An Evolving and Rare Entity: SMARCB1(INI-1)-Deficient Sinonasal Carcinoma

Öz

Malignant tumors of the paranasal sinuses and nasal cavity are rare. These tumors constitute very few of all head and neck tumors. With the developments in the field of molecular biotechnology, significant revisions have been made in The 2022 5th edition of the WHO Classification of the Head and Neck. Tumors with the definition of new entities. SWItch/Sucrose Non-Fermentable (SWI/SNF) complex-deficient carcinomas, which have been included as a separate entity under the general heading of sinonasal undifferentiated carcinomas, consist of two major subtypes caused by the loss of one of the SWI/SNF complex genes; SMARCB1-deficient sinonasal carcinoma and SMARCA4-deficient sinonasal carcinoma. The most common subtype is SMARCB1-deficient sinonasal carcinoma. These tumors have been misdiagnosed as neuroendocrine carcinoma, poorly differentiated carcinoma, sinonasal undifferentiated carcinoma and teratocarcinoma in previous years according to our current knowledge. Histopathologically, uniform cytologic features and appearance mimicking many tumors make it difficult to diagnose especially in small biopsies. Correctly naming this high-grade malignancy within the scope of molecular classification is important for treatment planning. Optimal treatment approaches are also limited. Although there is a consensus on radical resection/surgery followed by adjuvant treatment, the order of treatment may vary between institutions. Agents such as immune checkpoint inhibitors and EZH2 inhibitors are among the new treatment options. In this report, we present a case of SMARCB1-deficient sinonasal carcinoma according to the new molecular classification with recurrence at the age of 20. We aimed to emphasize the importance of histopathological and immunohistochemical findings and to raise awareness of the presence of this entity.

Anahtar Kelimeler

• Sinonasal carcinoma
• SMARCB1
• INI-1
• SMARCB1 (INI-1) deficient
• sinonasal undifferentiated carcinoma

SMARCB1 (INI-1) Eksikliği olan Sinonazal Karsinom

Öz

Paranazal sinüsler ve nazal kavitenin malign tümörleri nadirdir. Tüm baş-boyun tümörlerinin çok azını oluşturur. Moleküler biyoteknoloji alanındaki gelişmeler ile Dünya Sağlık Örgütü Baş ve Boyun Tümörleri 2022 yılı 5.baskısında yeni antitelerin tanımlanması ile önemli değişiklikler yapılmıştır. Sinonazal indiferansiye karsinomlar genel başlığı altında ayrı bir antite olarak yerini alan SWItch/Sucrose Non-Fermentable (SWI/SNF) kompleksi eksikliği olan karsinomlar SWI/SNF kompleks genlerinin birinin kaybı ile oluşan iki majör subtipten oluşmaktadır; SMARCB1-eksikliği olan sinonazal karsinom ve SMARCA4-eksikliği olan sinonazal karsinom. En yaygın subtip SMARCB1- eksikliği olan sinonazal karsinomdur. Bu tümörler önceki yıllarda nöroendokrin karsinom, kötü diferansiye karsinom, sinonazal indiferansiye karsinom, teratokarsinom gibi bugünkü bilgilerimize göre yanlış tanılar almıştır. Histopatolojik olarak uniform sitolojik özellikler ve birçok tümörü taklit eden görünüm özellikle küçük biyopsilerde tanı koymayı güçleştirmektedir. Yüksek dereceli olan bu maligniteyi moleküler sınıflama kapsamında doğru olarak isimlendirmek tedavi planlaması açısından önemlidir. Optimal tedavi yaklaşımları da sınırlıdır. Radikal rezeksiyon/cerrahi ve sonrasında adjuvan tedavi konusunda fikirbirliği olsa da tedavinin sırası kurumlar arasında değişebilmektedir. İmmun kontrol noktası inhibitörleri ve EZH2 inhibitörü gibi ajanlar da yeni tedavi seçenekleri arasındadır. Bu sunumda 20 yaşında nüks ile seyreden yeni moleküler sınıflamaya göre “SMARCB1- eksikliği olan sinonazaal karsinom” olgusu ile histopatolojik ve immunohistokimyasal bulguların önemini vurgulamak ve bu antitenin varlığının farkındalığını artırmak istedik.

Anahtar Kelimeler

• Sinonasal carcinoma
• SMARCB1
• INI-1
• SMARCB1 (INI-1) deficient
• sinonasal undifferentiated carcinoma

Kaynakça

1. 1. Contrera KJ, Woody NM, Rahman M, Sindwani R, Burkey BB. Clinical management of emerging sinonasal malignancies. Head Neck. 2020;42(8):2202-2212.
2. 2. Thompson LDR, Franchi A. New tumor entities in the 4th edition of the World Health Organization classification of head and neck tumors: nasal cavity, paranasal sinuses and skull base. Virchows Arch. 2018;472(3):315-330.
3. 3. Thompson LDR, Bishop JA. Update from the 5th edition of the World Health Organization classification of head and neck tumors: nasal cavity, paranasal sinuses and skull base. Head Neck Pathol. 2022;16(1):1-18.
4. 4. Rooper LM, Uddin N, Gagan J, et al. Recurrent loss of SMARCA4 in sinonasal teratocarcinosarcoma. Am J Surg Pathol. 2020;44(10):1331-1339.
5. 5. Agaimy A, Jain D, Uddin N, Rooper LM, Bishop JA. SMARCA4-deficient sinonasal carcinoma: a series of 10 cases expanding the genetic spectrum of SWI/SNF-driven sinonasal malignancies. Am J Surg Pathol. 2020;44(5):703-710.
6. 6. Agaimy A, Koch M, Lell M, Semrau S, Dudek W, Wachter DL, et al. SMARCB1(INI1)-deficient sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms. Am J Surg Pathol. 2014;38(9):1274-1281.
7. 7. Bishop JA, Antonescu CR, Westra WH. SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract. Am J Surg Pathol. 2014;38(9):1282-1289.
8. 8. Parsel SM, Jawad BA, McCoul ED. SMARCB1-deficient sinonasal carcinoma: systematic review and case report. World Neurosurg. 2020;136:305-310.

9. 9. Agaimy A, Hartmann A, Antonescu CR, 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(4):458-471.
10. 10. Lee VH, Tsang RK, Lo AWI, et al. SMARCB1 (INI-1)-deficient sinonasal carcinoma: a systematic review and pooled analysis of treatment outcomes. Cancers (Basel). 2022;14(13):3285.
11. 11. Chung SY, Kenee P, Mitton T, Halderman A. SMARCB1(INI-1)-deficient sinonasal carcinoma: an evolving entity. J Neurol Surg Rep. 2023;84(1):e1-e5.
12. 12. Zhang L, Gao AX, He YL, Xu MJ, Lu HJ. Immunotherapy in SMARCB1 (INI-1)-deficient sinonasal carcinoma: two case reports. World J Clin Cases. 2023;11(32):7911-7919.
13. 13. Agaimy A. Proceedings of the North American Society of Head and Neck Pathology, Los Angeles, CA, March 20, 2022: SWI/SNF-deficient sinonasal neoplasms: an overview. Head Neck Pathol. 2022;16(1):168-178.
14. 14. Lee VHF. Induction chemotherapy and tazemetostat for locally advanced SMARCB1-deficient sinonasal carcinoma. Available online: https://clinicaltrials.gov/ct2/show/NCT05151588. Accessed May 15, 2022.