuse infiltration have been reported in the English-language literature. Diagnostic imaging plays an important role in detecting metastasis because of the high frequency of distant metastasis in MRT of the liver.

Age, stage, and radiotherapy, but not primary tumor site, affects the outcome of patients with malignant rhabdoid tumors

Malignant rhabdoid tumors (MRTs) are aggressive and often fatal; the Surveillance, Epidemiology, and End Results (SEER) database offers an opportunity to study this rare malignancy. From the SEER database, we extracted records of patients with a reported diagnosis of MRT and analyzed them for clinical features and survival rates by univariate and multivariate analyses. For the 229 patients included in our data, who were diagnosed from 1986 to 2005, primary tumors were located in the central nervous system (CNS) (35%), kidneys (20%), and extra-renal non-cranial sites (ERNC-MRTs) (45%). Most patients with renal and CNS tumors were less than 18 years old (87% and 96%, respectively) while more than half of the patients with ERNC-MRTs (61%) were adults. Among staged tumors, 23% were localized, 34% regional, and 43% distant. Renal tumors had significantly more metastatic disease (47%; P = 0.006) than ERNC-MRTs. The estimated 5-year survival for the entire group was 33 +/- 3.4% (SE). Univariate and multivariate analyses showed that age at diagnosis (2-18 years), localized stage of tumors, and use of radiotherapy were significantly associated with improved survival. Adults had a better outcome than young children (<2 years old) but a poorer outcome than older children (2-18 years old); tumor stage, but not radiotherapy use, affected outcome in adults. The survival and prognostic factors of children diagnosed before and after 2000 did not differ significantly. Our population-based study indicates that age at diagnosis, tumor stage, and use of radiotherapy favorably impact survival rates of patients with MRTs.

Pediatric extra-renal rhabdoid tumors with unusual morphology: A diagnostic pitfall for small biopsies

The diagnosis of malignant rhabdoid tumor (MRT) is straightforward if the typical, large eosinophilic rhabdoid cells are identified. We report on two diagnostically challenging cases of pediatric extra-renal MRTs which, when evaluated at incisional biopsy, were composed exclusively of small- to medium-sized round cells with focal spindling, lacking rhabdoid phenotype. This morphology, along with a polyphenotypic immunoprofile, including the expression of vimentin/CD99/cytokeratins/α-smooth muscle actin and vimentin/CD99/S-100 protein in case 1 and case 2, respectively, suggested the possibility of Ewing sarcoma (EWS)/PNET. However, molecular analyses failed to show the presence of the EWS/FLI-1 and EWS/ERG fusion transcripts, indicative of the most common translocations, i.e., t(11;22)(q24;q12) and t(22;21)(q22;q12), occurring in this tumor family. The revision of both cases included an immunohistochemical analysis with a commercially available anti-INI1 protein antibody. Immunohistochemistry, showing the absence of INI1 expression in neoplastic cells, strongly supported the diagnosis of MRT. Ultrastructural studies, performed on formalin-fixed tissues, were consistent with the diagnosis of MRT. This study suggests including anti-INI1 protein antibody in the immunohistochemical panel when evaluating pediatric tumors with ambiguous morphological and immunohistochemical features, particularly from small biopsies. A careful evaluation of clinical, pathological, and molecular findings is the key to a correct diagnostic approach of pediatric tumors.

Infrequent SMARCB1/INI1 gene alteration in epithelioid sarcoma: a useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of epithelioid sarcoma. In addition, the histopathologic differences between proximal-type epithelioid sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 epithelioid sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type epithelioid sarcoma and 27 (93.1%) distal-type epithelioid sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type epithelioid sarcoma. Epithelioid sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type epithelioid sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type epithelioid sarcoma (P = .001). Therefore, proximal-type epithelioid sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type epithelioid sarcoma from malignant rhabdoid tumor.

SMARCB1/INI1 Protein Expression in Round Cell Soft Tissue Sarcomas Associated With Chromosomal Translocations Involving EWS: A Special Reference to SMARCB1/INI1 Negative Variant Extraskeletal Myxoid Chondrosarcoma

Several previous studies have demonstrated the lack of SMARCB1/INI1 protein expression in only the malignant rhabdoid tumor (MRT). Several sarcoma groups are associated with a tumor-specific translocation involving EWS. Moreover, the EWS and SMARCB1/INI1 genes are located on the same 22q chromosome. We analyzed the status of SMARCB1/INI1 protein expression in 93 cases of sarcomas associated with chromosomal translocation involving EWS, comprising 52 Ewing's sarcoma/primitive neuroectodermal tumors, 24 extraskeletal myxoid chondrosarcomas (EMCS), 14 clear cell sarcomas of soft tissue, 2 desmoplastic small round cell tumors, and 1 myxoid/round cell liposarcoma. In addition, we analyzed the detailed SMARCB1/INI1 gene alteration in cases, which lacked its protein expression. Consequently, 4 EMCS showed no SMARCB1/INI1 expression, and 2 of these 4 cases revealed homozygous deletion and frameshift mutation of the SMARCB1/INI1 gene, respectively. These cases showed histologic findings compatible with EMCS, according to the most recent WHO classification, but no major fusion gene transcripts were detected. Moreover, 3 out of 4 SMARCB1/INI1 negative variant EMCS disclosed rhabdoid features. Therefore, the lack of SMARCB1/INI1 protein expression may be associated with rhabdoid features. The immunohistochemical result of the SMARCB1/INI expression is not an absolute diagnostic criteria for MRT and careful histologic evaluation is required to make a precise diagnosis of MRT.

Uterine Neoplasms Composed of Rhabdoid Cells Do Not Exhibit Loss of INI1 Immunoreactivity and Are Not Related to Childhood Malignant Rhabdoid Tumor

Malignant rhabdoid tumors are rare childhood neoplasms which occur most commonly in the kidneys, soft tissue, and central nervous system. They are characterized by cells with eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. Recently, it has been demonstrated that malignant rhabdoid tumors in childhood are characterized by biallelic deletion or mutation involving the SMARCB1/INI1 gene on chromosome 22. These molecular events result in loss of immunohistochemical expression of INI1. Neoplasms with a similar morphology occur in adults, either in pure form or associated with a parent tumor. It is controversial whether such neoplasms in adults are related to childhood malignant rhabdoid tumor or whether a rhabdoid morphology represents a nonspecific phenotype which can occur in a variety of neoplasms. In this study, we stained a series of adult uterine neoplasms with a prominent component of rhabdoid cells with the Baf 47 antibody which detects INI1; we aimed to ascertain whether these are related to childhood malignant rhabdoid tumor. Neoplasms included were an undifferentiated sarcoma consisting entirely of rhabdoid cells, 2 carcinosarcomas with a mesenchymal component composed entirely of rhabdoid cells, and 3 uterine tumors resembling ovarian sex cord tumor with rhabdoid cells. In all cases, there was positive nuclear staining of the rhabdoid cells with Baf 47, suggesting an absence of gene deletion or mutation and that these neoplasms are not related to childhood malignant rhabdoid tumor. In adults, we suggest that a diagnosis of malignant rhabdoid tumor should not be made without genetic confirmation or loss of immunohistochemical expression of Baf 47. In the absence of these, an attempt should be made to classify such tumors on the basis of any associated parent neoplasm and/or immunohistochemical or ultrastructural evidence of specific differentiation. We reviewed uterine neoplasms with a rhabdoid phenotype.

PRIMARY THORACIC MYXOID VARIANT OF EXTRARENAL RHABDOID TUMOR IN CHILDHOOD

Primary extrarenal rhabdoid tumors (RT) are now recognized as a specific entity in pediatric oncological pathology practice. We present an unusual case of a small cell myxoid variant of a thoracic RT in an infant and highlight the importance of recent molecular developments in the diagnosis of these tumors. An 8-month-old child presented with a short history of cough and shortness of breath. Imaging demonstrated a large mass occupying the majority of the thoracic cavity on the right side. A percutaneous needle biopsy of the mass showed fragments of tissue composed of malignant tumor with a predominant “small ovoid cell” phenotype and extensive myxoid change, with small nests and islands of tumor cells; occasional cells demonstrated open vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasmic inclusions. Immunohistochemical staining revealed focal strong cytoplasmic positivity for cytokeratin, focal strong paranuclear cytoplasmic vimentin positivity, and INI1 staining showed normal nuclear positivity in control tissues but was negative in tumor cell nuclei. Electron microscopy demonstrated characteristic paranuclear whorls of intermediate filaments confirming the diagnosis of extrarenal malignant RT. The diagnosis of malignant rhabdoid tumor may be difficult, particularly in cases, such as the present, with a predominant small-cell myxoid phenotype. The characteristic expression patterns of cytokeratin and vimentin provide strong clues to the diagnosis, and the use of INI1 antibody now makes definitive diagnosis possible even on needle core biopsies.

Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis

Malignant rhabdoid tumors are high-grade neoplasms of the central nervous system (CNS), kidneys and soft tissue that usually occur in children. The histologic diagnosis of malignant rhabdoid tumor depends on identification of characteristic rhabdoid cells—large cells with eccentrically located nuclei and abundant, eosinophilic cytoplasm—and immunohistochemistry with antibodies to vimentin, keratin and epithelial membrane antigen. In most malignant rhabdoid tumors, the SMARCB1/INI1 gene, located in chromosome band 22q11.2, is inactivated by deletions and/or mutations, so genetic diagnosis is often possible. However, tissue may not be available for genetic analysis or studies not confirmatory. We assessed SMARCB1/INI1 expression in 17 rhabdoid tumors and 57 other tumors of the CNS, kidney or soft tissue using immunohistochemistry. In total, 12 brain, three renal and two soft tissue rhabdoid tumors were examined along with four glioblastomas, four pilocytic astrocytomas, four oligodendrogliomas, two ependymomas, two choroid plexus papillomas, five pituitary adenomas, four germinomas, four renal carcinomas with Xp11.2 translocations, two clear cell sarcomas, two Wilms' tumors, one renal medullary carcinoma, two desmoplastic small round cell tumors, two alveolar rhabdomyosarcomas, two embryonal rhabdomyosarcomas, one low-grade chondrosarcoma, two extraskeletal myxoid chondrosarcomas, one mesenchymal chondrosarcoma, four malignant peripheral nerve sheath tumors, five metastatic carcinomas and four epithelioid sarcomas, two primary and two metastatic. The neoplastic cells of all rhabdoid tumors, the four epithelioid sarcomas and the renal medullary carcinoma did not express SMARCB1/INI1 by immunohistochemistry; neoplastic cells of all other tumors expressed SMARCB1/INI1. Immunohistochemistry to assess expression of SMARCB1/INI1 may be useful in the diagnosis of rhabdoid tumors of the CNS, kidneys and soft tissue.