Vulvar Adenoid Cystic Carcinoma with Squamous Cell Carcinoma Component.

Adenoid cystic carcinoma (ACC) is a major histological type of salivary gland cancer but an uncommon form of vulvar cancer. Salivary gland ACC occasionally dedifferentiates into high-grade carcinoma, resulting in poor prognoses. The dedifferentiated component is usually a poorly differentiated cribriform or solid carcinoma, whereas squamous cell carcinoma (SCC) is exceptional. Herein, we report the case of a 78-year-old woman with vulvar ACC, including an SCC component. She presented with a vulvar nodule that had been present for 30 years and increased in size over the past few years. Magnetic resonance imaging showed a ball-like mass with high intensity on T1-weighted images and high intensity with non-uniformity on T2-weighted images. Considering the systemic and social conditions, the tumor was maximally resected without lymphadenectomy. Histologically, the tumor was composed of a marginal ACC component with a central SCC component. Stage IB vulvar cancer, which was assumed to originate from the Bartholin's gland, was diagnosed. She has survived over 2 years without additional treatments after the surgery. In this case, we assumed that slowly progressive indolent ACC could be dedifferentiated to high- grade SCC. According to our review of available literature, dedifferentiation of vulvar ACC with a high-grade SCC component has not been specifically documented. Although the nature of dedifferentiated vulvar cancer is unclear, it should be noted that high-grade dedifferentiation can occur in long-lasting vulvar masses.

Conducting and Writing Quantitative and Qualitative Research.

Comprehensive knowledge of quantitative and qualitative research systematizes scholarly research and enhances the quality of research output. Scientific researchers must be familiar with them and skilled to conduct their investigation within the frames of their chosen research type. When conducting quantitative research, scientific researchers should describe an existing theory, generate a hypothesis from the theory, test their hypothesis in novel research, and re-evaluate the theory. Thereafter, they should take a deductive approach in writing the testing of the established theory based on experiments. When conducting qualitative research, scientific researchers raise a question, answer the question by performing a novel study, and propose a new theory to clarify and interpret the obtained results. After which, they should take an inductive approach to writing the formulation of concepts based on collected data. When scientific researchers combine the whole spectrum of inductive and deductive research approaches using both quantitative and qualitative research methodologies, they apply mixed-method research. Familiarity and proficiency with these research aspects facilitate the construction of novel hypotheses, development of theories, or refinement of concepts.

Substantial improvement of histopathological diagnosis by whole-slide image-based remote consultation.

Consultation by subspecialty experts is the most common mode of rendering diagnosis in challenging cases in pathological practice. Our study aimed to highlight the diagnostic benefits of whole-slide image (WSI)-based remote consultation. We obtained diagnostically challenging cases from two institutions from the years 2010 and 2013, with histological diagnoses that contained keywords "probable," "suggestive," "suspicious," "inconclusive," and "uncertain." A total of 270 cases were selected for remote consultation using WSIs scanned at 40 × . The consultation process consisted of three rounds: the first and second rounds each with 12 subspecialty experts and the third round with six multi-expertise senior pathologists. The first consultation yielded 44% concordance, and a change in diagnosis occurred in 56% of cases. The most frequent change was from inconclusive to definite diagnosis (30%), followed by minor discordance (14%), and major discordance (12%). Out of the 70 cases which reached the second round, 31 cases showed discrepancy between the two consultants. For these 31 cases, a consensus diagnosis was provided by six multi-expertise senior pathologists. Combining all WSI-based consultation rounds, the original inconclusive diagnosis was changed in 140 (52%) out of 266 cases. Among these cases, 80 cases (30%) upgraded the inconclusive diagnosis to a definite diagnosis, and 60 cases (22%) changed the diagnosis with major or minor discordance, accounting for 28 cases (10%) and 32 cases (12%), respectively. We observed significant improvement in the pathological diagnosis of difficult cases by remote consultation using WSIs, which can further assist in patient healthcare. A post-study survey highlighted various benefits of WSI-based consults.

Reduced expression of programmed cell death 1 and programmed cell death ligand 1 in infiltrating inflammatory cells of lichen planus without administration of immune checkpoint inhibitors.

Keratinocytes are the main targets of infiltrating T cells in the pathogenesis of lichen planus. However, the mechanisms of dense inflammatory infiltrates beneath the epidermis remain unknown. The aim of the present study was to clarify the roles of programmed cell death 1 (PD-1) and its ligand (PD-L1) in the pathogenesis of lichen planus. Immunohistochemistry of PD-1 and PD-L1 in 12 cases each of lichen planus and dermal-type erythema multiforme was performed. The expression of PD-1 and PD-L1 on infiltrating inflammatory cells, predominantly lymphocytes in lichen planus, was significantly less compared to that in dermal-type erythema multiforme. By dual immunofluorescence, the overlap between PD-1 and leukocyte common antigen, CD4, CD8, CD68, and factor XIIIa was limited and found in only a very small portion of lichen planus cells. Our data suggest that decreased expression of PD-1 and PD-L1 could play a role in accelerating inflammatory cell infiltration targeting the epidermis in the pathogenesis of lichen planus.

Factors associated with the mental health status of medical students during the COVID-19 pandemic: a cross-sectional study in Japan.

OBJECTIVE: The COVID-19 pandemic had a substantial impact on university students, including those in medical schools, with disruption in routine education causing significant psychological distress. The objective of this study was to evaluate the factors associated with psychological distress among medical students during the period of enforced home quarantine from March through May 2020. DESIGN: A cross-sectional study. SETTING: One Japanese medical school. PARTICIPANTS: 571 medical students. PRIMARY AND SECONDARY OUTCOME MEASURES: Self-administered electronic questionnaires including the K-6 scale for psychological distress, the Rosenberg Self-Esteem Scale (RSES) for self-esteem and the General Self-Efficacy Scale (GSES) for self-efficacy were distributed. To assess the determinant factor for psychological distress, variables such as sex, grade in school, living conditions, and RSES and GSES scores were evaluated in regression analysis. RESULTS: 163 respondents (28.5%) scored ≥5 on the K-6 scale, indicating a significant degree of psychological distress. Logistic regression revealed that a higher score on RSES (p<0.001) and GSES (p<0.01) was an independent factor associated with lower levels of psychological distress. Multiple regression analysis focusing on students with a K-6 score ≥5 revealed that higher scores on RSES correlated with lower levels of psychological distress. By contrast, those with higher GSES scores also scored higher for indicators of psychological distress. CONCLUSIONS: This study identified that self-efficacy and self-esteem were both influential factors for predicting psychological distress during the current COVID-19 pandemic. Medical schools should provide support for mental health and educational initiatives directed at enhancing self-esteem and self-efficacy, with a focus on improving personal resilience. In emergency situations, such as that faced in response to the COVID-19 pandemic, initial programmes might target students with higher levels of self-efficacy. By contrast, under routine situations, these efforts should be directed towards students with lower self-esteem as primary means to prevent depression.

Brain metastasis from cutaneous squamous cell carcinoma coexistent with extramammary Paget's disease: A case report.

We report a case of cutaneous squamous cell carcinoma (CSCC), initially coexisting with invasive extramammary Paget's disease (EMPD), in the scrotum of an 84-year-old man. The patient initially had a rash and pruritus before presenting with a pedunculated scrotal mass surrounded by widespread erythema. He underwent total gastrectomy for adenocarcinoma 1 year previously and had been receiving TS-1 (Tegafur/Gimeracil/Oteracil pottasium) orally. Histopathologically, the tumor consisted of invasive SCC, with invasive EMPD in the erythematous region. From the clinical presentation and histopathological findings, we assumed that CSCC developed in the background of the EMPD. The CSCC metastasized to several inguinal lymph nodes and to the brain in the following years. While the histogenesis of each of the tumors remains to be elucidated, the fact that the CSCC rather than the EMPD metastasized to a distant site in this patient is to be noted for future treatment considerations.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs.

Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multi-organ systemic drug reaction characterized by hematological abnormalities and reactivation of human herpesvirus-6 (HHV-6). DIHS/DRESS is typically associated with a limited number of drugs, such as the anticonvulsants. Our group has treated 12 patients for DIHS/DRESS due to lamotrigine (LTG), but their presentation differed from that of patients with DIHS/DRESS caused by other drugs. The aim of the present study was to identify significant differences between DIHS/DRESS caused by LTG versus other drugs. We retrospectively reviewed data of 12 patients with DIHS/DRESS caused by LTG and 32 patients with DIHS/DRESS due to other drugs. The increase in alanine aminotransferase level was significantly milder in the LTG group than the DIHS/DRESS group due to other drugs. The percentage of atypical lymphocytes in the blood during DIHS/DRESS was lower in the LTG group. Serum levels of lactate dehydrogenase and thymus and activation-regulated chemokine were also lower in the LTG group. There were fewer DIHS/DRESS patients with HHV-6 reactivation in the LTG group than in the group treated with other drugs. Lymphocyte transformation after DIHS/DRESS onset was faster in the LTG group. The two groups did not differ with respect to the interval from first drug intake to rash, white blood cell count, blood eosinophilia or DRESS score. There were no significant histopathological differences between the two groups. The features of LTG-associated DIHS/DRESS and DIHS/DRESS due to other drugs differ.

A Case of Primary Cutaneous Basal Cell Carcinosarcoma.

A 94-year-old man consulted our hospital due to a rapidly growing tumor on the left cheek. The histological diagnosis of the tumor was basal cell carcinosarcoma, which was composed of intermingled epithelial and mesenchymal components. The former was basal cell carcinoma, while the latter was spindle cell sarcoma. The tumor was completely resected with a 3-mm margin and the patient remained free of local recurrence or distinct metastasis for 2 years. We report here a case of cutaneous basal cell carcinosarcoma and a review of the literature.

How do case presentation teaching methods affect learning outcomes?--SNAPPS and the One-Minute preceptor.

BACKGROUND: Various techniques have been developed to enable preceptors to teach residents effectively in outpatient settings to promote active learning, including SNAPPS and the One-Minute Preceptor (OMP). This study aimed to ascertain the differences between SNAPPS and the OMP in case presentation content and learner evaluation when used to teach residents about case presentation. METHODS: From 2011 to 2013, participants were 71 junior clinical residents employed in two hospitals for clinical training. They were randomly allocated to two groups, one using SNAPPS and the other the OMP. From recorded discussions, the "differential diagnoses", "questions and uncertainties", "treatment plans", and "learning issues" were counted. Also, a self-evaluation form was distributed at the end of the study to evaluate the residents' satisfaction with the case presentation. RESULTS: Members of the SNAPPS group used significantly more meaning units related to questions and uncertainties compared with those of the OMP group (P < 0.001). Self-evaluation sheets revealed that members of the SNAPPS group had significantly higher positive responses than those of the OMP group in terms of the following evaluations: "It was easy to bring up questions and uncertainties" (P = 0.046), "It was easy to present the case efficiently" (P = 0.002), "It was easy to present the case in the sequence given" (P = 0.029), and "I was able to give an in-depth case presentation" (P = 0.005). CONCLUSIONS: SNAPPS may induce more meaning units related to questions and uncertainties and give more satisfaction to residents than the OMP.

Low-grade cylindromatous adnexal carcinoma with unusual histopathological features: report of a case with comparative immunohistochemical study and meta-analysis of the literature.

We present an extremely rare case of low-grade cylindromatous adnexal carcinoma (CAC) on the right chest wall of a 77-year-old man. Histopathologically, the neoplasm was initially diagnosed as a cylindroma that developed over the course of 13 years. A diagnosis of low-grade CAC was rendered after the documentation of a local recurrence and histopathology of the recurrent tumor. To further assess the evolution of low-grade CAC over time, we compared the morphology, mitotic account, proliferative markers and adhesion molecule immunoreactivity among paired primary and recurrent tumors. Unlike those earlier reported, our case showed the maintenance of tumor morphology after a recurrence without areas of obvious malignant transformation or metaplastic change. We showed here for the first time the expression of adhesion molecules of CAC/spiradenoma and a comparison of proliferation indices between a primary tumor and its local recurrence. This peculiar tumor differs from previously reported cases and harbors a malignant potential although the histopathological features of malignancy are subtle. Our meta-analysis of the literature provided background information regarding this rare entity. Alterations of E-cadherin and GCDFP-15 expression may provide additional helpful clues in differential diagnosis and determining the clinical behavior of this unusual neoplasm. Further studies are warranted to confirm the potential discriminative role of these markers.

Validity of direct ophthalmoscopy skill evaluation with ocular fundus examination simulators.

OBJECTIVE: We examined how direct ophthalmoscopy (DO) skills can be evaluated in a clinical setting using a simulator, and determined the appropriate assessment criteria for the DO skills in practical tests such as the Objective Structured Clinical Examination (OSCE). DESIGN: Cross-sectional study. PARTICIPANTS: Medical students, residents, and attending physicians (73 total participants). METHODS: We selected the following 3 factors that may indicate the ability to perform nonmydriatic direct funduscopy: (i) experience: total number of cases examined (without mydriasis); (ii) frequency: number of cases examined during the previous month; and (iii) range: viewable fundus field range. We used a fundus simulator with 3-level adjustable pupil sizes (2, 3.5, and 5 mm) and created original test slides for use in the simulator. We counted the number of correct answers of each participant for each pupil size using the simulator and test slides. RESULTS: There were significant differences in the median number of correct answers for pupil diameters of 2 (p = 0.008) and 3.5 mm (p = 0.007) among groups divided according to the total number of cases examined (without mydriasis). There were no significant differences among groups divided according to the viewable fundus field range (2 mm: p = 0.103, 3.5 mm: p = 0.083, 5 mm: p = 0.347). CONCLUSIONS: The results suggest a possible relation between the surrogate indicators "experience" and "range" and DO skills using a fundus simulator. The surrogate indicator experience showed a strong relation to DO skills using a fundus simulator.

A case report of pigmented mammary Paget's disease mimicking nevus of the nipple.

A 43-year-old Japanese woman consulted our hospital for a pigmented lesion on her right nipple. Two years later, the lesion became enlarged, measuring 5 × 5 mm. It was dark brown, had an irregular shape and relatively clear borders. Incisional biopsy yielded a pathological diagnosis of junctional nevus of the skin. An additional 2 years later, a small mass developed under the right nipple area and core needle biopsy yielded a pathologic diagnosis of invasive ductal carcinoma. Partial resection of the right EC areas included the skin of the nipple and sentinel lymph node biopsy was performed. Histologically, the skin of the nipple demonstrated small clusters of pigmented carcinoma cells that were low molecular weight cytokeratin (CAM5.2) positive. Most of the carcinoma cells were small and did not have abundant cytoplasm, but nuclear enlargement and prominent nucleoli indicated malignancy, and the cytoplasm was pale compared with that of the surrounding squamous epithelial cells. Scattered dendritic melanocytes were identified by S-100 protein and HMB-45 immunohistochemically. In the upper dermis, carcinoma cells also involved the lactiferous ducts. A small focus of carcinoma cells that invaded the fat tissues did not contain melanin pigment. The final diagnosis was pigmented mammary Paget's disease. Pigmented lesions on the nipple should be carefully examined, because pigmented mammary Paget's disease sometimes mimics malignant melanoma or junctional nevus.

Inguinal porokeratosis in a Japanese man.

Inguinal and genital porokeratosis are rare but seem to be more common in Asians. We report a case of a 69-year-old Japanese man with multiple lesions of porokeratosis in both inguinal regions. The lesions first appeared in the inguinal region and subsequently spread to the trunk. The patient reported that his father had had similar lesions. Dermoscopy demonstrated central brown pigmentation and blue-gray dots surrounded by a single "white track" at the periphery. The exterior border of the white track also showed light brown pigmentation. Genital or inguinal porokeratosis is uncommon and may be misdiagnosed as Bowen's disease, lichen planus or extramammary Paget's disease. However, awareness of this entity and the use of dermoscopy are helpful to establish a correct diagnosis.

Gender role stereotype and poor working condition pose obstacles for female doctors to stay in full-time employment: alumnae survey from two private medical schools in Japan.

The shortage of physicians has become a serious problem in Japan. It has been pointed out that an increase in the number of female doctors may contribute to the aggravation of this shortage because it is known that women work fewer hours than male doctors. Here, we investigated how many female doctors had ever resigned from a full-time position, and elucidated the reasons why female doctors find it difficult to stay in full-time employment. An alumnae survey of 2 private medical schools was conducted in 2007. A self-administered questionnaire was sent to 1423 graduates and 711 responded with informed consent (response rate, 50%; mean age, 39 years). Overall, 55% of the respondents had previously resigned from full-time employment, of which 90% resigned within 10 years of graduating from medical school. The difficulty in balancing work, childbirth and child rearing (45%) were the top 2 reasons for resignation, followed by physical problems (12%) and long working hours (8%). Among those who resigned, only 33% returned to full-time employment. Women who had at least 1 child were only 30% of those who had never resigned and 84% of those who had previously resigned. The majority of study subjects, regardless of experience of resignation (88%), agreed that women should continue to work even after childbirth. In conclusion, the results of this study suggested that many female doctors resigned from a full-time position within 10 years of graduating from medical school, largely because of the gender role stereotype and poor working conditions.

Association of legumain expression pattern with prostate cancer invasiveness and aggressiveness.

OBJECTIVES: To investigate the clinical implication of legumain, an asparaginyl endopeptidase that is highly expressed in several types of cancer, expression in prostate cancer. METHODS: Legumain expression in prostate cancer cell lines was determined by real-time reverse transcriptase PCR and Western blot. Furthermore, legumain expression in 88 prostatectomy specimens was evaluated by immunohistochemistry. The association between legumain expression and clinicopathological factors was analyzed. RESULTS: Legumain expression was confirmed at the mRNA and protein levels in all the cells. Although all the cancer tissues were positive for legumain, 2 staining patterns were observed in the cytoplasm: diffuse cytoplasmic and vesicular positivity. The rates of Gleason score ≥8, extracapsular extension, and perineural invasion in the group with vesicular staining were significantly higher than those in the diffuse cytoplasmic group (p < 0.05). The maximum size of the tumor with vesicular staining was significantly greater than that of the tumor with diffuse cytoplasmic staining (p = 0.0302). The 5-year biochemical recurrence-free rate in the patients with vesicular legumain staining was 53.2%; this rate was significantly lower than that (78.8%) in the patients with diffuse cytoplasmic staining (p = 0.0269). CONCLUSIONS: Tumors that showed a vesicular staining pattern of legumain had the potential of being highly invasive and aggressive in patients with prostate cancer who were treated with radical prostatectomy. This suggests that legumain might contribute to the invasiveness and aggressiveness of prostate cancer.