A 60-year-old gentleman with past medical history of cervical disk herniation presented with a 3-year history of progressive fatigue and bilateral upper extremity weakness. MRI was performed to evaluate the spine and was consistent with cervical spinal stenosis. T2 non-contrast images incidentally revealed an infiltrating mass in the left thyroid that was incompletely visualized. Ultrasound-guided fine needle aspiration showed atypia of undetermined significance. The patient was referred to surgery and was noted to have dysphonia but no stridor or dysphagia. The differential diagnosis was felt to include papillary thyroid carcinoma, follicular thyroid carcinoma, rare thyroid neoplasms including Hurthle cell carcinoma or anaplastic carcinoma, abscess, or autoimmune thyroid disease. He underwent total thyroidectomy with central neck dissection. On exploration, the thyroid mass was seen encasing the left recurrent laryngeal nerve and was shaved off the nerve and the trachea. The nerve was not stimulatable after resection and the patient developed left vocal cord paralysis. The tumor grossly measured 7 cm with extrathyroidal extension. There was lymphvascular space invasion and perineural invasion. Three lymph nodes were identified, and all were negative. Surgical margins had extensive involvement of tumor. Histopathologic analysis of the specimen showed high-grade carcinoma with thymus-like differentiation. Immunohistochemical staining was positive for pan-CK, p63 (cyokeratin and epithelial markers) and negative for chromogranin, thyroglobulin, and calcitonin (neuroendocrine, papillary and follicular thyroid, and medullary makers, respectively).\nThe tumor was arranged in broad, pushing, smooth-bordered islands abutted against a lymphocyte rich stroma. The lobules of tumor were surrounded by lymphocytes and plasma cells (Figures and ). The tumor cells were squamoid and syncytial to spindled, with eosinophilic cytoplasm, and the nuclei show mild pleomorphism with pale vesicular chromatin. The neoplastic cells were strongly immunoreactive for pancytokeratin and p63, as shown in Figures and . These cells were also strongly positive for CD5, which marks background T lymphocytes (Figure ). The neoplastic cells were non-reactive with TTF1 and thyroglobulin.\nPostoperative staging surveillance with PET scan was performed for systemic staging and due to positive margins. It showed no abnormal FDG uptake at distant sites and increased uptake at the operative bed, indeterminate between residual disease and postoperative changes. The patient underwent adjuvant treatment with radiation therapy to 64 Gy in 32 fractions with intensity modulated radiotherapy. Concurrent chemotherapy was given based on his extensive positive margins for radiosensitization. A dose of 60 Gy was delivered to the bilateral neck including paratracheal nodes into the upper mediastinum, with a 4 Gy sequential boost to the operative site. A coronal section of the radiotherapy plan is shown in Figure . Six cycles of intravenous concurrent cisplatin 35 mg/m2 were infused. During therapy, he developed grade 2 skin reaction characterized by dry desquamation and moderate erythema of the neck and upper chest. Skin moisturizer was used for therapy. He experienced grade 2 esophagitis and mucositis of the oropharynx and grade 2 nausea requiring topical analgesics, oral narcotics, antiemetics, and intravenous fluid administration. Weight decreased from 108 to 95.5 kg by the end of therapy. Nutritional counseling by dietician and oral nutritional supplementation were provided. With chemotherapy, the patient developed a tinnitus grade 1. Toxicities are reported per the Common Terminology Criteria for Adverse Events ().\nAfter treatment, the patient initially experienced continued weight loss, and as a result underwent percutaneous endoscopic gastrostomy tube placement. Five months after end of treatment, the tube was removed after the patient was able to gain significant weight and completely obtain nutrition per oral route for 6 weeks. Dysphagia to solid foods is improving. He experienced persistent dysphonia secondary to left vocal cord paralysis since surgery and underwent left medialization thyroplasty 1 year later. He displayed improvement in voice quality. At 3-years follow-up after completion of radiotherapy, our patient is without evidence of locally recurrent or distant disease.
A 79-year old woman was hospitalized on April 25, 2018, at which time she had progressive dyspnea over the past 5 weeks, productive cough, poor appetite, and weight loss of 5 kg over the last 6 months currently weighing 81 kg. Her medical history included an invasive ductal breast cancer pT1cN0M0 G2 ER 90%, PR 20% 20 years ago treated with lumpectomy, radiotherapy, and tamoxifen until 2004, and an undifferentiated cancer of the right parotid pT1 (17 mm) pN2 (1/2 positive in level I, 1/11 positive in level II, no extranodal extensions) pM0 diagnosed 2008 and treated with a total parotidectomy achieving R0 margins and a selective neck dissection levels II-IV followed by radiotherapy.\nOn physical examination, the patient was in mild respiratory distress. The pulmonary exam revealed dullness to percussion, decreased fremitus, and decreased breathing sounds in up to two-thirds of the left lung field. Oxygen saturation was 92% with the patient breathing ambient air, and arterial blood gases showed partial respiratory insufficiency. A chest X-ray confirmed a left-sided pleural effusion, and thoracentesis removed 1.5 liters of turbid fluid. Biochemical analysis of the fluid established an exudative etiology. Atypical cells with immunocytochemical positivity for p40, cytokeratin 5, and p63 in the cytopathology specimen were primarily suggestive of a non-small cell lung cancer, and a CT scan of the thorax showed a mass (4.2 × 2.2 × 2.8 cm) in the right upper lobe and extensive cardiophrenic, mediastinal, and hilar lymphadenopathy as well as enlarged lymph nodes along the left arteria mammaria interna. An FDG PET/CT scan confirmed these findings, and the scan revealed a hypermetabolic activity in mesenteric lymph nodes and at the left pleura (). Thoracoscopy and biopsy of the parietal pleura were performed. Surprisingly, histopathological examination revealed a non-small cell carcinoma () expressing CD5 (), CD117 (), and p63 all indicating a carcinoma of thymic origin (). With no signs of a thymic pathology, the histopathological diagnosis of CASTLE was established, and as additional immunostainings for CD5 () and CD117 () in the specimen of the parotid cancer diagnosed 2008 were positive also, a rare case of a CASTLE tumor of the parotid healed at the primary and neck sites, but with late metastatic dissemination was diagnosed.\nAs CD117 was highly overexpressed in the tumor, exons 9, 11, 13, 14, and 17 of the C-KIT gene were analyzed after extraction of genomic DNA by PCR using specific primers, but no common mutation was found consistent with previous reports (, ). Anticancer immunity and potential response to immunotherapy were assessed by PD-L1 staining of the pleural tumor, which showed a high expression level of 60% ().\nThe patient underwent talc pleurodesis and left partial pleurectomy for recurrent pleural effusions. Systemically, disseminated metastatic disease was treated with the monoclonal PD-L1 inhibitor pembrolizumab at a dose 200 mg every 3 weeks. Four months after the start of immunotherapy a follow-up FDG PET/CT study showed a partial remission with a moderate morphologic reduction of the tumor load, but a markedly reduced metabolic activity at all tumor sites (). Pembrolizumab treatment continued at a dose of 200 mg IV every 3 weeks. The patient showed a mild skin rash treated with low dose prednisolone (20 mg with tapering) for 2 weeks. No other adverse events associated with pembrolizumab were observed, and the therapy was tolerated well. At the last follow-up, the patient was in good clinical condition and had gained 3 kg of weight. On March 28th, 2019, a second follow-up FDG PET/CT showed no residual pleural effusion (not shown) and a further regression of lesions in the right lung and lymph nodes. Residual focal FDG-Uptake was seen in the left pleura ().