Background

This is a highly malignant tumor, usually found in childhood. It was first described in the kidney as part of the National Wilm's Tumor Study, a comprehensive databank of pediatric renal tumors. Since the initial description, these tumors have been described in the soft tissue and in other organs. It is a highly aggressive neoplasm. Tumors in the kidney average less than 500 grams in weight. In some organs and cancers, poorly differentiated tumors may acquire a rhabdoid appearance. This change in phenotype is often associated with an aggressive behavior.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
AGE RANGE-MEDIAN	Kidney tumors Mean age at the time of diagnosis is 11 months
SEX (M:F)	Kidney 1.5 to 1.0

 

PATHOGENESIS	CHARACTERIZATION
Loss of heterozygosity at chromosome regions 22q11-12 and 11p15.5 in renal rhabdoid tumors. Schofield DE, Beckwith JB, Sklar J.	Genes Chromosom Cancer 1996; 15: 10–7
CYTOKERATIN 8 GENE
Mutation Analysis of Human Cytokeratin 8 Gene in Malignant Rhabdoid Tumor: A Possible Association with Intracytoplasmic Inclusion Body Formation Hideki Shiratsuchi, M.D., Tsuyoshi Saito, M.D., Akio Sakamoto, M.D., Eijun Itakura, M.D., Sadafumi Tamiya, M.D., Yumi Oshiro, M.D., Yoshinao Oda, M.D., Satoshi Toh, M.D., Sohtaro Komiyama, M.D. and Masazumi Tsuneyoshi, M.D. Department of Anatomic Pathology (HS, TS, AS, EI, SadT, YuO, YoO, MT) and Department of Otorhinolaryngology (SatT, SK), Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan	Mod Pathol 2002;15:146-153 Abstract quote The rhabdoid cell, which is typically observed in malignant rhabdoid tumor (MRT) and other malignant neoplasms, has an eosinophilic cytoplasm containing a spheroid perinuclear inclusion body. This distinct cell is known to act as a highly aggressive indicator in many types of malignant tumors and is characterized by aggregates of intermediate filaments, comprising both vimentin and cytokeratin (CK) 8, which is mainly expressed in simple-type epithelium such as liver and intestine. To clarify the cause of the inclusion body formation, we analyzed the alteration of the complete human CK8 gene (KRT 8: 1724 base pairs) in seven samples of MRT (three from frozen materials and four from cultured cell lines) by reverse-transcriptase polymerase chain reaction, followed by direct sequencing. In addition, the two cell lines, Huh7 and HeLa, which lacked rhabdoid feature, six pediatric malignant tumors, including three cases of primitive neuroectodermal tumor (PNET) and three of Wilms’ tumor; and 15 normal liver tissue (as a control) were also analyzed. All MRT samples had missense mutations in the human KRT 8 gene, i.e., Arg89 Cys (5/7); Arg Cys251 (3/7); Glu267 Lys (6/7); Ser290 Ile, Met; (7/7) and Arg301 His(4/7), none of which was detected in any control samples. Among these mutations, the most noteworthy findings were that Arg89 belongs to the H1 subdomain of the head domain and that Arg251 belongs to the short nonhelical linker segment, or L1–2. Both these mutations are noted for their relationships to lateral protofilament–protofilament interactions. In addition, Ser290 has been previously reported to be a phosphorylation site, which has been recognized to play an important role in filament organization, leading to conformational change of the CK8 filaments. In conclusion, mutated codons of CK8 gene in MRT were located in the important region involved in the conformational change of intermediate filament.

HISTOLOGICAL TYPES	CHARACTERIZATION
General	Rhabdoid appearance of cells with large hyalin-like globular inclusions at perinuclear regions of cytoplasm by hematoxylin-eosin stain Inclusions are composed of whorls of intermediate filaments
Rhabdoid tumor of kidney. A report of 111 cases from the National Wilms’ Tumor Study Pathology Center. Weeks DA, Beckwith JB, Mierau GW, Luckey DW.	Am J Surg Pathol 1989; 13: 439–58
With Rhabdoid features	Am J Surg Pathol 2000;24:1329-1338 Size of rhabdoid component varied from 1mm to >2cm and comprised 1-50% of the renal mass 52% of these cases (12/23) had extrarenal extension compared to 28% (24/92) of conventional renal cell carcinomas May indicate the emergence of an aggressive histologic and clinical element

 

SPECIAL STAINS/ IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
Special stains
Immunoperoxidase	Cytoplasm shows co-expression of cytokeratin and vimentin Usually CK 8 and 18, occasionally CK 19
Electron microscopy (EM)
Subcellular Distribution of Cytokeratin and Vimentin in Malignant Rhabdoid Tumor: Three-Dimensional Imaging with Confocal Laser Scanning Microscopy and Double Immunofluorescence Eijun Itakura, M.D., Sadafumi Tamiya, M.D., Keisuke Morita, M.D., Hideki Shiratsuchi, M.D., Yoshiaki Kinoshita, M.D., Yumi Oshiro, M.D., Yoshinao Oda, M.D., Shigeru Ohta, M.D., Masutaka Furue, M.D. and Masazumi Tsuneyoshi, M.D. Department of Anatomic Pathology (EIST, HS, YK, YO, YO, MT) and Department of Dermatology (KM, MF), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Department of Pediatrics, Shiga University of Medical Science (SO), Otsu, Shiga, Japan	Mod Pathol 2001;14:854-861 Abstract quote Malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm that mostly occurs in childhood, characterized histologically by rhabdoid cells as shown by eosinophilic intracytoplasmic inclusions. Although it is known that rhabdoid cells co-express cytokeratin (CK) and vimentin, the distribution patterns of these two kinds of intermediate filaments and structural relationship between them are still not known. We investigated the subcellular distribution of CKs 8 and 18 and vimentin in MRT cell lines (Tm87-16, STM91-01, TTC549, and TC289) using confocal laser scanning microscopy and double immunofluorescence, in addition to ultrastructural examination. Vimentin was diffusely expressed in the cytoplasm of MRT cells, focally forming a filamentous network. In contrast, CKs 8 and 18 were partially expressed in the cytoplasm of MRT cells, forming globules or a few vague agglomerates. Three-dimensional images in TC289 cells revealed distinct distribution patterns of cytokeratin and vimentin, showing agglomerates of cytokeratins within the vimentin filament network. We conclude that these globules and agglomerates of CKs 8 and 18 correspond with the characteristic ultrastructural finding, showing cytoplasmic bundles of intermediate filaments concentrated in whorled arrays.
hSNF5/INI1
Immunohistochemical Analysis of hSNF5/INI1 Distinguishes Renal and Extra-renal Malignant Rhabdoid Tumors From Other Pediatric Soft Tissue Tumors. Hoot AC, Russo P, Judkins AR, Perlman EJ, Biegel JA. From the Departments of *Pathology and daggerPediatrics, Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, PA; and double daggerDepartment of Pathology, Children's Memorial Hospital, Chicago, IL.	Am J Surg Pathol. 2004 Nov;28(11):1485-1491. Abstract quote Malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm that occasionally demonstrates phenotypic overlap with other soft tissue malignancies. Molecular genetic analysis of MRT frequently demonstrates deletion or mutation of the hSNF5/INI1 gene, with corresponding reduced expression at the protein level. INI1 immunohistochemistry was performed to determine the utility of this method in assessing loss of INI1 expression in rhabdoid tumors. Twenty-seven MRTs with molecular analysis (19 renal, 8 extra-renal) were evaluated. Seventeen additional MRT (10 renal, 7 extra-renal) without INI1 molecular analysis were also analyzed. Loss of INI1 expression was observed in the tumor cells in all 44 cases. To determine the specificity of this assay, a variety of 45 pediatric soft tissue tumors, some of which occasionally display rhabdoid differentiation, were investigated. These included Ewing's sarcoma, Wilms' tumor, desmoplastic small round cell tumor, clear cell sarcoma, congenital mesoblastic nephroma, synovial sarcoma, undifferentiated sarcoma, rhabdomyosarcoma, and epithelioid sarcoma. Positive nuclear staining was found in all nonrhabdoid tumors examined. Of interest, synovial and epithelioid sarcomas exhibited variable and/or focal staining. INI1 antibody immunohistochemistry is useful in confirming the histologic diagnosis of renal or extra-renal rhabdoid tumor, especially for cases with indeterminate histologic features, equivocal immunophenotypic profiles, or uninformative molecular studies.

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
RENAL CELL CARCINOMA
Renal cell carcinoma with rhabdoid features. Gokden N, Nappi O, Swanson PE, Pfeifer JD, Vollmer RT, Wick MR, Humphrey PA. Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes-Jewish Hospital and the Washington University School of Medicine, St. Louis, MO 63110, USA.	Am J Surg Pathol 2000 Oct;24(10):1329-38 Abstract quote Neoplasms with rhabdoid features have been reported at many anatomic sites. In the kidney, rhabdoid tumors are typically found in children, whereas only rare examples have been reported in adults. Little is known of renal cell carcinomas (RCCs) that exhibit rhabdoid features. The objective of this study was to determine the incidence of RCC with rhabdoid attributes and characterize the histologic, immunophenotypic, and ultrastructural features by retrospective analysis of 480 consecutively identified cases of RCC in radical nephrectomy specimens. Immunohistochemical evaluation was performed in cases with rhabdoid foci using a panel of antibodies to pancytokeratin (pan-CK), CK7, CK20, epithelial membrane antigen (EMA), S-100 protein, desmin, vimentin, neuron-specific enolase (NSE), muscle-specific actin (MSA), smooth muscle actin (SMA), human melanoma, black-45 (HMB-45), and glial fibrillary acidic protein (GFAP). Electron microscopy was also performed in selected cases. The presence and extent of rhabdoid foci in relation to pathologic stage and grade were assessed. Twenty-three of 480 cases of RCC (4.7%) exhibited rhabdoid features. The 23 patients were all adults with a mean age of 61.8 years (age range, 33-84 yrs). Fifteen of the patients were men and eight were women. Histologically, the rhabdoid foci were typified by sheets and clusters of variably cohesive, large epithelioid cells with vesicular and often eccentric nuclei, prominent nucleoli, and large, paranuclear intracytoplasmic hyaline globules (inclusions). The presence of these rhabdoid features was related to high histologic Fuhrman grade of the nonrhabdoid carcinoma component, with an incidence of 0 of 84 grade I cases, eight of 300 grade 2 cases (2.6%), six of 70 grade 3 cases (8.9%), and nine of 26 grade 4 cases (34.6%; p = 3 x 10(-9)). The rhabdoid foci were all high grade. The presence of rhabdoid foci was also found in higher stage carcinomas. A total of 52% (12 of 23) of RCC cases with rhabdoid features exhibited extrarenal extension compared with 28% (24 of 92) of contemporary RCCs without rhabdoid features (p = 0.03). The size of the rhabdoid component ranged from 1 mm to more than 2 cm and comprised 1% to 50% of the renal mass. Immunoreactivity for vimentin (100%), NSE (79%), and panCK (56%) was present in the majority of cases. Substantial percentages of cases were immunopositive for EMA (47%) and S-100 protein (37%), with minimal to no immunohistochemical reactivity for CK7 (5%), SMA (5%), CK20 (0%), desmin (0%), MSA (0%), HMB-45 (0%), and GFAP (O%). A distinctive globular, paranuclear reaction pattern was found for the cytokeratin, EMA, and vimentin immunostains. Ultrastructurally, the rhabdoid cells had paranuclear intermediate filament aggregates or paranuclear condensation of organelles, often associated with peripheral vacuolization. Adult RCCs may harbor a rhabdoid component, and these neoplasms can be regarded as "composite" tumors. Rhabdoid elements are important to identify because of their high-grade nature, and association with high stage. Adult RCC with rhabdoid elements should be distinguished from pure rhabdoid tumors of kidney, in light of their clinicopathologic differences. Rhabdoid differentiation in adult renal cell carcinoma may represent clonal divergence and/ or evolution, and emergence of a particularly aggressive element.
SYNOVIAL SARCOMA WITH RHABDOID FEATURES
Synovial Sarcoma of the Kidney With Rhabdoid Features: Report of Three Cases. Jun SY, Choi J, Kang GH, Park SH, Ayala AG, Ro JY. *Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Seoul National University College of Medicine, Seoul, Korea; Korea Cancer Center Hospital, Seoul, Korea; and University of Texas M. D. Anderson Cancer Center, Houston, TX.	Am J Surg Pathol. 2004 May;28(5):634-637. Abstract quote   We report 3 cases of synovial sarcoma with rhabdoid features, initially diagnosed as adult rhabdoid tumors. Two women (case nos. 1 and 2, 35 years and 27 years of age, respectively) and one man (case no. 3, 26 years of age) presented to their physicians with right flank pain. On physical examination, a poorly defined, firm, palpable mass was found in the upper right quadrant of the abdomen in all cases. Sonography and computed tomography revealed solid, cystic masses in the right kidneys that ranged in size from 8.5 to 20.0 cm. Right radical nephrectomies were performed in all patients. One patient died of disease, and the other two patients were alive and disease-free after chemotherapy and radiotherapy. Microscopic examination revealed that the tumors were composed mostly of rhabdoid cells with eccentrically located nuclei, prominent nucleoli, and eosinophilic cytoplasm. We also found areas of fasciculated spindle cells, sharply separated from or irregularly admixed with areas of rhabdoid cells. There was tumor necrosis, but no epithelial areas were seen. Hemangiopericytic vasculature was at least focally observed in all cases. The tumor cells were positive for CD99 and bcl-2 in all cases and for CD56 in two cases and negative for CD34 and smooth muscle actin in all cases. The cells in case no. 1 were focally positive for cytokeratin. To verify the possibility of synovial sarcoma with rhabdoid features, reverse transcriptase polymerase chain reaction using RNA extracted from frozen tissue in case no. 1 and formalin-fixed, paraffin-embedded tissue in case nos. 2 and 3 was performed. SYT-SSX2 transcripts were detected in all 3 cases. These cases indicate that synovial sarcoma of the kidney should be considered in the differential diagnosis of mesenchymal kidney tumors with prominent rhabdoid features. A subset of adult rhabdoid tumors may be a rhabdoid variant of synovial sarcoma, and molecular studies to detect SYT-SSX fusion transcripts are recommended for an accurate diagnosis.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors
Survival	Poor, most patients with kidney tumors die within a year of diagnosis

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Last Updated November 10, 2004

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