Introduction

Renal cell carcinoma (RCC) accounts for approximately 2–3% of all adult malignancies and is well known for its unpredictable metastatic pattern.[1] While the lungs, bones, liver, and brain are common sites of secondary involvement, metastases to the oral cavity are exceedingly rare, representing less than 1% of all RCC metastases. [1] Within the oral region, the jawbones, tongue, and gingiva are more frequently affected; involvement of the labial mucosa is exceptionally uncommon, with very few cases documented in the literature.[2] Such atypical presentations may mimic primary oral malignancies or benign lesions, posing a diagnostic challenge.[2] We report a rare case of metastatic RCC presenting as a swelling on the labial aspect of the lower lip.

Case History

An eighty-year-old male presented with swelling on the labial aspect his lower lip that had persisted for three months. He reported no associated pain but experienced mild discomfort during mastication. There were no systemic complaints such as haematuria, weight loss, or flank pain. He was a known hypertensive on medication. He had got his dentures about three months ago. There is no other significant past history. On examination, a firm, well defined, erythematous nodule was noted on the mucosal aspect of the lower lip. The overlying mucosa appeared stretched but intact. No cervical lymphadenopathy was detected.

The lesion was excised under local anaesthesia. Gross examination showed a reddish brown, well circumscribed soft tissue mass. Histopathological examination revealed an ulcerated lesion with dilated vascular spaces. Individual cells showed epithelioid morphology.(Figure 1) Our differential diagnosis included tumours of vascular, salivary gland or metastatic origin. Immunohistochemistry(IHC) showed strong positivity for PanCK, CD10, patchy strong nuclear staining with PAX8, weak staining of SMA and strong membrane staining of the epithelioid cells with CA IX.(Figure 2) Ki67 index was around 30%. IHC was negative for CD 34, CD31, p63, CK 7, CK20, HMB 45, S100 negating the possibility of melanocytic and salivary gland tumours. These markers confirmed the diagnosis of metastatic carcinoma of renal origin.

Figure 1: Histopathology section of the swelling displaying vascular channels(a) and epithelioid cells(b)

Figure 2: Immunohistochemistry markers a. Positive, b. Positive, c. Patchy strong nuclear staining, d. Strong membrane positivity, e. Weak staining, d. Negative

Postoperative recovery was uneventful. The patient was referred for systemic imaging and oncology evaluation. PET-CT demonstrated a heterogeneously enhancing mass lesion measuring 7.8x7.7x7cm in the mid and lower pole of left kidney along with non-occlusive thrombus in the left renal vein, multiple nodular lesions in the left lung and also a 7x6 mm lesion in the left post central gyrus.

Discussion

Renal cell carcinoma is the commonest primary renal neoplasm and accounts for approximately 80% of all renal malignancies.[3] Most cases of RCC are diagnosed incidentally during radiological investigations. [4] Haematuria, flank pain, and a palpable mass, collectively referred to as the "classical triad," are observed in merely 10% of patients.[5] A distinguishing trait of RCC is its long-term asymptomatic clinical behaviour and substantial risk of metastasis to distant organs in advanced stages. [5]

According to the literature, 18% of patients with RCC have metastases at the time of diagnosis. More than half of the cases show metastases during the follow-up period after nephrectomy. [4]

RCC typically metastasizes to the lungs, bones, liver and brain; cutaneous metastasis, particularly to the facial region, account for only 1-3% of cases.[3] Kidney is the third most common primary site for oral metastases.[3] Well known sites of metastasis in oral cavity include tongue, gingiva and mandible. [1] Other sites includes nasal cavity, hard palate, maxillary sinus, thyroid gland, larynx, lymph node, parotid gland, tonsils, facial muscles and orbit.[1, 5] Involvement of the lower lip is exceedingly rare, with only a small number of cases described in the literature.[1] In the present case, the swelling was present on the labial aspect of the lower lip, which is an incredibly uncommon location.

The mechanisms underlying RCC metastasis to the head and neck, specifically to the lower lip are not fully understood. Haematogenous dissemination is thought to be the likely route, given the abundant vascularity of the renal parenchyma and perioral region. [5] The rich vascular supply of perioral region, in conjunction with chemokine gradients and adhesion molecule expression, likely enhances tumour cell colonisation and growth. The abundant capillary bed within oral mucosa provides an ideal environment for metastatic proliferation.[5]

Clinically, metastatic lesions on the lip may present as rapidly enlarging, painless, erythematous nodules or ulcerative mass, sometimes mistaken for primary neoplasms such as squamous cell carcinoma or other vascular lesions. [4] Histopathological features and immunohistochemistry are indispensable for diagnosis of metastatic RCC.[5] Radiology imaging is helpful for detecting additional metastatic foci, as up to 90% of patients with cutaneous RCC metastasis have concurrent metastasis in organs such as the lungs or bones. [4]

In some cases, lip metastasis may be the initial or only manifestation of systemic disease and in others it can appear years after nephrectomy. [5] This highlights the need for long term follow-up of RCC survivors. Furthermore, the existence of such metastasis as the initial presentation of RCC highlights the importance of considering a metastatic origin for any atypical lip lesion, especially in patients with a history of malignancy. The prognosis of RCC patients with oral or lip metastasis is poor, reflecting advanced systemic disease. [5]

The first case of renal cell carcinoma (RCC) metastasis to the lip was reported by Bernier and Tiecke in 1951, involving the lower lip.[2] Subsequently, Fitzgerald described a case of upper lip metastasis in 1982.[2] A systematic review of published cases from 1911 to 2022 identified 250 cases of RCC metastasis to oral soft tissues, with only 12 cases involving the lip, underscoring the extreme rarity of this presentation.[5]

Metastasis of renal cell carcinoma to the lower lip is an unusual event, but signifies an advanced disease. It poses a diagnostic and therapeutic challenge due to its rarity and potential for misdiagnosis. Although a high index of suspicion is required, accurate diagnosis relies on histopathological examination and immunohistochemistry. Prompt recognition, histopathological confirmation, and multidisciplinary management are essential for optimising the patient outcomes.

References

1. Joy A, Kumar A, Radhakrishnan N. Metastasis from renal cell carcinoma-unusual presentations. J Cancer Res Ther. 2023 Dec 15. doi: 10.4103/jcrt.jcrt_2738_22.
2. Jatti D, Puri G, Aravinda K, Dheer DS. An atypical metastasis of renal clear cell carcinoma to the upper lip: a case report. J Oral Maxillofac Surg. 2015 Feb;73(2):371.e1-6. doi: 10.1016/j.joms.2014.09.006.
3. Sountoulides P, Metaxa L, Cindolo L. Atypical presentations and rare metastatic sites of renal cell carcinoma: a review of case reports. J Med Case Rep. 2011 Sep 2;5:429. doi: 10.1186/1752-1947-5-429.
4. Chen DY, Uzzo RG: Evaluation and management of the renal mass. Med Clin North Am 2011, 95(1):179-189.
5. Prajapati HV, Shreevats R, Gupta S, Sandhu H, Kaur J, Kaur J. Renal Cell Carcinoma Metastasizing to Oral Soft Tissues: Systematic Review. Avicenna J Med. 2024 May 6;14(2):75-109. doi: 10.1055/s-0044-1782202.