Search

Background:The polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) family of enzymes regulates the initial steps of mucin-type O-glycosylation. N-acetylgalactosaminyltransferases might show novel patterns of GalNAc-T glycosylation on tumour-derived proteins, which could influence cancer biology, but its mechanisms are unclear. We investigated the association of GalNAc-T3 and -T6 expressions with clinicopathological features and prognoses of patients with renal cell carcinomas (RCCs).Methods:Expressions of GalNAc-T3/6 and cell-adhesion molecules were analysed immunohistochemically in 254 paraffin-embedded tumour samples of patients with RCC.Results:Of 138 GalNAc-T3+ cases, 46 revealed significant co-expression with GalNAc-T6. N-acetylgalactosaminyltransferases-3+ expression showed a close relationship to poor clinical performance and large tumour size, or pathologically high Fuhrman's grading, and presence of vascular invasion and necrosis. The GalNAc-T3-positivity potentially suppressed adhesive effects with a significantly low β-catenin expression. Univariate and multivariate analyses showed the GalNAc-T3+ group, but not the GalNAc-T6+ group, to have significantly worse survival rates.Conclusion:N-acetylgalactosaminyltransferases-3 expression independently predicts high-grade tumour and poor prognosis in patients with RCC, and may offer a therapeutic target against RCC. [ABSTRACT FROM AUTHOR]

Background: The family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) is responsible for the altered glycosylation in cancer. The purpose of our study was to investigate the clinical significance of two isoforms, GalNAc-T6 and -T3, and their correlation with the prognosis of pancreatic cancer.Methods: Immunohistochemistry was used to analyse GalNAc-T6 and -T3 expressions in 70 clinicopathologically characterised pancreatic cancer cases.Results: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively. A close relationship was noted between GalNAc-T6 positive expression and pathological well/moderate differentiated type (P=0.001), small tumour size (P=0.044), absence of vascular invasion (P=0.009), and low stage of the American Joint Committee on Cancer systems (P=0.043). The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features. Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356).Conclusion: Both GalNAc-T6 and -T3 expressions correlated significantly with tumour differentiation, whereas only GalNAc-T6 expression predicted prognosis in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Y-box-binding proteins are members of the human cold-shock domain protein superfamily, which includes dbpA, dbpB/YB-1, and dbpC/contrin. dbpC/contrin is a germ cell-specific Y-box-binding protein and is suggested to function as a nuclear transcription factor and RNA-binding protein in the cytoplasm. Whereas ubiquitous dbpB/YB-1 expression has been well studied in various types of human carcinomas as a prognostic or predictive marker, the dbpC/contrin expression in human tumour cells has not been reported. In this report, we provide the first evidence showing that dbpC was highly expressed in human testicular seminoma and ovarian dysgerminomas, and in carcinomas in other tissues and that its expression in normal tissues is nearly restricted to germ cells and placental trophoblasts. These results indicate that dbpC/contrin would be a potentially novel cancer/testis antigen. [ABSTRACT FROM AUTHOR]

Abstract A history of a recent rapid increase in long-standing swelling mass was presented in the right parotid gland of an 85-year-old male. The inadequate cytologic specimens contained few small clusters of three-dimensional malignant epithelial cells having hyperchromatic pleomorphic nuclei and prominent nucleoli, adjacent to a cluster of benign monomorphic myoepithelial cells. We first interpreted it merely as an adenocarcinoma, not otherwise specified. A radical parotidectomy was performed, and gross examination revealed an encapsulated and firm tumor lesion, looking grayish-blue to yellowish-white, focally associated with extracapsular invasion. On microscopic examination, the tumor was predominantly composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, often arranged in a Roman-bridge appearance with foci of comedo necrosis, alternating with extensive infiltration to adjacent stroma in a trabecular or alveolar fashion with severe vessel permeation. Within the background of pleomorphic adenoma, the carcinoma cells sometimes replaced ductal luminal cells while retaining an intact-like myoepithelial layer. Therefore, we finally made a diagnosis of invasive salivary duct carcinoma ex pleomorphic adenoma. We should be aware that owing to its characteristic features, cytopathologists might be able to determine correct diagnosis, based on multiple and adequate samplings. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2126158270695815

Abstract Background Primary androgen deprivation therapy (ADT) is a treatment option not only for advanced but also for localized prostate cancer. However, the appropriate duration for primary ADT for localized prostate cancer has not been defined and few studies have addressed this issue. In this study, we aimed to determine the appropriate duration of ADT for localized prostate cancer. Methods Sixty-eight consecutive patients with localized prostate cancer who underwent a prostatectomy following neoadjuvant ADT were retrospectively reviewed. Factors associated with pT0, which is regarded as serious cancer cell damage or elimination, were investigated. Results Of the 68 males, 24 (35.3%) were classified as pT0. The median duration of neoadjuvant ADT in the pT0 and non-pT0 groups was 9 months and 7.5 months, respectively (p = 0.022). The duration of neoadjuvant ADT from when PSA reached < 0.2 ng/ml to surgery was longer in the pT0 group than that in the non-pT0 group (median 5 months against 3 months, p = 0.011). pT0 was achieved in 5 of 6 patients (83.3%) who received ADT for ≥10 months after PSA reached < 0.2 ng/ml. No other clinical characteristics predicted conversion to pT0. Conclusions Continuous ADT for ≥10 months after PSA reached < 0.2 ng/ml induced serious prostate cancer cell damage in most patients (> 80%) and may be sufficient to treat localized prostate cancer.

Podocyte detachment is a major trigger in pathogenesis of focal segmental glomerulosclerosis (FSGS). Detachment via β1 integrin (ITGB1) endocytosis, associated with endothelial cell injury, has been reported in animal models but remains unknown in human kidneys. The objectives of our study were to examine the difference in ITGB1 dynamics between primary FSGS and minimal change nephrotic syndrome (MCNS), among variants of FSGS, as well as between the presence or absence of cellular lesions (CEL-L) in human kidneys, and to elucidate the pathogenesis of FSGS. Thirty-one patients with primary FSGS and 14 with MCNS were recruited. FSGS cases were categorized into two groups: those with CEL-L, defined by segmental endocapillary hypercellularity occluding lumina, and those without CEL-L. The podocyte cytoplasmic ITGB1 levels, ITGB1 expression, and degrees of podocyte detachment and subendothelial widening were compared between FSGS and MCNS, FSGS variants, and FSGS groups with and without CEL-L (CEL-L( +)/CEL-L( -)). ITGB1 distribution in podocyte cytoplasm was significantly greater in CEL-L( +) group than that in MCNS and CEL-L( -) groups. ITGB1 expression was similar in CEL-L( +) and MCNS, but lower in CEL-L( -) compared with others. Podocyte detachment levels were comparable in CEL-L( +) and CEL-L( -) groups, both exhibiting significantly higher detachment than the MCNS group. Subendothelial widening was significantly greater in CEL-L( +) compared with CEL-L( -) and MCNS groups. The findings of this study imply the existence of distinct pathological mechanisms associated with ITGB1 dynamics between CEL-L( +) and CEL-L( -) groups, and suggest a potential role of endothelial cell injury in the pathogenesis of cellular lesions in FSGS., (© 2024. The Author(s).)

We present a non-smoker woman in her 40s with PLCH who presented with atypical imaging findings of multiple pulmonary noncavitary nodules without air cysts with repeated waxing and waning., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A 69-year-old ex-smoker Japanese man presented with a left mediastinal lymph node and left upper lobe tumour. Bronchoscopic biopsy specimens from the enlarged left mediastinal lymph node and left upper lobe tumour revealed small cell lung carcinoma (SCLC). He was treated with first-line chemotherapy with carboplatin, etoposide, and atezolizumab for four courses and subsequent atezolizumab maintenance therapy. However, his left upper lobe lung tumour only increased in size, and left upper lobectomy revealed combined SCLC (adenocarcinoma and chondrosarcoma-like features). Four months after lobectomy, liver metastasis of chondrosarcoma-like features (similar to pathological findings of the left upper lobe tumour) were observed. Combined SCLC, including sarcomatous components, is rare and poorly responds to chemotherapy. The metastases of combined SCLC in this patient were of only one type of histological component, making diagnosis and treatment difficult. If treatment for SCLC responds inadequately, considering combined SCLC and actively re-examining histological diagnosis is necessary., Competing Interests: None declared., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Purpose: Adipocytes around aggressive breast cancer (BC) are less lipid different from naive adipocytes (cancer-associated adipocytes, CAAs), and peritumoral edema caused by the release of cytokines from CAAs can conduce to decrease the peritumoral fat proportion. The purpose of this study was to correlate peritumoral fat content identified by using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with lymph node metastasis (LNM) and recurrence-free survival (RFS) in BC patients and to compare with T2-weighted (T2WI) and diffusion-weighted images (DWI) analyses., Methods: This retrospective study consisted of 85 patients who were diagnosed with invasive carcinoma of breast and underwent breast MRI, including IDEAL before surgery. The scan time of fat fraction (FF) map imaging using IDEAL was 33s. Four regions of interest (ROIs), which are 5 mm from the tumor edge, and one ROI in the mammary fat of the healthy side were set on the FF map. Then average peritumoral FF values (TFF), average FF values on the healthy side (HFF), and peritumoral fat ratio (PTFR, which is defined as TFF/HFF) were calculated. Tumor apparent diffusion coefficient (ADC) values were measured on ADC map obtained by DWI. Peritumoral edema was classified into three grades based on the degree of signal intensity around the tumor on T2WI (T2 edema)., Results: The results of stepwise logistic regression analysis for four variables (TFF, PTFR, T2 edema, and ADC value) indicated that TFF and T2 edema were significant factors of LNM (p < 0.01). RFS was significantly associated with TFF (p = 0.016), and 47 of 49 (95.9%) patients with TFF more than 85.5% were alive without recurrence., Conclusion: Peritumoral fat content identified by using IDEAL is associated with LNM and RFS and may therefore be a useful prognostic biomarker for BC.

We aimed to compare the prognostic impacts of adenocarcinoma subtypes, programmed death-ligand I (PD-L1), and CD155 expression on patients with resected pathological stage (p-stage) I lung adenocarcinoma. In total, 353 patients with completely resected p-stage I lung adenocarcinomas were retrospectively reviewed. The expression levels of PD-L1 and CD155 in tumour cells from each adenocarcinoma subtype were evaluated using several clinicopathological and histological features, such as the presence of a micropapillary pattern. A total of 52 patients (14.7%) had PD-L1-positive tumours, whereas 128 patients (36.3%) had CD155-positive tumours, with a tumour proportion score of 5% for both PD-L1 and CD155 expression. Compared with patients with other adenocarcinoma subtypes, those with solid-predominant adenocarcinomas were significantly more positive for PD-L1 and CD155. Multivariate analysis showed that PD-L1 expression status was significantly associated with progression-free survival and overall survival, whereas CD155 expression and the presence of a micropapillary pattern were not significantly associated with either parameter. Patients with PD-L1-positive tumours had poorer prognoses than those with CD155-positive tumours. Moreover, PD-L1 and CD155 were significantly expressed in solid-predominant adenocarcinomas. The results of this study suggest that immune checkpoint inhibitors can be used as adjuvants in the treatment of patients with p-stage I adenocarcinoma., (© 2023. The Author(s).)

Background: Acute aortic dissection has a high mortality rate, especially for Stanford type A with a dissected ascending aorta. Cardiac tamponade is one of the most common complications of acute type A aortic dissection (ATAAD) and can cause death. However, the pathogenesis is often unclear. We aimed to examine laboratory findings at the onset of disease and macrophage involvement., Methods: Hematological and biochemical parameters, and D-dimer, brain natriuretic peptide (BNP), and high-sensitivity troponin I (hs-cTnI) levels in 70 patients with ATAAD at our hospital were investigated. Additionally, the myocardium and aorta after autopsy of an ATAAD case with cardiac tamponade were pathologically examined., Results: Forty-four ATAAD cases were complicated by cardiac tamponade. The mean age of patients with cardiac tamponade and proportion of patients over 70 years of age were both significantly higher than for those without cardiac tamponade. Evaluable D-dimer values were higher than 0.5 μg/mL in all patients. Significantly elevated laboratory parameters in patients with cardiac tamponade included: lactate dehydrogenase, aspartate aminotransferase, C-reactive protein, lactate, BNP, and hs-cTnI. However, multivariate analysis showed only hs-cTnI was significantly associated with cardiac tamponade. Histological examination revealed numerous M2-like macrophages infiltrating the myocardium and dissecting aorta, expressing CC chemokine ligand (CCL)2 together with vascular endothelial growth factor-C and matrix metalloproteinase-9. The peripheral monocyte-to-neutrophil ratio (MNR) was also significantly higher in cardiac tamponade., Conclusions: In ATAAD patients with cardiac tamponade, hs-cTnI was significantly elevated and CCL2 expression was observed, which may be involved in the expression of M2-like macrophages via an increased MNR., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Tumor-associated macrophages in the tumor microenvironment (TME), as a factor affecting lymphocytes, have received much attention. Both lymphocytes and macrophages can switch the expression of histamine receptors. In this study, we investigated the role of histamine in the TME of tongue squamous cell carcinoma (SCC)., Methods: Sixty-seven patients with stage I tongue SCC were studied. Histamine was evaluated by the expression of L-histidine decarboxylase (HDC). Macrophages, T lymphocytes, and lymph vessel density, as well as the Ki-67 labeling index (LI) and depth of invasion (DOI), were compared with HDC expression., Results: HDC expression was significantly affected by the TME. The DOI, worst pattern of invasion, and Ki-67 LI were associated with histamine expression. C-C motif chemokine ligand (CCL) 2 and CCL22 were co-expressed with histamine H1 and H2 receptors. Histamine expression was most affected by the DOI., Conclusions: Tongue SCC expressing histamine affected the TME via histamine receptors and chemokines., (© 2022 Wiley Periodicals LLC.)

Background: Salvage surgery following definitive radiotherapy or systemic treatment has become a feasible treatment option in selected patients with advanced initially unresectable non-small cell lung cancer. Recent clinical trials of neoadjuvant treatment have showed that surgery following immuno-chemotherapy is safely performed. Here, we present the first case of salvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced lung large cell carcinoma., Case Presentation: A 44-year male was admitted to our hospital for salvage surgery. Ten months prior to this administration, he had been diagnosed with unresectable large cell carcinoma with malignant pericardial effusion (clinical stage IVA/T3N2M1A; no driver-gene alteration) originating from the right upper lobe (RUL). Due to rapid intrabronchial tumor growth causing severe dyspnea, emergency bronchial stenting in the right main bronchus using an expandable metallic stent had been performed. Thereafter, he had received immuno-chemotherapy with concurrent definitive radiotherapy. Despite dramatic radiographic response, he had suffered from persistent and refractory Pseudomonas aeruginosa lung infection associated with bronchial stent placement. As pericardial effusion had disappeared and no distant metastasis had developed, he was diagnosed with a potentially curable disease and was referred to our hospital. An extended sleeve resection was successfully performed, and pathological sections revealed that pathologic complete response was achieved with immuno-chemo-radiotherapy. The patient received no subsequent treatment, and is alive without tumor recurrence at 8 months after surgery., Conclusions: Salvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced non-small cell lung cancer may be feasible in selected patients, and may be considered as a treatment option to control local disease., (© 2022. The Author(s).)

Background: The clinicopathological characteristics and prognostic factors in nodal peripheral T-cell lymphomas (PTCLs) with two or more T follicular helper markers (TFH+) are not adequately investigated., Methods: Immunohistologically, we selected 22 patients with TFH+ lymphoma (PTCL-TFH) in 47 of PTCL-not otherwise specified (NOS), and subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH+ PTCLs., Results: Thirteen large cell and nine small cell PTCL-TFH patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell PTCL-TFH showed frequent CMYC expression in 10 patients (77%), and four of 11 large cell group (36%) had somatic RHOA G17V gene mutation by Sanger sequencing. Large cell PTCL-TFH patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). In TFH+ PTCLs, CMYC+ tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1+ non-neoplastic cells (high PD-L1+ cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC+ or PD-1+ tumour cells and high PD-L1+ cell group indicated significantly poor prognosis (p < 0.01)., Conclusion: Large cell PTCL-TFH indicated poor prognosis in TFH+ PTCLs. These data suggested that CMYC+ tumour cells and intense PD-L1+ cell reaction influenced tumour cell progression in TFH+ PTCLs, and PD-1+ tumour cell/intense PD-L1+ cell reactions may play a role in immune evasion., (© 2021. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

The induction of an anti-cancer immune responses is potentially associated with the efficacy of anti-cancer therapy. Recent studies have indicated that sinus macrophages in regional lymph nodes are involved in anti-cancer immune responses in the cancer microenvironment. In the present study, we investigated the correlation between lymphocyte infiltration in cancer tissues and macrophage activation in regional lymph nodes. We retrospectively identified 294 patients with gastric cancer who underwent surgery from 2008 to 2012. Using immunohistochemistry, we evaluated CD169-expression on CD68-positive macrophages, and the density of CD8-postive lymphocytes in tumor microenvironment. We statistically examined the correlation between CD169 and CD8 expression, and performed Cox regression analysis of potential prognostic factors, including CD169 and CD8 expression, for cancer-specific survival (CSS) in patients with total and advanced gastric cancer. CD169 overexpression in lymph node sinus macrophages (LySMs) was positively correlated to the density of CD8-positive lymphocytes in primary cancer tissues (R = 0.367, p < 0.001). A high density of CD8-positive T lymphocytes in the primary site and a high level of CD169 expression in LySMs were independently associated with greater CSS in patients with total and advanced gastric cancer ( p < 0.05 for all). The expression on CD169 in LySMs is a predictor of a favorable clinical course in patients with gastric cancer, and might be useful for evaluating anti-cancer immune responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kumamoto, Tasaki, Ohnishi, Shibata, Shimajiri, Harada, Komohara and Nakayama.)

Purpose: To correlate peritumoral fat content using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with histologic prognostic factors in breast carcinoma., Materials and Methods: This study consisted of 100 patients who were diagnosed with invasive carcinoma of breast and underwent breast MRI including IDEAL before surgery. The scan time of IDEAL fat fraction (FF) map imaging was 33 s. Four regions of interests (ROIs), which are a distance of 5 mm from the tumor edge, and one ROI in the mammary fat of the healthy side were set on the FF map. Then average peritumoral FF values (FFt), average FF values in the healthy side (FFh), and peritumoral fat ratio (pTFR: defined as FFt/FFh) were calculated. Histologically, the presence of lymph node metastasis and the MIB-1 index were evaluated., Results: FFt and pTFR for breast carcinoma with lymph node metastasis (79.27 ± 10.36 and 0.897 ± 0.078) were significantly lower than those without (86.23 ± 4.53 and 0.945 ± 0.032) (P < 0.001 and P = 0.005). Spearman rank correlation suggested that the FFt correlated with the MIB-1 index (r = -340, P = 0.001)., Conclusion: Quantification of peritumoral fat using IDEAL-iron quantification is associated with the histologic prognostic factors, and may be a practical tool for therapeutic strategy of breast carcinoma.

Hemochromatosis is a clinical syndrome characterized by iron overload in various organs. We present here a case of type 4 hereditary hemochromatosis due to heterozygous mutation in SLC40A1 gene (p.D157A). SLC40A1 encodes ferroportin, a macromolecule only known as iron exporter from mammalian cells. He first presented symptoms correlated with hypopituitarism. Furthermore, marked hyperferritinemia and high transferrin saturation were revealed in combination with the findings of iron overload in the liver, spleen and pituitary gland by computed tomography and magnetic resonance imaging. Liver biopsy revealed iron deposition in both hepatocytes and Kupffer cells. SLC40A1 mutations are considered to cause wide heterogeneity by various ferroportin mutations. Thus, clinicopathological examinations seem to be very important for diagnosing phenotype of type 4 hemochromatosis in addition to the gene analysis. We diagnosed him as type 4B hereditary hemochromatosis (ferroportin-associated hemochromatosis) by the findings of high transferrin saturation and iron deposition in hepatocytes, and then started iron chelating treatment. We should suspect the possibility of hereditary hemochromatosis even in Japanese with severe iron overload. Although the same mutation in SLC40A1 gene (p.D157A) had been reported to cause "loss of function" phenotype, we considered that the mutation of our case caused "gain of function" phenotype.

Actinomycosis is an infection caused by anaerobic bacteria, primarily from the genus Actinomyces, which normally colonize the several regions including the mouth. Disruption of mucosa may lead to infection of virtually any site, but reports of involvement of the sinuses are rare. We report a case of an actinomycosis infection in the unilateral maxillary sinus. A 47-year-old female visited our hospital with a complaint of mild pain of left buccal region. Computed tomography (CT) revealed that the left maxillary and anterior ethmoidal sinus cavities were opacified along with a calcified fragment located close to the natural ostium. Thus, we provisionally diagnosed as a fungal sinusitis. She underwent trans-nasal endoscopic sinus surgery. The sinuses were opened and the caseous material was removed. The histopathological examination suggested an actinomycosis, but not fungal, infection. The patient's postoperative course was uneventful. No evidence of recurrence has been seen over the 30 months of the postoperative follow-up period. In case of the aggressive actinomycotic sinusitis, extension into the adjacent organs could be occurred. We should be aware that sinusitis of actinomycosis infection could progress in patients with risk factors such as diabetes and immunodeficiency. J. Med. Invest. 68 : 202-204, February, 2021.

A 75-year-old-man experienced liver dysfunction and was diagnosed with decompensated liver cirrhosis. His serum hepatocyte growth factor (HGF) was very high (16.24 ng/ml). Because the etiology was unclear, we considered the possibility of amyloidosis. Biopsy of the mucosa of the stomach, duodenum and rectum demonstrated amyloid deposition. From the findings of Congo red staining and immunohistochemical analyses, we made a diagnosis of systemic amyloid light-chain amyloidosis. Unfortunately, the patient died one month after the diagnosis. We considered that serum HGF was useful for the diagnosis and prediction of prognosis of primary systemic amyloidosis.

Purpose: This study aims to investigate hippocampal subfield volumes in patients with hippocampal sclerosis (HS) without visually detectable MRI abnormalities and to determine the diagnostic accuracy using hippocampal subfield volumes., Materials and Methods: We examined 46 patients with unilateral HS who had a histopathological diagnosis, and 54 controls. The patients were divided into two groups; visually detectable HS (n = 26) and undetectable HS (n = 20) on MRI. The volumes of hippocampal subfield using FreeSurfer were compared among the three groups. Diagnostic accuracy was calculated as the AUC of ROC using cutoff values for each individual subfield., Results: Compared with the controls, visually detectable HS showed significantly reduced volumes of all the hippocampal subfields and entire hippocampus, whereas visually undetectable HS showed significant atrophy only in the CA3 and hippocampus-amygdala-transition-area. To diagnose visually undetectable HS, the CA3 volumes had AUC of 0.719, which was higher than AUC of 0.614 based on the entire hippocampal volumes., Conclusion: Visually undetectable HS demonstrated volume reductions in the CA3. Further, the CA3 volumes was more useful to diagnose visually undetectable HS compared with the entire hippocampal volumes.

We established a quantitative detection method for immunohistochemistry based on a reference standard light-emitting diode, protein microarray and antibody-fused bioluminescent protein. In this procedure, we calibrated the bioluminescence imaging system and prepared the calibration curve between antigen and antibody-fused bioluminescent protein using a protein microarray. Then we converted the detecting light signal to antigen count via absolute photon number in the bioluminescent images; there was a resulting threefold difference in the target antigen number between normal and cancerous tissues. Our technique can easily compare immunohistological images and evaluate tumor progression in quantitative pathological diagnosis.

Background: Aortic dilatation may occur in some patients even after complete repair of tetralogy of Fallot (TOF). The progression rate of the aortic diameter is so slow, and the incidence of aortic dissection is so low that it is suspected that frequent imaging of the aorta may not be necessary., Case Presentation: We describe an asymptomatic 41-year-old man with hypertension in whom aortic dilatation was accidentally discovered 39 years after TOF repair. He underwent ambulatory follow-up without any difficulty for 21 years after the repair. Contrast-enhanced computed tomography revealed significant aortic dilatation (maximum diameter of 88 mm at the sinus of Valsalva), and echocardiography revealed severe aortic regurgitation, which seemed to progress during the last 18 years without any evaluation or follow-up. The Bentall procedure was successfully performed using a valved graft, under deep hypothermic circulatory arrest with antegrade cerebral perfusion, and his postoperative course was uneventful. Histopathological examination of ascending aorta specimens revealed severe cystic medial degeneration., Conclusions: Keeping in mind that a patient with rapid progression of the aortic dilatation after TOF repair exist, periodic follow-up for evaluation of the aorta is essential in patients with TOF.

Heterotopic gastric mucosa in the duodenal bulb is a rare congenital disorder with varied clinical presentations. The mechanism of formation of a duodenal ulcer is failure of balance of the attack factor and the defense factor, which is the same as the mechanism of formation of a gastric ulcer. However, the true etiology of the duodenal ulcer remains unknown. Gastric mucosa can secrete gastric juice which injures itself, but the duodenal mucosa does not contain cells secreting a digestive enzyme. We assume that duodenal ulcers are caused by the presence of heterotopic gastric mucosa that can secrete gastric acid. This study was designed to assess the prevalence and associations of heterotopic gastric mucosa in duodenal ulcers. The present study included 137 patients who underwent biopsy or resection of duodenal ulcer. We detected gastric foveolar metaplasia due to inflammation from a heterotopic gastric mucosa using immunohistochemical staining. Heterotopic gastric mucosa consists of foveolar epithelium (MUC5AC-positive) and fundic gland (H⁺K⁺ ATPase-positive parietal cells, pepsinogen I-positive chief cells and MUC6-positive mucous neck cells), whereas gastric metaplasia is composed of foveolar epithelium without fundic glands. These specimens were stained with toluidine blue for detection of Helicobacter pylori infection. Among the 137 patients with duodenal ulcer, 76 cases (55%) had heterotopic gastric mucosa in the obtained specimens, and Helicobacter pylori was found in 45 cases (59%,45/76) among those with heterotopic gastric mucosa. Our results suggest that heterotopic gastric mucosa was strongly associated with concurrent duodenal ulcer.

Background: Metastatic brain tumors and glioblastomas are the 2 of the most common brain neoplasms in adults. However, distinguishing solitary metastatic brain tumors from glioblastomas on conventional magnetic resonance imaging remains particularly challenging. Thus, we aimed to retrospectively assess the role of contrast-enhanced fast imaging employing steady-state acquisition (CE-FIESTA) imaging in distinguishing between metastatic brain tumors and glioblastomas., Materials and Methods: Forty-three patients with metastatic brain tumors and 14 patients with glioblastomas underwent conventional magnetic resonance imaging and CE-FIESTA before surgery. First, 1 neuroradiologist and 1 neurosurgeon classified the CE-FIESTA findings for the peritumoral brain parenchyma by consensus. Next, the 2 neuroradiologists performed an observer performance study comparing tumor shape classification (smooth or irregular margins), a classic imaging finding, with the CE-FIESTA classification of the peritumoral brain parenchyma., Results: The CE-FIESTA findings for the peritumoral brain parenchyma were classified as follows: type A, no hyperintense rim; type B, partial hyperintense rim; and type C, extended hyperintense rim. With regard to the diagnosis of metastatic brain tumors, the observer performance study demonstrated that the mean sensitivity, specificity, and accuracy of an extended hyperintense rim classification (type C) on CE-FIESTA images were 95.3%, 85.7%, and 93.0%, respectively. The accuracy of the CE-FIESTA classification was significantly higher than that of the tumor shape classification., Conclusions: CE-FIESTA images may provide useful information for distinguishing metastatic brain tumors from glioblastomas, especially when focusing on differences in the peritumoral brain parenchyma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Pulmonary neuroendocrine tumor (NET) occurs with 20% of all lung cancers, and there are a limited number of literatures about the molecular aberrations, treatment and prognosis; especially in resected cases, as the operation indication for large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is rare due to their aggressive behaviors. We investigated the relationship between postoperative survival and molecular expression patterns of pulmonary NET to establish a more effective treatment strategy., Methods: In the present study, the curative surgical resection of pulmonary NET was reviewed retrospectively. A total of 105 patients with pulmonary NET, who underwent complete resection between 1978 and 2016, were subjected to analysis with respect to histological characterization and clinical behaviors of pulmonary NET using immunohistochemistry (IHC) of neuroendocrine markers and programmed cell death-ligand 1 (PD-L1)., Results: The pathological types included 67 SCLC, 18 LCNEC, 14 typical carcinoids (TCs) and 6 atypical carcinoids (ACs). The ACs had significantly worse prognosis than TCs. PD-L1 expression ratio in SCLC/LCNEC/TC/AC was 26.1%/50%/15.4%/20%, respectively. However, it was not significantly correlated with each prognosis. Therefore, the SCLC patients were analyzed, the overall 5-year survival of SCLC patients was found to be 47.3%. In the univariate analysis of the molecular expression of SCLC, neuroendocrine markers such as chromogranin-A (CGA) and synaptophysin (SYN) showed poor prognosis, albeit without significant differences., Conclusions: The neuroendocrine markers such as CGA and SYN might assist the prediction of prognosis and probably influence the decision for adjuvant chemotherapy or follow-up intervals after surgery in SCLC patients; however additional studies are essential., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Aims: Nephrotic syndrome (NS) is a major manifestation of lupus nephritis (LN). The dysregulation of podocytes, the glomerular basement membrane (GBM) and endothelial cells (ECs) results in proteinuria in glomerular diseases. The aim of our study was to clarify whether the dysregulation of these barriers is associated with NS in proliferative LN and membranous LN., Methods and Results: Fifty-six patients with NS, including minimal change NS in 15, primary membranous nephropathy (PMN) in 13, class III/IV LN in 15, and class V LN in 13, were enrolled in this study. Subjects with idiopathic haematuria were assigned as controls. Glomerular expression of Wilms tumour protein 1 (WT1), nephrin, synaptopodin and podocalyxin was evaluated by immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction. EC injury was evaluated by CD31 immunostaining and electron microscopy (EM). Reduced expression of WT1, nephrin and synaptopodin was found in PMN, class III/IV LN and class V LN as compared with controls by IHC and mRNA analysis. Reduced expression of these molecules was not different between class III/IV LN and class V LN. Reduced numbers of CD31-positive ECs were found in class III/IV LN as compared with class V LN. EC injury showing subendothelial widening on EM was apparent in class III/IV LN as compared with class V LN. Foot process effacement was found only along the GBM showing EC injury in class III/IV LN., Conclusions: Our study suggests that coexistence of podocyte and EC injury may lead to NS in proliferative LN. Podocyte damage alone leads to NS in membranous LN., (© 2017 John Wiley & Sons Ltd.)

Background and Objectives: Pulmonary pleomorphic carcinoma (PPC) is a rare and aggressive subtype of lung cancer. Programmed cell death-ligand 1 (PD-L1) expression may be induced in a variety of malignant tumors, but its prognostic implication in PPC remains unclear., Methods: Twenty-six patients with surgically resected PPC were retrospectively reviewed. Immuno-histochemical staining was used to detect PD-L1 expression, and PD-L1 status was classified into "high" or "low" according to the percentage of tumor cells (TCs) expressing PD-L1 (tumor proportion score, TPS)., Results: PD-L1 expression was positive in 20 (76.9%) patients at the cut-off TPS value of 1%. A receiver-operating characteristic (ROC) analysis showed that the optimal cut-off value was 15% for prediction of cancer-specific death with the area under ROC curve of 0.701 (P = 0.107). High PD-L1 expression was associated with a favorable overall survival (88.9% vs 37.5% at 5 years; P =.046) as well as a favorable cancer-specific (100% vs 45.9% at 5 years; P =.012). A multivariate analysis indicated a trend toward a favorable prognosis associated with high PD-L1 expression (hazard ratio [HR], 0.254 [95% confidence interval, 0.054-1.200]; P = 0.084)., Conclusions: PD-L1 expression was positive in most PPC cases, and high PD-L1 expression may predict a favorable prognosis in resected PPC., (© 2018 Wiley Periodicals, Inc.)

Objective: The study objective was to investigate the prognostic impact of programmed death-ligand 1 expression in correlation with human leukocyte antigen class I expression on tumor cells in early-stage adenocarcinoma of the lung, because both programmed death-ligand 1 and human leukocyte antigen class I molecules play important roles in cancer immunity., Methods: Ninety-four patients with completely resected pathologic stage I lung adenocarcinoma were retrospectively reviewed. Programmed death-ligand 1 expression on tumor cells was evaluated with immunohistochemistry in correlation with several clinicopathologic and molecular features, including human leukocyte antigen class I expression on tumor cells., Results: Fifteen patients (16.0%) had tumor with positive programmed death-ligand 1 expression (percentage of tumor cells expressing programmed death-ligand 1, ≥5%), and the incidence was significantly higher in poorly differentiated tumors. There was no significant correlation between human leukocyte antigen class I expression and programmed death-ligand 1 expression. Programmed death-ligand 1 positivity was a significant factor to predict a poor survival (5-year survival, 66.7% vs 85.9%; P = .049), which was enhanced in tumors with normal human leukocyte antigen class I expression (P = .029) but was not evident in tumors with reduced human leukocyte antigen class I expression (P = .552)., Conclusions: The prognostic impact of programmed death-ligand 1 expression on tumor cells in early-stage lung adenocarcinoma may be distinct according to concurrent human leukocyte antigen class I expression., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To correlate the R2* value obtained by iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL) with fibrotic focus (FF), microvessel density and hypoxic biomarker (HIF-1α) in breast carcinoma., Methods: Forty-two patients who were diagnosed with invasive ductal carcinoma (IDC) of the breast underwent breast MRI including IDEAL before surgery. The entire region of interest (ROI) was delineated on the R2* map, and average tumour R2* value was calculated for each ROI. Histological specimens were evaluated for the presence of FF, the microvessel density (the average microvessel density and the ratio of peripheral to central microvessel density), and the grading of HIF-1α., Results: FF was identified in 47.6% (20/42) of IDCs. Average R2* value for IDC with FF (42.4±13.2 Hz) was significantly higher than that without FF (28.5±13.9 Hz) (P = 0.01). Spearman rank correlation suggested that the average R2* value correlated with the grade of HIF-1α and the ratio of peripheral to central microvessel density for IDCs (P < 0.001)., Conclusion: Quantification of tumour R2* using IDEAL is associated with the presence of FF and the overexpression of HIF-1α, and may therefore be useful in predicting hypoxia of breast carcinoma., Key Points: • R2* value obtained by IDEAL correlates with the overexpression of HIF-1α. • R2* value obtained by IDEAL is associated with fibrotic focus. • R2* quantification may be useful in predicting hypoxia of breast carcinoma.

Background: We actually investigated the surgical and pathological findings in cases which tumor invasion of the major thoracic vessels was suspected based on the preoperative Computed tomography (CT) findings., Materials and Methods: We retrospectively reviewed our prospective database of all patients, who underwent lung resection for lung cancer from 2012 to 2014. 387 patients underwent lung cancer surgery. Among these patients, we analyzed 30 patients in whom pulmonary artery (PA) invasion was suspected and 11 patients in whom pulmonary vein (PV) or left atrium (LA) invasion was suspected based on the preoperative CT findings., Results: Among the 30 patients with suspected PA invasion, there were 9 patients in whom the tumor could be peeled off the PA in actual thoracotomy. Pathological invasion of the PA was observed in 6 of these patients. The positive predictive value of the preoperative CT findings was 20%. Among the 11 patients with suspected PV or LA invasion, there were 2 patients in whom the tumor could be peeled off the PV or LA in actual thoracotomy. Pathological tumor invasion of the PV or LA was observed in 4 of these patients. The positive predictive value of the preoperative CT findings was 36%., Conclusion: The positive predictive value of the preoperative CT findings for tumor invasion of the thoracic vessels was low. Therefore, surgical opportunities that offer the chance of a cure shouldn't be missed in advanced lung cancer patients because the tumor is located near the major thoracic vessels on preoperative CT.

We demonstrated an extremely unusual case of an 83-year-old male's sudden death secondary to characteristic myocardial necrosis and fibrosis with calcification and multinucleated giant cells infiltration, possibly due to sepsis and Stage IV pulmonary pleomorphic carcinoma-induced cachexia after postmortem study. We propose that this calcifying giant cell cardiomyopathy (CGC) would be a new entity especially from the pathological viewpoints and should be considered in the classification of noninfectious myocarditis. Further prospective studies are needed to validate the presence and significance of CGC and the association with any triggers of somewhat microvascular dysfunction and/or toxic agents, after collecting and investigating a larger number of CGC cases examined., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In patients with diffuse lung diseases, differentiating occupational lung diseases from other diseases is clinically important. However, the value of assessing asbestos and particles in bronchoalveolar lavage fluid (BALF) in diffuse lung diseases by electron microscopy (EM) remains unclear. We evaluated the utility of EM in detecting asbestos fibers and particles in patients with diffuse lung diseases., Methods: The BALF specimens of 107 patients with diffuse lung diseases were evaluated. First, detection of asbestos by EM and light microscopy (LM) were compared. Second, the detection of asbestos using surgically obtained lung tissues of 8 of 107 patients were compared with the results of EM and LM in BALF. Third, we compared the results of mineralogical components of particles in patients with (n = 48) and without (n = 59) a history of occupational exposure to inorganic dust., Results: BALF asbestos were detected in 11 of 48 patients with a history of occupational exposure by EM; whereas asbestos as asbestos bodies (ABs) were detected in BALF in 4 of these 11 patients by LM. Eight of 107 patients in whom lung tissue samples were surgically obtained, EM detected BALF asbestos at a level of >1,000 fibers/ml in all three patients who had ABs in lung tissue samples by LM at a level of >1,000 fibers/g. The BALF asbestos concentration by EM and in lung tissue by LM were positively correlated. The particle fractions of iron and phosphorus were increased in patients with a history of occupational exposure and both correlated with a history of occupational exposure by a multiple regression analysis., Conclusions: EM using BALF seemed to be superior to LM using BALF and displayed a similar sensitivity to LM using surgically-obtained lung tissue samples in the detection of asbestos. Our results also suggest that detection of elements, such as iron and phosphorus in particles, is useful for evaluating occupational exposure. We conclude that the detection of asbestos and iron and phosphorus in particles in BALF by EM is very useful for the evaluation of occupational exposure.

Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells. In addition, fluorescence-guided resection with 5-ALA is widely used for imaging HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble. It was speculated whether converting from 5-ALA to PpIX may relatively increase intracellular water content, and consequently, might enhance the T2 signal intensity in HGG. The aim of the present study was to assess whether 5-ALA-induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4 patients who were candidates for HGG surgical treatment were prospectively analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg) 3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via fluorescence using a modified operating microscope. Fluorescent tumor tissues were obtained to analyze the accumulation of 5-ALA-induced PpIX within the tumors, which was confirmed quantitatively by high-performance liquid chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was evaluated prior to and following 5-ALA administration. Three glioblastoma multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA-induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared with the AO sample. In total, 48 regions of interest were identified within the tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value within the tumors following 5-ALA administration was significantly increased compared with the T2 signal intensity value prior to 5-ALA administration (1.537±0.021 and 1.577±0.023, respectively; P=0.0055). No significant differences were observed in the AO group. These results suggest that the 5-ALA-induced PpIX enhanced the T2 signal intensity in HGG. Therefore, 5-ALA may be a potentially useful MRI contrast reagent for HGG.

Background: An intracranial neurenteric cyst (NC) is a rare congenital benign lesion that usually has a well-demarcated cystic appearance without contrast enhancement on magnetic resonance imaging (MRI). In particular, an intracranial NC with an enhanced mural nodule is extremely rare., Case Description: A 20-year-old man presented with left-sided hearing disturbance and headache. On MRI, a cystic mass was seen in the prepontine cistern that significantly compressed the brainstem. The lesion was hyperintense on T1-weighted images, and contained a solid component that appeared with marked hypointensity on T2*-weighted images and slight enhancement. The cystic wall was removed via a left transcondylar fossa approach. Histopathologic findings showed an NC with a solid component and melanin pigmentation. The solid component showed xanthogranulomatous changes, with evidence of an old hemorrhage, and was strongly adherent to the brainstem., Conclusions: We present this rare case and emphasize that an NC should be considered in the differential diagnosis of intracranial cystic lesions with an enhanced mural nodule., (Copyright © 2016 Elsevier Inc. All rights reserved.)

An 85-year-old male presented with 1-year history of a right breast mass. Needle biopsy of the mass revealed diffuse proliferation of large lymphoid cells that were positive for CD20, BCL2, BCL6, and MUM1 and negative for CD5, CD10, MYC, and EBER. The patient was diagnosed as having diffuse large B-cell lymphoma, a type of primary breast lymphoma (PBL). Sex hormone imbalance, which causes conditions such as gynecomastia, is associated with PBL development in males. Estramustine is a nitrogen mustard moiety linked to estradiol. For 5 years, the patient underwent estramustine therapy for treating prostate cancer. Our case suggests an important role of estrogen in PBL development.