SMARCB1 deficient sinonasal carcinoma: An emerging entity with a diagnostic challenge

KR Anila; V Ginju; VL Vishnu; Rejnish Kumar; K Jayasree

doi:10.4103/ijpm.ijpm_77_22

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CASE REPORT

Year : 2023 | Volume : 66 | Issue : 1 | Page : 159-161

SMARCB1 deficient sinonasal carcinoma: An emerging entity with a diagnostic challenge

KR Anila¹, V Ginju¹, VL Vishnu¹, Rejnish Kumar², K Jayasree¹
¹ Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
² Department of Radiation Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

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Date of Submission	22-Jan-2022
Date of Decision	07-Mar-2022
Date of Acceptance	12-Mar-2022
Date of Web Publication	18-Jan-2023

Abstract

SMARCB1 deficient sinonasal carcinomas are rare neoplasms, classified under sinonasal undifferentiated carcinomas by the fourth edition of the World Health Organization (WHO) classification of head and neck tumors. It is characterized immunohistochemically by loss of SMARCB1(INI1) expression. We are reporting the case of a 63-year-old man who was evaluated for nasal stuffiness of 3 months duration in another hospital where a radiological evaluation showed a polypoidal soft tissue lesion in the right maxillary sinus extending to the right nasal cavity and spheno-ethmoidal sinus. He underwent excision biopsy which was reported as non- keratinizing nasopharyngeal carcinoma. He was referred to our center with residual disease in spheno-ethmoidal recess for which radiotherapy was given. After completion of radiotherapy, the primary site had no residual disease, but while on follow-up he developed left sided neck nodes within 4 months of completion of treatment. Excision of the lesion was done and histopathological and immunohistochemical analysis revealed it to be metastasis from SMARCB1 deficient sinonasal carcinoma and not nasopharyngeal carcinoma as diagnosed from the other center. This case is being reported to highlight the diagnostic challenge associated with this rare entity.

Keywords: INI 1 deficient carcinoma, sinonasal carcinoma, SMARCB1 deficient carcinoma

How to cite this article:
Anila K R, Ginju V, Vishnu V L, Kumar R, Jayasree K. SMARCB1 deficient sinonasal carcinoma: An emerging entity with a diagnostic challenge. Indian J Pathol Microbiol 2023;66:159-61

How to cite this URL:
Anila K R, Ginju V, Vishnu V L, Kumar R, Jayasree K. SMARCB1 deficient sinonasal carcinoma: An emerging entity with a diagnostic challenge. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Mar 20];66:159-61. Available from: https://www.ijpmonline.org/text.asp?2023/66/1/159/367984

Introduction

Sinonasal undifferentiated carcinomas are rare tumors of the head and neck region, defined by WHO as an undifferentiated carcinoma of the sinonasal tract without glandular and squamous features and not otherwise classifiable.^[1] It is usually a diagnosis of exclusion. SWItch/Sucrose Non-Fermentable [SWI/SNF] -related matrix-associated actin-dependent regulator of chromatin [SMARC] subfamily B member 1 (SMARCB1) deficient sinonasal carcinoma is a comparatively newly recognized subset of sinonasal undifferentiated carcinoma. Morphologically they appear as poorly differentiated carcinoma with plasmacytoid/rhabdoid morphology with brisk mitotic activity, apoptosis, and necrosis. Although it is a difficult task to classify them correctly, correct diagnosis is essential for understanding the clinical behavior of this group of carcinomas and for research on better treatment options for individual patients and to assess the prognosis. SMARCB1(INI 1) deficient sinonasal carcinomas were first reported in 2014 by Agaimy et al.^[2] and Bishop et al. independently in two separate case report.[6]

Case Report

Our patient was a 63-year-old man who was evaluated at another center for complaints of nasal stuffiness of three months duration. Computed tomography (CT) scan revealed a polypoidal soft tissue lesion in the right maxillary sinus extending to the right nasal cavity and sphenoethmoidal sinus. He underwent Functional endoscopic sinus surgery (FESS) and histopathology was reported as non-keratinizing nasopharyngeal carcinoma. He was then referred to our center for further management. He had the residual disease in the sphenoethmoidal recess when he presented to us. He opted for radiotherapy. He completed radiotherapy and the primary site responded well with no residual disease on clinical and radiological evaluation. While on follow-up, after four months, he noticed a left sided preauricular swelling and another swelling at the left upper cervical region. CT imaging revealed it as a nodal mass about 5 × 2.5 cm at left level II with an enlarged left intraparotid node of size 2.4 × 2.2 cm. [Figure 1]a Fine needle aspiration of the preauricular swelling was done and was reported as a metastasis from a poorly differentiated carcinoma. He then underwent left semiconservative parotidectomy with left modified radical neck dissection.

Figure 1: (a) CT image showing left level II nodal mass, (b) Nodal mass in the neck dissection specimen showing a lobulated neoplasm. (c) Neoplasm composed of neoplastic cells with round nucleus and prominent nucleoli, arranged in nests and sheets (H&E × 200), (d) Cells with rhabdoid morphology (H&E × 400)

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Gross examination of the parotidectomy specimen revealed a well-circumscribed light brown fleshy intra-parotid node measuring 2.1 × 2 × 1.3 cm. The neck dissection specimen showed 31 lymph nodes, largest measuring 5 × 3.5 cm showing replacement by a fleshy lobulated mass [Figure 1]b.

Microscopy showed lymph nodes with metastasis from a neoplasm composed of cells arranged in nests and loosely cohesive sheets. Cells were medium-sized with a variable amount of cytoplasm, round nucleus with prominent nucleoli [Figure 1]c. Many large cells with rhabdoid morphology were seen [Figure 1]d. Mitotic count was in the range of 1 to 2 per high power field. No extra-nodal extension was seen. In the neck node dissection specimen, 2 out of –31 lymph nodes showed metastasis from the above neoplasm. Considering the sinonasal location of the primary tumor, the rhabdoid morphology of cells, we had a differential of SMARCBI deficient sinonasal carcinoma. The clinical presentation was also unusual, in that it was not usual for a nasopharyngeal carcinoma to present with recurrence within 4 months of completion of treatment. We put a panel of immunomarkers covering nasopharyngeal carcinoma and SMARCB1 deficient carcinoma.

Immunohistochemistry demonstrated strong positivity for cytokeratin and loss of INI1(SMARCB1) expression in the tumor cells, p63, and Epstein Barr virus encoded RNA (EBER) were negative, ruling out nasopharyngeal carcinoma. [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d Desmin was done because of the prominent rhabdoid morphology, however, it was negative. The previous biopsy from the outside center was reviewed and immunostaining was performed showing loss of expression of SMARCB1. Correlating morphology and immunoprofile, the diagnosis was given as metastasis from SMARCB1 deficient sinonasal carcinoma.

Figure 2: (a) Neoplastic cells showing strong positivity for cytokeratin (IHC × 200), (b) Loss of INI1(SMARCB1) expression by tumor cells with retained expression by lymphocytes (IHC × 200) (c) negative staining for p63(IHC × 200), (d) negative staining for EBER (IHC × 200)

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Discussion

The SMARCB1 protein is believed to prevent the rapid proliferation of cells by acting as a tumor suppressor. Loss of expression of SMARCB1 has been documented in several malignancies like atypical teratoid/rhabdoid tumor of the central nervous system, rhabdoid tumors of kidneys and soft tissues, medullary carcinoma of kidney, epithelioid malignant peripheral nerve sheath tumor, extraskeletal myxoid chondrosarcoma, epithelioid sarcoma, atypical chordoma, and myoepithelial carcinoma.^[3]

SMARCB1 deficient sinonasal carcinoma is a subset of undifferentiated carcinoma, classically presenting with a rhabdoid morphology in histopathology. It is also characterized by loss of expression of SMARCB1 (INI1) in immunohistochemistry. This entity can be frequently misdiagnosed in biopsy as non-keratinizing squamous cell carcinoma or as poorly differentiated carcinoma without further categorization. Much of the data regarding this entity is obtained from recently published literature. It was first described in 2014 by Agaimy et al.^[2] in a series of three cases and Bishop et al. in a report of nine cases.^[4],[5]

Agaimy et al.^[4] have described two distinct histomorphological appearances of this tumor. It can appear either as a basaloid looking or “blue cell” tumor, wherein it resembles nonkeratinizing SCC or SNUC, or as a “pink cell tumor “comprising of nests and sheets of predominantly plasmacytoid/rhabdoid cells. However even in typically basaloid appearing tumors singly dispersed rhabdoid/plasmacytoid cells could be identified by a thorough search. He has also described squamoid, spindle cell, sarcomatoid, adenoid variants, and the presence of focal clear cell features and non-specific empty vacuoles within the cells. Another study by Ayyanar et al.^[5] have described the presence of larger tumor cells having a moderate amount of eosinophilic cytoplasm, small cell carcinoma-like pattern, focal pseudo-alveolar pattern, perivascular pseudo-rosettes, and comedo-pattern of necrosis. Our case had nests and sheets of poorly differentiated cells along with many singly dispersed and sheets of rhabdoid/plasmacytoid cells with abundant eosinophilic cytoplasm and eccentrically placed nucleus. SMARCB1 deficient sinonasal carcinomas are characterized by loss of nuclear expression for SMARCB1(INI1). It consistently shows the positive expression for cytokeratin and variable immunoreactivity for p63, p40, and CK5/6. Focal positivity for S100, vimentin, and neuroendocrine markers chromogranin and synaptophysin may be seen. CK7, actin, EBER, and NUT are negative.^[6] Though SMARCB1-deficient sinonasal carcinoma usually resembles sinonasal undifferentiated carcinoma, sometimes glandular differentiation with the expression of markers like SALL4 and HepPar-1 has been reported, particularly in the oncocytoid/plasmacytoid form. This morphology and immunoprofile can be misleading and can lead to erroneous diagnoses of high-grade intestinal or non-intestinal sinonasal adenocarcinoma, myoepithelial carcinoma, or even yolk sac tumor or metastatic hepatocellular carcinoma.^[7]

SMARCB1 deficient sinonasal carcinomas are tumors with a poor prognosis. It occurs in a age range of 19 to 89 years with a slight predilection for males.^[8] Most tumors are diagnosed at an advanced stage with an average mortality rate of 45.3% and a median (range) overall survival of 22 (12–44) months.^[9] Treatment of SMARCB1 deficient sinonasal carcinoma is mainly through surgical excision followed by chemoradiation.^[10] Wasserman et al. reported a good response to cisplatin-based neo-adjuvant chemotherapy with a significant reduction in tumor bulk, but it has not been proved effective in preventing metastasis.^[10] Two specific enhancer of zeste homolog 2 (EZH2) inhibitors, EI1 and EPZ-6438, have shown promise in treating SMARCB1-deficient tumors.^[11] However further studies are needed to investigate the efficacy of this therapy.

Conclusion

SMARCB1 deficient sinonasal carcinomas are rare tumors with a poor prognosis. The presence of plasmacytoid/rhabdoid cells in an undifferentiated tumor of the sinonasal region wherein categorization into any specific entity is difficult should always raise suspicion of this entity. Loss of nuclear expression of SMARCBI (INI1) is the defining feature and is essential for diagnosis. Because of the rarity of this entity, there are not much data available in the literature. Hence, it is necessary to correctly identify this entity as more data and research is needed to establish the clinical and pathological features and to optimize the treatment options. Our patient is on follow-up and the follow-up period has been so far uneventful till the last follow-up on January 2022.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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