Combining chemotherapy with immune checkpoint inhibitors (ICIs) that target the programmed death-1 (PD-1) protein has been shown to be a clinically effective first-line treatment for human epidermal growth factor receptor 2 (HER2)-negative and -positive advanced or metastatic gastric cancer (GC). Currently, PD-1 inhibitors combined with chemotherapy are the standard treatment for patients with HER2-negative/positive locally advanced or metastatic GC. Programmed death-ligand 1 (PD-L1) expression, as assessed using immunohistochemistry (IHC), is a crucial biomarker for predicting response to anti-PD-1/PD-L1 agents in various solid tumors, including GC. In GC, the PD-L1 IHC test serves as a companion or complementary diagnostic test for immunotherapy, and an accurate interpretation of PD-L1 status is essential for selecting patients who may benefit from immunotherapy. However, PD-L1 IHC testing presents several challenges that limit its reliability as a biomarker for immunotherapy. In this review, we provide an overview of the current practices of immunotherapy and PD-L1 testing in GC. In addition, we discuss the clinical challenges associated with PD-L1 testing and its future use as a biomarker for immunotherapy. Finally, we present prospective biomarkers currently under investigation as alternative predictors of immunotherapy response in GC.

Combining chemotherapy with immune checkpoint inhibitors (ICIs) that target the programmed death-1 (PD-1) protein has been shown to be a clinically effective first-line treatment for human epidermal growth factor receptor 2 (HER2)-negative and -positive advanced or metastatic gastric cancer (GC). Currently, PD-1 inhibitors combined with chemotherapy are the standard treatment for patients with HER2-negative/positive locally advanced or metastatic GC. Programmed death-ligand 1 (PD-L1) expression, as assessed using immunohistochemistry (IHC), is a crucial biomarker for predicting response to anti-PD-1/PD-L1 agents in various solid tumors, including GC. In GC, the PD-L1 IHC test serves as a companion or complementary diagnostic test for immunotherapy, and an accurate interpretation of PD-L1 status is essential for selecting patients who may benefit from immunotherapy. However, PD-L1 IHC testing presents several challenges that limit its reliability as a biomarker for immunotherapy. In this review, we provide an overview of the current practices of immunotherapy and PD-L1 testing in GC. In addition, we discuss the clinical challenges associated with PD-L1 testing and its future use as a biomarker for immunotherapy. Finally, we present prospective biomarkers currently under investigation as alternative predictors of immunotherapy response in GC.

Combining chemotherapy with immune checkpoint inhibitors (ICIs) that target the programmed death-1 (PD-1) protein has been shown to be a clinically effective first-line treatment for human epidermal growth factor receptor 2 (HER2)-negative and -positive advanced or metastatic gastric cancer (GC). Currently, PD-1 inhibitors combined with chemotherapy are the standard treatment for patients with HER2-negative/positive locally advanced or metastatic GC. Programmed death-ligand 1 (PD-L1) expression, as assessed using immunohistochemistry (IHC), is a crucial biomarker for predicting response to anti-PD-1/PD-L1 agents in various solid tumors, including GC. In GC, the PD-L1 IHC test serves as a companion or complementary diagnostic test for immunotherapy, and an accurate interpretation of PD-L1 status is essential for selecting patients who may benefit from immunotherapy. However, PD-L1 IHC testing presents several challenges that limit its reliability as a biomarker for immunotherapy. In this review, we provide an overview of the current practices of immunotherapy and PD-L1 testing in GC. In addition, we discuss the clinical challenges associated with PD-L1 testing and its future use as a biomarker for immunotherapy. Finally, we present prospective biomarkers currently under investigation as alternative predictors of immunotherapy response in GC.

Background: The implication of the presence of tumor-infiltrating T lymphocytes (TIL-T) in diffuse large B-cell lymphoma (DLBCL) is yet to be elucidated. We aimed to investigate the effect of TIL-T levels on the prognosis of patients with DLBCL. Methods: Ninety-six patients with DLBCL were enrolled in the study. The TIL-T ratio was measured using QuPath, a digital pathology software package. The TIL-T ratio was investigated in three foci (highest, intermediate, and lowest) for each case, resulting in TIL-T–Max, TIL-T–Intermediate, and TIL-T–Min. The relationship between the TIL-T ratios and prognosis was investigated. Results: When 19% was used as the cutoff value for TIL-T–Max, 72 (75.0%) and 24 (25.0%) patients had high and low TIL-T–Max, respectively. A high TIL-T–Max was significantly associated with lower serum lactate dehydrogenase levels (p < .001), with patient group who achieved complete remission after RCHOP therapy (p < .001), and a low-risk revised International Prognostic Index score (p < .001). Univariate analysis showed that patients with a low TIL-T–Max had a significantly worse prognosis in overall survival compared to those with a high TIL-T–Max (p < .001); this difference remained significant in a multivariate analysis with Cox proportional hazards (hazard ratio, 7.55; 95% confidence interval, 2.54 to 22.42; p < .001). Conclusions Patients with DLBCL with a high TIL-T–Max showed significantly better prognosis than those with a low TIL-T–Max, and the TIL-T–Max was an independent indicator of overall survival. These results suggest that evaluating TIL-T ratios using a digital pathology system is useful in predicting the prognosis of patients with DLBCL.

Metastatic leiomyosarcoma to the thyroid is an extremely rare occurrence, and only 18 cases have been reported. Here, we report a case of a 37-year-old woman who presented with multiple masses on the scalp. Excisional biopsy was done and the mass revealed fascicles of smooth muscle fibers which showed positive staining for smooth muscle actin, thus confirming the diagnosis of leiomyosarcoma. The patient was also found to have a 0.9 cm mass within the left thyroid. Fine-needle aspiration was done and the cytological smear showed hypercellular spindle cell clusters with hyperchromatic and large nuclei. Normal thyroid follicular cells were found within or around tumor cells. In this report, we present the cytologic findings of metastatic leiomyosarcoma to the thyroid and offer differential diagnoses of the aspirated spindle cells.

Metastatic leiomyosarcoma to the thyroid is an extremely rare occurrence, and only 18 cases have been reported. Here, we report a case of a 37-year-old woman who presented with multiple masses on the scalp. Excisional biopsy was done and the mass revealed fascicles of smooth muscle fibers which showed positive staining for smooth muscle actin, thus confirming the diagnosis of leiomyosarcoma. The patient was also found to have a 0.9 cm mass within the left thyroid. Fine-needle aspiration was done and the cytological smear showed hypercellular spindle cell clusters with hyperchromatic and large nuclei. Normal thyroid follicular cells were found within or around tumor cells. In this report, we present the cytologic findings of metastatic leiomyosarcoma to the thyroid and offer differential diagnoses of the aspirated spindle cells.

BACKGROUND: SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC. METHODS: We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs. RESULTS: A loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancer-specific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022). CONCLUSIONS: We confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression.
Carcinogenesis ; Chemotherapy, Adjuvant ; Colorectal Neoplasms ; Disease-Free Survival ; Humans ; Lymphocytes, Tumor-Infiltrating ; Microsatellite Instability ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies