CPC08 Cutaneous squamous cell carcinoma and MYH9-associated elastin aggregation (MALTA) syndrome

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Abstract MYH9-associated elastin aggregation (MALTA) syndrome is a rare, inherited, irregular elastin aggregation and sweat duct proliferation syndrome caused by pathogenic variants in MYH9. MALTA syndrome was proposed in 2019, unifying Nicolau Balus and Rombo syndromes as phenotypes arising from pathogenic variants in the same gene, but it has not been associated with cutaneous squamous cell carcinoma (cSCC) [Fewings E, Ziemer M, Hörtnagel K et al. Malta (MYH9 associated elastin aggregation) syndrome: germline variants in MYH9 cause rare sweat duct proliferations and irregular elastin aggregations. J Invest Dermatol 2019; 139:2238–41]. Here, we report the clinical features of a family with a novel MYH9 c.1952A>C p.(Lys651Thr) pathogenic variant, providing evidence that cSCC may be an associated feature of MALTA syndrome. A 57-year-old woman presented with a longstanding skin lesion overlying her left infraorbital ridge, which had been present for 13 years. Lesion biopsy revealed a highly infiltrative tumour within the dermis that was composed of keratocysts with small islands of basaloid cells; immunostaining was positive for CK5/6, CK7, CK19, p63 and BerEP4. These histological features were consistent with a microcystic adnexal carcinoma (MAC)-like ductal proliferation, recognized in MALTA. In addition, she had previously developed one cSCC on her left shoulder and two basal cell carcinomas and had cutaneous milia. Her sister had a history of MAC-like ductal proliferation and cSCC, and her brother had two keratoacanthoma-like cSCCs. The copresentation of MAC-like ductal proliferations and early-onset cSCC in this family prompted targeted genetic testing of MYH9. This identified a heterozygous pathogenic variant in a highly conserved region of MYH9 [c.1952A>C p.(Lys651Thr)] that segregated with the phenotype in all three affected members. MYH9 has previously been identified as an important gene in the pathogenesis of cSCC in a genetic screen in transgenic mice, and our family adds novel clinical data, underscoring its importance in cSCC development (Schramek D, Sendoel A, Segal JP et al. Direct in vivo RNAi screen unveils myosin IIa as a tumor suppressor of squamous cell carcinomas. Science 2014; 343:309–13). Based on the recurrent presentation of early-onset cSCC in three members of this family, we propose the inclusion of cSCC in MALTA syndrome. This has implications for skin cancer surveillance of MYH9 pathogenic variant carriers, and the need to consider MALTA syndrome in patients presenting with multiple early-onset cSCC.