Crystal-storing histiocytosis (CSH) is a rare condition that results from crystals accumulating in the cytoplasm of macrophages. Most cases were associated with lymphoplasmacytic neoplasm [1]. Lymphoplasmacytic neoplasm with CSH is extremely rare. The probability of occurrence is less than 1/10000. The crystalline substance within the histiocytes is often associated with Ig kappa light chain [2], [3], [4]. Diagnosis of this disorder is challenging. CSH first manifested in the skin is even rarer, and only eight cases have been reported in the literature by far [1], [5], [6], [7], [8], [9], [10]. Some studies hypothesized that immunoglobulins would contribute to the pathogenic elements by abnormal production, impaired excretion, or a conformational alteration due to abnormal amino acid sequences [2]. At present, there is no conclusive evidence about its pathogenic mechanism and potential gene change in CSH. The reason why it happened is still a mystery.

Werner helicase (WRN, RECQL2; NM 000553GRCh38.p7) located on 8p12, spans approximately 150 kb, including 35 exons. It encodes a 1432 amino-acid multifunctional nuclear protein [11]. WRN protein is a member of the RecQ subfamily of DNA helicase proteins. It is important in the maintenance of genome stability and plays a role in DNA metabolism, including DNA repair, recombination, replication, transcription, and telomere maintenance [12], [13]. In WRN, a total of 83 different pathogenic variants have been discovered. 29 minor indels, 23 splicing mutations, 23 nonsense, three genomic rearrangements, and five missense variants have been documented. Numerous studies have shown a high degree of the helicase activity of WRN for the unwinding of unusual DNA structures [11]. The WRN gene mutation is the cause of Werner syndrome (WS). WS is an autosomal recessive disorder of premature aging characterized by short stature, alopecia, cataracts, and progressive subcutaneous atrophy [14], [15], [16]. c.3139–1 G>C mutation of WRN is the most frequent (70.7 %) mutation of WS in Japanese.

In this study, we describe a case of CSH of multiple myeloma in the skin of a 65-year-old man. It was difficult and challenging about the diagnosis. More specifically, we first showed a gross deletion (c.1316_1653–468del) including exon10-intron13 in WRN in our patient. A gross deletion must affect the level of WRN. Given the important functions that WRN plays in DNA metabolism, we hypothesize that WRN mutation would be a critical factor in the pathogenic mechanism of CSH.