Lichenoid lesions of the upper labial mucosa: a systematic review and a report of a new case with extensive follow-up

Figures & data

Figure 1. Flow diagram of the systematic review process, including searches of databases and other sources.

Figure 2. Histopathological findings from labial mucosal biopsies. (A, B) Hyperparakeratotic stratified squamous epithelium with saw-toothed rete ridges in some areas, basal cell degeneration, apoptotic basal keratinocytes (arrow in B) and inflammatory cell exocytosis. A dense band-like lymphocytic infiltration in the lamina propria and patchy inflammatory cell infiltrates in the submucosa. (C) An aggregate of monocytic inflammatory cells consisting mainly of lymphocytes, visible also perineurally (marked by the arrow). (D) Possible histiocytes visible in the infiltrate (indicated by the arrow). Haematoxylin and eosin stain, original magnification × 25 (A), × 200 (B), × 400 (C), × 400 (D).

Figure 3. Clinical presentation of the upper labial mucosa and upper anterior labial gingiva over a 10-year span (A, B, D, and E). White reticular striae or papular lesions with erythema were seen at most visits. (C) A faint white stria to the labial mucosa after treatment with intralesional methylprednisolone (40 mg/ml) injection. (F) Slight erythema of the labial mucosa and gingiva on the last follow-up visit. The patient used tacrolimus when needed.

Table 1. Details of the demographic and clinical characteristics of the patients.

Case	Reference	Country	Gender	Age	Medical history	Medication	Allergies	Location	Clinical appearance	Symptoms	Clinical differential diagnosis	Dental plaque/calculus of adjacent teeth	Composite resin restoration of adjacent teeth	Treatment	Reported follow-up/ duration*	Outcome
1	Robinson et al., 2006	United Kingdom	Female	58	Multiple sclerosis, asthma	n/a	n/a	Upper labial mucosa	Diffuse swelling with erythematous patch, size: 8 mm	Swelling of the upper lip	Mucocele	n/a	n/a	30 mg prednisolone for 14 days, then 5 mg on alternate days for 3 months	64 months	After 64 months no resolution. Periods of exacerbation and quiescence.
2	Robinson et al., 2006	United Kingdom	Female	55	Osteoarthritis	Naproxen, Atenolol	n/a	Upper labial mucosa and adjacent gingiva	Diffuse swelling with erythematous patch, size: 20 mm. Similar changes on gingiva.	Painful, tender upper lip	Lichenoid drug eruption, discoid lupus erythematosus	n/a	n/a	Naproxen discontinued. Adcortyl in orobase (Triamcinolone acetonide 0.1% in adhesive basis. Paste applied to lesion four times daily). Betnesol mouthwash (Betamethasone sodium phosphate tablets, 500 μg. One tablet dissolved in 10 ml of water used as a mouthwash for 4 min, four times daily). Becotide 100 (Beclometasone dipropionate, 100 μg/metered inhalation. One puff directed at the lesion four times daily).	59 months	After 59 months no resolution. Periods of exacerbation and quiescence.
3	Robinson et al., 2006	United Kingdom	Male	63	Prostate hyperplasia	n/a	n/a	Upper labial mucosa and adjacent gingiva	Erythematosus patch, no swelling, size: 15 mm. Similar changes on gingiva.	Sore gum above maxillary incisor teeth	Lichen planus, discoid lupus erythematosus	n/a	n/a	Difflam (Benzydamine hydrochloride 0.15% oral rinse. Rinse with 15 ml as required), Betnesol mouthwash (Betamethasone sodium phosphate tablets, 500 μg. One tablet dissolved in 10 ml of water used as a mouthwash for 4 min, four times daily). Becotide 100 (Beclometasone dipropionate, 100 μg/metered inhalation. One puff directed at the lesion four times daily).	40 months	After 40 months no resolution. Periods of exacerbation and quiescence.
4	Robinson et al., 2006	United Kingdom	Female	54	Hypertension	Ramipril, Bendrofluazide	Elastoplast	Upper labial mucosa and adjacent gingiva	Red erythematous granular patch with petechiae, size: 15 mm. Similar changes on gingiva.	Tender swelling on upper lip	Discoid lupus erythematosus, granulomatous lesion	n/a	n/a	Becotide 100 (Beclometasone dipropionate, 100 μg/metered inhalation. One puff directed at the lesion four times daily).	11 months	After 11 months no resolution. Periods of exacerbation and quiescence.
5	Robinson et al., 2006	United Kingdom	Male	65	n/a	n/a	n/a	Upper labial mucosa	Red erythematous patch, size: 5 mm	n/a	n/a	n/a	n/a	n/a	n/a	n/a
6	Robinson et al., 2006	United Kingdom	Female	60	n/a	n/a	n/a	Upper labial mucosa	Red erythematous patch with swelling	n/a	n/a	n/a	n/a	n/a	n/a	n/a
7	Ferrisse et al., 2017	Brazil	Female	50	n/a	n/a	n/a	Upper lip and gingiva	Erythematous area	Slightly symptomatic	Lichenoid lesion and contact hypersensitivity	n/a	n/a	Topical corticosteroids for 3 months	15 months	Complete resolution of the lesions
8-15	Mainville et al., 2017	n/a	Females (n = 8)	33-81, mean age 58	n/a	n/a	n/a	Upper labial mucosa (n = 8), with facial maxillary gingiva (n = 3)	Redness and swelling of upper labial mucosa. Erythema and swelling of the maxillary gingiva.	Burning	n/a	n/a	n/a	Topical steroid application, topical antifungal therapy	n/a	Lesions waxed and waned over time. Most patients reported relief of symptoms after therapy.
16	Rodrigues et al., 2017	Brazil	Female	72	Hypercholesterolaemia	Hypercholesteremia regularly treated	n/a	Upper lip and attached anterior gingiva	Erythematous	Mild symptoms	Oral lichenoid lesion, foreign body gingivitis, hypersensitivity reaction	n/a	n/a	Topical corticosteroid 2-3 times a day for 2 weeks	6 months and 2 weeks	Almost complete resolution of the lesions
17	Katsoulas et al., 2018	Greece	Female	62	n/a	No	n/a	Upper labial mucosa	White striations, erythema/erosions	Pain in affected area and spontaneous difficulties in mastication and oral hygiene	n/a	No	No/Unknown	Topical corticosteroids, antifungal gel	12 months	Improved and no new lesions developed
18	Katsoulas et al., 2018	Greece	Male	53	n/a	No	n/a	Upper labial mucosa with gingival involvement	White striae and erythema of upper labial mucosa, gingival erythema	Slight discomfort, mainly of the upper labial mucosa	n/a	Yes	No/Unkown	Chlorhexidine	1 month	n/a
19	Katsoulas et al., 2018	Greece	Female	50	n/a	No	n/a	Upper labial mucosa with gingival involvement	White striation and erythema, gingival erythema	Slight discomfort, mainly of the upper labial mucosa	n/a	Yes	Yes	Topical corticosteroids, chlorhexidine	36 months	Improved and no new lesions developed
20	Katsoulas et al., 2018	Greece	Female	46	n/a	No	n/a	Upper labial mucosa	White striations, erythema/erosions	Pain in affected area and spontaneous difficulties in mastication and oral hygiene	n/a	No	No/Unkown	Chlorhexidine	6 months	n/a
21	Hakeem et al., 2019	United States	Male	58	n/a	n/a	n/a	Upper lip	Erythroleukoplakic, red, or white, with ulceration	Pain or soreness	Lichenoid mucositis, oral lichen planus or chronic granulomatous inflammation	n/a	n/a	n/a	n/a	n/a
22	Hakeem et al., 2019	United States	Female	66	n/a	n/a	n/a	Upper lip	Erythroleukoplakic, red, or white	Pain or soreness	Lichenoid mucositis, oral lichen planus or chronic granulomatous inflammation	n/a	n/a	n/a	n/a	n/a
23	Hakeem et al., 2019	United States	Male	62	n/a	n/a	n/a	Upper lip	Erythroleukoplakic, red, or white	Pain or soreness	Lichenoid mucositis, oral lichen planus or chronic granulomatous inflammation	n/a	n/a	n/a	n/a	n/a
24	Hakeem et al., 2019	United States	Female	62	n/a	n/a	n/a	Upper lip, maxillary premolar and anterior gingiva	Erythroleukoplakic, red, or white	Pain or soreness	Lichenoid mucositis, oral lichen planus or chronic granulomatous inflammation	n/a	n/a	n/a	n/a	n/a
25	Hakeem et al., 2019	United States	Female	65	n/a	n/a	n/a	Upper lip, side lip	Erythroleukoplakic, red, or white	Pain or soreness	Lichenoid mucositis, oral lichen planus or chronic granulomatous inflammation	n/a	n/a	n/a	n/a	n/a
26	Halonen & Siponen, 2022	Finland	Female	56	Positional obstructive sleep apnoea	Hormone replacement therapy, glucosamine, etoricoxib	No	Upper labial mucosa and upper anterior labial gingiva	Erythema and white striation	Pain, smarting, difficulties in mastication and talking, taste of metal in mouth, sensation of swelling	Erythematous candidiasis	Yes	Yes	Local antifungal treatment (amphotericin lozenges), triamcinolone acetonide cream, 0,05% clobetasol cream, 0.1% and 0.03% tacrolimus, acitretin (p.o), 0.1% betamethasone valerate cream, nystatin suspension, fluconazole, miconazole gel, 1% chlorhexidine gel, prednisolone (p.o), Depo-medrol 40 mg/ml intralesionally, biostimulative laser therapy	157 months	Periods of exacerbation and quiescence. No complete resolution.

*There were cases in which reported data was described as ‘duration’, ‘follow up’ or both. We summed that data together.

n/a: data not available.

Table 2. Histopathological features of the lesions.

Case	Features of lichenoid inflammation	Features of granulomatous inflammation	Other findings	Foreign material	Fungal organism	ZN stain	Immunohistochemical studies*
1	Hyperkeratosis, basal cell damage, apoptotic bodies, band-like lymphohistiocytic infiltrate, present T‐cell infiltrate composed of CD4 and CD8 lymphocytes	Numerous, small, well‐formed granulomas	Deep lymphocytic infiltrate: nodules of medium‐sized lymphocytes, perineural distribution and mixture of B and T cells	Negative	PAS positive for fungal hyphae	Negative	CD20, CD3, CD4, CD8, CD68
2	Hyperkeratosis, basal cell damage, apoptotic bodies, band-like lymphohistiocytic infiltrate, present T‐cell infiltrate composed of CD4 and CD8 lymphocytes	Numerous, small, well‐formed granulomas	Deep lymphocytic infiltrate: nodules of medium‐sized lymphocytes, perineural distribution and mixture of B and T cells	Negative	PAS negative	Negative	CD20, CD3, CD4, CD8, CD68
3	Hyperkeratosis, basal cell damage, apoptotic bodies, band-like lymphohistiocytic infiltrate, present T‐cell infiltrate composed of CD4 and CD8 lymphocytes	Numerous, small, well‐formed granulomas	Deep lymphocytic infiltrate: nodules of medium‐sized lymphocytes, perineural distribution and mixture of B and T cells	Negative	PAS negative	n/a	CD20, CD3, CD4, CD8, CD68
4	Hyperkeratosis, basal cell damage, apoptotic bodies, band-like lymphohistiocytic infiltrate	Few, small, poorly formed granulomas	Deep lymphocytic infiltrate: nodules of medium‐sized lymphocytes, perineural distribution and mixture of B and T cells	Negative	PAS negative	n/a	CD20, CD3
5	Hyperkeratosis, basal cell damage, apoptotic bodies, band-like lymphohistiocytic infiltrate	Few, small, well‐formed granulomas	Deep lymphocytic infiltrate: nodules of medium‐sized lymphocytes and perineural distribution	Negative	PAS negative	n/a	n/a
6	Hyperkeratosis, basal cell damage, apoptotic bodies, band-like lymphohistiocytic infiltrate	Numerous, small, well‐formed granulomas	Deep lymphocytic infiltrate: nodules of medium‐sized lymphocytes and perineural distribution	Negative	n/a	n/a	n/a
7	Epithelial hyperplasia, lymphohistiocytic infiltration in subepitelial	n/a	Perivascular patterns	Negative	‘Infectious origin negative’	‘Infectious origin negative’	CD4, CD11e, CD68, CD63, CD1a, FOXP3, Ki67
8-15	Interface lymphohistiocytic mucositis	Granulomas	Perivascular, perineural lymhoid nodules	n/a	5 out of 8 had candidiasis	n/a	n/a
16	Epithelial hyperplasia, subepithelial lymphoplasmacytic inflammation	Multinucleated giant cells	Perivascular lymphoplasmacytic inflammation	Negative	‘Negative for fungal infection’	‘Bacterial infection negative’	n/a
17	Hydropic degeneration of basal cell layer, subepithelial band-like lymphohistocytic inflammatory infiltrate	No granulomas	Focally perivascular lymphohistocytic inflammatory infiltrate	Negative	PAS negative	Negative	CD68 (+)
18	Hydropic degeneration of basal cell layer, subepithelial band-like lymphohistocytic inflammatory infiltrate	No granulomas	Focally perivascular lymphohistocytic inflammatory infiltrate	Negative	PAS negative	Negative	CD68 (+)
19	Hydropic degeneration of basal cell layer, subepithelial band-like lymphohistocytic inflammatory infiltrate	No granulomas	Focally perivascular lymphohistocytic inflammatory infiltrate	Negative	PAS negative	Negative	CD68 (+)
20	Hydropic degeneration of basal cell layer, subepithelial band-like lymphohistocytic inflammatory infiltrate	No granulomas	Focally perivascular lymphohistocytic inflammatory infiltrate	Negative	PAS negative	Negative	CD68 (+)
21	Band-like lymphocytic infiltration	Superficially disposed loose histiocytic aggregates	Perivascular inflammatory infiltrate	Negative	PAS negative	n/a	CD68 (+)
22	Band-like lymphocytic infiltration	Small epitheloid granulomas	Perivasculitis	Negative	PAS negative	n/a	CD68 (+)
23	Band-like lymphocytic infiltration	Small epitheloid granulomas	Perivasculitis	Negative	PAS negative	n/a	CD68 (+)
24	Band-like lymphocytic infiltration	Small epitheloid granulomas	Perivasculitis	Negative	PAS negative	n/a	CD68 (+)
25	Band-like lymphocytic infiltration	Superficially disposed loose histiocytic aggregates	Perivascular inflammatory infiltrate	Negative	PAS negative	n/a	CD68 (+)
26	Saw toothed rete ridges, basal cell degeneration, apoptotic Civatte bodies, dense band-like lymphocytic infiltration under the epithelium	No granulomas, possibly some histiocytes in the submucosal lymphocytic aggregates	Lymphocytic aggregates in the submucosa, periductal and perineural chronic inflammatory infiltrate	Negative	PAS negative, oral yeast culture positive for candida	Not done	No

*Immunohistochemical markers used in the reports. The results of the staining were reported only in some studies.

n/a: data not available.