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Non-Hodgkin's lymphoma (NHL) is the fifth most common hematologic disorder in the United States, and its prevalence has been rising in Western countries. Among the subtypes of NHL, diffuse large B-cell lymphoma (DLBCL) mostly involves the lymph nodes, stomach, and gastrointestinal tract, whereas hepatic involvement of DLBCL is rare. On serologic testing, elevated immunoglobulin G (IgG) levels can be observed in DLBCL; however, elevated IgG levels are mainly observed in autoimmune hepatitis. A targeted-lesion biopsy is required for the diagnosis of DLBCL. Based on a final diagnosis, the patient was treated with rituximab-based chemotherapy, including cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP). Herein, we report a case of DLBCL mimicking antinuclear antibody-negative autoimmune hepatitis, which was finally diagnosed as DLBCL involving the liver, and was confirmed by liver biopsy. [ABSTRACT FROM AUTHOR]

Abstract Vascular abnormality of the intestine is rare, except angiodysplasia. We report on an unusual case of atypical florid vascular proliferations of the appendix. A 41-year old male presented with melena. Adhesioned blood clots in the appendiceal orifice were observed by colonoscopy. He underwent laparoscopic appendectomy. Microscopically, a tiny exophytic polypoid mass was observed. The mass showed pyogenic granuloma-like features in the superficial portion and infiltrative florid vascular proliferations in the deeper portion. Endothelial cells showed minimal nuclear atypia, and mitotic figures were observed infrequently and showed positivity for CD31 and CD34 and negativity for HHV-8. Differential diagnoses include from benign vascular tumor to angiosarcoma or Kaposi’s sarcoma, but this lesion does not fit the description of any defined vascular entity. We diagnosed atypical florid vascular proliferations and the patient has been well during the five-month postoperative follow-up. Virtual Slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1386921325843104

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)-a new category of anaplastic large cell lymphoma associated with textured breast implants-has a distinct variation in incidence and is especially rare in Asia. We report the first case of BIA-ALCL in Korea and present its histological and genetic characteristics. A 44-year-old female patient presented with a typical clinical course and symptoms, including breast augmentation with textured breast implants, late-onset peri-implant effusion, and CD30+ALK- histology, followed by bilateral implant removal and total capsulectomy. For histological analysis, we performed immunohistochemistry of the bilateral breast capsules. For transcriptome analysis, we identified highly upregulated gene sets employing RNA-sequencing and characterized the lymphoma immune cell components. In the lymphoma-associated capsule, CD30+ cells infiltrated not only the lymphoma lesion but also the peritumoral lesion. The morphologies of the myofibroblasts and vessels in the peritumoral lesion were similar to those in the tumoral lesion. We observed strong activation of the JAK/STAT3 pathway and expression of programmed death ligand-1 in the lymphoma. Unlike the molecular profiles of BIA-ALCL samples from Caucasian patients-all of which contained activated CD4+ T cells-the Asian patient's profile was characterized by more abundant CD8+ T cells. This study contributes to a better understanding of the pathogenesis and molecular mechanisms of BIA-ALCL in Asian patients that will ultimately facilitate the development of clinical therapies.Level Of Evidence:5: [ABSTRACT FROM AUTHOR]

We evaluated the association of cell adhesion molecule 4 ( CADM4) expression with clinicopathologic parameters and overall survival ( OS) in patients with small intestinal adenocarcinomas ( SIAs) and determined its prognostic significance. CADM4 immunohistochemical staining was performed for 170 SIA samples. Loss of or low CADM4 expression was observed in 26 (15.3%) and 50 (29.4%) cases, respectively, and it was significantly associated with undifferentiated histology (p < 0.044), high-grade tumor (p < 0.001), high pT3 or pT4 stage (p < 0.038), pancreatic invasion (p < 0.018), and lymphatic invasion (p < 0.020). Patients with CADM4 expression loss had significantly poorer OS (p < 0.042). On multivariate analysis, SIA in the jejunum and ileum, (hazard ratio [ HR], 2.465; 95% confidence interval [ CI], 1.288-4.720; p = 0.006 and HR, 3.407; 95% CI, 1.515-7.662; p = 0.003, respectively), signet ring cell carcinoma ( HR, 92.388; 95% CI, 14.813-576.230; p = 0.000), SIA with lymph node metastasis ( HR, 3.223; 95% CI, 1.697-6.124; p = 0.000), retroperitoneal seeding ( HR, 3.696; 95% CI, 1.303-10.479; p = 0.014), and CADM4 expression loss ( HR, 2.348; 95% CI, 1.130-4.882; p = 0.022) were associated with poor OS. CADM4 expression loss is an important prognostic marker for SIA. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis is a rare disease that is characterized by a localized or systemic proliferation of Langerhans dendritic cells and a wide spectrum of clinical presentations. We experienced an unusual case of occult Langerhans cell histiocytosis associated with clear cell renal cell carcinoma. A 62-year-old man underwent a partial nephrectomy for left renal mass. Histologic examination showed nests of clear cells with surrounding thin-walled vessel that were suggestive of clear cell renal cell carcinoma. A well-defined nodule composed of atypical mononuclear cells and plentiful eosinophils presented within clear cell renal cell carcinoma. The mononuclear cells were Langerhans cell histiocytes with S-100 and CD1a immunoreactivity. On follow-up comprehensive physical, laboratory, and radiologic examination, there were no other lesions of Langerhans cell histiocytosis. [ABSTRACT FROM AUTHOR]

Aims To investigate AT-rich interactive domain-containing protein 1A ( ARID1A) and p53 expression in small intestinal carcinoma ( SIC) and to determine its prognostic significance. Methods and results Immunohistochemical staining for ARID1A and p53 was performed in 178 SICs using a tissue microarray (TMA). Loss of or low ARID1A expression was observed in 36 (20.2%) and 60 (33.7%) of cases, respectively. Aberrant p53 expression was observed in 99 (55.6%) cases. Loss of or low ARID1A expression was found to be associated with signet ring cell carcinoma and undifferentiated carcinoma, a high-grade tumour, and a higher T stage. No relationship was found between aberrant p53 expression and clinicopathological factors or overall survival. Patients with loss of ARID1A expression, irrespective of p53 expressional status, showed significantly poorer overall survival than those expressing ARID1A. Multiple regression analysis revealed that grade and pT stage were associated significantly with ARID1A loss, and multivariate analysis showed that patients with high ARID1A expression had a lower risk of death than those with loss of ARID1A expression. Conclusions Low or loss of ARID1A expression is correlated significantly with a high-grade tumour, higher T stage, and poorer overall survival. These findings suggest that ARID1A expression could be used as a prognostic marker in SIC. [ABSTRACT FROM AUTHOR]

Several photographs are presented depicting results of positron emission tomography-magnetic resonance image fusion imaging and surgical and microscopic findings in a 36-year old patient that show a cardiac mass and neuroendocrine tumour of the rectum.

Prostate cancer is the most common malignancy in men, and biologically shows highly heterogeneous clinical outcomes, despite early detection. Therefore, the identification of novel molecular markers that are associated with biological aggressiveness is very important for prostatic cancer clinical outcome predictions and treatment choices. Here, we investigate quiescin sulfhydryl oxidase 1 (QSOX1) expression and evaluate its clinicopathological significance and prognostic impact in prostate cancers, with immunohistochemistry on tissue microarrays. QSOX1 over-expression was observed in 12 (11.2%) of prostate cancers. High QSOX1 expression significantly associated with prostate cancer with vascular invasion, neural invasion, extra prostatic extension, higher pT stage, higher pathological tumor stage, higher prognostic grouping, and higher grades groups, but did not associated with worse overall survival. High QSOX1 expression correlates with tumor invasiveness and Gleason grade, reflects aggressive tumor features, and could be an important biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

Background/aim: Claudin 18.2 (CLDN18.2) has emerged as a highly selective biomarker and its abnormal expression has been reported in various primary malignant tumors. Recently, CLDN18.2 has gained attention as both a prognostic biomarker and a potential therapeutic target in gastric and gastroesophageal junction cancer. The purpose of this study was to investigate CLDN18.2 expression in a large cohort of 168 prostate cancer (PC) tissues, assess its correlation with clinicopathological factors, and evaluate its potential as a therapeutic target for anti-CLDN18.2 therapy., Materials and Methods: Immunohistochemical staining was conducted using an approved diagnostic CLDN18.2 immunohistochemistry protocol (Ventana, 43-14A clone). Interpretation was carried out following the general rules for staining evaluation., Results: Non-neoplastic gastric mucosa, used as a positive control for CLDN18.2 immunostaining, exhibited strong membranous staining. In contrast, no CLDN18.2 expression was detected in normal ductal and acinar cells of prostate tissue, nor in any of the 168 variable PC tissues., Conclusion: CLDN18.2 is not expressed in normal prostate tissue or PC, suggesting that it is unlikely to serve as a prognostic marker or a potential target for immunotherapy in PC., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Diffuse large B-cell lymphoma (DLBCL) is a subtype of non-Hodgkin lymphoma (NHL) and is estimated to account for approximately 30% of all NHL cases. NHL can also occur in the female genital tract and accounts for approximately 1.5% of all NHL cases. Many doctors have difficulty diagnosing or treating vulvar DLBCL because of its very low prevalence. A 55-year-old woman presented with a solid mass on the right side of the vulva. No significantly enlarged lymph nodes were observed in the inguinal region. She underwent excisional biopsy at our institution. DLBCL was diagnosed based on histological examination. According to the Hans algorithm, the lesion was diagnosed as a non-germinal center B-cell-like subtype. The patient was referred to a hematologic oncologist. The disease stage was classified as IE according to the Ann Arbor staging classification. The patient received four cycles of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and localized radiation therapy with 36 Gy in 20 fractions. She showed complete remission and maintained this status on the latest computed tomography scan. Gynecologists should rule out lymphoma in patients presenting with a vulvar mass.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies., Competing Interests: S.H.L., a contributing editor of the Journal of Pathology and Translational Medicine, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2023. Korean Gastric Cancer Association.)

Non-Hodgkin's lymphoma (NHL) is the fifth most common hematologic disorder in the United States, and its prevalence has been rising in Western countries. Among the subtypes of NHL, diffuse large B-cell lymphoma (DLBCL) mostly involves the lymph nodes, stomach, and gastrointestinal tract, whereas hepatic involvement of DLBCL is rare. On serologic testing, elevated immunoglobulin G (IgG) levels can be observed in DLBCL; however, elevated IgG levels are mainly observed in autoimmune hepatitis. A targeted-lesion biopsy is required for the diagnosis of DLBCL. Based on a final diagnosis, the patient was treated with rituximab-based chemotherapy, including cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP). Herein, we report a case of DLBCL mimicking antinuclear antibody-negative autoimmune hepatitis, which was finally diagnosed as DLBCL involving the liver, and was confirmed by liver biopsy.

Objectives: Materials wrapping the bowel elicits tissue erosion gradually. We experienced several bowel wall erosions with no serious clinical consequences in our two previous animal experiments aimed at the safety and efficacy of the COLO-BT developed for intra-luminal fecal diversion. We tried to find out why the erosion is safe by investigating histologic changes of the tissue., Material and Methods: Tissue slides at the COLO-BT fixing area from the subjects which had COLO-BT over three weeks acquired from our two previous animal experiments were reviewed. For the classification of the histologic change, microscopic findings were classified for six stages (from minimal change of stage 1 to severe change of stage 6)., Results: A total of 26 slides of 45 subjects were reviewed in this study. Five subjects (19.2%) had stage 6 histological change; three of stage 1 (11.5%), four of stage 2 (15.4%), six of stage 3 (23.1%), three of stage 4 (11.5%), and five of stage 5 (19.2%). All subjects which had a stage 6 histologic change survived. The phenomenon from which the back of the band is passed through is replaced by a relatively stable tissue layer due to fibrosis of the necrotic cells in the stage 6 histologic change., Conclusion: We found that thanks to the sealing effect of the newly replaced layer, no leakage of the intestinal content occurs even if perforation by erosion develops according to this histologic tissue evaluation., Competing Interests: Conflict of Interest: The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2022, Turkish Surgical Society.)

Minichromosome maintenance (MCM) proteins are essential for the initiation of DNA replication and they are prognostic markers in various human cancers. The aim of this study was to investigate the role of the MCM6 protein in gastrointestinal stromal tumor (GIST) and its clinical and prognostic significance. We evaluated MCM6 expression in 211 GIST samples using immunohistochemistry. We used the receiver operating characteristic curve (ROC) to identify optimal cut-off values. High MCM6 expression was associated with tumor size, mitosis, tumor necrosis, presence of recurrence/metastasis, and the National Institute of Health (NIH) and Armed Forces Institute of Pathology (AFIP) malignant risk criteria. Patients with high MCM6 expression had significantly shorter overall survival (OS) and disease-free survival (DFS) than those with low MCM6 expression. Univariate analysis indicated that tumor size, mitosis, AFIP and NIH malignant risk criteria, and high MCM6 expression were significantly associated with poor OS and DFS. High MCM6 expression and high-risk group categorization based on the NIH criteria were independent prognostic factors for OS and DFS. High MCM6 expression is significantly associated with tumor progression and aggressiveness and is an independent factor for shorter survival in GIST patients. MCM6 expression could be a predictive biomarker for tumor aggressiveness as well as a treatment target., Competing Interests: None., (IJCEP Copyright © 2021.)

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a self-limiting lymphadenitis. It is a benign disease mainly characterized by high fever, lymph node swelling, and leukopenia. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease with clinical symptoms similar to those of KFD, but it requires a significantly more aggressive treatment. A 19-year-old Korean male patient was hospitalized for fever and cervical lymphadenopathy. Variable-sized lymph node enlargements with slightly necrotic lesions were detected on computed tomography. Biopsy specimen from a cervical lymph node showed necrotizing lymphadenitis with HLH. Bone marrow aspiration showed hemophagocytic histiocytosis. The clinical symptoms and the results of the laboratory test and bone marrow aspiration met the diagnostic criteria for HLH. The patient was diagnosed with macrophage activation syndrome-HLH, a secondary HLH associated with KFD. He was treated with dexamethasone (10 mg/m2/day) without immunosuppressive therapy or etoposide-based chemotherapy. The fever disappeared within a day, and other symptoms such as lymphadenopathy, ascites, and pleural effusion improved. Dexamethasone was reduced from day 2 of hospitalization and was tapered over 8 weeks. The patient was discharged on day 6 with continuation of dexamethasone. The patient had no recurrence at the 18-month follow-up.

Objective: Aberrant expression of cadherins is known to be associated with tumor aggression. However, their role in clear cell renal cell carcinoma (CCRCC) is not well elucidated. This study investigated the expression of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), and placental cadherin (P-cadherin) in CCRCC, and assessed their prognostic significance and clinicopathologic association., Materials and Methods: We enrolled 254 patients with CCRCC who underwent radical or partial nephrectomy. E-cadherin, N-cadherin, and P-cadherin expression was evaluated by immunohistochemistry in a tissue microarray., Results: Low E-cadherin expression was associated with larger tumor size, lymphovascular invasion, higher pT stage, lymph node and distant metastasis, and higher stage. High N-cadherin expression was significantly associated with larger tumor size, higher nuclear grade, and tumor necrosis. P-cadherin expression was found to be significantly associated with higher nuclear grade, distant metastasis, and higher stage. Univariate analysis revealed that aberrant expression of the 3 cadherins was significantly related to shorter overall survival (OS). Loss of E-cadherin, high P-cadherin expression, and higher stage were independent prognostic factors for OS. For recurrence-free survival, lymphovascular invasion, high P-cadherin expression, and higher stage were independent prognostic factors. Cadherin switch was significantly associated with aggressive clinicopathologic factors and poor outcomes., Conclusions: Aberrant expression of E-cadherin, N-cadherin, and P-cadherin was associated with adverse clinicopathologic factors and worse OS. Low E-cadherin and high P-cadherin expression were significantly associated with distant metastasis and independent prognostic factors. Therefore, cadherin expression may be used as a prognostic marker and therapeutic target, and cadherin switch plays an important role in CCRCC progression., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Minichromosome maintenance (MCM) proteins are involved in initiation of DNA replication and cell-cycle progression. Loss of MCM function results in genomic instability and causes carcinogenesis. Among MCM genes, the role and prognostic value of MCM6 expression in clear-cell renal cell carcinoma (ccRCC) has not been elucidated., Materials and Methods: We assessed the mRNA expression level of MCM6 using the Gene Expression Profiling Interactive Analysis database and investigated MCM6 protein expression by immunohistochemistry in 238 ccRCC cases., Results: High MCM6 expression was significantly associated with increasing tumor size, pT, stage, tumor necrosis, and metastasis. Furthermore, high MCM6 expression was significantly associated with shorter overall and disease-free survival, and was an independent unfavorable prognostic marker. Regarding patients with metastasis, high MCM6-expressing ccRCC conferred significantly shorter survival than for those with low expression., Conclusion: A high MCM6 expression level may be a promising biomarker to predict tumor progression, metastasis, and survival in patients with ccRCC., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Mucinous adenocarcinomas of the buttock are rare and have an uncertain etiology and natural course. They are usually related to chronic anal fistulas, hidradenitis suppurativa, or Crohn's disease. Here, we report a case of mucinous adenocarcinoma associated with hidradenitis and contradictory immunochemistry results., Case Summary: A 62-year-old man complained of recurrent abscesses of the buttock for 3 years. He had several scars and nodules in bilateral buttocks, with purulent discharge. The skin lesions did not appear to originate from the anus. The patient was diagnosed with recurrent abscesses due to hidradenitis suppurativa at the first visit. He showed purulent and subsequent mucin discharge in the first operation and was diagnosed with mucinous adenocarcinoma. Several examinations were performed to determine disease origin and staging. There were no significant findings or evidence of anal fistulas. Hence, he underwent wide local excision and V-Y advancement flap in the second operation. The final diagnosis was mucinous adenocarcinoma without any evidence of anal fistulas. Additional immunochemistry test results were negative for cytokeratin (CK) 7 and positive for CK20 and CDX2 , with a colorectal origin. A pathologist suggested that the disease originated from a chronic anal fistula. The patient has remained free of recurrence for 24 mo., Conclusion: Although the patient with mucinous adenocarcinoma showed an atypical course, immunochemistry helped detect the disease origin., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The Notch3 signaling pathway plays an important role in oncogenesis, tumor maintenance, and resistance to chemotherapy in human cancers. However, its role in prostate cancer (PC) is less clear. In this study, we investigated a total of 142 PC patients who underwent radical prostatectomy and examined the expression of Notch3 in PC cells using immunohistochemistry on tissue microarrays and evaluated their clinicopathological significance. The overexpression of Notch3 was observed in 22 (15.5%) out of 142 PC cases. The overexpression of Notch3 was significantly associated with lymph node metastasis ( P = 0.013), higher pT stages ( P = 0.033), higher pathological tumor stages ( P = 0.034), and higher grades groups ( P = 0.025). However, the overexpression of Notch3 was not correlated with lympho-vascular invasion, neural invasion, extra-prostatic extension, or the serum prostate-specific antigen level. This study demonstrates that Notch3 plays an oncogenic function in PC and the overexpression of Notch3 is correlated with invasiveness, metastasis, and higher Gleason grades, reflecting the features of aggressive tumors in PC, and could be an important biomarker and a possible therapeutic target. Further studies evaluating the association between Notch3 expression and survival are required., Competing Interests: None., (IJCEP Copyright © 2019.)

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Esophageal basaloid squamous carcinoma (BSC) is a rare, aggressive variant of squamous cell carcinoma. BSC is usually diagnosed in advanced stage and its prognosis is relatively poor. A 59-year-old male with subepithelial lesion of the esophagus that was incidentally discovered during health promotion examination was referred to our hospital. Esophagogastroduodenoscopy showed a 10-mm bulging mucosa with an intact surface at 34 cm from incisor teeth. Endoscopic ultrasonography revealed a smooth margined homogenous hypoechoic lesion, measuring 11.3×3.9 mm with a submucosal layer of origin. The patient underwent endoscopic mucosal resection of the subepithelial lesion. Pathologic examination of the resected specimen revealed BSC with involvement of vertical margin by tumor. The patient then underwent radiotherapy, and is doing well without recurrence for 35 months. We report a case of esophageal BSC confined to submucosal layer successfully treated with endoscopic resection followed by radiation.

Prostate cancer (PC) is the most common cancer in men with biologically highly heterogeneous clinical outcomes despite early detection. Therefore, the identification of novel molecular markers that are associated with biological aggressiveness is essential for predicting clinical outcomes and deciding the treatment of PC. We examined the expression of cluster of differentiation 44 (CD44) and heat shock protein 70 (HSP70) in PC cells using immunohistochemistry on tissue microarrays and evaluated their clinicopathological significance. A loss of CD44 expression and HSP70 overexpression were observed in 62 (57.9%) and 54 (50.5%) out of 107 cases of PC, respectively. CD44-negative PC showed more vascular invasion, more extra-prostatic extension, more capsular invasion, higher pT stages, higher pathological tumor stages, higher prostate-specific antigen levels (> 20 ng/mL), and higher grades groups. Overexpression of HSP70 was significantly associated with PC with capsular invasion, higher pT stages, and higher pathological tumor stages. The loss of CD44 expression is correlated with tumor invasiveness and higher Gleason grades, reflecting the features of aggressive tumors. Consequently, CD44 could be an important biomarker and a potential therapeutic target., Competing Interests: None., (IJCEP Copyright © 2018.)

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS ( KRAS and NRAS exon 2-4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 ( HER2 ) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus-positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.