Oncocytic Schneiderian papilloma-associated adenocarcinoma and KRAS mutation

Abstract

Rationale:Oncocytic Schneiderian papillomas (OSP) are an uncommon type of sinonasal papillomas that arise from the Schneiderian epithelium, accounting for only 6% of all sinonasal papillomas. Malignancies arising in OSP are rare and are almost always described as in situ or invasive squamous cell carcinoma, although mucoepidermoid, small cell carcinoma and sinonasal undifferentiated carcinoma have also been reported. To our knowledge, only 18 such instances have been reported in the medical literature.Patient concerns:Here, we report the case of an 81-year-old man presenting with a left sinonasal neoplasm, who had undergone 4 operations. The first postoperative pathology revealed a benign nasal polyp. The following several postoperative pathology revealed a novel, human papillomavirus-negative adenocarcinoma with increasing malignant features with each recurrence arising in an OSP. In addition, the most recent recurrences were associated with metastasis of cervical lymph nodes. And after the operation, the patient refused adjuvant radiotherapy. On 6-month follow-up after the last operation, the patient developed an in situ tumor recurrence 1 month after the fourth operation and refused to undergo surgery again.Diagnosis:Immunohistochemistry for Ki67, CK7, CK5/6, P53, and P63 showed a progression of malignancy. HPV assay presented the 21 most prevalent HPV types were negative. In addition, KRAS gene exon 2 G12C presented mutation in the OSP-associated adenocarcinoma.Interventions:During the whole course of the patient's disease, we performed four nasal endoscopic operations. And after the last operation, the patient refused adjuvant radiotherapy and KRAS-targeted therapy.Outcomes:We are the first to describe adenocarcinoma arising in an OSP. To our surprise, from the first benign neoplasm to the second OSP-associated adenocarcinoma, it went through a long period of 10 years. However, after the adenocarcinogenesis, the differentiation of tumor became worse with the shorter interval of each recurrence.Lessons:Therefore, for elderly patients with unilateral nasal polyps, long-term follow-up is necessary. Once OSP turns into malignant, radical resection should be performed as much as possible to reduce the irritability of tumors.

Sinonasal Squamous Cell Carcinoma: Etiology, Pathogenesis, and the Role of Human Papilloma Virus

“…Malignant transformation occurs in 4-17% of OSPs, most of these being SCC [69]; however, mucoepidermoid, small cell, adenocarcinoma, and sinonasal undifferentiated carcinomas have also been described [70,71]. In WHO 2017, and additional literature, HPV has not been found to be associated with OSP [70,72,73]. However, recent studies and meta-analysis found 22.5% of OSPs cases are HPV positive [62,63].…”

Sinonasal papillomas: A single centre experience on 137 cases with emphasis on malignant transformation and EGFR/KRAS status in “carcinoma ex papilloma”

“…Dabei ist in beiden Fällen das Plattenepithelkarzinom die am häufigsten assoziierte Tumorentität[13,26,30].Transformationen invertierter Papillome in beispielsweise verruköse Karzinome, Mukoepidermoidkarzinome und Spindelzellkarzinome sind in seltenen Fällen in der Literatur dokumentiert[11,13,31,32]. Onkozytäre Papillome wurden in Assoziation mit undifferenzierten und kleinzelligen Karzinomen, einem Mukoepidermoidkarzinom, papillären Transitionalzellkarzinom, papillären Schneiderkarzinom und einem Adenokarzinom beschrieben[30,[33][34][35].2.1.7 ÄtiologieDie Ätiologie der sinunasalen Papillome und ihrer assoziierten Malignome ist bislang weitgehend unbekannt und Thema aktueller Forschungen. Besonderes Augenmerk liegt dabei sowohl auf der Rolle der Humanpapillomviren als auch auf molekulargenetischen Tumoreigenschaften wie somatischen Mutationen oder der Expression von Tumorsuppressorproteinen.Humanpapillomviren (HPV)Während beim onkozytären Papillom die Infektion mit Humanpapillomviren keine Rolle in der Ätiologie zu spielen scheint, ist die Studienlage beim invertierten Papillom uneindeutig [1, 36, 37].…”