KRAS mutation-positive mucinous adenocarcinoma originating in the thymus

Abstract

Thymic carcinoma is a rare, aggressive disease with a low 5-year survival rate. The most common histological neoplastic thymic tumor subtype is squamous cell. We describe an interesting case of a 39-year-old woman who presented with mucinous adenocarcinoma that originated in the thymus and was treated via radical resection and venoplasty of the superior vena cava (SVC). Macroscopically, the resected tumor contained a solid region and multiple cysts with abundant mucin. Microscopic examination showed a papillary growth pattern of goblet cells with round nuclei. Based on the histopathological and immunohistochemical findings and other inspections, the tumor was eventually diagnosed as a mucinous adenocarcinoma of the thymus. It was classified as Masaoka-Koga stage III owing to tumor invasion into the left brachiocephalic vein and pericardium. Polymerase chain reaction identified a Kirsten rat sarcoma viral oncogene homolog (KRAS) G12V mutation in the tumor. There were no mutations in the epidermal growth factor (EGFR) gene or a fusion gene of the echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK). A year later, multiple lung metastases were detected, and the patient underwent chemotherapy. She is alive 34 months after the initial surgery. This is the first report of a KRAS mutation-positive mucinous adenocarcinoma originating in the thymus. The treatment, diagnosis, and pathological findings of the patient are discussed. 19-9 (CA19-9) was 80.5 U/mL (normal: 0-37 U/mL), while the levels of other markers were within the normal range. KeywordsThe patient underwent radical resection via median sternotomy following a preoperative clinical diagnosis of thymic carcinoma. During the operation, combined resection of the pericardium, right phrenic nerve, right internal artery, and left brachiocephalic vein was performed owing to tumor invasion. Partial resection and venoplasty with a pericardium patch for the superior vena cava (SVC) were also performed via a temporal bypass between the left brachiocephalic vein and right atrial appendage, using a 6-mm polytetrafluoroethylene graft. The total operation time was 699 min, and amount of blood lost was 702 mL.Macroscopically, the resected tumor was 6.5 cm × 3.5 cm in size and contained a solid region and multiple cysts with abundant mucin (Figure 2). Microscopic examination showed a papillary growth pattern of goblet cells with round nuclei ( Figure 3A). On immunohistochemistry, the resected tumor was positive for caudal type homeobox 2 protein, cytokeratin 7, and cytokeratin 20 ( Figure 3B-D), focally positive for CD5, and negative for thyroid transcription factor RNA polymerase I and surfactant apoprotein A; these findings suggest intestinal or ovarian differentiation of the tumor. Subsequent gastrointestinal endoscopy, colonoscopy, abdominopelvic sonography, and imaging analysis did not provide any indication of another primary origin. The serum level of CA19-9 temporarily decreased after the surgery.Based on the histo...

A primary thymic adenocarcinoma with two components that traced distinct evolutionary trajectories

“…To date, however, only a few English‐language reports have described the genetic abnormalities of thymic adenocarcinoma 5–7 . As such, our case exhibited several novel genetic features, namely, CDKN2A mutations/deletions, an MSI‐H phenotype, and whole‐genome doubling.…”

Thymic adenocarcinoma accompanied by type A thymoma and pulmonary minimally invasive adenocarcinoma and harboring distinct gene alterations

“…Previous studies identified many genetic aberrations in thymic adenocarcinoma, including a homozygous deletion at the HLA locus and KRAS mutation. [ 6 , 7 , 17 ] But due to the small number of cases, no genetic changes with high incidence were found in thymic adenocarcinomas. KMT2A-MAML2 gene fusion was reported in 4% thymomas (10 of 242), and was considered specific to type B2 and B3 thymomas.…”

Primary Thymic Mucinous Adenocarcinoma: A Case Report Focusing on Radiological Findings and Review of the Literature

“…Most cases of primary thymic mucinous adenocarcinoma are reported in pathology journals. CT figures and descriptions were found in 11 of 27 cases reported in the English literature (3)(4)(5)(6)(7)(11)(12)(13)(14)(15)(16). We analyzed a total of 12 cases of CT images, including the previous 11 cases and our case.…”