A 58-year-old man presented to us three years ago with a history of progressive anterior neck swelling and hoarseness of voice for the past one month. On clinical examination, there was palpable left anterior neck swelling with cervical lymphadenopathy. A core needle biopsy of the lesion revealed invasive poorly differentiated carcinoma. He defaulted our follow-up and opted for a left hemithyroidectomy at another institution. The histopathological report was intrathyroid thymic carcinoma. He refused adjuvant radiotherapy despite being counselled and subsequently defaulted follow-up.\nRecently, the patient presented to us again with progressive hoarseness of voice and intermittent haemoptysis. He had shortness of breath, especially when lying flat, but no difficulty in swallowing. On clinical examination, there was a left supraclavicular mass measuring 2 × 2 cm. The mass was immobile and hard in consistency. The anterior aspect of the neck showed an irregular hard mass measuring 3 × 4 cm. An indirect laryngoscopy examination revealed a left vocal cord palsy, likely from his previous presentation. An intraluminal mass was seen over the posterior tracheal wall, occupying a third of the tracheal lumen. We proceeded with a contrasted computed tomography (CECT) of the neck and thorax, which revealed a lobulated hypodense soft tissue mass measuring 4.3 × 3.9 × 5.2 cm. It occupied the left thyroid bed from the C7/T1 to the T2/T3 vertebral level, with left retrosternal extension and tracheal deviation to the right. The soft tissue mass had displaced the left common carotid artery and internal jugular vein laterally. As the CECT showed (, ), the soft tissue mass had caused more than 80% of tracheal luminal narrowing. At retrosternal, multiple matted lymph nodes were seen.\nImage-guided fine needle aspiration cytology (FNAC) of the soft tissue mass at the left thyroid bed showed malignant cells suggestive of intrathyroid thymic carcinoma (CASTLE). After a multidisciplinary meeting, we planned for curative resection and tracheostomy. Intraoperative tracheoscopic examination showed a soft tissue mass measuring 3 cm in length at the posterior tracheal wall, 2.1 cm from the vocal cord (). The mass was debrided to achieve an adequate diameter of tracheal lumen distal to the tracheostomy insertion. The left supraclavicular solid tumour densely adhered to the left great vessels. Due to a high risk of injury to the great vessels, we proceeded with tumour debulking only.\nThe histopathology report showed an unencapsulated tumour that displayed lobular architecture. The tumour lobules were composed of sheets of neoplastic polygonal cells rimmed by a variable amount of mature lymphocytes. The neoplastic cells were mildly pleomorphic, and lymphovascular invasion was present. Skeletal muscle bundles attached at the periphery showed focal tumour cell infiltration (, ). Immunohistochemical studies were immunoreactive for CD5 (membranous pattern) and CD117 but negative for thyroglobulin and TTF1 (, ). The proliferative index, Ki67, was approximately 20%.\nPostoperative care was unremarkable, and no immediate complications were noted. The patient was counselled for adjuvant chemoradiotherapy, but he was not amenable to this course of action. He is currently under regular follow-up with no disease progression six months after the operation.
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 ().