Cavitary lung metastases of mixed metaplastic breast cancer mimicking aspergilloma.

We report a case of a 57-year-old woman with pulmonary metastasis of breast cancer presenting with a characteristic cavitary shadow resembling aspergilloma. The primary tumor and metastases showed multiple histopathologic components, including squamous cell carcinoma. Although a fungal ball-like shadow may indicate the presence of a pulmonary aspergilloma, a comprehensive examination, including bronchoscopy, should be considered.

Physical health risks of middle-aged people with low social independence: fatal diseases in men, and little attendance to cancer screenings in both sexes.

Background: The existence of social withdrawal (Hikikomori), which meets the conditions "not attending school", "not working", and "isolated at home for more than 6 months", is gradually being discovered by the world, and their mental health and healing is being highlighted. However, there are very few Hikikomori-related surveys searching their physical health, as it is generally believed that most Hikikomori are adolescents. Middle-aged Hikikomori are also found outside Japan, and their physical health is more important, because Hikikomori have difficulty managing their health due to the socially isolated circumstances and lack of sociability. Although "isolated at home for more than 6 months" could not be used, we extracted a group with low social independence with reference to Hikikomori-related surveys. We estimate that people with low social independence have similar characteristics and problems to Hikikomori, because they share many causes for the problem of difficulty in managing their own health. People with low social independence were identified, and their physical health, such as smoking and drinking status, consultation rates of various diseases, and how often they attend cancer screenings, was analyzed. Methods: We extracted middle-aged people with low social independence and a control group from the national survey in Japan and stratified them by sex and age. Their health risks were assessed by univariate analysis. Criteria for the experimental group were set with reference to Hikikomori-related surveys. Criteria for the control group included "aged 40-69", "living with parents", "not receiving care for disabilities", and "working". Results: Low-social-independent men had higher consultation rates for diabetes, stroke or cerebral hemorrhage, myocardial infarction or angina, gastric and duodenum diseases, kidney disease, anemia, and depression, while lower consultation rates for dyslipidemia and hypertension. The tendency of non-smoking and non-drinking was found among them. They seldom attended cancer screenings. Low-social-independent women had higher consultation rates for liver and gallbladder diseases, other digestive diseases, kidney diseases, anemia, osteoporosis, and depression. The tendency of non-drinking was the same as men. More heavy smokers were found among those aged 40-49 years, with no significant differences in other age groups. They seldom attended cancer screenings, as well as men. Conclusions: In terms of current physical health, low-social-independent men have more fatal diseases. Both sexes with low social independence seldom attend cancer screenings and have an increased risk of developing progressive cancer in the future. At least in terms of non-smoking and non-drinking, they live healthier lives than the control group, and what makes low-social-independent men have various fatal diseases is still unclear.

Multidisciplinary management of disseminated Exophiala dermatitidis mycosis in an infant with mixed phenotype acute leukemia: a case report.

BACKGROUND: Exophiala dermatitidis is a dematiaceous fungus isolated from various environmental sources. Systemic E. dermatitidis infections can lead to fatal outcomes, and treatment has not yet been standardized. Although E. dermatitidis is also known to cause cutaneous infection, it has not been previously reported to appear as ecthyma gangrenosum (EG), an uncommon cutaneous lesion in neutropenic patients that is mainly caused by Pseudomonas aeruginosa. CASE PRESENTATION: A 2-month-old male infant with mixed-phenotype acute leukemia presented with prolonged fever unresponsive to antibacterial and antifungal agents during myelosuppression due to remission induction therapy. He also presented with skin lesions on the left wrist and left lower quadrant of the abdomen. The abdominal lesion gradually turned black and necrotic, which was consistent with the findings of the EG. E. dermatitidis was isolated from the blood, stool, wrist skin, and endotracheal aspirate. During hematopoietic recovery, consolidation in both lungs was evident. Multiagent antifungal treatment failed to eliminate E. dermatitidis from blood. In order to salvage the central venous catheter, ethanol lock therapy (ELT) was adopted, following which the blood culture became negative. The abdominal lesion that evolved as a necrotic mass connecting the small intestine and subcutaneous tissue adjacent to the skin was surgically resected. After these interventions, the general condition improved. CONCLUSION: Disseminated E. dermatitidis mycosis in the neutropenic infant was successfully managed with a multidisciplinary treatment consisting of multiagent antifungal treatment, ELT, and surgery.

Focal xanthogranulomatous inflammation of the kidney cyst without pyelitis: a rare presentation mimicking kidney cancer.

Xanthogranulomatous pyelonephritis (XGP) is one of the most common granulomatous diseases of the kidney. XGP is subdivided into diffuse, segmental, and focal subtypes. Preoperative diagnosis of focal XGP on radiological imaging can be challenging, especially without involvement of the renal pelvis. Here, we report the case of a 61 year-old male with focal xanthogranulomatous inflammation of the kidney without pyelitis. The lesion presented as a mural nodule on the left renal cortical cyst, and kidney cancer was suspected on the preoperative image. The patient underwent a successful partial nephrectomy. Pathological examination revealed that the mural nodule displayed xanthogranulomatous inflammation and was clearly distinct from the renal pelvis. Thus, it should be considered that a mural nodule in a renal cortical cyst could be xanthogranulomatous inflammation.

Advantages and challenges for noninvasive atrial fibrillation ablation.

PURPOSE: Although catheter ablation is an effective therapy for atrial fibrillation (AF), risks remain and improved efficacy is desired. Stereotactic radiotherapy is a well-established therapy used to noninvasively treat malignancies with precision. We sought to evaluate stereotactic arrhythmia radioablation (STAR) as a therapeutic option for treating AF. METHODS AND RESULTS: Three cancer patients with drug refractory AF were enrolled. Planning software using 3-D CT of the left atrium was used to design a desired ablation volume encompassing antral circumferential pulmonary vein isolation, roof and floor lines to create a "box" lesion set. After planning, patients were treated in the radioablation suite. STAR was able to deliver the intended radiation dose to the target in all 3 patients. No complications were observed over a follow-up period of 24 months. One patient with paroxysmal AF died from deterioration of cancer. The autopsy revealed evidence of fibroblasts and fibrogenesis in the region of atrial tissues targeted with radioablation. In one of these patients, left atrial posterior wall electrograms recorded from the esophagus before and 3 months after STAR indicated successful electrical isolation. CONCLUSIONS: This is the first report of non-invasive radioablation of the left atrium with demonstration of successful electrical isolation. Although STAR may be safe and effective in delivering ablative energy to the left atrium, further evaluation is warranted regarding effectiveness.

Chemotherapy-associated foam cell aggregates as a prognostic factor in patients with pelvic high-grade serous carcinoma receiving neo-adjuvant chemotherapy.

High-grade serous carcinoma (HGSC) tends to recur after treatment; therefore, the Chemotherapy Response Score (CRS) has been proposed as a histopathological prognostic scoring system for measuring the response to neo-adjuvant chemotherapy and the risk of recurrence. This study aimed to evaluate the CRS in only those with an R0 debulking status and to investigate new prognostic factors for progression-free survival (PFS). We reviewed the CRS of HGSC patients with R0 using surgical specimens of the omental sections. Patients were categorized according to foam cell change (FCC), defined as foam cells occupying more than half of the area of the chemotherapy-associated scar. In total, 100 HGSC patients were evaluated. PFS was significantly different according to the CRS. For CRSs of 1/2 and 3, the median PFS were 18 and 27 months, respectively (HR, 1.84; 95% CI 1.01-3.33, p = 0.045). Moreover, the FCC group showed significantly longer PFS than did the non-FCC group (20 vs 59 months; HR 2.43; 95% CI 1.15-5.14; p = 0.020). The present study validated the CRS of those in the R0 cohort. Furthermore, an increase in foam cells in the regression scar reflects the chemotherapy response and the FCC may be a useful novel prognostic factor for patients undergoing R0 resection. This finding must be further validated independently.

Characteristics and prognostic significance of incidentally detected cancer cells in uterine specimens of patients with pelvic high-grade serous carcinoma.

OBJECTIVE: Cases of pelvic high-grade serous carcinoma (HGSC) with incidentally detected cancer cells (ICCs) in endometrial and/or cervicovaginal cytology have been reported. This study aimed to clarify the incidence and characteristics of pelvic HGSC with ICCs and to determine whether ICCs have a negative prognostic impact. METHODS: Patients with ovarian/tubal/peritoneal HGSC who underwent pre-treatment uterine (endometrial/cervicovaginal) cytology or biopsy between January 2007 and May 2017 were included. We reviewed the frequencies of ICCs and compared the clinicopathological features and survival outcome between the ICC-positive and ICC-negative groups. RESULTS: Of the 160 patients evaluated, 69 (43.2%) had positive ICCs in at least one uterine specimen. There were no significant differences in clinicopathological characteristics, such as age, FIGO stage, serum CA125 level, ascites, and tubal lesion, between the two groups. Moreover, ICCs had no significant survival impact on progression-free survival or overall survival. CONCLUSION: Our study showed a high rate of pelvic HGSC with ICCs in pre-treatment uterine specimens. The ICCs per se had no negative impact on survival outcomes of pelvic HGSC. Furthermore, uterine biopsy and cytology can be useful and less-invasive methods to obtain tubo-ovarian/peritoneal cancer cells before treatment.

Primary Clear Cell Adenocarcinoma of the Vulva: A Case Study With Mutation Analysis and Literature Review.

Primary vulvar clear cell carcinoma (CCC) is extremely rare. In this article, we report a primary vulvar CCC along with immunohistochemical and gene mutation analyses results and literature review to discuss the clinicopathological features and tumorigenesis of this rare tumor. A 70-year-old (gravida 2 para 2) Japanese woman complained of bleeding from a vulvar mass at a past episiotomy site. A 1.8 × 1.8 × 0.5 cm exophytic sessile mass was present on the vestibular area inside the left labium minora. Radical local excision of the tumor and resection of the inguinal lymph nodes on both sides were performed. Histopathology revealed a vulvar CCC with immunohistochemical positivity for PAX8, HNF-1ß, ER, and CA125, and negativity for p16, CD10, GATA3, PTEN, and PAX2, suggesting its Müllerian origin. No lymph node metastasis was observed. The tumor was a 5-mm exophytic growth without deep stromal invasion; thus, it was difficult to measure the invasion depth assuming a squamous cell carcinoma. To investigate pathogenic/oncogenic mutations in 50 cancer-related genes, we used the AmpliSeq Cancer Hotspot Panel. However, no pathogenic/oncogenic mutations were detected. Literature review revealed that most cases of vulvar CCC are associated with vulvar endometriosis. In particular, cases with clinically evident endometriosis at the episiotomy scar should be carefully observed. Evidence-based pathological stages of vulvar adenocarcinoma including CCC remain to be established owing to its rarity, with nationwide or global accumulation of cases required in future.

Soluble α-klotho is a potential biomarker associated with neuropsychiatric systemic lupus erythematosus.

A reduced level of the single-pass transmembrane protein α-Klotho is known to be associated with neuronal damage. We investigated whether α-Klotho in cerebrospinal fluid (CSF) could be a candidate marker for the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE). We analyzed the laboratory data, symptoms and radiological image findings of 34 NPSLE patients. Patients with SLE without neuropsychiatric manifestations (SLE) (n=25), and patients with viral meningitis (VM) (n=19), multiple sclerosis (MS) (n=20) or neuromyelitis optica (NMO) (n=20) were included as controls. The multivariable analyses revealed that lower CSF α-Klotho level, lower serum anti-Smith antibodies (U/mL) and higher serum C3 (mg/dL) were significant factors for predicting NPSLE. The CSF α-Klotho levels of the NPSLE patients were inversely correlated with the level of granulocyte/macrophage-colony stimulating factor. Our data suggested that the determination of CSF α-Klotho levels will contribute to the diagnosis of NPSLE and help elucidate the mechanisms underlying this disease.

Lupus Nephritis IgG Induction of Calcium/Calmodulin-Dependent Protein Kinase IV Expression in Podocytes and Alteration of Their Function.

OBJECTIVE: Kidney podocytes and their slit diaphragms prevent urinary protein loss. T cells from patients with systemic lupus erythematosus display increased expression of calcium/calmodulin-dependent protein kinase IV (CaMKIV). The present study was undertaken to investigate the role of CaMKIV in podocyte function in lupus nephritis (LN). METHODS: We treated kidney podocytes with IgG derived from healthy individuals or patients with LN and then analyzed gene expression using a DNA microarray. The localization of IgG in podocytes was analyzed by immunofluorescence staining, with or without silencing of neonatal Fc receptor (FcRn). In addition, we silenced CAMK4 in podocytes and analyzed the expression of selected genes. We also examined the expression of CD86 in kidney podocytes from MRL/lpr, MRL/lpr.camkiv(-/-), and MRL/MPJ mice by in situ hybridization. RESULTS: We found that exposure of podocytes to IgG resulted in entry of IgG into the cytoplasm. IgG entered podocytes via the FcRn because less IgG was found in the cytoplasm of podocytes treated with FcRn small interfering RNA. DNA microarray studies of podocytes exposed to LN-derived IgG revealed up-regulation of genes related to the activation of immune cells or podocyte damage. Interestingly, CD86 expression decreased after silencing CAMK4 in podocytes. Also, in situ hybridization experiments showed that the expression of CD86 was reduced in podocytes from MRL/lpr.camkiv(-/-) mice. CONCLUSION: LN-derived IgG enters podocytes and up-regulates CAMK4, which is followed by increased expression of genes known to be linked to podocyte damage and T cell activation. Targeted inhibition of CAMK4 in podocytes may prove to be clinically useful in patients with LN.

Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication in SLE. Although the mechanism of NPSLE remains unclear, cytokines and chemokines are considered to be involved in their pathogenesis. Here we used Bio-Plex Pro assays to examine 27 types of cytokines and chemokines in the cerebrospinal fluid (CSF) of 32 NPSLE patients. We used the CSF of 20 patients with multiple sclerosis (MS) and 22 patients with neuromyelitis optica (NMO) as a disease control group. Fourteen of 27 cytokines/chemokines were significantly higher in the NPSLE patients compared to the MS/NMO patients. We could identify six "minimum predictive markers" by using a weighted-voting algorithm that could distinguish NPSLE from MS and NMO: interleukin (IL)-17, IL-2, interferon (IFN)-γ, IL-5, basic fibroblast growth factor (FGF)-basic and IL-15. The determination of various types of CSF cytokine profiles may contribute to the diagnosis of NPSLE and may help elucidate the mechanisms underlying this disease.