Background: A higher number of tumor buds in the invasive front of colorectal cancer (CRC) specimens has been shown to contribute to a poor prognosis in CRC patients. Because macrophages (Mφs) have been demonstrated to alter the phenotype of cancer cells, we hypothesized that the phenotype of CRC cells in the tumor budding (TB) area might be changed by the interaction between CRC cells and Mφs. Methods: We assessed the expression of topoisomerase 1 in CRC cells to estimate the acquisition of chemoresistance in CRC. To demonstrate the tumor–stromal interaction between CRC cells and Mφs, we assessed two histological findings, the number of Mφs per single CRC cell and the proximity between CRC cells and Mφs by histological spatial analysis using HALO software. Results: The expression levels of topoisomerase 1 in CRC cells were decreased in deeper areas, especially in the TB area, compared to the surface area. Our histological spatial analysis revealed that 2.6 Mφs located within 60 μm of a single CRC cell were required to alter the phenotype of the CRC cell. Double-immunofluorescence staining revealed that higher Mφs were positive for interleukin-6 (IL-6) in the TB area and that AE1/AE3-positive CRC cells were also positive for phospho-STAT3 (pSTAT3) in the TB area; thus, the IL-6 receptor (IL-6R)/STAT3 signaling pathway in CRC cells was upregulated by IL-6 derived from neighboring Mφs. Conclusion: IL-6 secreted from the neighboring Mφs would alter the phenotype of CRC cells via IL-6R/STAT3 signaling pathway.

The aim of this study was to examine whether lymphatic invasion in papillary thyroid carcinoma (PTC) occurs when tumour-associated macrophages (TAMs) injure lymphatic vessels together with cancer cells. While there was no difference in the lymphatic vessel density in PTC and follicular thyroid carcinoma (FTC), the number of TAMs around the lymphatic vessels was increased in PTC compared to that in FTC. In particular, TAMs were observed together with cancer cells in lymphatic invasive lesions, and the number of M2 cells inside and outside the lymphatic vessels showed a significant correlation. MMP-2 mRNA was expressed in nonneoplastic stromal cells as well as cancer cells, and double immunofluorescence staining confirmed M2 positivity. Consequently, this study reveals that M2 TAMs around lymphatic vessels within the tumour border of PTC may be associated with the lymphatic invasion of cancer cells. This study represents a step forward in elucidating the mechanism of lymphatic invasion.

Lymphoproliferative disorders may occur in patients with rheumatoid arthritis (RA) who are treated with methotrexate. However, follicular thymic hyperplasia (FTH) associated with RA (FTH‐RA) is generally not considered a lymphoproliferative disorder. To investigate the pathogenesis of FTH‐RA, we examined 12 cases of FTH involving thymic enlargement, four of FTH involving RA and eight of FTH involving myasthenia gravis (MG). Increased numbers and larger germinal center (GC) size were observed in FTH‐RA group. The percentage of distorted GCs was 13.3% in FTH‐RA group and 3.25% in FTH associated with MG (FTH‐MG) group. A greater meshwork of follicular dendritic cells was observed in the GCs of FTH‐RA group. Positive indices of CD27⁺ cells and PD‐1⁺ cells per GC in FTH‐RA group were significantly higher than those in FTH‐MG group, though positive indices of CD68⁺ cells and CD163⁺ cells were similar. Myoid cell proliferation, as evaluated by α‐SMA, tenascin‐C, and l‐caldesmon expression, was significantly increased in the FTH‐RA group compared with the FTH‐MG group. These results suggest that FTH should be considered in patients with RA treated with methotrexate. The pathogenesis of FTH‐RA includes GC expansion and increased numbers of memory B cells, follicular helper T cells, and myoid cells, indicating humoral immunity activation.

Background: Ulcerative colitis (UC) is one of the major types of inflammatory bowel diseases and is associated with a significantly increased risk of not only lymphoproliferative disorders but also lymphomas, of which most cases are related to the long-term usage of immunosuppressants. Here, we demonstrate a very rare case of other iatrogenic immunodeficiency-associated colonic diffuse large B-cell lymphoma (Oii-DLBCL) complicating UC and rectal perforation. In addition, we reviewed the clinicopathological features of previous cases of DLBCL related to UC.Case presentation: A 68-year-old man was diagnosed with left-sided UC 26 months prior. Although he was followed by immunosuppressive therapy with azathioprine and infliximab, an emergency total proctocolectomy was performed due to rectal perforation. The resected specimen exhibited irregular wall thickening and elevated multinodular lesions extending from the mid-transverse colon to the rectum, measuring up to 52 cm in length. Histologically, the lesion was diagnosed as Oii-DLBCL and crypt abscess surrounded by mixed inflammatory cell was remained.Conclusion: Oii-DLBCL complicating UC with rectal perforation is extremely rare. Macro- and microscopic findings are important for early diagnosis of the lesion.