The cytopathological features of neuroendocrine ductal carcinoma in situ (NE-DCIS) of the breast were evaluated. We reviewed the cases of 5 patients with cytological materials diagnosed as having NE-DCIS (age 50–80, mean 70.6 years old). The characteristic cytological findings were as follows: clear bleeding in the background, mucinous materials and vessel components, abundant cell components, cell clusters that show loose intercellular adhesion, no myoepithelial components, oval- to polygonal-shaped cells with a granular cytoplasm stained light green, uneven distribution of round- to oval-shaped nuclei, dense nuclear chromatin with a fine or minute granular pattern, and one or a few small nucleoli. The tumor size was less than 10 mm in 4 patients and 25 mm in one patient. Histopathologically, the tumor was located in dilated ducts and showed solid or tubular patterns with abundant vessels and mucinous components in the stroma. Immunohistochemically, the tumor cells were positive for synaptophysin (4/5), chromogranin A (4/5), and CD56 (3/5). The average Ki-67 index of 4 patients was 8.5% (0–19.1). As the differential diagnosis for these patients was intraductal papilloma (IDP), the characteristic cytological findings mentioned above were useful for distinguishing between NE-DCIS and IDP.
In a recent report, approximately 98% of polycythemia vera patients have JAK2-V617F or JAK2 exon12 mutation. There is a genetic mutation (JAK2-V617F, MPL, or CALR mutation) in approximately 80% of essential thrombocythemia patients. Genetic mutation analysis is necessary for the diagnosis of myeloproliferative neoplasms, but, at present, such analysis can be carried out in only a few facilities. This study is a retrospective analysis of the results of peripheral blood examination of PV and ET patients and secondary polycythemia and reactive thrombocytosis. The purpose of this analysis is to predict the JAK2-V617F mutation by establishing a screening examination method. Results showed that the IPF count was significantly higher in PV and ET patients. In addition, the NAP score was significantly higher in JAK2-positive PV and ET patients. Furthermore, the results of ROC analysis, AUC of IPF count, and NAP score were more than 0.9, and these had a high capability to predict the JAK2-V617F variation. For the IPF count, the cut-off level is 10,000/μL (100% true positive rate, 16.7% false positive rate), whereas for the NAP score, the cut-off level is 250 (85.7% true positive rate, 25.0% false positive rate). We divided these patients into 4 groups, namely, A (IPF count <10,000/μL & NAP score <250), B (IPF count <10,000/μL & NAP score ≥250), C (IPF count ≥10,000/μL & NAP score <250), and D (IPF count ≥10,000/μL & NAP score ≥250). 91.7% of secondary polycythemia and reactive thrombocytosis patients were classified in group A or B; on the other hand, the true positive rate of JAK2 mutations in group D was 94.7%. These study results indicate that the IPF count and NAP score in PV and ET are useful for the differentiation of treatment-responsive patients, and there is a possibility that they can be used to quickly and easily predict the JAK2-V617F mutation.
Dipstick urinalysis is useful and clinically available for the screening of kidney and urological diseases. Since the dipstick method is based on a chemical reaction, it is affected by chemical substances such as drugs that cause false positive or false negative results. In this study, three automatic urine analyzer models (AUTION MAX AX-4060: ARKRAY, Inc.; US-3100R plus: EIKEN Chemical, Inc.; Clinitek Novus: SIEMENS Healthcare Diagnostics, Inc.) were compared in terms of their basic performance and abnormal reaction detection system. In addition, the effect of ascorbic acid on the abnormal reaction detection systems of the three models for false-positive samples was examined. The rates of concordance of results with those of dipstick urinalysis were more than 95% in all three models. In contrast, the detection rate of false-positive samples differed among the three models examined, especially in terms of the effect of ascorbic acid, potentially due to the difference in their detection systems. In conclusion, in the case of routine urinary laboratory examination, the characteristic and/or the basic performance of automatic urine analyzer models need to be considered to avoid pitfalls of abnormal reaction.
Detection of the antinuclear antibody (ANA) is widely used for the screening of collagen diseases. Although indirect immunofluorescence (IIF) assay is considered as a standard test, it has disadvantages in terms of its specificity and rapidity. We performed basic and clinical evaluation of a new ANA assay by chemiluminescent enzyme immunoassay (CLEIA). The basic performance of the assay was within acceptable level. Its clinical sensitivity was 91.5% and its specificity was 74.2%, which are higher than those of the IIF assay. The measurement time of CLEIA was 19 minutes, which was shorter than that of the conventional method. On the basis of these results, it is considered that this method is useful for the screening of connective tissue diseases.
To date, acute coronary syndrome (ACS) has been mainly diagnosed on the basis of electrocardiographic changes and clinical symptoms and signs. When patients reveal no characteristic chest pain and electrocardiographic findings, it may not always be easy to reach a correct diagnosis of ACS. For the above-described reasons, myocardial biomarker measurement is becoming very important as an adjunct for the diagnosis of ACS. Patients with acute chest pain visiting the emergency room of our hospital and comprehensively diagnosed as having ACS were enrolled in this study. We compared the usefulness of high-sensitivity cardiac troponin (hs-cTn) measurement with that of H-FABP and CK-MB mass measurement. According to the results of ROC curve analysis, the AUC values were 0.955, 0.946, 0.827, and 0.896 for hs-cTnI, hs-cTnT, H-FABP, and CK-MB mass, and the cutoff values were 155.5 pg/mL, 91.0 pg/mL, 25.6 ng/mL, and 6.4 ng/mL, respectively. As a result of the test of the difference in AUC value between any two cardiac biomarkers, hs-cTns showed a higher diagnostic capability for ACS than H-FABP and CK-MB mass. In addition, CK-MB mass had a higher diagnostic capability than H-FABP. In conclusion, hs-cTnI and hs-cTnT were more organ-specific and practically more useful myocardial biomarkers for the early diagnosis and treatment of ACS than the other biomarkers tested. Whenever ACS is suspected, hs-cTns should be measured first if possible before deciding on the appropriate treatment.
We evaluated the performance of the HTLV-1/2 antibody measurement reagent “Elecsys HTLV-I/II”. A total of 899 serum samples were included in this study. The overall percent agreement between Elecsys HTLV-I/II and three conventional immunoassays was 99.7–99.8%. The detection limit was significantly lower than those of the conventional methods and the specificity was the highest among all the methods evaluated. Moreover, the measurement time was 18 min. Thus, Elecsys HTLV-I/II would be useful for routine tests.
The quality of medical care can be improved by detecting a patient’s condition early, leading to prompt diagnosis and treatment. We developed an organizational framework for preworking hour reporting of inpatients’ blood samples in April 2013; around 7:30 AM, medical technologists collected inpatients’ blood samples, which were immediately measured. Consequently, about 80% of urgently required blood test results were reported before 9:00 AM. In addition, the peak number of blood samples being analyzed at the laboratory and the mean turn-around time (TAT) of total blood tests between 8:30 AM and 9:30 AM decreased. We have been improving preworking hour reporting, and the mean TAT has decreased with increasing number of blood samples collected before 8:00 AM over 30 months since the new organizational framework was implemented.
Penicillins are the first-line drugs for the treatment of Streptococcus agalactiae (GBS) infections. Recently, GBS strains with reduced penicillin susceptibility (PRGBS) have been reported. We studied the annual trend of the antimicrobial susceptibility of about 1,465 GBS strains isolated from clinical specimens in 5 general hospitals during the past five years from 2010 to 2014 and also investigated the medical records of the patients from whom PRGBS strains were isolated. Of 51 PRGBS strains, 43 were from respiratory specimens, 5 from urogenital specimens, and 3 from decubitus ulcer. The susceptibilities of these strains were tested by the broth microdilution method. The MICs of penicillin G, erythromycin, levofloxacin, cefepime, and vancomycin were determined. The susceptibilities of these PRGBS strains were 0, 24, 27, 22, and 100%, respectively. Of the 43 patients whose respiratory specimens showed PRGBS strains, 38 were 60 years old or older and 39 were bedridden. These results suggest that PRGBS might cause a nosocomial infection via respiratory secretion.
In the outpatient clinic department of our hospital, we have established a blood collection support system that prioritizes patients’ clinical schedule in order to efficiently manage consultation appointments and medical examinations before the consultation. Precedence has been given to consultation appointment time, scheduled time for CT and echography, patients who are scheduled to have solid tumor treatment, and those referred from other clinics. This system relieved the congestion at the opening time of the blood collection room and consequently enabled us to distribute the patients throughout the day in accordance with their appointment time, which has brought about a significant reduction in patient waiting time for blood collection. In particular, those who are scheduled to have solid tumor treatment and those referred from other hospitals patients can have their blood drawn as top priority within 5 minutes of their arrival.
The EGFR gene mutation test is very important for selecting the optimal lung cancer molecular target therapy. Many of the analyzed specimens are formalin-fixed paraffin-embedded. However, DNA may become fragmented under such formalin fixation conditions, which thus can result in measurement errors. From August 2014 to July 2015, we obtained touch imprint cytology (TIC) specimens from 18 patients intraoperatively in our hospital and performed the EGFR gene mutation test. We then compared the DNA concentration and the proportion of mutations between the FFPE specimens and the TIC specimens, and also evaluated DNA quality by real-time PCR analysis. The FFPE specimens were found to demonstrate poorer DNA quality than the TIC specimens. As a result, EGFR gene mutations were found in 11 patients, while no mutations were found in 7 patients. There was no difference in the presence or absence of mutations according to specimen type. The mutated region did not show any differences in the specimen type. A higher proportion of mutations was found in the TIC specimens; in contrast, the DNA concentrations tended to be lower. In addition, the DNA quality index tended to be higher in the TIC specimens. Moreover, alcohol-fixed specimens demonstrated better DNA quality than the formalin-fixed ones. Finally, for TIC specimens, it is possible to selectively recover tumor cells. We therefore recommend the use of TIC techniques for performing the EGFR gene mutation test, which demands high precision and rapidity.
The brain natriuretic peptide (BNP) level is increased during heart failure. Herein, we report a case of markedly elevated BNP level with divergence of atrial natriuretic peptide (ANP) level and without severe heart failure, and discuss the possible cause of the elevated BNP level. A 70-year-old female with angina pectoris and hypertension was referred to our hospital because of a markedly elevated BNP level (35,347 pg/mL). The BNP level had been continuously elevated; however, the ANP level was slightly elevated (81.9 pg/mL) and no severe heart failure was present, as determined by echocardiography and electrocardiography. The BNP level was unchanged as determined by fluorescence enzyme immunoassay and chemiluminescence enzyme immunoassay. Dilution measurement revealed that the change ratio was within 6%, suggesting that no coexisting material was present. Moreover, neither a human anti-mouse antibody nor an anti-ALP antibody was present. Gel filtration analyses demonstrated the presence of an immunoreactive peak in the high-molecular-weight fraction, which was different from that of BNP-32. It is recognized that the BNP includes not only bioactive BNP-32 but also pro-BNP. Our analyses revealed that the markedly elevated BNP level in the present case is probably caused by the marked accumulation of pro-BNP owing to the bonding of the autoantibody to the pro-BNP or the lack of an enzyme that breaks down pro-BNP to BNP-32.
The Andersen-Tawil syndrome (ATS) is a disease entity characterized by 3 features: (1) ventricular arrhythmias with U waves, (2) periodic paralysis, and (3) dysmorphic features. The cause of ATS is mutations in KCNJ2, the gene encoding an inward rectifier potassium channel (Kir2.1). Electrocardiogram (ECG) manifestations of ATS include prominent U waves with QU prolongation, frequent premature ventricular contractions (PVCs), and bidirectional ventricular tachycardia (biVT). Previous case reports have demonstrated that flecainide is effective in VT suppression. Our patient was a 50-year-old woman who showed the three typical features of ATS. Genetic testing revealed a mutation in KCNJ2 (R218W). Her ECG showed a typical U wave with QU prolongation (723 ms) and frequent multifocal PVCs. In 24-hour Holter ECG, PVCs were 24% of the total QRS, and typical biVT was detected. After flecainide therapy (100 mg/day), the number of PVCs was reduced to 9%. Her palpitation was improved. Prominent U waves and biVT are key findings in ATS. Therefore, in ECG analysis, it is important to provide information on the QU interval, U wave amplitude, U wave duration, and polarity of PVCs.
Multiple myeloma is a cancer of plasma cells, which presents with symptoms such as anemia, osteolytic bone lesions, and renal dysfunction. Central nervous system (CNS) involvement in multiple myeloma is very uncommon. We report a case of CNS involvement in multiple myeloma, in which the detection of abnormal cells in cerebrospinal fluid in our laboratory resulted in early treatment. The patient was a 65-year-old man who had been diagnosed with multiple myeloma by bone marrow examination. Systemic malignant tumors were temporarily reduced in size or disappeared after chemotherapy. However, many abnormal cells such as plasma cells were morphologically confirmed in the cerebrospinal fluid after regular follow up over several months. Immediately, we contacted the attending doctor and performed additional tests. From the results of flow cytometric analysis and cytology, he was diagnosed as having CNS involvement in multiple myeloma. A quick report of the detection of abnormal cells in the cerebrospinal fluid results in the early diagnosis of CNS involvement. Treatment choice and prognosis may be affected by the presence or absence of CNS involvement. Therefore, careful observation of morphologically abnormal cells in the cerebrospinal fluid is very important.
Jerk-locked back averaging (JLA), a back averaging technique for EEGs that are time locked to the onset of jerks on the EMG, is used to detect the cortical spikes that precede jerks of cortical origin. JLA is mainly used to diagnose cortical myoclonus. In this report, we discuss a case in which we used JLA to detect cortical spikes preceding myoclonic jerks. We report the case of a 14-year-old boy who was diagnosed with cortical myoclonus by JLA. For 9 years and 8 months, whole body tonic seizures emerged after head injury, but CT and MRI revealed no abnormality. The patient was admitted to our hospital because of myoclonus and tremors in the hand from the age of 11 years. A trigger was evoked from the right abductor digiti minimi muscle of the hand. Concurrently, EEGs of the cerebrum area of the right hand were obtained from 140 ms before to 60 ms after the trigger. The JLA results revealed a positive–negative biphasic sharp wave, starting about 15.8 ms before the trigger, with the maximum amplitude observed in the left parietal region and the vicinity of the longitudinal cerebral fissure in the parietal region. Median nerve stimulation of somatosensory evoked potential (SEP) results revealed giant SEP and extended central conduction time (CCT). In this case report, we describe a positive–negative biphasic sharp wave that preceded a myoclonus, giant SEP and extended CCT. These observations suggested that the origin of the myoclonus is subcortical dysfunction.
Adenine phosphoribosyltransferase (APRT) deficiency results in 2,8-dihydroxyadenine (DHA) urolithiasis with the deposition of 2,8-DHA crystals of various sizes in the bladder. Here, we report the case of a male patient in his 60s, who was diagnosed as having diabetes in 2012, and regularly came to our hospital for the treatment of chronic renal failure caused by diabetic nephropathy. Crystals suspected to be composed of 2,8-DHA were first detected about 2 years later and were consistently detected thereafter. Inspection of their chemical properties suggested that these crystals were composed of 2,8-DHA. However, the final determination was difficult as they could not be identified by infrared spectroscopic analysis, and computed tomography did not show any urinary calculus. Genetic analysis showed the patient to be homozygous for the Japanese mutant gene APRT*J/APRT*J. The timing of the first detection of 2,8-DHA coincided with that of eGFR deterioration. Therefore, the possibility that 2,8-DHA crystals were the cause of the reduced renal function was suggested. As experiments in rats confirmed that 2,8-DHA crystals cause kidney toxicity, even in the absence of calculus, the patient was started on medication for hyperuricemia, which also controls 2,8-DHA biosynthesis. In this case, the diagnosis was made and treatment commenced on the basis of a report from a clinical laboratory regarding the crystals, and is an example whereby analysis of urinary sediment contributed to clinical management.