Seromucinous hamartoma with unique clinical and histopathological features: a case report and review of the literature

Abstract

Background

We present this case to highlight the importance of considering seromucinous hamartoma in the differential diagnosis of nasal cavity lesions, particularly due to its rarity and potential for being mistaken for more aggressive pathologies. Seromucinous hamartoma, although benign, can exhibit clinical and histological features that overlap with those of malignant tumors, posing a diagnostic challenge. This case is especially noteworthy due to the unusual presentation of sebaceous differentiation within seromucinous hamartoma, a feature not previously documented in the literature. Recognizing such rare entities is crucial for ensuring appropriate patient management and avoiding unnecessary interventions.

Case presentation

We report a unique case of a 41-year-old Caucasian man with seromucinous hamartoma, presenting with chronic left nasal obstruction and recurrent mild epistaxis. Nasal endoscopy revealed a well-defined, multilobulated lesion in the left nasal cavity. Computed tomography scans confirmed an anteromedial polypoid lesion, 31 mm × 15 mm. The lesion was endoscopically resected without complications, with no recurrence at 6-month follow-up. Pathological examination showed a filiform polypoid lesion with clusters of seromucinous glands, ducts, and tubules, and no invasive growth patterns. Immunohistochemical studies revealed distinct epithelial membrane antigen (EMA) and p63 staining patterns. Notably, mature sebaceous gland formation interspersed with seromucinous glands was observed, a novel finding in seromucinous hamartoma. Recognizing seromucinous hamartoma is crucial to avoid unnecessary treatments, and it should be included in differential diagnoses of nasal cavity lesions.

Conclusion

Seromucinous hamartoma is a rare and benign nasal cavity lesion that presents significant diagnostic challenges due to its potential to mimic more aggressive pathologies. This case highlights the importance of including seromucinous hamartoma in the differential diagnosis of sinonasal lesions, particularly when unusual histological features, such as sebaceous differentiation, are present.

Background

In otolaryngology, differentiating between benign and malignant nasal cavity lesions is crucial for proper diagnosis and treatment planning. Among the common benign lesions are inflammatory polyps, nasal polyps, and inverted papillomas. Although rare, hamartomas can also be present in the sinonasal cavity and require consideration [1]. Hamartomas are tumor-like proliferations made of an abnormal mixture of normal tissue components of the involved organs. In the sinonasal tract, they are classified into four distinct histological types: respiratory epithelial adenomatoid hamartoma (REAH), seromucinous hamartoma (SMH), chondro-osseous and respiratory hamartoma (CORE), and nasal chondromesenchymal hamartoma (NCH) [2]. REAH is the most frequently reported subtype, followed by SMH [3]. SMH is a benign condition characterized by the overgrowth of seromucinous glands and tubules. To date, SMH remains a rare entity, with only 56 cases reported in the medical literature [4]. Various clinical and histological features, as well as potential diagnostic challenges, are still being identified. Therefore, we report a unique case of an adult patient with SMH showing infrequent endonasal localization and focal sebaceous differentiation.

Case presentation

A 41-year-old Caucasian man was referred to our tertiary care hospital after experiencing chronic and progressively worsening left nasal obstruction with two episodes of mild self-resolved left anterior epistaxis, accompanied by recurrent episodes of self-limited left epistaxis over the past year. There were no other sinonasal complaints. He was not taking any anticoagulant or antiplatelet medication and had no history of trauma. Nasal endoscopy revealed an exophytic and multilobulated well-defined lesion obstructing the left nasal cavity (Fig. 1). Findings from the rest of the clinical examination were within normal limits. Computed tomography scans with contrast of paranasal sinuses revealed antero-medial lesion of the left nasal cavities showing a polypoid appearance, not enhanced by contrast, measuring up to 31 mm × 15 mm in diameter. Informed consent was obtained for endoscopic resection of the lesion. Under general anesthesia, using a 30-degree nasal rigid endoscope, the lesion was identified originating from the most superior part of the lateral nasal cavity one cm above the axilla. It was resected in 1-cm macroscopically tumor free margins using endoscopic scissors and bipolar. It was sent for a routine pathology examination. There were no intra- or postoperative complications. No clinical recurrence was detected on nasal endoscopy during the 6-month follow-up period. The surgical specimen consisted of a 4-cm filiform polypoid lesion. Microscopic examination revealed that the lesion was covered by ciliated respiratory epithelium. The core was made of clusters and lobules of small seromucinous glands, ducts, and tubules. The glands lacked back-to-back growth, epithelial tufting or papillae, invasive growth, or cribriform structures. The serous cells displayed bright eosinophilic zymogen granules and round regular nuclei, without atypia or mitotic activity. The tubules were lined by a single layer of bland cuboidal cells. Eosinophilic secretions were seen within the lumen of some dilated tubules. Focal REAH-like invagination of respiratory epithelium and large epithelium-lined retention cysts were present (Fig. 2). Additionally, a mature sebaceous gland formation was identified. The sebaceous gland was interspersed between the seromucinous glands and ducts. Immunohistochemical studies enabled the identification of several distinctive features. The glandular submucosal component was positive for epithelial membrane antigen (EMA) and cytokeratin 7 immunostains. Glands lacking a p63-positive basal layer displayed diffuse EMA positivity while glands with a p63-positive basal layer showed an apical EMA positivity. The S100 immunostain revealed a heterogeneous positivity in the glands and ducts of moderate intensity. The DOG1 immunostain showed weak apical staining. SOX10 displayed a diffuse intense nuclear positivity. The sebaceous cells were negative for cytokeratin 7 and SOX10 immunostains, while positive for the p63 immunostain (Figs. 3, 4). The lesion was also negative for B-catenin and exhibited a wild-type pattern on p53 immunostain.

Fig. 1

Left nasal endoscopy. S, septum; IT, inferior turbinate; MT, middle turbinate; asterisk, the lesion

Fig. 2

Histopathological features of sinonasal seromucinous hamartoma. A, B The polypoid lesion was covered by ciliated respiratory epithelium with epithelium-lined retention cysts (asterisk). The submucosa contained clusters (A) and lobules (B) of small glands, ducts, and tubules. [A: hematoxylin–eosin (H&E), × 4 magnification; B: H&E,× 10 magnification]. C, D Focal REAH-like invagination of respiratory epithelium was present. (C: H&E, × 4 magnification; D: H&E, × 10 magnification). E The seromucinous glands lacked any back-to-back growth, epithelial tufting, or cribriform structures. The tubules were lined by a single layer of bland cuboidal cells (black arrowhead). The serous cells displayed bright eosinophilic zymogen granules and round regular nuclei, without atypia or mitotic activity (white arrowhead). F Eosinophilic secretions were seen within the lumen of some dilated tubules (black arrow; E: H&E, × 40 magnification; F: H&E, × 20 magnification)

Fig. 3

Immunohistochemical features. A The glandular submucosal component was positive for EMA immunostain (× 10 magnification). B, C Glands lacking p63-positive basal layer (black arrow) displayed diffuse EMA positivity while glands with p63-positive basal layer (asterisk) showed an apical EMA positivity (× 40 magnification). S100 immunostain revealed a heterogeneous positivity in the glands and ducts of moderate intensity (× 10 magnification). E DOG1 immunostain showed a weak apical staining (× 20 magnification). F SOX10 displayed a diffuse intense nuclear positivity (× 10 magnification)

Fig. 4

Microscopic features of sinonasal seromucinous hamartoma with a sebaceous gland formation. A Hematoxylin eosin stain revealed a mature sebaceous gland (white arrow) interspersed between the seromucinous glands and ducts (× 20 magnification). B The sebaceous cells were negative with cytokeratin 7 immunostain (black arrow). Notably, the glands and ducts showed diffuse cytokeratin 7 positivity (× 40 magnification). C, D The sebaceous gland (black arrow) was positive with p63 immunostain (C) and negative with SOX10 immunostain (D) (× 20 and × 40 magnification, respectively)

Discussion and conclusions

SMH was first described in a case report by Bailie and Batsakis in 1974 [5], with approximately 56 cases described in the literature until this day. The infrequency of this disease makes it difficult to reach a consensus on its characteristics and pathological diagnostic criteria. The mean age of the patients is 55.5 years, and the incidence of sinonasal SMH is similar among females and males. Our case was a 41-year-old male. Unilateral nasal obstruction and rhinorrhea are the most common presenting symptoms, and hyposmia, facial pain, and epistaxis are sometimes recognized incidentally [6]. Macroscopically, SMH is described as a unilateral pedunculated polypoid mass that ranges in size from 0.6 to 6.0 cm. In our patient, the primary symptom was a progressively worsening unilateral nasal obstruction, accompanied by multiple episodes of epistaxis and a well-defined multilobulated lesion of the left nasal cavity. The coexistence of inflammatory nasal polyps is found in 20% of cases. Kim et al. found that about 50% of SMH tumors originated in the anterior nasal cavity with dysplasia occurring more frequently in tumors from the anterior nasal cavity compared with those from the posterior nasal cavity. Only one case in the literature was found to originate from the olfactory cleft [4]. In our patient, the tumor originated from the lateral wall of the nasal cavity. Furthermore, one case associated with tissue invasion (orbit infiltration) [7] and two cases diagnosed as low-grade adenocarcinoma [8] in primary clinics were associated with SMH located in the anterior nasal cavity. Simple surgical removal by endoscopic endonasal approach appears to be curative in the majority of cases with only one reported recurrence [9].

Histopathologically, SMH are formed by bland seromucinous glands, ducts, and tubules, usually lacking a myoepithelial layer. In our case, we describe a peculiar pattern of EMA immunostain. The glands lacking a p63-positive basal layer displayed diffuse EMA positivity while glands with a p63-positive basal layer showed an apical EMA positivity. This biphenotypic pattern may help to recognize this entity. Additionally, Michal et al. recently described atypical adenomatous sinonasal glands arising in SMH/REAH. Interestingly, three of the described SMH cases revealed sebaceous differentiation [10]. To our knowledge, our case is the first description of sebaceous differentiation in an otherwise typical SMH. Also, many authors consider that SMH and REAH belong to the same disease spectrum. To our knowledge, there is no report of sebaceous glands occurring in REAH. The main differential diagnosis is low-grade nonintestinal sinonasal adenocarcinoma (LGSNA). To date, no definitive immunohistochemical studies are available to distinguish between SMH and LGSNA. Morphological features of back-to-back growth, epithelial tufting and papillae, invasive growth, and cribriform structures favor the latter [4]. In addition, to date, there are no defined molecular alterations for the diagnosis of LGSNA. Some LGSNA cases have been found to be enriched in ETV6-RET/ETV6-NTRK3 fusions or CTNNB1 mutations, with occasional BRAF mutations [11,12,13]. In our case, there were no histopathological features of aggressive behavior, and no clinical recurrence was detected during a 6-month follow-up period. In conclusion, SMH is a rare tumor-like lesion with variable clinical and pathological features. Recognition of this benign entity is mandatory to avoid unnecessary aggressive treatment.