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Background

These tumors are the extra-renal and soft tissue tumor equivalents of the aggressive tumor first reported in the kidney. For many of these cases, the characteristic histologic finding of rhabdoid changes may represent an example of dedifferentiation by the original tumor cells to this pleomorphic cell type. The acquisition of this rhabdoid feature appears to impart an aggessive clinical course to many of these tumors.

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  

PATHOGENESIS CHARACTERIZATION
CHROMOSOMAL ABNORMALITIES  

Molecular sublocalization and characterization of the 11;22 translocation breakpoint in a malignant rhabdoid tumor.

Newsham I, Daub D, Besnard-Guerin C, Cavenee W.

Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla 92093-0660.

Genomics 1994 Feb;19(3):433-40 Abstract quote

Malignant rhabdoid tumors are extremely aggressive soft-tissue sarcomas that tend to be widely metastatic at diagnosis. These tumors were first described as variants of the kidney neoplasm Wilms' tumor, although tumors of similar clinicopathologic features have been cited in a variety of extrarenal sites.

Here, we have characterized the chromosomal translocation t(11;22)(p15.5;q11.23) from a retroperitoneal rhabdoid tumor. Somatic cell hybrids with segregated copies of the derivative 11 and derivative 22 chromosomes allowed sublocalization of the chromosome 11 breakpoint to a 1- to 2-Mb region between the proximal marker D11S12 and the distal locus tyrosine hydroxylase (TH). Translocation-associated aberrant fragments were identified by pulsed-field gel electrophoresis, with the smallest resulting from BssHII digestion as detected with a probe for TH. These data indicate that the locus or loci disrupted by this genetic abnormality might lie less than 60 kb proximal to this marker and place it in the chromosomal vicinity of genes involved in the etiologies of rhabdomyosarcoma, Wilms' tumor, and the congenital overgrowth disorder, Beckwith-Wiedemann syndrome. Analysis of two other tumor-associated loci, EWS1 and NF2, that have been mapped to the general region of 22q11.2 indicated that they were not involved in this translocation breakpoint.

Isolation of the genes present at this translocation junction on both chromosomes 11 and 22 may yield important clinicopathologic and genetic markers for this enigmatic tumor as well as other pediatric diseases.

Immunohistochemical and cytogenetic findings in malignant rhabdoid tumor.

Kaiserling E, Ruck P, Handgretinger R, Leipoldt M, Hipfel R.

Institute of Pathology, University of Tubingen, Germany.

Gen Diagn Pathol 1996 May;141(5-6):327-37 Abstract quote

BACKGROUND: The histogenesis of malignant rhabdoid tumor (RT) remains a matter of controversy. From published reports it appears that some extrarenal RT (ERRT) exhibit neural or neuroectodermal features. Systematic investigation of renal RT (RRT) for neural differentiation has not yet been published. In this study, two RRT and two ERRT were investigated by light and electron microscopy, immunocytochemistry, and cytogenetic analysis.

RESULTS: All four cases exhibited similar morphology and a largely consistent immunohistochemical staining profile. Both tumor types showed immunoreactivity for various cytokeratins, epithelial membrane antigen (EMA), vimentin, neurofilaments, S100 protein, neuron specific enolase, Leu7, CD34, p53, MB2, MIC2, VS38c, laminin and fibronectin. Reactivity was usually confined to a small proportion of the tumor cells, especially in the case of antibodies against neurofilaments, NSE, S100 proteins Leu7, CD34 and p53. Only a few of the antibodies (anti-vimentin, MB2, MIC2, anti-EMA, and VS38c) stained the majority of the tumor cells. Chromosome analysis revealed a discrete aberration in 11p (most probably a paracentric inversion in 11p15) in the one RRT investigated. One ERRT had a normal karyotype, but the other one exhibited various structural abnormalities on chromosomes 18 and 22.

CONCLUSIONS: The immunohistochemical investigations revealed many similarities between RRT and ERRT, and all four tumors investigated exhibited neuroectodermal differentiation. As far as histogenetic classification is concerned, our findings point in the direction of the group of tumors that includes Ewing's sarcoma and primitive neuroectodermal tumors

Cytogenetic and molecular analysis of a t(1;22)(p36;q11.2) in a rhabdoid tumor with a putative homozygous deletion of chromosome 22.

Rosty C, Peter M, Zucman J, Validire P, Delattre O, Aurias A.

Laboratoire de Genetique de Tumeurs, Institut Curie, Paris, France.

Genes Chromosomes Cancer 1998 Feb;21(2):82-9 Abstract quote

Malignant rhabdoid tumors are rare and aggressive neoplasms of childhood, occurring in the kidney or in various extrarenal locations. Most cytogenetic studies of these tumors have shown the frequent involvement of chromosome 22, including translocations and/or deletions, with a critical region for a rhabdoid tumor gene mapping to chromosome segment 22q11, close to BCR.

We report a case of an extrarenal rhabdoid tumor with a t(1;22)(p36;q11.2) that was associated with deletions of chromosomes 1 and 22. We have performed fluorescence in situ hybridization to bracket the translocation breakpoints on both chromosomes and microsatellite analysis to establish the deletion of chromosome 22 more precisely. The chromosome 22 translocation breakpoint is localized close to BCR, in the region covered by the overlapping YACs 446B5 and 361D9, and it is associated with a proximal hemizygous deletion of approximatively 2 Mb. On chromosome 1, the translocation breakpoint maps to a 25 cM region, proximal to D1Z2 and distal to PND, and is also associated with an estimated deletion of 8 Mb. Moreover, microsatellite analysis has demonstrated a homozygous deletion of chromosome 22 for three contiguous loci, immediately distal to BCR.

This result suggests that a tumor suppressor gene involved in rhabdoid tumor oncogenesis could be localized in this region of chromosome 22.


hSNF5/INI1 inactivation is mainly associated with homozygous deletions and mitotic recombinations in rhabdoid tumors.

Rousseau-Merck MF, Versteege I, Legrand I, Couturier J, Mairal A, Delattre O, Aurias A.

Pathologie Moleculaire des cancers INSERM U509, Institut Curie, Paris, France.

Cancer Res 1999 Jul 1;59(13):3152-6 Abstract quote

The chromatin-remodeling hSNF5/INI1 gene has recently been shown to act as a tumor suppressor gene in rhabdoid tumors (RTs).

In an attempt to further characterize the main chromosomal mechanisms involved in hSNF5/INI1 inactivation in RTs, we report here the molecular cytogenetic data obtained in 12 cell lines harboring hSNF5/INI1 mutations and/or deletions in relation to the molecular genetic analysis using polymorphic markers extended to both extremities of chromosome 22q. On the whole, mitotic recombination occurring in the proximal part of chromosome 22q, as demonstrated in five cases, and nondisjunction/duplication, highly suspected in two cases (processes leading respectively to partial or complete isodisomy), appear to be major mechanisms associated with hSNF5/INI1 inactivation. Such isodisomy accompanies each of the RTs exhibiting two cytogenetically normal chromosomes 22. This results in homozygosity for the mutation at the hSNF5/INI1 locus. An alternate mechanism accounting for hSNF5/INI1 inactivation observed in these tumors is homozygous deletion in the rhabdoid consensus region.

This was observed in each of the four tumors carrying a chromosome 22q abnormality and, in particular, in the three tumors with chromosomal translocations. Only one case of our series illustrates the mutation/deletion classical model proposed for the double-hit inactivation of a tumor suppressor gene.

Chromosome 22q dosage in composite extrarenal rhabdoid tumors: clonal evolution or a phenotypic mimic?

Fuller CE, Pfeifer J, Humphrey P, Bruch LA, Dehner LP, Perry A.

Division of Neuropathology, Department of Pathology and Immunology, Barnes-Jewish and St Louis Children's Hospitals, Washington University Medical Center, St Louis, MO 63110, USA.

Hum Pathol 2001 Oct;32(10):1102-8 Abstract quote

Composite extrarenal rhabdoid tumors (CERTs) represent a diverse group of neoplasms with rhabdoid shape in combination with one of several distinctive tumor types. Like the classic renal and extrarenal malignant rhabdoid tumor (MRT), as well as the atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, CERTs typically show aggressive clinical behavior.

Deletions and mutations of the INII gene on 22q11.2 have been identified in most classic MRTs and AT/RTs; however, it is not known whether the rhabdoid components in CERTs have similar genetic abnormalities. Using fluorescence in situ hybridization (FISH) on archival, paraffin-embedded tissue with a commercially available probe in close proximity to the INII locus (bcr), as well as other chromosome 22 probes, we studied 4 cases of MRT, 13 of AT/RT, and 16 of CERT (3 melanoma, 4 meningioma, 7 carcinoma, 1 rhabdomyosarcoma, and 1 neuroblastoma). Deletion of the 22q11.2 locus was demonstrated in 10 (77%) of 13 AT/RTs and 3 (75%) of 4 MRT, including 1 congenital MRT. Of the 16 CERTs, only 2 (a rhabdoid meningioma and a carcinoma with rhabdoid features; 13%) harbored a deletion at this locus. This difference was statistically significant (P <.001).

We conclude that deletion of 22q11.2, typical of most classic MRTs and AT/RTs, is infrequently seen in CERTs. This suggests that the rhabdoid component of CERTs does not evolve by way of the genetic alteration characteristic of MRTs or AT/RTs, but represents instead a distinct phenotype shared by a number of tumors as they undergo anaplastic progression.

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.

 

LABORATORY/
RADIOLOGIC/
OTHER TESTS

CHARACTERIZATION
RADIOLOGIC  

Imaging and pathological features of primary malignant rhabdoid tumours of the brain and spine.

Howlett DC, King AP, Jarosz JM, Stewart RA, al-Sarraj ST, Bingham JB, Cox TC.

Department of Radiology, Guy's Hospital, London, UK.

Neuroradiology 1997 Oct;39(10):719-23 Abstract quote

In this article two cases of primary malignant extrarenal rhabdoid tumour are described. In the affected children the brain and the spinal cord were the primary sites of origin of the tumour. The imaging findings are presented and the pathology discussed.

Although the imaging features are non-specific, rhabdoid tumour should be included in the differential diagnosis of childhood intracranial and spinal neoplasms.

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
GENERAL  

The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy.

Parham DM, Weeks DA, Beckwith JB.

Am J Surg Pathol 1994; 18: 101029.
VARIANTS  
CENTRAL NERVOUS SYSTEM  

Malignant rhabdoid tumor of the central nervous system.

Biggs PJ, Garen PD, Powers JM, Garvin AJ.

Hum Pathol 1987; 18: 3327.

Primitive cerebral tumor with rhabdoid features: a case of phenotypic rhabdoid tumor of the central nervous system.

Weeks DA, Malott RL, Zuppan CW, Liwnicz BH, Beckwith JB.

Department of Pathology and Laboratory Medicine, Loma Linda University School of Medicine, California 92350.

Ultrastruct Pathol 1994 Jan-Apr;18(1-2):23-8 Abstract quote

The rhabdoid tumor (RT) was first described as an aggressive neoplasm of unknown histogenesis affecting the kidneys of infants and young children, but has since been reported in all ages and in many other primary sites, including the central nervous system. It has been shown, however, that the histologic and cytologic features of RT can be mimicked by many other tumors of known histogenesis. For this and other reasons it remains controversial whether cases of putative extrarenal RT represent the same histogenetic entity as RT of the kidney (RTK), another entity or entities, or merely a diverse collection of unrelated tumors sharing a common morphologic phenotype.

The present paper describes a lethal primary cerebral tumor in a 26-month-old Hispanic boy that was composed predominantly of cells exhibiting the "classic" rhabdoid phenotype by light microscopy. Immunocytochemical and ultrastructural studies disclosed features of primitive neuroglial differentiation not seen in RTK.

The findings in this case, as well as evidence from other studies, would seem to support the notion that primary RT of the brain may in fact constitute a morphologic and clinicopathologic entity. However, that entity likely represents a distinctive type of neuroglial neoplasm, more closely related to other primitive brain tumors than to RTK.

Immunohistochemistry of primary central nervous system malignant rhabdoid tumors: report of five cases and review of the literature.

Behring B, Bruck W, Goebel HH, Behnke J, Pekrun A, Christen HJ, Kretzschmar HA.

Institute of Neuropathology, University of Gottingen, Germany.

Acta Neuropathol (Berl) 1996;91(6):578-86 Abstract quote

Malignant rhabdoid tumors (MRT) are characterized by a typical light microscopic morphology with uniformly round tumor cells, vacuolated cytoplasm with occasional round, hyaline intracytoplasmic, periodic acid-Schiff-positive inclusions, vesicular nuclei with prominent nucleoli and positive immunoreactivity for vimentin. The histogenesis of MRT is controversial.

Five cases of primary central nervous system (CNS) rhabdoid tumors in children are presented. Immunohistochemical, light and electron microscopic features are compared with primary CNS malignant rhabdoid tumors reported in the literature.

Expression of various neurofilaments in our cases of primary CNS rhabdoid tumors was prominent and we therefore favor a neural differentiation of extrarenal intracerebral rhabdoid tumors.

COLON  

Malignant rhabdoid tumor of the colon. Report of a case with molecular analysis.

Marcus VA, Viloria J, Owen D, Tsao MS.

Department of Pathology, Montreal General Hospital, Quebec, Canada.

Dis Colon Rectum 1996 Nov;39(11):1322-6 Abstract quote

PURPOSE: Malignant rhabdoid tumors were first described in the kidney as a rare variant of Wilms' tumor with a "rhabdomyosarcomatoid" pattern and a particularly poor prognosis. Further studies have demonstrated these neoplasms as a distinct clinicopathologic entity. Subsequently, tumors with a similar histologic appearance, demonstrating the "rhabdoid" cells, have been found in a variety of extrarenal sites.

METHODS: We report here a case of malignant rhabdoid tumor of the colon studied with selected molecular techniques.

RESULTS AND CONCLUSIONS: This tumor demonstrated several unusual findings for malignant rhabdoid tumors of renal or extrarenal sites, including aneuploidy by flow cytometric analysis and a positive nuclear immunohistochemical staining for p53 protein, which suggests presence of p53 gene mutation. DNA analyses, however, failed to demonstrate the presence of point mutation in any of the ras family genes.

DISSEMINATED  
Congenital Disseminated Malignant Rhabdoid Tumor and Cerebellar Tumor Mimicking Medulloblastoma in Monozygotic Twins
Pathologic and Molecular Diagnosis

C. Fernandez, M.D. ; C. Bouvier, M.D. ; N. Sévenet, Ph.D. ; A. Liprandi, M.D. ; C. Coze, M.D. , Ph.D. ; G. Lena, M.D. ; D. Figarella-Branger, M.D. , Ph.D.

From Service d'Anatomie Pathologique et de Neuropathologie (C.F., C.B., A.L., D.F.-B.), Service d'Oncologie Pédiatrique (C.C.), Service de Neurochirurgie Pédiatrique (G.L.), CHU Timone, Marseille, and Unité de Génétique Somatique (N.S.), Dr Delattre, Institut Curie, Paris, France.

Am J Surg Pathol 2002;26:266-270 Abstract quote

Malignant rhabdoid tumors are highly aggressive childhood tumors. Recently, all of the malignant rhabdoid tumors, whatever their location, have been related to the inactivation of the hSNF5/INI1 gene. A subset of cerebral tumors, associated with malignant rhabdoid tumors or isolated ones arising in siblings, showed similar molecular alterations.

We report for the first time in monozygotic twins a congenital disseminated malignant rhabdoid tumor in one twin and a cerebellar tumor mimicking a medulloblastoma in the other. Molecular analysis revealed similar alterations for both tumors: a deletion of exon 7 of the hSNF5/INI1 gene in one allele, and a point mutation in the same exon in the other, suggesting a common genetic pathway. Analysis of constitutional DNA revealed a germline mutation.

These findings are in favor of a common etiology for rhabdoid tumor and a subset of brain tumors developing in infancy.

DURA  

Primary malignant rhabdoid tumor of the spinal dura.

Rosemberg S, Menezes Y, Sousa MR, Plese P, Ciquini O.

Department of Pathology, University of Sao Paulo School of Medicine, Brazil.

Clin Neuropathol 1994 Jul-Aug;13(4):221-4 Abstract quote

We report a case of an intradural extramedullary malignant rhabdoid tumor (MRT) occurring in a 2-year-old girl. Histologically, immunohistochemically and ultrastructurally, the tumor fulfilled the diagnostic criteria for MRT. Many tumor cells contained typical cytoplasmic eosinophilic hyaline inclusions which were filamentous by electron microscopy. Positive vimentin staining was observed immunohistochemically but epithelial markers were negative.

Extrarenal MRT are rare. Ten instances in the central nervous system have been reported. This case is the first intradural MRT of the spinal canal. The differential diagnosis from other tumors of this region is important because the prognosis and therapeutic approaches are greatly different.

LIVER  

Malignant rhabdoid tumor of the liver. A distinct clinicopathologic entity.

Hunt SJ, Anderson WD.

Department of Pathology, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013.

Am J Clin Pathol 1990 Nov;94(5):645-8 Abstract quote

A malignant rhabdoid tumor occurring as a primary hepatic neoplasm in a six-month-old white infant is reported. It was treated by an attempt at total resection involving right hepatic lobectomy and by chemotherapy with cis-platinum, VP-16, and Adriamycin. Despite this, recurrence of the tumor resulted in the girl's death within three months. The neoplasm showed typical light microscopic features of malignant rhabdoid tumor as well as filamentous cytoplasmic inclusions by electron microscopic examination and staining for both cytokeratin and vimentin by immunohistochemistry.

The classic clinicopathologic features of this tumor support the concept that malignant rhabdoid tumors similar to those of the kidney may occur in extrarenal sites.

Malignant rhabdoid tumor of the liver. Evidence for epithelial differentiation.

Parham DM, Peiper SC, Robicheaux G, Ribeiro RC, Douglass EC.

Department of Pathology and Laboratory Medicine, St. Jude Children's Research Hospital, Memphis, TN 38101.

Arch Pathol Lab Med 1988 Jan;112(1):61-4 Abstract quote

Malignant rhabdoid tumors most commonly occur in the kidney. Rarely does this tumor arise in extrarenal sites; a single documented primary hepatic tumor has been described.

We describe two patients who had malignant tumors arising in the liver. These tumors demonstrated cytologic, histologic, and ultrastructural features typical of malignant rhabdoid tumor. By immunohistochemistry, the tumor cells from both patients expressed the epithelial membrane antigen, cytokeratin, and vimentin and cells from one patient contained alpha 1-antitrypsin. Neither patient had evidence of renal involvement at autopsy.

Thus, we demonstrate that this rapidly fatal tumor contains cells showing features of epithelial differentiation, and that it may occur as a primary hepatic tumor.

ORBIT  

Congenital malignant rhabdoid tumor of the orbit.

Stidham DB, Burgett RA, Davis MM, Plager DA.

Indiana University School of Medicine, Department of Ophthalmology, Indianapolis, USA.

J AAPOS 1999 Oct;3(5):318-20 Abstract quote

Malignant rhabdoid tumor is a rare and highly malignant renal tumor of infancy. Extrarenal tumors involving the orbit have been reported, but never at birth.

The authors describe a primary malignant rhabdoid tumor of the orbit in a neonate who had massive unilateral proptosis at birth. Clinical, radiographic, and histologic features of the tumor are discussed.

SOFT TISSUE  

Rhabdoid tumors of soft tissues: a clinicopathologic study of 26 cases enrolled on the Intergroup Rhabdomyosarcoma Study.

Kodet R, Newton WA Jr, Sachs N, Hamoudi AB, Raney RB, Asmar L, et al.

Hum Pathol 1991; 22: 67484.

Extrarenal rhabdoid tumors of soft tissue: a clinicopathologic and immunohistochemical study of 18 cases.

Fanburg-Smith JC, Hengge M, Hengge UR, Smith JS Jr, Miettinen M.

Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.

Ann Diagn Pathol 1998 Dec;2(6):351-62 Abstract quote

Rhabdoid tumor is a well-accepted clincopathologic entity among childhood renal neoplasms; similar tumors have been described in extrarenal locations.

We present the clinicopathologic profile and the immunohistochemical features of a series of soft tissue rhabdoid tumors. Twenty-eight cases coded as extrarenal rhabdoid tumor (ERRT), RT, possible ERRT, and "large cell sarcoma" were retrieved from the Armed Forces Institute of Pathology soft tissue registry. The tumors were reclassified according to strict criteria by light microscopy, clinical information, immunohistochemistry, and, in some cases, electron microscopy.

Soft tissue rhabdoid tumor (STRT) was defined as (1) a tumor composed of noncohesive single cells, clusters, or sheets of large tumor cells with abundant glassy eosinophilic cytoplasm, an eccentric vesicular nucleus, and an extremely large nucleolus; (2) positivity for vimentin and/or cytokeratin or other epithelial markers by immunostaining; and (3) exclusion of other tumor types with rhabdoid inclusions (melanoma, other sarcomas, carcinoma).

Eighteen cases met our criteria for soft tissue rhabdoid tumors. The median patient age was 13 years (range, 6 months to 56 years). Ninety-four percent of STRT cases were positive for vimentin and 59% for pan-cytokeratin. Sixty-three percent and 60% were positive for CAM 5.2 and EMA, respectively. Seventy-nine percent stained for at least one epithelial marker; 76% stained for both vimentin and epithelial markers simultaneously. Forty-two percent stained for MSA, and 14% for CEA and SMA. CD99, synaptophysin, CD57 (Leu-7), NSE, and focal S100 protein were identified in 75%, 66%, 56%, 54%, and 31% of the STRT cases, respectively. All STRT cases examined were negative for HMB-45, chromogranin, BER-EP4, desmin, myoglobin, CD34, and GFAP.

Follow-up examination in 61% of the STRT patients revealed that 64% of patients died of disease within a median follow-up interval of 19 months (range, 4 months to 5 years); 82% had metastases to lung, lymph nodes, or liver; 22% had local recurrences before metastasis; and 18% were alive without known disease status (median, 5.5 years). Soft tissue rhabdoid tumor is a highly aggressive sarcoma, predominantly of childhood. Besides having nearly consistent coexpression of vimentin and epithelial markers, STRTs show positivity for multiple neural/neuroectodermal markers that overlap with those of primitive neuroectodermal tumor.

UTERUS  

Malignant rhabdoid tumor of the uterus.

Cho KR, Rosenshein NB, Epstein JI.

Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland 21205.

Int J Gynecol Pathol 1989;8(4):381-7 Abstract quote

Rhabdoid tumors are highly malignant neoplasms resembling rhabdomyosarcomas, which most commonly occur in the kidney in young children. Several cases of extrarenal malignant rhabdoid tumors have been described, many in adolescents and young adults.

We describe a 46-year-old woman with a primary uterine tumor that has the histologic, immunohistochemical, and ultrastructural characteristics of a malignant rhabdoid tumor.

To our knowledge, this is the first report of a rhabdoid tumor in this site. Furthermore, this woman's age expands the range for which pathologists and clinicians should consider this diagnosis, even in extrarenal sites.

Malignant rhabdoid tumor of the uterine corpus.

Hsueh S, Chang TC.

Department of Anatomic Pathology, Chang Fung Memorial Hospital and Chang Gung College of Medicine and Technology, Taipei, Taiwan, Republic of China.

Gynecol Oncol 1996 Apr;61(1):142-6 Abstract quote

Malignant rhabdoid tumor (MRT) was first described as a variant of Wilms' tumor but was subsequently found to be a highly malignant tumor composed of primitive cells that resemble rhabdomyoblasts.

In the past decade, extrarenal MRTs were reported in different locations and organs throughout the body including the female genital tract. We here report an MRT that arose in the corpus uteri, the second such case reported.

Collision of uterine rhabdoid tumor and endometrioid adenocarcinoma: a case report and review of the literature.

Gaertner EM, Farley JH, Taylor RR, Silver SA.

Department of Pathology, Walter Reed Army Medical Center, Washington, DC, USA.

Int J Gynecol Pathol 1999 Oct;18(4):396-401 Abstract quote

Extrarenal malignant rhabdoid tumors have been reported in a variety of anatomic sites but infrequently in the female genital tract. In the uterus, they have been described as a pure tumor, in association with endometrial stromal sarcomas, and as a component of a malignant mullerian mixed tumor.

This study reports an unusual uterine neoplasm in a 49-year-old woman, in which a malignant rhabdoid tumor occurred as a collision tumor with a well-differentiated endometrioid adenocarcinoma. The tumor was a 14-cm polypoid mass that filled the endometrial cavity. The two neoplastic components were distinct on microscopic and immunohistochemical examination. Ultrastructural examination confirmed the rhabdoid phenotype of the sarcomatous component. The patient died of disease 4 months after diagnosis with progression of the malignant rhabdoid tumor.

The highly aggressive behavior of the rhabdoid (i.e., nonepithelial) component in this collision tumor lends support for a distinction of this neoplasm from a malignant mullerian mixed tumor, with which it may be confused.

Aggressive uterine sarcoma with rhabdoid features: diagnosis by peritoneal fluid cytology and absence of INI1 gene mutation.

Knapik J, Yachnis AT, Ripley D, Biegel JA, Rathor S, Hardt NS, Talerman A, Wilkinson EJ.

Department of Pathology, University of Florida College of Medicine, Gainesville, FL 32610-0275, USA.

Hum Pathol 2001 Aug;32(8):884-6 Abstract quote

We report a primary uterine sarcoma with classic histologic, immunohistochemical, and ultrastructural features of a malignant extrarenal rhabdoid tumor (MERT). It arose in a 71-year-old woman who presented with postmenopausal bleeding, ascites, and a right pelvic mass.

Malignant cells with rhabdoid morphology were identified by cytologic examination of the peritoneal fluid. Exploratory laparotomy revealed a 10-cm right adnexal mass and disseminated peritoneal tumor. Pathologic study showed diffuse expansion of the endometrial stroma by rhabdoid-like cells with transmural infiltration of the myometrium and extensive involvement of uterine serosa and right ovary by tumor. Neoplastic cells were immunoreactive for vimentin, cytokeratin, and epithelial membrane antigen, and cytoplasmic whorls of intermediate filaments were observed by electron microscopy.

Fluorescence in situ hybridization (FISH) studies with chromosome 22-specific probes showed no loss of the INI1 gene, and no coding sequence mutation was identified.

VULVA  

Malignant rhabdoid tumor of the vulva: case report and review of the literature with emphasis on clinical management and outcome.

Brand A, Covert A.

Division of Gynecologic Oncology, QE II Health Sciences Center, Halifax, Nova Scotia, Canada.

Gynecol Oncol 2001 Jan;80(1):99-103Abstract quote

BACKGROUND: Malignant extrarenal rhabdoid tumors (ERTs) of the vulva are rare but aggressive neoplasms. We describe the eighth reported case and the first to have long-term survival despite initial rapid recurrence.

CASE: A 40-year-old woman presented with a painless lump on the mons pubis. It was excised and revealed an ERT. One month later, the tumor had regrown. A wide local excision and superficial right groin node dissection was performed. Local recurrence was noted 11 months after the initial excision and was treated by wide excision and radiotherapy. She is without evidence of disease 61 months after initial presentation.

CONCLUSION: A review of previously reported cases of ERT reveals that the median survival is 9 months. Local recurrences are common and the appearance of distant metastases is almost invariably rapidly fatal. Chemotherapy and radiotherapy do not appear to be effective in controlling disease. Initial surgical extirpation may offer the best chance of cure.

 

HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL  
VARIANTS  
ENDOMETRIAL STROMAL SARCOMA  

Endometrial stromal sarcoma with sex cord-like areas and focal rhabdoid differentiation.

McCluggage WG, Date A, Bharucha H, Toner PG.

Institute of Pathology, Royal Group of Hospitals Trust, Belfast, Northern Ireland.

Histopathology 1996 Oct;29(4):369-74 Abstract quote

An unusual uterine lesion is described in a patient with postmenopausal bleeding. Grossly, a yellow, polypoid mass projected into the uterine cavity. Histological examination showed a distinct biphasic pattern with areas of typical low-grade endometrial stromal sarcoma and areas where tumour cells were arranged in cords and trabeculae, resulting in a sex cord-like pattern. In these areas the cells assumed a rhabdoid morphology with eccentric vesicular nuclei, prominent nucleoli and eosinophilic hyaline cytoplasmic inclusions.

Immunohistochemistry showed positive cytoplasmic staining of both components for vimentin, desmin and the cytokeratin marker CAM 5.2, but no staining for CEA and EMA. Electronmicroscopy revealed prominent paranuclear arrays of intermediate filaments. This is the second reported case of endometrial stromal sarcoma with rhabdoid differentiation and the first documented example of rhabdoid cells in sex cord-like areas. The report adds to the list of diverse neoplasms which may display a characteristic rhabdoid morphology and supports the hypothesis that extrarenal rhabdoid tumours are not a distinct clinicopathological entity.

A diagnosis of malignant rhabdoid tumour of the uterus should be considered only when extensive sampling fails to disclose areas with an appearance typical of an endometrial stromal lesion.

FOLLICULAR CARCINOMA OF THYROID  

Follicular thyroid carcinoma with rhabdoid phenotype.

Chetty R, Govender D.

Department of Pathology, University of Natal School of Medicine, Durban, South Africa.

Virchows Arch 1999 Aug;435(2):133-6 Abstract quote

The aim of this paper is to highlight the occurrence of an unusual histological variant of follicular carcinoma of the thyroid.

Three cases are presented: each of the tumours contained a significant population of rhabdoid cells (accounting for 30-40% of the total tumour content). They were all found in female patients aged 65, 43 and 56 years, who presented with enlarged thyroid glands and were subjected to lobectomies. The tumours contained foci of well-differentiated follicular carcinoma, with areas of capsular and vascular invasion, and an accompanying rhabdoid cell component that merged with the neoplastic follicles. Immunohistochemically, the follicular component was positive with thyroglobulin, but the rhabdoid cells were negative in all three cases. The cytoplasmic aggregates in the rhabdoid cells were strongly positive for epithelial markers and vimentin. Two tumours pursued an aggressive biological course similar to other composite extrarenal rhabdoid tumours.

A rhabdoid component accompanying thyroid follicular carcinomas is an adverse prognostic factor.

MALIGNANT MIXED MULLERIAN TUMOR  

Malignant mixed Mullerian tumor with rhabdoid features: a report of two cases and a review of the literature.

Baschinsky DY, Niemann TH, Eaton LA, Frankel WL.

Departments of Pathology and Obstetrics and Gynecology, The Ohio State University Hospital, Columbus, Ohio, 43210, USA.

Gynecol Oncol 1999 Apr;73(1):145-50 Abstract quote

Rhabdoid tumors were originally described as a type of pediatric renal neoplasm that contains cells resembling rhabdomyoblasts but lacking muscle differentiation.

Extrarenal rhabdoid tumors have since been reported in multiple anatomic sites in the pediatric and adult population. These tumors are characterized by an aggressive clinical course, resistance to treatment, and a rapidly fatal outcome. Eight cases of uterine neoplasms with rhabdoid differentiation have been previously reported. In the three cases where clinical follow-up was available, the patients died of disease within 3 to 17 months after the diagnosis was established.

We report two cases of uterine malignant mixed Mullerian tumor (carcinosarcoma) with rhabdoid differentiation. The findings and clinical outcome confirm the aggressive nature of uterine tumors with rhabdoid differentiation. One of the patients died of disease 3 months after initial operative treatment while the other patient's tumor recurred in 1 month and she died within 10 weeks. The poor prognosis of these neoplasms makes their histopathologic recognition important.

MALIGNANT PERIPHERAL NERVE SHEATH TUMOR  

Cutaneous epithelioid malignant nerve sheath tumor with rhabdoid features: a histologic, immunohistochemical, and ultrastructural study of three cases.

Morgan MB, Stevens L, Patterson J, Tannenbaum M.

Department of Pathology, James Haley Veteran's Administration Hospital, Tampa, Florida, USA.

J Cutan Pathol 2000 Nov;27(10):529-34 Abstract quote

INTRODUCTION: Malignant rhabdoid tumors are morphologically defined as sheets of loosely cohesive cells with eccentric nuclei and hyaline, paranuclear inclusions. Although originally described as a distinctive renal neoplasm of childhood, these tumors have since been described in all age groups and in a variety of extrarenal sites. In the latter setting, it is thought that the rhabdoid phenotype is comprised of histogenetically unrelated tumors, that regardless of histogenesis, pursue a biologically aggressive behavior.

METHODS: We report on the clinical, histologic, immunophenotypic, and ultrastructural characteristics of three cases of cutaneous malignant rhabdoid tumor.

RESULTS: Each of the cases arose on the trunk or the extremity of elderly men. None of the patients had neurofibromatosis. All of the lesions histologically showed sheets of loosely cohesive polygonal cells with eccentric nuclei and hyaline paranuclear inclusions. Each of the cases showed the following immunophenotype: S-100 (+), synaptophysin(+), vimentin (+), alpha smooth muscle actin (-), CD-30 (-), HMB-45 (-), and pankeratin(-). Ultrastructure of two of the cases yielded similar results showing paranuclear filamentous aggregates of intermediate filaments, cell membrane dense plaques, and rudimentary cell junctions consistent with nerve sheath differentiation. Tonofilaments, dense bodies, microtubules, neurosecretory granules, and melanosomes were not identified. Each of the patients died of widely metastatic disease within 1 year of diagnosis.

CONCLUSIONS: Cutaneous epithelioid malignant nerve sheath tumor is a potentially aggressive tumor capable of showing rhabdoid differentiation thus simulating a variety of neoplasms. Immunophenotyping and ultrastructural analysis reliably discriminates these lesions from melanoma, de-differentiated carcinoma, lymphoma, and rhabdomyosarcoma.

MELANOMA  

Metastatic malignant melanoma with "rhabdoid" features.

Chang ES, Wick MR, Swanson PE, Dehner LP.

Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes Hospital, Washington University Medical Center, St. Louis, Missouri 63110.

Am J Clin Pathol 1994 Oct;102(4):426-31 Abstract quote

The authors propose the addition of malignant melanoma to the list of extrarenal neoplasms that may be predominantly composed of polygonal cells with the cytologic features of "rhabdoid" tumor.

A review of 313 metastatic melanomas disclosed 49 examples with rhabdoid features, from which 31 had sufficient material for further pathologic and immunohistologic characterization. A control group of 46 nonrhabdoid metastatic melanomas was examined in parallel fashion. In 39% of cases, rhabdoid melanomas manifested relative deletion of S100 protein compared with the control tumors. However, there were no differences in staining with HMB-45. Vimentin immunoreactivity was concentrated in the paranuclear cytoplasm of rhabdoid melanoma cells. However, ultrastructural studies of these cases failed to show corresponding whorls of intermediate filaments and instead demonstrated paracrystalline paranuclear inclusions in profiles of rough endoplasmic reticulum.

It is concluded that metastatic rhabdoid melanoma exhibits significant morphologic similarity to other rhabdoid tumors at a light-microscopic level. However, it usually retains enough melanocytic attributes to allow for accurate diagnostic recognition. Probably because patients with metastatic melanoma have an extremely poor prognosis overall, no worsening of biologic behavior was associated with rhabdoid cytomorphologic findings in this tumor type when compared with the control cases.

Primary malignant melanoma with rhabdoid features: a histologic and immunocytochemical study of three cases.

Borek BT, McKee PH, Freeman JA, Maguire B, Brander WL, Calonje E.

Department of Histopathology, UMDS (St Thomas' Campus), London, UK.

Am J Dermatopathol 1998 Apr;20(2):123-7 Abstract quote

Malignant rhabdoid tumors are morphologically characterized by the presence of sheets of large polygonal cells with abundant cytoplasm containing eosinophilic inclusions. They have vesicular nuclei, often with prominent central nucleoli. The term rhabdoid tumor was originally coined to describe a group of rare, aggressive renal neoplasms of childhood. Since then, similar lesions, so-called extrarenal malignant rhabdoid tumors have been increasingly reported. The evidence to date suggests that, at least in extrarenal locations, rhabdoid tumors do not constitute a homogeneous entity, but rather represent the shared morphological pattern of a diverse range of malignant neoplasms. Although such rhabdoid features are not uncommon in metastatic malignant melanoma, they have only once been briefly described in a primary lesion.

We report three further cases of cutaneous primary malignant melanoma with rhabdoid morphology.

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.

 

SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHER
CHARACTERIZATION
SPECIAL STAINS  
IMMUNOPEROXIDASE  

The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy.

Parham DM, Weeks DA, Beckwith JB.

Department of Pathology and Laboratory Medicine, St. Jude Children's Research Hospital, Memphis, TN 38105.

Am J Surg Pathol 1994 Oct;18(10):1010-29 Abstract quote

The existence of extrarenal rhabdoid tumor (ERRT) as a discrete pathologic entity has been controversial despite frequent reports of its occurrence.

We performed immunohistochemistry, electron microscopy, or both on 42 cases with this diagnosis sent in consultation to us. Only 12 of the 42 neoplasms had the histological findings of "classic" malignant rhabdoid tumor of the kidney; the remainder displayed a variety of neural, epithelial, myoid, mesenchymal, or ependymal patterns. Electron microscopy also showed that most possessed neural, epithelial, or ependymal features. Immunohistochemistry generally revealed marked polyphenotypia, with immunoreactivity to a wide array of antibodies against neural, epithelial, glial, and myogenic markers. A specific tissue-based diagnostic category could not be assigned in only 11 of the 42 cases, seven of which lacked material for a comprehensive ultrastructural or immunohistochemical study.

We conclude that tumors currently diagnosed as ERRT represent a heterogeneous group of neoplasms that may form unique subsets of known entities within the specific site where they arise or that may defy classification into a specific alternative category.

Our findings lead us to believe that the term ERRT is not valid as representing a specific diagnostic entity and to prefer the term "poorly differentiated neoplasm with rhabdoid features" for undifferentiated tumors.

CYTOKERATIN  

Cytokeratin subunits of inclusion bodies in rhabdoid cells: immunohistochemical and clinicopathological study of malignant rhabdoid tumor and epithelioid sarcoma.

Shiratsuchi H, Oshiro Y, Saito T, Itakura E, Kinoshita Y, Tamiya S, Oda Y, Komiyama S, Tsuneyoshi M.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Int J Surg Pathol 2001 Jan;9(1):37-48 Abstract quote

Extrarenal malignant rhabdoid tumor (MRT), which is recognized as being histologically similar to renal MRT, is characterized by the presence of "rhabdoid cell" (RC) and a highly aggressive biological behavior.

Recently it has been proposed that "proximal variant" of epithelioid sarcoma (ES), whose morphology is similar to that of MRT, actually has a more aggressive clinical course than classical type ES. Detailed immunohistochemical analysis of cytokeratin (CK) subunits was performed in 3 cases of extrarenal MRT, 3 cases of renal MRT, and 11 cases of ES comprising 2 "proximal variants" and 9 classical types. Renal and extrarenal MRTs showed positive immunoreactivity for both CK8 and CK18. Classical type ESs were diffusely positive, not only for CK8 and CK18, but also for other cytokeratin subunits including CK4, 6, 10, 13, 16, 17, and "high-molecular-weight" CKs (CK1, 5, 10, and 14). On the other hand, proximal ES revealed limited immunohistochemical reactivity for cytokeratins, compared with classical ES.

In conclusion, the inclusion bodies of RCs show immunoreactivity confined to CK8, CK18, and vimentin. Furthermore, ES has additional CK expressions, while proximal ES possesses characteristics intermediate between those of classical ES and those of external MRT.

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.
DYSADHERIN  
 
Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor.

Izumi T, Oda Y, Hasegawa T, Nakanishi Y, Iwasaki H, Sonobe H, Goto H, Kusakabe H, Takahira T, Kobayashi C, Kawaguchi K, Saito T, Yamamoto H, Tamiya S, Iwamoto Y, Tsuneyoshi M.

1Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Mod Pathol. 2006 Jun;19(6):820-31. Abstract quote  

Dysadherin is a cancer-associated cell membrane glycoprotein, which downregulates E-cadherin and promotes metastasis.

We studied the clinicopathological features in 72 cases of epithelioid sarcoma and in six cases of malignant rhabdoid tumor, and also assessed the immunohistochemical expression of dysadherin, E-cadherin and MIB-1 in epithelioid sarcoma and malignant rhabdoid tumor cases. In addition, we compared dysadherin mRNA expression between epithelioid sarcoma and malignant rhabdoid tumor cell lines, using RT-PCR and real-time quantitative RT-PCR analysis.

Immunohistochemical dysadherin expression was more frequently observed in proximal-type epithelioid sarcoma (71%) in comparison with distal-type epithelioid sarcoma (36%) (P=0.037). Furthermore, seven proximal-type epithelioid sarcoma cases mimicking malignant rhabdoid tumor (histologically classified as the large cell type, accompanied by frequent rhabdoid cells and located in deep soft tissue) were all positive for dysadherin (100%), whereas dysadherin expression was not detected at all in any of the true six malignant rhabdoid tumors (0%). Cell lines established from proximal-type epithelioid sarcoma revealed significantly higher levels of dysadherin mRNA expression, compared with the levels seen in malignant rhabdoid tumor cell lines by real-time quantitative RT-PCR (P=0.0433). Epithelioid sarcoma patients with dysadherin expression survived for a significantly shorter time than those without dysadherin expression (P=0.001). In multivariate analysis, dysadherin immunopositivity (P=0.0004) was one of the two independent adverse prognostic factors.

We conclude that dysadherin expression in epithelioid sarcoma is a significant poor prognostic factor and that it is a powerful diagnostic marker for distinguishing epithelioid sarcoma, including the proximal-type epithelioid sarcoma, from malignant rhabdoid tumor. In epithelioid sarcoma, especially in proximal-type epithelioid sarcoma, increased cell disadhesion and motility by dysadherin plays an important role to acquire aggressive biological behavior. However, in malignant rhabdoid tumor, cell growth cycle that is regulated by hSNF5/INI1 gene seems to be critical to lethal biological behavior rather than dysadherin.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
EPITHELIOID SARCOMA  

"Proximal-type" epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series.

Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD.

Institut Universitaire de Pathologie, Lausanne, Switzerland.

Am J Surg Pathol 1997 Feb;21(2):130-46 Abstract quote

Eighteen examples of an unusual malignant soft-tissue neoplasm, the morphology of which ranged from that of "atypical" epithelioid sarcoma to that of a rhabdoid tumor or undifferentiated carcinoma (with transitional forms) are described.

Patients included 11 males and seven females; their median age was 35.5 years with most patients aged 20 to 40 years. Development of a mass was the main presenting symptom. Six tumors developed in the pelvis and perineal region, four in the pubic region and vulva, three in the buttocks, one in the deep soft tissues of the left hip, one on the penis, one in left forearm, one in left axilla, and one on the occiput. Tumor size ranged from 1 to 20 cm (median, 4 cm). On microscopic examination, the tumor cells invaded the subcutaneous or deep soft tissues, had prominent epithelioid or rhabdoid features, had marked cytologic atypia, and grew in a multinodular pattern in half of the cases. Areas of necrosis were often seen. A granuloma-like pattern reminiscent of that observed in classic epithelioid sarcoma was observed in only two cases.

Immunohistochemically, positivity for cytokeratin, epithelial membrane antigen, and vimentin was seen in all but one of the cases. Of 16 cases, 10 and eight tumors reacted with desmin and CD34, respectively; five of 15 reacted at least focally with smooth-muscle actin, whereas three of 13 and one of 10 reacted for HMB-45 and carcinoembryonic antigen, respectively. S-100 protein and CD31 yielded negative results. Seven tumors were investigated at the ultrastructural level, four of which showed prominent intracytoplasmic intermediate filament aggregates, often accumulating into paranuclear whorls, which is in keeping with the rhabdoid phenotype. Five tumors showed features of epithelial differentiation (i.e., tonofilament-like structures or desmosomes or both), whereas one tumor displayed features of myofibroblastic differentiation.

Differential diagnoses include mainly conventional epithelioid sarcoma, extrarenal malignant rhabdoid tumor, epithelioid malignant peripheral nerve sheath tumor, melanoma, rhabdomyosarcoma, and undifferentiated carcinoma.

Follow-up information on 14 patients (range, 4 months to 8 years; median, 19 months) revealed local recurrence in one case and metastatic dissemination in six patients, leading to death in five.

In our opinion, the above-described neoplasms represent a usually "proximal-type" of epithelioid sarcoma. In contrast to the conventional, "distal-type" epithelioid sarcoma, the proximal variant is characterized by a predominantly large-cell, epithelioid cytomorphology, marked cytologic atypia, frequent occurrence of rhabdoid features, and lack of a granuloma-like pattern in most cases. It appears to be somewhat more aggressive (or at least metastasizes earlier) than usual epithelioid sarcoma.

Expression of intercellular adhesion molecules in epithelioid sarcoma and malignant rhabdoid tumor.

Saito T, Oda Y, Itakura E, Shiratsuchi H, Kinoshita Y, Oshiro Y, Tamiya S, Hachitanda Y, Iwamoto Y, Tsuneyoshi M.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Pathol Int 2001 Jul;51(7):532-42 Abstract quote

We clinicopathologically evaluated 31 cases of epithelioid sarcoma (ES; 25 'classical' type and six 'proximal variant' type) and six cases of malignant rhabdoid tumor (MRT; three extrarenal and three renal). We also did immunohistochemical studies on 12 classical and three proximal variant cases of ES, and six cases of MRT, to clarify the differences in biological behavior in these tumors. E-cadherin, beta-catenin and CD34 expression was evaluated.

We also carried out mutational analysis of exon 3 of the beta-catenin gene by polymerase chain reaction-single-strand conformation polymorphism analysis. In ES, the 5- and 10-year survival rates were 71.1 and 55.3%, respectively. A high mitotic rate (>15/10 high-power fields) was significantly correlated with a poor overall survival rate in ES (P = 0.0248). E-cadherin expression was observed in nine cases (69.2%) of ES and in four cases (66.7%) of MRT. Most of these tumors showed aberrant E-cadherin expression. Seven cases (46.7%) of ES were positive for CD34, although none of the cases of MRT were CD34 positive. Eleven cases (73.3%) of ES were positive for beta-catenin, which was localized to the cellular membrane, whereas all of the cases of MRT were beta-catenin negative. Mutational analysis for the beta-catenin gene was done in nine cases of ES and six cases of MRT, however, genetic alteration was not found.

From our results, we conclude that beta-catenin membranous expression could be a useful marker for distinguishing ES, including the proximal variant, from MRT.

MALIGNANT MYOEPITHELIOMA  

Malignant myoepithelioma of the vulva resembling a rhabdoid tumour.

Hinze P, Feyler S, Berndt J, Knolle J, Katenkamp D.

Institute of Pathology, District Hospital Bernburg, Teaching Hospital of the Martin-Luther-University Halle-Wittenberg, Germany.

Histopathology 1999 Jul;35(1):50-4 Abstract quote

AIMS: We report an example of malignant myoepithelioma of the vulva, which has not been hitherto described. We discuss the differential diagnosis and briefly review the literature.

METHODS AND RESULTS: The lesion was found in an 81-year-old woman as an indolent 40 mm tumour. The neoplastic cells showed a myoid, spindled, epithelioid and plasmacytoid phenotype. Hyalinization of extracellular material and myxoid changes were present. There was a partly solid and microcystic pattern and a tight cohesiveness of cells was lacking. The circumscribed multinodular tumour somewhat resembled an extrarenal rhabdoid tumour, having large tumour cells with prominent nucleoli and large amounts of acidophilic cytoplasm. Immunohistochemically, the tumour cells were immunoreactive for cytokeratin, vimentin, muscle-specific actin, alpha-smooth muscle actin, and S100 protein, but not for desmin, epithelial membrane antigen, factor VIII-related antigen, CD34 and CD31.

CONCLUSIONS: The histological and cytomorphological appearance of the tumour well as the immunohistochemical findings suggest the diagnosis of malignant myoepithelioma, possibly derived from minor vestibulary glands or ectopic breast tissue. Differential diagnoses are, in particular, extrarenal rhabdoid tumour and 'proximal type' epithelioid sarcoma. Differentiation is important, because the tumours show a different behaviour and prognosis.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSTIC FACTORS  

Renal and extrarenal rhabdoid tumors in children: a clinicopathologic study of 14 patients.

Sotelo-Avila C, Gonzalez-Crussi F, deMello D, Vogler C, Gooch WM 3rd, Gale G, Pena R

Semin Diagn Pathol 1986 May;3(2):151-63 Abstract quote

The clinical and pathologic features of 14 children with rhabdoid tumors are presented. Eight patients had primary renal neoplasms and six had extrarenal tumors. The eight renal rhabdoid tumors were identified among 514 primary renal neoplasms collected at four pediatric institutions. Six patients were under 1 year of age; five children died of tumor-related causes, four of them within 4 months of diagnosis and one 17 months postnephrectomy. Another patient died of sepsis 12 days postnephrectomy. One is alive 13 months postnephrectomy, and one was lost to follow-up evaluation.

The most common sites of metastasis were the lymph nodes (seven children) and the lungs (three patients). Three infants with renal rhabdoid tumors had, in addition, intracranial masses, two of which manifested clinically before the detection of the renal tumors, in one confirmed to be a primitive neuroectodermal tumor.

Five of the 6 extrarenal tumors were identified among 155,926 surgical pathology specimens examined in the same children's hospitals over the same period of time; the remaining extrarenal rhabdoid tumor was received in consultation from a community hospital.

The extrarenal rhabdoid tumors occurred in the dorsum of the right foot, liver, soft tissue of the right chest wall, left temporal lobe, left leg, and left thoracic paraspinal region. The ages ranged from 6 weeks to 15 years and two months. Three patients died of tumor-related causes within 4 months of diagnosis; one was a term stillborn. Two are alive, 1 month and 70 months postdiagnosis. Common sites for metastases included the lungs (three patients), and liver and lymph nodes (two children each).

Patients with renal and extrarenal rhabdoid tumors are of similar age, have a similar clinical course, with early metastases and poor response to therapy. Primitive neuroectodermal intracranial tumors have been identified in several reported patients with renal rhabdoid tumors; similar brain tumors have not been documented in patients with extrarenal rhabdoid tumors. The histogenesis of this tumor remains unknown.

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