Diagnostic accuracy of preoperative quantitative susceptibility mapping for detecting histologic intraplaque hemorrhage in cervical ICA stenosis in patients undergoing carotid endarterectomy.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping (QSM) has been proposed to assess intraplaque hemorrhage (IPH) in the carotid artery. The purpose of this study was to compare the diagnostic accuracy of preoperative QSM with that of the conventional T1-weighed (T1W) three-dimensional (3D)-FSE sequence for detecting IPH in cervical ICA stenosis in patients undergoing carotid endarterectomy (CEA) using histology as the reference standard. MATERIALS AND METHODS: Carotid T1W 3D-FSE and QSM images were obtained from 16 patients with cervical ICA stenosis before CEA. Relative signal intensity (RSI) and susceptibility of the ICA were measured on three axial images including the location of most severe stenosis on T1W 3D-FSE and QSM images, respectively. Three transverse sections of carotid plaques excised by CEA, which corresponded with images on MRI, were stained with H&E, antibody against glycophorin A and Prussian blue, and the relative area (RA) of histologic IPH was calculated. RESULTS: The correlation coefficient was significantly greater between susceptibility and RA-histologic IPH (ρ = 0.691) than between RSI and RA-histologic IPH (ρ = 0.413; P = .0259). The areas under the receiver operating characteristic curves for detecting histologic sections consisting primarily of IPH (RA-histologic IPH > 40.7%) tended to be greater for susceptibility (0.964) than for T1WI FSE-RSI (0.811). Marginal homogeneity was observed between susceptibility and histologic sections consisting primarily of IPH (P = .0412) but not between T1W FSE-RSI and histologic sections consisting primarily of IPH (P = .1824). CONCLUSIONS: Pre-CEA QSM detects histologic IPH in cervical ICA stenosis more accurately than preoperative T1W 3D-FSE imaging. ABBREVIATIONS: QSM = quantitative susceptibility mapping; IPH = intraplaque hemorrhage; T1W = T1-weighed; 3D = three-dimensional; CEA = carotid endarterectomy; RSI = relative signal intensity; RA = relative area.

Spontaneous reactivation of hepatitis B virus with multiple novel mutations in an elderly patient with resolved hepatitis B virus infection.

Spontaneous reactivation of the Hepatitis B virus (HBV) is rare in individuals with previously resolved infections. This report presents the case of a 71 year-old Japanese woman who experienced HBV reactivation without any prior immunosuppressive therapy or chemotherapy. Before the onset of liver injury, the patient was negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B surface antibody. She subsequently developed liver injury, with the reappearance of HBsAg and HBV DNA. The patient was successfully treated with tenofovir alafenamide, and prednisolone. Full-genome sequencing of HBV revealed subgenotype B1 without hepatitis B e-negative mutations in the precore and core promoter regions and 12 amino acid alterations in the pre-S1/S, P, and X genes. Notably, the S gene mutations D144A and K160N, which alter the antigenicity of HBsAg and potentially contribute to its reactivation, were identified. This case emphasizes the importance of vigilance for spontaneous reactivation of resolved HBV, highlighting the need for comprehensive genomic analysis to understand the associated virological intricacies.

A gastric invasive tubular adenocarcinomatous lesion arising from foveolar-type neoplasia: molecular histogenesis.

Here, we report a rare case of a depressed lesion exhibiting both tubular differentiated adenocarcinomatous (TDA) and intraepithelial foveolar neoplasia (IFN) components (with the histological appearance of foveolar hyperplasia due to low-grade atypia). Histologically, the TDA surrounded the IFN, suggesting that the TDA may have originated from the IFN. Therefore, we examined molecular alterations in the TDA and IFN components separately. MUC5AC and MUC6 expression was observed immunohistochemically in both components. p53 expression was wild type in both components, suggesting no mutation of TP53. We investigated allelic imbalances at multiple loci (1p, 3p, 4p, 5q, 8q, 9p, 13q, TP53, 18q, and 22q), mutations (KRAS, BRAF, and GNAS), and DNA methylation and microsatellite status in both components using PCR-based analyses. Although multiple allelic imbalances were common to both components, allelic imbalances at 3p and TP53 were found only in the TDA component. No mutations were found, and DNA methylation status was low epigenotype for both components. Ultimately, this tumor was considered microsatellite stable. Considering the origin of TDA, which is frequently encountered in routine practice, IFN may develop into TDA.

A rare case of neuroendocrine cell tumor mixed with a mucinous component in the ampulla of Vater.

BACKGROUND: A rare case of neuroendocrine cell tumor (NET) having both conventional and mucinous components was reported. Mucinous NET is rarely encountered in the pathological diagnosis of gastrointestinal (GI) tumors. Here we examined the mechanism for transformation of conventional NETs into mucinous NETs. CASE PRESENTATION: Macroscopic examination revealed a tumor with ulceration in the ampulla of Vater that measured 1.7 cm in its largest diameter. Histologically, the tumor comprised two components: a tubular/ribbon-like feature and small nests floating in a mucinous lake. The tumor nests showed sheet, nest and ribbon-like structures of small cells having eosinophilic cytoplasm as well as small-sized nuclei with dense hyperchromatin. Immunohistochemical analysis showed tumor cells positive for pan-endocrine markers (synaptophysin, CD56, INSM1 and chromogranin). Based on the histological findings, the solid and mucinous components were diagnosed as conventional and mucinous NETs, respectively. Grading was NET G2 based on 12.8% and 13.2% Ki-67-positive cells in the solid and mucinous components, respectively. Immunohistochemically, the mucin phenotype of this tumor was gastric and intestinal. Only the mucinous NET component had cytoplasmic CD10 expression. Examination using a customized gene panel detected only a DPC4 mutation, which was limited to the mucinous component. CONCLUSIONS: Coexistence of conventional and mucinous NETs could provide important insight into evaluating the NET subtype histogenesis. Moreover, molecular alterations including cytoplasmic expression of CD10 and the DPC4 mutation can contribute to interpretation of tumor pathogenesis.

A genome-wide study of gastric intramucosal neoplasia based on somatic copy number alterations, gene mutations, and mRNA expression patterns.

We performed comprehensive analyses of somatic copy number alterations (SCNAs) and gene expression profiles of gastric intramucosal neoplasia (IMN) using array-based methods in 97 intestinal-type IMNs, including 39 low-grade dysplasias (LGDs), 37 high-grade dysplasias (HGDs), and 26 intramucosal carcinomas (IMCs) with stromal invasion of the lamina propria to identify the molecular mechanism of IMN. In addition, we examined gene mutations using gene panel analyses. We used cluster analyses for exclusion of arbitrariness to identify SCNA patterns and expression profiles. IMNs were classified into two distinct subgroups (subgroups 1 and 2) based on SCNA patterns. Subgroup 1 showed a genomic stable pattern due to the low frequency of SCNAs, whereas subgroup 2 exhibited a chromosomal instability pattern due to the high frequencies of SCNAs and TP53 mutations. Interestingly, although the frequencies of LGD and HGD were significantly higher in subgroup 1 than in subgroup 2, IMC was commonly found in both types. Although the expression profiles of specific mRNAs could be used to categorise subgroups 1 and 2, no clinicopathological findings correlated with either subgroup. We examined signalling pathways specific to subgroups 1 and 2 to identify the association of each subgroup with signalling pathways based on gene ontology tree visualisation: subgroups 1 and 2 were associated with haem metabolism and chromosomal instability, respectively. These findings reveal a comprehensive genomic landscape that highlights the molecular complexity of IMNs and provide a road map to facilitate our understanding of gastric IMNs.

The pattern-based interpretation of p53 immunohistochemical expression as a surrogate marker for TP53 mutations in colorectal cancer.

Mutations in the TP53 gene, most commonly observed in colorectal cancer (CRC), play an essential role in colorectal carcinogenesis. Although p53 immunohistochemical (IHC) expression patterns have been argued to serve as an excellent surrogate marker for TP53 mutations, its performance has not been confirmed in CRC. We aimed to determine whether p53 IHC expression patterns accurately predict TP53 mutation status as examined by next-generation sequencing (NGS). We performed p53 IHC and sequencing of TP53 by NGS in 92 CRC cases with a microsatellite stable phenotype to investigate the correlation between TP53 mutation status and p53 IHC expression. The concordance between p53 IHC and TP53 mutation was 84/92 (91.3%) overall. However, 6 mutant cases were found in 39 cases with a wild-type IHC pattern. Additionally, there were two discordant cases in which an abnormal p53 IHC pattern (overexpression or cytoplasmic pattern) was found, while NGS detected wild-type p53. Therefore, the optimized p53 IHC performs well and serves as a surrogate test for TP53 mutation in CRC cases. Furthermore, it demonstrates excellent reproducibility between two independent experienced pathologists and may have novel clinical utility for molecular classification algorithms in CRC. We suggest that the four-tier classification of p53 IHC patterns is helpful to evaluate molecular colorectal carcinogenesis.

A single-institution retrospective exploratory analysis on the effectiveness and safety of lenvatinib plus pembrolizumab for advanced endometrial cancer: insights from ProMisE molecular classification system.

BACKGROUND: The Proactive Molecular Risk Classifier for Endometrial Cancer has identified four risk groups for the prognosis of endometrial cancer. Lenvatinib plus pembrolizumab was recently approved as a second-line treatment for unresectable endometrial cancer, but reports in clinical practice are lacking. The relationship between the efficacy of lenvatinib/pembrolizumab and Proactive Molecular Risk Classifier for Endometrial Cancer classification is unclear. METHODS: This single-centre retrospective study included patients who underwent lenvatinib/pembrolizumab therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient, p53 abnormal and no specific molecular profile subtypes using immunohistochemistry. The response rate, progression-free survival and adverse events were evaluated using electronic medical records. The study was approved by the hospital's ethics committee (approval number: MH2022-093). RESULTS: This study enrolled 20 patients, who underwent a median follow-up of 17.8 months (95% confidence interval: 16.6-18.9). The best overall response rate was 60.0% (36.1-80.9), and the median progression-free survival was 11.6 months (2.9-20.3). The median progression-free survival in the p53 abnormal group (n = 9) was 3.4 months (3.0-3.8); however, progression-free survival did not reach the median (P < 0.001) in the mismatch repair-deficient/no specific molecular profile group (n = 11). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and partial responses were observed in all cases. No treatment-related deaths occurred. CONCLUSION: The p53abn group in the Proactive Molecular Risk Classifier for Endometrial Cancer classification has a poor prognosis even after treatment with lenvatinib/pembrolizumab.

Characterization of sessile serrated adenomas with dysplasia including intramucosal adenocarcinoma and colorectal carcinoma with a microsatellite instability phenotype.

Recent studies have shown that sessile serrated lesions (SSLs) lead to the development of colorectal cancer (CRC) with a microsatellite instability (MSI) phenotype via a dysplasia-carcinoma sequence. However, the pathological and molecular mechanisms of SSL with dysplasia (SSLD) are unclear. Here, we aimed to examine the clinicopathological and molecular alterations in SSLD and to evaluate the significance of such alterations with regard to lesion progression. Fifty-four SSLDs (20 serrated dysplasia cases and 17 intestinal dysplasia cases, including 30 low-grade dysplasia [LGD] cases, 7 high-grade dysplasia [HGD] cases, and 17 intramucosal adenocarcinomas [IMAs]) were evaluated. Molecular alterations, including immunohistochemical expression of various markers, DNA methylation status, and multiple genetic mutations (using next-generation sequencing), were assessed. Additionally, such alterations were also investigated in 41 CRCs with an MSI phenotype (invasion beyond submucosa). The frequency of mismatch repair (MMR) deficiency in SSLD was 12 of 39 cases (32.4 %), whereas the MMR proficient type was observed in 17 of 39 SSLD cases. SSLD with serrated dysplasia showed a significantly higher frequency of loss of MMR protein expression and methylation status. Moreover, loss of MMR protein expression differed significantly between LGD and IMA. Furthermore, the frequency of TP53 mutation was significantly higher in IMA than in LGD. The current findings demonstrated that SSL with serrated dysplasia may be associated with an increased risk of malignant transformation compared with intestinal dysplasia. Loss of MMR proteins and mutation of TP53 may play important roles in tumor progression from dysplasia to carcinomatous lesions.

Polyclonal Hyperglobulinemia with Multiple Pulmonary Cysts and Nodules: Concerning the Mechanism Underlying Cyst Formation.

We herein report a case of polyclonal hyperglobulinemia with multiple pulmonary cysts and nodules. The histopathological findings allowed us to speculate about the mechanism underlying cyst formation in these pathological conditions, which has not yet been thoroughly elucidated. The patient was a 49-year-old woman who presented with multiple pulmonary multilocular cysts and nodules. A lung biopsy revealed features of nodular lymphoid hyperplasia. Notably, lung structure fragmentation was evident, suggesting that structural destruction may have accompanied the disease during its course. The cysts were considered to have formed due to destruction of the lung structures.

The clinicopathological impact of tumor-associated macrophages in patients with cutaneous malignant melanoma.

BACKGROUND: Tumor-associated macrophages (TAMs) are an immune component of the cutaneous malignant melanoma (CMM) microenvironment and affect tumor growth. TAMs can polarize into different phenotypes, that is, proinflammatory M1 and anti-inflammatory M2 macrophages. However, the role of the macrophage phenotype in CMM remains unclear. METHODS: We examined 88 patients with CMM. Tissue microarrays were constructed, and the density of M1 and M2 macrophages was analyzed by immunohistochemistry. Immune cells coexpressing CD68 and phosphorylated signal transducer and activator of transcription 1 (pSTAT1) were considered M1 macrophages, whereas those coexpressing CD68 and c-macrophage activating factor (c-Maf) were defined as M2 macrophages. These TAMs were counted, and the relationships between the density of M1 and M2 macrophages and clinicopathological factors including prognosis were investigated. RESULTS: The CD68/c-Maf score ranged from 0 to 34 (median: 5.5). The patients were divided based on the median score into the CD68/c-Maf high (≥5.5) and low (<5.5) expression groups. Univariate and multivariate analyses revealed that CD68/c-Maf expression was an independent predictive factor for progression-free survival and an independent prognostic factor for overall survival. CD68/pSTAT1 expression was found in only two patients. CONCLUSION: We suggest that CD68/pSTAT1 coexpression is rarely observed in patients with CMM, and high CD68/c-Maf expression is a predictor of worse prognosis in these patients.

A Case of Autoimmune Hepatitis Complicated by Undiagnosed Factor VII Deficiency: A Pitfall of Coagulopathy.

Prothrombin time (PT) is a key parameter for assessing the severity of liver disease. We present the case of a 37-year-old woman with severe acute liver injury due to autoimmune hepatitis. Although prednisolone drastically improved her hepatocyte function, her PT did not recover to the reference range. A review of her medical records revealed that the patient had normal transaminase levels and prolonged PT 2 years previously. Further examinations of her coagulopathy revealed that she had low factor VII activity, suggesting a diagnosis of factor VII deficiency. Our experience suggests that altered coagulopathy should be considered in cases of liver injury with an extraordinary PT.

Improved Diagnosis of Adjacent Organ Invasion of Extrahepatic Cholangiocarcinoma by Adding Arterial and Delayed Phases.

PURPOSE: To clarify the role of dynamic computed tomography (CT) in diagnosing extrahepatic cholangiocarcinoma (eCCA) involving adjacent organs. MATERIAL AND METHODS: We retrospectively analyzed patients diagnosed with eCCA in Iwate Medical University Hospital (Morioka, Japan) during January 2011-December 2021 who underwent dynamic contrast-enhanced CT before biliary intervention, surgery, or chemotherapy. For surgical cases, two radiologists independently reviewed CT images in the portal, dual (adding arterial phase), and triple (adding delayed phase) phases. The mean attenuations of the abdominal aorta, portal vein (PV), hepatic parenchyma, pancreatic parenchyma, and eCCA were measured. The biliary segment-wise longitudinal tumour extent, arterial and PV invasion, organ invasion (liver, pancreas, and duodenum), and regional lymph node metastasis were assessed on a five-point scale. Image performances were compared using the sensitivity, specificity, and area under the curve (AUC). RESULTS: We included 120 patients (mean age, 71.7 ± 8.9; 84 males). The PV and liver differed most from the bile duct tumour in the portal phase. The abdominal aorta and pancreas differed most from eCCA in the arterial phase. For 80 patients evaluated on the five-point scale, adding phases increased the AUC for pancreatic, duodenal, and arterial invasion for each observer (observer 1, 0.79-0.93, p<0.01, 0.71-0.86, p = 0.04, 0.74-0.99, p = 0.02; observer 2, 0.88-0.96, p = 0.01, 0.73-0.94, p<0.01, 0.80-0.99 p = 0.04; respectively). The AUC for biliary segment-wise longitudinal tumor extent, hepatic, and PV invasion remained unchanged with additional phases. CONCLUSIONS: Portal-phase information is sufficient to evaluate the segmental extent of bile duct and liver/PV invasion. Arterial- and delayed-phase information can help evaluate pancreatic, duodenal, and arterial invasion.

Metastatic bladder cancer forming a sigmoidorectal fistula after enfortumab vedotin therapy: a case report.

We report the case of a 68-year-old man who developed a sigmoidorectal fistula after marked response to enfortumab vedotin for advanced bladder cancer. The patient had undergone radical cystectomy with ileal conduit after neoadjuvant chemotherapy. Six months after surgery, local recurrence in the pelvic cavity and multiple lung metastases were found, and the patient was administered pembrolizumab as second-line therapy. Due to worsening local recurrence and suspected invasion of the sigmoid colon and rectum, enfortumab vedotin was initiated as third-line therapy and comprehensive genomic profiling was simultaneously performed. Enfortumab vedotin was remarkably effective, the lung metastases disappeared, and the local recurrent lesion shrank in volume although a sigmoidorectal fistula was found to form through the tumor cavity. Immunohistochemical analysis of the tumor specimens exhibited increased nectin-4 expression. This rare case of metastatic bladder cancer with sigmoidorectal fistula associated with effective enfortumab vedotin therapy suggests that nectin-4 expression and comprehensive genomic profiling might be useful in predicting treatment response to enfortumab vedotin.

Characteristics and prognostic analysis of patients with detected KRAS mutations in resected lung adenocarcinomas by peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method.

Background: Kirsten rat sarcoma virus (KRAS) gene mutations are a type of driver mutation discovered in the 1980s, but for a long time no molecular targeted drugs were available for them. Recently, sotorasib was developed as a molecular targeted drug for KRAS mutations. It is therefore necessary to identify the characteristics of patients with KRAS mutations. Methods: This was the single-institution retrospective study. Surgically resected tumors from lung adenocarcinoma patients were collected at a single institution from June 2016 to September 2019. Peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp analysis of KRAS G12X mutations was compared with analysis by therascreen KRAS RGQ kit. The association between KRAS mutation status and patient characteristics and prognosis was assessed. Results: Among 499 lung adenocarcinomas, KRAS mutations were evaluated in 197 cases, excluding stage IV lung cancer and tumors with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations. KRAS G12X mutations were detected in 59 cases (29.9%). The highest frequency by gene mutation subtype was G12V in 23 cases (39.0%), followed by G12C in 16 cases (27.1%), G12D in 12 cases (20.3%), G12S in 4 cases (6.8%) and G12A in 2 cases. For the G12C mutation, the PNA-LNA PCR clamp and therascreen methods were consistent, but for the G12D and G12S mutations, the PNA-LNA PCR clamp method showed higher detection rates. In operable tumors, G12C mutations were more frequent in males, smokers, and patients with high expression of programmed death-ligand 1 (PD-L1), and had no correlation with prognosis. Conclusions: By the PNA-LNA PCR clamp method, G12C mutation of surgical specimens was detected successfully. The PNA-LNA PCR clamp method is expected to be applied to the detection of druggable G12C mutations.

Prognostic Impact of Tumor-Associated Macrophage-Related Markers in Patients with Adenocarcinoma of the Lung.

BACKGROUND: Macrophage polarization is an important pathogenetic factor in neoplastic diseases. Phosphorylated signal transducer and activator of transcription 1 (phospho-STAT1) regulates the M1 phenotype, and c-Maf regulates the M2 phenotype. However, the role of macrophage phenotype in lung adenocarcinoma (LAD) remains unclear. PATIENTS AND METHODS: We examined whether the density of M1 and M2 macrophages was associated with prognosis in patients with LAD using double-labeling immunohistochemistry. In addition, programmed death ligand 1 (PD-L1) expression was investigated. Immune cells coexpressing CD68 and phospho-STAT1 were considered M1 macrophages, whereas those coexpressing CD68 and c-Maf were recognized as M2 macrophages. Patients with LAD (N = 307) were divided into two cohorts (n = 100 and n = 207) to evaluate the associations of M1 and M2 phenotypes with prognosis in patients with LAD. We determined the cut-off values of CD68/phospho-STAT1-positive cells and CD68/c-Maf-positive cells to assess correlations with overall survival (OS) using receiver operating characteristic curve analysis in the first cohort. RESULTS: According to the cut-off values of 5 or less CD68/phospho-STAT1-positive cells and more than 11 CD68/c-Maf-positive cells, high expression of CD68/c-Maf and low expression of CD68/Phospho-STAT1 were identified as independent prognostic markers for OS and disease-free survival (DFS). Moreover, the M1/M2 ratio (0.19 or less) was a poor prognostic factor for OS and DFS. However, PD-L1 expression did not correlate with patient outcomes. CONCLUSIONS: Overall, these findings suggest that double immunostaining of markers of phospho-STAT1 (M1) and c-Maf (M2) can be used as prognostic indicators for patients with LAD.

Surgical treatment for lung metastasis of inflammatory myofibroblastic tumor of the lung: A case report.

Inflammatory myofibroblastic tumor (IMT) is a rare disease that is considered an intermediate neoplasm, with the risk of recurrence and metastasis. Surgical treatment is the standard therapy for IMT, although there are only a few reports of surgery for lung metastasis of pulmonary IMT. We opine that surgical treatment might be effective not only for localized tumors, but also for cases of lung metastasis of IMT.

Prognostic and predictive value of CD163 expression and the CD163/CD68 expression ratio for response to adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinoma.

BACKGROUND: Macrophages infiltrating the tumor microenvironment are defined as tumor-associated macrophages (TAMs). TAMs can be polarized into different phenotypes, that is, proinflammatory M1 macrophages or anti-inflammatory M2 macrophages. Particularly, M2 macrophages promote angiogenesis, wound healing, and tumor growth. This study aimed to evaluate whether M2 TAMs can serve as a useful marker to predict prognosis and benefit from adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinomas (SCCs). METHODS: We examined 104 patients with SCC. Tissue microarrays were constructed, and the density of TAMs was analyzed by immunohistochemistry for expression of CD68 and CD163. The relationship between CD68 and CD163 expression and the CD163/CD68 expression rate and clinicopathological characteristics including patient outcomes were investigated. In addition, propensity score matching (PSM) analysis was conducted to test the hypothesis that these cells significantly influenced chemotherapy responses. RESULTS: Univariate analysis revealed that pathological stage, CD163 expression, and the CD163/CD68 expression ratio were significant prognostic factors. Multivariate analysis showed that these factors were all independent prognostic factors. Thirty-four pairs were determined by using PSM analysis. Patients with a low CD163/CD68 expression ratio benefited more from adjuvant chemotherapy than those with a high ratio. CONCLUSION: We suggest that M2 TAMs may be a useful marker to predict prognosis and differential benefit from adjuvant chemotherapy in patients with surgically resected lung SCCs.

Rectal Carcinoma With a Sarcomatoid Component: A Case Report With Detailed Immunohistochemistry, Molecular Analysis, and Literature Review.

Introduction. Carcinoma with sarcomatoid components is a highly malignant tumor exhibiting both epithelial and stromal malignant differentiation. Its tumorigenesis is associated with epithelial-mesenchymal transition (EMT), and phenotypic changes from carcinoma to sarcoma are associated with TP53 mutations. Case presentation. A 73-year-old female with bloody stool was diagnosed with rectal adenocarcinoma. She underwent trans-anal mucosal resection. Histopathologically, the tumor cells showed 2 morphologically distinct populations. One was composed of well-formed to fused glands or cribriform glands and was considered a moderately differentiated adenocarcinoma. The other consisted of pleomorphic discohesive atypical tumor cells with spindle and/or giant cell features, which was considered a sarcomatous tumor. Immunohistochemistry analysis showed that E-cadherin expression changed from positive to negative in the sarcomatous component. On the other hand, ZEB1 and SLUG were positive. Finally, she was diagnosed with carcinoma with a sarcomatoid component. We performed a mutation analysis by next genome sequencing and found KRAS and TP53 mutations in both carcinomatous and sarcomatous components. Conclusions. Immunohistochemistry and mutation analyses revealed tumorigenesis of rectal carcinoma with sarcomatoid components correlated with EMT and TP53 mutations.

Gastroblastoma mimics the embryonic mesenchyme of the foregut: a case report.

BACKGROUND: Gastroblastoma is a rare gastric tumor composed of epithelial and spindle cell components. The characteristic MALAT-GLI1 fusion gene has only been identified in 5 reported cases. We report the morphological characterization of gastroblastoma with the MALAT1-GLI1 fusion gene in a young Japanese woman. CASE PRESENTATION: A 29-year-old Japanese woman visited Iwate Medical University Hospital with upper abdominal pain. Computed tomography revealed a tumor in expansive lesions involving the gastric antrum. Histologically, we observed a biphasic morphology composed of epithelial and spindle cell components. The epithelial components appeared as slit-like glandular structures with tubular or rosette-like differentiation. The spindle cell components consisted of short spindle-shaped oval cells. Immunohistochemical (IHC) analysis revealed that the spindle cell component was positive for vimentin, CD10, CD56, GLI1, and HDAC2, and focally positive for PD-L1. The epithelial component was positive for CK AE1/AE3, CAM5.2, and CK7, and negative for CK20 and EMA. Both components were negative for KIT, CD34, DOG1, SMA, desmin, S100 protein, chromogranin A, synaptophysin, CDX2, and SS18-SSX. The MALAT-GLI1 fusion gene was detected molecularly. CONCLUSIONS: We report the following new findings with this case: (i) gastric tumors mimic the gastrointestinal mesenchyme in the embryonic period; (ii) nuclear expression of PD-L1 and HDAC2 were observed in the spindle cell component of a gastroblastoma. We speculate that histone deacetylase (HDAC) inhibitors may offer a promising treatment option for gastroblastoma.