[Retroperitoneal Dedifferentiated Liposarcoma with No Recurrence after 5 Years of Postoperative Radiation Therapy --A Case Report-].

A 49-year-old woman presented to our hospital with right lower back pain and epigastric pressure. A computed tomographic scan showed a 12×7×20 cm retroperitoneal mass comprising fatty components and contrast areas around the right kidney. Based on the results, a right retroperitoneal liposarcoma was suspected. Thus, right retroperitoneal tumor resection combined with right kidney resection was performed. Instances of tumor adhesion were found in the ascending colon, duodenum, and the iliopsoas muscle, which could be dissected ; therefore, combined resection of the intestinal tract was not performed. The resected tumor was found to be mixed with dedifferentiated and well-differentiated components and was diagnosed as dedifferentiated liposarcoma. Due to the presence of positive margins, the patient received 50 Gy in 25 fractions of radiation therapy to the right side of the retroperitoneum as postoperative adjuvant therapy. During the irradiation period, vomiting and anorexia were observed as adverse events. Five years have passed since the surgery, and no local recurrence or late complications due to radiation have been observed. Although dedifferentiated liposarcoma is a highly malignant histological type with a very high local recurrence rate, no adjuvant therapy has been established. Some reports have suggested that postoperative radiation therapy for retroperitoneal sarcoma is effective in terms of survival and local control. However, there are no reports of prospective clinical trials, and the evidence is expected to widen in the near future.

Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8+ T Cells.

The thymoproteasome subunit ß5t is specifically expressed in cortical thymic epithelial cells (TECs) and generates unique peptides to support positive selection. In this study, using a mouse model ubiquitously expressing ß5t, we showed that aberrant expression of self-peptides generated by ß5t affects CD8+ T cell homeostasis, including thymic selection and maintenance of the peripheral naive pool of CD8+ T cells. In mice in which ß5t was expressed both in cortical and medullary TECs, the abundance of CD8+ lineage thymocytes was reduced, and extra-thymic expression of ß5t caused accumulation of CD8+ T cells with the memory or exhausted phenotype and induced autoreactive T cell responses. We found that thymoproteasomes are essential for positive selection but that the subsequent change in peptide repertoire in the medulla is also crucial for thymic selection and that ß5t-derived peptide must be confined to the thymus to avoid autoimmunity in peripheral tissues.

The Effectiveness of Afatinib in a Patient with Advanced Lung Adenocarcinoma Harboring Rare G719X and S768I Mutations.

The uncommon mutations in the EGFR (the epithelial growth factor receptor) gene include a heterogeneous group of genomic alterations within exons 18-21. The clinical response of patients with such mutations to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, however, remains unclear. We herein report a case of advanced lung adenocarcinoma harboring complex exon 18 G719X (Gly719Xaa) and exon 20 S768I (Ser768Ile) mutations. The patient started to receive afatinib and has exhibited good response without progression for 12 months. Second-generation EGFR-TKIs might be an optimal treatment option for non-small cell lung cancers harboring these types of rare EGFR mutation.

Expression of cathepsins V and S in thymic epithelial tumors.

Cathepsins are a group of proteolytic enzymes of the endosomal/lysosomal pathway involved in the thymic development of T cells restricted by major histocompatibility complex class II molecules. In the normal thymus, cathepsin V (CTV) and cathepsin S (CTS) are expressed in cortical and medullary epithelial cells, respectively. To investigate whether cathepsins could serve as a diagnostic marker, we performed immunohistochemical analysis for CTV and CTS in 77 cases of thymic epithelial tumors. Almost all cases (59/60) of thymoma expressed CTV, whereas 28 of 60 cases of thymoma expressed CTS. Notably, CTS was expressed in most cases of type A and type AB thymomas, but not in type B thymoma. The expression of cathepsins in type AB thymoma showed a clear correlation with histologic features; CTV was found predominantly in the type B component, and CTS was frequently expressed in the type A component. In thymic carcinoma, CTV was expressed in less than half cases (7/17), and the ratio of CTS-positive cases was equivalent to that of thymoma (8/17). Cases of CTV-negative thymic carcinoma tended to have a higher incidence of recurrence than did CTV-positive cases. Although further studies with a larger number of cases are required to confirm the utility of cathepsin immunostaining, CTV and CTS appear to serve as auxiliary diagnostic and/or prognostic markers in thymic epithelial tumors.

Branchial cleft-like cysts in Hashimoto's thyroiditis: A case report and literature review.

We report an extremely rare case of branchial cleft-like cysts in Hashimoto's thyroiditis. The patient was a 77-year-old man with a growing mass in the anterior neck. Ultrasonography and computed tomography revealed a cystic lesion with septum in the left thyroid and multiple small cystic lesions in the right thyroid. Lymph node swelling of the cervical region, supraclavicular fossa and submandibular region was also observed. Left thyroidectomy and lymph node dissection were performed. Histologically, cysts were lined by stratified squamous epithelium and dense lymphoid tissue having conspicuous follicle formation surrounded the epithelial lining. Solid cell nest (SCN)-like aggregations were seen in the thyroid parenchyma adjacent to the cyst walls and a small number of thyroid follicles were observed in the fibrous wall. Immunohistochemically, it is suggested that both the cyst lining and SCN-like aggregations are originally from thyroid follicles. Although, the exact histogenesis of branchial cleft-like cysts remains unclear, there are probably two different processes for its development, one is of branchial cleft origin and the other is mere squamous metaplasia, while in our case the latter is suggested. Herein, we report our new case and update information about branchial cleft-like cysts that appears in the literature.

Decreased expression of thymus-specific proteasome subunit ß5t in Down syndrome patients.

AIMS: The majority of patients with Down syndrome (DS), trisomy 21, have morphologically abnormal thymuses and present with intrinsic immunological abnormalities affecting mainly the cellular immune response. The aim of this study was to examine whether the expression of functionally important molecules is altered in thymic stromal cells in patients with DS. METHODS AND RESULTS: We analysed thymic tissues from patients with trisomy 13 (n = 4), trisomy 18 (n = 14) and trisomy 21 (n = 13) for histological alterations, and for the expression of functionally important molecules such as ß5t, a thymoproteasome subunit, and cathepsins L and S. In patients with trisomy 13 and trisomy 18, the thymus was morphologically normal or showed only mild depletion of cortical thymocytes. In contrast, the thymus showed variable histological changes in patients with trisomy 21; six of 13 cases showed severe depletion of thymocytes accompanied by the disappearance of thymic lobular architecture. In such thymuses, spindle-shaped keratin-positive cells were densely distributed, and expression of ß5t, but not of cathepsin L, was markedly decreased. CONCLUSIONS: The present study suggests that abnormal thymic architecture and decreased expression of functionally important molecules in thymic stromal cells may be involved in immunological abnormalities in DS patients.

Pancreatic cancer cells express CD44 variant 9 and multidrug resistance protein 1 during mitosis.

Pancreatic cancer is one of the most lethal cancers with high metastatic potential and strong chemoresistance. Its intractable natures are attributed to high robustness in tumor cells for their survival. We demonstrate here that pancreatic cancer cells (PCCs) with an epithelial phenotype upregulate cell surface expression of CD44 variant 9 (CD44v9), an important cancer stem cell marker, during the mitotic phases of the cell cycle. Of five human CD44(+) PCC lines examined, three cell lines, PCI-24, PCI-43 and PCI-55, expressed E-cadherin and CD44 variants, suggesting that they have an epithelial phenotype. By contrast, PANC-1 and MIA PaCa-2 cells expressed vimentin and ZEB1, suggesting that they have a mesenchymal phenotype. PCCs with an epithelial phenotype upregulated cell surface expression of CD44v9 in prophase, metaphase, anaphase and telophase and downregulated CD44v9 expression in late-telophase, cytokinesis and interphase. Sorted CD44v9-negative PCI-55 cells resumed CD44v9 expression when they re-entered the mitotic stage. Interestingly, CD44v9(bright) mitotic cells expressed multidrug resistance protein 1 (MDR1) intracellularly. Upregulated expression of CD44v9 and MDR1 might contribute to the intractable nature of PCCs with high proliferative activity.