Cervical Lymph Node Metastasis of Squamous Cell Carcinoma from Unknown Primary Tumor

The first aim of the study was to determine the survival rate of the patients with Carcinoma of the Unknown Primary (CUP) in relation to lymph node status and eventual later identification of the primary tumor. To second one was to investigate the impact of PET-CT on identification of the primary tumor.We studied 97 patients sent to our University Medical Center with diagnosis of metastasis of unknown primary tumor between 1.1.1997 and 1.9.2009. All patients had panendoscopy and some had PET-CT at later period. All susceptible patients had a surgery and postoperative radiation therapy. After the completed their treatment they were followed up at ENT department. With preoperative examinations we discovered 48 primary tumors. Only in one case of 13 the PET-CT detected the primary tumor not confirmed with other examination methods. After the treatment we found primary tumors in 10 patients. In 39 patients we didn’t discover any primary tumor. The 2-year overall survival for 10 patients with found tumor was 80.0%, the 2-year overall survival for the 39 patients without discovered tumor was 73.8%. The 2-year disease-specific survival for 10 patients with found tumor was 90.0%, the 2-year disease-specific survival for 39 patients without discovered tumor was 81.6%. The 2-year overall survival for high neck level lymph node metastasis group (N=36) was 80.1%, the 2-year overall survival for low neck level lymph node group (N=13) was 61.5%. PET-CT method was not particularly useful in detecting primary tumors in patients with metastasis with unknown primary. Patients with high neck level lymph node metastasis had statistically significant better survival

Sphenoclival Intraosseus Lipoma: Case Report and Literature Review

Objective: To present the case of a rare tumor in the sphenoidoclival area and discuss potential pitfalls in diagnosis and management. Design: Case report with literature review. Setting: Tertiary referral center. Case Summary: Our patient presented with headache, vertigo, vision problems, and feeling of pressure in the central segment of the face. MR and CT showed a lesion in the body of the sphenoid, with signs of bone destruction and irregular borders. Differential diagnosis included intraosseous meningioma, chordoma, and inflammatory process. Results: Endoscopic/microscopic transnasal approach was performed to reach clival bone and to biopsy the tumor. Histopathological examination showed intraosseous lipoma. Conclusion: Intraosseous lipoma is a rare tumor, or more accurately a hamartoma, and is usually found in the calcaneus or in the proximal femur. It is even rarer in the skull base. Usually it does not present any symptoms and is an incidental finding during imaging for other symptoms. As a rule it runs an indolent course and does not require any treatment. Since no definitive diagnosis can be made only on the basis of imaging (CT and MRI), it requires an open biopsy that if possible should be made in accordance with the principles of minimally invasive surgery

An evaluation of SOX2 and hTERC gene amplifications as screening markers in oral and oropharyngeal squamous cell carcinomas

Background: Oral and oropharyngeal squamous cell carcinomas (OSCC) are among the most common cancers. The poor survival rate among oral cancer patients can be attributed to several factors, one of them being lack of early detection. A key approach to this problem would be to detect potentially malignant lesion at their early stage. Using the FISH technique, oral brush cytology slides can be an easy and rapid screening approach for malignant cell detection. The present study was designed to detect hTERC and SOX2 amplifications in OSSC exfoliative tumor cells and evaluate whether those two gene amplifications might serve as a supportive biomarker in early detection and diagnosis of oral and oropharyngeal SCC. Results: Brush biopsies were collected from exophytic and exulcerated oral and oropharyngeal lesions of the oral cavity of 71 patients and 22 healthy controls. FISH techniques using a TERC-specific DNA probe and a SOX2 DNA specific probe both combined with a centromere 3-specific control probe was performed on the cytology slides. A 100 squamous epithelial cell nuclei of the smears per slide were analysed. As abnormal FISH pattern were considered amplified and polyploid patterns. From 71 brush biopsies of oropharynx and other locations in oral cavity analysed by FISH 49 were considered to be abnormal (69%). The over representation of polyploidy and/or TERC/SOX2 amplification in tumour samples was statistically significant when compared to controls (p = 0.01). Conclusion: SOX2 and TERC gene amplifications are common in all squamous cell carcinomas and their detection in early stages could be crucial for early detection and more accurate prognosis. Our study strongly suggests that early detection by FISH on cytobrushed samples could be a possible non-invasive screening method even before a tissue biopsy is performed

Neuroendocrine carcinoma of the larynx and pharynx

Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995%2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein%Barr virus (EBV) was performed. Twenty patients (larynx, 12pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs % 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is neededthe optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information

Jugular paraganglioma treatment at the UMC Maribor

Background: Jugular paragangliomas are rare, almost exclusively benign and slowly growing tumors. Arising from the cells of paraganglia in jugular bulb, they infiltrate the temporal bone and later grow intracranially. Because of insidious onset, their diagnosis is relatively late. Patients at presentation usually complain of pulsatile tinnitus and hearing loss, lasting for years. Also common are palsies of the cranial nerves in the area of tumor growth – i.e., facial, glossopharyngeal, vagal, accessory and hypoglossal nerves. Surgical resection is the standard treatment, though technically demanding because of difficult approach to the lateral cranial base and vital structures in the area. The team for treating such patients comprises an ENT specialist, interventional radiologist and a neurosurgeon. The purpose of this article is to review clinical experiences with the treatment of jugular paragangliomas at our Department of ENT and Maxillofacial Surgery of the University Medical Centre Maribor. Methods: We reviewed the documentation of ten patients treated for jugular paraganglioma in the last 15 years, and presented the clinical data in a table. Results: Nine patients were treated by preoperative embolization and surgical resection. Surgery was contraindicated in one patient with highly dominant venous drainage on the side of the tumor and aplastic transverse sinus on the opposite side. She was treated by primary radiotherapy. One patient with intracranial tumor growth was treated by subtotal resection and adjuvant radiotherapy. At presentation, lower cranial nerve palsies were present in 60 % of our patients. With the other 40 % we managed to preserve the nerve function postoperatively. Facial nerve function practically normalized in all patients with anterior transposition of the nerve. Our patients were provided with postoperative rehabilitation and corrective procedures such as vocal cord medialization and BAHA hearing aid implantation. Discussion: Despite the risks, the surgical treatment is effective in halting the disease and preserving cranial nerve function. The results of our work demonstrate that our patients are provided with a thorough and comprehensive care

Gene Expression Profiles of Methyltransferases and Demethylases Associated with Metastasis, Tumor Invasion, CpG73 Methylation, and HPV Status in Head and Neck Squamous Cell Carcinoma

Epigenetic studies on the role of DNA-modifying enzymes in HNSCC tumorigenesis have focused on a single enzyme or a group of enzymes. To acquire a more comprehensive insight into the expression profile of methyltransferases and demethylases, in the present study, we examined the mRNA expression of the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B, the DNA demethylases TET1, TET2, TET3, and TDG, and the RNA methyltransferase TRDMT1 by RT-qPCR in paired tumor–normal tissue samples from HNSCC patients. We characterized their expression patterns in relation to regional lymph node metastasis, invasion, HPV16 infection, and CpG73 methylation. Here, we show that tumors with regional lymph node metastases (pN+) exhibited decreased expression of DNMT1, 3A and 3B, and TET1 and 3 compared to non-metastatic tumors (pN0), suggesting that metastasis requires a distinct expression profile of DNA methyltransferases/demethylases in solid tumors. Furthermore, we identified the effect of perivascular invasion and HPV16 on DNMT3B expression in HNSCC. Finally, the expression of TET2 and TDG was inversely correlated with the hypermethylation of CpG73, which has previously been associated with poorer survival in HNSCC. Our study further confirms the importance of DNA methyltransferases and demethylases as potential prognostic biomarkers as well as molecular therapeutic targets for HNSCC