A Rare Nasopharyngeal Adenoid Cystic Carcinoma: Case Report and Literature Review

Background

Adenoid cystic carcinoma (ACC) is a malignant tumor that involves the salivary glands and is rarely seen in the nasopharynx [1]. ACC was first described in 1856 by Theodor Billroth as “cylindroma” due to its long amorphous compartments, which look like cylinders [2]. ACC accounts for about 4% of all epithelial salivary neoplasms and 1% of all head and neck malignancies [3,4]. Previous studies have concluded that nasopharyngeal ACC accounts for 0.48% of all nasopharyngeal cancers [5,6]. ACC is characterized by pain, a high rate of recurrence, poor survival rate, and poor prognosis as it tends to invade the perineurium [7].

Although ACC is considered a rare disease, the purpose of the present study is to highlight the discrepancy and complexity of patients’ presentations and the intricacy of its management approach. In this paper, we report a case of a nasopharyngeal mass diagnosed as ACC. Also, a comprehensive literature search was conducted using the PubMed, Web of Science, Google Scholar, and Saudi Digital Library databases. The articles were examined to extract information on treatment modalities and outcomes for ACC.

Case Report

The patient in this case report was an otherwise healthy 56-year-old male smoker who presented to the clinic in March 2022 complaining of nasal obstruction, mouth breathing, recurrent epistaxis, headache, and facial pain. He reported significant weight loss in the past 6 months. The nasal scope showed nasopharyngeal fullness due to an intact mass in the mucus with no ulceration or asymmetry. The tympanic membranes and cranial nerves were bilaterally intact. Computed tomography (CT) of the nasopharynx and sinuses with intravenous contrast reported a large nasopharyngeal mass with necrotic changes and invasion of the skull base, sphenoid, and pterygoid bones; more extensive destruction was seen on the right side; and abutment of the inferior aspect of the temporal lobe on the right side, with invasion of the sphenoid air sinus. An intraoperative biopsy was thus warranted and arranged; it was done on the mass located in the pharyngeal recess (Rossen Müller fossa). The results confirmed intermediate- to high-grade ACC. The biopsy confirmed that the tumor exhibited tubular, solid, and focal cribriform growth patterns (Figure 1). Magnetic resonance imaging (MRI) of the neck was then performed, and it showed a locally advanced nasopharyngeal carcinoma measuring 5.7×4.8×4.4 cm with parapharyngeal invasion of the clivus and base of the skull with intracranial extension. Invasion was also seen into the left cavernous sinus and left carotid canal, associated with multiple sites with small upper cervical lymphadenopathy (Figure 2). CT of the chest abdomen and pelvis revealed innumerable bilateral lung nodules in keeping with metastasis (Figure 3). There was no evidence of metastasis in the abdomen or pelvis.

The final staging of the mass was an advanced nasopharyngeal carcinoma with parapharyngeal invasion and intracranial extension with multiple sites of small upper cervical lymph-adenopathy and innumerable bilateral lung nodules, indicating lung metastasis suggestive of T4N1M1 (stage IVb). A board meeting was held, and a decision was made for palliative concurrent radiotherapy and chemotherapy. The patient was started on 1480 cGy in 4 fractions to the nasopharynx and skull base and was administered cisplatin, doxorubicin, and cyclophosphamide. In addition, the patient was referred to a pain management service.

In the 1-year followup period, the patient demonstrated significant improvement with regard to pain and discomfort. Also, he tolerated the chemoradiation sessions with minimal adverse effects. A followup MRI after therapy showed an interval decrease in the size of the invasive nasopharyngeal mass and a reduced enhancement pattern, with signal characterization of the central aspect of the tumor as well as the skull base indicating good local response (Figure 2). A fluorodeoxyglucose-positron emission tomography (PET) scan was performed after therapy showed significant interval decreases in size and number of previous multiple pulmonary nodules (Figure 3). As a result of this good initial response, additional high-dose radiation consisting of 5000 cGy in 20 fractions was offered to the patient. However, although this further measure might improve the disease control, it was still considered a component of a palliative management strategy. The patient agreed and is continuing his therapeutic plan, with satisfactory symptomatic control.

Discussion

ACC is a malignant epithelial tumor that commonly affects patients in the fifth decade of life [1]. Some studies have concluded that ACC accounts for 0.5–4% of all carcinomas in the nasopharynx [8,9]. Genetic susceptibility is thought to play a role in the development of ACC. Translocations resulting in fusion of the vMYB gene on chromosome 6 to the NFIB gene on chromosome 9 are seen in most cases and appear to be involved in the pathogenesis [10,11].

The typical histopathological features of ACC show 3 growth patterns: cribriform, tubular, and solid. Tubular patterns display the best prognosis, while solid patterns usually have the worst prognosis and a high incidence of distant metastasis [12,13]. Frequently, more than one subtype is seen, and occasionally, the 3 subtypes are seen together, which led Szanto et al to classify ACC into 3 grades: Grade 1, with tubular and crib-riform patterns without the solid pattern; Grade 2, mainly involving the cribriform pattern, with a less than 30% solid pattern; and Grade 3, which is mainly solid [14]. According to the World Health Organization, ACC tumors have “the propensity for perineural invasion,” “facial nerve paralysis may occur,” and ACC “can extend along nerves for a considerable distance beyond the clinically apparent boundaries of the tumor” [15].

The main challenge with regard to ACC is that it has an insidious onset and a slow growth rate. Thus, the tumor may go unnoticed as it can commonly present with nonspecific symptoms, such as epistaxis, aural fullness, nasal obstruction, or headaches. The interval between the onset of the disease and the onset of the first complaint is around 2–5 years [16,17].

ACC tumors tend to metastasize but seldom involve the lymph nodes [18]. Distant metastasis is present in about 30–60% of the cases, with the lung as the most involved site [1,19,20]. ACC is among the most common malignancies and is prone to perineural invasion (PNI). When PNI is present, it is considered a poor prognostic factor as it is sometimes believed to be the fourth pathway of metastasis after hematogenous spread, lymphatic spread, and direct invasion of the adjacent organs by the tumor [21].

A retrospective study performed by Liu et al concluded that the optimal therapy for patients with nasopharyngeal ACC should involve surgical intervention, followed by radiotherapy; this approach has been shown to be most beneficial in patients with local infiltration and neural extension [19]. This approach has also been supported by many other authors [22–24]. A study conducted in 1993 on patients with ACC of the head and neck investigated the use of neutron radiotherapy for ACC. The results showed the superiority of the combined surgical-radio-therapeutic approach over surgical management alone [25]. However, radical surgical resection of malignant tumors in the nasopharynx is considered to be technically challenging and carries a high risk of morbidity and mortality due to presence of vital adjacent structures. This explains why most of the patients in the literature received chemotherapy and radiation rather than radical surgical excision (Table 1). Some reports have revealed good results and remission when chemotherapy was used concurrently with radiotherapy; however, the role of chemotherapy in ACC is not well understood, and no clear consensus exists [1].

In the presented case, the short-term outcome of concurrent chemoradiation was excellent in terms of symptom control and local regression of the tumor. As a result of this, in ACC cases where the tumor is surgically unresectable, concurrent chemoradiation may be offered as an alternative.

Radical surgical resection of ACC is challenging as it carries a high risk of morbidity and mortality due to the invasive nature of the tumor to adjacent structures, such as the cranial nerves and other vital organs [8,26,27]. However, the reported cases in the literature in which surgical management was undergone had a good disease-free interval (Table 1).

The prognosis of ACC depends on multiple factors, including tumor size, histopathologic characteristics, primary location of the tumor, metastasis, and cranial nerve involvement [14]. The 5-year survival rate ranges from 54.8% to 100% [19,27], while in cases with cranial nerve involvement or skull base invasion, the prognosis is generally dire [28].

Conclusions

ACC is a malignant disease that is rarely seen in the nasopharynx. When a mass is encountered in the nasopharynx alongside a clinical suspicion of ACC, MRI should be performed to determine the invasiveness of the mass. A biopsy is mandatory to confirm the diagnosis. Currently, the most commonly agreed upon management for resectable ACC cases in the literature is through surgical resection with adjuvant radiotherapy. However, in our reported case, the patient received concurrent chemoradiation and showed excellent results after 6 months in terms of symptom control and local regression of the tumor. Patients should be followed up to rule out any local recurrence or distant metastasis.