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Year : 2022  |  Volume : 18  |  Issue : 3  |  Page : 780-783

Reappraisal of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1/INI-1 deficient tumor: Report of two cases

1 Department of Lab Medicine, Max Super Speciality Hospital, New Delhi, India
2 Department of Lab Medicine, Max Hospital Vaishali, Ghaziabad, Uttar Pradesh, India

Date of Submission06-May-2020
Date of Decision16-Jul-2020
Date of Acceptance01-Oct-2020
Date of Web Publication25-Jul-2022

Correspondence Address:
Anuj Khurana
98 SFS Flats, Phase 4 Ashok Vihar, New Delhi - 110 052
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_577_20

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 > Abstract 

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 is a tumor suppressor gene located at chromosome 22q11.2. In the past decade, a major stride has been taken for decoding the molecular genesis of various tumors which has resulted in the addition of newer tumors harboring loss of this gene.

Keywords: Malignant extrarenal rhabdoid tumor, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 deficient sinonasal carcinoma, subfamily B member 1/INI-1

How to cite this article:
Gurung N, Kapoor N, Mukherjee U, Khurana A. Reappraisal of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1/INI-1 deficient tumor: Report of two cases. J Can Res Ther 2022;18:780-3

How to cite this URL:
Gurung N, Kapoor N, Mukherjee U, Khurana A. Reappraisal of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1/INI-1 deficient tumor: Report of two cases. J Can Res Ther [serial online] 2022 [cited 2022 Aug 10];18:780-3. Available from: https://www.cancerjournal.net/text.asp?2022/18/3/780/348230

 > Introduction Top

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) is a nuclear protein, ubiquitously expressed in all cells. Oncogenesis related to this gene has been established by various mechanisms such as biallelic inactivation, homozygous deletions,[1] loss of heterogeneity or truncating, and nontruncating mutations. Prototypically, its loss was described in the rhabdoid tumor of the kidney, followed by a number of tumors, i.e., atypical teratoid rhabdoid tumor, rhabdoid tumor of the kidney, epithelioid sarcoma (ES), renal medullary carcinoma, epithelioid malignant peripheral nerve sheath tumor, extraskeletal myxoid chondrosarcoma, cribriform neuroepithelial tumor of the ventricle, undifferentiated chordomas, and the list is still expanding. By default, these tumors are diagnosed by variable loss of SMARCB1/INI-1 on immunohistochemistry (IHC). Recently, described in the literature is a novel distinct entity, SMARCB-1 deficient sinonasal carcinoma (SDSC) which exhibits a peculiar varied spectrum of histomorphology.

 > Case Reports Top

Case 1

A 72-year-old woman presented with profuse bleeding from the nose. Positron emission tomography-computed tomography scan showed a large heterogeneous enhancing expansile mass lesion with increased fludeoxyglucose uptake epicentered at the left nasal cavity and bilateral ethmoid sinuses with a contiguous expansion of the mass in the left maxillary sinus, sphenoid sinus, and bilateral orbits [Figure 1]. Superiorly, the mass was protruding into the floor of the anterior cranial fossa and posteriorly extending up to the posterior wall of the nasopharynx. On microscopic hemotoxylin and eosin, section a tumor was seen in the subepithelium [Figure 2], arranged in a solid and nested pattern with plasmacytoid/rhabdoid morphology; composed of monomorphic medium-sized rounded nuclei with dispersed chromatin, variably prominent nucleoli and high mitotic rate [Figure 3]. No conventional squamous dysplasia/carcinoma in situ was seen in the overlying epithelium. IHC shows a strong and diffuse expression for cytokeratin (CK) (AE1/3) and epithelial membrane antigen (EMA) in the tumor cells with a focal variable expression for p16 and neuron-specific enolase. The tumor cells showed a complete loss of INI-1 [Figure 4] with retained strong reactivity in the background inflammatory, stromal, and epithelial cells. They are negative for CK7, CK20, p40, p63, CK5/6, HMWCK, CD99, chromogranin, synaptophysin, vimentin, desmin, GFAP, MelanA, S100, CD56, CD34, and CD45. A final diagnosis of SDSC was rendered. On follow-up, she received two doses of neoadjuvant chemotherapy, including injection paclitaxel and cisplatin. Post two cycles of chemotherapy she underwent re-evaluation with contrast-enhanced computed tomography-paranasal sinus (CECT-PNS), which revealed a massive increase in size and was planned for chemotherapy-radiotherapy (CT-RT). After completing seven cycles of CT-RT, she succumbed to the disease within 4 months of the diagnosis.
Figure 1: Positron emission tomography-computed tomography revealing a large heterogeneous enhancing mass lesion with increased FDG uptake epicentered at left nasal cavity and bilateral ethmoid sinuses with a contiguous expansion of the mass in the left maxillary sinus, sphenoid sinus, and bilateral orbits

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Figure 2: The tumor is located in the subepithelium, without any squamous dysplasia/in situ lesion in the overlying mucosa (H and E, ×100)

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Figure 3: The tumor is arranged in solid nests comprising monomorphic round/plasmacytoid cells with dispersed chromatin and conspicuous nucleoli (H and E, ×400)

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Figure 4: The tumor cells show loss of INI-1 (immunohistochemistry, ×400)

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Case 2

A 70-year-old male presented with the complaint of swelling and pain in the right testis radiating to back for 2 months. On CECT, there was right testis enlargement with a heterogeneous enhancing mass. On gross examination, the testis was enlarged with an intact tunica vaginalis. On the cut section, a variegated tumor was identified with necrosis measuring 5 cm × 4.9 cm × 4 cm. Microscopic examination revealed a poorly differentiated tumor arranged in sheets and lobules with large areas of necrosis. Individual tumor cells have moderate eosinophilic cytoplasm, with centrally and occasionally eccentrically/plasmacytoid placed nuclei, fine granular chromatin, and conspicuous nucleoli [Figure 5]. Frequent mitotic figures were noted. Lymphovascular invasion was seen. On IHC, the tumor cells were diffusely positive for vimentin with patchy positivity of WT-1. Focal CK and CK18 expression were also seen with trace synaptophysin. The tumor cells showed a complete loss of INI-1. They were negative for EMA, CD34, S-100, PLAP, calretinin, Iinhibin, Leukocyte common antigen (LCA), CD30, CD20, CD138, CD3, MPO, HMB-45, Melan-A, CD1a, desmin, myogenin, TLE-1, CD99, MDM2, chromogranin, and CK5/6. A diagnosis of a malignant extrarenal rhabdoid tumor (MERT) of the testis was made. On follow-up, the patient died within 2 months of surgery without any history of additional treatment.
Figure 5: Sheets of tumor cells exhibiting eccentric/plasmacytoid appearance with frequent mitosis (H and E, ×400)

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 > Discussion Top

Tumors express a variable loss of SMARCB1 ranging from 100% in the malignant rhabdoid tumor (MRT) to 10% in myoepithelial carcinomas of adult.[2] It can occur by mutation, deletion, or any somatic alterations in the INI-1 gene, that encodes a subunit of SWI/SNF chromatin remodeling complex. Reduced expression of SMARCB1 protein, demonstrated by IHC has been observed in synovial sarcoma, which can propose a theory that SMARCB1 might be regulated posttranscriptional through SS18-SSX.[3] Recently, loss of SMARCB1 was described among the undifferentiated sinonasal tumors almost simultaneously by Agaimy et al. and Bishop et al.[4],[5]

SDSC is rare, recently recognized distinct novel entity with <60 cases reported in the literature.[5],[6] They have a dismal prognosis irrespective of aggressive therapy, mean survival of 22 months.[5] They can occur in both male and female with a wide age range (19–89 years), mean age being 52 years. They have a predilection for nasal sinuses, mainly ethmoid sinus with variable involvement of the nasal cavity. Our case is a 72-years-old male with a mass in the left nasal cavity having extensive involvement of the PNSs. These tumors exhibit a wide histomorphological spectrum. Major chunk of these tumors exhibited basaloid features resembling basaloid squamous cell carcinoma, sinonasal undifferentiated carcinoma followed by plasmacytoid/rhabdoid features. Surprisingly, few of them also displayed frankly sarcomatoid histology and variable adenoid features with mucin production which necessitated exclusion of a primary sarcoma and an adenocarcinoma.[4] Most recent addition to this broad variety of histology is tumor cells eliciting entirely oncocytoid features with abundant glassy cytoplasm, having centrally placed, round vesicular nuclei with prominent eosinophilic nucleoli arranged in well-formed tubular/glandular structures.[7] Thus, with this knowledge of the fact that these tumors can show a wide range of histology, it justifies the judicial use of SMARCB1/INI-1 IHC in routine practice for workup of a poorly differentiated tumor in the sinonasal tract. The phenomenon of tumors showing secondary rhabdoid morphology in the setting of a high-grade malignancy, i.e., carcinomas, sarcomas, melanocytic, glial are meningothelial are known. However, in the index case, there was no histological evidence of any other conventional malignancy.

MRTs were introduced as a distinct entity in 1978 by Beckwith and Palmer.[8] They are highly aggressive tumors with a dismal prognosis, generally affecting children <2 years with renal involvement.[9] Extrarenal sites are known to occur and are referred to as MERTs. A minority of these cases have also been reported in adults. MERTs have been observed in various anatomic sites including the perineum, vulva, lung, orbit, urinary bladder, gastrointestinal tract, and liver. Our case is unique, it being likely the first case to be reported in a primary testicular location and in an elderly male patient. Unlike SDSC, these tumors demonstrate a characteristic cytological feature that is common in all MRTs popularly known as “rhabdoid cell.” The rhabdoid cells are large oval to polygonal with abundant eosinophilic cytoplasm, eccentrically placed vesicular nuclei with prominent nuclei, and an eosinophilic cytoplasmic inclusion. On initial microscopic examination, the histological differentials were a high-grade large-cell lymphoma, melanoma, rhabdomyosarcoma, germ cell tumor (embryonal carcinoma), ES-proximal type (PT), and MERT. The tumor was negative for LCA, MPO, CD3, CD20, CD30, CD138, S-100, HMB-45, Melan-A, Desmin, and Myogenin which ruled out all the former possibilities except ES. INI-1 loss was seen in the tumor cells, which is known to occur in MERT and also in 86%–93% of ES.[10] About 96% of ES show EMA expression, which was lacking in our case.[11] In addition, they were also negative for CD34, which is seen in 50%–60% of ES. Whereas, in our case, a subset of the tumor cells was positive for synaptophysin and WT-1 which is a rare aberrant phenomenon that has been reported in MERT.[12] Therefore, despite our case being present in an elderly male, in view of the observed immuno-histology (tumor cells negative for EMA and CD34 and focal expression of synaptophysin and WT-1), we favored the diagnosis of MERT over ES-PT.

 > Conclusion Top

In the past few decades, there has been an ascending trend in recognition, diagnosis, and addition of newer entities of SMARCB1 deficient tumors. INI-1 IHC has been proven as a highly reliable tool for establishing their diagnosis and therefore should be integrated in routine workup of any poorly differentiated tumor with or without the presence of the classical rhabdoid morphology.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Versteege I, Sévenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 1998;394:203-6.  Back to cited text no. 1
Hollmann TJ, Hornick JL. INI1-deficient tumors: Diagnostic features and molecular genetics. Am J Surg Pathol 2011;35:e47-63.  Back to cited text no. 2
Kohashi K, Oda Y, Yamamoto H, Tamiya S, Matono H, Iwamoto Y, et al. Reduced expression of SMARCB1/INI1 protein in synovial sarcoma. Mod Pathol 2010;23:981-90.  Back to cited text no. 3
Agaimy A, Hartmann A, Antonescu CR, Chiosea SI, El-Mofty SK, Geddert H, et al. SMARCB1 (INI-1)-deficient sinonasal carcinoma: A series of 39 cases expanding the morphologic and clinicopathologic spectrum of a recently described entity. Am J Surg Pathol 2017;41:458-71.  Back to cited text no. 4
Bishop JA, Antonescu CR, Westra WH. SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract. Am J Surg Pathol 2014;38:1282-9.  Back to cited text no. 5
Rooper LM, Westra WH. A protein lost, a diagnosis gained: A review of SMARCB1-deficient sinonasal carcinomas. AJSP Rev Rep 2018;23:13-8.  Back to cited text no. 6
Kakkar A, Antony VM, Pramanik R, Sakthivel P, Singh CA, Jain D. SMARCB1 (INI1)-deficient sinonasal carcinoma: A series of 13 cases with assessment of histologic patterns. Hum Pathol 2019;83:59-67.  Back to cited text no. 7
Beckwith JB, Palmer NF. Histopathology and prognosis of wilms tumors: Results from the first national wilms' tumor study. Cancer 1978;41:1937-48.  Back to cited text no. 8
Peng HQ, Stanek AE, Teichberg S, Shepard B, Kahn E. Malignant rhabdoid tumor of the kidney in an adult: A case report and review of the literature. Arch Pathol Lab Med 2003;127:e371-3.  Back to cited text no. 9
Chbani L, Guillou L, Terrier P, Decouvelaere AV, Grégoire F, Terrier-Lacombe MJ, et al. Epithelioid sarcoma: A clinicopathologic and immunohistochemical analysis of 106 cases from the French sarcoma group. Am J Clin Pathol 2009;131:222-7.  Back to cited text no. 10
Miettinen M, Fanburg-Smith JC, Virolainen M, Shmookler BM, Fetsch JF. Epithelioid sarcoma: An immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis. Hum Pathol 1999;30:934-42.  Back to cited text no. 11
Goyal S, Mishra K, Sarkar U, Sharma S, Kumari A. Diagnostic utility of wilms' tumour-1 protein (WT-1) immunostaining in paediatric renal tumours. Indian J Med Res 2016;143:S59-67.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]


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