A 68-year-old female patient with a 35-year 2 months of history of a large mass on the anterior neck was admitted to the National Institute of Oncology due to progressive dyspnoe, hoarseness and swallowing problems. In her previous medical history hypertension, diabetes and GERD appeared. With physical examination a fixed hard neck mass was palpable in the thyroid gland mostly on the right side with right sided lymphadenopathy. Laryngoscopy showed a right sided vocal cord palsy. The neck and chest CT showed a huge solid mass in the thyroid region dislocating and compressing the trachea, which reached the superior mediastinal region . (Figure 1.) Thyroid ultrasound was performed revealing a mass of the right lobe measuring 8.3 × 5.8 × 5.0 cm with retrosternal extension, and with a 1.8x1.7cm calcified mass in the middle of the lobe. The ultrasound also showed the presence of enlarged metastatic lymph nodes in the right lateral neck regions. Fine needle aspiration (FNA) cytology was performed two times, which showed squamous cell carcinoma with metastatic lymph nodes in the lateral neck region. Core biopsy was taken with the result of squamous cell carcinoma showing CK5, p40 co-expression. Oesophagoscopy was unremarkable. The patient was prepared for operation. A paratracheal and modified lateral neck dissection on the right side of the neck were performed. Regarding the prominent extra capsular invasion, only an extended R1 resection could be done instead of total thyroidectomy. The tumor infiltrated the trachea, esophagus and the surrounding soft tissues. The larger part of the tumor was removed from the trachea with shaving technique, the recurrent nerves could not be identified on either side. The patient's hospitalization was uneventful and was discharged on the fourth postoperative day.
Histology and molecular pathology analysis of the resection specimen.:
Histological examination showed the presence of well differentiated invasive SCC with keratinization, infiltrating mainly the right lobe of the thyroid gland (Figure 2, Figure 3). The tumor showed typical immunophenotype, it was CK5 and p40 positive. Large areas of fibrosis with calcification and foci of necrosis were observed in the central area of the tumor. There were no sign of other component (e.g. papillary area) suggestive of primary thyroid cancer. Out of the 40 resected lymph nodes, 10 showed metastasis of the SCC. Extranodal extension of the tumor was present on multiple lymph node levels.
Biomarker analysis showed prominent PD-L1 expression. PD-L1 expression was detected with DAKO 22C3 PharmDx kit according to the manufacturer instructions. 40% of tumor cells showed complete or partial PD-L1 expression, tumor proportion score (TPS) was 40%. Combined positive score (CPS) was 50. Detailed molecular analysis was also performed using Oncomine Focus Assay on IonTorrent S5 platform. The kit contains the following genes. Oncomine focus hotspot: AKT1, ALK, AR, BRAF, CDK4, CTNNB1, DDR2, EGFR, ERBB2, ERBB3, ERBB4, ESR1, FGFR2, FGFR3, GNA11, GNAQ, HRAS, IDH1, IDH2, JAK1, JAK2, JAK3, KIT, KRAS, MAP2K1, MAP2K2, MET, MTOR, NRAS, PDGFRA, PIK3CA, RAF1, RET, ROS1, SMO Oncomine focus copy number: AKT1, ALK, AR, BRAF, CCND1, CDK4, CDK6, EGFR, ERBB2, FGFR1, FGFR2, FGFR3, FGFR4, KIT, KRAS, MET, MYC, MYCN, PDGFRA, PIK3CA Oncomine focus gene fusion: ABL1, AKT3, ALK, AXL, BRAF, EGFR, ERBB2, ERG, ETV1, ETV4, ETV5, FGFR1, FGFR2, FGFR3, MET, NTRK1, NTRK2, NTRK3, PDGFRA, PPARG, RAF1, RET, ROS1. Both DNA and RNA based sequencing were performed. After macro-dissection tumor cell content of the sample was 60%. We detected NRAS exon 3 mutation, p.Gln61Lys, c.181C>A, with 24,32% mutant allele ratio and amplification of EGFR gene with copy number 17,18.
The patient was referred to multidisciplinary tumor board before further therapy. Regarding the PDL-1 positivity immunotherapy and radiotherapy was recommended. On the 34th postoperative day, urgent tracheotomy was needed due to heavy dyspnoe. PET/CT scan was recommended which showed a huge mass between the upper parajugular region down to the anterior mediastinum surrounding the trachea and infiltrating the vessels on both sides of the neck and reaches the hypopharynx and larynx as well and also ruled out the possibility of other primary malignancies. Lymphadenopathy was observed in the mediastinum and on both sides of the neck. FDG dense nodules were found in the lungs on both sides, as well as in the thoracal vertebrae, in the sacrum and in the pelvis. Lymphadenopathy was detected in the cervical, right hilar and right inguinal region. Multidisciplinary tumor board offered palliative radiotherapy with 10x3 Gray. Patient received 5x3 Gray radiation, when severe renal failure developed , which ended up with dialysis. She was admitted to the uro-oncology department . Due to her physical status, active oncotherapy could not be carried out. After 5x3 Gray palliative radiation the patient died.