A rare presentation of plasma cell cheilitis: case report and review of management strategies

Abstract

Introduction and importance:

Plasma cell cheilitis is a rare, benign, and idiopathic inflammatory disorder that affects the lips. This report presents an uncommon case involving the lower lip, successfully treated by surgical excision. Additionally, a concise review of the literature on its management is provided.

Presentation of the case:

A 63-year-old female patient presented with a nonhealing lesion on the left side of her lower lip, persisting for 1 year. Clinical evaluation identified a nontender, firm, crusted lesion with distinct margins, measuring approximately 2 cm × 1 cm. The lesion was excised, involving the underlying connective tissue. Biopsy confirmed that the surface was lined by keratinized stratified squamous epithelium, with dense inflammatory infiltrates in the dermis, predominantly consisting of mature plasma cells. Immunohistochemistry analysis demonstrated polyclonal plasma cell positivity for both kappa and lambda light chain markers and significant expression of CD138. Additionally, minor populations of lymphoid cells were identified using CD5, while CD45 positivity indicated lymphoplasmacytic infiltration. The postoperative period was uncomplicated, with no adverse events reported during the 2-year follow-up.

Clinical discussion:

Some lesions have shown resistance or recurrence following medical therapy, and malignant transformation has been reported in a few long-standing cases. Therefore, surgical excision may serve as the primary treatment modality for plasma cell cheilitis.

Conclusion:

Plasma cell cheilitis should be included in the differential diagnosis of persistent lesions of the lower lip. Accurate diagnosis necessitates comprehensive histopathological and immunohistochemical evaluation. Further research with a higher level of evidence is recommended to validate these findings.

Introduction

Plasma cell cheilitis (PCC) is a rare, benign, idiopathic inflammatory disorder predominantly affecting the lips^[1–4]. The exact etiopathogenesis remains unclear^[1,5,6]. Clinically, PCC presents as a well-circumscribed, flat or slightly elevated lesion with prominent erythema or a dark red to brownish patch or plaque, typically involving the lower lip^[2,3,7–9]. Associated features may include erosion, ulceration, fissuring, bleeding, crusting, and edema^[6,10,11]. The condition mainly affects elderly individuals^[3,6,8,9]. Histopathologically, PCC exhibits a dense, band-like infiltrate of plasma cells in the dermis^{[2–4,12,13]}, and spontaneous resolution is uncommon^[7,10].

HIGHLIGHTS

• Plasma cell cheilitis (PCC) is a rare, benign, and idiopathic inflammatory disorder that affects the lips.

• This report details a rare case of PCC affecting the lower lip, which was effectively managed through surgical excision.

• No complications were observed during the 2-year follow-up period.

• Additionally, this article includes a mini-review of the literature regarding the management of PCC.

Due to its rarity, standardized treatment guidelines are lacking, and available evidence is largely anecdotal^[5,10,11]. Topical and intralesional corticosteroids and topical immunomodulators, such as tacrolimus and pimecrolimus, have occasionally achieved complete resolution^[4,6,10,11]. However, many cases are resistant to topical therapies^[5,7,8,14], prompting the use of alternative modalities including surgical excision, radiation, laser therapy, electrocauterization, photodynamic therapy, brachytherapy, and cryosurgery^[1,7,10]. Rarely, progression to squamous cell carcinoma has been reported following various treatments^[12,14,15].

To the best of our knowledge, no similar cases have been managed surgically as the primary treatment modality. All previously reported cases were treated medically with variable outcomes (Table 1). This report presents a rare case of PCC of the lower lip successfully treated by surgical excision, with no recurrence at 2-year follow-up along with a concise review of current management strategies. The work follows the SCARE criteria^[16].

Table 1.

Overview of 29 documented cases of plasma cell cheilitis

SN	Study	Age (yr)/sex	Duration of lesion (mo)	Type of treatment	Follow-up (mo)	Inference
1	Cortonesi et al (2024)	40/F	18	Topical steroid and tacrolimus for 6 months f/b 3 cycles of fractional CO2 laser and PDT	12	Refractory to topical steroid and tacrolimus, responsive to fractional CO2 laser and PDT
2	Sudhesan et al (2023)	40/F	132	Griseofulvin f/b oral prednisolone for 1.5 months	12	Refractory to griseofulvin, responsive to oral prednisolone
3	Nishimori et al (2022)	88/F	24	Topical steroid and tacrolimus	29	SCC developed after 2 years, refractory to topical steroids and tacrolimus
4	Truffello et al (2022)	52/M	120	Topical and intralesional steroid f/b oral prednisolone	U	Little response to topical and intralesional steroids, responsive to oral prednisolone but recurs on tapering
5	Chowdhary et al. (2021)	65/M	3	Medical treatment for 3.5 years f/b Brachytherapy	24	Refractory to medical treatment, responsive to brachytherapy.
6	Cohen et al (2021)	80/M	6	Topical clobetasol for 6 weeks	U	Responsive to topical steroid
7	Yokoi et al (2020)	75/F	U	Topical hydrocortisone and triamcinolone	102	SCC developed after 8 years, refractory to topical steroids
8	Santos et al (2019)	56/M	72	Topical triamcinolone for 10 days f/b lip balm cream and sunscreen	6	Responsive to topical steroids
9	Lee et al (2016)	58/F	U	Topical tacrolimus 0.1%	9	Partial remission
10		82/M		Intralesional steroid and topical tacrolimus 0.1%	11	Relapsed
11		52/M		Intralesional steroid and topical tacrolimus 0.1%	6	Complete remission
12		75/M		Intralesional steroid and topical tacrolimus 0.1%	13	Partial remission
13		39/M		Intralesional steroid and topical tacrolimus 0.1%	4	Partial remission
14		53/M		Intralesional steroid and topical tacrolimus 0.3%	3	Complete remission
15		65/M		Intralesional steroid and topical tacrolimus 0.3%	7	Complete remission
16		79/M		Topical steroid and topical tacrolimus 0.1%	17	Relapsed
17		75/F		Intralesional steroid, topical tacrolimus 0.1%, and systemic methylprednisolone	6	Relapsed
18		65/F		Intralesional steroid, topical tacrolimus 0.1%, and systemic methylprednisolone	5	Relapsed
19		86/F		Intralesional steroid, topical steroid, and systemic methylprednisolone	39	Relapsed
20		55/M		Topical tacrolimus 0.1%, systemic methylprednisolone, and cryotherapy	18	Partial remission
21		57/M		Intralesional steroid, topical pimecrolimus, and systemic methylprednisolone	8	Partial remission
22	Yamaguchi et al (2016)	58/M	24	Topical triamcinolone, dexamethasone, clobetasone, dimethylisopropylazulene f/b 0.1 % tacrolimus	12	Refractory to topical steroids and dimethylisopropylazulene and responsive to 0.1% tacrolimus
23	Sarkar et al (2016)	52/M	4	Intralesional triamcinolone and topical tacrolimus 0.1%	U	Responsive to intralesional triamcinolone and topical tacrolimus 0.1%
24	Pepper et al (2009)	77/M	U	Tacrolimus, betamethasone, methotrexate, CO2 laser	240	SCC developed after 20 years. Refractory to tacrolimus, betamethasone, methotrexate, CO2 laser
25	Farrier et al (2008)	53/F	2-3	Topical hydrocortisone cream 1% f/b oral prednisolone	U	Refractory to topical hydrocortisone and sensitive to oral prednisolone
26	Tseng et al. (2008)	55/F	7	Topical steroid, antibiotic ointment, topical acyclovir, tacrolimus 0.03% f/b intralesional triamcinolone injection	12	Refractory to topical steroid, topical antibiotic, topical acyclovir. Responsive to intralesional triamcinolone
27	Yang et al (2005)	56/M	5	Topical fluticasone f/b intralesional triamcinolone	U	Refractory to topical fluticasone and responsive to intralesional triamcinolone
28		69/F	12	Antiviral, topical steroid f/b intralesional triamcinolone		Refractory to topical steroid and antiviral drug and responsive to intralesional triamcinolone
29		63/F	4	Topical methylprednisolone f/b intralesional triamcinolone		Refractory to topical methylprednisolone and responsive to intralesional triamcinolone

F, female; f/b, followed by; M, male; PDT, photodynamic therapy; SCC, squamous cell carcinoma; U, unknown; Yr, year; mo, months.

Case presentation

A 63-year-old female patient presented to the Oral and Maxillofacial Surgery outpatient department with a chief complaint of a nonhealing wound on the left side of the lower lip, persisting for 1 year. The lesion was asymptomatic, with no associated pain or discomfort. The family history was unremarkable, with no genetic abnormalities identified. The patient was a farmer with chronic sun exposure, a nonsmoker, a nonalcoholic, and had no systemic disease.

Clinical examination revealed a nontender, firm lesion with well-defined margins, crusted erosion, and a rough surface, measuring approximately 2 cm × 1 cm on the left vermilion border of the lower lip. Mild induration was detected on palpation (Fig. 1). No abnormalities were noted on the inner labial mucosa, other oral mucosal surfaces, or gingiva. There were no clinical signs of infection or regional lymphadenopathy. Laboratory investigations, including VDRL, TPHA, and viral markers for HIV, hepatitis B, and C, were negative.

Figure 1.

Preoperative clinical image demonstrating a crusted lesion on the left side of the lower lip.

Differential diagnoses included actinic cheilitis, allergic contact cheilitis, exfoliative cheilitis, granulomatous cheilitis, lichen planus, and lip squamous cell carcinoma. Histopathological evaluation was required for definitive diagnosis; thus, an incisional biopsy was performed, which confirmed PCC. Surgical excision was subsequently planned. The procedure was planned under general anesthesia due to the patient’s marked apprehension and fear of surgery, as well as her explicit preference for general over local anesthesia. Furthermore, general anesthesia offers greater comfort and operative control for the surgical team.

After preanesthetic evaluation, the patient was deemed fit for surgery under general anesthesia. Surgical risks, including bleeding, infection, and recurrence, were explained, and informed consent was obtained. Under general anesthesia with nasotracheal intubation, the surgical field was prepared, and a throat pack was placed. To minimize bleeding from labial arteries, the lip was ligated with 2-0 black silk sutures at mesial and distal ends. An incision was made with a 0.5 mm margin, and the lesion was excised to the level of the underlying connective tissue (Fig. 2). Hemostasis was achieved, and primary closure was performed using 3-0 90/10 polyglycolide-co-L-lactide braided absorbable sutures (Novosyn, B. Braun Surgical, S.A., Rubi, Spain). The excised specimen was fixed in 10% buffered formalin and submitted for histopathological examination (Fig. 3).

Figure 2.

Intraoperative image presenting the surgical site following excision of the lesion from the lower lip.

Figure 3.

Intraoperative image showing excised specimen.

Histopathology revealed keratinized stratified squamous epithelium overlying dense dermal inflammatory infiltrates composed predominantly of mature plasma cells, with few lymphocytes and monocytoid cells. Plasma cells displayed eccentric nuclei and abundant cytoplasm, with typical bipolar mitoses and no malignant features (Fig. 4). Immunohistochemistry demonstrated polyclonal plasma cell positivity for kappa and lambda light chains (kappa:lambda = 4:1), CD138 positivity in plasma cells, and CD5 and CD45 positivity in lymphoid populations (Fig. 5). A final diagnosis of PCC was confirmed.

Figure 4.

Microscopic examination: (A) 4X magnification; section from lower lip lesion showed tissue lined by keratinizing stratified squamous epithelium (yellow arrow), and underlying dermis shows dense band-like subepithelial infiltrate (green arrow). (B) 10X magnification showing dermis inflammatory cells comprising predominantly mature plasma cells along with a few monocytoid cells and small lymphocytes (blue arrow). (C) 40X magnification; showing predominantly plasma cells characterized by round to oval-shaped cells with a large eccentrically placed nucleus and abundant cytoplasm (orange arrow), few monocytoid cells (red arrow), and mature lymphocytes (green arrow). (D) 40X magnification showing a few bipolar mitosis (blue arrow) with plenty of plasma cells.

Figure 5.

Immunohistochemistry markers (A) plasma cells showing cytoplasmic positivity for kappa light chain, (B) plasma cells showing cytoplasmic positivity for lambda light chain, (C) CD138: Dense positivity in cell membrane and cytoplasm of plasma cells, (D) CD5; highlights membrane positivity in few lymphoid cells, (E) CD45; membrane positivity shown by lymphoplasmacytic inflammatory infiltrate.

Patient follow-up and progress: Postoperative recovery was uneventful. The patient was reviewed weekly for 1 month, monthly for 6 months, and every 3 months for 2 years. Wound healing, recurrence, and subjective symptoms were monitored, with no complications observed during follow-up (Supplementary digital content Fig. 1, available at: http://links.lww.com/IJSCR/A1).

Discussion

PCC is a rare, benign, idiopathic inflammatory disorder affecting the lips^[1–4]. Although its precise etiopathogenesis remains unclear^[1,5,6,9], it is generally considered an immune-mediated reactive process triggered by factors such as mechanical friction, solar radiation, infections, trauma, and exposure to certain dental products like mouthwashes^[5,6,10,11]. The mechanisms underlying plasma cell infiltration are not fully understood; however, T cells and macrophages are thought to regulate B-cell growth and differentiation within mucosal and cutaneous environments^[1,8,9,11]. In the present case, chronic solar exposure was considered the likely etiological factor, as the patient, a farmer, had long-term daily sun exposure without ultraviolet protection.

PCC predominantly affects older adults, with reported ages ranging from 40 to 88 years and a mean of 62.8 years^{[1,2,4–12,14–17]}. Clinically, it usually presents as a circumscribed, flat to slightly raised lesion with well-defined margins and dark red to brownish discoloration, most commonly on the lower lip^[2,3,6,8,9]. Associated features include erosion, ulceration, fissuring, bleeding, crusting, and edema^[5,6,10,11]. The lesion in this case was a firm, nontender, slow-growing plaque on the lower vermilion border, which matched typical descriptions.

PCC is considered the oral counterpart of plasma cell balanitis (Zoon’s balanitis)^[4,17], first described by Zoon in 1952 as an inflammatory disorder of the glans penis characterized by dense plasma cell infiltration of the upper dermis^[3,8,17]. Histopathologically and clinically, PCC resembles plasma cell mucositis, which involves mucosal surfaces such as the vulva, buccal mucosa, palate, tongue, epiglottis, and larynx^[1,8,9,17].

No standardized treatment protocol exists for PCC due to its rarity^[5,10,17]. Reported therapeutic modalities include topical corticosteroids (e.g., clobetasol, triamcinolone)^[6,11], intralesional corticosteroids (e.g., triamcinolone)^[4,9,10,17], systemic corticosteroids^[5,8], topical immunomodulators (e.g., tacrolimus, pimecrolimus)^[4,10,13], laser therapy, photodynamic therapy^[7], brachytherapy^[1], and surgical excision^{[1,8,9,11,17]}. Some authors report favorable responses to potent topical corticosteroids^[6,11], while others note therapeutic resistance^{[7–9,13,17]}. Intralesional corticosteroids, especially triamcinolone, can bypass the epidermal barrier and provide enhanced anti-inflammatory effects^[9,10,17], with several successful outcomes reported^[9,17]. Systemic corticosteroids have shown variable efficacy^[5,8]. Topical tacrolimus, which inhibits T-lymphocyte signal transduction, has been effective as monotherapy or in combination with steroids^[4,10], though some lesions remain resistant^[10].

Despite its benign nature, PCC often demonstrates resistance to multiple treatments, including corticosteroids, immunomodulatory agents, antibiotics, antifungals, antivirals, methotrexate, and CO₂ laser therapy^{[1,5,7–9,12–15,17]}. Brachytherapy has been successful in select refractory cases^[1]. Of clinical significance, three cases of secondary squamous cell carcinoma (SCC) arising from PCC have been reported, all affecting the lower lip of elderly patients following treatment with topical corticosteroids, tacrolimus, and methotrexate^[12,14,15]. The intervals between PCC diagnosis and SCC development were 2, 8, and 20 years, respectively^[12,14,15], underscoring the need for long-term clinical surveillance. In a series of 13 cases, various treatments – including intralesional steroids, topical tacrolimus, systemic steroids, topical pimecrolimus, and cryotherapy – resulted in complete remission in three patients, partial response in five, and relapse in five^[10].

Given the small but documented risk of malignant transformation, surgical excision was selected as the primary treatment in this case. Literature supports surgical excision as a reliable and effective option for localized PCC^{[1,8,9,11,17]}. Complete excision was achieved, with no recurrence after 2 years of follow-up.

Histopathologically, PCC shows a dense, band-like infiltrate of mature plasma cells in the upper dermis—a finding uncommon in most inflammatory dermatoses^[2,7,12,14]. The infiltrate typically lacks cytological atypia, and Russell bodies may be present^[11]. Additional features may include hyperkeratosis, dyskeratosis, intercellular edema, epidermal erosion, and vacuolar degeneration at the dermoepidermal junction^[10,11]. Immunohistochemically, PCC demonstrates polyclonal plasma cell populations expressing both kappa and lambda light chains, with kappa predominance^[6]. This polyclonality differentiates PCC from neoplastic plasma cell proliferations, which are monoclonal^[11]. In this case, a kappa:lambda ratio of 4:1 confirmed polyclonality.

The differential diagnosis of PCC includes allergic contact cheilitis, secondary syphilis, actinic cheilitis, squamous cell carcinoma, cheilitis granulomatosa, plasmacytoma, angioedema, cheilitis glandularis, exfoliative cheilitis, lichen planus, candidiasis, and bacterial infections^{[5,6,8,9,11,17]}. Clinicopathological correlation and immunohistochemistry are essential for accurate diagnosis. Allergic contact cheilitis typically shows spongiosis and lymphocytic infiltration^[11], syphilis demonstrates perivascular plasma cells and positive Treponema pallidum serology^[11], actinic cheilitis reveals solar elastosis^[3,11], and SCC shows stromal invasion^[11]. Plasmacytoma exhibits monoclonal atypical plasma cells^[11], while other conditions can be excluded based on histological and microbiological findings^{[5,9,11,16,17]}.

Conclusion

PCC is a rare idiopathic inflammatory lesion of the lower lip that should be considered in the differential diagnosis of persistent lower lip lesions. Definitive diagnosis requires thorough histopathological examination and immunohistochemical analysis. Further research with a higher level of evidence is recommended to validate these findings.

Ethical approval

It is our routine standard surgical procedure, so ethical clearance was not required from the Institutional Review Committee of the Nepalese Army Institute of Health Sciences.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

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

Author contributions

MA: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing original draft, writing – review and editing. KJ: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, supervision, validation, visualization, writing – original draft, writing – review and editing. TR: conceptualization, data curation, formal analysis, funding acquisition, investigation, resources, supervision, validation, visualization, writing – original draft, writing – review and editing. SK: conceptualization, data curation, formal analysis, methodology, resources, software, supervision, validation, visualization, writing – original draft, writing – review and editing. MG: conceptualization, data curation, formal analysis, software, supervision, validation, visualization, writing – original draft, writing – review and editing. SKC: conceptualization, data curation, formal analysis, software, supervision, validation, visualization, writing – original draft, writing – review and editing.

Conflicts of interest disclosure

The authors declare that there is no conflict of interest regarding the publication of this paper.

Guarantor

Dr. Manoj Adhikari.

Registration of research studies

Not applicable.

Patient perspective

The patient expressed high satisfaction with the successful treatment outcome, achieved without complications.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.