Respiratory epithelial adenomatoid hamartoma originating from the nasal floor: A case report

Abstract

Respiratory epithelial adenomatoid hamartoma (REAH) is a relatively rare disease that commonly occurs in the olfactory cleft, followed by the posterior nasal septum within the nasal cavity. We herein report a case of REAH on the nasal floor, which is an extremely rare anatomical site for the occurrence of REAH. A 63-year-old man was referred to our department because he had developed right epistaxis. Endoscopic examination revealed a protruding lesion on the floor of the right nasal cavity. The tumor was endoscopically removed and histopathological examination revealed that the tissue was characterized by proliferation of glandular duct structures composed of multiciliated cells and glandular cells, consistent with isolated REAH. No evidence of recurrence was observed endoscopically 14 months after surgery. The findings indicate that REAH can occur in the nasal cavity at sites covered by the respiratory mucosa that have not been previously reported and should be treated with caution.

Keywords:

• Nasal floor
• hamartoma
• endoscopic sinus surgery

Introduction

Respiratory epithelial adenomatoid hamartoma (REAH) has mainly been sporadically described in case reports [1]. In 1995, however, Wenig and Heffner [2] systematically reported REAH in a case series of 31 patients. REAH is histologically characterized by proliferation of secretory glands with multiciliated cells whose motile cilia on the apical side, as in the respiratory epithelium. These proliferative glandular structures arise in direct continuity with the surface epithelium and proliferate toward the submucosa, forming a polypoid mass lesion [1].

Hamartomas can occur anywhere in the body. They are commonly found in the lungs, kidneys, liver, spleen, and intestines, but rarely in the nose and nasopharynx [1]. REAH is defined as hamartoma arising in the nasal cavity, paranasal sinuses, and nasopharynx [2]. Historically, early reports suggested that the most common site of REAH was the posterior nasal septum [2]. More recently reported sites include the olfactory cleft, posterior nasal septum, and middle turbinate [3–6]. However, there have been no reports of REAH occurring on the nasal floor. We herein present a rare case of REAH occurring on the nasal floor.

Patient information

A 63-year-old man was scheduled to undergo mitral valvuloplasty for mitral regurgitation. However, he developed right epistaxis 2 days before the surgery and was referred to our department.

Clinical findings

Endoscopic examination of the right nasal cavity revealed a mass lesion approximately 5 mm in size located on the floor of the nasal cavity (Figure 1(A)); the tumor was suspected to be the source of the bleeding. Computed tomography revealed a 5-mm-long mass located posterior to the floor of the right nasal cavity, at the level of the soft palate (Figure 1(B)). Short TI inversion recovery magnetic resonance imaging showed a mass with isosignal intensity on the floor of the right nasal cavity, in the area consistent with that in the computed tomography scan (Figure 1(C)).

Figure 1. (A) Endoscopic examination of the right nasal cavity showed a mass on the nasal floor. (B, C) Coronal computed tomography and coronal Short TI inversion recovery magnetic resonance imaging showed an approximately 5-mm mass on the nasal floor (arrowhead).

Diagnostic assessment

Histopathologic examination of the tumor showed proliferation of glandular ducts with a mixed epithelium of both multiciliated cells and secretory cells on hematoxylin and eosin staining (Figure 2(A–C)). These features were consistent with our previous case of REAH occurring in the olfactory cleft (Figure 2(D,E)). Immunohistochemical staining and Alcian blue/periodic acid-Schiff staining were also performed to compare this case with that of REAH occurring in the olfactory cleft. Sections were cut to 4-µm thickness and mounted on glass slides. After deparaffinization and rehydration, heat-induced epitope retrieval was performed with a PT Link Pre-Treatment module (Agilent Technologies, Santa Clara, CA, USA) using Dako Target Retrieval Solution, pH 9 (Agilent Technologies) at 95 °C for 10 min with subsequent cooling to 65 °C. The sections were then blocked in 5% normal donkey serum in TBS-T at room temperature for 1 h, followed by incubation with primary antibodies in the blocking solution. After overnight incubation with the primary antibodies at 4 °C, the sections were incubated with the appropriate secondary antibodies for 1 h. Hoechst 33342 (Thermo Fisher Scientific, Waltham, MA, USA) was used for nuclear staining. The primary antibodies were rabbit anti-acetyl-α-tubulin (ACTUB) (1:800, 5335S; Cell Signaling Technology, Danvers, MA, USA) and mouse anti-MUC5AC (1:2000, ab3649; Abcam, Cambridge, UK), and the secondary antibodies were highly cross-adsorbed donkey anti-rabbit Alexa Fluor Plus 488 (1:500, A32776; Thermo Fisher Scientific) and highly cross-adsorbed donkey anti-mouse Alexa Fluor Plus 555 (1:500, A32773; Thermo Fisher Scientific). ACTUB was positive at the upper end of the epithelial cells that formed the proliferative glandular structure, indicating that the lumen was composed of multiciliated cells. MUC5AC was positive in some cells in the lumen, suggesting the presence of goblet cells in the glandular structure (Figure 3(A)). Alcian blue/periodic acid-Schiff staining revealed proliferation of glandular cells and accumulation of mucus inside the lumen of the glandular ducts surrounded by respiratory epithelium (Figure 3(C)). Similar findings were observed in REAH of the olfactory cleft (Figure 3(B,D)).

Figure 2. (A) Hematoxylin and eosin staining showed proliferation of glandular elements throughout the mass. (B, C) Magnification showed that the glandular elements were composed of pseudostratified respiratory epithelial cells on a thick basal membrane; these were multiciliated cells (containing motile cilia on their surface) and glandular cells. (D, E) A previously examined respiratory epithelial adenomatoid hamartoma in the olfactory cleft showed similar findings.

Figure 3. Immunohistochemical staining revealed acetyl-α-tubulin (ACTUB)-positive cilia on the apical side of the lumen of the proliferative glandular structure, as well as scattered mucin 5AC (MUC5AC)-positive goblet cells. Alcian blue/periodic acid-Schiff staining revealed mucin-producing cells in the epithelium, forming proliferating glandular ducts. Mucin accumulation was also seen in the endomysium of the epithelium. Hoechst: Hoechst 33342.

Therapeutic intervention

Before performing mitral valvuloplasty, the tumor was endoscopically resected on the same day to prevent epistaxis due to the use of postoperative anticoagulants. The tumor was totally removed from the nasal floor after exfoliation of the surrounding normal mucosa, ensuring an adequate safety margin. In addition, a flattened raised lesion with tiny blood vessels was observed on the surface of the inferior turbinate mucosa. We could not rule out the possibility that this area was the source of the bleeding, and we therefore cauterized the area.

Follow-up and outcomes

Anticoagulants were initiated the day after surgery, and the patient did not develop recurrence of epistaxis. Endoscopic examination 2 weeks after surgery confirmed epithelialization of the excision site, and no recurrence had developed at 14 months after the surgery (Figure 4).

Figure 4. Endoscopic examination 14 months after the surgery showed no recurrence on the nasal floor.

Discussion

A hamartoma is a mass of disorganized but maturely differentiated cells and tissues specific to the site, defined as aberrant differentiation. Unlike neoplasms, hamartomas are characterized by a lack of the ability to continuously grow because their proliferation remains under strict control. These entities may manifest in various anatomical regions. According to the definition established by Wenig and Heffner [2], REAH is a specific type of hamartoma that forms in the respiratory epithelium within the nasal cavity, paranasal sinuses, and nasopharynx. In this study, we experienced a case of REAH that manifested on the nasal floor, which has not been previously reported.

The initial case series by Wenig and Heffner [2] described REAH as a solitary lesion. However, REAH with concomitant inflammatory processes has been reported, leading to the categorization of REAH into isolated REAH and associated REAH [3–8]. The most common comorbidity in patients with associated REAH is chronic rhinosinusitis (CRS), but allergic fungal rhinosinusitis, inverted papilloma, and cancer have also been reported [6,7]. In a systematic review of REAH, 34.9% of patients had isolated REAH, whereas 50.1% had associated REAH [6]. Associated REAH may be misdiagnosed because of its overlapping characteristics with nasal and sinonasal diseases; recently, however, the disease concept has become more apparent and the histopathological diagnosis more accurate, which may be one of the reasons for the increase in reported cases [6]. Our case was diagnosed as isolated REAH because the entire mass showed pathologic evidence of REAH, presented as a solitary lesion on the nasal floor, and had no association with other nasal or sinonasal diseases.

REAH is a benign lesion that predominantly occurs among middle-aged individuals in their fifth and sixth decades of life, and a slightly higher incidence is observed in men than in women [2,4–11]. The clinical presentation is nonspecific and may include nasal obstruction, rhinorrhea, epistaxis, and olfactory disturbance, thus exhibiting similarities with CRS [2,4–8,10]. The absence of distinctive characteristic symptoms renders the differentiation of REAH from other nasal and sinonasal diseases difficult [5]. Moreover, depending on the site of origin, REAH is often difficult to differentiate from nasal polyps based on endoscopic findings alone because of the lack of characteristic endoscopic findings [3,5,8,10]. Therefore, histopathologic examination is required to distinguish REAH from the seromucous gland proliferation seen in nasal polyps [1]. Endoscopic examination in the present case showed that the mass was round in shape and slightly yellow in color, and the surface appeared to be covered with clusters of capillary vessels. Because it was relatively small and occurred on the nasal floor, the only symptom was epistaxis. Isolated REAH is reportedly less symptomatic than associated REAH [3,4]. Although epistaxis is an infrequent symptom of REAH, there have been reports of cases in which preoperative embolization was performed because epistaxis was the primary complaint and intraoperative bleeding was anticipated [12].

Initial reports of REAH indicated that it most often occurred as an isolated mass at the posterior aspect of the nasal septum [2]. Prior to 2006, REAH occurring in the olfactory cleft had not been reported [8]; however, REAH has since been frequently reported at this site [3–6,8]. The reason for this is that many cases of REAH associated with inflammatory polyps of CRS with nasal polyps (CRSwNP) in the olfactory cleft have been reported since introduction of the concept of associated REAH. Since its discovery in the olfactory cleft, REAH has also been reported to develop in the nasopharynx, lateral nasal wall, and sinonasal cavities [2,4,8]. However, REAH occurring on the nasal floor, as in the present case, has not been reported for either isolated or associated REAH.

The histopathologic examination in the present case included immunohistochemical staining as well as hematoxylin and eosin staining to evaluate the proliferating glandular structure composed of multiciliated cells and secretory cells in REAH. In the comparison of the isolated REAH that occurred in the olfactory cleft with the REAH on the nasal floor of the present case, the lumens composed of multiciliated and secretory cells were found to be similar in that they were not only present within the epithelium of the proliferative glandular structures but also proliferated and penetrated from the epithelium present on the surface of the mass. Based on these findings, we diagnosed this case as REAH originating from the nasal floor.

The standard treatment of REAH is complete surgical resection. The procedure for isolated REAH is similar to the standard surgical procedure for inverted papilloma, including subperiosteal dissection and bone debridement [2,6]. However, some authors have indicated that no recurrence develops even with standard endoscopic sinus surgery [5,8]. Therefore, depending on the location of the REAH, it may be better to perform surgery similar to that for inverted papilloma if the complication is minimal, or to perform a more conservative surgery to preserve the sense of smell if the REAH is present in the olfactory cleft. Because the lesion in our patient occurred at the base of the nasal cavity, total excision was performed with a margin of normal mucosa, and no recurrence was observed.

Conclusion

We have reported the first case of isolated REAH occurring on the nasal floor. This case indicates that REAH can arise from anatomic sites not previously reported within the nasal cavity where respiratory epithelium is present. REAH should thus be considered as a differential diagnosis when mass lesions are seen in the nasal and sinonasal cavities.

Informed consent

The authors confirm that consent was obtained from the patient.

Acknowledgment

We thank Angela Morben, DVM, ELS, from Edanz (https://jp.edanz.com/ac), for editing a draft of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

No funding was received for conducting this case report.