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The migration of neurons from their birthplace to their correct destination is one of the most crucial steps in brain development. Incomplete or incorrect migration yields ectopic neurons, which cause neurologic deficits or are negligible at best. However, the granule cells (GCs) in the cerebellar cortex may challenge this traditional view of ectopic neurons. When animals are born, GCs proliferate near the pia mater and then migrate down to the GC layer located deep in the cerebellar cortex. However, some GC-like cells stay in the molecular layer, a layer between the pia mater and GC layer, even in normal adult animals. These cells were named ectopic GCs nearly 50 years ago, but their abundance and functional properties remain unclear. Here, we have examined GCs in the molecular layer (mGCs) with a specific marker for mature GCs and transgenic mice in which GCs are sparsely labeled with a fluorescent protein. Contrary to the previous assumption that mGCs are a minor neuronal population, we have found that mGCs are as prevalent as stellate or basket cells in the posterior cerebellum. They are produced during a similar period as regular GCs (rGCs), andin vivotime-lapse imaging has revealed that mGCs are stably present in the molecular layer. Whole-cell patch-clamp recordings have shown that mGCs discharge action potentials similarly to rGCs. Since axonal inputs differ between the molecular layer and GC layer, mGCs might be incorporated in different micro-circuits from rGCs and have a unique functional role in the cerebellum.

Aim Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC. Methods Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest. Results For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002). Conclusion Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC.

Synapses are continuously formed and eliminated throughout life in the mammalian brain, and emerging evidence suggests that this structural plasticity underlies experience-dependent changes of brain functions such as learning and long-term memory formation. However, it is generally difficult to understand how the rewiring of synaptic circuitry observed in vivo eventually relates to changes in animal's behavior. This is because afferent/efferent connections and local synaptic circuitries are very complicated in most brain regions, hence it is largely unclear how sensorimotor information is conveyed, integrated, and processed through a brain region that is imaged. The cerebellar cortex provides a particularly useful model to challenge this problem because of its simple and well-defined synaptic circuitry. However, owing to the technical difficulty of chronic in vivo imaging in the cerebellum, it remains unclear how cerebellar neurons dynamically change their structures over a long period of time. Here, we showed that the commonly used method for neocortical in vivo imaging was not ideal for long-term imaging of cerebellar neurons, but simple optimization of the procedure significantly improved the success rate and the maximum time window of chronic imaging. The optimized method can be used in both neonatal and adult mice and allows time-lapse imaging of cerebellar neurons for more than 5 mo in ∼80% of animals. This method allows vital observation of dynamic cellular processes such as developmental refinement of synaptic circuitry as well as long-term changes of neuronal structures in adult cerebellum under longitudinal behavioral manipulations.

In many regions of the developing mammalian nervous system, functional synaptic circuitry is formed by competitive elimination of early formed redundant synapses. However, how winning synapses emerge through competition remains unclear in the brain largely because of the technical difficulty of directly observing this dynamic cellular processin vivo. Here, we developed a method of two-photon multicolor vital imaging to observe competitive elimination of supernumerary climbing fibers (CFs) in the cerebellum of live mouse pups. At birth, each Purkinje cell (PC) in the cerebellar cortex is innervated by multiple CFs; an activity-dependent regression of supernumerary CFs ultimately yields a single innervation for most PCs by postnatal day 21. As supernumerary CFs are pruned, the terminal field of CFs translocates from the soma to the dendrites of PCs.In vivotime-lapse imaging of CF elimination revealed that (1) CF terminals were highly motile on the soma, but their motility was significantly reduced on dendrites; (2) only one CF could translocate to the dendrites whereas their competitors were restricted to perisomatic regions; and (3) the CF that began dendritic translocation became the winner. Moreover, selective photo-ablation of the winning CF (that undergoes dendritic translocation) reversed the fate of its losing competitor. These results indicate that dendritic translocation is a key cellular event that determines the winner during CF elimination. We propose that CF terminals are selectively stabilized on dendrites, providing irreversible competitive vigor to the first CF to form dendritic synapses.

Recently molecular targeting therapies such as inhibition of enzyme activities associated with gene mutations responsible for lung carcinogenesis have been demonstrating promising outcomes, increasing the importance of gene analysis using clinical samples. Cytomorphologic findings with predictive value toward specific gene mutation such as EGFR mutation could be a useful tool to select appropriate gene analyses using limited clinical samples.Morphometrical and cytomorphological evaluations were performed in 7 cultured lung cancer cell lines and 51 lung adenocarcinoma clinical samples to identify specific cytomorphologic characterization of EGFR-mutated cancer cells compared to the wild type.Morphometry demonstrated that the EGFR mutated cell lines had significantly smaller nuclear area and perimeter and more circular nuclei compared to the wild type. In contrast, EGFR-mutated clinical samples had significantly greater nuclear area and perimeter compared to the wild type EGFR samples. There were no clear differences in cytomorphologic parameters assessing nuclear atypicality between EGFR mutated cells and wild type EGFR cells in either cultured cell lines or clinical samples.Although our study suggested that EGFR mutation may have specific effects on nuclear morphology, no consistent characteristics of EGFR-mutated cells were identified in the clinical samples, probably due to various factors such as different pathologic stages and various incidences of lepidic growth. Further assessment of morphological characterization of EGFR-mutated cells in lung adenocarcinoma is warranted, increasing the number of samples and considering the effects of polyploidy, other gene mutations, pathology stage and tumor subtypes such as lepidic growth. Diagn. Cytopathol. 2016;44:717-724. © 2016 Wiley Periodicals, Inc.

The member organizations of the CETC feel strongly that there are significant flaws associated with the proposed proficiency test and its implementation. The most immediate modifications include lengthening the required testing interval, utilizing stringently validated and continuously monitored slides, changing the grading scheme and changing the focus of the test from individuals to laboratory level testing, as described above. Integration of new computer-assisted and location-guided screening technologies into the testing protocol is necessary for the testing program to be compliant with the current CLIA law. The regulation also needs to be flexible enough to accommodate new technologies that are implemented in laboratory practice, education and administration of the test. The changes recommended in this document address the most immediate technical and scientific concerns with the current implementation of PT for gynecologic cytology. The CETC will be submitting a subsequent document, following full review of the current regulations, with recommendations for changes, justifications and impact.

Objective To clarify the usefulness of endometrial scraping smears in women with extragenital malignancies. Study Design A total of 4,335 endometrial scraping smears were obtained during the 5-year period 1995-1999 at the National Kyushu Cancer Center and were retrospectively analyzed regarding extragenital malignancies. Results There were 88 cases of extragenital malignancies. Extragenital malignant cells were detected in endometrial smears in 13 cases. The cases consisted of 4 gastric cancers, 4 breast cancers, 2 lung cancers, 1 rectal cancer, 1 gastrointestinal stromal tumor of the small intestine and 1 case of adenocarcinoma of unknown origin. The patients' average age was 52.5 years. The symptoms and signs included abnormal vaginal bleeding, abdominal and lumbar pain, lower limb edema, abdominal mass and neck lymph node swelling. Both ascites and peritoneal dissemination were found in 8 cases. Ten of the 13 cases were diagnosed as of extrauterine origin based on the characteristic cancer cell appearance, the absence of cellular detritus among the poorly differentiated adenocarcinomas and, above all, the morphologic difference between normal endometrial cells and cancer cells. Conclusion Endometrial scraping smears are useful for detecting extragenital malignant cells that enter the uterine cavity.

背景:Stage IVの胃癌 (中～ 低分化型腺癌) 症例の術中に提出された腹腔洗浄液細胞診にて, 砂粒小体を伴った無数の乳頭状集塊を認め, 卵巣癌が疑われたserous adenofibromaの1例を経験したので報告する.症例:59歳, 女性.12ヵ月前より腹痛あるも放置していたが, 症状増悪のため当センター受診, 入院となる.精査の結果, 胃癌と診断され胃全摘術となった.術中の腹腔洗浄液細胞診にて, 卵巣腫瘍の存在が疑われたため, 1ヵ月後再度開腹術となり単純子宮全摘出術, 両側付属器切除術が施行された.洗浄腹水の細胞像は胃癌の細胞像とは明らかに異なっており, 細胞異型, 核異型は軽度ながらも無数の砂粒小体を伴った乳頭状集塊を認め, serous papillary adenocarcinomaの存在を否定できなかった.結論:術中腹腔洗浄細胞診においては他臓器に由来する悪性腫瘍の存在も考慮しなければならないが, 良性腫瘍においても多量の腫瘍細胞が洗浄液中に出現する可能性を一考する必要があると考えられた.

Gingival fibromatosis is a rare clinical finding of non-inflammatory gingival overgrowth. Here we present 2 cases of children with gingival fibromatosis and provide a longitudinal analysis of the correlation between the presence of periodontal bacteria and clinical condition. The first case, a boy treated from age 2 to 6, showed periodontitis in the lower anterior region, which recovered to a good periodontal condition by a professional therapeutic approach. The second case is a girl, treated for 2 years from age 10, who presented with extremely enlarged gingiva and severe gingivitis, and a gingivectomy was carried out to eliminate the dental plaque accumulation. In both cases, periodontal bacteria were assessed periodically using PCR (Polymerase Chain Reaction) method, and the results compared with the clinical conditions. In both cases, increased numbers of periodontal bacteria were detected during the bad gingival condition period. In addition, Prevotella nigrescens and Prevotella intermedia were especially detected. Clinical condition seems to be influenced by the number of the periodontal bacteria present, which indicates that an effective monitoring of such bacteria would be beneficial for not only evaluating the current periodontal condition, but also for making an appropriate prognosis of a lesion.

背景:若年者の乳腺に原発した血管肉腫を経験し, その捺印細胞像を組織像との対比を含めて検索する機会を得たので報告する.症例:患者は, 18歳女性, 左乳房の増大に気付くが放置. 7ヵ月後に急激な増大を認めたために当院受診. 乳房切除術が施行されたが, 再発を繰り返し術後9ヵ月に永眠した. 摘出標本の捺印細胞診における細胞学的特徴は,(1) 血管腔の形成を示唆する集塊,(2) ふさ (tuft) 状の乳頭状集塊,(3) N/C比の高い未分化な細胞集塊,(4) 核の抱き込み像,(5) 腺癌様の細胞集塊であり, 病理学的に血管肉腫と診断された.結論:血管肉腫は他の非上皮性腫瘍と同様にきわめて多彩な細胞像を示し, その診断は困難とされるが, 臨床情報も併せて総合的に判断することにより適確な診断も可能と考えられた.

Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC.Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest.For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002).Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC.

– Objectives: To examine the occurrence of specific periodontal bacteria in children and adolescents. Methods: Ten putative periodontal bacteria were longitudinally examined in plaque and saliva samples from 119 periodontally healthy children (2–15 years old) using a polymerase chain reaction method. Results:Capnocytophaga ochracea, C. sputigena, and Actinobacillus actinomycetemcomitans were frequently found in saliva, and tended to persist in saliva for the remainder of the study, whereas Porphyromonas gingivalis, Treponema denticola, and Prevotella intermedia were rarely detected. P. nigrescens was more frequently detected in plaque and its prevalence increased with age. Eikenella corrodens and Campylobacter rectus were sometimes detected in both plaque and saliva, while Tannerella forsythensis was occasionally detected in saliva. Conclusion:A. actinomycetemcomitans, C. ochracea, C. sputigena, P. nigrescens, C. rectus, and E. corrodens are common members of the oral microbial flora of healthy children, whereas P. gingivalis, P. intermedia, and T. denticola appear to be transient organisms.

A 10-year-old Japanese girl with severe tooth mobility in her lower permanent incisors was examined clinically, as well as radiographic and microbiological means. The incisors had severe alveolar bond loss and pocket depths exceeding 7 mm at the first visit, however, 10 periodontal bacteria were not detected in subgingival plaque samples taken from the lower central incisors using a 16S rRNA-based polymerase chain reaction method. Periodontal treatment consisting of mechanical debridement and antibiltic medication resulted in a significant improvement of the clinical parameters. Three months after the first examination, dental radiographs showed refilling of alveolar bone in the region. Further, microbiological examinations after remission detected only oral microflora commonly found in health children including A. actinomycetemcomitans. Based on the clinical, readiographic, and microbiological findings, the present case was diagnosed as acute periodontitis.