1-month-old male with a 3 cm mass involving the paraspinal soft tissues of the upper back.
The mass measured approximately 3 cm in greatest dimension and involved the deep soft tissues. The cut
surface was tan in color with extensive necrosis. Histologically, the lesion was composed of sheets of
polygonal cells with a moderate amount of eosinophilic cytoplasm and eccentric vesicular nuclei with
irregular nuclear borders and prominent nucleoli. Occasional cells had multiple nuclei while some cells
had prominent hyaline intracytoplasmic inclusions. Mitotic figures were numerous and there was extensive
necrosis and vascular invasion.
Immunohisochemical studies revealed the neoplastic cells to be diffusely and strongly positive for
vimentin and negative for pan-cytokeratin, epithelial membrane antigen, smooth muscle actin, muscle
specific actin, desmin, MyoD1, myogenin, S-100 protein, HMB-45, and CD30.
Case 5 - Figure 1 - Medium power view showing a sheet of neoplastic cells with with a moderate amount of eosinophilic cytoplasm and eccentric nuclei with a vesicular chromatin pattern, irregular nuclear borders and prominent nucleoli.
Case 5 - Figure 2 - High power view showing several cells with prominent hyaline intracytoplasmic inclusions.
Rhabdoid tumor was originally described by Beckwith and Palmer as an aggressive renal neoplasm of
childhood that had histologicical features suggestive of rhabdomyosarcoma, but that lacked skeletal
muscle differentiation.1-2 While originally thought to occur exclusively in the kidney, over time it
has been realized that lesions with similar histology can occur in extrarenal locations. These neoplasms
have been classified collectively as extrarenal rhabdoid tumors (ERT).3-7
Extrarenal rhabdoid tumor is a rare neoplasm that arises in infants and children, and may be congenital.
The majority of lesions arise within the first 2 years of life. ERT can involve a wide variety of sites
including the central nervous system (CNS), soft tissue, bone, skin and subcutis, brain, heart,
mediastinum, lungs, liver, pancreas, adrenal glands, gastrointestinal tract, and lymph nodes. Congenital
cases can present with disseminated disease without an apparent primary .8 CNS lesions, known as
atypical teratoid/rhabdoid tumors of the CNS, are typically thought of as a separate entity since they
display neuroepithelial, mesenchymal, and epithelial differentiation, in addition to the areas with
rhabdoid morphology.5,7 However, as pointed out in the section on genetics; renal, CNS, and
extrarenal tumors are all related at the genetic level. ERT has a predilection for soft tissues of the
head and neck and the paraspinal soft tissues and is a clinically aggressive neoplasm. Most patients die
from widely disseminated metastasis within weeks to months after diagnosis.
Upon gross examination, ERT varies in size, but most lesions are less than 5 cm in greatest dimension.
The cut surface is generally soft, fleshy, and grey to tan in color. Hemorrhage and necrosis are
Histologically, ERT is identical to renal rhabdoid tumor and is composed of a monotonous population of
polygonal to spindle shaped cells with scant to moderate eosinophilic cytoplasm, and round, eccentrically
located nuclei with prominent nucleoli. Lesional cells with large, hyaline (rhabdoid) intracytoplasmic
inclusions are variable in number but are identified at least focally, in most cases. Typically, the
cells are arranged in infiltrating sheets of neoplastic cells but other archtitectural patterns have been
described including organoid (nested) and trabecular patterns. Mitotic figures including atypical
mitotic figures, are variable but usually numerous. Necrosis is present in about 50% of cases reported
in the literature and vascular invasion is common.
Immunohistochemical studies reveal ERT to be a polyphenotypic tumor with an array of immunoreactivities.3,4,6,8,9
Most cases of ERT exhibit diffuse and strong immunoreactivity for vimentin and focal
immunoreactivity for pan-cytokeratin, low-molecular weight cytokeratin, and epithelial membrane antigen.
Muscle specific actin, smooth muscle actin, desmin, S-100 protein, neuron specific enolase,
synaptophysin, neruofilament protein, CD57, alpha fetoprotein, CD99, and WT-1 have all been described to
be at least focally positive in a subset of cases. However, the majority of lesions are negative for
desmin and other myogenic markers which is helpful in distinguishing ERT from rhabdomyosarcoma.
Electron microscopy reveals the intracytoplasmic hyaline inclusions to be composed of whorls of
intermediate filaments which displace other organelles.2,4
A relationship between renal and extrarenal rhabdoid tumors had been hypothesized on the basis of similar
histological and clinical characteristics and this relationship has been confirmed by the finding that
they possess the same cytogenetic and molecular alterations. Renal and extrarenal rhabdoid tumors are
characterized cytogenetically by monosomy 22 or partial deletion of chromosome band 22q11.2, which
contains the hSNF5/INI1 gene.10-12 Homozygous inactivation of INI1results from the deletion of one or
both copies, and/or mutation of INI1. Moreover, rare cases of patients with germline INI1mutations have
been identified which predispose to the formation of one or more extrarenal or renal rhabdoid tumors.11,13
These findings are consistent with the model that INI1functions as a classical tumor suppressor
gene. INI1 is a member of the SWI/SNF chromatin remodeling complex, and thus is thought to have a direct
role in activation/suppression of gene expression.14 It is known that INI1 interacts directly with
other well known oncogenes such as c-Myc.
Recently, two mouse Ini1/Snf5 "knockout" models have been described and both of these models develop
rhabdoid tumors.15,16 Interestingly, neither mouse model develops renal rhabdoid tumors. These
models should be of great use in clarifying different aspects of the function of INI1 in tumorigenesis
and may be useful in the development of therapeutic strategies as well.
Composite Extrarenal Rhabdoid Tumors and Rhabdoid Tumors in Adults
Various examples of extrarenal neoplasms composed of an admixture of rhabdoid tumor and a differentiated
neoplasm such as carcinoma, melanoma, or various subtypes of sarcoma, have been identified and are known
as composite extrarenal rhabdoid tumors (CERTs).3 Genetic analysis by fluorescence in-situ
hybridization has demonstrated that almost all CERTs lack deletion of 22q11.2, suggesting that they
retain INI1 function, and therefore possess a different pathogenetic mechanism.17 Furthermore, most
of these lesions arise in adults and are thus clinically distinct as well. As far as I know, there are
no convincing examples of rhabdoid tumors in adults with demonstrated abnormalities of INI1. Therefore,
a careful search for a more differentiated neoplasm should be undertaken in cases of apparent rhabdoid
tumor in adults, and these lesions should be classified and treated according to the more differentiated
- Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms' tumor. Cancer 1978;41:1937-48.
- Haas JE, Palmer NF, Weinberg AG, Beckwith JB. Ultrastructure of malignant rhabdoid tumor of the
kidney. A distinctive renal tumor of children. Hum Pathol 1981;12:646-57.
- Wick MR, Ritter JH, Dehner LP. Malignant rhabdoid tumors: a clinicopathologic review and
conceptual discussion. Semin Diagn Pathol 1995;12-233-48.
- Parham DM, Weeks DA, Beckwith JB. The clinicopathologic spectrum of putative extrarenal rhabdoid
tumors. An analysis of 42 cases studies with immunohistochemistry or electron microscopy. Am J Surg
- Burger PC, Yu IT, Tihan T et al. Atypical teratoid/rhabdoid tumor of the central nervous system: A
highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma. A Pediatric
Oncology Group study. Am J Surg Pathol 1998;22:1083-92.
- Kodet R, Newton WA Jr, Sachs N, et al. Rhabdoid tumors of soft tissues: a clinicopathologic study
of 26 cases enrolled on the intergroup rhabdomyosarcoma study. Hum Pathol 1991;22:674-84.
- Lefkowitz I, Rorke LB, Packer RJ. Atypical teratoid tumor of infancy: definition of an entity.
Ann Neurol 1987;22:448-9.
- White FV, Dehner LP, Belchis DA, et al. Congenital Disseminated malignant rhabdoid tumor: A
distinct clinicopathologic entity demonstrating abnormalities of chromosome 22q11. Am J Surg Pathol
- Fanburg-Smith JC, Hennge M, Hengge UR, et al. Extrarenal rhabdoid tumors of soft tissue: a
clinicopathologic and immunhistochemical study of 18 cases. Ann Diagn Pathol 1998;2:351-62.
- Versteege, I, Sevenet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive
paediatric cancer. Nature 1998;394:203-6.
- Biegel JA, Zhou JY, Rorke LB, et al. Germ-line and acquired mutations of INI1 in atypical teratoid
and rhabdoid tumors. Cancer Res 1999;59:74-9.
- Rousseau-Merck MF, Versteege I, Legrand I, et al. hSNF5/INI1 inactivation is mainly associated with
homozygous deletions and mitotic recombination in rhabdoid tumors. Cancer Res 1999;59:3152-6.
- Sevenet N, Sheridan E, Amram D, et al. Constitutional mutations of the hSNF5/INI1 gene predispose
to a variety of cancers. Am J Hum Genet 1999;65:1342-8.
- Biegel JA, Kalpana G, Knudsen ES, et al. The role of INI1and the SWI/SNF complex in the development
of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors.
Cancer Res 2002;62:323-8.
- Roberts CW, Galusha SA, McMenamin ME, et al. Haploinsufficiency of Snf5 (integrase interactor 1)
predisposes to malignant rhabdoid tumors in mice. Proc Natl Acad Sci USA 2000;97:13796-800.
- Klochendler-Yeivin A, Fiette L, Barra J et al. The murine SNF5/INI1 chromatin remodeling factor is
essential for embryonic development and tumor suppression. EMBO Rep 2000;1:500-6.
- Fuller CE, Pfeifer J, Humphrey P, et al. Chromosome 22q dosage in composite extrarenal rhabdoid
tumors: clonal evolution or a phenotypic mimic? Hum Pathol 2001;32:1102-8.