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 ().
A 52-year-old woman was referred to our hospital because of severe dyspnea and the presence of a neck tumor. She had experienced dyspnea for the past 6 months and had recently noticed bloody sputum. A computed tomography examination of the neck revealed a thyroid tumor about 8 cm in size. The tumor had invaded the trachea, obstructing 90% of the tracheal lumen (fig. ). An emergency tracheotomy was performed to maintain an airway through the tumor tissue. On biopsy, the tumor was diagnosed as CASTLE, suggesting a favorable prognosis if a complete resection could be performed. Magnetic resonance imaging and an esophageal fibroscopy examination revealed a low possibility of esophageal invasion (fig. ). Under general anesthesia, a thyroidectomy was initially performed via a neck incision. The invaded portion of the trachea was sharply dissected. A partial sternotomy was performed at the level of the 2nd intercostal space to identify the distal portion of the intact trachea and to mobilize the inferior tracheal segment. The trachea was transversely opened to find the intact portion. The length of the resected trachea was 6 cm (fig. ). Bilateral recurrent nerves were macroscopically preserved. We performed a suprahyoid release to mobilize the superior tracheal segment, but these mobilizations were insufficient to perform an anastomosis. Thus, to allow additional mobilization, we performed a clamshell thoracotomy and incised the pericardium 360° around the hilum, dissecting the pulmonary ligament bilaterally. These procedures allowed an anastomosis. An end-to-end bronchial anastomosis was carried out using running 4-0 PDS II sutures (Ethicon, Somerville, N.J., USA) for the membranous portion and interrupted 4-0 PDS II sutures for the cartilaginous portion. The bronchial anastomosis was wrapped with an omental pedicle flap that was lifted up through a retrosternal route via a laparotomy. A gastrostomy was also performed for postoperative enteral nutrition. For management after surgery, a chin suture was placed. Neck mobilization was restricted for the placement of the chin suture and airway fixation. After confirming an improvement in the laryngeal edema using a laryngoscopy, extubation was performed on postoperative day (POD) 17. The patient exhibited swallowing disturbances and underwent swallowing rehabilitation. Enteral nutrition was provided through the gastrostomy. The patient was discharged on POD 31, and per os feeding was started on POD 51. Radiotherapy (60 Gy in 40 daily fractions of 1.5 Gy) was performed as an adjuvant therapy. Throughout the clinical course, no major complications, including swallowing disturbances, hoarseness or anastomotic problems, were observed. A histopathological examination of the resected specimen revealed the characteristic morphology of CASTLE (fig. ); immunohistochemistry was positive for CD5 (fig. ) but negative for thyroid transcription factor 1 (TTF-1; fig. ).\nEleven months after surgery, lower back pain and right leg numbness developed and led to gait inability. Multiple lung and bone recurrences were observed, but no local recurrence. In order to ease the back pain, palliative radiotherapy (35 Gy in 14 fractions) to the bone metastasis was administered. Twelve months after surgery, drainage of pleural effusion was performed. She died of pleural metastasis 14 months after the initial diagnosis of CASTLE.