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. 2023 Jan 23;10(2):154.
doi: 10.3390/bioengineering10020154.

Exfoliative Cytology and Genetic Analysis for a Non-Invasive Approach to the Diagnosis of White Sponge Nevus: Case Series

Carlo Lajolo  1 , Concetta Cafiero  2 , Egidio Stigliano  3 , Francesca Romana Grippaudo  4 , Pietro Chiurazzi  5 , Cristina Grippaudo  1
Affiliations

Exfoliative Cytology and Genetic Analysis for a Non-Invasive Approach to the Diagnosis of White Sponge Nevus: Case Series

Carlo Lajolo et al. Bioengineering (Basel). .

Abstract

Background: White Sponge Nevus (WSN) is a rare benign disorder associated with mutations in genes coding for cytokeratin 4 (KRT4) and 13 (KRT13) characterized by dyskeratotic hyperplasia of mucous membranes. This study was aimed at examining different approaches (cytology, pathology and genetic analysis) to WSN diagnosis.

Methods: A series of four patients with asymptomatic white diffuse oral lesions were evaluated and, before performing an incisional biopsy for pathology, an oral brush Thin Prep was collected for exfoliative liquid-based cytology (LBC). DNA for genetic analysis was also obtained from patients and both their parents, using buccal swabs.

Results: Pathology and cytology showed similar results, leading to the same diagnosis of hyperkeratotic epithelium with acanthosis and spongiosis, without atypia, demonstrating the efficiency of LBC for the differential diagnosis. Sequencing analysis revealed at least 6 rare variants in the KRT4 and KRT13 genes in each patient, contributed in part by both unaffected parents.

Conclusions: Thin Prep for oral exfoliative cytology and genetic analysis are sufficient for an accurate diagnosis of WSN. The combination of cytological and genetic analyses could substitute the histologic exam, providing a non-invasive alternative for incisional biopsy.

Keywords: Cell Block; KRT13; KRT4; White Sponge Nevus (WSN); incisional biopsy; liquid-based cytology.

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Conflict of interest statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Figures

Figure 1
Figure 1
Clinical appearance of the same patient (right cheek (A), left cheek (B), right tongue (C), left tongue (D) with White Sponge Nevus: the mucosa appears bilaterally whitish, thickened and spongy texture.
Figure 2
Figure 2
(A)—Histological analysis of paraffin-embedded section from oral biopsy shows the presence of edema and acanthosis (H&E 4×); the lower half of the epithelium appears normal. No evidence of dysplasia and no basal cell degeneration. At higher magnification (in the lower box), cells of the prickle cell (spinous) layer displayed marked intracellular edema and nuclear pyknosis (H&E 40×). (B)—Overexpression of KRT13 was observed in the same sample (CK13 immunohistochemistry 4× and 40× in the lower box).
Figure 3
Figure 3
(A)—Liquid based cytology from cytobrush with Papanicolaou staining shows scattered cells with no nuclear atypia and no relevant morphological alteration (Cytobrush 4×); (B)—Positive immunohistochemical staining for KRT13 (Cytobrush 10×); (C)—Positive immunohistochemical staining for KRT13 (Cytobrush 20×); (D)—Cell Block shows higher number of cells and aggregates of dyskeratotic keratinocytes from the spinous layer cells and from corneous layer (Cell Block—H&E 10× and 60× in the higher magnification detail); (E)—Positive immunohistochemical staining for KRT13 (Cell Block-40×); (F)—Positive immunohistochemical staining for KRT4 (Cell Block-20×).
Figure 4
Figure 4
Proposed diagnostic workflow for White Spongeous lesions of the oral cavity.
See this image and copyright information in PMC

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