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. 2021 May 31;15(4):1235–1245. doi: 10.1007/s12105-021-01333-5

Gingival Leukoplakia: Hyperkeratosis with Epithelial Atrophy Is A Frequent Histopathologic Finding

Lama Alabdulaaly 1,2,3,✉, Asma Almazyad 2,3, Sook-Bin Woo 1,4,5
PMCID: PMC8633201  PMID: 34057694

Abstract

White lesions on the gingiva and palatal mucosa may represent reactive keratoses, including specific diseases such as benign alveolar ridge keratosis, or nonreactive keratoses, such as true leukoplakia, the latter being associated with a high recurrence rate at this site. The aim of this study is to determine the histopathologic features of gingival keratoses. Hyperkeratotic lesions from the gingiva, palatal mucosa, and alveolar ridge mucosa were available for evaluation after excluding specific keratotic lesions such as candidiasis. There were 321 biopsies from 296 patients and approximately half of the cases (159/321, 49.5%) were reactive keratoses. The rest of the 162 biopsies from 149 patients (76 females; 51.0%) represented true leukoaplakias. The most common location was the gingiva (73.2%) followed by the palatal mucosa (17.0%). Hyperkeratosis/parakeratosis not reactive (HkNR) represented 43.8% of cases; 45.7% were dysplasia or carcinoma, and the rest were not readily classifiable as reactive or non-reactive keratoses. Histopathologic features commonly noted in the HkNR lesions include sharp demarcation (72.7%), corrugated surface (53.5%), and epithelial atrophy (48.1%). A lymphocytic band was noted in 8.5% of the cases, mostly associated with epithelial atrophy (5/6 cases). Seven patients with 17 biopsies from noncontiguous sites likely had proliferative leukoplakia; the most common location was the gingiva (88.2%) and the most common diagnosis was HkNR (52.9%). HkNR is a common histopathologic diagnosis for leukoplakias on the gingiva, and these lesions frequently exhibit thick hyperkeratosis, epithelial atrophy and a lymphocytic band at the interface.

Keywords: Gingiva, Leukoplakia, Oral, Atrophy, Recurrence, Keratosis

Introduction

Oral leukoplakia is defined as a “predominantly white plaque of questionable risk, having excluded (other) known diseases or disorders that carry no increased risk for cancer” [1]. It is the most common oral precancerous lesion and by definition, oral leukoplakia excludes white lesions such as frictional keratoses, namely, benign alveolar ridge keratosis (BARK) [2, 3], morsicatio mucosa oris, and other specific diagnoses such as leukoedema, oral hairy leukoplakia, and candidiasis to name a few [4].

The most common sites for oral leukoplakia are the tongue (36–50%), buccal mucosa (18–26%), floor of mouth (8–22%), gingiva (6–22%), and hard palatal mucosa (7%) [5–7]. The spectrum of histopathologic diagnoses of oral leukoplakia includes oral epithelial dysplasia (OED), atypical verrucous hyperplasia, squamous cell carcinoma, and the so-called ‘simple’ or ‘benign’ hyperkeratosis (Hk) that lacks features of dysplasia as defined by the World Health Organization (WHO) [1, 8]. Oral epithelial dysplasia is present in 15–79% [6, 7, 9–15] of all leukoplakias and the malignant transformation rate of oral leukoplakia ranges from 6 to 24% [1]. Common sites for malignant transformation are the tongue, buccal mucosa, gingiva, and floor of mouth [5–7, 10–12, 16], and 4–20% of gingival leukoplakias undergo malignant transformation [5, 10]. Importantly, even leukoplakias without dysplasia exhibit malignant transformation in 3–11% of the cases [6, 7, 10, 14, 17, 18].

Although the gingiva is not the most common site for leukoplakia, it is a site with a high recurrence rate of 42–53% [13, 18, 19]. Furthermore, atypical verrucous hyperplasia occurs most commonly on the gingiva [9]. This is characterized by marked papillary or verruciform architecture with or without OED and has a high association with malignant transformation [20]. More recently, other architectural features of OED have been proposed besides papillary/verrucous morphology and these include Hk with epithelial atrophy, bulky squamous proliferation, and demarcated Hk with or without “skip segments” [4, 8].

Proliferative leukoplakia is a form of leukoplakia characterized by multi-focal leukoplakias that are relentless in their progression, with a malignant transformation rate that ranges between 29 and 90% depending on the length of follow-up [21]. The gingiva is affected in 61–87% of cases of proliferative leukoplakia and is the most common location for malignant transformation [21–23].

The aim of this study is to analyze the histopathologic features of gingival, palatal and alveolar ridge keratoses and to further define keratotic lesions that lack features of dysplasia.

Materials and Methods

The database of StrataDx, a surgical pathology laboratory affiliated with Harvard School of Dental Medicine was queried for all cases with a clinical diagnosis of “hyperkeratosis” or “leukoplakia” from January 1st, 2017 to December 31st, 2017 that occurred on the gingiva, palatal mucosa, alveolar mucosa, or retromolar pad. Patients’ demographics, lesion description, and clinical diagnoses were obtained from the requisition forms. Lichen planus, candidiasis and cases with poor orientation or major artifacts that precluded optimal evaluation were excluded.

Histopathologic Diagnosis

The histopathological slides were reviewed by two board-certified oral and maxillofacial pathologists (A.A. and S.W.). Reactive cases that met the criteria for BARK [2, 3, 24], namely corrugated hyperkeratosis, wedge-shaped hypergranulosis, mild acanthosis, and tapered and confluent rete ridges, were diagnosed as such (Fig. 1). Cases which did not meet the BARK criteria but had reactive features [25], namely hyper(ortho)keratosis (Hk)/parakeratosis (Pk) and acanthosis with or without inflammation, were diagnosed as “Hk/Pk and acanthosis, reactive” [20, 26]. Thirty-eight BARK cases were previously published in Almazyad et al. [3]. The remaining cases that were not reactive were then evaluated for the presence of squamous cell carcinoma, atypical verrucous hyperplasia which is now widely accepted as a dysplastic lesion [20], and OED by WHO criteria [1]. The rest of the non-reactive non-dysplastic cases were then evaluated by the architectural criteria of corrugated/verrucous/papillary morphology, Hk with epithelial atrophy (less than 15 cells thick), demarcated keratosis with skip segments, and atypical bulky squamous proliferation [4, 8, 27]. These were broadly designated as “Hk/Pk not reactive (HkNR)” (Fig. 1).

Fig. 1.

Fig. 1

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Histopathologic diagnosis flowchart. *WHO criteria

Descriptive and inferential statistics were calculated using JMP Pro 15 software (SAS Institute Inc.). Pearson correlation was used to assess the difference in histopathologic features of HkNR compared to Hk/Pk of uncertain etiology (HkUNC) cases. A p-value of less than 0.05 was considered significant. Graphs were generated using GraphPad Prism version 8 software (La Jolla, CA, USA). Figures 1 and 9 were created with BioRender.com.

Fig. 9.

Fig. 9

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a Excision of gingival leukoplakia involving the crevicular epithelium. b Residual leukoplakia in the crevicular epithelium (arrow). c Residual leukoplakia repopulates the gingiva resulting in recurrence (curved arrow)

Results

Prevalence of Reactive Keratoses and True Leukoplakia

There were 321 biopsies from 296 patients. Approximately half of the cases (159/321, 49.5%) were reactive and the remaining 162 cases (50.5%) were true leukoplakias. Of the 159 reactive cases, 67 were cases of classic BARK (Fig. 2a, b) and 92 were non-specific reactive keratoses (Fig. 2c, d). These were excluded since by definition, these are not leukoplakias because they are frictional/reactive in nature with no malignant transformation risk [3].

Fig. 2.

Fig. 2

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Benign alveolar ridge keratosis. a Hyperkeratosis with a corrugated surface and acanthosis. b Tapered rete ridges, no dysplasia and vertically oriented blood vessels. c Hyperkeratosis, acanthosis and vertically oriented blood vessels, non-specific reactive. d Tapered rete ridges without evidence of dysplasia

Demographic data and clinical characteristics of the 162 true leukoplakia cases from 149 patients are presented in Table 1. The median age was 71 (range 28–100) with an equal sex distribution. The most common location was the gingiva (73.2%), followed by the palatal mucosa (17.0%) and alveolar mucosa (7.2%). OED was noted in 32.1% of leukoplakias, atypical verrucous hyperplasia in 11.1% and squamous cell carcinoma in 2.5%, for a total of 45.7% of leukoplakias. The category of HkNR constituted 43.8% of leukoplakias. Hyperkeratoses that may or may not have been reactive constituted 10.5%; these were termed “Hk/Pk of uncertain etiology (HkUNC)”. Figure 3 shows the distribution of histopathologic diagnoses by site.

Table 1.

Demographics, clinical characteristics, and histopathologic diagnoses of true leukoplakia

N (%)
Number of patients 149
Number of biopsies 162
Sex
 Female 76 (51.0%)
 Male 73 (49.0%)
Age, median (range) 71 (28–100)
Anatomic site
 Gingiva 112 (73.2%)
 Palatal mucosa 26 (17.0%)
 Alveolar mucosa 11 (7.2%)
 Retromolar pad 4 (2.6%)
 NOS 9 (NA)
Histopathologic diagnosis
 HkNR 71 (43.8%)
  With atypia 7 (9.9%)
 OED 52 (32.1%)
  Mild 36 (69.2%)
  Moderate 15 (28.9%)
  Severe 1 (1.9%)
Atypical verrucous hyperplasia 18 (11.1%)
Squamous cell carcinoma 4 (2.5%)
HkUNC 17 (10.5%)
Total 162 (100%)
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HkNR Hk/Pk not reactive, HkUNC Hk/Pk of uncertain etiology, NOS site not specified (excluded from percentage calculation), OED oral epithelial dysplasia

Fig. 3.

Fig. 3

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The distribution of histologic diagnoses of all hyperkeratoses by site. AVH atypical verrucous hyperplasia, BARK benign alveolar ridge keratosis, HkNR hyperkeratosis not reactive, NSR non-specific reactive, OED oral epithelial dysplasia, HkUNC, hyperkeratosis uncertain, SCCa squamous cell carcinoma

Histopathologic Features of HkNR and HkUNC

The histopathologic features of HkNR and HkUNC are presented in Table 2. Histopathologic features that characterized HkNR were Hk (100%), with more than half (52.1%) of cases exhibiting an orthokeratin layer that was greater than half the thickness of the epithelium (Fig. 4b), correlating to the thick white plaques noted clinically. Sharp demarcation was observed in 72.7% of cases where margins were present (Fig. 4b) and surface corrugation was seen in 53.5% of HkNR cases (Fig. 4b). Skip segments were present in 8.5% of lesions, all associated with Hk, and not Pk. Epithelial atrophy was present in 48.1% of HkNR cases (Fig. 5) notable for absence of inflammation in the epithelium (such as spongiosis and leukocyte exocytosis) and variable inflammation in the lamina propria, sometimes in a form of a lymphocytic band (Fig. 6). Interestingly, of the 6 cases with a lymphocytic band, 5 exhibited epithelial atrophy. In contrast, these features were less prominent in cases of HkUNC (Fig. 7). They had more spongiosis and leukocyte exocytosis and more lesions were parakeratotic and acanthotic (Table 2). HkNR cases were more likely to have Hk greater than half the thickness of the epithelium and to exhibit epithelial atrophy than HkUNC cases (p < 0.05, Table 2). Based on the histopathology alone without clinical photographs, it was not possible to be certain if these HkUNC were reactive or not reactive.

Table 2.

Histopathologic features of HkNR and HkUNC

Histopathologic feature HkNR
N (%)		 HkUNC
N (%)		 p-value
Total number of cases 71 (100.0%) 17 (100.0%)
Hyper(ortho)keratosis 71 (100.0%) 15 (88.2%) 0.0035
 Hk greater than half the epithelial thickness 37 (52.1%) 2 (11.8%) 0.0039
Parakeratosis 10 (14.1%) 4 (23.5%) 0.3389
Sharp demarcation 24/33 (72.7%) 2/3 (67.7%) 0.8225
Skip lesions 6 (8.5%) 0 (0%) 0.2144
Corrugated surface 38 (53.5%) 6 (35.3%) 0.2047
Epithelial thickness 0.0005
 Usual 8 (10.1%) 3 (15.8%)
 Acanthosis 26 (32.9%) 10 (52.6%)
 Atrophy 38 (48.1%) 6 (31.6%)

 Acanthosis and

atrophy

 7 (8.9%) 0 (0.0%)
Spongiosis 5 (7.0%) 5 (29.0%) 0.0240
Leukocyte exocytosis 9 (12.7%) 5 (29.4%) 0.2334
Inflammation in the lamina propria 49 (69.0%) 10 (58.8%) 0.4220
 Mild 42 (85.7%) 7 (70.0%)
 Moderate 5 (10.2%) 1 (10.0%)
 Intense 0 (0%) 0 (0%)
Band infiltrate 6 (8.5%) 1 (5.9%%) 0.7252
 With atrophy 5 (83.3%) 0 (0%)
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Hk hyperkeratosis, HkNR Hk/Pk not reactive, HkUNC Hk/Pk of uncertain etiology

Fig. 4.

Fig. 4

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a Normal gingival epithelium that is usually 15–25 cells thick. b demarcated and corrugated hyperkeratosis with lack of cytologic features of dysplasia (inset)

Fig. 5.

Fig. 5

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a Demarcated leukoplakia on the left maxillary gingiva (Courtesy of Dr. Matthew Jackobson, South Portland, ME). b Photomicrograph from “a” showing hyperkeratosis with epithelial atrophy. c High power view minimal cytologic atypia

Fig. 6.

Fig. 6

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a Leukoplakia presenting as a demarcated and fissured white plaque on the gingiva (Courtesy of Dr. David Feinerman, Boynton Beach, FL). b Photomicrograph from a showing hyperkeratosis with epithelial atrophy and mild chronic inflammation without dysplasia, not reactive. c High power view of b showing focal basal cell degeneration with colloid body formation (arrows)

Fig. 7.

Fig. 7

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a Hyperkeratosis, acanthosis with a focal lymphocytic infiltrate, unclear if reactive. b High power view of a showing minimal cytologic atypia

Proliferative Leukoplakia

Patients who had more than one biopsy showing Hk with or without dysplasia, from noncontiguous sites were considered suspicious for having proliferative leukoplakia. Seven such patients were identified with a total of 17 biopsies (Table 3). There were 5 males (71.4%) and 2 females and the median age was 58 (range 39–84). Fifteen of the 17 biopsies were from the gingiva and two were from the palatal mucosa (Fig. 8). One patient had a third biopsy from the tongue that was not included in this study. The most common diagnosis was HkNR (n = 9, 52.9%) followed by OED (n = 6, 35.3%) and HkUNC (n = 2, 11.8%). Eleven biopsies (64.7%) had a corrugated surface, 9 (52.9%) showed epithelial atrophy, and 4 (23.5%) had a lymphocytic band at the interface.

Table 3.

Presumptive proliferative leukoplakia cases

No Age Sex Biopsy location Diagnosis Corrugated surface Epithelial atrophy Lymphocytic
1 51 M Gingiva, tooth # 18 Mild OED Yes No No
Gingiva, tooth # 32 Mild OED No Yes No
2 58 F Gingiva, right maxillary HkNR Yes No No
Gingiva, right palatal HkNR Yes Yes Yes
Gingiva, left maxillary HkNR No No Yes
Gingiva, left palatal HkNR Yes Yes Yes
Gingiva, left mandibular HkNR No Yes Yes
3 73 M Palatal mucosa, left HkUNC Yes No No
Palatal mucosa, right HkUNC Yes No No
4 65 M Gingiva, left maxillary Mild OED Yes No No
Gingiva, right mandibular Mild OED Yes No No
5 54 M Gingiva, tooth # 20 HkNR Yes Yes No
Gingiva, tooth # 27 HkNR No Yes No
6 39 M Gingiva, right mandibular HkNR Yes No No
Gingiva, left mandibular HkNR Yes Yes No
7 84 F Gingiva, teeth #s 4–5 Moderate OED No Yes No
Gingiva, teeth # 21–22 Mild OED No Yes No
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HK hyperkeratosis, HkNR Hk/PK not reactive, HkUNC Hk/Pk of uncertain etiology, OED oral epithelial dysplasia

Fig. 8.

Fig. 8

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Proliferative leukoplakia (case #2). a–c Proliferative leukoplakia involving the right and left buccal gingiva and left palatal mucosa. d Biopsy from a showed thick hyperkeratosis with surface corrugations corresponding to the fissured surface clinically. e High power view of d. The biopsy did not show features of cytologic atypia, and a sparse lymphocytic band. f Biopsy from c showed hyperkeratosis with epithelial atrophy without cytologic atypia (HkNR)

Discussion

The worldwide prevalence of oral leukoplakia is estimated to be 1–5% [1, 28, 29], and the most common sites for oral leukoplakia and malignant transformation are the tongue, buccal mucosa, floor of mouth, and gingiva. Although the gingiva is not the most common site for oral leukoplakia, it does show a tendency for a higher recurrence rate compared to other mucosal sites, ranging from 42 to 53% [13, 18, 19]. For example, Kuribayashi et al. [19] found that recurrence of oral leukoplakia occurred in 6% and 50% of tongue and gingival lesions, respectively. One possible explanation for recurrence is that the complete removal of such gingival leukoplakias is almost impossible if the associated teeth are not removed, because of involvement of the crevicular/sulcular epithelium so that any remnant dysplastic cells repopulate the surface (Fig. 9). It is also common to see leukoplakia on the buccal gingiva extending inter-dentally to involve the palatal/lingual gingiva and vice versa, again leading to “recurrence” which likely represents disease progression from residual dysplastic cells.

Recently, architectural features of OED were described in oral leukoplakia cases that lack cytologic atypia, namely, corrugated/verrucous/papillary surface, Hk with epithelial atrophy, bulky squamous proliferation, and demarcated Hk with skip segments [8]. In this series, more than half of HkNR cases (52.1%) had Hk greater than half the thickness of the epithelium; interestingly, Pk is not a common finding. Additionally, 48.1% of HkNR showed epithelial atrophy, a feature not commonly observed in reactive keratoses. Demarcated hyperkeratosis, skip segments, epithelial atrophy, and an orthokeratin layer greater than half the thickness of the epithelium are also features of proliferative leukoplakia in the absence of dysplasia in a recent study by Thompson et al. [27]. Verrucous/corrugated architecture was noted in just over half of localized gingival leukoplakias in this study (Table 2) and this feature should not be interpreted reflexively to mean that it arises from the clinical entity proliferative leukoplakia since not all proliferative leukoplakias are verrucous and localized verrucous leukoplakia with corresponding atypical verrucous hyperplasia by histology is well-recognized [8].

A lymphocytic band was seen in 8.5% of HkNR cases as has been reported [9, 30]. In Fig. 1b from a series of cases of proliferative leukoplakia from Upadhyaya et al. [30], a lymphocytic band was present at the interface associated with epithelial atrophy in a biopsy from the gingiva, as we frequently observed in this study. In two recent reviews, Muller [20, 31] emphasized the importance of recognizing this lymphocytic band as present not only in lichen planus but also in OED so as not to erroneously diagnose OED as lichen planus/lichenoid mucositis. Others have reported that 29% of OED/squamous cell carcinoma [32] and 25% of atypical verrucous hyperplasia and verrucous carcinoma [33] have a lichenoid appearance. These cases were termed “lichenoid” based on the presence of a lymphocytic band that may or may not be associated with other important features of lichen planus/lichenoid mucositis such as basal cell degeneration and colloid body formation. However, the presence of a lymphocytic band remains to be the most common of these features [32, 33]. T-cells play an important role in the destruction of tumor cells by innate and adaptive mechanisms. They are activated by tumor metabolites and neoantigens, and, in turn, produce a number of cytokines that lead to tumor cell destruction [34, 35]. Their presence is associated with improved prognosis in oral squamous cell carcinoma [36, 37]. Indeed, checkpoint inhibitors targeting such T-cells are now used in the treatment of many advanced cancers [38, 39] and were recently approved by the US Food and Drug Administration for the treatment of advanced and recurrent squamous cell carcinoma of the head and neck [40, 41]. As such, we believe that lymphocytic band in the setting of marked hyperkeratosis and epithelial atrophy is likely an important and early hallmark of a neoplastic alteration of the oral mucosa [42]. It is suggested that the term “lichenoid” not be used as a diagnostic sign-out phrase to refer just to the lymphocytic band, because it may be erroneously interpreted by the clinician as a lesion of lichen planus.

The prevalence of OED and squamous cell carcinoma in oral leukoplakia varies from 15 to 79% [6, 9, 12–15, 43]. In 5071 cases of oral potentially malignant disorders reported by Wang et al. [10], 48% of their cases showed Hk and acanthosis without OED, which is comparable to our findings (43.8%) and close to what had been previously reported by Woo et al. (57%) [9]. Nagao et al. [44] compared 88 gingival leukoplakias to 63 oral leukoplakia on other mucosal sites and found that gingival leukoplakia cases showed OED in 37% of the biopsies compared to 55% at other mucosal sites [44]. This is similar to the findings of Woo et al. [9] where 30.6% of gingival leukoplakias were dysplasia or carcinoma. In this series, 48.2% of gingival leukoplakia showed OED/squamous cell carcinoma/atypical verrucous hyperplasia and the rest were HkNR and HkUNC.

The biologic nature of HkNR and HkUNC that do not show reactive features nor obvious dysplasia is uncertain. The overall malignant transformation rate of oral leukoplakia has been reported to be as low as 3% and as high as 50% [45], and malignant transformation occurs not only from dysplastic keratoses, but also from ‘simple’ or ‘benign’ keratotic lesions that do not show OED. In research published after 2000, the malignant transformation of these latter keratoses occurred in 3–11% of the cases [6, 7, 10, 14, 17, 18, 46]. Recently, Chaturvedi et al. [14] reported an overall malignant transformation rate of oral leukoplakia of 19.2%, with 9% of hyperkeratotic lesions without OED progressing to carcinoma. It is becoming evident that the usual cytologic and organizational criteria for oral epithelial dysplasia do not reflect the biology of such lesions.

To address this, Villa et al. [47] analyzed 20 oral leukoplakias (both localized and proliferative) by next generation sequencing and showed that both HkNR (referred to then as keratosis of unknown significance) and OED have structural variants in KMT2C, TP53 and TIAM1 similar to what is reported oral squamous cell carcinoma [48], and that the mutational frequency was similar between HkNR and OED, regardless of whether the lesions were localized oral leukoplakia or proliferative leukoplakia. However, single nucleotide variants were significantly fewer in HkNR compared to OED. During follow-up, 31% and 71% of HkNR and OED transformed to squamous cell carcinoma, respectively. On the other hand, Farah and Fox [49] analyzed 25 oral leukoplakias by RNA sequencing and showed that dysplastic cases had a significantly different mutational signature from non-dysplastic cases. The dysplastic cases from the two studies did not share the same genetic alterations, possibly owing to the small number of cases. Additionally, although cases that lack OED are less likely to have aneuploid DNA than OED cases, non-dysplastic cases have a higher frequency of DNA aneuploidy than lichen planus cases [50, 51]. HkNR may represent an early phase or “the first strike” in the “three strikes” theory of carcinogenesis as reviewed by Vogelstein and Kinzler [52], and that these phenotypically “benign”-appearing keratinocytes have already accumulated activating mutations that enable them to persist and progress to invasive carcinoma.

Not only is the gingiva the most common site involved by proliferative leukoplakia, it is the single site with the highest rate of malignant transformation in the proliferative leukoplakia setting, ranging from 28.6–38.2% [21, 22, 30]. In their series of 54 cases, Silverman and Gorsky [22] reported that the gingiva and the tongue were the two sites with the highest malignant transformation rates. Bagan et al. [23] compared patients with squamous cell carcinoma with or without proliferative leukoplakia as a precursor condition and found that the gingiva was the most common site for squamous cell carcinoma development in the proliferative leukoplakia group while the tongue was the most common site for squamous cell carcinoma development in the non-proliferative leukoplakia group. Furthermore, the gingiva was the most common location for squamous cell carcinoma/verrucous carcinoma development in cases of proliferative leukoplakia reported by Upadhyaya et al. [30].

In contrast to the gingiva, only 4% (n = 2/50) of the retromolar pad keratoses showed OED, 4% were HkNR and the remaining 92% were benign alveolar ridge/frictional keratoses. Similarly, Chi et al. [24] found that only 2.1% of keratoses on the retromolar pad were dysplastic, concluding that most of the keratoses on the retromolar pad are frictional in nature. It is likely that these represent BARK.

One of the shortcomings of such a retrospective study is the lack of follow up of such patients. Another is that many lesions lack accompanying photographs which may have been very helpful especially in the category of HkUNC. Further research is needed to validate the implications of these histopathologic features frequently seen in HkNR cases on the malignant transformation and recurrence rates.

Conclusions

This study showed that the most common location for oral leukoplakia of the orthokeratinized oral mucosa was the gingiva (73.2%). Oral epithelial dysplasia/atypical verrucous hyperplasia/squamous cell carcinoma occurred in 45.7% of cases and HkNR in 43.8% of the cases, frequently with hyperkeratosis greater than half the thickness of the epithelium associated with epithelial atrophy. A lymphocytic band was noted in a subset of cases, mostly associated with epithelial atrophy. A verrucous/corrugated architecture is present in just over half of cases of localized gingival leukoplakias. We recommend adding “not reactive” in diagnostic sign-outs of lesions that lack OED as evidence is emerging on the malignant transformation potential of HkNR cases. This should prompt the need for clinical follow up in patients with hyperkeratosis and epithelial atrophy, in constrast to the reassuring diagnosis of “hyperkeratosis, no dysplasia”.

Disclosures

Conflict of interest

No conflict of interest to disclose.

Ethical approval

The data included in this study includes retrospective histopathological assessment of specimens obtained for diagnostic purposes.

Footnotes

Publisher's Note

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