Sir,

An 86-year-old female presented with a painful, brownish-red nodule on her right cheek, measuring approx. 5 mm in diameter (Fig. 1). Symptoms had persisted for one month. Her medical history included hypertension, Meniere’s disease, angina, ileus, and hepatitis C. Given the palpable induration and pain, an external dental fistula was initially suspected. However, computed tomography (CT) revealed localized skin thickening with contrast enhancement yet no evidence of oral skin continuity, invasion, or metastasis. Contrast-enhanced MRI displayed a high-intensity area approx. 4 cm in size along the cutaneous surface in the right buccal region, with underlying subcutaneous fat showing a faint high signal (Fig. 2). A skin biopsy revealed keratin-producing atypical keratinocytes infiltrating the deep dermis and subcutaneous fat (Fig. 3a). The lesion was excised with a 6 mm margin. Histopathological analysis confirmed infiltrative tumor growth with perineural invasion (Figs. 3b and 3c), and tumor thickness was 3 mm. Immunostaining showed positivity for cytokeratin AE1/AE3 (Fig. 3d), focally positive for vimentin, and negativity for S-100, leading to a diagnosis of poorly to moderately differentiated squamous cell carcinoma (SCC) with perineural invasion (PNI). Despite re-excision with a 1 cm margin, the posterior margin remained positive. Due to surgical limitations, the patient underwent radiotherapy, which led to gradual tumor regression.

	Figure 1: Brownish-red nodule on the cheek (arrow).
	Figure 2: High-intensity area (~4 cm) along the cutaneous surface in the right buccal region with the underlying subcutaneous fat showing a faint high signal (arrow).
	Figure 3: (a) Skin biopsy showing a keratin-producing proliferation of atypical keratinocytes within the deep dermis and subcutaneous fat (H&E, ×4). (b) Infiltrative growth of tumor cells (H&E, ×10). (c) Tumor cells with perineural invasion (H&E, ×20). (d) Immunostaining for cytokeratin AE1/AE3 showing positivity in tumor cells (×10).

Perineural invasion (PNI), defined as tumor invasion into adjacent peripheral nerves, occurs in <6 % of cutaneous SCCs [1,2]. Reports of SCC with PNI describe nodules of varying sizes, including a 3 cm malar nodule, a 12 mm subcutaneous nodule on the dorsum of the hand, and a 16 × 6 cm ulcerated tumor in the popliteal fossa [3–5], often accompanied by paresthesia and/or pain [3–5]. Symptoms of cutaneous SCC with PNI in the head and neck include numbness (56.7%), neuropathic pain (43.3%), facial palsy (39.2%), subcutaneous mass (34.2%), and paresthesia (30.8%) [6]. In this case, the tumor was notably small, measuring only 5 mm in diameter, yet demonstrated extensive PNI and subcutaneous invasion, highlighting the disproportionate extent of nerve infiltration. MRI findings, including a high-intensity area along the cutaneous surface and faint high signals in subcutaneous fat, were likely indicative of nerve invasion. Tumor invasion extended deeply into the subcutaneous induration. These findings emphasize the critical role of dermatopathological evaluation and advanced imaging such as MRI in identifying PNI in small, painful facial nodules.

In conclusion, SCC with PNI, although rare, should be considered in the differential diagnosis of painful facial nodules, even when the lesion is small. Comprehensive dermatopathological examination and MRI are invaluable for the early identification and management of PNI.

REFERENCES

1. Warren TA, Nagle CM, Bowman J, Panizza BJ. The natural history and treatment outcomes of perineural spread of malignancy within the head and neck. J Neurol Surg B. 2016;77:107-12.

2. Leibovitch I, Huilgol SC, Selva D, Hill D, Richards S, Paver R. Cutaneous squamous cell carcinoma treated with Mohs micrographic surgery in AustraliaII. Perineural invasion. J Am Acad Dermatol. 2005;53:261-6.

3. Sarsam S, Gunatheesan S, Mann N. Cutaneous squamous cell carcinoma of the hand presenting as clinical perineural invasion. EMJ 2023 May [cited 2023 May 16]. Available from:URL:https://doi.org/10.335990/emj/10308127.

4. Bard JT, Duran SF, Roberts AA, and Wentzell JM. A Distinctive histological form of squamous cell carcinoma with perineural invasion. Cureus. 2022;14:25111.

5. Miyagawa F, Hirose C, Fukumoto T, Asai H, Kobayashi N, Asada H. Cutaneous squamous cell carcinoma with extensive perineural invasion and perineural cyst formation without regional lymph node metastases. J Dermatol. 2015;42:930-1.

6. Warren TA, Whiteman DC, Porceddu SV, Panizza BJ. Insight into the epidemiology of cutaneous squamous cell carcinoma with perineural spread. Head Neck. 2016;38:1416-20.