Familial Intraductal Papillary Mucinous Neoplasm Associated With the Germline MSH6 Missense Variant and Progression of Pancreatic cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasm (IPMN) in individuals with at least one first-degree relative with IPMN is defined as familial IPMN. However, few studies have reported on familial IPMN, its clinical characteristics, or the associated genetic factors. MATERIALS AND METHODS: We report the case of a 58-year-old woman with multifocal IPMN and a mural nodule in the pancreatic body. The patient underwent a distal pancreatectomy and developed pancreatic head cancer 1 year and 6 months postoperatively. The patient had a family history of multifocal IPMN in her father. Therefore, a genetic predisposition to IPMN and pancreatic cancer was suspected. The patient was analyzed for germline variants, and the resected IPMN was subjected to immunohistochemical and somatic variant analyses. RESULTS: Next-generation sequencing revealed a heterozygous germline missense variant in exon 5 of MSH6 (c.3197A>G; Tyr1066Cys). The pathogenicity of this variant of uncertain significance was suspected based on multiple in silico analyses, and the same MSH6 variant was identified in the patient's father's colonic adenoma. The mural nodule in the pancreatic body was pathologically diagnosed as a high-grade IPMN with ossification and somatic KRAS and PIK3CA variants. CONCLUSIONS: This case revealed a possible genetic factor for familial IPMN development and presented interesting clinicopathological findings.

Preferential Expression of Ca2+-Stimulable Adenylyl Cyclase III in the Supraventricular Area, including Arrhythmogenic Pulmonary Vein of the Rat Heart.

Ectopic excitability in pulmonary veins (PVs) is the major cause of atrial fibrillation. We previously reported that the inositol trisphosphate receptor in rat PV cardiomyocytes cooperates with the Na+-Ca2+ exchanger to provoke ectopic automaticity in response to norepinephrine. Here, we focused on adenylyl cyclase (AC) as another effector of norepinephrine stimulation. RT-PCR, immunohistochemistry, and Western blotting revealed that the abundant expression of Ca2+-stimulable AC3 was restricted to the supraventricular area, including the PVs. All the other AC isotypes hardly displayed any region-specific expressions. Immunostaining of isolated cardiomyocytes showed an enriched expression of AC3 along the t-tubules in PV myocytes. The cAMP-dependent response of L-type Ca2+ currents in the PV and LA cells is strengthened by the 0.1 mM intracellular Ca2+ condition, unlike in the ventricular cells. The norepinephrine-induced automaticity of PV cardiomyocytes was reversibly suppressed by 100 µM SQ22536, an adenine-like AC inhibitor. These findings suggest that the specific expression of AC3 along t-tubules may contribute to arrhythmogenic automaticity in rat PV cardiomyocytes.

Pathogenesis of follicular thymic hyperplasia associated with rheumatoid arthritis.

Lymphoproliferative disorders may occur in patients with rheumatoid arthritis (RA) who are treated with methotrexate. However, follicular thymic hyperplasia (FTH) associated with RA (FTH-RA) is generally not considered a lymphoproliferative disorder. To investigate the pathogenesis of FTH-RA, we examined 12 cases of FTH involving thymic enlargement, four of FTH involving RA and eight of FTH involving myasthenia gravis (MG). Increased numbers and larger germinal center (GC) size were observed in FTH-RA group. The percentage of distorted GCs was 13.3% in FTH-RA group and 3.25% in FTH associated with MG (FTH-MG) group. A greater meshwork of follicular dendritic cells was observed in the GCs of FTH-RA group. Positive indices of CD27+ cells and PD-1+ cells per GC in FTH-RA group were significantly higher than those in FTH-MG group, though positive indices of CD68+ cells and CD163+ cells were similar. Myoid cell proliferation, as evaluated by α-SMA, tenascin-C, and l-caldesmon expression, was significantly increased in the FTH-RA group compared with the FTH-MG group. These results suggest that FTH should be considered in patients with RA treated with methotrexate. The pathogenesis of FTH-RA includes GC expansion and increased numbers of memory B cells, follicular helper T cells, and myoid cells, indicating humoral immunity activation.

Rosai-Dorfman disease of thymus with elevated serum anti-acetylcholine receptor antibody: a case report.

Rosai-Dorfman disease is a rare disorder of histiocytic proliferation in lymph nodes and at extranodal sites. We herein describe a patient with isolated Rosai-Dorfman disease in the thymus with elevated anti-acetylcholine receptor antibody. We examined the relationship between Rosai-Dorfman disease and elevated anti-acetylcholine receptor antibody. To our knowledge, elevated anti-acetylcholine receptor antibody has not been reported in isolated thymic Rosai-Dorfman disease.

Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.

Background: Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function. Case Presentation: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation. Conclusion: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.

Developmental retardation in neonates of aldehyde reductase (AKR1A)-deficient mice is associated with low ascorbic acid and high corticosterone levels.

Aldehyde reductase encoded by the Akr1a gene catalyzes the NADPH-dependent reduction of a variety of aldehyde compounds, and it plays a role in the biosynthesis of ascorbic acid (AsA) by converting D-glucuronate to L-gulonate. Although supplementing drinking water with AsA (1.5 mg/mL) ameliorates the fertility of Akr1a-/- (KO) female mice, litter sizes in the KO mice are typically smaller than those for Akr1a+/+ (WT) mice, and about one-third of the neonates have a reduced stature. Half of the neonates in the smallest, developmentally retarded group died before weaning, and the remaining half (less than 6 g in weight) also barely grew to adulthood. While no difference was found in the number of fetuses between the KO and WT mice at 14.5-embryonic days, the sizes of the KO fetuses had already diverged. Among the organs of these retarded KO neonates at 30 d, the spleen and thymus were characteristically small. While an examination of spleen cells showed the normal proportion of immune cells, apoptotic cell death was increased in the thymus, which would lead to thymic atrophy in the retarded KO neonates. Plasma AsA levels were lower in the small neonates despite the fact that their mothers had received sufficient AsA supplementation, and the corticosterone levels were inversely higher compared to wild-type mice. Thus, insufficient AsA contents together with a defect in corticosterone metabolism might be the cause of the retarded growth of the AKR1A-deficient mice embryos and neonates.

Nodal histiocytic sarcoma with prominent eosinophilic infiltration: expression of eotaxin-2 on tumor cells.

BACKGROUND: Histiocytic sarcoma (HS) is a rare neoplasm showing morphological and immunophenotypic features of mature tissue histiocytes. We report a patient with nodal HS exhibiting prominent reactive eosinophilic infiltration. CASE PRESENTATION: A 68-year-old man presented with intermittent left lower abdominal pain and weight loss over 3 months. A computed tomography scan revealed multiple abdominal nodules. Open biopsy of the mesenteric tumors was performed for definitive diagnosis. Histologically, the tumor was comprised of a diffuse noncohesive proliferation of pleomorphic large cells, including multinucleated cells. Neoplastic cells were positive for histiocytic markers (CD68, CD163, and LIGHT) and PD-L1 but lacked markers of Langerhans cells, follicular dendritic cells, and epithelial cells. Frequent reactive inflammatory cells were intermingled in the background. Interestingly, prominent eosinophilic infiltration was also noted. Spindle neoplastic cells were prone to be present around areas with little to no eosinophilic infiltration and exhibiting fibrosis and lymphatic vessel proliferation. Conversely, polygonal neoplastic cells were prone to be present around areas with relatively large amounts of eosinophilic infiltration without fibrosis or lymphatic vessel proliferation. Immunohistochemically, the tumor cells and reactive eosinophils expressed eotaxin-2 and eotaxin-3, respectively. CONCLUSION: We revealed that eotaxins induced the selective migration of eosinophils into tissues in this case. These eosinophils may affect the tumor remodeling and tumor biology characteristics of HS, such as fibrosis and lymphatic vessel proliferation.

Potential role of M2 TAMs around lymphatic vessels during lymphatic invasion in papillary thyroid carcinoma.

The aim of this study was to examine whether lymphatic invasion in papillary thyroid carcinoma (PTC) occurs when tumour-associated macrophages (TAMs) injure lymphatic vessels together with cancer cells. While there was no difference in the lymphatic vessel density in PTC and follicular thyroid carcinoma (FTC), the number of TAMs around the lymphatic vessels was increased in PTC compared to that in FTC. In particular, TAMs were observed together with cancer cells in lymphatic invasive lesions, and the number of M2 cells inside and outside the lymphatic vessels showed a significant correlation. MMP-2 mRNA was expressed in nonneoplastic stromal cells as well as cancer cells, and double immunofluorescence staining confirmed M2 positivity. Consequently, this study reveals that M2 TAMs around lymphatic vessels within the tumour border of PTC may be associated with the lymphatic invasion of cancer cells. This study represents a step forward in elucidating the mechanism of lymphatic invasion.

Comparative study of HO-1 expressing synovial lining cells between RA and OA.

OBJECTIVES: We aimed to clarify the characteristics of heme oxygenase (HO)-1 expressing cells in the synovium from rheumatoid arthritis (RA) and osteoarthritis (OA), and to investigate the co-expression of HO-1 and IgG-Fc/HLA-DR complex. METHODS: The characteristics of HO-1 expressing cells in the synovium were investigated by using immunohistochemistry. The co-expression of HO-1 and IgG-Fc/HLA-DR complex was examined by an in situ proximity ligation assay (PLA) with immunofluorescence. HO-1 mRNA was investigated by reverse transcription-polymerase chain reaction. RESULTS: The number of HO-1+ cells from the RA synovium is higher than that from OA synovium. The double positive cells of HO-1 and IgG-Fc/HLA-DR complex were detected by the in situ PLA with immunofluorescence in RA synovium. HO-1 mRNA was detected in both RA and OA synovium. CONCLUSION: A portion of HO-1+ cells with IgG-Fc/HLA-DR complex in lining layer of RA may be concluded as one of antigen presenting cells in RA and may be involved in production of RF.

Cytokeratin-positive interstitial reticulum cell (CIRC) tumor in the lymph node: a case report of the transformation from the epithelioid cell type to the spindle cell type.

BACKGROUND: Cytokeratin-positive interstitial reticulum cells (CIRCs), which are a subgroup of fibroblastic reticular cells (FRCs), are known to be present in the lymph nodes. There have been only a few cases of tumors derived from CIRCs. CASE PRESENTATION: We have reported a new case involving a CIRC tumor in a 75-year-old man and reviewed the literature. The resected mediastinal lymph nodes showed epithelial-like proliferation of large atypical round and polygonal epithelioid cells. The tumor cells expressed CK8, CK18, CAM5.2, AE1/AE3, epithelial membrane antigen, vimentin, fascin, and some FRC markers, which is consistent with the diagnosis of a CIRC tumor. Following chemotherapy, the CIRC tumor was observed to have responded very well and became difficult to confirm on imaging, but a small cell lung carcinoma developed 12 months later. Chemoradiotherapy was performed, but the patient passed away 29 months after the initial diagnosis. The autopsy revealed the recurrence of the CIRC tumor, residual small cell lung carcinoma, and a very small latent carcinoma of the prostate. The relapsed CIRC tumor cells had a spindle shape; they were highly pleomorphic and had invaded the superior vena cava. CONCLUSION: We first reported autopsy findings of CIRC tumors and demonstrated the transformation of the tumor from the epithelioid cell type to the spindle cell type.

Iron loading exerts synergistic action via a different mechanistic pathway from that of acetaminophen-induced hepatic injury in mice.

Acetaminophen (APAP) overdose is a major cause of drug-induced acute liver failure. In such cases, free iron is released from lysosomes and is transported to mitochondria where it plays a pivotal role in APAP-induced liver injury. We previously reported that ascorbic acid (Asc) markedly mitigates APAP-induced hepatic damage in aldehyde reductase (Akr1a)-knockout (KO) mice that produce about 10% Asc as wild-type (WT) mice. However, the issue of the protective mechanism of Asc in association with the status of iron remains ambiguous. To gain additional insights into this issue, we examined effects of APAP (500 mg/kg) on female KO mice under conditions of iron loading. While the KO mice without AsA supplementation were more sensitive to APAP toxicity than the WT mice, FeSO4 loading (25 mg/kg) to WT mice aggravated the hepatic injury, which was a similar extent to that of the KO mice. Supplementation of Asc (1.5 mg/ml in the drinking water) ameliorated KO mice irrespective of iron status but did not change the iron-mediated increase in the lethality in the WT mice. Hepatic cysteine and glutathione levels declined to similar extents in all mouse groups at 3 h irrespective of the iron status and largely recovered at 18 h after the APAP treatment when liver damage was evident. Asc prominently mitigated APAP toxicity in KO mice irrespective of the iron status but had no effect on the synergistic action of iron and APAP in the WT mice, suggesting that the mechanism for the deteriorating action of loaded iron is different from that of APAP toxicity.

A Patient with 22q11.2 Deletion Syndrome Presenting with Systemic Skin Rash and Dermatopathic Lymphadenitis of Unusual Histology.

BACKGROUND Chromosome 22q11.2 deletion syndrome (22q11.2 DS) currently includes DiGeorge syndrome, conotruncal anomaly face syndrome, and velocardiofacial syndrome. We present the case of a male infant with 22q11.2 DS exhibiting generalized skin rash and dermatopathic lymphadenitis. CASE REPORT The patient was born at 40 weeks of gestation with interruption of aortic arch, ventricular septal defect, and thymic defect. Fluorescence in situ hybridization method performed on buccal smears detected the deletion of 22q11.2. On day of life 33, diffuse erythema appeared on the entire body. A skin biopsy detected vacuolar interface dermatitis with superficial perivascular infiltration. Laboratory examinations revealed eosinophilia and hypocalcemia. Clinically, cutaneous inflammation was correlated with the abnormal immune response in 22q11.2 DS. On day of life 210, the patient died due to sepsis caused by Pseudomonas aeruginosa. An autopsy revealed lymph nodes swellings in the bilateral axillar and subclavicular areas and around the bilateral iliac arteries. Histology of the lymph nodes demonstrated sparse distribution of atrophic germinal centers surrounded by wide zones of proliferating spindle cells, as well as macrophages, Langerhans cells, and interdigitating dendritic cells. Fontana-Masson staining revealed abundant melanin particles in the macrophages. Accordingly, we diagnosed this case as dermatopathic lymphadenitis. Interestingly, CD123 and CD56 double-positive spindle cells also proliferated around the germinal center. CONCLUSIONS This case had an unusual histological feature of dermatopathic lymphadenitis. Considering the wide variety of unusual immune conditions in 22q11.2 DS, the lymph nodes in the systemic skin inflammation may exhibit an extraordinary histology of spindle cells proliferation.

Immunohistochemical staining as supportive diagnostic tool for pseudomyxoma peritonei arising from intraductal papillary mucinous neoplasm: A report of two cases and literature review.

BACKGROUND/OBJECTIVES: Pseudomyxoma peritonei (PMP) arising from an intraductal papillary mucinous neoplasm of the pancreas (IPMN) is a rare condition. The diagnosis of IPMN as the origin of PMP is mainly inferred from the clinical course and the exclusion of PMP from other organs. The pathological diagnosis has not yet been established. To evaluate the usefulness of immunohistochemical staining for the diagnosis of the primary lesion of PMP as IPMN. METHODS: There are 2 cases of PMP arising from IPMN between March 2010 and December 2019 at National Center for Global Health and Medicine. A PubMed search that reported PMP arising from IPMN identified 16 additional cases. Diagnostic methods and clinicopathological features of 18 cases were compared. RESULTS: Four cases including our two cases used immunohistochemical staining for the diagnosis of PMP arising from IPMN. The correspondence of the immunohistochemical staining between PMP and IPMN was shown in the three cases including previously reported two cases and one of our two cases to identify the primary lesion of PMP as IPMN. In addition, we revealed that the comparison of the immunostaining pattern of PMP with the representative immunostaining pattern of the candidate primary lesions is helpful for the diagnosis of the primary lesion of PMP. CONCLUSIONS: Immunohistochemical staining is helpful to identify the primary lesion of PMP as IPMN.

[A case of fibrinogen storage disease with primary biliary cholangitis].

A 66-year-old woman was diagnosed as primary biliary cholangitis (PBC) and was previously hospitalized for ascites and jaundice. She came to our hospital for further examination of the liver by needle biopsy, which showed interface hepatitis that mainly comprised lymphocytes and inflammatory infiltrates in the bile duct in the portal area. On the other hand, numerous intracytoplasmic inclusions that were positive for fibrinogen immunostaining were seen in the lobular area. Finally, we histologically diagnosed as PBC with fibrinogen storage disease (FSD). FSD is rare disease that leads to liver damage caused by abnormal fibrinogen storage in the endoplasmic reticulum of hepatocytes, with only four cases reported in Japan until now.

The distribution of macrophage subtypes and their relationship to bone morphogenetic protein 2 in calcified aortic valve stenosis.

Activation of the osteogenic signaling cascade (OSC) is thought to be involved in aortic valve stenosis. The aim of this study was to clarify the distribution of macrophage (M) subtypes in the calcified aortic valve and to clarify the relationship between osteoblast-like cells (OLC) and OSC activation. Thirty-six cases of calcified aortic valve were set as the calcification group, and six autopsy cases of aortic valve without pathological calcification comprised the noncalcification group. Aortic valve tissues were used in histological studies including single and double immunostaining to identify M subtypes, bone morphogenetic protein 2 (BMP2) and osteopontin, reverse transcription polymerase chain reaction (RT-PCR) for CD206, heme oxygenase-1 (HO-1), and BMP2 mRNAs and in situ RT-PCR for BMP2 mRNA. Ms positive for CD68, CD163, CD206, and HO-1 were significantly higher in the calcification group than in the noncalcification group (P < 0.01). Comparison of the positive cells in each section of the calcification group showed that cells of all M subtypes were found around calcifications. Osteopontin+ cells were also observed around calcifications. CD163+/CD206+ M2 and CD163+/HO-1+ Mox were significantly higher in the sponge layer in both groups. In double immunofluorescence, CD206+ and a portion of HO-1+ Ms expressed BMP2, and in RT-PCR, CD206 or HO-1 mRNA was expressed in cases in which BMP2 was expressed. In in situ RT-PCR, expression of BMP2 mRNA was observed around calcifications. This work clarifies the distribution of M subtypes in calcified aortic valves. In addition, the results suggest that CD206+ M2 and HO-1+ Mox, which express BMP2 in calcified aortic valves, are OLC candidates.

A case of iatrogenic immunodeficiency-associated colonic lymphoma complicating ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is one of the major types of inflammatory bowel diseases and is associated with a significantly increased risk of not only lymphoproliferative disorders but also lymphomas, of which most cases are related to the long-term usage of immunosuppressants. Here, we demonstrate a very rare case of other iatrogenic immunodeficiency-associated colonic diffuse large B-cell lymphoma (Oii-DLBCL) complicating UC and rectal perforation. In addition, we reviewed the clinicopathological features of previous cases of DLBCL related to UC. CASE PRESENTATION: A 68-year-old man was diagnosed with left-sided UC 26 months prior. Although he was followed by immunosuppressive therapy with azathioprine and infliximab, an emergency total proctocolectomy was performed due to rectal perforation. The resected specimen exhibited irregular wall thickening and elevated multinodular lesions extending from the mid-transverse colon to the rectum, measuring up to 52 cm in length. Histologically, the lesion was diagnosed as Oii-DLBCL and crypt abscess surrounded by mixed inflammatory cell was remained. CONCLUSION: Oii-DLBCL complicating UC with rectal perforation is extremely rare. Macro- and microscopic findings are important for early diagnosis of the lesion.

Diabetes mellitus exacerbates citrin deficiency via glucose toxicity.

AIMS: Citrin is an aspartate/glutamate carrier that composes the malate-aspartate reduced nicotinamide adenine dinucleotide (NADH) shuttle in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), failure to thrive and dyslipidemia (FTTDCD) and adult-onset type II citrullinemia (CTLN2). Hepatic glycolysis is essentially impaired in citrin deficiency and a low-carbohydrate diet was recommended. The lethal effect of infusion of glycerol- and fructose-containing osmotic agents was reported in these patients. Hyperalimentation was also reported to exacerbate CTLN2; however, glucose toxicity was unclear in citrin deficiency. METHODS: We studied two CTLN2 patients complicated with type 2 diabetes mellitus (DM), Case 1 presented with hyperammonemic encephalopathy accompanied with DM, while Case 2 presented with hyperammonemic encephalopathy relapse upon the onset of DM after several years' remission following supplementation with medium-chain triglycerides (MCT) and adherence to a low-carbohydrate diet. RESULTS: Insulin therapy with MCT supplementation and a low-carbohydrate diet improved hyperammonemia and liver function in Case 1. Additional insulin therapy improved hyperammonemia in Case 2. CONCLUSION: Glucose is not toxic for citrin deficiency in normoglycemia because glucose uptake and metabolism by hepatocytes are limited in normoglycemia. However, glucose becomes toxic during persistent hyperglycemia and antidiabetic therapy is indispensable for CTLN2 patients with DM.

Good prognosis for follicular lymphoma with estrogen receptor α-positive follicular dendritic cells.

Follicular lymphoma (FL) has a meshwork of follicular dendritic cells (FDCs). We previously demonstrated the presence of estrogen receptor alpha (ERα)+ CD23+ FDCs in grades 1-2 FL. The significance of FDCs as a prognostic factor in FL remains unknown. The current study aimed to compare clinicopathological features, including prognosis, between FL with and without ERα+ FDCs. This study evaluated the clinicopathological significance of ERα expression in 70 FL patients by immunostaining. The presence of ERα mRNA on FDCs from 5 FL patients was confirmed by CD21/ERα double staining (immunohistochemistry and in situ hybridization). We defined patients with frequent ERα expression as the ERαhigh group and those with infrequent ERα expression as the ERαlow group. Thirty-two patients were assigned to the ERαhigh group (45.7%), and 38 patients were assigned to the ERαlow group (54.3%). Both overall survival (OS) and progression-free survival (PFS) were significantly better in the ERαhigh group than in the ERαlow group (OS, log-rank, P = .0465; PFS, log-rank, P = .0336). Moreover, high ERα expression on FDCs was an independent prognostic factor for OS in both the univariate ([hazard ratio] HR, 0.163; P = .0260) and multivariate (HR, 0.050; P = .0188) analyses and for PFS in both the univariate (HR, 0.232; P = .0213) and multivariate (HR, 0.084; P = .0243) analyses. ERα mRNA expression was detected in CD21+ FDCs within the neoplastic follicles of FL patients. In conclusion, a neoplastic follicular microenvironment with ERα-positive FDCs might affect the grade and presence of the follicular pattern of FL and improve patient prognosis.

Relationships between recurrence patterns and subventricular zone involvement or CD133 expression in glioblastoma.

INTRODUCTION: We previously reported that CD133 expression correlated with the recurrence pattern of glioblastoma (GBM). Subventricular zone (SVZ) involvement may also be associated with distant recurrence in GBM. Therefore, we herein investigated whether the combined analysis of SVZ involvement and CD133 expression is useful for predicting the pattern of GBM recurrence. MATERIALS AND METHODS: We retrospectively analyzed 167 cases of GBM. Tumors were divided into four groups based on spatial relationships between contrast-enhanced lesions (CEL) and the SVZ or cortex (Ctx) on MRI. The initial recurrence pattern (local/distant) was obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by immunohistochemical, clinical (age, sex, KPS, Ki-67 labeling index, surgery, and MRI characteristics), and genetic (IDH1, MGMT, and BRAF) factors. RESULTS: The CD133 expression rate was higher in SVZ-positive tumors than in SVZ-negative tumors (P = 0.046). Distant recurrence was observed in 21% of patients, and no significant difference was noted in recurrence patterns among the four groups. However, strong CD133 expression was associated with a shorter time to distant recurrence in univariate, multivariate, and propensity-matched scoring analyses (P < 0.0001, P = 0.001, and P = 0.0084, respectively). In the combined analysis, distant recurrence was the most frequent (70%) in group III (SVZ-negative, Ctx-positive) GBM and those with high CD133 expression rates (≥ 15%). CONCLUSION: An integrated analysis of CD133 expression and MRI-based tumor classification may be useful for predicting the recurrence pattern of GBM.