Thymic Squamous Carcinoma Research Articles

PD-1/PD-L1 inhibitors combined with chemotherapy in the treatment of thymic carcinoma metastasis to the liver

Epithelial neoplasms of the thymus is a relatively rare malignancy. In this report, we present a case of thymic carcinoma of a 68-yearold man with hepatic metastasis, which with the severe hypokalemia, hypoproteinemia, and fatigue of concomitant symptom. After positive symptomatic treatment such as correction of electrolyte disorder, supplementation of albumin and nutritional support, the patient’s general condition recovered and improved. Then, we reviewed the literature on the treatment of thymic carcinoma, and decided to use immunotherapy combined with chemotherapy to treat this case of advanced thymic squamous carcinoma, expecting to have a good efficacy and improve the progression-free and overall survival.

Squamous Cell Carcinoma of the Thymus Arising in a Spindle Cell Thymoma With Prominent Langerhans Cell Infiltrate

Abstract The authors present a case of mixed thymoma and thymic squamous carcinoma. Pleural metastases from the thymoma, which was of the spindled phenotype (type A) were identified in the radical resection specimen. Lymph node metastasis from the carcinoma element was also identified. The thymoma was unique in that there was a prominent Langerhans cell background, a feature previously associated with micronodular thymoma.

P26.05 Comprehensive Genomic Sequencing in Thymic Epithelial Tumors: Identification of Multiple Poor Prognosis Biomarkers in Chinese Patients

Thymic squamous carcinomas (TSCC) and thymic neuroendocrine tumor (NETT) are two types of thymic tumor which have higher risk of relapse and death. TSCC is a malignant neoplasm of the thymus with morphological features of squamous cell carcinoma as seen in other organs. However, the research about genetic profile and its relationship with prognosis of both tumors are rare. 47 patients who diagnosed with TSCC/NETT at Shanghai Jiao tong University Affiliated Chest Hospital between 2015 and 2017 were sequenced by FoundationOne CDx (F1CDx) which is a FDA approved platform conducted by DIAN (Hangzhou Lab) with the licensed technologies. During the follow up, the clinical information and the survival information was also collected. The cox regression model was used to analyze the relationship between genomic alteration and the survival data. A total of 47 patients’ (including 29 men, 14 ever smokers) surgical specimens were sequenced. The histological types include TSCC(N=27), NETT (N=14) and mixed of both(N=6). The median age of TSCC, NETT and mixed subtype was 59.5, 65 and 74, respectively. The top ranked altered genes in TSCC were TP53 (30%), CDKN2A (26), CDKN2B (19%) and ASXL1 (15%). In NETT, the top mutated genes were MEN1 (36%), STAG2 (14%), CDKN2A (14%) and HRAS (14%). The top ranked mutated genes in mixed subtype were TP53 (29%) and CDKN2A (29%). Notably, TP53, ASXL1, TET2, MLL2, EP30, BAP1 were only mutated in TSCC or mixed subtypes. However, mutated of MEN1, STAG2 and HRAS were also founded in NETT subtype. The TMB of three groups have no significant differences. 13 of 47 patients (27.7%) showed CDKN2A deletion and 7 of 47 tumors (14.9%) showed CDKN2B deletion which both were correlated with worse recurrence-free survival (RFS) (P<0.001). 5 (10.6%) patients showed MTAP loss, which was correlated with worse RFS (P =0.018). 6 (12.8%) patients showed TSC2 missense, which was correlated with worse RFS (P =0.017). 3 (6.4%) patients showed EPHB4 missense, which was also correlated with worse RFS (P =0.0081). Our study found that: TSCC and NETT have very different gene alternation landscape, while the mixed subtype was more similar with TSCC than with NETT. The most altered genes are focused on signal pathways of cell cycle control, Chromatin remodeling/DNA methylation, PI3K/AKT1/MTOR, MAP kinase signaling and others.In addition, we firstly identified multiple poor prognosis biomarkers in Chinese thymic epithelial tumors patients. These poor prognosis biomarkers are mainly enriched in cell cycle control and PI3K/AKT1/MTOR pathways.

P.038 A case report of an interesting paraneoplastic voltage-gated channelopathy

Background: Morvan syndrome is an autoimmune paraneoplastic disorder affecting of voltage-gated potassium channels, most commonly the CASPR-2 subunit. The disorder is primarily characterized by hyperexcitability of both the central and peripheral nervous system accompanied by autonomic dysfunction. Clinically, the syndrome manifests as confusion, hallucinations, insomnia, hyperhidrosis, orthostatic hypotension, and muscle cramps with myoclonus. Methods: Patient chart, imaging, electrophysiology, and laboratory findings were reviewed from the time of MS diagnosis and through the course of treatment until symptom resolution. Results: Here we report a case of Morvan Syndrome in a 56 year old male with a previous history of thymic squamous carcinoma accompanied by paraneoplastic myasthenia gravis and myositis. His clinical presentation was notable for subacute onset of muscle cramping, insomnia, which progressed to also include visual and auditory hallucinations. He also had notable dysautonomic symptoms including orthostatic blood pressure changes, sialorrhea, and hyperhidrosis. The diagnosis was confirmed with a positive serum assay for antibodies against the CASPR-2 subunit of voltage-gated potassium channels. Conclusions: This case is notable because to our knowledge it one of the first to document a voltage-gated channelopathy in association with previous thymic cancer (and not thymoma). Moreover, this is a patient presenting with two other other autoimmune syndromes, i.e. myasthenia gravis and myositis.

Desmoglein 3 and p40 immunoreactivity in neoplastic and nonneoplastic thymus: a potential adjunct to help resolve selected diagnostic and staging problems.

The potential usefulness of the squamous markers p40 and desmoglein 3 (DSG-3) for the diagnosis and staging of selected thymic lesions is uncertain. We investigated their expression and distribution pattern in 66 thymomas, 12 thymic squamous carcinomas, 6 undifferentiated thymic carcinomas, 5 hyperplastic thymi, and 5 normal thymi. p40 nuclear and DSG-3 cytoplasmic/membranous immunoreactivity in greater than or equal to 10% of thymic epithelial cells was interpreted as positive, and DSG-3 distribution pattern was classified as organotypic and nonorganotypic. All nonneoplastic thymic tissues, 100% of thymic squamous carcinomas, 97% of thymomas, and 50% of undifferentiated thymic carcinomas were positive for p40. Expression of p40 in almost all thymomas and in 50% of undifferentiated carcinomas that lacked squamous features suggests that p40 is not a good marker for the diagnosis of thymic squamous carcinoma. All normal and hyperplastic thymi, 51.5% of thymomas, and 0% of thymic squamous carcinomas expressed DSG-3 in an organotypic pattern, and 13.6% of thymomas and 83% of thymic squamous carcinomas were DSG-3 positive in a nonorganotypic pattern. Findings suggest that nonorganotypic DSG-3 expression favors the diagnosis of squamous cell carcinoma over thymoma. In 26 (60.5%) of the 43 cases where neoplastic and nonneoplastic thymus were present on the same slide, the presence/absence or distribution pattern of DSG-3 immunoreactivity was different in the 2 components, suggesting that this marker can be helpful in staging thymomas with incomplete encapsulation. The presence of DSG-3-positive and DSG-3-negative thymomas raises the possibility that these tumors may originate from 2 different types of thymic epithelial cells.