Diagnosis and treatment of verrucous carcinoma of the lip: a case report

Article information

Arch Craniofac Surg. 2025;26(3):124-128
Publication date (electronic) : 2025 June 20
doi : https://doi.org/10.7181/acfs.2024.0058
Department of Plastic and Reconstructive Surgery, Wonkwang University Hospital, Iksan, Korea
Correspondence: Young Cheon Na, Department of Plastic and Reconstructive Surgery, Wonkwang University Hospital, 895 Muwang-ro, Iksan 54538, Korea, E-mail: ycnadr@hanmail.net
Received 2024 July 16; Revised 2024 September 12; Accepted 2025 June 20.

Abstract

Verrucous carcinoma, a variant of squamous cell carcinoma, is notable for its lower aggressiveness; however, it presents considerable diagnostic challenges. This tumor is often misdiagnosed, leading to delays in treatment. We describe the case of an 84-year-old woman with verrucous carcinoma presenting as a warty lesion on the lip. The initial biopsy established a diagnosis of verrucous carcinoma, after which wedge resection with a lateral advancement flap was performed. Although the operation was successful, tumor recurrence was observed at the surgical site within several weeks, and a subsequent biopsy identified squamous cell carcinoma. Further surgical intervention proved effective, with no recurrence observed 6 months after treatment. This case emphasizes the importance of precise diagnosis and vigilant management in verrucous carcinoma, highlighting the need for clinicians and pathologists to recognize atypical progression, including hybrid variants. Further research is needed to refine diagnostic criteria and therapeutic strategies for this distinctive and unpredictable malignancy.

INTRODUCTION

Verrucous carcinoma (VC), a variant of squamous cell carcinoma (SCC), is characterized by a lower tendency for local invasion than conventional SCC, with rare involvement of adjacent tissues or lymph nodes [1]. VC usually originates from the squamous epithelium and can manifest in various anatomical sites, including the oral mucosa, genitalia, and feet, although the oral cavity is most commonly affected. The disease generally follows a relatively indolent clinical course. The peak of incidence is among men aged 40 to 60 years, and common risk factors include tobacco use, alcohol consumption, and previous traumatic scars [2].

Due to its rarity and clinical presentation that often resembles benign conditions, VC is frequently misdiagnosed or subject to diagnostic delay, especially if initial treatments are ineffective. This delay in diagnosis and initiation of therapy complicates the management of VC, especially compared to more readily identifiable malignancies.

Herein, we present a case report describing the diagnostic and therapeutic interventions for warty VC of the lip, illustrating potential diagnostic pitfalls and underscoring the importance of prompt recognition and appropriate management. Our aim is to provide guidance for surgeons regarding the accurate diagnosis and optimal treatment of VC of the lip.

CASE REPORT

An 84-year-old woman presented to the dermatology department with a 1.5-cm warty lesion on the left lower lip. She had first noticed the lesion 1 month prior to presentation, during which time it had grown and become ulcerated. The patient reported intermittent bloody discharge from the lesion and persistent pain. She had no history of smoking or alcohol consumption, and her medical history was notable only for hypertension. The initial biopsy indicated a verrucous lesion, and cryotherapy was attempted but yielded no improvement. Due to rapid progression of the lesion, a second biopsy was performed, confirming VC. The patient was then referred to our department for surgical management (Figs. 1, 2).

Fig. 1

An 84-year-old woman with a painful warty lesion on the lower lip.

Fig. 2

Histological results of excisional biopsy (hematoxylin and eosin, ×100).

Contrast-enhanced computed tomography (CT) was performed to determine the depth of the lesion and visualize any metastases. No metastases were detected, but thyroid cancer was discovered; therefore, combined surgery was performed, and a biopsy performed during thyroidectomy confirmed papillary thyroid carcinoma. For the lip mass, a 0.5-cm safety margin was established. Wedge-shaped excision and a lateral advancement flap were performed, with negative margins found on intraoperative frozen biopsy. A nasogastric tube was inserted to minimize wound contamination (Fig. 3). The patient’s postoperative care included wound dressing and dietary counseling, and she was discharged following improvement in all surgical wounds.

Fig. 3

Postoperative status on day 1 after the operation.

One month later, tumor recurrence with different radiological features was observed on the left side adjacent to the primary surgical site. A third biopsy and CT scan were performed (Fig. 4). The biopsy revealed well-differentiated SCC, and the CT scan showed that the lesion had invaded the adjacent mandibular and buccal spaces, which was interpreted as local invasion due to the regrowth of an incompletely resected tumor. The lymph node was also found to be pathologically swollen. After discussion with the otolaryngology team, wide excision of the mass and neck dissection to prevent further recurrence was considered. However, these procedures were deferred due to the high surgical risk associated with the patient’s advanced age. After confirming the absence of thyroid cancer recurrence, a second operation was performed. As in the initial surgery, a 0.5-cm safety margin was maintained. The extent of lip involvement was less than in the first operation, and the defect was closed primarily after resection.

Fig. 4

(A) Recurrent lesion on the left side of the lower lip adjacent to the primary lesion. (B) Computed tomography scan showing a pathologic lymph node at left level I, appearing enlarged and irregularly shaped (yellow arrows).

Frozen section analysis showed negative margins in all four directions, and permanent pathology revealed spread of the lesion to the submental region without pathological lymph nodes. No invasion of blood vessel walls was observed. The patient remained hospitalized for 1 week and was discharged after significant improvement at the surgical site (Fig. 5).

Fig. 5

Healed lesion on postoperative day 14.

Two weeks after the second operation, chemotherapy was initiated due to the possibility of incomplete resection and the potential malignant lymph nodes in the neck. Cisplatin and fluorouracil were administered intravenously, for a total of six cycles at 3-week intervals. The patient continued outpatient follow-up, receiving intravenous anticancer drugs as indicated. No recurrence was observed at 6 months following the second operation.

DISCUSSION

VC, a rare subtype of SCC, resembles verruca vulgaris. Its symptoms are often not evident until the lesion enlarges and invades surrounding structures, resulting in missed opportunities for timely treatment. Dermatological interventions such as cryotherapy and laser therapy are often attempted prior to surgical management; however, if no improvement is observed after more than 3 months of treatment, a definitive diagnosis should be established by biopsy. VC is characterized by lower levels of mitotic activity and cellular atypia than conventional SCC, as well as the absence of adjacent lymphovascular invasion. VC may arise from the malignant transformation of verrucous hyperplasia. Although there are few obvious differences on gross examination, pathologically VC demonstrates more superficial projections and broader, deeper, rete ridges compared to adjacent normal epithelium [3]. After diagnosis, CT or magnetic resonance imaging is performed to determine whether there is invasion into adjacent structures, lymph nodes, or distant metastases. All lesions are then excised with clear margins, confirmed by immediate frozen section biopsy. The effects of recent anticancer drugs on VC remain unclear due to its rarity, although some reports have stated that chemotherapy was effective in patients unsuitable for surgery. Chemotherapy may also be combined with radiotherapy [4]. Long-term follow-up is essential to monitor for recurrence.

In this case, our patient exhibited several features that distinguished her presentation from typical VC. First, the lesion was found on the lip of an 84-year-old woman who had never smoked or consumed alcohol and denied any previous scarring or habitual lip biting. Second, unlike conventional VC, which typically progresses slowly, the lesion in this case grew and became aggravated within approximately 2 months, resulting in severe pain that interfered with eating. Third, just 2 weeks after her first operation, erythema and pain developed in the adjacent area, and a repeat biopsy revised the diagnosis to well-differentiated SCC. Finally, imaging revealed tumor invasion into adjacent mandibular and buccal spaces. Based on these findings, additional local dissection was performed during the second operation, and the patient received chemotherapy.

We suggest two possible explanations for the unusual course observed in this case: (1) the initial pathological diagnosis of VC was misleading, or (2) VC coexisted with SCC, a scenario consistent with one of the recognized types of VC. In the first scenario, the warty appearance and thickened epithelium of VC may have prevented adequate sampling of deeper tissue during the initial biopsy, making it difficult to distinguish VC from benign conditions such as verrucous hyperplasia or verrucous leukoplakia, as well as from malignant lesions such as squamous papilloma and SCC. The second possibility involves the concept of hybrid VC, first described by Batsakis, in which the pathological features of conventional SCC and VC are present in the same lesion [5]. Medina reported that hybrid VC may be present in up to 20% of patients with oral VC [6]. If areas with increased cytologic atypia and mitotic activity characteristic of SCC are observed within a VC lesion, the tumor should be considered a hybrid VC. In such cases, treatment should follow SCC guidelines, including a comprehensive evaluation for metastasis and extensive resection with lymph node dissection [7]. Even after surgery, aggressive adjuvant therapy with chemotherapy or radiotherapy may be required to optimize prognosis.

When lip reconstruction is needed due to tumor excision or congenital deformity, the surgical method should be chosen based on the size and location of the defect. The lower lip allows for a wider range of primary closure than the upper lip; if the defect involves less than 30% of the lip in adults, primary closure can generally be attempted. Local flaps may also be used to minimize scar formation and improve cosmetic outcomes [8]. Larger defects may necessitate treatment with a wedge excision and Estlander flap or vermilionectomy. If the defect exceeds 80%, total lip reconstruction, including a bilateral Karapandzic flap, may be required [9]. In our patient, the initial surgery involved a defect of approximately 40%, for which a local flap based on the inferior labial artery was utilized, taking into account her advanced age and preference for a less invasive approach. The incision was approximately twice the diameter of the defect to allow tissue advancement. In the second operation, the smaller defect permitted primary closure.

This study has several limitations regarding generalizability, including difficulty in establishing the optimal criteria for lymph node dissection in VC. The patient’s advanced age also limited the range of possible surgical options, necessitating a more cautious treatment strategy. Further studies are needed to determine the optimal management of VC and improve diagnostic accuracy. The prognosis of SCC varies widely by subtype, with sarcomatoid SCC carrying a particularly poor prognosis and higher mortality [10]. Despite increasing evidence on VC, comprehensive studies remain limited due to its rarity. This case underscores the importance of precise diagnosis and individualized management of VC, particularly for lip lesions where diagnostic confusion is common. If there are no significant perioperative risks, treatment should follow established SCC protocols. If perioperative risk is elevated and the patient prefers minimal intervention, less aggressive surgical management with close monitoring for recurrence or local invasion is recommended.

Notes

Conflict of interest

Young Cheon Na is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Funding

This work was supported by Wonkwang University in 2023.

Ethical approval

The study was approved by the Institutional Review Board of Wonkwang University Hospital (WKUH 2024-05-031).

Patient consent

The patient provided written informed consent for the publication and use of her images.

Author contributions

Conceptualization: Young Cheon Na. Data curation: Hye Mi Lee. Writing - original draft: Eun Jung Jang. Writing-review&editing: Hye Mi Lee, Young Cheon Na. Investigation: Eun Jung Jang. Resources: Eun Jung Jang. Supervision: Hye Mi Lee. All authors have reviewed and approved the final manuscript.

Abbreviations

CT

computed tomography

SCC

squamous cell carcinoma

VC

verrucous carcinoma

References

1. Patel KR, Chernock RD, Zhang TR, Wang X, El-Mofty SK, Lewis JS Jr. Verrucous carcinomas of the head and neck, in cluding those with associated squamous cell carcinoma, lack transcriptionally active high-risk human papillomavirus. Hum Pathol 2013;44:2385–92.
2. Rekha KP, Angadi PV. Verrucous carcinoma of the oral cavity: a clinico-pathologic appraisal of 133 cases in Indians. Oral Maxillofac Surg 2010;14:211–8.
3. Sharma P, Wadhwan V, Aggarwal P, Sharma A. Oral verrucous hyperplasia versus oral verrucous carcinoma: a clinicopathologic dilemma revisited using p53 as immunohistochemical marker. J Oral Maxillofac Pathol 2016;20:362–8.
4. Wu CF, Chen CM, Shen YS, Huang IY, Chen CH, Chen CY, et al. Effective eradication of oral verrucous carcinoma with continuous intraarterial infusion chemotherapy. Head Neck 2008;30:611–7.
5. Batsakis JG, Hybels R, Crissman JD, Rice DH. The pathology of head and neck tumors: verrucous carcinoma, Part 15. Head Neck Surg 1982;5:29–38.
6. Medina JE, Dichtel W, Luna MA. Verrucous-squamous carcinomas of the oral cavity: a clinicopathologic study of 104 cases. Arch Otolaryngol 1984;110:437–40.
7. Devaney KO, Ferlito A, Rinaldo A, El-Naggar AK, Barnes L. Verrucous carcinoma (carcinoma cuniculatum) of the head and neck: what do we know now that we did not know a decade ago? Eur Arch Otorhinolaryngol 2011;268:477–80.
8. Kim HI, Kim HS, Park JH, Yi HS, Kim YS, Kim HY. Reconstruction of a small defect of the lower vermilion adjacent to white roll using a modified O-Z flap. Arch Craniofac Surg 2021;22:164–7.
9. Rudkin GH, Carlsen BT, Miller TA. Nasolabial flap reconstruction of large defects of the lower lip. Plast Reconstr Surg 2003;111:810–7.
10. Lee Y, Lee D, Yeo H, Park H, Park H. Extraordinarily aggressive cutaneous sarcomatoid squamous cell carcinoma of the face: a case report. Arch Craniofac Surg 2022;23:77–82.

Article information Continued

Fig. 1

An 84-year-old woman with a painful warty lesion on the lower lip.

Fig. 2

Histological results of excisional biopsy (hematoxylin and eosin, ×100).

Fig. 3

Postoperative status on day 1 after the operation.

Fig. 4

(A) Recurrent lesion on the left side of the lower lip adjacent to the primary lesion. (B) Computed tomography scan showing a pathologic lymph node at left level I, appearing enlarged and irregularly shaped (yellow arrows).

Fig. 5

Healed lesion on postoperative day 14.