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 ().
The patient, a 28-year-old man with a 3-month-old mass in the neck was referred to our department. The mass, located on the left thyroid lobe, was elastic, hard, showed limited mobility, and measured approximately 30 × 20 mm. There was no remarkable tenderness over the mass.\nBlood examination results were normal, including levels of thyroid-stimulating hormone, free thyroid hormone, and thyroglobulin (Table ). Ultrasonography revealed a hypoechoic solid mass in the lower pole of the left thyroid lobe with a poorly marginated heterogeneous pattern (Fig. ). Computed tomography revealed a heterogenic tumor in the left thyroid lobe (Fig. ). 18F-fluorodeoxyglucose (18F-FDG) accumulated in the thyroid tumor on positron-emission tomography. The standardized uptake value of 18F-FDG was 5.29 (Fig. ). Fine-needle aspiration cytology (FNAC) showed a number of lymphoid cells without atypia that were similar to those seen in malignant lymphoma of the thyroid (Fig. ).\nAs we diagnosed a highly malignant thyroid cancer (cT2N0M0), we performed a left hemithyroidectomy with central neck dissection (ND). Histopathological findings showed that the tumor was composed of irregular insular nests of neoplastic cells and had an expansive growth pattern in the thyroid (Fig. ). The carcinoma cells had round nuclei or polymorphonuclei with well-defined nucleoli and ill-defined cell borders (Fig. ). Immunohistochemical studies showed that the tumor was partially positive for CD5, positive for Ki-67 (approx. 30%), and negative for CD20, calcitonin, and thyroglobulin (Fig. ). Based on these histopathological findings, the tumor was finally diagnosed as CASTLE. There were no signs of recurrence without additional treatment after 10 years of follow-up.