Prognostic impact of tumor-associated neutrophils in breast cancer.

OBJECTIVES: Neutrophils are the most common type of leukocyte in mammals and play an essential role in the innate immune system and anti-cancer responses. However, recent studies identified the presence of tumor-associated neutrophils (TANs) as a poor prognostic factor. The present study investigated whether relationships exist between TANs and the clinicopathological factors and genetic status of breast cancer. METHODS: A total of 196 breast cancer patients with sufficient biopsy, breast-conserving surgery, or mastectomy specimens between 2014 and 2021 in Hokuto Hospital were included. RESULTS: TANs were individually counted in the tumor stroma (TS) and tumor nest (TN). A higher density of TANs in both TS and TN correlated with tumor size (TS P = 0.010; TN P = 0.001), a high histological grade (TS P < 0.001; TN P < 0.001), the histological type (TS P = 0.009; TN P = 0.034), a high ratio of lymph node metastasis (TS P < 0.001; TN P < 0.001), an advanced stage of cancer (TS P < 0.001; TN P = 0.002), intrinsic subtypes (TS P < 0.001; TN P < 0.001), ERBB2 (TS P < 0.001; TN P < 0.001), MAP3K1 (TS P = 0.002; TN P = 0.023), and TP53 (TS P < 0.001; TN P < 0.001). A higher density of TANs in TS and TN also correlated with shorter disease-free survival and overall survival (P < 0.001). CONCLUSION: The present results suggest that a higher density of TANs correlates with unfavorable prognostic factors in breast cancer. Further research on clinicopathological and genetic factors associated with TANs in breast cancer is needed.

Primary Hepatic Angioleiomyoma: A Case Report.

BACKGROUND Primary hepatic angioleiomyoma is a rare mesenchymal tumor that is characterized by blood vessels and smooth muscle. Herein, we report an extremely rare case of primary hepatic angioleiomyoma and discuss the clinicopathological features. CASE REPORT A 60-year-old Mongolian man was diagnosed with a hepatic tumor in the second and third segments of screening in 2012. It had been under control by a physician for 10 years. The patient had discomfort and vague pain in the right side of the abdomen since April 2022. Hepatitis virus markers (hepatitis B and hepatitis C) were negative. Plain computed tomography revealed an 80-mm solitary liver lesion in the left lobe with well-defined margins and heterogeneous enhancement. A left hepatectomy was performed in May 2022. The cut surface of the tumor showed a grayish-white, elastic, hard mass with a diameter of 50×80 mm. Histological findings of the tumor revealed that it was clearly demarcated from the surrounding liver tissues with relatively clear boundaries showing thick, muscle-coated blood vessels with perivascular smooth muscle bundles. Immunohistochemical staining showed that the smooth muscle cells were strongly diffuse and positive for smooth muscle actin. CONCLUSIONS Clinically, primary hepatic angioleiomyoma should be distinguished from other types of liver tumors, especially liver cancer. In combination with our long-term observation and other case reports, we recommend general follow-up if the preoperative pathological diagnosis can be confirmed and the patient has no other symptoms.

Gastric Adenocarcinoma of the Fundic Gland Type: A Case Report.

BACKGROUND Gastric adenocarcinoma of the fundic gland type (GAFG) is an extremely rare neoplasm that consists of a mixed proliferation of oxyntic and chief cells. Differential diagnosis of GAFG is difficult in the absence of infiltration. Here, we report a case of GAFG and discuss the clinicopathological features. CASE REPORT A 78-year-old man was diagnosed with gastritis and reflux esophagitis, status after esophagectomy for carcinoma of the esophagus in 2015. The patient underwent repeated gastric biopsies in 2017 and an atypical epithelium was observed, but no diagnosis was confirmed. There was no evidence of tumor extension in the submucosa. The tumor was resected via endoscopic mucosal resection, and pathological examination was performed. Microscopic findings revealed an oxyntic-type gastric mucosa with atypical dense or dilated glands with abundant pale basophilic cytoplasm and round nuclei with prominent nucleoli. The majority of the tumor cells resembled chief cells, suggesting they were derived from gastric fundic glands. However, the tumor appeared to have no submucosal infiltration or focal stromal desmoplastic reaction. Sections stained positive for MUC6 and pepsinogen-I in chief cells, and H+/K+ ATPase and PDGFRa in parietal cells, but were mostly negative for CDX2, chromogranin A, synaptophysin, and CD10. Sections stained for mib-1 expressed very low proliferative activity, with an average of 10%. Staining for TP53 overexpression was negative. CONCLUSIONS Immunostaining markers are a supportive tool for histological diagnosis of GAFG. However, if there is no infiltration, as in our case, it is difficult to consider it as a malignant tumor. Further elucidation is needed in the future, including an officially accepted diagnostic name.

Tumor-infiltrating B cells and T cells correlate with postoperative prognosis in triple-negative carcinoma of the breast.

BACKGROUND: In this study, we investigated CD20+ TILs in triple-negative breast cancer (TNBC) and their relationship with T lymphocyte subsets (CD4+, CD8+, CD25+, and FOXP3+), including their combined prognostic value using an immunohistochemical staining method. METHODS: We investigated 107 patients with TNBC for whom a full-face section stained by hematoxylin and eosin between 2006 and 2018 at Dokkyo Medical University Hospital was available. RESULTS: The strongest association of infiltrating CD20+ TILs was with CD4+ TILs. There was a significant relationship between CD20+ and CD4+ TILs (r = 0.177; p < 0.001), CD8+ TILs (r = 0.085; p = 0.002), and FOXP3+ TILs (r = 0.0043; p = 0.032). No significant relationships were observed between the CD20+ and CD25+ TILs (r = 0.012; p = 0.264). Multivariate analysis revealed that only the CD20+/FOXP3 ratio was an independent factor for relapse-free survival (p < 0.001) and overall survival (p < 0.001). Patients with tumors highly infiltrated by CD4+, CD8+, and CD20+ TILs had a good prognosis. In contrast, those with tumors weakly infiltrated by CD20+ TILs but highly infiltrated by CD25+ and FOXP3+ TILs had a poor prognosis. CONCLUSIONS: CD20+ TILs may support an increase in CD4+ and CD8+ TILs, which altered the anti-tumor response, resulting in a positive prognosis. CD20+ TILs correlated with FOXP3+ Treg lymphocytes, which were reported to be correlated with a poor prognosis. Our study suggested that TIL-B cells have dual and conflicting roles in TIL-T immune reactions in TNBC.

Prognostic value of tumor-infiltrating B lymphocytes and plasma cells in triple-negative breast cancer.

BACKGROUND: Recent investigations have demonstrated that the tumor microenvironment, including tumor-infiltrating lymphocytes (TILs), is an important factor in tumor growth and development. While the prognostic correlation of tumor-infiltrating T cells has been widely studied in breast cancer, that of tumor-infiltrating B cells and plasma cells has not received so much attention, especially in triple-negative breast cancer (TNBC). METHODS: We investigated 114 patients with TNBC who had surgery between 2006 and 2019 at Dokkyo Medical University Hospital. Intratumoral (i) TILs were considered to be lymphocytes within cancer cell nests and directly infiltrating tumor cells. Similarly, stromal (s) TILs were considered to be lymphocytes within the tumor stroma, but not directly infiltrating tumor cells. CD20 + , CD38 + and CD138 + staining was determined by estimating the number of positive B cells. RESULTS: sCD20 + TILs had prognostic significance for relapse-free survival (RFS) (p = 0.043) and overall survival (OS) (p = 0.027). The sCD38 + TILs were significantly related to favorable RFS (p = 0.042). iCD38, iCD138, and sCD138 was not significantly correlated with RFS (p = 0.065, p = 0.719, p = 0.074) or OS (p = 0.071, p = 0.689, p = 0.082). CONCLUSIONS: The present study demonstrated that a high density of sCD20 + TILs was significantly related to favorable prognosis in both RFS and OS. Increased sCD38 + TILs in TNBC were correlated with a significantly favorable prognosis in RFS. These results indicate that TILs-B may have a profound influence on the clinical outcome of TNBC.