Sporadic white sponge nevus caused by a mutation in the keratin 4 gene

Abstract

Herein, we present a sporadic case of white sponge nevus (WSN) on the cheek mucosa in a 27-year-old Japanese man. A definite diagnosis of WSN was obtained using the typical clinical appearance and microscopic features of the lesions. Histopathological and cytological studies should be conducted to differentiate this condition from other oral premalignant white lesions. A molecular mutation analysis revealed a missense mutation in exon 1A of the keratin 4 gene, which is correlated with the development of WSN. Hence, genetic analysis must be performed to obtain an accurate diagnosis in sporadic cases. The temporary regression of the lesion after treatment with oral amoxicillin hydrate (AMPC) 750 mg/day indicates that antibiotics are effective in symptomatic cases.

Highlights

  • White sponge nevus is a rare genetic disorder.

  • We report a sporadic case of white sponge nevus on the cheek mucosa.

  • The lesion disappeared temporarily after treatment with oral amoxicillin hydrate.

  • Mutation analysis revealed a missense mutation in exon 1A of the keratin 4 gene.

Introduction

White sponge nevus (WSN) is an inherited autosomal dominant disorder of the nonkeratinized oral mucosa. The condition is caused by defects in normal keratinization due to mutations in either the keratin type 4 (KRT4) or 13 (KRT13) gen [ ]. Moreover, it is clinically characterized by the presence of white plaques in the tissues, which is referred to as nevus. These plaques appear predominantly as thick, velvety, spongy-like tissues on the bilateral cheek mucosa. The exact prevalence is not known. However, it affects less than 1 in 200,000 individuals worldwide without racial and gender predilection [ , ].

WSN is not commonly treated because the condition is benign without any potential risk for malignant transformation [ ]. Therefore, an accurate diagnosis of the condition is important to prevent unnecessary treatments. Serious white lesions such as oral potentially malignant disorders (OPMDs), including leukoplakia and oral lichen planus (OLP), should be initially considered in the differential diagnosis with histopathological examination [ ].

Herein, we present a sporadic (non-familial) case of WSN in a Japanese young adult. Moreover, the results of mutation analysis and response to antibiotic treatment were discussed.

Presentation of case

A 27-year-old Japanese man with a chief complaint of painless white plaques on the cheek mucosa was referred to our clinic. He first noticed the altered texture of the mucosa about 1 year back. He was a non-smoker and had no habit of chewing the cheek mucosa. Oral examination revealed white, thick, velvety plaques on the overall bilateral cheek mucosa ( Fig. 1 ). No other sites in the oral cavity were affected. The white lesion did not disappear upon stretching the affected mucosa. However, the surface of the plaque could be slightly removed from the underlying tissue by gentle rubbing, and bleeding was not observed. The patient had no similar lesions elsewhere on the body based on the examination conducted by a medical doctor. A history review revealed no similar lesions in other immediate family members including the parents, two older sisters, and a three-year-old nephew.

Fig. 1
Intraoral image showing white, velvety plaques on the overall surface of the bilateral cheek mucosa.

Exfoliative cytology with Papanicolaou staining showed a unique perinuclear eosinophilic condensation in the surface of the epithelial cells ( Fig. 2 ). Biopsy and histopathological examination revealed hyperplastic keratinized squamous epithelium with prominent hyperparakeratosis and marked acanthosis ( Fig. 3 A) and extensive vacuolation with perinuclear eosinophilic condensation of the spinous cells ( Fig. 3 B). There was no evidence of epithelial dysplasia, basal cell degeneration, and subepithelial lymphocyte infiltration. The white oral lesion was diagnosed as WSN.

Fig. 2
Photomicrograph of exfoliative cytology (with Papanicolaou staining) showing epithelial cells with perinuclear eosinophilic condensation.

Fig. 3
Photomicrograph of the microscopic specimen (hematoxylin and eosin staining) showing prominent hyperparakeratosis and acanthosis (A, low power), and vacuolation and perinuclear eosinophilic condensation of the spinous cells (B, high power).

Since there were no clinical complaints, the patient did not take any medications at our clinic. However, after 2 months, he visited our clinic again and reported that the white lesions had almost completely disappeared 3 days after treatment with oral antibiotics and amoxicillin hydrate (AMPC) 750 mg/day for 7 days. The medications were prescribed by a medical doctor for acute tonsillitis ( Fig. 4 A and B). The white lesions had gradually returned to the original condition after treatment completion, and no clinical regression was observed during a follow-up period of 2 years.

Fig. 4
Intra oral image showing the disappearance of white plaques on the bilateral cheek mucosa (A: right cheek mucosa, B: left cheek mucosa) after treatment with oral amoxicillin hydrate.

Ethical approval and informed consent: The Medical Ethics Committee of Sanmu Medical Center and Chiba University Graduate School of Medicine approved the gene mutation analysis. A written informed consent was obtained from the patient and healthy individuals.

A gene mutation analysis was performed to identify the causative mutation in keratins, which is correlated with WSN. RNA samples were obtained from a biopsy formalin-fixed paraffin-embedded (FFPE) sample. Normal control DNA samples were collected from the venous blood of healthy donors. Total RNA was isolated from the tissue sections of the FFPE samples. Genomic DNA was isolated from peripheral blood lymphocytes. cDNA was generated using total RNA, and DNA samples were amplified at the segments of the KRT4 and KRT13 genes using the polymerase chain reaction (PCR) method. The PCR product was electrophoresed on 3% agarose gel and was visualized by staining with ethidium bromide. Then, the PCR products were subcloned using a Zero Blunt TOPO PCR Cloning Kit (Invitrogen, Carlsbad, CA, the USA). Plasmid DNAs were confirmed using the DNA sequencer (ABI PRISM 377, PerkinElmer Life Sciences, North Billerica, MA, the USA) of the entire product in both directions. We identified a heterozygous missense mutation at 254 (T <SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='→’>

A) in exon 1 of the KRT4 gene collected from the PCR product of the affected patient. This mutation can change codon 95 of the KRT4 coding sequence from phenylalanine (F) to tyrosine (Y) ( Fig. 5 ). No mutation was found in the KRT13 gene. Moreover, the normal controls did not present with any mutation.

Mar 21, 2021 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Sporadic white sponge nevus caused by a mutation in the keratin 4 gene
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