Malignant rhabdoid tumor

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Synonyms and Keywords: Malignant rhabdoid tumour; Malignant rhabdoid neoplasm; Atypical teratoid rhabdoid tumor

Overview

Historical Perspective

  • In 1978, Beckwith and Palmar described malignant rhabdoid tumor of the kidney as a "rhabdomyosarcomatoid variant of wilms tumor" because the cells resembled rhabdomyoblasts. Although with further studies, it was recognized as a distinct clinicopathologic entity because of the inability to demonstrate myogenic differentiation.[1]
  • In 1982, Gonzalez-Crussi et al first described malignant rhabdoid tumor of the liver.[2][3]
  • In 1989, Rootman et al were the first to originally describe primary malignant tumor of the orbit.[4][5]

Classification

There is no established system for the classification of malignant rhabdoid tumor.

Pathophysiology

Staging Characteristic findings

Stage I

  • Tumor is involving single kidney and its completely resectable. behind. No tumor mass left behind. Renal capsule isn't breached by surgery. Blood vessels are not involved.

Stage II

  • Tumor invades beyond the renal capsule into the neighboring fatty tissue or blood vessels, but its completely resectable. No tumor mass left behind. Abdominal or pelvic lymph nodes are tumor-free.

Stage III

  • Tumor mass that is not completely resectable. Residual tumor is confined to the abdomen. One or more features that may be present that include:
    • Tumor involves abdominal and pelvic lymph nodes
    • Tumor invades the nearby vital structures
    • Tumor implants deposited on the peritoneal surface
    • Spillage of the tumor into th peritoneal cavity before or after surgery
    • Separate excision of the tumor at multiple sites (e.g., kidney and adrenals)
    • Pre-operative biopsy is done

Stage IV

  • Hematogenous spread of the tumor to distant organs such as lung, brain, bones, liver, or to the distant lymph node meetastasis

Stage V

  • Tumor observed in bilateral kidneys

Causes

There is no clear cause of malignant rhabdoid tumor but it is believed that the loss-of-function mutation of SMARCB1 tumor suppression gene contributes to the oncogenesis.[1][6]

Differentiating Malignant Rhabdoid Tumor from Other Diseases

Malignant rhabdoid tumor of the kidney should be differentiated from other diseases that present with hemeturia, abdominal pain and abdominal mass. The following are the differentials:[9][10][11][12][13][14][15][16][17]

S.No. Disease Symptoms Signs Diagnosis Comments
Abdominal Pain Hematuria Headache Abdominal mass Abdominal tenderness Ultrasonography CT scan Histology
1. Wilms tumor + + - + +
  • Wilms tumor has a triphasic appearance.
  • It is comprised of 3 types of cells:
  • All the 3 types are not required for the diagnosis of Wilms tumor.
  • Primitive tubules and glomeruli are often seen comprised of neoplastic cells.
  • Beckwith and Palmer reported in NWTS the different histopathologic types of Wilms tumor to categorize them based on prognosis.[21]
2. Renal cell carcinoma + + +/- + -
  • Ultrasound (US) may be helpful when CT scan results are equivocal. It is noteworthy to mention that not all renal cell carcinomas are detectable on ultrasound.
Both CT and MRI may be used to detect neoplastic masses that may define renal cell carcinoma or metastasis of the primary cancer. CT scan and use of intravenous (IV) contrast is generally used for work-up and follow-up of patients with renal cell carcinoma. The histological pattern of renal cell carcinoma depends whether it is papillary, chromophobe or collecting duct renal cell carcinoma.
3. Rhabdoid kidney disease + + - + -
  • CT scan may be diagnostic of malignant rhabdoid tumor. Findings on CT scan suggestive of malignant rhabdoid tumor include a large, heterogenous, centrally located mass, which is lobulated with individual lobules separated by intervening areas of decreased attenuation, relating to either previous hemorrhage or necrosis. Enhancement is similarly heterogeneous. Calcification is relatively common, observed in 20-50% of cases and is typically linear and tends to outline tumor lobules.
  • Malignant rhabdoid tumor is characterized by the round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of eosinophilic cytoplasm with frequent mitotic figures.
4. Polycystic kidney disease + + + (from hypertension) + -

Ultrasound may be helpful in the diagnosis of polycystic kidney disease. Findings on an ultrasound diagnostic of polycystic kidney disease include:[22][23]

  • At least three unilateral or bilateral cysts in patients 15 - 39 years old
  • Atleast two cysts in each kidney in patients 40 - 59 years old
  • Atleast four cysts in each kidney in patients 60 years of age or older

Renal CT scan may be helpful in the diagnosis of polycystic kidney disease. Findings on CT scan diagnostic of ADPKD include:

  • Numerous renal cysts of varying size and shape with little intervening parenchyma with water attenuation and very thin wall.
  • Reduction in sinus fat due to expansion of the cortex
  • Occasional complex cysts with hyperdense appearance, with possible septations or calcifications
  • Multiple homogeneous and hypoattenuating cystic lesions in the liver in patients with liver involvement
  • On microscopic histopathological analysis, interstitial fibrosis, tubular atrophy, thickening and lamellation of tubular basement membranes, microcysts and negative immunofluorescence for complement and immunoglobulin are characteristic findings of ADPKD.[24][25][26][27]
5. Pheochromocytoma - - + (as a part of the hypertension paroxysm) - -
  • CT is the preferred imaging modality for the diagnosis of pheochromocytoma.
The following findings may be observed on CT scan:[28]
  • On microscopic pathology, Pheochromocytoma typically demonstrates a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumor cells containing eosinophilic cytoplasm separated by fibrovascular stroma.
6. Burkitt lymphoma +/- (in non-endemic or sporadic form of the disease) - - - -
  • Chest, abdomen, and pelvis CT scan may be helpful in the diagnosis of Burkitt's lymphoma but it is not done routinely.[32]
  • On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:[33]
  • Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- key feature (i.e. tumor nuclei size similar to that of histiocytes or endothelial cells)
  • Round nucleus
  • Small nucleoli
  • Relatively abundant cytoplasm (basophilic)
  • Brisk mitotic rate and apoptotic activity
  • Cellular outline usually appears squared off
  • "Starry-sky pattern":
  • The stars in the pattern are tingible-body macrophages (macrophages containing apoptotic tumor cells.
  • The tumour cells are the sky
7. Intussusception + - - +/- +
  • Ultrasound is the gold standard imaging modality used to diagnose intussusception[34]
    • Target or doughnut sign[35]
      • Edematous intussuscipien forms an external ring around the centrally located intussusceptum
      • Target sign is usually seen in right lower quadrant
    • Layers of intussusception forms pseudo-kidney appearance on the transverse view
  • CT scan may be helpful in the diagnosis of intussusception. CT scan maybe used when other image modalities like x-ray and ultrasound have not given positive results but suspicion of intussusception is high.
  • Intussusception occurs if there is an imbalance between the longitudinal and radial smooth muscle forces of intestine that maintain its normal structure. This imbalance leads to a segment of intestine to invaginate into another segment and cause entero-enteral intussusception. Etiology of intussusception is either idiopathic or pathologic (lead point). 
8. Hydronephrosis + +/- - - + (CVA tenderness in case of pyelonephritis)
  • In the case of renal colic (one sided loin pain usually accompanied by a trace of blood in the urine) the initial investigation is usually an intravenous urogram. This has the advantage of showing whether there is any obstruction of flow of urine causing hydronephrosis as well as demonstrating the function of the other kidney. Many stones are not visible on plain x ray or IVU but 99% of stones are visible on CT and therefore CT is becoming a common choice of initial investigation.
  • The kidney undergoes extensive dilation with atrophy and thinning of the renal cortex.
9. Dysplastic kidney N/A N/A N/A N/A N/A

MCDK is usually diagnosed by ultrasound examination before birth.

  • Mass of non-communicating cysts of variable size.
  • Unlike severe hydronephrosis, in which the largest cystic structure (the renal pelvis) lies in a central location and is surrounded by dilated calices, in multicystic dysplastic kidney the cyst distribution shows no recognizable pattern.
  • Dysplastic, echogenic parenchyma may be visible between the cysts, but no normal renal parenchyma is seen.
  • MCKD can be discovered accidentally on CT scan.
  • CT scan shows myltiple cysts with absence of renal parenchyma.
  • MCKD is the result of abnormal differentiation of the renal parenchyma.
10. Pediatric Neuroblastoma + - - +/- +/-
  • CT scan is the investigation of choice for the diagnosis of neuroblastoma.[37]
  • On CT scan, neuroblastoma is characterized by:[38]
  • On microscopic histopathological analysis the presence of round blue cells separated by thin fibrous septa are characteristic findings of neuroblastoma.
  • Other findings of neuroblastoma on light microscopy may include:[39]
  • Homer-Wright rosettes (rosettes with a small meshwork of fibers at the center)
  • Neuropil-like stroma (paucicellular stroma with a cotton candy-like appearance)
11. Pediatric Rhabdomyosarcoma + +/- +/- - +/- On CT scan, rhabdomyosarocma is characterized by:
  • Soft tissue density
  • Some enhancement with contrast
  • Adjacent bony destruction (over 20% of cases)
12. Mesoblastic nephroma + + - + -
  • Ultrasound may be helpful in the diagnosis of mesoblastic nephroma.
  • Mesoblastic nephroma may presents as a well-defined mass with low-level homogeneous echoes.[40]
  • The presence of concentric echogenic and hypoechoic rings can be a helpful diagnostic feature of mesoblastic nephroma.
  • CT scan may be helpful in the diagnosis of mesoblastic nephroma.
  • Findings on CT scan suggestive of mesoblastic nephroma include:
  • Solid hypoattenuating renal lesion
  • Variable contrast enhancement
  • No calcification

Classic mesoblastic nephroma

Cellular mesoblastic nephroma

  • Plump cells with vesicular nuclei
  • Well-defined border
  • Mitotically active

Mixed mesoblastic nephroma

  • Both classic pattern and cellular pattern areas are present
Most common renal tumor that occurs in 1st month of life

Epidemiology and Demographics

  • The incidence of malignant rhabdoid tumor of the kidney is approximately 0.019 per 100,000 individuals per year in the US. That of atypical teratoid/rhabdoid tumor is 0.089 per 100,000 per year, and 0.032 per 1000,000 yearly for the tumors found in other sites.[41]
  • Malignant rhabdoid tumor of the kidney accounts for about 2% of all pediatric renal malignancies.[8]
  • The mortality rate of malignant rhabdoid tumor is approximately 80%.[42]
  • Malignant rhabdoid tumor mostly occur in infants. The median reported age is about 22.5 months.[43]
  • Although malignant rhabdoid tumors usually affect children, some cases in adults have been reported with the age at diagnosis ranging from 32 to 60 years.[1]
  • Malignant rhabdoid tumor affects females and males equally.[41]

Risk Factors

There are no established risk factors for malignant rhabdoid tumor.

Screening

There is insufficient evidence to recommend routine screening for malignant rhabdoid tumor.

Natural History, Complications, and Prognosis

  • Malignant rhabdoid tumors are prone to metastasize early with metastasis being the most common cause of death among patients. Most cases may have already metastasized before the diagnosis is made.[43][42]
  • In most cases, patients die at an average of 6 months after diagnosis.[44]
  • Common complications of malignant rhabdoid tumor include spontaneous tumor rupture and thrombotic pulmonary microangiopathy (pulmonary tumor embolism syndrome) which may be seen in adult patients with metastasis to the lungs.[2][1]
  • The 5-year survival rate of malignant rhabdoid tumor is 33%.[41]
  • The overall survival rate ranges from between 22% to 42%.[45]
  • In adults, the prognosis is poor with the survival time after diagnosis being only a few months.[1]
  • Factors associated with significantly reduced survival include metastases/multifocal disease, younger age, infratentorial location, and less than complete remission at the end of chemotherapy.[45][46]
  • Neither tumor volume at diagnosis nor pre-operative chemosensitivity affects the outcome.[47]

Diagnosis

Diagnostic Study of Choice

History and Symptoms

  • Common symptoms of malignant rhabdoid tumor of the liver include:[2]
  • Common symptoms of malignant rhabdoid tumor of the head (atypical teratoid/rhabdoid tumor) include:[49]

Physical Examination

Laboratory Findings

  • Depending on the location of the tumor, there may be different lab findings in patients. The lab findings that may be seen according to the location of the tumor include:[44][8][1]

Electrocardiogram

  • There are no ECG findings associated with malignant rhabdoid tumor.

X-ray

There are no x-ray findings associated with malignant rhabdoid tumor.

Echocardiography or Ultrasound

  • Ultrasound may be helpful in the diagnosis of malignant rhabdoid tumor. Findings on an ultrasound suggestive of/diagnostic of malignant rhabdoid tumor include:[8]

CT Scan

  • After the diagnosis of malignant rhabdoid tumor in a patient, further imaging of other parts of the chest, liver, brain, and other parts of the body is recommended in order to search for distant metastasis.[44]

MRI

  • Abdominal MRI may be helpful in the diagnosis of malignant rhabdoid tumor. Findings on MRI suggestive of/diagnostic of malignant rhabdoid tumor include:[2]
  • A lobulated mass with hypointense lesions on T1-weighted (W) and hyperintense on T2-W images

Other Imaging Findings

There are no other imaging findings associated with malignant rhabdoid tumor.

Other Diagnostic Findings

There are no other diagnostic studies associated with malignant rhabdoid tumor.

Treatment

Medical Therapy

Surgery

Primary Prevention

There are no established measures for the primary prevention of malignant rhabdoid tumor.

Secondary Prevention

There are no established measures for the secondary prevention of malignant rhabdoid tumor.

References

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