Efficacy and Safety of Warfarin for the Treatment of Venous Thromboembolism　- A Multicenter Prospective Observational Cohort Study in Japan (AKAFUJI Study).

BACKGROUND: A large-scale prospective study of the efficacy and safety of warfarin for the treatment of venous thromboembolism (VTE) has not been conducted in Japan. Therefore, we conducted a real-world prospective multicenter observational cohort study (AKAFUJI Study; UMIN000014132) to investigate the efficacy and safety of warfarin for VTE.Methods and Results: Between May 2014 and March 2017, 352 patients (mean [±SD] age 67.7±14.8 years; 57% female) with acute symptomatic/asymptomatic VTE were enrolled; 284 were treated with warfarin. The cumulative incidence of recurrent symptomatic VTE was higher in patients without warfarin than in those treated with warfarin (8.7 vs. 2.2 per 100 person-years, respectively; P=0.018). The cumulative incidence of bleeding complications was not significantly different between the 2 groups. The mean prothrombin time-international normalized ratio (PT-INR) during warfarin on-treatment was <1.5 in 180 patients, 1.5-2.5 in 97 patients, and >2.5 in 6 patients. The incidence of bleeding complications was significantly higher in patients with PT-INR >2.5, whereas the incidence of recurrent VTE was not significantly different between the 3 PT-INR groups. The cumulative incidence of recurrent VTE and bleeding complications did not differ significantly among those in whom VTE was provoked by a transient risk factor, was unprovoked, or was associated with cancer. CONCLUSIONS: Warfarin therapy with an appropriate PT-INR according to Japanese guidelines is effective without increasing bleeding complications, regardless of patient characteristics.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants for Japanese Patients With Venous Thromboembolism　- The Primary Results From the KUROSIO Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended as the first-choice anticoagulation therapy in the acute phase of venous thromboembolism (VTE). However, there is limited real-world data for Japanese VTE patients.Methods and Results: The KUROSIO study (UMIN000023747) was a prospective long-term observational study comprising 1,017 patients with concurrent acute symptomatic pulmonary thromboembolism and proximal deep vein thrombosis (DVT) or isolated calf DVT initially treated with DOACs. After excluding 24 patients, 993 (mean age, 66.3±15.1 years; 58.6% females) were analyzed. The incidences of recurrent symptomatic VTE and major bleeding for up to 52 weeks after diagnosis were 3.2% and 2.2%, respectively. Multivariate analyses revealed chemotherapy and anemia as significant risk factors associated with recurrent symptomatic VTE and major bleeding, respectively. CONCLUSIONS: The efficacy and safety of DOACs in Japanese patients with VTE were determined in this real-world observational study.

Efficacy of Endoscopic Resection for Rectal Neuroendocrine Tumors Smaller than 15 mm.

BACKGROUND: Local resection, including endoscopic resection, is recommended for rectal neuroendocrine tumors (NETs) < 15 mm in patients without risk factors for metastasis, though the short- and long-term outcomes are unclear. AIMS: This study investigates the efficacy of endoscopic resection for rectal NETs < 15 mm. METHODS: The short- and long-term outcomes of patients with rectal NETs < 15 mm who underwent endoscopic resection and the outcomes of each endoscopic technique were analyzed. The tumors were stratified as < 10 mm (small-size group, SSG) and 10-14 mm (intermediate-size group, IMG). RESULTS: Overall, 139 lesions (SSG, n = 118; IMG, n = 21) were analyzed. All tumors were classified as G1 (n = 135) or G2 (n = 4) according to the 2019 World Health Organization grading criteria. The complete resection rate was not different between the groups (P = 0.151). Endoscopic submucosal dissection (ESD) and endoscopic submucosal resection with a ligation device (ESMR-L) achieved complete resection rates > 90% in the SSG. The ESMR-L procedure time (P < 0.001) and hospitalized period (P < 0.001) were significantly shorter than those of ESD. ESD achieved a complete resection rate of 80.0% in the IMG. The tumor size did not affect the overall survival or rate of lymph node/distant metastases. CONCLUSIONS: Endoscopic resection is a feasible and effective treatment for patients with rectal NETs < 15 mm without the risk factors of metastasis. ESMR-L and ESD are optimal techniques for resecting tumors smaller than 10 mm and 10-14 mm, respectively.

[The "Ethical Guidelines for Medical and Biological Research Involving Human Subjects" and the "Act on the Protection of Personal Information"-Revisions in 2022 and 2023, Expectations, and Challenges].

The relationship between the" Act on the Protection of Personal Information" and the" Ethical Guidelines for Medical and Biological Research Involving Human Subjects" will be explained, along with their respective revisions. It is highly desirable to consider and develop Japanese regulations that allow researchers to devote more time to their research.

Platelet-Rich Plasma-Releasate (PRPr) for the Treatment of Discogenic Low Back Pain Patients: Long-Term Follow-Up Survey.

Background and Objectives: Clinical studies of platelet-rich plasma (PRP) for the treatment of low back pain (LBP) have been reported; however, less is known about its long-term efficiency. Materials and Methods: This study was a long-term follow-up of a previous prospective clinical feasibility study for the use of PRP releasate (PRPr) to treat discogenic LBP patients. Among 14 patients, 11 patients were evaluated for a long-term survey. The efficacy was assessed by a visual analogue scale (VAS) for LBP intensity and the Roland-Morris Disability Questionnaire (RDQ) for LBP-related disability. Radiographic disc height was evaluated for seven patients. Results: Improvements in VAS and RDQ were sustained at an average of 5.9 years after the intradiscal injection of PRPr (p < 0.01 vs. baseline, respectively). Clinically meaningful improvements (more than 30% decrease from baseline) in VAS and RDQ were identified in 91% of patients at final survey. The radiographic measurement of disc height of PRPr-injected discs showed a mild decrease (13.8% decrease compared to baseline) during the average 5.9 years. Conclusions: The results of this study with a small number of patients suggest that the intradiscal injection of PRPr has a safe and efficacious effect on LBP improvement for more than 5 years after treatment. Further large-scale studies would be needed to confirm the clinical evidence for the use of PRPr for the treatment of patients with discogenic LBP.

DA-EPOCH-R combined with high-dose methotrexate in patients with newly diagnosed stage II-IV CD5-positive diffuse large B-cell lymphoma: a single-arm, open-label, phase II study.

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by poor prognosis and a high frequency of central nervous system relapse after standard immunochemotherapy. We conducted a phase II study to investigate the efficacy and safety of dose-adjusted (DA)- EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) combined with high-dose methotrexate (HD-MTX) in newly diagnosed patients with CD5+ DLBCL. Previously untreated patients with stage II to IV CD5+ DLBCL according to the 2008 World Health Organization classification were eligible. Four cycles of DA-EPOCH-R followed by two cycles of HD-MTX and four additional cycles of DAEPOCH- R (DA-EPOCH-R/HD-MTX) were planned as the protocol treatment. The primary end point was 2-year progression-free survival (PFS). Between September 25, 2012, and November 11, 2015, we enrolled 47 evaluable patients. Forty-five (96%) patients completed the protocol treatment. There were no deviations or violations in the DA-EPOCH-R dose levels. The complete response rate was 91%, and the overall response rate was 94%. At a median follow up of 3.1 years (range, 2.0-4.9 years), the 2- year PFS was 79% [95% confidence interval (CI): 64-88]. The 2-year overall survival was 89% (95%CI: 76-95). Toxicity included grade 4 neutropenia in 46 (98%) patients, grade 4 thrombocytopenia 12 (26%) patients, and febrile neutropenia in 31 (66%) patients. No treatment-related death was noted during the study. DA-EPOCH-R/HD-MTX might be a first-line therapy option for stage II-IV CD5+ DLBCL and warrants further investigation. (Trial registered at: UMIN-CTR: UMIN000008507.).

[A Case of Poorly Differentiated Carcinoma of Unknown Primary Site with Risk of Choriocarcinoma Syndrome Effectively Treated with Reduced Bleomycin,Cisplatin ,Etoposide Combination Regimen(BEP Regimen)].

A 64-year-old man visited his physician complaining of bilateral gynecomastia and left shoulder pain. Chest X-ray showed multiple bilateral masses in the lung, and he was referred to our hospital. Radiographical findings, elevation of serum total hCG, and histological findings of the cervical lymph node revealed multiple pulmonary, nodal, and brain metastases of poorly differentiated carcinoma of an unknown primary site with choriocarcinoma components. He was administered a regimen of reduced bleomycin, cisplatin, etoposide combination(reduced BEP regimen)to reduce the risk of acute respiratory failure with intra-alveolar hemorrhage related to post-chemotherapy early tumor necrosis. After chemotherapy, the tumor marker hCG levels were almost restored to normal levels, and radiography showed he had achieved a clinical partial response.

Lansoprazole Ameliorates Isoniazid-Induced Liver Injury.

Isoniazid is a first-line drug in antitubercular therapy. Isoniazid is one of the most commonly used drugs that can cause liver injury or acute liver failure, leading to death or emergency liver transplantation. Therapeutic approaches for the prevention of isoniazid-induced liver injury are yet to be established. In this study, we identified the gene expression signature for isoniazid-induced liver injury using a public transcriptome dataset, focusing on the differences in susceptibility to isoniazid in various mouse strains. We predicted that lansoprazole is a potentially protective drug against isoniazid-induced liver injury using connectivity mapping and an adverse event reporting system. We confirmed the protective effects of lansoprazole against isoniazid-induced liver injury using zebrafish and patients' electronic health records. These results suggest that lansoprazole can ameliorate isoniazid-induced liver injury. The integrative approach used in this study may be applied to identify novel functions of clinical drugs, leading to drug repositioning.

[Evaluation of Pharmacy Students' Understanding of Clinical Trials and Research through Questionnaires Before and After the Hospital Practical Training].

A questionnaire survey was conducted to evaluate practical training and improve education on clinical trial and research. This survey was based on the results of questionnaire before and after the practical training undertaken by 240 pharmaceutical students (Kanto region; 1 university, Tokai region; 2 university, Kinki region; 9 university) at Mie University Hospital between 2011 and 2022. In the questionnaire before practical training, lectures in university (n=219, 91%) were the main source of information on clinical trials and research. Fifty-two students (22%) correctly answered the contents of phase 1-4 trials. As an occupation that can perform clinical research coordinator (CRC)'s work, only 7 students (3%) answered that "all medical and non-medical professionals" can perform the CRC's duties. Regarding the understanding of terms related to clinical trials and research, more than 90% of the students understood the meaning of "subjects," "informed consent," and "placebo" even before practical training. Otherwise, even after practical training, students' understanding of "reimbursement," "follow-up period," "audit," or "direct access" was less than 80%. Practical training improved the understanding of terms such as clinical trial (Wilcoxon signed-rank test, p<0.001), clinical research phase 1-4 trials (Wilcoxon signed-rank test, p<0.001), interest in clinical trials and research (McNemar-Bowker test, p<0.001), and understanding of CRC's work (McNemar-Bowker test, p<0.001). We will improve the content of practical training and bequeath the knowledge and importance of drug discovery and development to the next generation.

Relationship between CYP2C19 loss-of-function polymorphism and platelet reactivities with clopidogrel treatment in Japanese patients undergoing coronary stent implantation.

BACKGROUND: CYP2C19 loss-of-function genotype (*2 and/or *3 alleles) is related to low responsiveness to clopidogrel, which is a risk factor for ischemic cardiac events. The contribution of these genotypes to platelet reactivity in Japanese patients in a steady state receiving dual antiplatelet therapy after coronary stenting was evaluated. METHODS AND RESULTS: A total of 155 Japanese patients were classified according to their CYP2C19 loss-of-function genotype. Platelet reactivity was assayed by plasma levels of soluble P-selectin and platelet-derived microparticles, light transmittance aggregometry induced by ADP (ADP-LTA), shear stress-induced platelet aggregometry, vasodilator-stimulated phosphoprotein phosphorylation (VASP) index and the VerifyNow-P2Y12 assay. Linear and logistic regression models were used to assess the associations between CYP2C19 loss-of-function genotype and high on-treatment platelet reactivity. In total, 62 patients (40.0%) were extensive metabolizers (EMs), 70 (45.2%) were intermediate metabolizers (IMs) and 23 (14.8%) were poor metabolizers (PMs). ADP-specific assays (ADP-LTA, the VASP index and VerifyNow-P2Y12) differed according to CYP2C19 genotype, with a significant gene-dose effect (PMs>IMs>EMs). CYP2C19 loss-of-function carrier status was associated with more frequent high platelet reactivity. CYP2C19 loss-of-function genotype alone could explain 12.2%, 14.3%, and 14.7% of the variability in the ADP-LTA, VASP and VerifyNow-P2Y12 assays, respectively. CONCLUSIONS: CYP2C19 loss-of-function genotype is associated with more frequent high platelet reactivity, as assessed by ADP-specific platelet function tests, in Japanese patients.

Difference in survival and prognostic factors between smokers and never-smokers with advanced non-small-cell lung cancer.

BACKGROUND: Our aims were to investigate whether the association between smoking and survival is significant when adjusted for prognostic factors including use of epidermal growth factor tyrosine kinase inhibitors and the Glasgow Prognostic Score, an established score for inflammation, and to explore prognostic factors. METHODS: We analyzed 244 patients with stage IIIB or IV non-small-cell lung cancer in a registry, including only chemotherapy-receiving outpatients with performance status zero. RESULTS: Of 244 patients, 170 had died and the median follow-up time for the 74 surviving patients was 12.0 months. In multivariate Cox regression, smoker (hazard ratio compared to never-smoker: 1.67, P < 0.01), stage IV (hazard ratio compared to IIIB: 1.72, P < 0.01), and elevated C-reactive protein level (hazard ratio per 1 mg/dL increase: 1.08, P < 0.01) were significantly associated with shorter survival. The association between survival and smoking was significant, even after adjustment for the Glasgow Prognostic Score and regimens of chemotherapy (hazard ratio: 1.72, P = 0.02). In never-smokers, increased neutrophils were a major determinant of shorter survival and the interaction test between smoking and neutrophils was significant (hazard ratio per 1,000/mm(3) increase for smokers: 1.01; hazard ratio per 1,000/mm(3) increase for never-smokers: 1.44, P for interaction <0.01). CONCLUSIONS: Known factors including treatment response or inflammatory process are not responsible for the fact that advanced non-small-cell lung cancer patients without any history of smoking have better survival than those who have smoked.

[A case report of a well-differentiated neuroendocrine tumor in which sunitinib treatment resulted in stable disease].

A 52-year-old woman had a primary neuroendocrine tumor, Grade 2(NET G2)with multiple liver metastases and a mesenteric tumor. Since no drugs were approved for NET at that time in Japan, we treated her with sunitinib after approval by the Ethics Committee of Mie University Hospital and obtaining informed consent. Sunitinib was administered at a daily dose of 37.5mg/day, but the dose was reduced to 12.5mg/day because of thrombocytopenia(G3)and neutropenia(G3). CT revealed stable disease after 3 months of treatment, but disease progression was observed after 11 months. The non-hematological toxicity was hypertension(G3), which was controlled with antihypertensive agents. Although there are no previous reports of the treatment of well-differentiated NET with sunitinib in Japan, sunitinib may be effective against this disease.

Negative effect of prolonged cecal intubation time on adenoma detection in female patients.

Background and Aim: Withdrawal time of the colonoscope is associated with adenoma detection. However, the association between cecal intubation time and adenoma detection remains unclear. This study aimed to evaluate the association between cecal intubation time and adenoma detection. Methods: This retrospective study analyzed prospectively collected data from a randomized controlled trial on female patients who underwent colonoscopy in an academic hospital. The primary outcome was the mean number of all adenomas detected per patient. Secondary outcomes included the mean number of advanced, diminutive, small/large, right-sided colonic, and left-sided colonic adenomas detected per patient. Furthermore, the detection rates of all categories of adenoma were evaluated. Results: The analysis included 216 female patients aged ≥20 years. The correlation analysis did not reveal a significant relationship (P = 0.473) between cecal intubation and withdrawal times. The mean number of all adenomas detected per patient declined by approximately 30% (1.05-0.70) from the fastest to the slowest insertion time quartile. Adjusted regression analysis showed a significant decrease in the mean number of all adenomas detected per patient with increased intubation time (relative risk, RR = 0.87; 95% confidence interval, 0.76-0.99, P = 0.045), whereas the mean number of other categories of adenomas detected per patient and the detection rates of all categories of adenoma were not associated with the cecal intubation time. Conclusions: This study showed a significant association between prolonged cecal intubation time and decreased adenoma detection. The cecal intubation time may be a significant quality indicator for colonoscopy.

The usefulness of image-enhanced endoscopy to distinguish gastric carcinoma in tumors initially diagnosed as adenomas by endoscopic biopsy: A retrospective study.

Superficial epithelial gastric neoplasms can be divided into adenomas and early carcinomas. Histological diagnosis by endoscopic forceps biopsy is crucial for the diagnosis and management of gastric neoplasms. It is difficult to distinguish features of gastric neoplasms in small biopsy specimens; hence, gastric carcinomas can be underdiagnosed as adenomas. Recent developments in image-enhanced endoscopy have improved the ability to differentiate between carcinomatous and non-carcinomatous lesions. To investigate the prevalence of gastric carcinoma in lesions initially diagnosed as adenomas by forceps biopsy and assess the usefulness of image-enhanced endoscopy in distinguishing carcinomas. A total of 142 lesions of gastric adenomas, diagnosed by biopsy and resected endoscopically between January 2010 and May 2020, were retrospectively evaluated. Images were captured by white-light endoscopy (WLE), magnifying endoscopy with narrow-band imaging (M-NBI), and magnifying endoscopy with acetic acid and narrow-band imaging (M-AANBI); they were analyzed and compared with histopathological results. The diagnostic performance of M-AANBI was compared with that of M-NBI. Of the 142 lesions, 58 (40.8%) were pathologically diagnosed as adenocarcinomas. On WLE images, a depressed macroscopic type and size ≥20 mm were significant predictors of carcinoma (P < .001); however, they displayed low sensitivities (32.8% and 41.4%, respectively). M-AANBI displayed significantly higher sensitivity, specificity, and accuracy for distinguishing carcinomas than M-NBI (94.8% vs 74.1%, 81.0% vs 72.6%, and 86.6% vs 73.2%, P < .05). In conclusion, carcinoma was prevalent in 40.8% of gastric lesions initially diagnosed as adenomas by forceps biopsy. M-AANBI may be more useful than M-NBI and WLE in distinguishing gastric carcinomas from adenomas.

Repositioning of Lansoprazole as a Protective Agent Against Cisplatin-Induced Ototoxicity.

Cisplatin (CDDP) is a well-known chemotherapeutic drug approved for various cancers. However, CDDP accumulates in the inner ear cochlea via organic cation transporter 2 (OCT2) and causes ototoxicity, which is a major clinical limitation. Since lansoprazole (LPZ), a proton pump inhibitor, is known to inhibit OCT2-mediated transport of CDDP, we hypothesized that LPZ might ameliorate CDDP-induced ototoxicity (CIO). To test this hypothesis, we utilized in vivo fluorescence imaging of zebrafish sensory hair cells. The fluorescence signals in hair cells in zebrafish treated with CDDP dose-dependently decreased. Co-treatment with LPZ significantly suppressed the decrease of fluorescence signals in zebrafish treated with CDDP. Knockout of a zebrafish homolog of OCT2 also ameliorated the reduction of fluorescence signals in hair cells in zebrafish treated with CDDP. These in vivo studies suggest that CDDP damages the hair cells of zebrafish through oct2-mediated accumulation and that LPZ protects against CIO, possibly inhibiting the entry of CDDP into the hair cells via oct2. We also evaluated the otoprotective effect of LPZ using a public database containing adverse event reports. The analysis revealed that the incidence rate of CIO was significantly decreased in patients treated with LPZ. We then retrospectively analyzed the medical records of Mie University Hospital to examine the otoprotective effect of LPZ. The incidence rate of ototoxicity was significantly lower in patients co-treated with LPZ compared to those without LPZ. These retrospective findings suggest that LPZ is also protective against CIO in humans. Taken together, co-treatment with LPZ may reduce the risk of CIO.

Incidence of stroke, systemic embolism and bleeding events in patients without anticoagulation based on real-world data in Japan: a retrospective cohort study.

OBJECTIVES: To examine the incidence of stroke or systemic embolic events (SSEs) and bleeding events in untreated patients with non-valvular atrial fibrillation (NVAF) after widespread use of direct oral anticoagulant agents (DOACs). DESIGN: Multicentre, non-interventional, observational, retrospective cohort study using real-world data in Japan (2016-2018). SETTING: The Mie, Musashino University study of NVAF, which used the Mie-Life Innovation Promotion Center Database. This is a regional clinical database involving one university hospital and eight general hospitals in Mie Prefecture in Japan. PARTICIPANTS: Japanese patients with NVAF (n=7001). PRIMARY AND SECONDARY OUTCOME: The incidence of SSEs and bleeding events. RESULTS: A total of 7001 patients with NAVF were registered, and 53.0% were treated with DOACs, 10.6% were treated with warfarin and 36.4% had no treatment. Additionally, 29.5% of patients with a CHADS2 (congestive heart failure, hypertension, age≥75 years, diabetes, previous stroke or transient ischemic attack) score of 3-6 were untreated. In the no treatment group, the SSE rates by the CHADS2 score (0, 1, 2 and 3-6) were 1.4%, 1.4%, 3.2% and 8.0%, respectively. The rates of bleeding events by the CHADS2 score (0, 1, 2 and 3-6) in the no treatment group were 0.7%, 1.0%, 1.2% and 2.9%, respectively. A multivariate analysis of SSEs in components of the CHADS2 showed that the adjusted HRs were 2.32 for heart failure, 1.66 for an age ≥75 years, 1.81 for diabetes mellitus and 5.84 for prior stroke or transient ischaemic attack. CONCLUSIONS: Approximately one-third of the patients do not receive any anticoagulation in the modern DOAC era in Japan. The SSE rate increases by the CHADS2 score. The SSE rate is low in patients with a CHADS2 score <1, supporting no indication of anticoagulation in current guidelines. In patients with a CHADS2 score >1, the use of anticoagulant drug therapy is recommended because of a higher risk of stroke.

Atezolizumab-Induced Sarcoidosis-Like Reaction in a Patient with Metastatic Breast Cancer.

Tumor-related sarcoidosis-like reactions (SLR) have been reported with the use of immune checkpoint inhibitors (ICIs). We report a case of 50-year-old woman who observed an enlarged lymph node in the right hilar region and the appearance of a subcutaneous mass in the extremities during chemotherapy with atezolizumab plus nab-paclitaxel for metastatic triple-negative breast cancer (TNBC). Skin biopsy revealed the formation of epithelioid granulation species with the Langhans giant cell. After discontinuing atezolizumab in the treatment procedure, the hilar lymph nodes and the subcutaneous mass were reduced. A pathological examination was effective in differentiating tumor exacerbation from SLR. Owing to limited information on ICI-related SLR in breast cancer, future studies are recommended to properly manage immune-related adverse effects during cancer treatment.

Platelet-Rich Plasma Releasate versus Corticosteroid for the Treatment of Discogenic Low Back Pain: A Double-Blind Randomized Controlled Trial.

Clinical application of platelet-rich plasma is gaining popularity in treating low back pain (LBP). This study investigated the efficacy and safety of platelet-rich plasma releasate (PRPr) injection into degenerated discs of patients with discogenic LBP. A randomized, double-blind, active-controlled clinical trial was conducted. Sixteen patients with discogenic LBP received an intradiscal injection of either autologous PRPr or corticosteroid (CS). Patients in both groups who wished to have PRPr treatment received an optional injection of PRPr eight weeks later. The primary outcome was change in VAS from baseline at eight weeks. Secondary outcomes were pain, disability, quality of life (QOL), image analyses of disc degeneration, and safety for up to 60 weeks. The VAS change at eight weeks did not significantly differ between the two groups. Fifteen patients received the optional injection. Compared to the CS group, the PRPr group had a significantly improved disability score at 26 weeks and walking ability scores at four and eight weeks. Radiographic disc height and MRI grading score were unchanged from baseline. PRPr caused no clinically important adverse events. PRPr injection showed clinically significant improvements in LBP intensity equal to that of CS. PRPr treatment relieved pain, and improved disability and QOL during 60 weeks of observation.

Combined use of pathological and genomic alteration analyses for the diagnosis of gray zone lymphoma.

Histiocytic sarcoma (HS) is a rare malignancy showing morphologic and immunophenotypic features of histiocytes. HS has morphologic overlap with many other diseases, including various kinds of lymphomas. Gray zone lymphoma (GZL) is a rare B-cell lymphoma subtype characterized by overlapping features between diffuse large B-cell lymphoma and classic Hodgkin lymphoma. The histologic overlap with other diverse diseases of HS and the pathological diversity of GZL make it difficult to render a diagnosis. A 44-year-old woman who was initially diagnosed with HS was diagnosed with GZL after reexamination, including a genetic alteration test. After 6 cycles of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine, she achieved a complete response. Genomic alteration assessment may be useful for the accurate diagnosis of malignant lymphomas, which are difficult to diagnose, such as GZL.