Squamous Cell Carcinoma of the Larynx Arising in Multifocal Pharyngolaryngeal Oncocytic Papillary Cystadenoma

We report on a rare case of a laryngeal carcinoma arising in a multifocal pharyngolaryngeal oncocytic papillary cystadenoma (OPC). The disease of a 63-year-old man is well documented by computed and positron emission tomography, histology, and electron microscopy. We could show that an OPC can even develop in the pharynx. The coexistence of both tumors makes this a challenging diagnosis for pathologists. Treated by surgery and radiotherapy, both lesions dissolved. Based on the literature available, we discuss the theory that the laryngeal carcinoma might be the result of a true metaplasia facilitated by chronic irritation and recommend a regular follow-up for OPC too. As in benign oncocytic lesions, we could show that the detection of numerous mitochondria is a diagnostic indicator for malignant variants as well. (Medicine 93(12):e70) Abbreviations: CT = computed tomography, OPC = oncocytic papillary cystadenoma, PET-CT = positron emission tomographyCT, SUV = standardized uptake value. INTRODUCTION Warthin tumor, also known as papillary cystadenoma lymphomatosum, is the second most frequent benign tumor of the salivary glands after pleomorphic adenoma. It is a unique neoplasm composed of oncocytic epithelium with a prominent lymphoid infiltrate. In cases without lymphatic tissue in the subepithelial layer, these tumors are called oncocytic papillary cystadenoma (OPC). OPCs rarely occur in major salivary glands and generally account for <1% of all salivary tumors. The cytologic features may vary and diagnosis is difficult especially in fine-needle aspiration. Histology mainly shows cystic, oncocytic neoplasms with variable papillary projections. Warthin tumor, oncocytoma, intraductal papilloma, and acinic cell carcinoma may arise in the differential diagnosis. An antimitochondrial monoclonal antibody that recognizes a nonglycosylated mitochondrial protein of 60 kDa in the diagnosis and categorization of salivary tumors recognizes all salivary tumors with oncocytic differentiation. In pancreatic cancer, oncocytic types of intraductal papillary neoplasms are discussed as precursors for pancreatic cancer. CASE REPORT A 63-year-old man presented to our outpatient department with the diagnosis of a nasopharyngeal carcinoma with ipsilateral neck metastasis. His chief complaint was a progressive indolent swelling of the left neck for 3 weeks. Next, he reported a prolonged dysphonia, having a history of smoking of 30 pack-years. The otorhinolaryngological examination showed a smooth swelling of the left nasopharyngeal recess, a supraglottic mass, a 1-sided vocal cord palsy, and a hard swelling of the left neck. The remaining otorhinolaryngological examination was without any pathologic findings. A computed tomography (CT) scan of the head and neck showed an inhomogeneous soft tissue mass of the whole pharyngeal wall with an implied parietal contrast enhancement and cystic lesions (Figure 1A and C). In level II of the left neck, a tumor measuring 3.9 2.3 2.2 cm with compression of the internal jugular vein could be seen (Figure 1C). Besides that, the laryngeal mucosa appeared irregular with inhomogeneous contrast enhancement (Figure 1C). An endoscopy under general anesthetic was performed and revealed a laryngeal squamous cell carcinoma of both arytenoids and vestibular folds, the laryngeal epiglottis, and the anterior commissure. Beyond that, multiple excisional biopsies (>10) of the whole left pharyngeal wall, the base of the tongue, the tonsils, the soft palate, and the nasopharynx up to 1.3 cm huge and up to 1 cm deep, were without any signs of malignancy. Here, the histopathologic examination showed oncocytic metaplasia in excretory ducts of the small salivary glands with cystadenolymphoma-like lesions in the mucosa of all biopsies. The diagnosis was an OPC (Figure 2A–C). For further exclusion of malignancy, a positron emission tomography-CT (PET-CT) was performed. It showed a leftsided supraglottic fluorodeoxyglucose (FDG) uptake with standardized uptake values (SUVs) of up to 16.3 (reference value of the liver parenchyma 2.1) (Figure 1D). The leftsided neck mass showed an FDG uptake of 8.9 (Figure 1D). The whole left pharyngeal wall showed SUV of up to 5.7 (Figure 1B). The pharyngeal lesion thus was interpreted to be nonmalignant. The general clinical examination as well Editor: Tuck Yean Yong. Received: May 12, 2014; revised: June 28, 2014; accepted: July 7, 2014. From the Department of Otorhinolaryngology, Head and Neck Surgery (MS, MK, CR); and Institute of Pathology, University Hospital of M€unster, M€unster, Germany (K-MM). Correspondence: Markus Stenner, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of M€unster, Kardinalvon-Galen-Ring 10, 48149 M€unster, Germany (e-mail: markus. [email protected]). The authors have no funding and conflicts of interest to disclose. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ISSN: 0025-7974 DOI: 10.1097/MD.0000000000000070 Medicine • Volume 93, Number 12, September 2014 www.md-journal.com | 1 as vital signs, laboratory evaluation, and an electrocardiogram were without pathologic findings. The patient was free of distant metastasis as evaluated by means of a CT scan of the thorax, an ultrasound examination of the abdomen, and a PET-CT scan. The final clinical staging of the supraglottic laryngeal carcinoma was cT3 cN+ cM0. A total laryngectomy with a bilateral selective neck dissection was performed. The final diagnosis was a pT3 pN2a (1/59) G3 R0 L1 Pn1 V1 M0 supraglottic laryngeal carcinoma (stage IVA, American Joint Committee on Cancer) (Figure 2D). The margins of excision were clear (7mm), and the lymph node was without extracapsular FIGURE 1. CT (A, C, E) and PET-CT (B, D, F) scans of the patient before (A–D) and after (E and F) therapy. (A) OPC with characteristic cystic lesions (asterisks) of the left epipharyngeal wall. (B) Mild FDG uptake of the OPC (white arrow). (C) OPC of the pharynx (black arrows), swelling of the supraglottic region (white arrowheads), and left-sided neck mass (plus sign). (D) High FDG uptake of supraglottic mass and neck metastasis (white arrows). (E and F) Epipharyngeal wall after therapy. CT1⁄4 computed tomography, FDG1⁄4 fluorodeoxyglucose, OPC1⁄4oncocytic papillary cystadenoma, PET-CT1⁄4positron emission tomography-CT. 2 | www.md-journal.com ã 2014 Lippincott Williams & Wilkins Stenner et al Medicine • Volume 93, Number 12, September 2014