Late-Onset Metastasis of Renal Cell Carcinoma: A Rare Case of Sinonasal Malignancy Post-Nephrectomy

Abstract

This case report highlights a rare case of renal cell carcinoma metastasis to nose and paranasal sinuses in a 55-year-old male 8 years post-nephrectomy. Contrast imaging revealed a vascular mass and histopathology confirmed metastatic RCC. Partial maxillectomy was done and patient remained disease free at 6 month follow up.

Introduction

Unilateral nasal masses always pose a diagnostic challenge with their rare presentations. Sinonasal tumors are often found to have localized primary in origin. Metastasis to the nasal cavity and the paranasal sinuses, although rare, is not uncommon. However, in case of suspicion of metastasis to this region, Renal Cell Carcinoma (RCC) is one of the common primary tumors which can metastasize to the sinonasal tract [1]. RCC is predominant in males in the fifth-sixth decade of life and accounts for 2% global cancers and deaths [2]. Delayed metastases can occur after many years of resection of the primary tumor without the recurrence of the primary [3]. With very few cases reported in the literature, there are no definite guidelines described for metastatic sinonasal RCC [4].

In this case report, the authors present one such unique case of late metastasis of RCC to the maxillary sinus and nasal cavity 9 years after nephrectomy and complete treatment of the primary tumor.

Case Report

A 55-year-old, male, chemical factory worker came with chief complaints of left side nasal obstruction since 7 months. Patient underwent tooth extraction of last two upper molars on left side 6 months back and left nephrectomy due to Renal Cell Carcinoma (RCC) 9 years back. He was a known tobacco chewer, smoker and alcoholic for 30 years. On local examination of nose, a single, pale-pinkish mass was seen in the left nasal cavity at the level of anterior end of inferior turbinate. On probing, it was soft to firm in consistency, tender, did not bleed on touch and probe was negotiable superiorly and medially around the mass. Right nasal cavity was clear. Septum was slightly deviated to the right side. Diagnostic Nasal Endoscopy (Fig. 1) revealed a single, smooth surfaced, globular, pulsatile mass was visualized arising from the middle meats with widening of the maxillary sinus ostia and extending posteriorly up to the choana of the left nasal cavity. Oral cavity examination showed a bulge in place of the left upper two molars. On palpation, the bulge was soft, non-tender, diffuse with possible bony breach of maxilla. Laryngeal examination (IDL) was normal and no lymphadenopathy. CT scan of Nose and PNS (Fig. 2) showed a solitary heterogeneously enhancing soft tissue attenuation mass lesion involving the entire left maxillary sinus. Posterior extent till just before the left choana; inferiorly, the lesion causing destruction of inferior and medial walls of maxillary sinus with lesion extending into left nasal cavity; rarefaction of maxillary sinus wall anterior-laterally. CE-MRI of PNS and Nose (Fig. 3) revealed a well-defined enhancing mass lesion seen encapsulated in left maxillary sinus infiltrating into the left superior alveolar arch of maxilla inferiorly, inferior walls of the orbit superiorly; extending medially into the nasal cavity through eroded anterior and medial wall of sinus. A small branch of Left internal maxillary artery was seen as the primary supplying vessel to the mass lesion on MR Angiography. Biopsy was done under local anesthesia and the histopathological report revealed fibroconnective and fibromyxoid stoma with tumor cells arranged in sheets and nests separated by many dilated blood vessels suggestive of Metastatic renal Cell Carcinoma. PAX8, CD10 and Vimentin were positive on immunohistochemistry (IHC). A preoperative PET CT was done to rule out metastasis elsewhere in the body and was found to be negative; following which, the patient was taken up for left partial maxillectomy and tumor resection under general anesthesia. As the tumor mass was well encapsulated, it was easily dissected from the lateral and anterior walls of the maxillary sinus. As the dissection proceeded posteriorly, the feeding vessel was identified and cauterized. After complete resection of the tumor with clear margins, the resection specimen was sent for histopathological examination which also showed Metastatic RCC. Whole body PET CT done 6 months later showed no evidence of recurrence or residual disease.

Fig. 1.

Nasal endoscopy findings of the sinonasal mass: (a) Mass filling the nasal cavity seen arising from the lateral wall and involving the inferior turbinate. (b) Minor blood vessels seen on the surface of the globular mass. (c) Mass arising from the left maxillary sinus obliterating the osteo-meatal region

Fig. 2.

CT findings showing soft tissue attenuation in left maxillary sinus with destruction of medial and inferior and lateral maxillary walls

Fig. 3.

Contrast Enhanced MRI showing well defined encapsulated enhancing mass lesion with lobulated margins in left maxillary sinus eroding the left superior alveolar arch of maxilla

Discussion

Typically, tumors in the nasal cavity and paranasal sinuses originate as primary tumors. Metastasis to these sites is quite uncommon, however, among those that occur, RCC is the most common tumor documented in literature to metastasize to this region. Other tumors with metastasis to the sinonasal region are tumors of lungs, breast, regional lymph nodes, urogenital and gastrointestinal tract [5]. Maxillary sinus (36%) is the most commonly involved region in sinonasal metastasis followed by ethmoids (25%), frontal and sphenoid sinuses (17%) and nasal cavity (11%) [6]. While RCC is the third most common cancer that metastasizes to head and neck region with 15% incidence, it is extremely rare to have isolated metastasis to the nose and paranasal sinuses, comprising fewer than 1% of all RCC metastases [7].

In 1982, Matsumoto and Yanagihara were the first to describe metastasis of renal cell carcinoma to paranasal sinuses [8]. There are less than 60 cases of sinonasal metastasis of RCC reported in the literature. About 20% patients tend to develop metastasis after initial diagnosis of RCC in early stage and after having undergone previous nephrectomy before recurrence in the sinonasal region [3]. Sinonasal metastasis form renal malignancy can occur even several years after the primary is treated with nephrectomy [9]. According to existing literature, approximately 20–30% of patients with RCC develop metastases usually within 5 years of curative nephrectomy, with about 11% exhibiting late recurrence and metastasis, 10 years or more post nephrectomy [9]. Friberg proposed mechanisms for late metastasis in cancer suggesting that after the primary tumor is removed, metastatic cells can remain dormant for decades before dormancy breaking leads to late recurrence [10]. Late metastasis to sinonasal region is rare and recurrence is even rarer in absence of primary tumor [3].

Two potential routes of metastatic spread of RCC to the nose and paranasal sinuses have been described. Hematogenous spread is the most common route which includes spread either via inferior vena cava, heart, lungs and up to maxillary artery or via retrograde flow through avalvular vertebral venous plexus, intracranial venous plexus, and cavernous venous plexus to the paranasal sinuses [11]. Nahum and Bailey proposed hematogenous spread by Batson’s venous plexus wherein RCC metastasis to head and neck region potentially bypasses the lungs through the fine pulmonary filter beds [12]. The other route is via retrograde flow through the lymphatic channels involving the intercostal, mediastinal, or supraclavicular lymph nodes [6].

These tumors are known to be highly vascular mostly due to VHL mutation resulting in up-regulation of HIF 1- alpha which in turn results in VEGF up-regulation and increased angiogenesis [13]. Mutations with loss of heterozygosity in a large group of chromatin remodeling genes are also associated genetic events occurring in RCC metastasis. The most common histological subtype of RCC to show metastasis is Clear Cell Carcinoma (70%) [14].

Petruzzelli et al., reported the most common presenting sign to be epistaxis (55%) followed by nasal obstruction (28%) [4]. Although, in our case, the tumor was not associated with epistaxis, despite being hypervascular similar to a case reported by Joo et al. [3]

CT scan provide information about a lesion being benign or malignant in terms of bone erosion, remodeling and hypervascularity [4]. Contrast Enhanced CT of thorax should be done to rule out any lung metastasis. MRI with contrast is sought after when the extent of the lesion is too large to be confirmed by CT alone for a potential diagnosis [11]. Given the hypervascular nature of the tumor mass, it is better to get MR angiography done as well in order to identify the tumor feeding vessels. To minimize the risk of bleeding intraoperatively such as intralesional vasoconstriction or topical decongestion [15]. Once histopathology results confirm metastatic RCC, the renal system and other areas prone to RCC metastasis such as the lungs, bone, and brain should also be examined, with urinalysis, ultrasonography, and whole-body PET-CT scan [11].

Differentiating a primary sinonasal clear cell carcinoma from a metastatic RCC is based on a number of factors like complete history and examination of the patient, whether any history of previous RCC, and most importantly, radiological imaging like MRI of whole abdomen and paranasal sinuses or one can go for whole body PET-CT as well. Absence of active kidney disease or enhancement on the scan, but enhancement with features of clear cell RCC in the paranasal sinus region may indicate primary sinonasal clear cell carcinoma. However, an enhancement in the sinonasal region with features consistent with post op nephrectomy or with mild enhancement of kidney, may indicate metastasis.

Treatment of metastatic RCC depends on the tumor location, number of sites of metastasis and the status of the primary tumor. Usually, RCC metastasize to multiple sites such as lung or liver, which is best suited for palliative treatment. However, in cases of single site metastasis to nasal cavity and paranasal sinuses, surgical resection is the ideal treatment of choice [16]. For limited and localized disease, endoscopic resection (medial maxillectomy) is recommended as it offers effective control and better recovery. In case of extensive sinonasal spread, Maxillectomy via open approach is recommended [3]. Given the heterogeneity of this disease, treatment algorithm for patients with metastatic RCC maybe variable and even case specific, including active surveillance, surgery (open or endoscopic), stereotactic ablation radiotherapy, and multidisciplinary systemic therapies with appropriate risk stratification [17]. In unresectable cases, other options like radiotherapy, chemotherapy and targeted immunotherapy should be considered.

Conclusion

ENT specialists should remain vigilant for metastatic disease in patients with nasal or paranasal masses, especially those with hypervascular features, history of significant nasal bleeding and previous history of cancer. Conducting a comprehensive preoperative workup, including total body CT scans, is essential to assess the extent of metastasis. Surgeons must be prepared for substantial hemorrhage during surgical removal due to the highly vascular nature of metastatic tumors from primary kidney masses. Early detection and diagnosis of metastatic renal cell carcinoma (RCC) can lead to better management of perioperative complications and improved survival outcomes. For isolated sinonasal metastasis, surgical management is the ideal treatment.

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