A 77-year-old woman was diagnosed with advanced transverse colon cancer(poorly differentiated adenocarcinoma)cT3N3H0P0, cStage Ⅲc and underwent extended left hemicolectomy in April 2020. The tumor tissue revealed RAS: wild type, BRAF: mutant type, dMMR(MLH1 deficiency)by immunochemical staining, and MSI-H by CDx. She received CAPOX as adjuvant chemotherapy after surgery. At the end of the 3 courses, she developed abdominal aortic lymph nodes recurrence( diameter 32×18 mm)and began to receive pembrolizumab therapy in August 2020. But the tumor re-grew 6 months after the start of this regimen. However the recurrent lesion was localized, radiation therapy(IMRT: 54 Gy/27 Fr) was added in combination with pembrolizumab. Two months later the tumor had shrunk significantly. As of June 2024, the patient has remained recurrence-free, suggesting that the abscopal effect may have been involved by immuno-radiotherapy in this case.

During oncogenesis and proliferation of cancer cells, numerous alterations occur in genomic DNA and mRNA, and these alterations consequently result in the production and presentation of cancer-specific epitopes(neoantigens)on cancer cell surface through the major histocompatibility complex(MHC). These neoantigens then mark cancer cells as"non-self"leading to elimination by the immune system. One of the major insights from cancer genome studies is the detection of neoantigens. Some cancer genome mutations produce neoantigens, enhancing the responsiveness to immune checkpoint blockade (ICB)therapies. The tumor mutation burden(TMB)is used as a surrogate metric for the rate of neoantigen production, and practically used as a biomarker to determine suitability of pembrolizumab, an anti-PD-1 ICB. The focus of neoantigen analysis has been on mutations in genomic DNA. However, recent studies revealed cancer-specific mRNA arising from RNA splicing also provides a source of neoantigens. These findings would provide more detailed insights into cancer immune response and improve the predictive accuracy of ICB effects. In this article, recent progress about RNA splicing-associated neoantigens is summarized.

Conventionally, hereditary tumor syndromes have been identified on the basis of clinical features, including characteristic tumor types and family history. Therefore, it is important for clinicians to consider hereditary tumor syndromes and collect detailed patient background information. However, recent advancements in genetic analyses have enabled the molecular diagnosis of these syndromes. This review addresses the recommendation of genetic counseling for affected patients and their families. In addition, the key points of the updated World Health Organization classification of central nervous system tumors are summarized.

The current main treatment goal of polycythemia vera (PV) is preventing thromboembolic and hemorrhagic complications. However, these therapeutic strategies cannot delay progression of PV. Therefore, there is an unmet need for next-generation therapeutic strategies to slow disease progression and improve survival in patients with PV. One of the most promising agents for modifying the disease course of myeloproliferative neoplasms is interferon alpha, which has been used to treat PV since the 1980s. Notably, it achieved cytogenetic or molecular responses in some patients. However, conventional interferon was not widely used due to its high incidence of adverse events and poor tolerance. Ropeginterferon alfa-2b (ropeg) is a unique, site-selective polyethylene glycol-conjugated form of recombinant interferon alpha. A phase 1/2 study of ropeg for PV patients showed low toxicity and improved tolerability, along with significant molecular response. A phase 3 randomized study (PROUD-PV/CONTINUATION-PV) revealed that treatment with ropeg continuously decreased the JAK2V617F allele burden compared to hydroxyurea and improved event-free survival (with events defined as thromboembolic events, disease progression, or death). A phase 2 study in Japanese patients with PV further confirmed the efficacy of ropeg.

Synovial sarcoma is a type of soft tissue sarcoma that predominantly occurs near the joints of the extremities in young adults. Its hallmark is a recurrent and pathogenic chromosomal translocation, t(X;18)(p11.2;q11.2), which results in the fusion of the SSX1 or SSX2 gene with SS18. The expressed SS18-SSX fusion protein induces abnormalities in the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, a chromatin remodeling complex. In this paper, we refer specifically to the human SWI/SNF complex as mSWI/SNF. Since 2020, significant progress has been made in elucidating the molecular mechanisms underlying the initial event in synovial sarcomagenesis, particularly in structural biology, thereby opening new possibilities for structure-based drug design (SBDD). SS18-SSX1 replaces the wild-type SS18, an essential subunit of mSWI/SNF, and in turn ejects SMARCB1, another core subunit of the complex. This aberrant mSWI/SNF complex (ssSWI/SNF) is then relocated to nucleosomes containing H2A K119Ub. H2A is one of the core histone proteins, and its 119th lysine residue is ubiquitinated to form H2A K119Ub. Chromatin domains harboring nucleosomes with this modification typically exhibit suppressed gene expression patterns. Furthermore, this region is occupied by polycomb complexes, but ssSWI/SNF competes with them, leading to gene activation, which constitutes the initial event in synovial sarcomagenesis. Given that SSX1 is normally expressed primarily in the testes, it is plausible that its ectopic expression leads to aberrant function within the chromatin remodeling complex. Ultimately, the C-terminal region of SSX1 was found to bind to the acidic patch within the nucleosome, and its structural details have been elucidated through cryo-electron microscopy.

Molecularly targeted drugs currently used in breast cancer target the epidermal growth factor receptors, and are less effective when used against breast cancer subtypes with low levels of these receptors. There is therefore an urgent need to identify a new target molecule for such breast cancer subtypes. Vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is a G-protein-coupled receptor that binds to Gαs, Gαi, and Gαq proteins to regulate their downstream signaling. VIPR2 is known to be highly expressed in the suprachiasmatic nucleus of the brain, but is also expressed in many peripheral organs. VIPR2 expression has also been reported in thyroid cancer, gastric cancer, lung cancer, pancreatic adenocarcinoma, sarcoma, and neuroendocrine tumors, and VIPR2 mRNA expression and VIPR2 gene copy number are particularly elevated in breast cancer. We therefore investigated the involvement of VIPR2 in the proliferation and migration of breast cancer cells. We showed that VIP-VIPR2 is a novel molecular mechanism that controls cell migration by activating phosphatidylinositol-3 kinaseγ (PI3Kγ), promoting the production of phosphatidylinositol 3,4,5-triphosphate, and then regulating the formation and extension of pseudopodia. VIP-VIPR2 also regulated cyclin D1 levels through the cAMP/PKA/extracellular signal-regulated kinase and PI3K/AKT/Akt-glycogen synthase kinase-3β signaling pathways, thereby controlling cell proliferation by regulating the G1/S transition in the cell cycle. Treatment with a selective VIPR2 antagonist peptide KS-133 suppressed VIP-induced cell proliferation and migration. These results suggest that VIPR2 is a novel target molecule associated with breast cancer and that KS-133 is a potential molecular targeted drug for breast cancer.

A 69-year-old woman was diagnosed with extrahepatic portal vein occlusion and liver cirrhosis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a ring-enhanced liver tumor. A liver tumor biopsy detected small bile duct proliferation without atypia and a map-like pattern on immunostaining for glutamine synthetase, resulting in a focal nodular hyperplasia diagnosis. CT after 4 years revealed the increased liver tumor. The patient was suspected of intrahepatic cholangiocarcinoma based on MRI findings. A liver tumor biopsy was re-conducted, and the patient was diagnosed with intrahepatic cholangiocarcinoma (small duct type), which was positive for BRAF V600E on immunostaining. We re-investigated the initial liver tumor biopsy tissue and diagnosed the BRAF V600E-positive bile duct adenoma, indicating a malignant transformation of the bile duct adenoma to an intrahepatic cholangiocarcinoma.

The patient was a 90-year-old man with a PS score of 0 and no underlying disease. He visited our hospital with a fever and was diagnosed with cancer of the ascending colon with abscess formation due to retroperitoneal perforation. First, he underwent ileostomy with double orifices and abscess puncture drainage, followed by right semicolon resection plus ileostomy closure to resect the primary tumor. Three months after the surgery, metastases were found in the left cervical supraclavicular and periaortic lymph nodes. The primary tumor was a poorly differentiated adenocarcinoma, RAS wild, BRAF mutation(+), and MSI-high(+). Therefore, pembrolizumab therapy was initiated, which resulted in a complete response(CR) at the end of 6 courses. After 2 years of pembrolizumab treatment, the patient's CR status was maintained, with only Grade 1 hypothyroidism. We believe that pembrolizumab therapy for MSI-high, unresectable, advanced, recurrent colorectal cancer is useful in older patients with good PS, no major underlying disease, and a medical system that can respond to irAE.

An 80-year-old woman presented with fatigue. Routine blood tests at her previous medical institution revealed a decreased white blood cell count, leading to a diagnosis of low-risk myelodysplastic syndrome. During observation, the disease progressed to acute myeloid leukemia (AML), and she was subsequently referred to our hospital. At the time of AML diagnosis, bone marrow examination detected minor BCR-ABL mRNA. Fluorescence in situ hybridization showed a positive BCR-ABL fusion signal in 7.5% of bone marrow cells. Treatment with venetoclax and azacitidine was initiated, and led to hematological remission after one cycle. A bone marrow examination after two cycles confirmed the maintenance of hematological remission, and RT-PCR showed reduced minor BCR-ABL mRNA levels. AML with BCR-ABL1 fusion generally has a poor prognosis and has no established treatment, but in this case, treatment with venetoclax and azacitidine successfully induced remission and demonstrated potential efficacy against BCR-ABL fusion-positive clones.

A 60-year-old male was admitted to the hospital with abdominal pain and diagnosed with microsatellite instability-high (MSI-H)sigmoid colon cancer. Computed tomography revealed an obstructive mass in the sigmoid colon along with swelling of the para-aortic lymph nodes. The patient initially underwent loop transverse colostomy, followed by treatment with the immune checkpoint inhibitor(ICI)pembrolizumab. After 5 courses of ICI, the tumor significantly shrank; therefore, radical resection was performed. The patient has been monitored without adjuvant chemotherapy, and recurrence has not occurred after 1 year. This case shows that ICI may be an effective rescue treatment for colorectal cancer patients with unresectable distant metastasis.

The proband is a 47-year-old woman who underwent a posterior total pelvic exenteration for Stage Ⅲb rectal cancer. Microsatellite instability(MSI)test and immunohistochemistry(IHC)for mismatch repair(MMR)proteins using the resected tumor tissue showed MSI-High and loss of MLH1/PMS2 expression. In addition, although BRAF V600E variant was not identified, MLH1 methylation was detected. Therefore, this patient was diagnosed as having sporadic deficient MMR(MSI-High) rectal cancer. However, the possibility of Lynch syndrome could not be ruled out because of her family history and young age of onset, then we performed a multigene panel testing including MMR genes. Subsequently, a likely pathogenic variant of MSH2(c.2260A>G)was identified. This case suggests that MLH1-methylated rectal cancer can develop in patients with Lynch syndrome and that multigene panel test using next-generation technology would be useful for searching hereditary cancer predisposition syndromes such as Lynch syndrome even in patients with sporadic dMMR colorectal cancer.

Muir-Torre syndrome(MTS)is a disease characterized by the simultaneous occurrence of sebaceous tumors and visceral malignant tumors. This syndrome is now considered to be a phenotypic variant of Lynch syndrome(LS). Our patient was a 58-year-old woman with a history of endometrioid adenocarcinoma of the uterine isthmus at the age of 40 years and left-sided triple negative breast cancer at the age of 44 years. At the age of 52 years, a multigene panel testing revealed a pathogenic variant in MSH2, and the patient was diagnosed with LS. During surveillance for LS in our department, a 2-mm sized intradermal nodule was found on the patient's left shoulder, at the age of 58 years. Histopathological examination of the resected intradermal nodule revealed a sebaceous adenoma. LS can present as MTS, and it is, therefore, important to conduct surveillance not only for visceral malignant tumors but also for skin tumors.

More than 90% of Lynch syndrome(LS)associated colorectal cancers show high-frequency microsatellite instability(MSI-H). It is known that ulcerative colitis(UC)is associated with a high incidence of colorectal cancer due to chronic inflammatory changes in the intestinal mucosa. MSI-H is also found in 2.6-40% of ulcerative colitis associated neoplasia(UCAN), and much neoplasia occur at a young age. Our case was a 35-year-old man who had developed ulcerative colitis at the age of 20 and was undergoing treatment. At the age of 35, he complained of right lower abdominal pain and was diagnosed with ascending colon cancer by colonoscopy. As the first stage of a 3-stage operation, laparoscopic total colectomy with ileostomy was performed. The histological type was poorly differentiated adenocarcinoma, and the progression was pT4a pN1bcM0, pStage Ⅲb. Before the start of adjuvant chemotherapy, MSI testing was performed, and the result was MSI-H. Immunohistochemistry revealed loss of expression of MSH2 and MSH6. Although there was no strong family history suggestive of LS, the patient's clinical characteristics, such as early age onset, location in the right-sided colon, and poorly differentiated adenocarcinoma as the primary histological type, were consistent with LS. As he requested genetic testing, Sanger sequencing of MSH2 was performed using peripheral blood, which revealed a likely pathogenic variant in MSH2 (NM_000251.3 c.1045C>T)and led to a diagnosis of LS. MSI-H may be observed in UCAN, and there are many similarities between the clinical and histopathological findings of UCAN and LS. Although the coexistence of UC and LS is rare, it is important to keep this possibility in mind when managing clinical cases.

A 35-year-old woman was diagnosed as triple-negative breast cancer(TNBC)by a core needle biopsy and referred to our hospital. She was diagnosed as cT2N3M1, cStage Ⅳ TNBC because of metastasis in the right axilla, supraclavicular and internal mammary lymph node, and the contralateral supraclavicular lymph node in addition to the primary tumor. No obvious visceral metastasis was observed. Immunohistochemical assay showed SP142 PD-L1-positive and CPS 10 or more by 22C3. The patient was started on atezolizumab+nab-paclitaxel(PTX)therapy, but progression disease(PD)was observed without obvious effect. Pembrolizumab+carboplatin+gemcitabine was started as second-line therapy, and the tumor achieved partial response(PR)but developed PD within 6 months. After that, she was administrated olaparib, but PD was observed, and after the therapy with PTX+bevacizumab, she is now treated with eribulin.

Breast cancer therapy based on the pathogenic variants of BRCA is entering a new era with the expanded use of olaparib in adjuvant chemotherapy. This study examined the timing of olaparib administration in patients with BRCA pathogenic sequence variant (PSV).

The patient was a 56-year-old woman. At the age of 41, she underwent partial mastectomy and sentinel lymph node biopsy for right breast cancer. At the age of 55, she fell and bruised her left chest. An 8 cm subcutaneous hemorrhage and swelling was found in the left breast. We diagnosed intramammary hematoma and performed hemostasis and drainage of hematoma cavity. As she had undergone surgery for contralateral breast cancer, the possibility of a positive BRCA1/2 gene mutation was considered, and part of the inner wall of the hematoma cavity was removed during surgery and submitted for pathological tissue diagnosis. She was diagnosed with left breast cancer. Considering the possibility of HBOC, a BRCA1/2 genetic test was performed, which revealed a positive BRCA2 gene mutation. We performed an additional total mastectomy and sentinel lymph node biopsy. Breast cancer is often discovered during screening or when patients visit the hospital due to the feeling of a mass, but it is rare for it to be discovered through an intramammary hematoma. Here we report a case in which an intramammary hematoma following surgery for contralateral breast cancer was diagnosed as breast cancer based on histopathological examination of the inner wall of the hematoma cavity, in a patient who was highly likely to have a BRCA gene mutation.

T-cell acute lymphocytic leukemia (T-ALL) with SPI1 fusion, a leukemia subtype first identified in Japan, has a very poor prognosis. A 7-year-old boy was admitted to our hospital with fever, cervical lymphadenopathy, eyelid edema, and purpura. White blood cell count was markedly increased (551,000/µl). Flow cytometric analysis revealed cyCD3, CD1a, CD8, and HLA-DR positive T-ALL, and fusion gene screening identified TCF7::SPI1 fusion. The patient was treated according to the JPLSG ALL-T11 protocol. He responded poorly to prednisolone, but favorably to L-asparaginase. After completion of early intensification therapy, molecular remission was confirmed. However, due to the patient's poor response to prednisolone, and the presence of the SPI1 fusion gene, hematopoietic stem cell transplantation from an HLA-matched unrelated donor was performed in first remission. So far, the patient has been in remission for 36 months from the time of onset. Hematopoietic stem cell transplantation in first remission may be effective treatment for patients with T-ALL and SPI1 fusion.

[Patient] A 65-year-old man. [History of present illness] An abnormal chest shadow was noted in March of 2011, and hoarseness was observed in November of 2017. Both times, AL amyloidosis was diagnosed by biopsy. The patient was admitted to our department for treatment in March 2018, and received 6 cycles of melphalan plus dexamethasone for systemic AL amyloidosis in May. His condition was good, but a blood test in August 2019 showed white blood cells 50,000/µl and 44.9% blasts in the peripheral blood, leading to a diagnosis of treatment-related acute leukemia (AML with inv (16)(p13.1q22);CBFB::MYH11). He achieved complete remission with standard treatment, but relapsed in May 2020, CNS relapsed in September 2020, CNS relapsed again in July 2021, and CNS relapsed a third time in May 2022. He underwent intensive chemotherapy, whole brain radiation therapy, 13 rounds of intrathecal injection, and five cycles of venetoclax plus azacitidine, but his general condition gradually worsened. He was transferred to best supportive care in November and died in June 2023. [Discussion] Although advances in treatment have extended survival in systemic AL amyloidosis, long-term follow-up for secondary cancer is important for patients with long-term exposure, as in this case.

Hereditary breast and ovarian cancers (HBOC) carry a high risk of breast cancer, and detailed screening with contrast-enhanced breast MRI (breast MRI surveillance) is recommended. With the increase in the number of individuals diagnosed with HBOC, the demand for breast MRI surveillance is also rising. However, the current system is inadequate, with factors such as lack of knowledge and indifference among healthcare professionals, and insufficient understanding of breast MRI surveillance being cited. This study aims to investigate the knowledge of HBOC and the awareness of breast MRI surveillance among radiological technologists, and to analyze the factors that promote these practices.

Claudins(CLDNs)are essential components of tight junctions, which are the most apical elements of apical junctional complexes. The family consists of more than 20 members in humans and shows distinct expression patterns in a tissue- and cell-type-specific manner. Recently, many studies have shown that CLDNs overexpressed in cancer cells positively regulate their malignant behavior. First, fusion genes between CLDNs and signaling molecules produce chimeric proteins that act as drivers. Second, cancer and non-cancer cells form heterocellular adhesions via CLDNs and they act as a metastatic niche. Third, CLDNs enhance cancer cell nutrition by conjugating with amino acid transporters on the cell membrane. Fourth, CLDN acts as an activation trigger for signalling cascades. In this review, we present these 4 representative examples of how CLDNs positively regulate cancer progression.