Rim Enhancement on Contrast-Enhanced CT as a Predictor of Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

This study investigated the utility of imaging features, such as rim enhancement on contrast-enhanced CT (CECT), in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 158 patients (84 men; mean age, 68 years) with pathologically confirmed PDAC. The following imaging features were evaluated on CECT by two radiologists: tumor size, tumor attenuation, and the presence of rim enhancement. Cox proportional hazards analysis was performed to identify the imaging and clinicopathological features for predicting disease-free survival (DFS) and overall survival (OS). Pathological features were compared with the presence of rim enhancement. Among the 158 patients, 106 (67%) underwent curative surgery (surgery group) and 52 (33%) received conservative treatment (non-surgery group). Rim enhancement was observed more frequently in the non-surgery group than in the surgery group (44% vs. 20%; p < 0.001). Rim enhancement showed significant associations with shorter DFS and OS in the surgery group (hazard ratios (HRs), 3.03 and 2.99; p < 0.001 and p = 0.003, respectively), whereas tumor size showed significant associations with shorter OS (HR per 1 mm increase, 1.08; p < 0.001). PDACs with rim enhancement showed significant associations with higher histological tumor grades (p < 0.001). PDAC with rim enhancement on CECT could predict poorer prognosis and more aggressive tumor grades.

Spontaneous rupture of splenic hilar lymph node metastasis from hepatocellular carcinoma.

Spontaneous rupture of a primary hepatocellular carcinoma (HCC) is a frequently observed and fatal complication. However, the rupture of lymph node (LN) metastases from HCC is rare. A 79 year-old male with hepatitis B underwent three liver resections for HCC. Two years and 6 months after the last liver resection, enhanced computed tomography (CT) revealed a nodule with a diameter of 3 cm in the lower pole of the spleen. Splenic metastasis of HCC was suspected, and splenectomy was scheduled. During our hospital stay for a urinary tract infection before the scheduled operation, he complained of acute left-sided abdominal pain, and CT showed intra-abdominal hemorrhage due to rupture of the splenic tumor. Emergency splenectomy was performed, and the postoperative course was uneventful. Histopathological examination revealed a poorly differentiated HCC in the lower splenic pole lesion, which contained LN structures. The ruptured lesion was diagnosed as splenic hilar LN metastasis of HCC. Although laparoscopic partial liver resection was performed for intrahepatic recurrence, and atezolizumab plus bevacizumab therapy was administered for peritoneal metastases, the patient was alive 25 months after the splenectomy. Our case suggests that emergency surgery for LN metastatic rupture can achieve hemostasis and lead to improved survival outcomes.

CYP1A1 Is a Useful Diagnostic Marker for Angiofibroma of Soft Tissue.

Angiofibroma of soft tissue (AFST) is a recently described benign fibroblastic neoplasm composed of uniform bland spindle cell proliferation in fibrous and fibromyxoid stroma with prominent thin-walled small branching vessels. A major recurrent genetic abnormality in AFST is t(5;8)(p15;q13), which results in the rearrangement of AHRR and NCOA2 . Owing to a lack of discriminatory IHC markers and potential overlap with other mesenchymal neoplasms, it may be difficult to confirm the diagnosis of AFST in some cases. Triggered by a recent gene expression profile study of AFST, which showed the significant upregulation of AhR/AHRR/ARNT downstream genes (including CYP1A1 ), we used a mouse monoclonal antibody to explore the diagnostic significance of CYP1A1 expression in histologically confirmed AFST cases along with 224 control cases, consisting of 221 neoplastic mimickers and 3 non-neoplastic lesions. We found moderate to strong cytoplasmic expression of CYP1A1 in 13 of 16 AFST cases (sensitivity, 81.3%). In contrast, the vast majority of other examined histologic mimickers exhibited no expression of CYP1A1 (specificity, 97.3%), except for 3 myxofibrosarcomas (3/31), 2 solitary fibrous tumors (2/22), and 2 neurofibroma (1/27). Our results indicate that CYP1A1 immunohistochemistry may aid in the diagnosis of AFST by distinguishing among various kinds of tumors, particularly those harboring prominent vasculature.

Diagnostic usefulness of SpyGlass in intracholecystic papillary neoplasm with pancreaticobiliary maljunction: a case report and comparison with conventional gallbladder cancer with pancreaticobiliary maljunction.

BACKGROUND: Intracholecystic papillary neoplasm (ICPN) is one of the precursors of gallbladder cancer defined in the 2010 World Health Organization classification of tumors. We herein report ICPN with pancreaticobiliary maljunction (PBM), which is a high-risk factor for biliary cancer. CASE PRESENTATION: A 57-year-old female presented with abdominal pain. Computed tomography showed a swollen appendix and gallbladder nodules with bile duct dilatation. Endoscopic ultrasonography revealed a gallbladder tumor spreading into the cystic duct confluence accompanying PBM. Based on papillary tumors around the cystic duct detected using the SpyGlass DS II Direct Visualization System (SpyGlass DS), ICPN was suspected. We performed extended cholecystectomy, extrahepatic bile duct resection, and appendectomy with a diagnosis of ICPN and PBM. The pathological diagnosis was ICPN (90 × 50 mm) with high-grade dysplasia spreading into the common bile duct. The absence of residual cancer in the resected specimen was pathologically confirmed. P53 staining was totally negative in both the tumor and normal epithelium. The overexpression of CTNNB1 was not observed. CONCLUSIONS: We encountered a patient with a very rare gallbladder tumor, ICPN with PBM. SpyGlass DS contributed to a precise assessment of the extent of the tumor as well as a qualitative diagnosis.

Clinicopathological Features and the Prevalence of Oxyntic Gland Neoplasm: A Single-center Retrospective Study.

Objective We explored the clinicopathological characteristics and disease frequency of oxyntic gland neoplasms (OGNs). Methods We retrospectively evaluated the data of patients pathologically diagnosed with OGN at an internal medicine clinic. Patients A total of 13,240 upper gastrointestinal endoscopies were performed on 7,488 patients between December 1, 2017, and March 31, 2021. Results We identified 27 patients with 30 histopathologically confirmed OGNs, yielding a disease frequency of 0.36% (27/7,488). Furthermore, multiple simultaneous lesions were found in 3 of 27 patients (11%). One (3.3%) of the 30 lesions was present in the antrum, whereas the remaining lesions occurred in the body of the stomach. Nine (33%) of the 27 patients had no history of Helicobacter pylori infection, whereas the remaining 18 (67%) were either currently or had been previously infected. Nevertheless, 27/30 lesions (90%) still occurred in non-atrophied regions. After endoscopic treatment, a histopathological examination of the resected specimens revealed submucosal infiltration in 8 (44%) of the 18 lesions; however, none of the lesions showed submucosal desmoplasia. For all patients with submucosal involvement, only observation was performed. There were no recurrent lesions found on follow-up. Conclusion The period prevalence of OGN was 0.36%, which is much higher than previously reported. The discovery of a small submucosal appearing lesion with a faded yellow or white color and dilated microvasculature, especially in a non-atrophic area of the stomach, should raise suspicion for an OGN, which can be endoscopically managed.

Uterine rupture in intramural ectopic pregnancy: A case report.

Intramural pregnancy is a rare form of ectopic pregnancy. It is defined by a gestation within the uterine wall, completely surrounded by myometrium and separated from the uterine cavity and the fallopian tube. We report a rare case of intramural ectopic pregnancy. If a patient has a history of intrauterine surgery or myomectomy, the possibility of intramural pregnancy, although rare, should not be ruled out.

2-Hydroxyglutarate magnetic resonance spectroscopy in adult brainstem glioma.

OBJECTIVE: Adult brainstem gliomas (BSGs) are rare tumors of the CNS that are poorly understood. Upregulation of the oncometabolite 2-hydroxyglutarate (2HG) in the tumor indicates the mutation of isocitrate dehydrogenase (IDH), which can be detected by magnetic resonance spectroscopy (MRS). Although histological examination is required for the definitive diagnosis of BSG, 2HG-optimized MRS (2HG-MRS) may be useful, considering the difficult nature of brainstem lesion biopsy. The aim of this study was to evaluate the utility of 2HG-MRS for diagnosing IDH-mutant adult BSG. METHODS: Patients with a radiographically confirmed brainstem tumor underwent 3T MRS. A single voxel was set in the lesion with reference to the T2 or fluid-attenuated inversion recovery image and analyzed according to the 2HG-tailored MRS protocol (point-resolved spectroscopic sequence; echo time 35 msec). All patients underwent intraoperative navigation-guided or CT-guided stereotactic biopsy for histopathological diagnosis. The status of IDH and H3K27M mutations was confirmed by immunohistochemistry and direct DNA sequencing. In addition, the authors examined the relationship between patients' 2HG concentrations and survival time. RESULTS: Ten patients (7 men, 3 women; median age 33.5 years) underwent 2HG-MRS and biopsy. Four patients had an H3K27M mutation and 4 had an IDH1 mutation (1 R132H canonical IDH mutation, 2 R132S and 1 R132G noncanonical IDH mutations). Two had neither H3K27M nor IDH mutations. The H3K27M and IDH mutations were mutually exclusive. Most tumors were located in the pons. There was no significant radiological difference between mutant H3K27M and IDH on a conventional MRI sequence. A 2HG concentration ≥ 1.8 mM on MRS demonstrated 100% (95% CI 28%-100%) sensitivity and 100% (95% CI 42%-100%) specificity for IDH-mutant BSG (p = 0.0048). The median overall survival was 10 months in IDH-wild-type BSG patients (n = 6) and could not be estimated in IDH-mutant BSG patients (n = 4) due to the small number of deaths (p = 0.008). CONCLUSIONS: 2HG-MRS demonstrated high sensitivity and specificity for the prediction of IDH-mutant BSG. In addition, 2HG-MRS may be useful for predicting the prognosis of adult BSG patients.

Expressions of NeuroD and GAP43 as diagnostic markers for olfactory neuroblastoma.

OBJECTIVE: Olfactory neuroblastoma (ONB) is often difficult to pathologically distinguish from other small round cell tumors (SRCTs) arising in the nasal cavities. Although there are several diagnostic markers used for differential diagnosis of ONB, these molecules are also expressed in various neuronal derived tumors. Here, we examined the expression of NeuroD, GAP43, and olfactory marker protein (OMP) in ONB and non-ONB SRCT to determine their utility in the differential diagnosis of ONB. METHODS: Twenty-six patients diagnosed with and treated for ONB at Kobe University Hospital between 1997 and 2017 with formalin-fixed, paraffin-embedded biopsy or surgical resection specimens were included. The expressions of NeuroD, GAP43, and OMP were immunohistochemically examined in these 26 ONB specimens and specimens from 13 SRCTs arising in the nasal cavities for reference. RESULTS: Among the 26 ONB samples, focal, patchy, and marked staining for NeuroD was observed in 4, 3, and 9 samples, respectively. Focal, patchy, and marked GAP43 staining was observed in 5, 3, and 11 samples, respectively. Consequently, marked positive staining for either NeuroD or GAP43 was observed in 54% (14/26) of ONBs. Among the 13 SRCTs, marked staining for NeuroD was observed in two small cell carcinomas, one undifferentiated carcinoma, and one neuroendocrine carcinoma, whereas marked positive staining for GAP43 was observed only in one undifferentiated carcinoma. No specimen in this study exhibited OMP staining. CONCLUSIONS: Our results suggest possible roles of GAP43 immunostaining in the differential diagnosis of ONB.

Spindle cell sarcoma with KIAA1549-BRAF resembling infantile fibrosarcoma morphologically: A case report and literature review.

Infantile fibrosarcoma (IFS) commonly harbors ETS variant transcription factor 6 (ETV6)-neurotrophic receptor tyrosine kinase 3 (NTRK3) fusion. However, the recent accessibility to clinical next-generation sequencing (NGS) has revealed ETV6-NTRK3 negative spindle cell sarcomas resembling IFS morphologically, involving NTRK1/2, MET, RET and BRAF. The present report describes a pediatric case of spindle cell sarcoma with KIAA1549-BRAF resembling IFS morphologically. A 20-month-old female patient was referred to Kobe Children's Hospital (Kobe, Japan) for the treatment of intrathoracic spindle cell sarcoma. Pathologically, the intrathoracic tumor cells were composed of spindle cells with focal hemagiopericytomatous pattern. In immunohistochemistry analysis, the intrathoracic tumor cells focally expressed desmin and WT-1 and were negative for pan-tropomyosin receptor kinase (TRK), S-100 and CD34. Fluorescence in situ hybridization analysis for ETV6 and capicua transcriptional repressor revealed negative split signals. Although the patient was initially diagnosed with IFS morphologically, KIAA1549-BRAF fusion transcript was detected by comprehensive genomic profiling with NGS using intrathoracic tumor tissues and confirmed by reverse transcription-PCR. Chemotherapy induced a reduction in the tumor size. At present, the patient is alive with the disease and has been receiving therapy for 8 months since the initiation of chemotherapy. Review of BRAF-altered spindle cell sarcomas resembling IFS morphologically revealed the inconsistency in immunohistochemical expression patterns and the diversity of BRAF fusion genes and mutations. Therefore, the elucidation of genomic profiling by NGS may assist in making an appropriate diagnosis and selecting novel alternative therapies in ETV6-NTRK3-negative spindle cell sarcomas resembling IFS morphologically.

Heterogeneity or transformation? A whack-a-mole case of EGFR-mutant lung adenocarcinoma and small cell carcinoma: A case report.

Histological transformation from adenocarcinoma to small cell lung cancer (SCLC) occurs ~10% after acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. Transformed SCLC generally responds well to chemotherapy regimens for SCLC such as platinum plus etoposide. After the response, histological nature and clinical course could be complicated by possible heterogeneity or transformation. Therefore, monitoring rebiospy is desirable to seize its histological nature at that moment. We report a case of EGFR-mutated adenocarcinoma, where histological transformations from adenocarcinoma and SCLC alternated. In this case, first rebiopsy after gefitinib revealed adenocarcinoma, but second rebiopsy after osimertinib identified SCLC transformation. After failure of platinum plus etoposide, adenocarcinoma-induced leptomeningeal metastases were controlled by osimertinib reintroduction. Optimal therapies could be provided according to the result of monitoring rebiopsy.

Pancreatic hamartoma: detection of harbouring NAB2::STAT6 fusion gene.

Hamartomas in the pancreas are rare and are often histologically and morphologically similar to solitary fibrous tumours (SFTs). We examined the differences between hamartomas and SFTs at the molecular level. METHODS AND RESULTS: Thirteen patients histopathologically diagnosed with pancreatic hamartoma were included in the study. We also performed STAT6 immunohistochemistry (IHC), which is used in the diagnosis of SFT. Furthermore, for the three cases in which RNA was extracted, reverse transcription polymerase chain reaction to search for NAB2::STAT6 fusions was used. Macroscopically, 13 patients had well-demarcated tumour lesions. Histologically, no islets of Langerhans were observed in the lesions, acinar tissue and ducts were unevenly distributed and elastic fibres were not observed around the ducts by Elastica van Gieson staining. One case contained a lipomatous hamartoma composed mainly of adipose tissue. Seven of the 13 cases demonstrated expression of STAT6 in the nuclei of intervening spindle cells. NAB2::STAT6 fusions were observed in two of the three cases in which RNA was extracted. These two cases also demonstrated STAT6 expression in spindle cells using STAT6 IHC. In one case of lipomatous hamartoma, we did not confirm NAB2::STAT6 fusion or STAT6 expression in STAT6 IHC. CONCLUSION: Of the 13 patients histopathologically diagnosed with hamartoma, two demonstrated NAB2::STAT6 fusions, suggesting the existence of pancreatic hamartomas with molecular-level components identical to those of SFT.

Immunohistochemical analysis revealed the expression of bone morphogenetic proteins-4, 6, 7, and 9 in human induced membrane samples treated with the Masquelet technique.

BACKGROUND: Induced membrane (IM) is the key component of Masquelet reconstruction surgery for the treatment of bone defects. IM is formed around the cement spacer and is known to secrete growth factors and osteoinductive factors. However, there is limited evidence available concerning the presence of osteoinductive factors in IM. This study aimed to investigate the existence of bone morphogenetic proteins (BMPs) in IM harvested from patients during the treatment of bone defects using the Masquelet technique. METHODS: This study involved six patients whose bone defects had been treated using the Masquelet technique. The affected sites were the femur (n = 3) and the tibia (n = 3). During the second-stage surgery, 1 cm2 pieces of IM were harvested. Histological sections of IM were immunostained with anti-BMP-4, 6, 7, and 9 antibodies. Human bone tissue served as the positive control. RESULTS: The presence of BMP-4, 6, 7, and 9 was observed in all IM samples. Further, immunolocalization of BMP-4, 6, 7, and 9 was observed in blood vessels and fibroblasts in all IM samples. Immunolocalization of BMP-4, 6, 7, and 9 was also observed in bone tissue within the IM in one sample, in which osteogenesis inside the IM was observed. CONCLUSIONS: This study showed that osteoinductive factors BMP-4, 6, 7, and 9 were present in the IM harvested from patients, providing evidence indicating that the Masquelet technique effectively contributes to healing large bone defects. Therefore, it may be possible for surgeons to omit the addition of BMPs to bone grafts, given the endogenous secretion of BMPs from the IM.

Pineal gland differentiation in mature teratoma: An under-recognized condition and potential pitfalls for overdiagnosis.

We herein report three cases of mature teratomas with pineal gland differentiation, which is a less recognized phenomenon. Case 1 was a 6-year-old male with a neck mass, Case 2 was a 23-year-old female with a retroperitoneal mass, and Case 3 was a 45-year-old female with a retroperitoneal mass. Each case showed the typical macroscopic and histological findings of mature teratoma, such as solid and cystic lesions mainly lined with a mature squamous epithelium. All cases also showed glial differentiation. Small foci of lobulated cell nests were detected in the center of or adjacent to mature glial tissue. Cells had a clear to pale eosinophilic cytoplasm with small round nuclei. Immunohistochemically, cells were positive for synaptophysin, neurofilament protein with a perivascular "club-shaped swelling" pattern, and cone-rod homeobox protein. To the best of our knowledge, this is the first report of pineal gland differentiation arising in mature teratoma, which may be easily overlooked or misdiagnosed as somatic-type tumors, particularly neuroendocrine tumors. To avoid overtreatment, pathologists need to be aware that pineal gland differentiation may occur in mature teratomas.

Histological analysis of induced membranes in patients whose bone defects were treated with the Masquelet technique to identify factors affecting the vascularity of induced membranes.

BACKGROUND: Rich vascularity of the induced membrane (IM) is important for Masquelet reconstruction surgery. The factors affecting IM vascularity are not completely understood. This study aimed to investigate these factors using histological samples of human IMs. METHODS: We retrospectively evaluated 36 patients whose bone defects were treated using the Masquelet technique. Two clinical pathologists analyzed histological sections of IM pieces (1 cm2). The number of blood vessels per 1 mm2 was counted and compared among men and women, femur or tibia, with and without free flap surgery, antibiotic impregnation to the cement, osteogenesis inside the membrane, smoking, and diabetes mellitus. The number of blood vessels within the same patient was compared among different time points. Correlation analysis was performed among blood vessel numbers and patient age, duration of cement spacer placement, and histological grading scales (inflammation, foreign body reaction, and fibrosis). RESULTS: IM formation with rich vascularity and some inflammation, foreign body reaction, and fibrosis were histologically confirmed in all patients. We found 37.4 ± 19.1 blood vessels per 1 mm2. The number of blood vessels was significantly lower in patients with than in those without free flap surgery; it was higher in patients with osteogenesis inside the IM. No significant correlations were found in any of the analyses. CONCLUSION: Sex, patient age, smoking, diabetes mellitus, femur or tibia, duration of cement spacer placement, and antibiotic impregnation to the cement did not affect IM vascularization. IM vascularization was reduced in patients with than in those without free flap surgery.

An immunostaining panel of C-reactive protein, N-cadherin, and S100 calcium binding protein P is useful for intrahepatic cholangiocarcinoma subtyping.

This study aimed to establish an immunohistochemical panel useful for subclassification of intrahepatic cholangiocarcinoma (iCCA) into small- and large-duct types. Fifty surgical cases of iCCA consisting of small- (n = 31) and large-duct types (n = 19) were examined. To imitate liver needle biopsies, tissue microarrays were constructed using three tissue cores (2 mm in diameter) obtained from one representative paraffin block of each case. Immunostaining for C-reactive protein (CRP), N-cadherin, tubulin beta-III (TUBB3), neural cell adhesion molecule (NCAM), and S100 calcium binding protein P (S100P) was conducted. Most cases of small-duct iCCA were immunoreactive to CRP and N-cadherin, whereas expressions of these markers were markedly less common in large-duct iCCA (CRP, 97% vs. 5%, P < 0.001; N-cadherin, 87% vs. 16%, P < 0.001). TUBB3 and NCAM were also more frequently expressed in small-duct iCCA (65% vs. 32%, P = 0.006; 58% vs. 5%, P < 0.001), but their sensitivities were lower than those of CRP and N-cadherin. S100P was more commonly expressed in large-duct iCCA than in small-duct iCCA (95% vs. 29%, P < 0.001), and diffuse expressions were observed in 17 of 19 cases of large-duct iCCA (90%). All cases with a CRP+/S100P- immunophenotype were of small-duct type, whereas all but one case with a CRP-/S100P+ immunophenotype were of large-duct type. Of 10 cases with a double-positive or double-negative immunophenotype, 7 were appropriately classified based on immunoreactivity to N-cadherin. In conclusion, CRP, N-cadherin, and S100P form a useful immunohistochemical panel for iCCA subclassification, and correct subclassification was possible in 92% of cases based on a proposed, simple algorithm.

Neuroendocrine carcinoma and mixed neuroendocrine‒non-neuroendocrine neoplasm of the stomach: a clinicopathological and exome sequencing study.

The gene mutation profiles of gastric neuroendocrine neoplasms are incompletely understood. The purpose of this study was to characterize the molecular pathology of poorly differentiated neuroendocrine carcinoma (NEC) and mixed neuroendocrine‒non-neuroendocrine neoplasm (MiNEN) of the stomach. Surgical cases of gastric NEC (n = 7) and MiNEN (n = 6) were examined by clinical review, immunohistochemistry, microsatellite instability (MSI) analysis and whole-exome sequencing. NEC cases consisted of small- (n = 2) and large-cell types (n = 4). All cases of MiNEN were histologically composed of large-cell type NEC and tubular adenocarcinoma. Whole-exome sequencing analysis detected recurrent mutations in TP53 in 8 cases (62%), and they were more frequently observed in MiNEN than in NEC (100% vs. 29%). Frameshift mutations of APC were observed in two cases of MiNEN. One case of large-cell type NEC had a frameshift mutation with loss of heterozygosity in RB1. The other mutated genes (e.g., ARID1 and KRAS) were detected in a single case each. A high level of MSI was confirmed in one case of MiNEN, which harbored mutations in two well-differentiated neuroendocrine tumor (NET)-related genes (MEN1 and ATRX1). In cases of MiNEN, two histological components shared mutations in TP53, APC and ZNF521, whereas alterations in CTNNB1, KMT2C, PTEN and SPEN were observed in neuroendocrine components only. In conclusion, TP53 is a single, frequently mutated gene in gastric NEC and MiNEN, and alterations in other genes are less common, resembling the mutation profiles of gastric adenocarcinomas. Gene mutations frequently observed in well-differentiated NET were uncommon but not entirely exclusive.

A Rare Case of Löffler "Pancarditis" Associated with Hypereosinophilic Syndrome.

A 53-year-old woman was admitted to another hospital because of a 2-month history of repeated chest pain and breathlessness. Laboratory examinations demonstrated the presence of hypereosinophilia (absolute count of 6,500/µL). An endomyocardial biopsy confirmed eosinophilic infiltration with myocardial destruction. On cardiac magnetic resonance imaging, late gadolinium enhancement was clearly observed along the visceral pericardium as well as on the endocardial layer. Based on the multimodal imaging and histopathological findings, the final diagnosis of "Löffler pancarditis" was made. After the introduction of steroid therapy, the left ventricular contractile function significantly recovered. Furthermore, the late gadolinium enhancement of the visceral pericardium had attenuated.