|Year : 2015 | Volume
| Issue : 4 | Page : 963-966
Malignant extra-renal rhabdoid tumor with unusual presentation: A report of two cases
Rakesh Kumar Gupta1, Vineeta V Batra1, Mridul Chandra Das2, Ajay Sharma3, Poonam Narang4
1 Department of Pathology, G B Pant Hospital, New Delhi, India
2 Department of Paediatrics, Lady Hardinge Medical College, New Delhi, India
3 Department of Neurosurgery, G B Pant Hospital, New Delhi, India
4 Department of Radio Diagnosis, G B Pant Hospital, New Delhi, India
|Date of Web Publication||15-Feb-2016|
Vineeta V Batra
Department of Pathology, Academic Block, G B Pant Hospital, Jawaharlal Nehru Marg, New Delhi - 110 002
Source of Support: None, Conflict of Interest: None
Malignant extra-renal rhabdoid tumor (MERT) is a rare highly aggressive tumor that occurs in young children with the very poor clinical outcome. The tumor is characterized by a diffuse proliferation of "rhabdoid cells," which are round or polygonal with eccentric nuclei, prominent nucleoli, and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies. However, rhabdoid cells are also seen in certain other soft tissue sarcomas such as proximal-type epithelioid sarcoma, rarely synovial sarcoma, and extra-skeletal myxoid chondrosarcoma. Because of its poor prognosis and histomorphological similarities with other soft tissue tumors, an accurate diagnosis is required using a wide immunohistochemical panel. Very few cases of MERT have been reported in the literature and to our knowledge none in the supra-glottis area. Due to the rarity and poor outcome of this tumor, we are reporting two cases of MERT.
Keywords: INI-1, malignant extra-renal rhabdoid tumor, rhabdoid cells, soft tissue tumor
|How to cite this article:|
Gupta RK, Batra VV, Das MC, Sharma A, Narang P. Malignant extra-renal rhabdoid tumor with unusual presentation: A report of two cases. J Can Res Ther 2015;11:963-6
|How to cite this URL:|
Gupta RK, Batra VV, Das MC, Sharma A, Narang P. Malignant extra-renal rhabdoid tumor with unusual presentation: A report of two cases. J Can Res Ther [serial online] 2015 [cited 2019 May 26];11:963-6. Available from: http://www.cancerjournal.net/text.asp?2015/11/4/963/163668
| > Introduction|| |
Malignant extra-renal rhabdoid tumor (MERT) is a rare highly aggressive tumor occurring in young children and carries a very poor outcome. This is a recently described entity with distinct diagnostic features and genetic aberrations. Molecular analysis has shown loss of the hSNF5/INI-1 (SMARCB1) gene in the long arm of chromosome 22.  Due to its poor prognosis and morphological similarities with other round cell tumors, an accurate, timely diagnosis, is mandatory for proper management. We present here two cases of MERT arising in the spinal region and supra-glottis of two children, 3 years and 6 months old respectively.
| > Case reports|| |
A 3-year-old child was brought to our hospital with the chief complaints of the weakness of all four limbs for 25 days duration. The weakness was gradually progressive and associated with increased bilateral planter reflexes and ankle clonus and 3/5 strength. He was conscious, well oriented with normal vitals and systemic examination. There was no significant family history.
MRI revealed an intradural extra-medullary tumor in the C4-T2 region extending into the posterior mediastinum, neck, and axilla [Figure 1]. He underwent decompression surgery of the cervical mass.
|Figure 1: Sagittal, coronal and axial MRI scans showing a large intradural extra-medullary mass lesion at C4-T2 level extending through neural foramina to involve posterior mediastinum, neck, and axilla|
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The patient was shifted to the intensive care unit due to continuous postoperative deterioration. On postoperative day 18, the patient went into a sudden cardio-respiratory arrest for which all necessary life support measures were given without success.
A 6-month-old female child was admitted with the complaints of fever, cough, and respiratory distress for 45 days duration. Contrast enhanced computed tomography showed diffuse consolidation in both the lungs and the left sided hemorrhagic pleural effusion. No icterus, clubbing, lymphadenopathy or organomegaly was noted.
Laryngoscopy showed a pale, firm, irregular, friable growth in the bilateral arytenoids measuring approximately 2 cm × 1.5 cm which was biopsied. The patient's family refused chemotherapy. The child was discharged and died at home 1-month later.
Microscopic examination in both the cases showed a similar morphology. The tumors were richly cellular predominantly comprised of large atypical rhabdoid cells arranged in sheets [Figure 2]a and [Figure 3]a]. The individual tumor cell showed vesicular nuclear chromatin, prominent eccentric nucleoli, and abundant glassy eosinophilic cytoplasm with hyaline-like inclusion bodies [Figure 2]b and [Figure 3]b]. Frequent mitotic figures and areas of necrosis were noted.
|Figure 2: Histomorphology and immunohistochemistry features of case report 1. (a) Tumor cells arranged in a diffuse sheet (H and E, ×100). (b) Arrow showing eosinophilic inclusion like cytoplasm (H and E, ×400). (c) Epithelial membrane antigen stain showing dot like positivity (Arrow) (×200). (d) Vimentin stain showing cytoplasmic positivity (×200). (e) INI-1 stain showing false cytoplasmic positivity in tumor cells, arrow showing true nuclear stain in endothelial cell control (×400). (f) High MIB-1 labeling index (×100)|
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|Figure 3: Histomorphology and immunohistochemistry features of case report 2. (a) Subepithelial tumor cells arranged in a diffuse sheet (H and E, ×100). (b) Arrow highlighting eosinophilic inclusion like cytoplasm (H and E, ×400). (c) Cells showed immunopositivity for cytokeratin (×100). (d) Epithelial membrane antigen (×100). (e) Vimentin (×200). (f) Negativity for INI-1 (×200), false cytoplasmic positivity being seen in tumor cells; arrow showing true nuclear stain in endothelial cell (internal control)|
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An immunohistochemical panel was performed including desmin, vimentin, cytokeratin (CK), epithelial membrane antigen (EMA), synaptophysin, CD99, HMB-45, MIB-1, and INI-1 to rule out various round cell tumors with rhabdoid morphology. In both the cases, the tumor cells showed intense immunopositivity for vimentin and epithelial markers (CK and EMA) [Figure 2]c, [Figure 2]d and [Figure 3]c- [Figure 3]e] with a MIB-1 labeling index of 65-70% [Figure 2]f]. However INI-1 expression was lost [Figure 2]e and [Figure 3]f]. Immunostaining for synaptophysin, CD99 and HMB-45 were negative.
| > Discussion|| |
Malignant rhabdoid tumor was first described in 1978 by Beckwith and Palmer.  It was subsequently reported in various extra-renal sites including central nervous system, stomach, colon, liver, bladder, uterus, ovary, and soft tissues.  These are rare highly aggressive tumors which usually occur in early childhood, mostly before 2 years of age.
The tumor has characteristic microscopic features which include a diffuse proliferation of "rhabdoid cells," which are round or polygonal with eccentric nuclei, prominent nucleoli, and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies.  However, rhabdoid cells are also seen in certain other soft tissue sarcomas such as proximal type epithelioid sarcoma (PES), rarely synovial sarcoma,  and extra-skeletal myxoid chondrosarcoma. Thus, it is challenging to make an accurate diagnosis based on histology. An immunohistochemical panel usually resolves this problem.
Expression of vimentin and CK, along with a lack of staining for desmin, myogenin, smooth muscle actin, INI-1, and HMB-45 is characteristic, but nonspecific.  Loss of expression of INI-1 is also seen in PES, about 70% cases of synovial sarcoma  and half of the epithelioid malignant peripheral nerve sheath tumor. 
Cytogenetic and molecular analyzes have shown abnormalities in the long arm of chromosome 22 (22q11.2) which encodes the INI-1 gene which is a core subunit of the SWI/SNF ATP-dependent chromatin remodeling complex.  This gene alteration has been considered to be a specific molecular event in MERT.
INI-1 is ubiquitously expressed in nuclei of all normal cells. Earlier, some experimental studies have shown that INI-1 heterozygous-deficient mouse develop undifferentiated sarcomas with rhabdoid cytologic features, suggesting that INI-1 is an important tumor suppressor gene. Germline INI-1 mutations have been identified in up to 35% of patients with sporadic MERTs, and these patients present very early in life and carry a worse prognosis. 
PES and MERT share a number of histomorphological, immunohistochemical, and genetic features. Both result from the inactivation of INI-1.  However, prognosis of MERT is significantly worse in comparison to PES. Frank et al. described that PES and MERT could be a single entity with similar morphological and immunohistochemical features but with different molecular genetic alterations.
Although Sparano et al. reported a case of MERT involving parapharyngeal space, supraglottic MERT to our knowledge has been not described to date.  Treatment includes complete surgical removal with wide margins. The role of radiotherapy and chemotherapy is doubtful and needs to be explored further. Both our patients did not receive chemotherapy, one because of nonaffordability and the other due to nonrecovery after postsurgical treatment.
| > Conclusion|| |
MERT are an heterogeneous group of aggressive tumors with polyphenotypia and immunoreactivity to a wide array of antibodies. The characteristic rhabdoid histomorphology, immunoreactivity to vimentin, and epithelial markers and INI-1 loss are important diagnostic clues.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]