A 91-year-old man with thoracic esophageal cancer(pT3N1M0, pStage Ⅲ)and gastric cancer(pT1b2N0M0, pStage ⅠA)underwent esophagectomy. Three years and 4 months postoperatively, chest computed tomography revealed a mass shadow near the aortic arch. Upper gastrointestinal endoscopy revealed a submucosal tumor-like lesion on the left wall of the gastric tube, which was identified as recurrent esophageal cancer. The patient and his family strongly requested nivolumab administration and initiated treatment. The tumor shrank remarkably after 6 months of nivolumab therapy. Although an immune-related adverse event(irAE)was observed, no other adverse events occurred. After 1 year of administration, the tumor did not increase, and remained under control. We suggest that nivolumab therapy is an effective regimen for older patients with recurrent or inoperable esophageal cancer that is difficult to treat with conventional anticancer drugs, provided that strong irAEs do not occur.

Malignant psoas syndrome(MPS)is characterized by intractable pain in the region innervating the first to fourth lumbar nerves resulting from the invasion of malignant tumors into the psoas muscle. A 57-year-old man underwent a right upper lobectomy with lymph node dissection for pStage ⅠB combined small cell lung cancer(SCLC). Adjuvant chemotherapy was subsequently administered in 2022. At 9 months postoperatively, metastases to the liver and lymph nodes of the hepatic portal region were detected. After multidisciplinary treatment, the recurrent lesions were identified as progressive disease. Eight months after the recurrence, the patient complained of severe pain in the left leg. Contrast-enhanced CT showed swelling of the left psoas muscle, and the patient was diagnosed with MPS. Usually caused by cancer of the abdominal organs, MPS is uncommon in patients with lung cancer. Here we report a case of combined SCLC presenting as MPS.

HER2, a member of the human epidermal growth factor receptor(HER)family, exhibits gene amplification, protein overexpression, or both in 13-27% of gastric cancer(GC)cases. Through the activation of downstream Akt and ERK pathways, HER2 promotes the survival and proliferation of gastric cancer cells. The impact of HER2 signaling on the tumor microenvironment(TME)in GC remains unclear, and the heterogeneity of HER2 overexpression in GC tissues is considered a contributing factor. In this study, we focused on differences in the TME between HER2-positive and HER2-negative areas in HER2-positive GC and found that HER2 signaling, particularly the HER2-Akt cascade, may suppress stimulator of interferon genes (STING)expression and reduce CD8+ T cell infiltration in tumor cells. Overall, our findings suggest the potential for a novel therapeutic approach to activate the anti-tumor immune response in HER2-positive GC.

Overall assessment of KEYNOTE-164 study, KEYNOTE-158 study and CheckMate 142 study demonstrated the clinical benefits of immune checkpoint inhibitors(ICIs)among patients with mismatch repair deficient(dMMR)/high microsatellite instability(MSI-H)cancer. As a result, ICIs have been approved for treatment of MSI-H solid tumor regardless of the tumor type. However, the frequency of real-world diagnosed dMMR gastrointestinal cancer were rarely reported. Therefore, the results of immunohistochemical staining for DNA mismatch repair proteins was investigated. 175 samples of gastrointestinal cancers were examined between November 2019 and June 2023. Clinical and pathological characteristics were obtained from clinical and histopathological records. In real world populations with high proportion of elderly people, the frequency of diagnosed dMMR gastrointestinal cancer may be high compared with previous reports. Furthermore, based on the deficient pattern of mismatch repair protein and age, most cases classified as dMMR may be sporadic. Right side tumors and female may increase the likelihood of dMMR colorectal cancer. The current results justified immunohistochemical staining for DNA mismatch repair proteins, strongly involved in the appropriate patient selection for ICIs therapy, should be conducted for elderly patients newly diagnosed as gastrointestinal cancer. We believe that further clinical cancer immunology research, and then challenging insight targeting dMMR gastrointestinal cancer will result in future development of novel immunotherapy combination strategies well tolerated even in elderly patients.

The patient was a 51-year-old man who had undergone living donor liver transplantation for type B cirrhosis at the age of 37 years, and had a history of immunosuppressive drug use. He had developed focal seizures starting from his right upper limb, and MRI showed a lesion in the subcortical white matter of his left parietal lobe. Sensory disturbance and paralysis progressed in his right upper and lower limbs, and his brain lesion rapidly enlarged. A brain biopsy revealed diffuse large B-cell lymphoma, and Epstein-Barr virus-encoded small RNA in situ hybridization was positive. The patient was diagnosed with primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) with no lesions in other organs. There are few reports of PCNS-PTLD cases after living donor liver transplantation in Japan. Although rare, it is nevertheless important to consider this disease in patients receiving immunosuppressive drugs after organ transplantation who develop brain lesions, regardless of which organ was transplanted.

Biliary amputation neuroma is a rare benign tumor that develops due to the peribiliary dissection of nerve fibers during cholecystectomy, a common bile duct surgery, or lymph node dissection performed in gastric cancer surgery. We report a case of amputation neuroma that presented a challenging differential diagnosis from perihilar cholangiocarcinoma. A 64-year-old man, who had undergone open cholecystectomy 30 years ago, was incidentally found to have a bile duct tumor during computed tomography (CT) following surgery for renal cell carcinoma. He had no specific symptoms, and blood test results showed only a slight elevation in alkaline phosphatase levels. Contrast-enhanced CT revealed a 10-mm solid tumor with contrast effect in the common bile duct. On cholangiography, the tumor appeared as a protruding lesion with a smooth surface unilaterally. Given the atypical findings suggestive of cholangiocarcinoma, three bile duct biopsies were performed. Pathological examination did not rule out adenocarcinoma. The patient opted for surgery;however, an intraoperative rapid histological examination confirmed a benign disease, thereby avoiding extensive surgery. Consequently, a minimally invasive bile duct resection was performed. Postoperative histopathological examination revealed the tumor to be an amputation neuroma. Biliary amputation neuromas are characterized as unilateral protruding lesions with contrast effect or benign strictures. If such findings are observed in a patient with a history of surgery around the bile duct, the possibility of an amputation neuroma should be considered. However, completely ruling out malignancy preoperatively, even when suspecting amputation neuroma, can be challenging;therefore, considering surgery to achieve a definitive diagnosis is reasonable. During surgery, a rapid intraoperative histological examination is useful to avoid extensive procedures. In conclusion, diagnosing an amputation neuroma before surgery can be difficult, as it can mimic malignant tumors such as bile duct cancers. In this case, although a preoperative diagnosis of amputation neuroma was not feasible, performing a rapid intraoperative pathological examination helped avoid extensive surgery.

A 79-year-old woman was revealed to have an abnormal shadow in the right upper lung field by a chest radiography at the time of medical examination. Contrast-enhanced chest computed tomography( CT) revealed a solid, irregularly-shaped nodule with pleural indentation and total/solid diameter of 26 mm in the S3 segment of the right upper lobe. A diagnosis could not be made with bronchoscopy, although positron emission tomography( PET)-CT showed accumulation of 18F-fluoro-2-deoxy-D-glucose( FDG) in the same area. The lung cancer in the right upper lobe was considered to be cT1cN0M0 stage ⅠA3, and surgery (thoracoscopic right upper lobectomy ND2a-1) was performed for diagnostic and therapeutic purposes. The histopathological diagnosis was high-grade fetal adenocarcinoma of the lung with metastasis to the #12 lymph node, pT1cN1M0 stage ⅡB. Currently, 3.5 years postoperatively, the patient has shown no apparent metastasis or recurrence. In future, the epidemiology and treatment methods of high-grade fetal adenocarcinoma of the lung should be established by accumulating more cases.

A 41-year-old asymptomatic male with no significant medical history had a heterogenous cystic tumor with a diameter of 5.1 cm containing fatty density in the anterior mediastinum and a nearby homogeneous enhancing nodule with a diameter of 2.0 cm were observed on chest computed tomography( CT). A malignant teratoma with mediastinal lymph node metastasis was suspected preoperatively. The tumor was completely removed via median sternotomy, with concomitant resection of the lung, pericardium, and right phrenic nerve. Postoperative pathological examination revealed a large mature cystic teratoma, 6.0 cm in diameter, and a small nodule, 3.7 cm in diameter, diagnosed as stageⅠ, type B2 thymoma. The postoperative course was uneventful, with no recurrence 30 months later. The simultaneous occurrence of mature teratoma and stageⅠthymoma is extremely rare. When suspecting a teratoma with small satellite nodules preoperatively, consideration of concurrent small thymoma is suggested.

Mitochondrial metabolic dependencies characteristic of acute myeloid leukemia (AML) have recently been identified, demonstrating that metabolic enzymes regulate AML gene expression and control cell differentiation and stemness. These mitochondrial metabolic adaptations occur independently of underlying genomic abnormalities and contribute to chemotherapy resistance and relapse. Mitochondrial alterations also lead to metabolic vulnerability of AML cells, whose metabolism is characterized by dependence on oxidative phosphorylation, fatty acid oxidation, reactive oxygen species (ROS) production, and mitochondrial dynamics. Currently, mitochondrial properties of AML cells and leukemia stem cells are being investigated, focusing on metabolism, signal transduction, mitochondrial respiration, ROS generation, and mitophagy. In addition, mitochondria-targeted agents have shown promising results in clinical trials. This paper outlines recent findings from preclinical and clinical trials on the utility of agents targeting mitochondria-related molecules and metabolic pathways and their efficacy in combination with existing chemotherapies.

EVI1 is a zinc finger transcription factor encoded by the MECOM locus and is essential for the development and maintenance of hematopoietic stem cells. However, overexpression of EVI1 in various myeloid malignancies is associated with aggressive clinical behavior and poor outcome. The locus encodes multiple isoforms that are differentially acting and independently regulated. EVI1 interacts with a variety of transcription and epigenetic factors via different domains. It also regulates cell survival, differentiation, and proliferation through a variety of mechanisms, including transcriptional activation and repression, regulation of other transcription factors' activity, and chromatin remodeling. While the mechanism by which 3q26 translocation leads to high EVI1 expression through enhancer hijacking of genes active in myeloid development is now better understood, regulation of EVI1 expression in the absence of chromosomal translocations and in normal hematopoiesis remains unclear. Recent studies have provided insight into the regulatory mechanisms of EVI1 expression and action, which may lead to development of targeted therapies in the near future.

Flow cytometry (FCM) remains an essential test in the diagnosis of leukemia despite advances in genomic testing. However, the role of FCM results as a risk factor is already extremely limited. International diagnostic criteria for leukemia already prioritize diagnosis based on genetic abnormalities, with FCM diagnosis only serving as an aid to morphological diagnosis for subtypes without genetic abnormalities. However, rapid lineage diagnosis of leukemia by FCM remains important for selecting initial treatment. FCM is also an important tool for evaluating response to molecular targeted therapy, which requires repeated measurements and rapid results. Furthermore, FCM enables prediction of specific genetic abnormalities by immunophenotypic patterns, which could make it useful for verifying the clinical impact of genetic abnormalities detected by multi-gene panel testing.

Histiocytic sarcoma (HS) is a rare aggressive hematological malignancy reported to occur secondary to B cell lymphoma. We report a case of HS secondary to splenic marginal zone lymphoma (SMZL) complicated by autoimmune hemolytic anemia (AIHA) in a 64-year-old man. He was referred to our department with anemia and was diagnosed as having AIHA. After starting treatment with prednisolone, atypical lymphocytes appeared in his blood tests, and a bone marrow biopsy revealed invasion by B cell lymphoma. A CT scan showed splenomegaly and a pancreatic mass, which confirmed the diagnosis of SMZL. The patient received bendamustine and rituximab as chemotherapy, which rapidly improved the anemia and splenomegaly and reduced atypical lymphocytes. However, left lumbar back pain appeared along with an increase in the pancreatic mass, and he died suddenly of acute renal failure. An autopsy revealed that the tumor had invaded several organs including the pancreas, and immunohistochemistry was positive for CD163, leading to the diagnosis of HS. Furthermore, the specimens of SMZL and HS were positive for IgH gene reconstitution, and exome analysis showed genetic abnormalities in 226 genes including CARD11, suggesting that the SMZL and HS had the same origin.

Combined small cell lung cancer is the only subtype of small cell lung cancer and is a relatively rare histology. However, its histopathological and molecular biological characteristics are not well understood to date.

The patient was a 35-year-old man who saw his first doctor with the chief complaint of painful urination. A contrast- enhanced CT scan of the abdomen revealed a diagnosis of abscess-forming appendicitis with inflammatory spread to the bladder, and conservative treatment was decided. Since antibiotic treatment failed to reduce the size of the abscess, he underwent surgery. The bladder wall was highly inflamed, only appendectomy was performed. Pathology revealed appendiceal mucinous carcinoma invading the bladder, so he was referred to our department. Because a total cystectomy was required for curative resection and there was concern about seeding associated with the initial surgery, he was judged to be unresectable, and received chemotherapy. After 6 courses of CAPOX+bevacizumab therapy, he was able to have a bladder- sparing curative resection because of the absence of distant metastasis and shrinkage of the tumor. He remains stable without recurrence 6 months after surgery. We herein report, with some discussion of the literature, this case of bladder-invading appendiceal mucinous carcinoma arising from abscess-forming appendicitis, for which a curative resection was possible after chemotherapy.

A 49-year-old man underwent an open cholecystectomy for advanced gallbladder cancer in 2021. Three months after surgery, the patient underwent an additional resection, which showed no malignant findings, but 12 months after surgery, contrast-enhanced CT and MRI showed a new mass lesion in segment 8 of the liver, and the patient was diagnosed with postoperative hepatic metastatic recurrence of gallbladder cancer. After referral to our institution, he received 1 course of gemcitabine+cisplatin(GC)therapy and 8 courses of gemcitabine+cisplatin+durvalumab(GCD)therapy. Contrast- enhanced CT and MRI showed that the metastases had shrunk, and PET scan showed no FDG accumulation. Two months after completion of chemotherapy, there was no evidence of metastatic enlargement and new metastasis including distant metastasis, and the patient was referred to our department. Since curative resection was expected, a laparoscopic partial hepatectomy of segment 8 of the liver was performed. Pathological diagnosis revealed no residual tumor. If the metastases could be well controlled by systemic chemotherapy, hepatectomy for hepatic metastases of biliary tract cancer could be a treatment option.

We experienced a case of resection of a pancreatic body bearing a serotonin-producing pancreatic neuroendocrine neoplasm( PanNEN). The patient was a female in her 70s. Contrast-enhanced CT of the pancreatic body showed a 12 mm tumor that was well enhanced in the early, portal, and equilibrium phases. The main pancreatic duct was stenosed at the tumor position, and the distal side was dilated. Although the contrast pattern was indicative of PanNEN, the stenosis of the main pancreatic duct suggested the possibility of invasive pancreatic ductal carcinoma. A serotonin-producing subtype of PanNEN, which causes stenosis of the main pancreatic duct despite its small diameter, was included in the differential diagnoses. We performed resection of the pancreatic body and tail with lymph node dissection. Pathological examination indicated that the tumor was PanNEN G1, and immunostaining revealed positivity for serotonin. Most PanNENs are not accompanied by stenosis of the main pancreatic duct. However, it has been reported that even a small-sized serotonin-producing PanNEN is likely to cause main pancreatic duct stenosis owing to its proliferation pattern. Although there are few reports of serotonin-producing PanNENs, an understanding of the characteristic imaging findings of this disease may be useful in the differential diagnosis of pancreatic tumors.

We report a case of pathological complete response to neoadjuvant chemotherapy for abscess-forming rectal cancer. A woman in her 60s visited her primary care physician because she noticed an increase in the quantity of vaginal discharge. An irregular mass of goose-egg size found on the right vaginal wall was diagnosed as adenocarcinoma on biopsy, and she was referred to our hospital. After further examination, the mass was diagnosed as RbP, cT4b(vaginal), cN1a, cM0, cStage Ⅲc rectal cancer with abscess formation. After 6 courses of CAPOX as neoadjuvant chemotherapy, rectal resection(combined resection of the posterior vaginal wall) was performed. Pathological diagnosis showed no tumor cells and lymph node metastasis. Four courses of CAPOX were administered as postoperative adjuvant chemotherapy. The patient is still alive 4 years after surgery, without recurrence. When neoadjuvant chemotherapy is successful, radical resection is possible, even in cases with abscess formation, and long-term survival can be expected.

MANEC, a subtype of MiNEN, is a rare disease, even rarer when found in the remnant stomach. We report a residual gastric MANEC case found 44 years after subtotal gastrectomy. The patient was an 80-year-old female who underwent subtotal gastrectomy at 36 years old and was referred to our hospital for anorexia and weight loss. An elevated lesion(tub2> tub1)was found on the oral side of the anastomosis. Endoscopic submucosal dissection(ESD)was performed, which revealed MANEC with SM or deeper, ly1, HM?, and VM1, prompting referral for additional surgical resection. Completion remnant gastrectomy was performed. Pathological results showed 2 metastases in the left cardia lymph node and no residual cancer in the remnant stomach. The patient had a recurrence 9 months later and died 11 months after surgery. This case corresponds to not only MiNEN but also MANEC, and only 2 cases of remnant stomach MANEC(MiNEN)could be retrieved in PubMed. MANEC(MiNEN)is considered to have a poor prognosis. In this case, left cardia lymph node metastasis prompted a splenectomy, aiming to improve curability. However, the death of the patient 11 months post-surgery suggested that the disease displayed high malignant potential. Considering the high invasiveness of MANEC, lymphadenectomy and multidisciplinary treatment strategies should be considered. However, careful examination is necessary to see if they contribute to the prognosis.

A 36-year-old woman presented to our hospital with a complaint of melena. Examinations revealed type 3 gastric cancer with left supraclavicular lymph node(Virchow's node)and para-aortic lymph node(PAN)metastases. The patient was treated with S-1 and CDDP combination chemotherapy. After 2 courses of chemotherapy, the lymph node metastases were significantly reduced. Subsequently, a total gastrectomy with D2 plus PAN dissection was performed. Histopathological examination revealed the complete absence of cancer cells in both the primary lesion of the stomach and all dissected lymph nodes. No additional surgery or radiation therapy was performed for Virchow's node metastasis. Postoperatively, she received S-1 chemotherapy for 2.5 years. She remains well 9.5 years after the surgery, without any evidence of recurrent disease.