Malignant transformation of sinonasal inverted papilloma invading the external nose: A case report and literature review

Abstract

Sinonasal inverted papilloma (SIP) is a benign neoplasm of the nasal cavity and sinuses, with a certain risk of malignant transformation. The malignant transformation of SIP is uncommon, and the invasion of malignant tumors into the facial skin is even rarer. This report describes the case of a male patient in his 20 s who underwent two endoscopic resections for SIP in the nasal cavity within a 6-year period. Histopathological analysis during the second surgery revealed the malignant transformation of the tumor into squamous cell carcinoma. Despite receiving conventional postoperative radiotherapy, the tumor was not effectively controlled and had invaded the external nasal region. Following a multi-disciplinary team discussion, a treatment plan was established for tumor excision and simultaneous repair using a frontal musculocutaneous flap. The patient received chemotherapy and anti-EGFR therapy following surgery. Tumor recurrence was not observed during the 2-year postoperative follow-up period. The malignant transformation of SIP requires a comprehensive treatment strategy that includes surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Additionally, a thorough assessment and preparation are crucial before flap reconstruction if the tumor invades the external nasal structures and affects appearance.

Introduction

Sinonasal inverted papilloma (SIP) accounts for 0.5–4% of all nasal tumors and predominantly affects individuals in their 50 s and 60 s,^1,2 with a male-to-female ratio of approximately 2–3:1. ³ The exact etiology of SIP remains to be elucidated to date, ⁴ and endoscopic surgery remains the primary method for tumor excision in the treatment of SIP. ⁵ A recent meta-analysis evaluating the efficacy of endoscopic surgery for SIP reported that the recurrence rates range from 3% to 33%, with an average rate of 13.8%. ⁶ Kim et al. reported that 5–15% of cases of SIP can progress to squamous cell carcinoma (SCC) during the course of the disease. ⁷ The incomplete resection of the primary tumor is a potential risk factor for the recurrence and malignant transformation of SIP.

This report presents the case of a patient with residual malignant transformation of SIP. The tumor had progressed and invaded the external nasal structures even after radiotherapy, thus significantly affecting overall health. A treatment plan involving surgical resection of the tumor and simultaneous reconstruction using a superficial temporal artery (STA) island musculocutaneous flap was established for the patient, following a multi-disciplinary team (MDT) discussion. This case underscores the significance of comprehensive preoperative evaluation, adequate MDT discussions, detailed surgical implementation, and extensive postoperative treatment in the management of advanced malignancy resulting from SIP.

Case report

A male patient in his 20 s with SIP underwent endoscopic resection in both 2016 and 2022. Determination of the postoperative pathology of the nasal tumor resected in 2022 revealed a localized malignant transformation of SIP, atypical hyperplasia with focal cancer. The patient therefore received intensity-modulated radiotherapy (dose 66Gy, 33 fractions) following surgery. However, the tumor recurred 6 months after the completion of the radiotherapy regimen, and the biopsy revealed poorly differentiated SCC. Physical examination revealed the presence of a tumor in the nasal root and nasal cavity (Figure 1A–B). The patient was admitted to Tsinghua Changgeng Hospital affiliated to Tsinghua University in Beijing in November 2022.

Figure 1.

Preoperative (1A), endoscopic (1B), and axial (1C) views from enhanced CT scans of the sinuses. The mass was located in the ethmoid sinus and had invaded the external nasal region. Axial (1D), sagittal (1E), and coronal (1F) views from PET-CT scans. PET-CT: positron emission tomography-computed tomography.

An enhanced computed tomography (CT) scan of the sinuses revealed an annular isodense nodule at the nasal root, with a CT value of approximately 44 HU and exhibiting an uneven annular enhancement. The solid portion of the nodule had CT values of 56–75 HU, accompanied by damage to the adjacent nasal bone. The surrounding bone structures exhibited significant deterioration in the medial portion of the left maxillary sinus. The density of the bone structures surrounding the bilateral maxillary sinus, frontal sinus, and ethmoid sinus was higher, although no enhancement was detected (Figure 1C).

The results of positron emission tomography-computed tomography scanning revealed a tumor extending from the nasal root to the forehead, affecting the nasal bone, nasal septum, bilateral sieve plate, and a portion of the frontal sinus wall, standard uptake value max 42.6. This was accompanied by bone resorption and destruction, along with an increased uptake of fluorodeoxyglucose (FDG), suggestive of malignant tumor. The density of the bones surrounding the bilateral maxillary sinuses, bilateral ethmoid sinuses, and frontal sinuses appeared to be low, with no detectable increase in FDG uptake, indicating chronic inflammation (Figure 1D–F). Additionally, distant metastasis was not observed.

Following enhanced preoperative preparation and obtaining the patient's consent for treatment, the patient underwent surgery under general anesthesia for the resection of a nasal tumor with extensive invasion into the nasal root and facial structures with open approach combined with nasal endoscopic approach. After the bone removal of the posterior wall of frontal sinus, the dural membrane of the anterior skull base was smooth, no tumor invasion was observed, and no cerebrospinal fluid rhinorrhea was observed during and after the operation. Tumor margins included the posterior wall mucosa of frontal sinus, bilateral medial orbital wall margins, frontal skin margins, bilateral inner canthus skin margins, and external nose inferior margins. Pathology showed no tumor invasion at each incisal margin. The surgical procedure involved reconstructing the nasal structures using an ultra-long STA island musculocutaneous flap, along with a right thigh dermectomy. The right STA was identified by preoperative ultrasound (Figure 2A–B), and the operative procedures were completed seamlessly without complications. The stitches from the forehead and the outer nasal flap, as well as the iodoform gauze, were removed after 14 days of surgery (Figure 2C). Subsequent pathological analysis revealed moderately to poorly differentiated SCC, characterized by significant bleeding and necrosis, corresponding to post-treatment changes, with a tumor size of 5.5 cm × 5 cm × 4.5 cm (Figure 2D). No lesions were observed at the incisal margin. Immunohistochemical analysis of the tumor revealed a P16(+), P53(+), P40(+), Ki67(85%+), and EGFR(1+) profile (Figure 2E), and the patient subsequently received TPF (docetaxel 75 mg/m² + cisplatin 75 mg/m², iv q3w for 6 courses; capecitabine 1250 mg/m², po bid for 2 weeks) chemotherapy and anti-EGFR therapy(Nimotuzumab 200 mg, iv qw for 7 courses). Currently, after 2 years of postoperative follow-up, the STA island frontal muscle flap has healed successfully, with no signs of necrosis (Figure 3A). A CT scan of the sinuses revealed no signs of tumor recurrence (Figure 3B-D). The reporting of this study conforms to CARE guidelines. ⁸ This article has been published with the informed consent of the patient.

Figure 2.

Preoperative preparation and postoperative evaluation. A frontal muscle flap measuring 9 cm × 7.5 cm was selected for repair (2A,B). Postoperative view after 14 days of surgery (2C). HE staining ×40 (2D). Immunohistochemical staining of EGFR ×40 (2E).

Figure 3.

Postoperative view after 24 months of surgery (3A). Coronal (3B), sagittal (3C), and axial (3D) views from enhanced CT scans of the sinuses, 24 months post-surgery. CT: computed tomography.

Discussion

SIP is a benign tumor that originates from the nasal cavity and sinuses, and is characterized by a propensity to recur, local aggressiveness, and a potential for malignant transformation. ⁹ The patient underwent two endoscopic procedures over a period of 6 years, and tumor recurrence was especially rapid following the second surgery. However, the SIP continued to recur despite surgical resection and eventually progressed to malignancy. Targeted surgery at the origin and proper management of the attachment site are key to achieving complete surgical resection of SIP. ¹⁰ The complete removal of the tumor from the frontal sinus, including the surrounding bone, was a critical step during the operation. After 24 months of comprehensive treatment, the patient currently shows no signs of recurrence of the sinonasal carcinoma, indicating successful therapy.

SIP was first described by William Ward 150 years ago, while Ringertz recognized its endophytic growth pattern and coined the term “inverted papilloma” in 1938. ¹¹ In 1991, the World Health Organization classified sinonasal papilloma into three distinct histopathological subtypes, namely, exophytic, inverted, and oncocytic. ¹ Several factors are associated with the occurrence of SIP, including chronic inflammation, infection with human papilloma virus (HPV) or Epstein-Barr virus, smoking, occupational and environmental exposures, cell cycle-related proteins, and angiogenic factors.^4,12

CT is the preferred imaging technique for SIP, ¹³ which frequently presents with bone remodeling, as observed in 43% of cases in a previous study, which may appear as calcifications and swelling in the paranasal sinuses, accompanied by erosion and sclerotic changes in certain instances. ¹⁴ SIP can be distinguished from inflammation by magnetic resonance imaging due to its distinctive streaky delineation and convoluted cerebriform patterns, which are visible on both T2-weighted and contrast-enhanced T1-weighted images.^13,15

Comprehensive analyses of HPV infections, mutations in exon 20 of EGFR, and the hypomethylation of LINE1 are extremely crucial as they pose as risk factors for the malignant transformation of SIP to SCC.^16,17 Additionally, the presence of HPV DNA subtypes 6, 11, 16, and 18, along with a history of smoking and advanced age, are associated with an increased risk of recurrence and malignant transformation of SIP.^12,18–20 The malignant transformation of SIP can lead to the development of keratinizing or non-keratinizing SCC, and other less frequent histologies such as mucoepidermoid carcinoma. ²¹ Preoperative biopsies are therefore critical for excluding malignant inverted papilloma or malignant neoplasm. ¹⁴ Surgical intervention combined with cervical lymph node dissection is generally recommended in cases of metastasis. ²² However, a combination of surgical resection and radiation therapy is also prescribed, at radiation doses similar to those used for invasive SCC (66–70 Gy).^3,22

Reconstructive procedures are performed following the radical excision of primary tumors, typically with a musculocutaneous flap from the pectoralis major; however, alternatives such as submental flaps, free forearm flaps, or free musculocutaneous flaps from the rectus abdominis may also be utilized. ²² The present case is unique in that the total resection of the tumor from the external nasal structures and intranasal region resulted in a prominent defect in the central region of the face, which necessitated a suitable reconstructive strategy. The color and texture of the frontal flap supplied by the superficial temporal blood vessels are similar to those of the skin around the facial defect. ²³ The STA flap has a large surface area, a thin and pliable texture, and a certain degree of firmness that enables easy shaping and transfer. The morphological and functional attributes were preserved following operation, and the repair and reconstruction of the defects in the vital regions were notably superior to those achieved with other distal pedicled traditional flaps or free flaps anastomosed with blood vessels.

Although the transplantation of STA flaps is an ideal strategy for facial reconstruction, it is important to note that the forehead constitutes a significant morphological component of the face, and any malformations in this area are likely to compromise overall facial harmony. The guiding principle during the selection of flaps should be to repair the essential tissues using secondary tissues, while preserving both the esthetics and functionality of the donor site. In the present case, the STA island flap healed successfully post-repair, thus effectively preserving the integrity of the facial appearance. However, a pronounced facial deformity was still evident following repair, and the defect in the donor site greatly affected the appearance. Therefore, flap selection should be stringently confined to cases involving severe defects or deformities in facial tissue.

Conclusion

The significance and uniqueness of the present case lie in the comprehensive management of the malignant transformation of SIP, as well as the strategies employed for reconstructing the facial defect following surgical resection. Due to the aggressive nature and potential malignancies associated with SIP, diagnosis and radical surgery should be planned carefully to enhance the quality of life of patients. Endoscopic resection and attachment-oriented surgery have emerged as the predominant treatment strategies for SIP. Chemotherapy or radiotherapy should be considered in conjunction with surgical resection for cases with malignant transformation of SIP. Although the STA island flap can serve as a feasible option for reconstructing extensive facial defects, detailed assessment and preparation are crucial prior to its application.