Involvement of TRPV4 in temperature-dependent perspiration in mice.

Reports indicate that an interaction between TRPV4 and anoctamin 1 (ANO1) could be widely involved in water efflux of exocrine glands, suggesting that the interaction could play a role in perspiration. In secretory cells of sweat glands present in mouse foot pads, TRPV4 clearly colocalized with cytokeratin 8, ANO1, and aquaporin-5 (AQP5). Mouse sweat glands showed TRPV4-dependent cytosolic Ca2+ increases that were inhibited by menthol. Acetylcholine-stimulated sweating in foot pads was temperature-dependent in wild-type, but not in TRPV4-deficient mice and was inhibited by menthol both in wild-type and TRPM8KO mice. The basal sweating without acetylcholine stimulation was inhibited by an ANO1 inhibitor. Sweating could be important for maintaining friction forces in mouse foot pads, and this possibility is supported by the finding that wild-type mice climbed up a slippery slope more easily than TRPV4-deficient mice. Furthermore, TRPV4 expression was significantly higher in controls and normohidrotic skin from patients with acquired idiopathic generalized anhidrosis (AIGA) compared to anhidrotic skin from patients with AIGA. Collectively, TRPV4 is likely involved in temperature-dependent perspiration via interactions with ANO1, and TRPV4 itself or the TRPV4/ANO 1 complex would be targeted to develop agents that regulate perspiration.

Stress, spicy foods and elevated temperatures can all trigger specialized gland cells to move water to the skin ­ in other words, they can make us sweat. This process is one of the most important ways by which our bodies regulate their temperature and avoid life-threatening conditions such as heatstroke. Disorders in which this function is impaired, such as AIGA (acquired idiopathic generalized anhidrosis), pose significant health risks. Finding treatments for sweat-related diseases requires a detailed understanding of the molecular mechanisms behind sweating, which has yet to be achieved. Recent research has highlighted the role of two ion channels, TRPV4 and ANO1, in regulating fluid secretion in glands that produce tears and saliva. These gate-like proteins control how certain ions move in or out of cells, which also influences water movement. Once activated by external stimuli, TRPV4 allows calcium ions to enter the cell, causing ANO1 to open and chloride ions to leave. This results in water also exiting the cell through dedicated channels, before being collected in ducts connected to the outside of the body. TRPV4, which is activated by heat, is also present in human sweat gland cells. This prompted Kashio et al. to examine the role of these channels in sweat production, focusing on mice as well as AIGA patients. Probing TRPV4, ANO1 and AQP5 (a type of water channel) levels using fluorescent antibodies confirmed that these channels are all found in the same sweat gland cells in the foot pads of mice. Further experiments highlighted that TRPV4 mediates sweat production in these animals via ANO1 activation. As rodents do not regulate their body temperature by sweating, Kashio et al. explored the biological benefits of having sweaty paws. Mice lacking TRPV4 had reduced sweating and were less able to climb a slippery slope, suggesting that a layer of sweat helps improve traction. Finally, Kashio et al. compared samples obtained from healthy volunteers with those from AIGA patients and found that TRPV4 levels are lower in individuals affected by the disease. Overall, these findings reveal new insights into the underlying mechanisms of sweating, with TRPV4 a potential therapeutic target for conditions like AIGA. The results also suggest that sweating could be controlled by local changes in temperature detected by heat-sensing channels such as TRPV4. This would depart from our current understanding that sweating is solely controlled by the autonomic nervous system, which regulates involuntary bodily functions such as saliva and tear production.

Hereditary Gastric Cancer Is Linked With Hereditary Breast and Ovarian Cancer.

Background: Helicobacter pylori (H. pylori), a bacterium which chronically infects the stomach of approximately half the world's population, is a risk factor for the development of gastric cancer (GC). However, the underlying mechanism whereby H. pylori infection induces GC development remains unclear. Intermittent injection of the H. pylori cytotoxin-associated gene A antigen (CagA) protein into its host cell inhibits nuclear translocation of BRCA1/BRCA2, DNA repair proteins involved in the development of breast cancer/ovarian cancer. Interestingly, hereditary breast and ovarian cancer (HBOC) syndrome is associated with GC development. Here, we aimed to clarify the molecular link between H. pylori infection, BRCA1/2 pathogenic variants (PVs), GC and higher GC incidence in HBOC families. Methods: We retrospectively reviewed data from Japanese patients undergoing precision treatment using cancer genomic medicine. Results: We found a higher GC incidence in HBOC families having germline pathogenic variants (GPVs) of BRCA1/2 (2.95% vs. 0.78% in non-HBOC families). Next, we found that 96.1% of H. pylori-infected patients received cancer genomic medicine for advanced GC, and > 16% advanced GC patients had gBRCA2 PVs. Furthermore, expressing wild-type BRCA1/2 in Gan mice (a mouse model of human GC) inhibited GC development. Thus, gBRAC1/2 PVs and H. pylori infection synergistically increase the risk of GC development. Conclusion: Our study highlights the need to investigate the potential of therapeutic agents against BRCA1/2 PVs to avoid the development of GC in HBOC families. In addition, our results suggest that poly (ADP-ribose) polymerase (PARP) inhibitors could potentially inhibit GC development and progression with gBRCA1/2 PVs.

High Transferability of Neutralizing Antibodies against SARS-CoV-2 to Umbilical Cord Blood in Pregnant Women Vaccinated with BNT162b2 XBB.1.5: A Retrospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to severe respiratory illness, rapid disease progression, and higher rates of intensive care unit admission in pregnant women. Infection during pregnancy is associated with an increased risk of preterm delivery, cesarean section, fetal dysfunction, preeclampsia, and perinatal death. Vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from pregnant women to their fetuses has also been observed. Although severe infections in neonates and infants are rare, newborns can experience serious consequences from COVID-19 due to their suboptimal humoral immune system protection. The amino acids in the structural proteins of SARS-CoV-2 are constantly mutating. Since around January 2023, COVID-19, caused by omicron-type SARS-CoV-2 variants, has been prevalent globally. These variants can evade the immune response triggered by traditional mRNA-based COVID-19 vaccines, such as BNT162b2. Therefore, vaccination with BNT162b2 XBB.1.5, which provides protection against omicron-type SARS-CoV-2 variants, is recommended. METHODS: This retrospective cohort study included 148 pregnant women who received the BNT162b2 XBB.1.5 vaccine at 30 partner medical institutions from September 2023 to January 2024. We examined the titers of anti-spike glycoprotein SARS-CoV-2 immunoglobin G (IgG) and IgA in the blood and umbilical cord blood obtained from the participants using ELISA. FINDINGS: Anti-spike glycoprotein SARS-CoV-2 IgG and IgA titers were highest in the blood and cord blood at late gestational age (28-34 weeks). No serious side effects or adverse events were observed in either the pregnant women or their newborns. INTERPRETATION: Pregnant women who received the BNT162b2 XBB.1.5 vaccine during gestational weeks 28 to 34 had the highest titers of anti-omicron SARS-CoV-2 variant antibodies in their blood. Moreover, these antibodies were transferred to their umbilical cord blood. To validate our findings, large cohort clinical studies involving numerous pregnant women are warranted. FUNDING: This study was funded by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and Grants-in-Aid for Medical Research from the Japan Agency for Medical Research and Development (AMED).

Sirt3 Regulates Proliferation and Progesterone Production in Leydig Cells via Suppression of Reactive Oxygen Species.

Sirt3 is a mitochondrial protein deacetylase functioning in energy metabolism, regulation of intracellular reactive oxygen species (ROS) levels, and aging. Although Sirt3 loss has negative effects on fertility of oocytes during in vitro fertilization and on progesterone production in granulosa cells, Sirt3's function in Leydig cells remains unclear. Therefore, we investigated Sirt3 activity in Leydig cells, focusing on androgen production. To do so, we performed immunohistochemistry to confirm Sirt3 localization in gonads and observed strong Sirt3 immunostaining in Leydig cells of human testes and of Sirt3+/+ and Sirt3+/- mouse testes, while Sirt3-/- mouse testis tissue was negative. In human ovary, hilus cells were strongly Sirt3-positive, theca cells showed weak positivity, and granulosa cells showed very weak or almost no immunostaining. Next, we used the murine Leydig tumor cell line MA-10 as a model. We overexpressed Sirt3 but observed no changes in proliferation, expression of Star, Cyp11a1 (p450scc gene), and Hsd3b, or progesterone production in MA-10 cells. Sirt3 knockdown significantly reduced proliferation, suppressed expressions of steroidogenic enzymes and of transcription factors Ad4bp (Sf-1 gene) and Gata4, and decreased progesterone production. Sirt3 knockdown in MA-10 cells also increased intracellular ROS levels based on CM-H2DCFDA fluorescence dye analysis and increased the proportion of both early and late apoptotic (necrotic) cells based on Annexin V/7AAD assays. These results indicate that Sirt3 has a potential function in androgen production in Leydig cells by regulating intracellular ROS levels.

Characteristic of Endometrial Stromal Sarcoma by Algorithm of Potential Biomarkers for Uterine Mesenchymal Tumor.

The benign tumor uterine leiomyoma (UL) develops from the smooth muscle tissue that constitutes the uterus, whereas malignant tumor uterine sarcoma develops from either the smooth muscle tissue or stroma and is different from UL and endometrial cancer. Uterine sarcoma is broadly classified into three types: uterine leiomyosarcoma, endometrial stromal sarcoma (ESS), and carcinosarcoma. Although uterine leiomyosarcoma and ESS are both classified as uterine sarcoma, they significantly differ in terms of their sites of occurrence, symptoms, and treatment methods. Uterine leiomyosarcoma develops from the muscle tissue constituting the wall of the uterus and accounts for approximately 70% of all uterine sarcoma cases. In contrast, ESS develops from the stromal tissue beneath the endometrium and accounts for approximately 25% of all uterine sarcoma cases. ESS is classified as either low grade (LG) or high grade (HG). This case report aimed to highlight the importance of histopathologic examinations based on surgical specimens. Herein, we reported the case of a 45-year-old woman suspected of having submucosal leiomyoma of the uterus based on imaging results. Transvaginal ultrasonography and endometrial biopsy or partial dilation and curettage were performed. Contrast-enhanced magnetic resonance imaging (MRI) revealed a 32-mm mass projecting from the posterior wall of the uterus into the uterine cavity. T2-weighted imaging revealed a low signal within the mass; thus, submucosal UL was suspected. Histopathologic examination of surgical specimens obtained from a patient suspected of having submucosal UL after contrast-enhanced MRI indicated that the patient had ESS. Despite the remarkable advancements in medical imaging technology, the accuracy of contrast-enhanced MRI for detecting uterine mesenchymal tumors is limited. Therefore, histopathologic diagnosis based on surgical specimens should be performed when medical grounds for diagnosing a benign tumor on contrast-enhanced MRI are lacking.

Histopathological Findings of Ectopic Pregnancy in Contraceptive-Wearing Woman.

In normal pregnancy, the egg is fertilized in the fallopian tube. It later moves into the uterus, where it implants into the uterine endometrium. Therefore, implantation of the fertilized egg into the endometrium is not observed in many women using contraceptives. However, if the fallopian tubes are diseased or abnormal, the fertilized egg cannot travel to the endometrium. Thus, the fertilized egg is implanted in tissues other than the uterus, resulting in an ectopic pregnancy. In most cases of ectopic pregnancy, the fertilized egg is implanted into the left or right fallopian tube or in tissues other than the fallopian tubes such as the ovary. With laparoscopic surgery, the scars are small, and the pain and physical burden are also much lesser than those with open surgery; thus, the patient can be rehabilitated immediately. Laparoscopic surgery is preferred for the termination of ectopic pregnancies because the patients recovered quickly physically after surgery and can be discharged in a short period. This paper presents our experience in treating a 37-year-old woman who had a tubal pregnancy despite using a contraceptive. Contrast-enhanced magnetic resonance imaging showed a gestational sac within the right fallopian tube. Laparoscopic surgery was performed to resect the right fallopian tube. Pathological examination suggested that the ectopic pregnancy occurred at the organogenesis stage 9 weeks after fertilization. The pathological findings revealed subpopulations of cells from the ectoderm that were separated from other cells and more specifically formed spinal and ovarian structures. The implantation of the fertilized egg into the endometrium is not observed in many women using contraceptives. However, in rare cases, ectopic pregnancy occurs in women using contraceptives; thus, caution is necessary in diagnosis and treatment. This report presents valuable surgical pathological findings from such a rare case of ectopic pregnancy to understand the differentiation into each tissue during organogenesis.

Mucinous carcinoma originating from uterine adenomyosis: a case report.

BACKGROUND: Uterine adenomyosis is rarely a precursor of malignant tumors, but the most frequent histological subtype is endometrioid carcinoma. We observed a rare case of mucinous carcinoma originating from uterine adenomyosis. CASE PRESENTATION: A 63-year-old Japanese woman presented to our hospital with lower abdominal pain. She had no atypical genital bleeding. Ultrasound demonstrated thickening of the entire uterine wall, but the endometrium was not thick. Magnetic resonance imaging demonstrated an enlarged uterus with thickening of the entire uterine wall, suggesting adenomyosis. On the basis of the specimen of endocervical curettage, adenocarcinoma originating from the endometrium was suspected. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed to confirm the diagnosis. Macroscopically, the resected enlarged uterus had no nodules and exudation of mucin was observed from the cut surface of the thickened myometrium. The surface of the endometrium was smooth. On histological examination, mucinous carcinoma invaded almost the entire myometrium. Adenomyotic lesions were distributed focally in the uterine wall, and transition from adenomyotic glandular epithelium to mucinous carcinoma was detected within several foci. Although adenocarcinoma cells proliferated adjacent to the endometrium, the primary endometrial epithelium was atrophic without atypia. Throughout the myometrium, the mucinous carcinoma cells proliferated and floated in dilated lymph vessels with abundant mucin pools. We diagnosed this case as mucinous carcinoma originating from adenomyosis. Although the patient received 11 courses of intravenous adjuvant chemotherapy, she died of disease 18 months after the first operation. CONCLUSION: As only one case of mucinous carcinoma originating from adenomyosis has been reported to date, this is the second case report of mucinous carcinoma. Moreover, an abnormal manner of proliferation with marked lymphatic permeation of the tumor cells throughout the myometrium was observed.

Pathological Evidence for Residual SARS-CoV-2 in the Micrometastatic Niche of a Patient with Ovarian Cancer.

In previous clinical studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients has a high risk of aggravation and mortality than in healthy infected individuals. Inoculation with coronavirus disease 2019 (COVID-19) vaccine reduces the risk of SARS-CoV-2 infection and COVID-19 severity. However, vaccination-induced anti-SARS-CoV-2 antibody production is said to be lower in cancer patients than in healthy individuals. In addition, the rationale for why the condition of patients with cancer worsens with COVID-19 is not well understood. Therefore, we examined the infection status of SARS-CoV-2 in the primary tumor and micrometastasis tissues of the patient with cancer and COVID-19. In this study, the expression of angiotensin-converting enzyme 2 (ACE2) was observed, and SARS-CoV-2 particles was detected in ovarian tissue cells in contact with the micrometastatic niche of the patient with high-grade serous ovarian cancer. We believe that the severity of COVID-19 in patients with cancer can be attributed to these pathological features. Therefore, the pathological findings of patients with advanced and recurrent ovarian cancer infected with SARS-CoV-2 may help decrease COVID-19 severity in patients with other cancer types.

Possibility of SARS-CoV-2 Infection in the Metastatic Microenvironment of Cancer.

According to a report from the World Health Organization (WHO), the mortality and disease severity induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are significantly higher in cancer patients than those of individuals with no known condition. Common and cancer-specific risk factors might be involved in the mortality and severity rates observed in the coronavirus disease 2019 (COVID-19). Similarly, various factors might contribute to the aggravation of COVID-19 in patients with cancer. However, the factors involved in the aggravation of COVID-19 in cancer patients have not been fully investigated so far. The formation of metastases in other organs is common in cancer patients. Therefore, the present study investigated the association between lung metastatic lesion formation and SARS-CoV-2 infectivity. In the pulmonary micrometastatic niche of patients with ovarian cancer, alveolar epithelial stem-like cells were found adjacent to ovarian cancer. Moreover, angiotensin-converting enzyme 2, a host-side receptor for SARS-CoV-2, was expressed in these alveolar epithelial stem-like cells. Furthermore, the spike glycoprotein receptor-binding domain (RBD) of SARS-CoV-2 was bound to alveolar epithelial stem-like cells. Altogether, these data suggested that patients with cancer and pulmonary micrometastases are more susceptible to SARS-CoV-2. The prevention of de novo niche formation in metastatic diseases might constitute a new strategy for the clinical treatment of COVID-19 for patients with cancer.

Successful Radiotherapy of Primary Malignant Peripheral Nerve Sheath Tumor of the Lung.

A 71-year-old man presented with cough and bloody sputum. Computed tomography showed a mass in the lower lobe of the left lung. Histological findings in biopsy tissue revealed a malignant peripheral nerve sheath tumor (MPNST). The patient was diagnosed with primary lung MPNST based on a systemic examination. Although initial chemotherapy treatment with doxorubicin failed to control the disease, radiotherapy considerably shrank the tumor. Primary lung MPNSTs are rare, and there is no established treatment for inoperable cases. This case suggests that radiotherapy is a treatment option for primary lung MPNST.

2-Step PLT16-AST44 method: Simplified liver fibrosis detection system in patients with non-alcoholic fatty liver disease.

AIM: Accurate detection of the hepatic fibrosis stage is essential to estimate the outcome of patients with non-alcoholic fatty liver disease (NAFLD). Many formulas, biomarkers, and imaging tests are being developed to predict advanced liver fibrosis without performing a liver biopsy. However, these tests do not have high efficiency in detecting early-stage hepatic fibrosis. Therefore, we aimed to detect the presence of hepatic fibrosis (≥F1) merely by using only standard clinical markers. METHODS: A total of 436 patients with NAFLD who underwent liver biopsy were retrospectively enrolled as the discovery cohort (316 patients) and the validation cohort (120 patients). Liver biopsy and laboratory data were matched to extract simple parameters for identifying ≥F1. RESULTS: We developed a novel simplified ≥F1 detecting system, designated as 2-Step PLT16-AST44 method, where (1) PLT of 16 × 104 /µl or less, or (2) PLT greater than 16 × 104 /µl and AST greater than 44 U/L is determined as having ≥F1 fibrosis. The 2-Step PLT16-AST44 method had a sensitivity of 68%, a specificity of 90%, a positive predictive value (PPV) of 97%, a negative predictive value (NPV) of 40%, and an accuracy of 72% to detect ≥F1 fibrosis in the discovery cohort. Validation studies further supported these results. Despite its simplicity, the 2-Step PLT16-AST44 method's power to detect ≥F1 fibrosis in total NAFLD patients was comparable to hyaluronic acid, type 4 collagen 7S, FIB-4, and APRI. CONCLUSIONS: We propose the 2-Step PLT16-AST44 method as a simple and beneficial early-stage hepatic fibrosis detection system.

Maffucci Syndrome with Intrahepatic Cholangiocarcinoma: A Case Report.

Maffucci syndrome is characterized by multiple hemangiomas and enchondromas. Somatic mutations in IDH1 and IDH2 are associated with the development of Maffucci syndrome, and these patients develop various malignant nonskeletal tumors in addition to malignant skeletal tumors. We report a case of Maffucci syndrome with IDH1 mutation complicated by intrahepatic cholangiocarcinoma. The patient was a 35-year-old woman who was diagnosed with Maffucci syndrome in childhood. She was referred to our department because of a large hepatic tumor. Serum carcinoembryonic antigen was 27.1 ng/mL upon laboratory examination. CT scanning showed a large low-density tumor (90 × 70 mm) in the right lobe of the liver, and MRI revealed a multilobulated and fibrous tumor, which was observed as high signal intensity on T2- and diffusion-weighted images and low signal intensity on T1-weighted images. Positron emission tomography-CT revealed peritoneal dissemination and cancer spread to the muscles of the back. Finally, she was diagnosed with intrahepatic cholangiocarcinoma with dissemination and metastases. We performed a tumor biopsy to determine a treatment plan for chemotherapy. Sanger sequencing of a tumor biopsy identified a mutation in IDH1 at c.394C>T (R132C), but the patient died of rapid cancer progression before the chemotherapy could be initiated. Although rare, malignant tumors can develop in patients with Maffucci syndrome; therefore, it is necessary to monitor these tumors through careful and periodic observation.

Development of Uterine Leiomyosarcoma During Follow-up After Caesarean Section in a Woman With Uterine Leiomyoma.

BACKGROUND/AIM: During pregnancy, uterine leiomyomas may cause problems and treatment typically entails uterine conservation. However, for cases of leiomyomas larger than a particular size with some clinical symptoms, enucleation should be performed. In clinical practice, the importance of postpartum follow-up of pregnancies with uterine fibroids must be established. PATIENTS AND METHODS: A 47-year-old female visited an obstetrics and gynecology clinic with a primary complaint of irregular bleeding. We suspected an 8.4×6.6 cm myoma uteri and recommended immediate surgery. During the next visit, a pregnancy test was positive and the patient requested a follow-up for her myoma uteri diagnosis. Because of a breech presentation, we performed an elective cesarean section (CS) at 38 weeks and 1 day. The patient's myoma uteri was stable throughout the pregnancy, and after delivery, we continued to follow her up as an outpatient. RESULTS: Two years after the CS, the myoma uterus was 6 cm in size, and 6 months later, it had increased to 10 cm. Magnetic resonance imaging (MRI) supported a diagnosis of uterine leiomyosarcoma and she underwent surgery. Ultimately, she was pathologically diagnosed with uterine leiomyoma, uterine leiomyoma with bizarre nuclei, and uterine leiomyosarcoma following examination of the excised tissue by using molecular pathological examination with anti-cyclin E antibody and anti-Ki-67 antibody. CONCLUSION: Notably, this case demonstrated the usefulness of cyclin E and Ki-67 as biomarkers for the malignancy of uterine mesenchymal tumors. Presently, she is being monitored for tumor recurrence and metastases on a quarterly basis. In order to detect the rapid increase in uterine mesenchymal tumor, regular follow-up after birth is important.

Mucosal defect size predicts the adequacy of resection of ≤10 mm nonpedunculated colorectal polyps using a new cold snare polypectomy technique.

OBJECTIVES: There is still room for improvement in the methods used to achieve complete polyp resection. The aim of this study was to develop a cold snare polypectomy technique that will reliably result in resections containing the muscularis mucosae and the lateral polyp margins. MATERIALS AND METHODS: Nonpedunculated polyps ≤10 mm were resected using a dedicated cold snare with the goal of creating a mucosal defect approximately 1 cm in dia. The completeness of resection of the lateral and vertical polyp margins was examined histologically. RESULTS: The cases of 201 patients (mean age 67 ± 13 years; 115 men) with 500 eligible polyps were enrolled. The mean polyp size was 6.1 ± 1.8 mm (range 1-10 mm). The mean mucosal defect size immediately after resection was 7.7 ± 2.5 mm (range 3-15 mm). Overall, the complete resection rate in which the lateral and vertical margins were free from the neoplasia tissue was 92% (417/454, 95% CI, 89-94); in the remaining 8% of cases, the vertical margins showed complete resection but the lateral margins could not be evaluated due to the fragmentation of resected polyps. A mucosal defect ≥7 mm predicted complete resection of the mucosal layer containing the muscularis mucosae. CONCLUSION: Complete mucosal layer resection of nonpedunculated colorectal polyps ≤10 mm was reliably achieved using a cold snare technique that produced a mucosal defect ≥7 mm in dia.

Clear cell injury associated with reduced expression of carbonic anhydrase II in eccrine glands consistently occurs in patients with acquired idiopathic generalized anhidrosis.

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. It has been believed that AIGA patients usually present no significant morphological alterations in the secretory portion of eccrine glands consisting of clear, dark and myoepithelial cells. However, we have recently revealed morphological damage of eccrine glands in AIGA patients by immunohistochemistry. Moreover, inhibitory side-effects against carbonic anhydrase II (CA II) by the antiepileptic reagent topiramate have been reported to cause heat intolerance mimicking AIGA. To determine the precise morphological changes and CA II expression in eccrine glands of AIGA patients, electron microscopic observation and immunohistochemistry were applied to skin of both anhidrotic (non-sweating) and normohidrotic (sweating-preserved) sites, taken from each patient clinically diagnosed with AIGA. We found consistent clear cell injury in eccrine glands in anhidrotic skin samples of AIGA patients. Electron micrographs demonstrated edematous, swollen and destructive damage in clear cells of eccrine glands from non-sweating areas of almost all AIGA patients. Immunohistochemically, clear cells showed reduced CA II expression that was heterogeneously distributed in non-sweating skin. Some areas showed almost complete loss of CA II expression in spite of preserved dark cells, and others showed mild or moderate loss of it. Selective destruction of clear cells resulting in heterogenous atrophy in AIGA patients may be important to elucidate its etiology.

Synchronous triple primary lung cancer with three different histological subtypes in the same lobe: A case report.

Although the number of patients diagnosed with synchronous multiple primary lung cancer is growing because of increased screening and improved imaging technology, synchronous triple primary lung cancer with different histological tumor subtypes occurring in the same lobe of the lung is extremely rare. In this report, we encountered a 64-year-old male patient with three different types of nodule in the right lower lobe of the lung found on chest computed tomography (CT) scan. We believed that the patient had triple primary lung cancer, and subsequently performed a right lower lobectomy using video-assisted thoracoscopic surgery (VATS). The pathological diagnosis was the same as the presurgical diagnosis, but all the nodules were different histological subtypes. To the best of our knowledge, this is the first case reported in the literature of synchronous triple primary lung cancer with three different histological subtypes in the same lobe of the lung. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This is the first case of synchronous triple primary lung cancer with three different histological subtypes in each tumor in the same lobe of the lung. WHAT THIS STUDY ADDS: We report the details of the case with immunohistochemical and gene mutation findings, and a literature review of synchronous primary lung cancer.

Supratentorial Intraparenchymal Neurenteric Cyst Treated by Neuroendoscopic Fenestration: A Case Report and Review of Literature.

Neurenteric cysts (NCs) are rare benign congenital neoplasms in the central nervous system that originate from endodermal elements. NCs are more commonly located in the spine than in the brain. Although almost all intracranial NCs are found in the posterior fossa, some have reported supratentorial NCs. The complete excision of the cyst wall is suggested as a curative treatment; however, endoscopic treatment is less discussed. We present a supratentorial intraparenchymal NC in the frontal lobe treated by neuroendoscopic fenestration and review the literature regarding supratentorial NCs. A 43-year-old woman presenting with right hemiparesis and gait disturbance who was found to have a huge cystic lesion with calcification in her left frontal lobe underwent endoscopic fenestration to the ipsilateral lateral ventricle and biopsy. The histopathological diagnosis was consistent with NC. Postoperatively, her right hemiparesis and gait disturbance disappeared. Postoperative MRI showed shrinkage of the cyst. She was discharged without neurological deficits and no recurrence was seen 1 year after surgery. To the best of our knowledge, there have been no reports of a supratentorial intraparenchymal NC treated by neuroendoscopic fenestration. Minimally invasive treatments, such as neuroendoscopic cyst fenestration, can be considered depending on the location of the cyst.