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A Difficult Diagnosis

A man with an enlarging lower lip lesion

Colon, Alysha; Saikaly, Sami K. MD; Ramos-Caro, Francisco A. MD

Author Information
Journal of the American Academy of Physician Assistants: January 2021 - Volume 34 - Issue 1 - p 55-57
doi: 10.1097/01.JAA.0000723968.13786.c4
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A 55-year-old man presented to the dermatology clinic with an abnormal-appearing lesion on his lower lip.


The patient noticed the lesion about a year ago, when he tried to pull an ingrown hair from the area. He stated that the lesion is painful and started growing 6 months ago but doubled in size in the past 2 months. He tried over-the-counter topical antibiotics, which did not help. He denied constitutional symptoms or history of previous lip lesions. He smokes tobacco cigarettes and has a 37-year smoking history. He denied a previous history of extensive sun exposure, head and neck radiation, skin cancer, or sunscreen use. His family history was noncontributory.

Physical examination

An ulcerating 5.5x3x2 cm indurated, fungating plaque involving the lower vermillion/cutaneous lip was noted (Figure 1). The patient had no cervical lymphadenopathy and the rest of the skin examination was unremarkable.

The patient's lip lesion


  • basal cell carcinoma (BCC)
  • squamous cell carcinoma (SCC)
  • granulomatous cheilitis
  • actinic cheilitis


A shave biopsy from the lesion displayed a tumor composed of keratinocytes with prominent intercellular bridges and dyskeratotic cells. Pleomorphic keratinocytes and occasional mitoses were also present confirming the diagnosis of invasive SCC. Because of the lesion's size and location, the patient agreed to excisional surgery and was referred to an ear, nose, and throat (ENT) specialist, who performed a wide local excision with a left radial forearm free flap repair.

The patient's postoperative course was complicated by an orocutaneous fistula and left forearm donor site dehiscence, which have both since healed. Initial CT of the head and neck did not demonstrate any metastatic adenopathy or spread. However, several months later, the patient received imaging for an unrelated issue that was concerning for left submandibular lymphadenopathy. Fine-needle aspiration was performed and revealed markedly atypical epithelial cells with inflammation and necrotic debris consistent with SCC. The patient's case was presented at the ENT head and neck tumor board, where palliative systemic chemotherapy was recommended. The patient has not received further treatment.


Cutaneous SCC is the second most common nonmelanoma skin cancer.1 Because nonmelanoma skin cancers are not accounted for in the US national cancer registries, the exact incidence of SCC is unknown. In the literature, SCC is projected to have a lifetime incidence of 7% to 11% in the United States.1 A study by Muzic and colleagues found that the overall incidence of cutaneous SCC increased 263% between 1976 and 2010.2 The average age of onset is in the patient's 50s, and the incidence is higher in men.1 Fair skin, sun exposure, ultraviolet radiation, and smoking are major risk factors for SCC.1 The case patient had many of these risk factors. Although patients with fair skin are at an increased risk, SCC can occur in those with darker skin. In patients with darker skin, SCC often is associated with greater morbidity and mortality due to atypical clinical presentations that delay diagnosis and treatment.3 Compared with White patients, in Black patients SCC can present as keratotic brown or black hyperpigmented papules or plaques, and is more likely to be distributed in non-sun-exposed areas such as the lower legs and anogenital region.3

Similar to the case patient, patients with invasive SCC often present with a history of a persistent ulcer or nonhealing wound.1 However, the definitive diagnosis of SCC is made through biopsy and histopathology. Although the term persistent may have varying meanings among clinicians, our office recommends patients return for a biopsy if a lesion has not healed or resolved within 3 to 4 weeks. SCC tumors involving the lip, temple, or dorsal side of the hands carry a higher risk of metastasis.4 SCC accounts for about 20% of skin cancer deaths because of its ability to metastasize.4 In cutaneous SCC, the most common site of metastasis is the regional lymphatic nodes found in the parotid gland.4

Treatment for SCC typically is surgical excision with 4-mm margins for low-risk tumors less than 2 cm in diameter, and 6-mm margins for tumors greater than 2 cm or those with high-risk features.1 High-risk features include moderate, poor, or lack of differentiation and lesions presenting on the ear, eyelid, lip, scalp, or nose.1 Tumors with a diameter greater than 2 cm are highly associated with disease-specific death.1 The patient in this case presented with a tumor greater than 2 cm on a high-risk location, which prompted urgent evaluation and treatment.

The differential diagnosis of SCC on the lip includes BCC, granulomatous cheilitis, and actinic cheilitis. BCC (Figure 2) is the most common nonmelanoma skin cancer.1 Although exact numbers are difficult to determine, BCC is estimated to have a lifetime incidence of 28% to 33% in the United States.1 As seen in the case patient, lower-lip cancers most often are due to SCC, and upper lip cancers usually are BCC.5


On physical examination, SCC usually presents as an erythematous papule with keratin crust or scale. In contrast, BCC usually presents as pearly pink papules with arborizing telangiectasias, which was not seen in the case patient's physical examination. BCC can be a locally destructive skin cancer but rarely metastasizes or results in skin cancer-related death.4 Because of the patient's history, physical examination, and the location of the lesion, clinicians had a higher suspicion for SCC than BCC. However, the definitive diagnosis was made through biopsy and histopathology.

Granulomatous cheilitis (Figure 3) is a rare, chronic, idiopathic lip swelling caused by noncaseating granulomatous inflammation and can affect one or both lips.6 The initial episode subsides within hours or days; however, the frequency and duration of these episodes of lip swelling progressively rise until they become persistent.6 The condition has no definitive treatment but numerous treatments are available, including dietary modifications, antibiotics, corticosteroids, and surgery. However, treatment is not always necessary.6 Although the case patient presented with lower-lip swelling, the growth of his lesion was gradual and had never occurred before, making the diagnosis of granulomatous cheilitis less likely.

Granulomatous cheilitis of the upper lip, left sideReprinted with permission from Critchlow WA, Chang D. Cheilitis granulomatosa: a review. Head Neck Pathol. 2014;8(2):209-213

Actinic cheilitis (Figure 4), a premalignant process of the lower lip related to sun exposure, can eventually undergo malignant development into SCC.7 Lesions typically occur along the vermillion border and appear rough and scaly, with some sites developing focal ulceration.7 Biopsy is recommended for cases in which there is loss of the demarcation between the mucosal and cutaneous lip, change in texture of the lip, change in thickness, and presence of ulceration.7 The goal of treatment is to remove the atypical epithelium, which can be accomplished with surgery, topical 5-fluorouracil, laser ablation, cryotherapy, or electrocauterization.7 Because actinic cheilitis is a premalignant process of SCC, the risk factors and history for both conditions can be similar. However, based on the clinical appearance of the case patient's fungating lesion, SCC was of higher suspicion, which was later confirmed with the histopathology.

Actinic cheilitis


With the increasing overall incidence of SCC and the poor outcomes associated with large tumors of the lip, early diagnosis and treatment is crucial. Refer patients to dermatology if they have persistent or nonhealing lesions anywhere on the body, especially on the lip given the high risk of metastasis. This case highlights the importance of clinicians being aware of differing skin lesions involving the lip and to be able to identify high-risk features to provide proper counseling, education, and coordination of care for patients.


1. Kallini JR, Hamed N, Khachemoune A. Squamous cell carcinoma of the skin: epidemiology, classification, management, and novel trends. Int J Dermatol. 2015;54(2):130–140.
2. Muzic JG, Schmitt AR, Wright AC, et al. Incidence and trends of basal cell carcinoma and cutaneous squamous cell carcinoma: a population-based study in Olmsted County, Minnesota, 2000 to 2010. Mayo Clin Proc. 2017;92(6):890–898.
3. Higgins S, Nazemi A, Chow M, Wysong A. Review of nonmelanoma skin cancer in African Americans, Hispanics, and Asians. Dermatol Surg. 2018;44(7):903–910.
4. Burton KA, Ashack KA, Khachemoune A. Cutaneous squamous cell carcinoma: a review of high-risk and metastatic disease. Am J Clin Dermatol. 2016;17(5):491–508.
5. Queen D, Knackstedt T, Polacco MA, et al. Characteristics of non-melanoma skin cancers of the cutaneous perioral and vermilion lip treated by Mohs micrographic surgery. J Eur Acad Dermatol Venereol. 2019;33(2):305–311.
6. Critchlow WA, Chang D. Cheilitis granulomatosa: a review. Head Neck Pathol. 2014;8(2):209–213.
7. Vieira RA, Minicucci EM, Marques ME, Marques SA. Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects. An Bras Dermatol. 2012;87(1):105–114.
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