White sponge nevus (WSN) is a rare autosomal dominant disorder characterized by a widespread white, soft, thick plaques with a spongy texture, and it predominantly affects on the oral mucosa. The diagnosis of WSN is performed by clinical findings and histologic features. Recent reports have identified point mutations in the keratin 4 and keratin 13 genes in familial cases. Non-familial or sporadic cases have been also known.  In the previous study, tonofilament aggregation has been reported to be a characteristic ultrastructural finding in WSN. Most of the reports are a single case study. 
To clarify the pathogenetic mechanisms of familial and non-familial WSN, we analyzed 10 patients with WSN (including two familial and eight non-familial cases) by electron microscopic study. 
Ultrastructurally, one familial case showed aggregation of the tonofilaments at the perinuclear areas and the other familial case of WSN demonstrated numerous tonofilament-related keratohyaline granules in the vacuolated keratinocytes. In non-familial cases, one showed also increased electron density due to aggregation of the tonofilaments in the cytoplasm but other seven cases demonstrated no tonofilament aggregation. The previous studies suggested that a dense aggregation of tonofilaments was a cardinal feature in WSN. However, only two cases showed dense aggregation of tonofilaments and other patients with familial and non-familial WSN demonstrated the sparse distribution of tonofilaments with few tonofilament bundles in the vacuolated cells. We suggest that impaired tonofilament bundle formation with sparse tonofilament distribution is a common significant finding in both types of WSN. Accordingly, dense tonofilaments aggregation described in the previous literature is not necessarily for the diagnosis of WSN.  WSN might be caused by heterogeneous pathogenetic factors. The comparative study of ultrastructure and keratin mutation is needed to clarify the pathogenetic mechanisms of WSN

An ultrastructural study of familial type and non-familial type of white sponge nevus