Cancer of the nasal vestibule

INTRODUCTION — Cancers of the nasal vestibule are rare and account for less than 1 percent of all tumors of the head and neck [1]. The nasal vestibule is separated anatomically from the nasal cavity by the limen nasi. Although they are often classified with nasal cavity cancers, cancers originating from the nasal vestibule behave like squamous cell carcinomas of the skin and are distinct histologic and clinical cancers compared with tumors arising from the nasal cavity. Thus, these tumors are considered separately for diagnosis and treatment.

The presentation and treatment of nasal vestibule cancers are discussed here. Cancers arising in the nasal cavity and paranasal sinuses are discussed separately. (See "Tumors of the nasal cavity" and "Paranasal sinus cancer".)

PRESENTATION

Anatomy and pathology — The nasal vestibule is a pear-shaped opening that functions as the entrance to the nasal cavity. Its borders are the nasal septum and columella medially, the lower lateral nasal cartilage laterally, and the premaxilla inferiorly. The vestibule terminates posteriorly at the limen nasi, the junction of the lower and upper lateral cartilages (scroll region), as well as the transition from skin to mucosa (figure 1 and figure 2). The vestibule is lined with skin-bearing hair follicles, sebaceous glands, and sweat glands.

The majority of nasal vestibule cancers are squamous cell carcinomas that have a natural history similar to that of squamous cell skin cancer. Other types of skin cancers, such as basal cell carcinoma, Merkel cell carcinoma, and melanoma, can also arise in the nasal vestibule. (See "Treatment and prognosis of low-risk cutaneous squamous cell carcinoma (cSCC)" and "Pathogenesis, clinical features, and diagnosis of Merkel cell (neuroendocrine) carcinoma" and "Melanoma: Clinical features and diagnosis".)

Epidemiology and risk factors — The incidence of nasal vestibule cancers has been estimated to be between 0.32 and 0.41 per 100,000 in a Danish national registry [2,3]. The average age of patients with nasal vestibule cancer is between 60 and 70 years [2,4]. Nasal vestibule cancer is more common in males, who constitute 55 to 70 percent of cases. Risk factors include sun exposure and, potentially, smoking [2,5].

Clinical presentation and diagnosis — Due to their external location, tumors of the nasal vestibule are usually relatively limited at presentation and exhibit a more favorable prognosis than tumors of the nasal cavity.

Superficial ulcerations or masses of the membranous septum or columella with crusting, scabbing, and occasional minor bleeding (picture 1) are common presentations. More advanced lesions can perforate the septum or invade the alar cartilage and grow through the skin surface (picture 2 and picture 3). There can also be extension inferiorly into the gingivolabial sulcus, invasion of the premaxillary soft tissues, or osseous invasion of the premaxilla. Growth into the posterior nasal cavity occurs late or with recurrences.

The nasal vestibule lymphatics drain primarily to the submandibular lymph nodes (level Ib). The facial lymph nodes are second-echelon nodes, which may become involved with recurrent disease. The incidence of clinical lymph node involvement at presentation has varied from 0 to 40 percent in various studies [3,4,6-8].

Biopsy is required for pathologic confirmation to establish the diagnosis [9]. The role of additional pathologic evaluations is not clearly defined. Expression of EGFR and p53 has been reported to correlate with worse prognosis [3]. In one observational series of 46 patients with cancers of the nasal vestibule, human papillomavirus and p16^INK4a positivity were reported in 20 percent of cases and did not correlate with outcomes [10].

Staging — Evaluation should include physical examination, computed tomography (CT) scan to assess bone invasion or regional adenopathy, and magnetic resonance imaging (MRI) if there is suspicion for perineural spread or skull base invasion for very advanced tumors.

Two different staging systems are used to describe cancers arising in the nasal vestibule:

●AJCC/UICC staging system – The eighth edition (2017) tumor, node, metastasis (TNM) system developed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) includes cancers of the nasal vestibule (edge of the naris to the mucocutaneous junction) with those arising in the nasal cavity and ethmoid sinus (table 1) [11]. With the exception of tumors that are very advanced or histologically more consistent with nasal cavity origin, we do not recommend using this staging system. (See "Paranasal sinus cancer", section on 'Diagnosis and staging'.)

●Wang staging system – The Wang staging system, which is the most specific to the nasal vestibule, divides cancers of the nasal vestibule into three groups [12]:

•T1 – T1 lesions are relatively superficial and are limited to the nasal vestibule.

•T2 – T2 lesions extend from the nasal vestibule into adjacent structures, such as the nasal septum, upper lip, or skin of the nose, but are not fixed to underlying bone.

•T3 – T3 lesions include those tumors with extension to the hard palate, buccogingival sulcus, upper nasal septum, turbinates, or paranasal sinuses, or those that are fixed to deep muscle or bone.

Several contemporary groups advocate use of the Wang staging system rather than the TNM system for staging of the primary tumor because of its simplicity and better correlation with prognosis [2,4,8].

TREATMENT — The goal of therapy is to achieve the best oncologic outcome with the least morbidity in terms of both cosmesis and nasal function. There are no clinical trials that have established the optimal treatment for these patients; treatment recommendations are based upon observational data from single-institution case series.

For T1 to T2 tumors, primary treatment consists of either surgery or radiation therapy (RT), with either option carrying very high rates of disease control. The choice of modality depends upon the ability to achieve an optimal balance between eradicating the cancer, cosmesis, and nasal function. Surgical excision of very early lesions can be used to avoid the long-term toxicity of RT (dry nose, nasal crusting, recurrent epistaxis, nasal stenosis); however, in many situations, surgery cannot be performed without significant morbidity. In patients with T3 disease, primary surgery with the addition of adjuvant RT, if indicated, is expected to result in higher disease control and is preferred compared with primary RT.

Surgery — Surgery of nasal structures consists of two parts: resection and reconstruction.

Tumor resection — Depending on the extent of the cancer, resection may consist of wide local excision or Mohs micrographic surgery. Deep structures, such as the upper and lower nasal cartilages, septal cartilage, and maxillary bone, may need to be resected. If negative margins cannot be realistically achieved without extensive morbidity, surgery should be avoided. The goal of resection is complete tumor removal with microscopically tumor-free margins. It is critical for the surgeon to appreciate the complex functional and aesthetic anatomy of the nose since it is frequently possible to customize the cancer operation so that optimal reconstruction is feasible. In early tumors, it may be feasible to perform skin-preserving excision to help further preserve cosmesis and function [13].

Outcomes of patients treated with primary surgery generally report favorable outcomes. As an example, one study included 10 patients with limited T1 to T2 lesions who underwent endonasal resection resulting in 100 percent local control with a median follow-up of 37 months [14]. Two patients underwent adjuvant RT for a close margin and positive lymph nodes. In another series of 16 patients with T1 to T2 lesions treated with skin-preserving excision, five-year local control was 83 percent with ultimate local control of 100 percent after salvage for recurrence.

However, other studies report less favorable disease control with primary surgery. As an example, in a series of 45 patients (T1 to T2 disease, 89 percent) treated with primary surgery alone or with postoperative RT (9 percent), five-year local-regional control was only 66 percent [15].

Defect reconstruction — The nose is the central aesthetic feature of the face; thus, meticulous reconstruction of any nasal defect is critical to minimize obvious disfigurement. Nasal reconstructions are typically performed by a fellowship-trained facial plastic or head and neck surgeon.

The nose is divided into subunits: root, dorsum, sidewall, ala, tip, soft tissue triangles, and columella. The units most affected by nasal vestibule cancers include the ala, tip, soft tissue triangles, and columella.

The nose is also considered in terms of three layers: the external lining (skin), supportive structure (cartilage), and internal lining (mucosa).

Optimal nasal reconstruction requires an individualized reconstructive plan for each nasal subunit and each layer. Full-thickness defects require reconstruction of the intranasal lining, cartilaginous skeleton, and overlying skin. The internal lining can be reconstructed with skin grafts or mucosal flaps/grafts. Supportive structures are reconstructed with cartilage grafts (eg, ear conchal cartilage, rib, nasal septum). The external lining can be reconstructed with secondary intention, skin grafts, local flaps (eg, advancement/rotational flaps, bilobed flaps), or regional pedicled flaps (eg, melolabial, paramedian forehead flaps) [16]. Large defects extending into the lips, cheek, maxilla, or oral cavity may require free flaps for reconstruction and/or prosthetic devices. To achieve an optimal aesthetic outcome, multiple surgeries or revisions may be necessary in complex reconstructions.

Radiation therapy — Primary RT may be delivered exclusively with external beam radiation therapy (EBRT) or a combination of EBRT and an interstitial brachytherapy implant. EBRT has traditionally been delivered with photon beams and electron beams. More contemporary radiation techniques like intensity-modulated RT (IMRT) have also been used. The role of proton therapy is not established. (See "General principles of radiation therapy for head and neck cancer".)

Photon EBRT can be delivered either with opposed lateral fields using megavoltage photons or a single anterior portal using a 4:1 mix of high-energy electrons and megavoltage photons; a single en face electron beam can be used alone. The mixed electron-photon technique allows for some sparing of the skin in patients with disease limited to the mucosal surface. Photon IMRT using volumetric modulated arc or static step and shoot techniques can be used to improve the conformity of high-dose target coverage or normal tissue sparing on a case-by-case basis [17].

For any of these techniques, a tissue-equivalent compensator can be placed over the entire nose to convert the irregular nasal surface to a box-like contour to improve the dose distribution. Additionally, tissue equivalent bolus may be placed in the nose to reduce the impact of tissue density inhomogeneity. The dose delivered to the initial EBRT fields is usually 50 Gy given in once daily 2 Gy fractions. This is followed by a boost to the tumor of 20 to 25 Gy using either EBRT or interstitial brachytherapy.

When treating the regional lymph nodes electively, the regional lymphatics are treated to 45 to 50 Gy using conventional or intensity-modulated photon fields. In cases of positive adenopathy, patients may undergo neck dissection followed by regional lymph node irradiation to 50 to 60 Gy or primary RT to 70 Gy. In cases where there is positive adenopathy in level Ib, we recommend elective irradiation of the facial lymph node using superficial electron beams. These are often referred to as "Fu Manchu" fields and are typically matched to the primary site with a 5 mm skin gap.

Acute side effects during RT are moderate desquamation of the skin of the nose and mucosa of the nasal and oral cavity. Following recovery from RT, most patients have permanent dryness and crusting of the nasal cavity, which is best treated with saline washes and daily lubricant ointment. The risk of serious complications in the years after RT, such as cosmetic deformity, pain from tissue necrosis, or severe nasal stenosis/obstruction, is less than 5 percent. Epiphora (excessive tearing of the eyes) from nasal-lacrimal duct stenosis is another rare late complication from RT.

Although interstitial implants of the nasal vestibule are individualized, the implant generally consists of two to four planes of needles inserted through the dorsum of the nose (figure 3). The source is typically low-dose-rate iridium-192. When given as a boost after EBRT, the dose delivered by the interstitial implant is usually 25 Gy. Very early T1 tumors can be treated with interstitial brachytherapy alone, usually 55 to 75 Gy, depending on the tumor size [18]. While brachytherapy alone can yield high cure rates in most patients with T1 tumors [19,20], the incidence of chondronecrosis may be as high as 19 percent [21], suggesting the outcomes may be more favorable when brachytherapy is combined with EBRT.

Locally advanced lesions — More extensive tumors should be treated with a combination of surgery and RT, as these tumors have a low rate of local control with either modality alone [22]. When a combined modality approach is used, RT can be given either pre- or postoperatively. Preoperative RT offers the possibility of shrinking the tumor to allow for a less extensive resection, whereas postoperative RT results in fewer wound complications. The EBRT dose is usually 50 to 60 Gy delivered in 2 Gy fractions.

Resection of advanced-stage lesions may require total rhinectomy. The principles of reconstruction are similar to those for less advanced lesions and may require a free flap, titanium mesh, or multiple flaps. Often a simpler and more cosmetically pleasing alternative may be a nasal prosthesis. (See 'Defect reconstruction' above.)

Management of the neck — A review of the literature analyzed the frequency of lymph node involvement in 20 case series that included over 1000 patients with cancer of the nasal vestibule [8]. The risk of lymph node metastasis at presentation is approximately 6 percent, and another 12 percent develop delayed lymph node metastases.

Patients who present with lymph node-positive disease should be treated with neck dissection at the time of surgery or RT. Lymph node levels included in the treatment should include levels I to III at minimum (figure 4). The decision to pursue elective contralateral neck treatment is based upon whether the lesion encroaches or crosses the midline.

Elective ipsilateral treatment of the neck is generally limited to patients with locally advanced lesions (T3/T4) [22]. In patients with early-stage disease and no clinical evidence of lymph node involvement, some studies advocate against the role of routine elective neck dissection [3]. In one analysis of 30 patients treated with primary resection, including 20 with elective neck dissection, there were no cases of occult lymph metastases among patients with early (Wang T1 to T2) tumors [3].

PROGNOSIS — The key factors influencing long-term outcome after treatment are the extent of local disease (T stage) and the presence or absence of regional lymph node metastases.

The most extensive data using contemporary treatment techniques come from a series of 174 patients treated over a 10-year period at five centers in Denmark [2]:

●The five-year locoregional control rate was 69 percent in the 164 patients without regional lymph node involvement, but none of the 10 patients who had positive lymph nodes at presentation achieved five-year locoregional disease control.

●The five-year locoregional control rate for the 109 patients with T1 lesions according to the Wang system was 79 percent. (See 'Staging' above.)

●Among the 47 patients with T2 primary tumors, the five-year locoregional control rate was 54 percent.

●For the 18 patients with T3 lesions, the five-year locoregional control rate was 35 percent.

●Disease-specific survival decreased with increasing T stage according to the Wang classification (83, 63, and 39 percent for T1, T2, and T3 lesions, respectively).

Additional information about prognosis comes from a single-institution series. This includes a series of 99 patients with squamous cell carcinoma of the nasal vestibule treated at the University of Florida with external beam radiation therapy (EBRT), brachytherapy, EBRT and brachytherapy, or surgery and EBRT [23]. In this series, most T1 to T2 tumors were treated with EBRT. For the entire cohort, the 10-year rates of local control, locoregional control, and disease-specific survival were 82, 73, and 86 percent, respectively. The rate of local control following EBRT alone was 93 percent for T1 to T2 lesions and 77 percent for T3 to T4 lesions. In contrast, the local control rate for T3 to T4 lesions treated with surgery and EBRT was 90 percent.

Other contemporary studies have reported local control rates for T1 to T2 tumors with radiation therapy ranging from 80 to 97 percent, with ultimate local controls of >90 percent after surgical salvage for recurrence [7,21,24].

POSTTREATMENT SURVEILLANCE — Regular posttreatment follow-up is an essential part of the care of patients after potentially curative treatment of head and neck cancer. For patients with nasal vestibule cancers, recurrences can often be salvaged successfully [13]. Patients should be educated about possible signs and symptoms of tumor recurrence. Our approach in these patients is to perform a follow-up examination every two months for the first year, every three months in the second year, every six months during years 2 to 5, and then annually thereafter. Most patients can be followed adequately with clinical exam. Imaging with computed tomography (CT) is warranted if there is suspicion for recurrence with bone involvement or for more thorough evaluation of the regional lymphatics. (See "Posttreatment surveillance of squamous cell carcinoma of the head and neck".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Head and neck cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Throat cancer (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Prognosis – Carcinomas of the nasal vestibule are essentially skin cancers, and the prognosis is related to the stage of tumor at presentation. (See 'Presentation' above and 'Prognosis' above.)

●Early-stage disease – For patients with early-stage tumors, either surgery or radiation therapy (RT) is an effective treatment option, with surgery preferred if minimal morbidity can be achieved with reconstruction. RT alone is also an excellent treatment modality (Grade 2C). (See 'Radiation therapy' above and 'Surgery' above.)

●Locally advanced disease – For patients with more extensive tumors that involve bone, we suggest surgical resection followed by adjuvant RT (Grade 2C). (See 'Locally advanced lesions' above.)

●Management of the neck – For patients with advanced (T3/T4) disease, we suggest elective treatment of the neck with either neck dissection or RT (Grade 2C). (See 'Management of the neck' above.)

ACKNOWLEDGMENTS — The editorial staff at UpToDate acknowledge Anamaria Yeung, MD, and John Werning, MD, DMD, FACS, who contributed to an earlier version of this topic review.