Rhabdoid tumor is an aggressive pediatric embryonal neoplasm spanning renal, extrarenal soft-tissue, and central nervous system sites. Across these anatomic presentations, the defining molecular lesion is loss of the BAF/SWI-SNF core subunits SMARCB1 and, rarely, SMARCA4. This shared chromatin-remodeling defect gives rise to a remarkably simple but highly lethal cancer spectrum, with especially poor outcomes in infants, patients with metastatic disease, or those with germline rhabdoid tumor predisposition syndromes.
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name: Rhabdoid Tumor
creation_date: '2026-04-12T05:17:45Z'
updated_date: '2026-05-17T14:00:00Z'
description: >-
Rhabdoid tumor is an aggressive pediatric embryonal neoplasm spanning renal,
extrarenal soft-tissue, and central nervous system sites. Across these anatomic
presentations, the defining molecular lesion is loss of the BAF/SWI-SNF core
subunits SMARCB1 and, rarely, SMARCA4. This shared chromatin-remodeling defect
gives rise to a remarkably simple but highly lethal cancer spectrum, with
especially poor outcomes in infants, patients with metastatic disease, or those
with germline rhabdoid tumor predisposition syndromes.
categories:
- Pediatric Cancer
- Embryonal Neoplasm
- Molecularly Defined Tumor
- SWI/SNF-Deficient Tumor
has_subtypes:
- name: RTK
display_name: Rhabdoid Tumor of the Kidney
description: >-
Renal rhabdoid tumor is the kidney-predominant form of the rhabdoid tumor
spectrum, typically presenting in infancy as a rapidly progressive renal mass
with a high risk of metastatic dissemination.
evidence:
- reference: PMID:33249395
reference_title: Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK).
supports: SUPPORT
snippet: "A total of 70 patients presented with extracranial, extrarenal tumours (eMRT) and 30 with renal rhabdoid tumours (RTK)."
explanation: EU-RHAB registry data directly identifies renal rhabdoid tumor as a major extracranial subtype within the rhabdoid tumor spectrum.
- name: eMRT
display_name: Extrarenal Malignant Rhabdoid Tumor
description: >-
Extrarenal malignant rhabdoid tumor arises outside the kidney and CNS,
usually in deep axial soft tissues such as the neck or paraspinal region.
evidence:
- reference: PMID:16704491
reference_title: "Extrarenal rhabdoid tumors of soft tissue: clinicopathological and molecular genetic review and distinction from other soft-tissue sarcomas with rhabdoid features."
supports: SUPPORT
snippet: "Malignant rhabdoid tumor (MRT) of the soft tissue is a rare and highly aggressive tumor that occurs in infancy or childhood. It predominantly involves a deep axial location such as the neck or paraspinal region."
explanation: This review defines the extracranial soft-tissue subtype and its typical deep axial distribution.
- name: AT/RT
display_name: Atypical Teratoid/Rhabdoid Tumor
description: >-
Atypical teratoid/rhabdoid tumor is the CNS presentation of rhabdoid tumor,
usually arising in infancy or early childhood and sharing the same SMARCB1 or
SMARCA4-deficient biology as extracranial disease.
evidence:
- reference: PMID:39088359
reference_title: "Malignant Rhabdoid Tumor and Related Pediatric Tumors: Multimodality Imaging Review with Pathologic Correlation."
supports: SUPPORT
snippet: "While the central nervous system is the most common site of occurrence, tumors can develop at other sites, including the kidneys and soft tissues throughout the body."
explanation: This review supports AT/RT as the CNS arm of the shared rhabdoid tumor spectrum.
pathophysiology:
- name: SMARCB1 or SMARCA4 Loss
description: >-
Biallelic loss of SMARCB1, and rarely SMARCA4 loss, disables the core
BAF/SWI-SNF chromatin-remodeling machinery and unifies renal, soft-tissue,
and CNS rhabdoid tumors as one molecular disease spectrum.
protein_complexes:
- preferred_term: BAF complex
term:
id: GO:0016514
label: SWI/SNF complex
biological_processes:
- preferred_term: chromatin remodeling
modifier: ABNORMAL
term:
id: GO:0006338
label: chromatin remodeling
downstream:
- target: EZH2-Driven H3K27 Methylation
description: Loss of BAF antagonism creates dependency on PRC2/EZH2 activity
evidence:
- reference: PMID:39088359
reference_title: "Malignant Rhabdoid Tumor and Related Pediatric Tumors: Multimodality Imaging Review with Pathologic Correlation."
supports: SUPPORT
snippet: "Irrespective of the site of occurrence, somatic and germline mutations in SMARCB1, and rarely in SMARCA4, underlie the entire spectrum of rhabdoid tumors."
explanation: This review directly supports SMARCB1 loss, with rare SMARCA4 loss, as the shared defining lesion across rhabdoid tumor sites.
- reference: PMID:23432645
reference_title: "Rhabdoid tumors: an initial clue to the role of chromatin remodeling in cancer."
supports: SUPPORT
snippet: "SMARCB1 is a core subunit of the SWI/SNF chromatin remodeling complex"
explanation: This mechanistic review links the defining driver gene to the BAF/SWI-SNF complex disrupted in rhabdoid tumor.
- name: EZH2-Driven H3K27 Methylation
description: >-
SMARCB1 loss creates functional dependence on PRC2/EZH2, increasing H3K27
methylation and epigenetic gene repression that helps sustain the malignant
state.
molecular_functions:
- preferred_term: histone H3K27 methyltransferase activity
modifier: INCREASED
term:
id: GO:0046976
label: histone H3K27 methyltransferase activity
biological_processes:
- preferred_term: negative regulation of gene expression, epigenetic
modifier: INCREASED
term:
id: GO:0045814
label: negative regulation of gene expression, epigenetic
downstream:
- target: Aberrant MRT Cell Growth
description: EZH1/2 activity supports continued MRT cell growth
- target: Blocked Cellular Differentiation
description: EZH2 dependence helps maintain an undifferentiated tumor state
- target: CDKN2A/p16 Epigenetic Silencing
description: Epigenetic repression by PRC2/EZH2 contributes to CDKN2A/p16(INK4a) silencing following SMARCB1 loss
evidence:
- reference: PMID:36212776
reference_title: Dual targeting of EZH1 and EZH2 for the treatment of malignant rhabdoid tumors.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "MRTs are characterized by loss of SMARCB1, which results in upregulated expression of enhancer of zeste homolog 2 (EZH2), which is responsible for the methylation of lysine 27 of histone H3 (H3K27me3), leading to the repression of gene expression."
explanation: This study directly supports the mechanistic link between SMARCB1 loss, EZH2 upregulation, H3K27 methylation, and epigenetic repression.
- name: CDKN2A/p16 Epigenetic Silencing
description: >-
SMARCB1 loss removes its direct transcriptional support for CDKN2A/p16(INK4a)
expression, while unopposed PRC2/EZH2 activity further enforces epigenetic
silencing of the locus. The net effect is loss of p16(INK4a) protein, which
normally restrains CDK4-Cyclin D1 kinase activity.
biological_processes:
- preferred_term: CDKN2A/p16(INK4a) epigenetic silencing
modifier: INCREASED
term:
id: GO:0045814
label: negative regulation of gene expression, epigenetic
downstream:
- target: CDK4-Cyclin D1 Hyperactivation and G1-S Bypass
description: Loss of p16(INK4a) restraint unleashes CDK4-Cyclin D1 kinase activity
evidence:
- reference: PMID:14604992
reference_title: P16INK4a is required for hSNF5 chromatin remodeler-induced cellular senescence in malignant rhabdoid tumor cells.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "Following hSNF5 expression, we observed transcriptional activation of the tumor suppressor p16(INK4a) but not of p14(ARF), repression of several cyclins and CD44, a cell surface glycoprotein implicated in metastasis."
explanation: Restoring SMARCB1/hSNF5 in MRT cells transcriptionally activates p16(INK4a); SMARCB1 loss therefore silences p16(INK4a) — the single event this node captures.
- name: CDK4-Cyclin D1 Hyperactivation and G1-S Bypass
description: >-
Without p16(INK4a) restraint, CDK4-Cyclin D1 kinase activity is left
unopposed, driving RB1 phosphorylation and inactivation, and bypassing the
G1-S restriction point. Cyclin D1 is the critical downstream effector: its
genetic ablation fully abrogates rhabdoid tumorigenesis caused by
SMARCB1/Ini1 loss in vivo.
biological_processes:
- preferred_term: G1-S restriction-point bypass
modifier: INCREASED
term:
id: GO:0000082
label: G1/S transition of mitotic cell cycle
molecular_functions:
- preferred_term: CDK4-Cyclin D1 kinase activity
modifier: INCREASED
term:
id: GO:0004693
label: cyclin-dependent protein serine/threonine kinase activity
downstream:
- target: Aberrant MRT Cell Growth
description: Loss of the G1-S checkpoint drives unchecked rhabdoid tumor proliferation
evidence:
- reference: PMID:14604992
reference_title: P16INK4a is required for hSNF5 chromatin remodeler-induced cellular senescence in malignant rhabdoid tumor cells.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "Expression of a p16(INK4a)-insensitive form of CDK4 obstructs hSNF5-induced cell cycle arrest."
explanation: A p16(INK4a)-insensitive CDK4 bypasses SMARCB1-induced arrest, establishing CDK4 as the effector kinase that drives proliferation when p16(INK4a) is lost.
- reference: PMID:12226744
reference_title: A key role of the hSNF5/INI1 tumour suppressor in the control of the G1-S transition of the cell cycle.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "This arrest can be reverted by coexpression of cyclin D1, cyclin E or viral E1A, whereas it cannot be counteracted by pRB-binding deficient E1A mutants."
explanation: SMARCB1/INI1-induced G1 arrest is reversed by Cyclin D1 and requires functional pRB, placing the Cyclin D1-CDK4-RB1 axis directly downstream of SMARCB1 loss.
- reference: PMID:16099835
reference_title: Genetic ablation of Cyclin D1 abrogates genesis of rhabdoid tumors resulting from Ini1 loss.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: "We crossed Ini1+/- mice to Cyclin D1-/- mice and found that Ini1+/- mice with Cyclin D1 deficiency did not develop any spontaneous tumors, in contrast to the parental Ini1+/- mice."
explanation: In vivo genetic proof that Cyclin D1 is the critical effector downstream of SMARCB1/Ini1 loss — Cyclin D1 deficiency fully abrogates rhabdoid tumorigenesis.
- name: Aberrant MRT Cell Growth
description: >-
EZH1 and EZH2 activity sustains malignant rhabdoid tumor cell growth,
helping maintain the aggressive proliferative phenotype downstream of
SMARCB1 loss.
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:36212776
reference_title: Dual targeting of EZH1 and EZH2 for the treatment of malignant rhabdoid tumors.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "Here, we show that EZH1, as well as EZH2, contributes to MRT cell growth and H3K27 methylation."
explanation: This study directly supports EZH-dependent malignant rhabdoid tumor cell growth downstream of the repressive chromatin state.
- name: Blocked Cellular Differentiation
description: >-
SMARCB1-deficient rhabdoid tumor cells are maintained in an undifferentiated
state, and EZH2 inhibition can trigger differentiation.
biological_processes:
- preferred_term: cell differentiation
modifier: DECREASED
term:
id: GO:0030154
label: cell differentiation
evidence:
- reference: PMID:23620515
reference_title: Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "The compound induces apoptosis and differentiation specifically in SMARCB1-deleted MRT cells."
explanation: Induction of differentiation after EZH2 inhibition supports a baseline differentiation block in SMARCB1-deleted rhabdoid tumor cells.
histopathology:
- name: Rhabdoid Cell Morphology
finding_term:
preferred_term: Rhabdoid Tumor
term:
id: NCIT:C3808
label: Rhabdoid Tumor
description: >-
Classic rhabdoid tumors are composed of poorly differentiated cells with
eccentric nuclei, prominent nucleoli, and glassy eosinophilic cytoplasm with
hyaline inclusions.
evidence:
- reference: PMID:16704491
reference_title: "Extrarenal rhabdoid tumors of soft tissue: clinicopathological and molecular genetic review and distinction from other soft-tissue sarcomas with rhabdoid features."
supports: SUPPORT
snippet: "Microscopically, the tumor is composed of a diffuse proliferation of rounded or polygonal cells with eccentric nuclei, prominent nucleoli and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies, arranged in sheets and nests."
explanation: This pathology review describes the defining rhabdoid cell morphology.
phenotypes:
- category: Genitourinary
name: Abdominal Mass
subtype: RTK
diagnostic: true
description: >-
Renal rhabdoid tumors commonly present as a large abdominal or flank mass in
infancy.
phenotype_term:
preferred_term: Abdominal mass
term:
id: HP:0031500
label: Abdominal mass
evidence:
- reference: PMID:8732342
reference_title: "Rhabdoid tumour of the kidney: a clinicopathological study of 22 patients from the International Society of Paediatric Oncology (SIOP) nephroblastoma file."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Clinically, they presented with an abdominal mass but four (18%) children also had hypercalcaemia"
explanation: SIOP clinicopathological series of 22 children with rhabdoid tumour of the kidney documents abdominal mass as the dominant presenting finding.
- category: Genitourinary
name: Hematuria
subtype: RTK
description: >-
Gross or microscopic hematuria can accompany kidney involvement and collecting
system invasion.
phenotype_term:
preferred_term: Hematuria
term:
id: HP:0000790
label: Hematuria
evidence:
- reference: PMID:11216700
reference_title: "Clinical presentation of rhabdoid tumors of the kidney."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Either gross or microscopic hematuria was present in 84.4% (27/32) of the patients with RTK."
explanation: National Wilms Tumor Study Group review of 50 RTK patients shows hematuria is a near-universal presenting feature, supporting its inclusion as a characteristic phenotype of renal rhabdoid tumor.
- category: Musculoskeletal
name: Soft Tissue Mass
subtype: eMRT
diagnostic: true
description: >-
Extrarenal disease often presents as a rapidly enlarging deep axial soft-tissue
mass.
phenotype_term:
preferred_term: Soft tissue neoplasm
term:
id: HP:0031459
label: Soft tissue neoplasm
evidence:
- reference: PMID:36720509
reference_title: "Extrarenal rhabdoid tumour of axillary soft tissue: a diagnostic challenge resolved by immunohistochemistry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "We report one such rare case in a female infant presenting as left axillary mass."
explanation: Case report of extrarenal rhabdoid tumour presenting as an axillary soft-tissue mass in an infant illustrates the typical eMRT presentation as a deep soft-tissue mass.
- category: Neurological
name: Headache
subtype: AT/RT
description: >-
AT/RT commonly causes headache from intracranial mass effect or obstructive
hydrocephalus.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
evidence:
- reference: PMID:27307151
reference_title: "Atypical teratoid/rhabdoid tumors with multilayered rosettes in the pineal region."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Patient 1, a 23-month-old girl, presented with a history of gait unsteadiness and headache"
explanation: Case series of two children with intracranial AT/RT in the pineal/third ventricular region documents headache as a presenting symptom consistent with intracranial mass effect.
- category: Neurological
name: Vomiting
subtype: AT/RT
description: >-
Vomiting, often worse in the morning, reflects increased intracranial pressure
in CNS rhabdoid tumor.
phenotype_term:
preferred_term: Vomiting
term:
id: HP:0002013
label: Vomiting
evidence:
- reference: PMID:27307151
reference_title: "Atypical teratoid/rhabdoid tumors with multilayered rosettes in the pineal region."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Patient 2, a 26-month-old girl, presented with headache and vomiting"
explanation: Same AT/RT case series documents vomiting accompanying headache, consistent with raised intracranial pressure from posterior third ventricular AT/RT.
biochemical:
- name: SMARCB1 (INI1/BAF47) Immunohistochemistry
notes: >-
Loss of nuclear INI1/BAF47 staining is the canonical diagnostic biomarker
for most rhabdoid tumors and mirrors biallelic SMARCB1 inactivation.
- name: SMARCA4 (BRG1) Immunohistochemistry
notes: >-
Rare SMARCA4-deficient rhabdoid tumors show loss of BRG1 staining and should
prompt consideration of rhabdoid tumor predisposition syndrome type 2.
genetic:
- name: SMARCB1
gene_term:
preferred_term: SMARCB1
term:
id: hgnc:11103
label: SMARCB1
association: Somatic/Germline Loss-of-Function
notes: >-
SMARCB1 is the dominant driver gene across the rhabdoid tumor spectrum. Both
somatic and germline loss can occur, and germline variants define rhabdoid
tumor predisposition syndrome type 1.
evidence:
- reference: PMID:39088359
reference_title: "Malignant Rhabdoid Tumor and Related Pediatric Tumors: Multimodality Imaging Review with Pathologic Correlation."
supports: SUPPORT
snippet: "Irrespective of the site of occurrence, somatic and germline mutations in SMARCB1, and rarely in SMARCA4, underlie the entire spectrum of rhabdoid tumors."
explanation: This review supports SMARCB1 as the principal shared somatic and germline driver across renal, extrarenal, and CNS rhabdoid tumors.
- reference: PMID:23432645
reference_title: "Rhabdoid tumors: an initial clue to the role of chromatin remodeling in cancer."
supports: SUPPORT
snippet: "Indeed, the mutation rate in RTs is among the lowest of all cancers sequenced, with loss of SMARCB1 as essentially the sole recurrent event."
explanation: This review emphasizes how dominant SMARCB1 loss is in the otherwise genetically simple rhabdoid tumor genome.
- name: SMARCA4
gene_term:
preferred_term: SMARCA4
term:
id: hgnc:11100
label: SMARCA4
association: Rare Somatic/Germline Loss-of-Function
notes: >-
SMARCA4 loss is an uncommon alternative driver in rhabdoid tumor and is the
basis of rhabdoid tumor predisposition syndrome type 2.
evidence:
- reference: PMID:39088359
reference_title: "Malignant Rhabdoid Tumor and Related Pediatric Tumors: Multimodality Imaging Review with Pathologic Correlation."
supports: SUPPORT
snippet: "Irrespective of the site of occurrence, somatic and germline mutations in SMARCB1, and rarely in SMARCA4, underlie the entire spectrum of rhabdoid tumors."
explanation: This review supports rare but disease-defining SMARCA4-driven rhabdoid tumors alongside the more common SMARCB1-deficient cases.
treatments:
- name: Multi-Agent Chemotherapy
description: >-
Intensive multi-agent chemotherapy remains part of front-line treatment for
most newly diagnosed patients, usually combined with surgery and local
radiotherapy according to age, site, and resectability.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
- name: Gross Total Resection
description: >-
Maximal safe resection is pursued whenever anatomically feasible because gross
total resection is one of the strongest favorable prognostic factors in
extracranial disease.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:33249395
reference_title: Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK).
supports: SUPPORT
snippet: "On univariate analyses, age at diagnosis (≥12 months), M0-stage, absence of synchronous tumours, absence of a GLM, gross total resection (GTR), radiotherapy and achieving a CR were significantly associated with favourable outcomes."
explanation: EU-RHAB registry data identifies gross total resection as a favorable prognostic factor in extracranial rhabdoid tumor.
- name: Radiation Therapy
description: >-
Radiotherapy is used for local control, especially after incomplete resection
or in high-risk disease, and contributes to outcome in multimodality therapy.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
evidence:
- reference: PMID:33249395
reference_title: Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK).
supports: SUPPORT
snippet: "On univariate analyses, age at diagnosis (≥12 months), M0-stage, absence of synchronous tumours, absence of a GLM, gross total resection (GTR), radiotherapy and achieving a CR were significantly associated with favourable outcomes."
explanation: The same EU-RHAB analysis supports radiotherapy as part of the treatment factors associated with improved extracranial outcomes.
- name: EZH2 Inhibitor Therapy
description: >-
EZH2-targeted therapy is an investigational mechanism-based strategy for
relapsed or refractory SMARCB1/SMARCA4-deficient disease. Preclinical data
support strong EZH2 dependence, and early pediatric trials have tested
tazemetostat in molecularly selected tumors.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: tazemetostat
term:
id: NCIT:C107506
label: Tazemetostat
target_mechanisms:
- target: EZH2-Driven H3K27 Methylation
treatment_effect: INHIBITS
description: >-
Tazemetostat selectively inhibits EZH2 methyltransferase activity, blocking
the H3K27 methylation dependency that SMARCB1-deficient rhabdoid tumors
acquire when BAF-mediated antagonism of PRC2 is lost.
evidence:
- reference: PMID:23620515
reference_title: Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: "These data demonstrate the dependency of SMARCB1 mutant MRTs on EZH2 enzymatic activity and portend the utility of EZH2-targeted drugs for the treatment of these genetically defined cancers."
explanation: Preclinical MRT models provide direct proof that EZH2 is a targetable dependency downstream of SMARCB1 loss.
- reference: PMID:37228094
reference_title: "Tazemetostat for tumors harboring SMARCB1/SMARCA4 or EZH2 alterations: results from NCI-COG pediatric MATCH APEC1621C."
supports: PARTIAL
snippet: "Patients whose tumors harbored EZH2 mutations or loss of SMARCB1 or SMARCA4 by immunohistochemistry were treated with EZH2 inhibitor tazemetostat."
explanation: This pediatric MATCH trial shows that EZH2 inhibition has been clinically tested in SMARCB1/SMARCA4-deficient pediatric tumors, including rhabdoid tumors, although efficacy was limited.
disease_term:
preferred_term: rhabdoid tumor
term:
id: MONDO:0002728
label: rhabdoid tumor
mappings:
mondo_mappings:
- term:
id: MONDO:0002728
label: rhabdoid tumor
mapping_predicate: skos:exactMatch
mapping_source: MONDO
mapping_justification: MONDO provides an exact disease term for rhabdoid tumor.
ncit_mappings:
- term:
id: NCIT:C3808
label: Rhabdoid Tumor
mapping_predicate: skos:exactMatch
mapping_source: NCIT
mapping_justification: NCIT provides an exact neoplasm term for rhabdoid tumor; the same identifier is used in this entry's histopathology block.
classifications:
icdo_morphology:
classification_value: Embryonal Neoplasm
harrisons_chapter:
- classification_value: cancer
- classification_value: solid tumor
review_notes: >-
This entry deliberately models the multisite rhabdoid tumor spectrum rather than
a single organ-specific disease. Shared chromatin-remodeling mechanisms are
represented at the umbrella level, while clinical features are tagged to RTK,
eMRT, and AT/RT subtypes because presentation and local therapy are strongly
site dependent.