Two cases of concurrent carcinoma showing thymus-like differentiation (CASTLE) coexisting with papillary thyroid carcinoma.

Carcinoma showing thymus-like differentiation (CASTLE), which emerges within the thyroid gland or the adjacent soft tissues of the neck, is a rare malignant neoplasm found globally. The occurrence of CASTLE in conjunction with papillary thyroid carcinoma is an even more infrequent phenomenon. The ensuing sections elaborate upon the clinical attributes characteristic of CASTLE.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy.

BACKGROUND: To review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT). METHODS: From April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28-30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0. RESULTS: Among the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153). CONCLUSION: Distant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

Carcinoma Showing Thymus-like Differentiation (CASTLE) with Synchronous Papillary Thyroid Carcinoma: A Case Report and Review.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant tumor that accounts for 0.1%-0.15% of all thyroid cancers. More than half of the patients have tumor extension to adjacent organs, including the recurrent laryngeal nerve, trachea, and esophagus. The diagnosis of CASTLE is based on histology and immunohistochemistry. A 58-year-old female patient complained of hoarseness for one and half years. Right side vocal cord palsy was diagnosed by fiberscopy. Thyroid sonography revealed right thyroid tumors, which were reported to be papillary thyroid carcinoma through FNAC. Total thyroidectomy with central lymph node dissection was performed. Pathologist found 2 isolated malignancy tumors. One patient in the right thyroid lobe had papillary thyroid carcinoma features. The other extrathyroid tumor seemed to be separated from the first tumor and invaded the thyroid capsule. After multiple immunohistochemical studies, PTC synchronous CASTLE was the final diagnosis. Coexisting PTC and CASTLE is very rare. This is the first report to describe a case showing PTC at first, while subsequent pathologic examination revealed the presence of CASTLE in addition to PTC. Since the prognosis of CASTLE is favorable, the treatment is different from other aggressive thyroid cancers, such as poorly differentiated or anaplastic thyroid carcinoma.

Carcinoma showing thymus-like differentiation (CASTLE) of the salivary gland: Report of 2 cases of a hitherto under-recognized extrathyroid counterpart.

Carcinoma showing thymus-like differentiation (CASTLE) outside the thyroid gland is extremely rare. Here we report two cases of CASTLE of the major salivary gland. The tumors occurred in the parotid gland of a 31-year-old female (Case 1) and in the submandibular gland of a 40-year-old female (Case 2). Both tumors showed a lobulated growth pattern, and were histologically composed of a nested or sheet-like proliferation of carcinoma cells with round- to oval-shaped nuclei, distinct nucleoli and pale eosinophilic cytoplasm, accompanied by various degrees of lymphocytic infiltration. Immunohistochemical staining revealed that the tumors were positive for pan-cytokeratin, p40, CD5, CD117 and bcl-2. In addition, PD-L1 expression was seen in 10-90% of tumor cells. After the initial surgery, Case 1 remained tumor-free for 20 months, while Case 2 suffered lymph node recurrence at 4 months, followed by lung metastasis, which was treated with chemoradiotherapy and anti-PD-1 immune checkpoint inhibitor, resulting in a partial response. The present findings indicate that an extrathyroid counterpart of CASTLE can occur as a primary salivary gland neoplasm. Salivary CASTLEs seem to show a wide range of biological behavior, and long-term follow-up may be needed. Immune checkpoint inhibitor targeting PD-1 might become a promising treatment option in patients with CASTLE; however, further study with a larger number of cases is necessary to establish the optimal therapeutic strategy and prognostic factors for this rare cancer.

Whole exome sequencing and establishment of an organoid culture of the carcinoma showing thymus-like differentiation (CASTLE) of the parotid gland.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumor, especially in the parotid gland. We encountered a CASTLE of the parotid gland and analyzed its clinicopathological features, as well as the genotype using whole exome sequencing (WES). Moreover, we successfully established an organoid culture cell line from the primary tumor tissue. The patient was a 23-year-old woman who underwent superficial parotidectomy with peripheral neck dissection, followed by radiotherapy. Pathologically, the resected specimen showed atypical epithelioid nests and trabeculae with squamous differentiation, separated by thick fibrous septa, accompanied by dense lymphocytes and plasma cell infiltration. Immunohistochemistry revealed that the tumor cells were positive for AE1/AE3, p40, p63, p16, CK5/6, and CD5, and the background lymphocytes were positive for CD5 and CD99. Based on these findings, the tumor was diagnosed as CASTLE. WES uncovered five nonsynonymous and splicing somatic mutations, namely, FREM2 p.Val861Phe, CLK3 p.Phe376Leu, DLGAP1 p.Lys294Asn, NOX1 p.Val165Met, and PSG9 c.430 + 4A > T. Organoid culture cells preserved the histopathological characteristics of the epithelioid component of CASTLE and harbored all five somatic mutations detected in the primary tumor. In conclusion, for the first time to the best of our knowledge, we successfully analyzed a comprehensive genotype and established an organoid culture cell line of a parotid gland CASTLE, which should serve for analyzing the nature of this rare tumor.

Carcinoma Showing Thymus-Like Differentiation (CASTLE) Arising in the Sublingual Gland.

Carcinoma showing thymic-like differentiation (CASTLE) is a rare tumor most commonly occurring in the thyroid and soft tissues of the neck. We report the first case of CASTLE occurring in the sublingual gland. The patient, a 35-year-old healthy man, presented with a submucosal lesion located in the anterior right floor of the oral cavity and an ipsilateral neck mass. The lesion had been previously investigated by neck computed tomography and ultrasound-guided fine needle aspiration cytology and diagnosed as metastatic squamous cell carcinoma. After oral cavity magnetic resonance imaging, positron emission tomography, and a non-diriment, fine needle aspiration cytology of the sublingual mass, the patient was treated as affected by a sublingual gland malignancy with removal of primary tumor and neck dissection. Morphological and immunohistochemical findings were diagnostic for primary sublingual gland CASTLE. The patient received adjuvant radiotherapy and is free of disease 2 years after treatment. We describe the pathological features of the lesion and discuss the possible differential diagnoses.

Intrathyroidal thymic carcinoma misdiagnosed as a medullary thyroid carcinoma.

The intrathyroidal thymic carcinoma is a rare neoplasm. The probable origin of this neoplasm is the presence of ectopic thymic tissue or remnants of the third and fourth branchial arch. The case of a 49-year-old female with an initial diagnosis of medullary thyroid cancer is presented. When she was operated for regional recurrence, 16 years later, the pathology report demonstrates the presence of a intrathyroidal thymic carcinoma. Intrathyroidal thymic carcinoma is considered an independent type of thyroid carcinoma because this entity has specific clinical-pathological characteristics similar to thymic carcinomas and different prognosis than known thyroid carcinomas. We present the case of a patient initially treated as having a medullary thyroid carcinoma who, upon presenting recurrence, the presence of intrathyroidal thymic carcinoma was demonstrated.

El carcinoma tímico intratiroideo es una neoplasia rara. El origen probable de esta neoplasia es la presencia de tejido tímico ectópico o de restos del tercer y cuarto arcos branquiales. Se presenta el caso de una mujer de 49 años con diagnóstico inicial de cáncer medular de tiroides. Cuando fue operada por recurrencia regional, 16 años después, se demostró la presencia de un carcinoma tímico intratiroideo, que se considera un tipo independiente de carcinoma tiroideo debido a que tiene características clínico-patológicas específicas similares a los carcinomas tímicos y un pronóstico diferente a los carcinomas de tiroides conocidos. Este caso se trató inicialmente como carcinoma medular de tiroides y al presentar recurrencia se demostró la presencia de un carcinoma tímico intratiroideo.

[A Case of Carcinoma Showing Thymus-Like Differentiation (CASTLE) of the Thyroid].

The case presented herein was a 70-year-old woman who had no compliant, but had a mass in the lower part of the right lobe of the thyroid detected by ultrasound (US). The US image of the tumor, measuring 13 mm in diameter, showed a low and heterogeneous internal echo level with calcification and an irregular margin. The tumor appeared to extend to the adjacent sternothyroid muscle, and cervical lymph node swelling was detected in a computer tomography (CT) image, but no metastatic lesion was found by positron emission tomography (PET)-CT. In a fine needle aspiration cytology of the tumor, papillary thyroid carcinoma was suggested because of the atypical epithelial cells having some changes other than intranuclear inclusion bodies. A subtotal thyroidectomy and central neck lymph node dissection were performed. The excised tumor was histologically composed of irregular nests or sheets of atypical squamoid epithelial cells with some ductal structures that leached to the sternothyroid muscle and involved the right lower parathyroid gland. Carcinoma showing thymus-like differentiation (CASTLE) was diagnosed histopathologically and immunohistochemically with the following immunohistochemical results: Cluster of differentiation 5 (CD5) (+), tumor protein p63 (p63) (+), KIT proto-oncogene receptor tyrosine kinase (c-KIT(CD117)) (+), thyroglobulin (-), and thyroid transcription factor-1 (TTF-1) (-). CASTLE is a rare carcinoma of the thyroid that architecturally resembles thymic epithelial tumors. Many CASTLE patients have been misdiagnosed as other carcinomas, such as anaplastic carcinoma, poorly differentiated carcinoma or squamous cell carcinoma of the thyroid. Immunohistochemical examination, including CD5 played an important role in the final diagnosis of CASTLE, although the distinction from diagnosis as squamous cell carcinoma or mucoepidermoid carcinoma in Hematoxylin-Eosin staining was challenging in our case. Nodal metastasis and perithyroidal tumor extension of CASTLE can predict its worse prognosis. Thus, at least careful follow-up studies are mandatory in cases of CASTLE.

Clinical outcome of intensity modulated radiotherapy for carcinoma showing thymus-like differentiation.

PURPOSE: To evaluate the efficacy and toxicity of adjuvant intensity-modulated radiotherapy (IMRT) after surgery for carcinoma showing thymus-like differentiation (CASTLE). METHODS: Between September 2008 and June 2015, 14 CASTLE patients were retrospectively enrolled. The clinical features, treatment procedure and clinical outcomes were reviewed. All patients received postoperative IMRT. The radiation doses ranged from 56Gy/28 fractions to 66Gy/33 fractions. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. RESULTS: After a median follow-up period of 42 months, only one patient suffered local recurrence and distant metastasis. The most frequently seen acute toxicities were mucositis and dermatitis (grade 1-2). No grade 3-4 toxicities were observed. CONCLUSIONS: Although based upon a small series of consecutively treated patients, our study showed that adjuvant IMRT provides satisfactory local-regional control for CASTLE, with acceptable toxicities. Further studies are still warranted to clarify our findings.

Clinical analysis of 82 cases of carcinoma showing thymus-like differentiation of the thyroid.

The aim of the present study was to summarize the clinical characteristics, diagnosis, treatment and prognosis of carcinoma showing thymus-like differentiation of the thyroid (CASTLE). A search of the relevant literature was conducted, which identified 82 cases of CASTLE reported to date. A review of the clinical and auxiliary examination data, treatment, pathological findings and follow-up of these cases was performed. The clinical manifestations of CASTLE varied and did not demonstrate specificity. During ultrasound examination, CASTLE was described as a solid and hypoechoic mass, and the echo was typically observed to be heterogeneous. In computed tomography (CT), CASTLE was demonstrated to be a well-defined, soft tissue density mass without calcification, which appeared enhanced following administration of contrast medium. In emission CT, CASTLE was revealed as a 'cold nodule'. A total of 78 patients underwent radical surgery, and 12 patients experienced recurrence. Lymph node metastasis did not promote recurrence, and postoperative radiation was not able to reduce the recurrence rate (P=0.144 and 1.000, respectively). The median follow-up time was 14 months (range, 1-312 months). Typical immunohistochemical examinations demonstrated the specimens to be positive for cluster of differentiation (CD)5, CD117, cytokeratin 19, epithelial membrane antigen and tumor protein 63, and negative for calcitonin, thyroglobulin and thyroid transcription factor-1. Thyroid CASTLE is a rare malignancy whose exact diagnosis relies on pathological examination, particularly immunohistochemistry, since preoperative examinations are usually unable to provide an exact diagnosis. Radical resection is the primary treatment for CASTLE, which presents favorable prognosis.

Thyroid carcinoma showing thymus-like differentiation: Case presentation of a young man.

Ectopic thymic tissue can be present in the thyroid gland and a carcinoma showing thymus-like differentiation (CASTLE) may arise from such tissue. We are reported the case of a 26-year-old man with CASTLE, with cervical subcutaneous nodules relapse, who showed a good response to treatment with surgery, chemotherapy and radiotherapy. The problematic aspect of this case was the diagnosis; only on review were we able to make a final diagnosis. CASTLE is a very rare neoplasm. It is important to differentiate this cancer from others tumors such as primary or metastatic squamous cell carcinoma of the head and neck or squamous cell thyroid carcinoma, because the therapy and prognosis are different. Diagnosis is complicated and requires careful histological analysis (CD5- and P63-positive with presence of Hassall's corpuscles); unfortunately there is no gold standard treatment so, in this case, we administered a sandwich of chemotherapy and radiotherapy.

A case of carcinoma showing thymus-like differentiation with a rapidly lethal course.

A 55-year-old woman underwent a total thyroidectomy for carcinoma showing thymus-like differentiation (CASTLE). The patient was referred to our hospital after the tumor was found to have directly invaded the cervical esophagus and the entire circumference of the trachea. A total thyroidectomy was performed, followed by end-to-end anastomosis of the trachea, suprahyoid release and dissection of bilateral pulmonary ligaments. No major complications, including anastomotic dehiscence or stenosis, were observed. The patient experienced some swallowing disturbances and hoarseness during the perioperative period but fully recovered. Radiotherapy to the neck was performed as an adjuvant therapy. Eleven 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. Palliative radiotherapy to the bone metastasis was performed. The patient died of pleural metastasis 14 months after the initial diagnosis of CASTLE.