Clonal identity and differences in primary cutaneous B-cell lymphoma occurring at different sites or time points in the same patient.

Primary cutaneous B-cell lymphomas (PCBCL) are rare. Marginal zone lymphomas and follicle center lymphomas (FCL) represent a majority of these cases, and a significant number of cases present with multiple lesions. It is unclear whether multiple lesions in PCBCL represent dissemination of a single clone or multiple new primary lymphomas. In the current study, we analyzed paired samples from 20 PCBCL patients at more than 1 site (16) or at the same site at different time points (4) and 12 patients with benign lymphoid infiltrates to investigate for the presence or absence of a clone, and if present, whether the clones were identical. Both IGH@ and IGK@ rearrangements were tested using the BIOMED-2 protocol. We identified a clone (IGH@ and/or IGK@) in 19 of 20 (95%) PCBCL patients and 2 of 12 (17%) benign lymphoid infiltrate patients. The B-cell clones were proven to be identical in 11 of 20 (55%) PCBCL patients, including 7 of 16(44%) biopsies from patients with 2 different sites and 4 of 4 biopsies (100%) from patients at the same site but different time points. In 4 cases (3 FCL and 1 marginal zone lymphoma), different clones were detected at different sites, suggesting the possibility of a second simultaneous primary lymphoma. Our results indicate that the presence of identical clones is highly suggestive of lymphoma. To our knowledge, this is the first report to investigate the detection of identical clones in 2 distinct biopsies in PCBCL patients. Although the study is small and the results need to be confirmed in a larger study, these findings suggest that a subset of PCBCL at different sites may represent different primary tumors rather than occurrence of a single disease.

Cardiac and vascular point-of-care ultrasound: current situation, problems, and future prospects.

Although clinical application of ultrasound to the heart has a history of about 80 years, its big turning point was the emergence of a portable ultrasound diagnostic machine. As a result, the place, where echocardiography is performed widely spread outside the examination room, and the people who perform echocardiography have also greatly increased. Emergency physicians, anesthesiologists, and primary care physicians became interested in echocardiography and started using it. Such ultrasound examinations performed by a doctor for assessment of disease condition, management, or guidance of treatment at bedside has been called point-of-care ultrasound (POCUS). Cardiac POCUS is divided into a focused cardiac ultrasound examination (FoCUS) and limited echocardiography. The former is performed by non-experts in echocardiography, such as emergency physicians and anesthesiologists, whereas the latter is usually performed by cardiologists who are experts in echocardiography. FoCUS has an established protocol and evaluation method, and evidence to prove its effectiveness is accumulating. In addition, the COVID-19 outbreak reaffirmed the importance of POCUS. Although FoCUS is becoming popular in Japan, an educational program has not been established, and discussion on how to educate medical students and residents will be necessary. Even if POCUS in cardiovascular medicine becomes widespread, auscultation will still be necessary. Rather, adding cardiac and vascular POCUS to inspection, palpation, and auscultation in the flow of physical examinations will benefit patients greatly.

Quantification of Carotid Plaque Histology Using iPlaque Software.

The iPlaque software package can use integrated backscatter (IB) values of carotid plaque to extract information on tissue composition. The aim of this study was to evaluate the association between the plaque histologic classification and IB values evaluated by iPlaque. In 49 patients undergoing carotid endarterectomy, IB values of whole carotid plaque were measured using iPlaque from the long-axis ultrasonographic image. Histologic findings of resected plaques were defined using the classification of the American Heart Association. The average IB values were statistically compared with the classification. Plaque samples from 49 patients were categorized into V, VI and VII, (13, 32 and 4 cases, respectively). Both the average and standard deviation of the IB values in each plaque sample significantly differed among the three classifications (p = 0.001). The IB of carotid plaque obtained by iPlaque analysis was associated with its histologic characteristics.

PAX8 discriminates ovarian metastases from adnexal tumors and other cutaneous metastases.

BACKGROUND: The distinction of metastatic ovarian carcinoma from other metastatic carcinomas and primary adnexal lesions in the skin is often difficult. PAX8 is a transcription factor that plays a critical role in development of the Müllerian system and has been shown to be a useful discriminatory marker between ovarian and breast carcinomas. Identification of ovarian cutaneous metastases may be of benefit in patients with familial breast-ovarian carcinoma syndrome. METHODS: PAX8 immunohistochemical analysis was performed on 24 cases of metastatic adenocarcinomas to the skin and compared with 7 cases of primary adnexal lesions and also compared with p63 immunohistochemical staining results. Patients with metastatic adenocarcinomas had clinically documented primary malignancies, and patients with primary adnexal carcinomas had no known history of another adenocarcinoma. RESULTS: Cutaneous ovarian and renal cell carcinoma metastases (2/2 and 8/8, respectively) showed positive nuclear expression of PAX8. PAX8 immunohistochemical staining in primary adnexal and other cutaneous metastases was completely negative (0/7 and 0/16, respectively). The p63 expression profile supported the distinction between adnexal and metastatic adenocarcinomas. CONCLUSIONS: Although cutaneous ovarian metastasis is a rare phenomenon, the prognosis is extremely poor. PAX8 expression is a useful marker that effectively discriminated metastatic ovarian carcinomas from metastatic breast carcinomas and primary adnexal tumors.

Cardiogenic cerebral embolism caused by a severe hypoglycemic attack†:†a case report.

The direct relationship between a hypoglycemic attack and cerebral infarction remains unknown. It has been reported that a hypoglycemic attack can result in takotsubo syndrome, leading to cerebral infarction. We report a case of a cardiogenic cerebral embolism caused by a hypoglycemic attack, with additional literature review. A 71-year-old woman was admitted to our hospital in a semi-comatose state due to a severe hypoglycemic attack ; she developed hemiplegia one day after admission. Magnetic resonance imaging revealed cerebral infarction in the area supplied by the left middle cerebral artery. Takotsubo syndrome was suspected based on echocardiography. We diagnosed cerebral embolism due to takotsubo syndrome, caused by the hypoglycemic attack. J. Med. Invest. 67 : 362-364, August, 2020.

Deterioration of biventricular strain is an early marker of cardiac involvement in confirmed sarcoidosis.

AIMS: Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients. METHODS AND RESULTS: LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: -18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001). CONCLUSION: Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.

Molecular organization of 5S rDNA in bitterlings (Cyprinidae).

Molecular organization and nucleotide sequences of the 5S rRNA gene and NTS were investigated in freshwater fish, bitterlings (Acheilognathinae), including 10 species/subspecies of four genera, Acheilognathus, Pseudoperilampus, Rhodeus, and Tanakia, to understand the evolutionary trait of 5S rDNA arrays. Southern hybridization analysis revealed a general trend with tandem repeats of 5S rDNA in all the examined bitterlings. Sequence analysis demonstrated a conserved 120 bp sequence of the 5S rRNA gene and a short NTS of 56-67 bp with two distinct portions, a conserved (5'-flanking portion; at positions -1 to -38) and a variable part (3'-flanking portion), in 6 of 10 species/subspecies examined. The conserved NTS region was most likely an external promoter so far observed in various vertebrates, whereas the variable NTS region could be divided into two types due to its nucleotide polymorphisms. Molecular phylogeny using the 5S rRNA gene and NTS sequences suggested the occurrence of 5S rDNA duplication before speciation and a concerted evolution for the gene and conserved NTS regions, but a birth-and-death process to maintain the variable NTS region. Thus, the 5S rDNA in the examined bitterlings might have evolved under a mixed process of evolution.

Development, progression, and regression of microalbuminuria in Japanese patients with type 2 diabetes under tight glycemic and blood pressure control: the Kashiwa study.

OBJECTIVE: The goal of this study was to know the fate of albuminuria in Japanese patients with type 2 diabetes under tight blood pressure and glycemic control. RESEARCH DESIGN AND METHODS: Patients having normoalbuminuria (urinary albumin excretion <30 mg/g creatinine, n = 179) or microalbuminuria (albumin excretion 30-299 mg/g creatinine, n = 94) at baseline have been followed up for 8 years: ratio of men to women was 160/113, the mean age was 58 years, pretreatment HbA(1c) (A1C) was 8.8%, and blood pressure was 136/76 mmHg. A1C <6.5% and blood pressure <130/80 mmHg were targeted, and the A1C of 6.5 +/- 0.7% (mean +/- SD) and blood pressure of 127 +/- 11/72 +/- 6 mmHg have been maintained during the 8 years. Development of microalbuminuria or macroalbuminuria (albumin excretion > or =300 mg/g creatinine) in initially normoalbuminuric patients and progression to macroalbuminuria or regression to normoalbuminuria in initially microalbuminuric patients were assessed at year 8. RESULTS: Development occurred in 27 (15%) of the normoalbuminuric patients and progression and regression in 16 (17%) and 20 (21%), respectively, of the microalbuminuric patients. Significant independent relationships existed between development and higher achieved mean systolic blood pressure (SBP) and regression and lower achieved mean SBP. In the patients with achieved mean SBP <120 mmHg, development was 3%, progression was 11%, and regression was 44% during 8 years. Prediction for nephropathy by blood pressure and glycemia alone was limited. Nevertheless, albumin excretion at year 8 was positively correlated with achieved mean SBP and baseline albuminuria. CONCLUSIONS: Development and progression were low and regression was high with SBP of 120 mmHg, provided A1C was maintained at 6.5%.

Arginase-1 is a more sensitive marker of hepatic differentiation than HepPar-1 and glypican-3 in fine-needle aspiration biopsies.

BACKGROUND: Distinguishing hepatocellular carcinoma (HCC) from adenocarcinoma in fine-needle aspiration biopsies (FNAB) is often diagnostically challenging. Arginase-1 was recently described as a marker of hepatic differentiation in surgical resection specimens. We compared the expression of arginase-1, HepPar-1, and glypican-3 in FNAB of HCC and adenocarcinoma involving the liver. METHODS: Ninety-eight FNABs including 37 primary or metastatic HCCs (30 well or moderately differentiated and 7 poorly differentiated) and 61 adenocarcinomas involving the liver were evaluated for immunohistochemical expression of arginase-1, HepPar-1, and glypican-3 using formalin-fixed paraffin-embedded cell block material. RESULTS: Arginase-1 was more sensitive (81%) than HepPar-1 (70%) or glypican-3 (54%) for HCC. Arginase-1 more often demonstrated diffuse staining, defined as reactivity in >50% of the tumor, in HCC (21 of 37; 57%) compared with HepPar-1 (15 of 37; 41%) and glypican-3 (12 of 37; 32%). Of the 7 poorly differentiated HCCs, 3 (43%) were immunoreactive for both arginase-1 and glypican-3, whereas only 1 (14%) demonstrated HepPar-1 staining. Arginase-1 expression was identified in adenocarcinomas of pancreatic, colorectal, and breast origin, and reactivity was diffuse in 2 pancreatic adenocarcinomas (2 of 15; 13%). CONCLUSIONS: Arginase-1 is a more sensitive marker of hepatic differentiation than either HepPar-1 or glypican-3 in FNAB. In addition, arginase-1 exhibits more diffuse staining in HCC than either HepPar-1 or glypican-3, making interpretation easier in limited FNAB samples. Arginase-1 is not entirely specific for hepatic differentiation, as immunoreactivity can be identified in adenocarcinomas, particularly of pancreatic origin.

Prediction of BRCA1 germline mutation status in women with ovarian cancer using morphology-based criteria: identification of a BRCA1 ovarian cancer phenotype.

Specific morphologic features that may predict BRCA1 germline mutation in ovarian cancer have neither been well described nor independently tested. We identified 5 morphologic features associated with BRCA1 mutation status in a series of 20 ovarian cancers from BRCA1 mutation carriers: (1) modified Nottingham grade 3; (2) serous/undifferentiated histology; (3) prominent intraepithelial lymphocytes; (4) marked nuclear atypia with giant/bizarre forms; and (5) abundant mitotic figures. These morphologic features were then tested on 325 ovarian tumors drawn from a population-based Greater Bay Area Cancer Registry and classified into 3 categories independent of the BRCA1 status: "Compatible with BRCA1," "Possibly compatible with BRCA1," and "Not compatible with BRCA1." All "Compatible with BRCA1" tumors were additionally investigated for presence of dominant adnexal mass, fallopian tube mucosal involvement, and uterine cornu involvement. The positive and negative predictive values for "Compatible with BRCA1" were 11/42 (26.2%) and 267/283 (94.3%), respectively, whereas combining the "Compatible with BRCA1" and "Possibly compatible with BRCA1" had positive and negative predictive values of 18/85 (21.2%) and 231/240 (96.3%), respectively. Although dominant adnexal mass and uterine cornu involvement did not add further predictive value, the likelihood of BRCA1 positivity increased to 42.9% when a tumor with "Compatible with BRCA1" histology was also associated with fallopian tube mucosal involvement. The combination of modified Nottingham grade 3 serous or undifferentiated histology, prominent intraepithelial lymphocytes, marked nuclear atypia with giant/bizarre nuclei, and high mitotic index should help to identify women for BRCA1 mutational analysis in the appropriate clinical setting. Ovarian tumors lacking this specific phenotype are unlikely to be associated with BRCA1 and should not undergo mutational analysis in the absence of other indications.

Low-grade mucinous adenocarcinoma of the uterine corpus: a rare and deceptively bland form of endometrial carcinoma.

Uterine corpus mucinous epithelial proliferations present diagnostic challenges due to histologic similarities to cervical lesions. We present a rare but distinctive endocervical-like mucinous carcinoma of the uterine corpus resembling adenoma malignum of the cervix that can be mistaken for a benign endometrial process. The clinical-pathologic features of 16 endometrial carcinomas exhibiting a pure endocervical-like mucinous proliferation were evaluated. Hysterectomy and available prehysterectomy specimens were assessed for architectural complexity, nuclear pleomorphism, macronucleoli, nuclear pseudostratification, mitotic index, necrosis, prominent neutrophils, and voluminous extracellular mucin (mucin encompassing >50% of a ×40 field). Cases involving the cervix or lower uterine segment were confirmed as endometrial in origin based on immunohistochemical stains (estrogen receptor, progesterone receptor, p16, and vimentin). Patient age ranged from 45 to 70 years; 6 of 16 (38%) were premenopausal, 11 of 16 (69%) had abnormal bleeding, and 7 of 16 (44%) had a history of hormonal therapy. Prehysterectomy diagnoses were benign in 2 of 16 (13%) cases, borderline in 9 of 16 (56%) cases, and carcinoma in 5 of 16 (31%) cases, whereas 8 of 16 (50%) hysterectomy specimens showed myoinvasive adenocarcinoma. With the exception of 2 cases, architectural complexity was low-to-moderate and no specimens showed marked nuclear pleomorphism. Macronucleoli and abundant mitotic activity were absent. Nuclear pseudostratification was present in 7 of 16 (44%) cases, necrosis in 1 of 16 (6%) cases, prominent neutrophils in 7 of 16 (44%) cases, and voluminous extracellular mucin in 9 of 16 (56%) cases. Cytologically bland mucinous epithelial proliferations should be diagnosed with caution in endometrial samplings. The presence of an endocervical-like mucinous epithelial process in association with voluminous extracellular mucin should prompt consideration for a low-grade mucinous adenocarcinoma of the uterine corpus.

Rapid rehydration and moderate plasma glucose elevation by fluid containing enzymatically synthesized glycogen.

Enzymatically synthesized glycogen (ESG) has high solubility and its solution has low osmotic pressure. Therefore ESG solution could be rapidly absorbed and could be adequate for water rehydration and carbohydrate supplementation during exercise. The object of this study was to evaluate the gastric emptying time and plasma glucose elevation after an administration of ESG solution in comparison with another carbohydrate solution by using a laboratory animal. Male BALB/c mice were administered 10% w/v solution of glucose, maltodextrin, starch, naturally synthesized glycogen (NSG) and ESG at a dose of 20 µL/g body weight for the measurement of gastric emptying rate (Experiment 1) and 10 µL/g body weight for the measurement of plasma glucose elevation (Experiment 2). The osmolarity of gastric content was lower in the ESG and maltodextrin group than the other carbohydrate group. Weight of gastric fluid was significantly lower in the ESG and water group than the glucose group (p<0.01). Plasma glucose level was significantly lower in the ESG group than the glucose group from 0 to 60 min after administration (p<0.01), whereas plasma glucose level was same from 60 to 120 min for the ESG and glucose group (p=0.948). In Experiment 3, BALB/c mice ran on a treadmill for 2 h and were administered 8% of ESG or glucose solution (1.75, 3.5 or 7.0 µL/g body weight) every 20 min during running. There was no difference in post-exercise muscle glycogen level. These data suggest that 1) ESG beverage does not disturb water absorption because of its short gastric emptying time and 2) ESG slowly elevates plasma glucose level and maintains it for a prolonged time compared to the glucose solution.

Immunohistochemical distinction of primary adrenal cortical lesions from metastatic clear cell renal cell carcinoma: a study of 248 cases.

The diagnosis of metastatic clear cell renal cell carcinoma (CC-RCC) can be difficult because of its morphologic heterogeneity and the increasing use of small image-guided biopsies that yield scant diagnostic material. This is further complicated by the degree of morphologic and immunophenotypic overlap with nonrenal neoplasms and tissues, such as adrenal cortex. In this study, a detailed immunoprofile of 63 adrenal cortical lesions, which included 54 cortical neoplasms, was compared with 185 metastatic CC-RCCs using traditional [anticalretinin, CD10, antichromogranin, antiepithelial membrane antigen, anti-inhibin, antimelanA, anticytokeratins (AE1/AE3 and AE1/CAM5.2), antirenal cell carcinoma marker, and antisynaptophysin)] and novel [anticarbonic anhydrase-IX, antihepatocyte nuclear factor-1b, antihuman kidney injury molecule-1 (hKIM-1), anti-PAX-2, anti-PAX-8, antisteroidogenic factor-1 (SF-1), and anti-T-cell immunoglobulin mucin-1] antibodies. Tissue microarray methodology was used to simulate small image-guided biopsies. Staining extent and intensity were scored semiquantitatively for each antibody. In comparing different intensity thresholds required for a "positive" result, a value of ≥2+ was identified as optimal for diagnostic sensitivity/specificity. For the distinction of adrenal cortical lesions from metastatic CC-RCCs, immunoreactivity for the adrenal cortical antigens SF-1 (86% adrenal; 0% CC-RCC), calretinin (89% adrenal; 10% CC-RCC), inhibin (86% adrenal; 9% CC-RCC), and melanA (86% adrenal; 10% CC-RCC) and for the renal epithelial antigens hKIM-1 (0% adrenal; 83% CC-RCC), PAX-8 (0% adrenal; 83% CC-RCC), hepatocyte nuclear factor-1b (0% adrenal; 76% CC-RCC), epithelial membrane antigen (0% adrenal; 78% CC-RCC), and carbonic anhydrase-IX (3% adrenal; 87% CC-RCC) had the most potential use. Use of novel renal epithelial markers hKIM-1 (clone AKG7) and/or PAX-8 and the adrenocortical marker SF-1 in an immunohistochemical panel for distinguishing adrenal cortical lesions from metastatic CC-RCC offers improved diagnostic sensitivity and specificity.

Characterization of Japanese flounder karyotype by chromosome bandings and fluorescence in situ hybridization with DNA markers.

The chromosomes of Japanese flounder, Paralichthys olivaceus, were examined by conventional differential staining methods including G-, Q-, C-, silver (Ag)-, fluorochrome, and replication R-bandings and by fluorescence in situ hybridization (FISH) with 5S and 18S rDNAs and telomeric DNA as probes. Replication R-banding substantially made it possible to identify 24 homologous pairs by their RBG-banding pattern and relative length. Both rDNA loci were mapped to chromosome 1, where 5S and 18S rDNA loci were located at the centromeric region and secondary constriction, respectively. C-banding revealed that both rDNA loci were heterochromatic, and 18S rDNA loci were positive for chromomycin A(3) but negative for 4',6-diamidino-2-phenylindole (DAPI) staining. Telomeric FISH signals were observed at all chromosome ends and at the interstitial region of some chromosomes. The observed results were discussed in relation to the karyotype evolution in the order Pleuronectiformes.

Molecular profiling reveals synaptic release machinery in Merkel cells.

Merkel cell-neurite complexes are somatosensory receptors that initiate the perception of gentle touch. The role of epidermal Merkel cells within these complexes is disputed. To ask whether Merkel cells are genetically programmed to be excitable cells that may participate in touch reception, we purified Merkel cells from touch domes and used DNA microarrays to compare gene expression in Merkel cells and other epidermal cells. We identified 362 Merkel-cell-enriched transcripts, including neuronal transcription factors, presynaptic molecules, and ion-channel subunits. Antibody staining of skin sections showed that Merkel cells are immunoreactive for presynaptic proteins, including piccolo, Rab3C, vesicular glutamate transporter 2, and cholecystokinin 26-33. These data indicate that Merkel cells are poised to release glutamate and neuropeptides. Finally, by using Ca(2+) imaging, we discovered that Merkel cells have L- and P/Q-type voltage-gated Ca(2+) channels, which have been shown to trigger vesicle release at synapses. These results demonstrate that Merkel cells are excitable cells and suggest that they release neurotransmitters to shape touch sensitivity.