Reactivated Toxoplasmic Encephalitis-A case report with histopathology, ultrastructure and pathogenesis analysis.

We report a patient who developed reactivated toxoplasmic encephalitis due to human immunodeficiency (HIV)-associated immune compromise, resulting in a breakdown of the balance between the host immunity and toxoplasma cyst. Through detailed pathological analysis, spilling of tachyzoites from the ruptured wall of toxoplasma cyst can be identified. It was also proved that Toxoplasma gondii would infect endothelial cells of blood vessels, leading to vasculitis and brain ischemic necrosis. By transmission electron microscope (TEM), apical complex of the parasite can be identified, as well as tachyzoites in rapid reproduction through fission. Rhoptry, a club-shaped specialized organelle, which is characteristic of the motile stages of Apicomplexa protozoans, was also identified. The prevention of toxoplasma infection is still an issue to be emphasized in public health. This article is special in its pathophysiology-based description of the morphology. 'Form ever follows function' is a famous quote from the architect Louis Sullivan. In this case report, we make effort to depict a pathophysiology-based or a 'form-function correlation' interpretation of the histopathological findings by light microscope, IHC and ultrastructural examination. We believe such an approach should also be included in the daily pathology resident training program.

Ulcerative Warthin Tumor: A Case Report and Review of the Literature.

Warthin tumor with ulceration of the surrounding skin is extremely rare, making it difficult to differentiate from parotid cancer in the clinical setting. We report a 65-year-old man with a Warthin tumor in the right parotid gland that had ulceration of the overlying skin. The patient presented with right upper neck mass 2 years ago. Ultrasound and fine needle aspiration were done, and Warthin tumor was suspected. One year later, the mass was enlarged with ulceration of the skin. Superficial parotidectomy with fusiform excision of the skin was performed, and histopathological diagnosis revealed a Warthin tumor with inflammatory change. We proposed that this unique manifestation may have been induced by fine needle aspiration, enlargement of the tumor, and ischemic changes secondary to pulmonary arteriovenous malformations.

Contrast-enhanced ultrasound features of breast capillary hemangioma: a case report and review of literature.

Breast capillary hemangioma is a rare benign vascular tumor. A 59-year-old asymptomatic woman underwent screening mammography and breast ultrasound. B-mode ultrasound revealed a lobulated, hypoechoic mass. Color Doppler ultrasound showed no intratumoral blood flow. Contrast-enhanced ultrasound (CEUS) revealed internal fast homogeneous contrast enhancement of the mass and persistent enhancement after 4 min. A 14-gauge core needle biopsy was then performed. The radiologic and pathologic appearances were concordant with breast capillary hemangioma. The ultrasonic manifestations of breast hemangioma may vary, and differentiation from other inflammatory diseases and malignancies is challenging. CEUS may help in observing the vascular characteristics of breast capillary hemangioma.

Association of exposure to air pollutants with gestational diabetes mellitus in Chiayi City, Taiwan.

Introduction: We investigated the associations of exposure to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and several gaseous pollutants with risk of gestational diabetes mellitus (GDM) in Taiwan. Methods: We retrospectively identified pregnant women who underwent a two-step approach to screen for GDM between 2006 and 2014. Information on concentrations of air pollutants (including PM2.5, sulfur dioxide [SO2], nitrogen oxides [NOx], and ozone [O3]) were collected from a single fixed-site monitoring station. We conducted logistic regression analyses to determine the associations between exposure to air pollutants and risk of GDM. Results: A total of 11210 women were analyzed, and 705 were diagnosed with GDM. Exposure to PM2.5 during the second trimester was associated with a nearly 50% higher risk of GDM (odds ratio [OR] 1.47, 95% CI 0.96 to 2.24, p=0.077). The associations were consistent in the two-pollutant model (PM2.5 + SO2 [OR 1.73, p=0.038], PM2.5 + NOx [OR 1.52, p=0.064], PM2.5 + O3 [OR 1.96, p=0.015]), and were more prominent in women with age <30 years and body mass index <25 kg/m2 (interaction p values <0.01). Discussion: Exposure to PM2.5 was associated with risk of GDM, especially in women who were younger or had a normal body mass index.

Immunohistochemistry Helps to Distinguish Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features/Noninvasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma with Other Follicular Thyroid Lesions.

Background and Objectives: We aimed to assess the diagnostic value of various immunohistochemical (IHC) markers and panels for differentiation among benign follicular nodules (BFNs), noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), noninvasive encapsulated follicular variants of papillary thyroid carcinoma (NEFVPTCs), and infiltrative FVPTC (IFVPTC). Materials and Methods: Sixty-three cases were classified as BFNs, NIFTPs, NEFVPTCs, or IFVPTCs and were evaluated using the following markers: CK19, CD56, galectin-3, CITED1, HBME-1, VE1, and TROP-2. Results: The IHC results for NIFTP and NEFVPTC exhibited no statistically significant differences. In differentiating IFVPTCs from BFNs and NIFTPs/NEFVPTCs, galectin-3 and TROP-2 were the markers with the highest sensitivity plus high specificity, respectively. In various combinations, panel co-expression of two markers, including galectin-3 and/or HBME-1 and/or TROP-2, and the combination of galectin-3 and TROP-2 co-expression could achieve 100% in all aspects. In terms of discrimination of BFNs from NIFTP/NEFVPTC, CK19 was the single most sensitive marker (81.3%), while CD56 was the most specific (100%). The panel consisting of CK19 and/or HBME-1 exhibited the greatest sensitivity (96.9%), but the panel with CD56 and/or HBME-1 exhibited the greatest specificity (90.5%). Conclusions: Our results broaden the use of IHC markers for differential diagnoses among the four groups of follicular-based lesions. In addition, the similar IHC profiles of NIFTP and NEFVPTC also suggest the original criterion of <1% papillae within tumors, providing a reliable NIFTP diagnosis. Their close relationship may represent a spectrum of progressing neoplasia.

Prognostic role of RECK in pathological outcome-dependent buccal mucosa squamous cell carcinoma.

BACKGROUND: Buccal mucosal squamous cell carcinoma (BMSCC) is an aggressive oral cancer. Moreover, reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a well-known tumor suppressor in many cancers. Our aim was to investigate the association of RECK expression with prognosis in BMSCC patients with different clinicopathological features. MATERIALS AND METHODS: The expression level of RECK was determined by immunohistochemistry using tissue microarrays containing specimens from 193 BMSCC patients. The association of RECK expression with outcomes in BMSCC patients stratified by different clinicopathological features was analyzed by Cox proportional hazards models. RESULTS: The low expression level of RECK was associated with shorter disease-specific survival, especially in patients with age >40 years, moderate or poor cell differentiation, advanced pathological stage, and history of postoperative radiotherapy. However, the low expression level of RECK was not associated with poor disease-free survival, except in BMSCC patients with age ≦40 years, advanced pathological stage and lymph node metastasis. Furthermore, RECK-knockdowned cells showed higher cell viability and abilities of invasion/migration, indicating that RECK might be a tumor suppressor for tumor progression in oral cancer. CONCLUSION: The low expression of RECK might be a potential prognostic biomarker for pathological outcome-dependent BMSCC patients.

Cerebellar PACNS in an Elderly Patient Present as a Tumor-Like Mass Lesion: A case Report.

PURPOSE: PACNS has a broad spectrum of clinical manifestations without typical features, and its clinical diagnosis is challenging. We report an elderly patient of cerebellar PACNS (Primary angiitis of central nervous system) presented as a brain tumor by MRI, and primary angiitis was proven by pathology. CASE REPORT: We report an 81-year-old female who complained about vertigo for 3 weeks with right arm dysmetria. There were no other neurologic symptoms/signs, and the patient was free from headache. Brain CT showed a space-occupying lesion over the right cerebellum, and a high-grade glioma was suspected by brain MRI and MRS. The pathologic result of brain biopsy showed granulomatous variant of PACNS. The patient received immunosuppressant therapy as long-term therapy, and had favorable response during a 2-year follow up. CONCLUSION: Due to variations in clinical presentation and nonspecific findings on imaging studies, PACNS is not easily diagnosed, especially in the aged population. PACNS should be considered as one of the differential diagnoses of any CNS dysfunction. PACNS is also an exclusionary diagnosis, so although brain biopsy is limited for its low sensitivity, its application is still important to exclude the possibility of other diseases. Although there have been reports of fulminant cases, PACNS can be treated successfully with immunosuppressant as maintaining therapy.

Peritoneal lymphoma with ascites mimicking portal hypertensive ascites: A case report.

RATIONALE: Lymphoma with an initial manifestation of ascites and peritoneal invasion is rare. PATIENT CONCERNS: A 65-year-old woman presented to the emergency department with a 3-week history of abdominal distention, anorexia, and night sweating, and a 2-week history of melena. She was a silent hepatitis B virus carrier. Abdominal ultrasound showed massive ascites without cirrhosis. Abdominal computed tomography revealed ascites, infiltrative peritoneal lesions with omental cake appearance, and lymphadenopathies. DIAGNOSIS: We performed paracentesis and the ascites cytology was obtained. The patient also underwent esophagogastroduodenoscopy, which showed ulcerative tumors in the stomach. Both ascites cytology and pathology of the gastric tumors confirmed the diagnosis of B-cell lymphoma. INTERVENTIONS: This patient received 7 cycles of chemotherapy. OUTCOMES: Follow-up imaging studies revealed partial remission of lymphoma, but an enlargement of residual tumors in omentum and mesentery, which resulted in intractable ascites and rapid deterioration of performance status. Despite a change of regimen of chemotherapy, this patient expired 10 months after diagnosis. LESSONS: Lymphoma should be one of the differential diagnoses in patients with intractable ascites not attributable to other comorbidities.

Occurrence of paratesticular ganglioneuroma 18 years after concurrent adrenal ganglioneuroma and papillary thyroid carcinoma - a case report.

BACKGROUND: Ganglioneuromas (GNs) are composed of mature ganglion cells and Schwann cells with a fibrous stroma; GNs are most often observed in children and young adults. The majority of non-cranial GNs are located in the retroperitoneum and posterior mediastinum. Other reported rare sites include the adrenal gland, small intestine, colon and urinary bladder. However, para-testicular GNs are even more rare. CASE PRESENTATION: Herein, we report the case of a patient with concurrent adrenal GN and thyroid papillary carcinoma who developed paratesticular GN eighteen years later. CONCLUSIONS: We conclude that there is an association among papillary thyroid carcinoma, GN and MEN2 syndromes. This case report may provide important information for the proposed association. However, further studies are required.

Endometrioid Intraepithelial Neoplasia: An Endometrial Precancer Detected by 18F-FDG PET/CT.

The report describes a 55-year-old woman with postmenopausal abnormal vaginal spotting. PET/CT revealed focal hot F-FDG uptake in the fundus portion of the uterine cavity, and pathology of hysteroscopic dilation and curettage showed endometrioid intraepithelial neoplasia of uterine endometrium, an endometrial precancer. This case points to the significance of F-FDG PET/CT in determining the dilation and curettage site for the postmenopausal women with abnormal vaginal spotting. Increased F-FDG activity in the region of the uterus must be investigated to determine the possibilities of primary malignancies, metastases, and benign diseases.

Caspase-3 expression in tumorigenesis and prognosis of buccal mucosa squamous cell carcinoma.

Buccal mucosa squamous cell carcinoma (BMSCC) is the most common oral cancer in Southeast Asia. Caspase-3, a key molecule in regulating apoptosis, promotes the malignancy of various cancers. However, its role in BMSCC is unknown. Herein, we evaluated the association of caspase-3 expression with tumorigenesis and prognosis in BMSCC patients. Immunohistochemical staining indicated that the expression levels of cleaved caspase-3 (p<0.001) and caspase-3 (p<0.001) in 185 BMSCC tissues were significantly higher compared to those in the tumor adjacent normal tissues. Moreover, the high expression of caspase-3 was associated with poor pathological outcomes [advanced pathological stage (p=0.029) and larger tumor size (p=0.002)] and poor disease-free survival in patients receiving postoperative radiotherapy (p=0.030). Moreover, the low co-expression of cleaved caspase-3 and caspase-3 was associated with better disease-specific survival in patients with early pathological stage (I + II, p=0.018) or without lymph node invasion (p=0.043) compared to the positive/high expression of either or both cleaved caspase-3 and caspase-3. Taken together, cleaved caspase-3 and caspase-3 could be biomarkers for tumorigenesis in BMSCC patients. Cleaved caspase-3 and/or caspase-3 might be prognostic biomarkers for certain stages of BMSCC.

Sustained renal inflammation following 2 weeks of inhalation of occupationally relevant levels of zinc oxide nanoparticles in Sprague Dawley rats.

Exposure to zinc oxide (ZnO) has been linked to adverse health effects, but the renal effects of ZnO nanoparticles (ZnONPs) remain unclear. The objective of this study was to determine the renal toxicity of inhaled ZnONPs. Sprague Dawley (SD) rats were exposed to occupationally relevant levels of 1.1 (low dose) and 4.9 mg/m3 (high dose) ZnONPs or high-efficiency particulate arresting-filtered air (HEPA-FA) via inhalation for 2 weeks. Histopathological examinations of rat kidneys were performed at 24 hours, 7 days, and 1 month after exposure. A significant increase in microscopic inflammatory foci with pronounced periglomerular inflammation and interstitial lymphocytic infiltration was found in rats exposed to low and high doses of ZnONPs compared with rats exposed to HEPA-FA at the three time points following 2 weeks of exposure. Tubulitis featuring lymphocytic infiltrate within the tubular epithelium was found after 24 hours but had disappeared at 7 and 30 days in both the low- and high-dose exposure groups. Our findings demonstrate that inhaled ZnONPs cause sustained renal periglomerular and interstitial inflammation through lymphocytic infiltration. These findings provide histopathological evidence regarding sustained renal inflammation of nanoparticle exposure in rats and may provide some insight into the occupational health effects of ZnONPs on exposed workers.

The variant of pri-mir-26a-1 polymorphism is associated with decreased risk of betel quid-related oral premalignant lesions and oral squamous cell carcinoma.

OBJECTIVES: This case-control study evaluated the association of the single nucleotide polymorphism rs7372209 (T>C) in pri-mir-26a-1 with the risk and progression of betel quid (BQ)-related oral premalignant lesions (OPLs) and oral squamous cell carcinoma (OSCC). STUDY DESIGN: In total, 597 BQ chewers were recruited: 196 healthy controls, 241 patients with OPLs, and 160 patients with OSCC. Genotypes were determined using the TaqMan real-time assay. RESULTS: The C/T + T/T genotypes and T allele in pri-mir-26a-1 were correlated with a decreased risk of BQ-related OPLs (P = .038 and .005, respectively), oral leukoplakia (P = .01 and .001, respectively), and advanced-stage OSCC (P = .021 and .004, respectively). The effects of the C/T + T/T genotypes and T allele on the decreased risk of OPLs were potent in the older age group (both Pinteraction < .001), heavy smokers (Pinteraction ≤ .003 and .006, respectively) and alcohol drinkers (Pinteraction ≤ .004 and .001, respectively). Furthermore, among patients with OSCC, the C/T + T/T genotypes and T allele were associated with a decreased risk of advanced pathologic stage (P = .032) and lymph node involvement (P = .017). CONCLUSIONS: BQ chewers carrying the T allele or C/T + T/T genotypes in pri-mir-26a-1 may have a decreased risk of oral leukoplakia, OPLs, and advanced-stage OSCC.

Antioxidant enzymes in oral verrucous carcinoma.

BACKGROUND: Verrucous carcinoma is a non-metastasizing variant of welldifferentiated squamous cell carcinoma, which has been associated with reactive oxygen species generated by betel quid chewing. Salivary antioxidant systems have been suggested to play a protective role in reducing the oxidative damage. Herein, we investigated the difference of the enzymatic antioxidant system expressions in oral verrucous carcinoma and oral squamous cell carcinoma. METHODS: The enzymatic antioxidant system expressions, including manganese superoxide dismutase, glutathione peroxidase, and catalase were evaluated by immunohistochemistry in a series of 202 surgically resected oral squamous cell carcinoma and 20 oral verrucous carcinoma specimens, using tissue microarray slides. RESULTS: The immuno-staining intensities of superoxide dismutase and glutathione peroxidase were strongest in the oral squamous cell carcinoma group than in verrucous carcinoma. The catalase expression showed no difference between different pathological groups. CONCLUSIONS: The different degrees of superoxide dismutase and glutathione expressions in verrucous carcinoma and squamous cell carcinoma may be helpful for pathologists to differentiate these two entities, especially between oral verrucous carcinoma and well differentiated oral squamous cell carcinoma.

Global DNA hypomethylation is associated with the development and poor prognosis of tongue squamous cell carcinoma.

BACKGROUNDS: Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC. METHODS: The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues. RESULTS: We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009). CONCLUSIONS: Global hypomethylation was an independent biomarker for the development and poor prognosis of TSCC.

Increased Risk of Herpes Zoster Following Dermatomyositis and Polymyositis: A Nationwide Population-Based Cohort Study.

This study explored the possible association between dermatomyositis or polymyositis (DM or PM) and the subsequent risk of herpes zoster (HZ). We used data from the Taiwan National Health Insurance (NHI) system to address the research topic. The exposure cohort comprised 2023 patients with new diagnoses of DM or PM. Each patient was frequency matched according to age, sex, index year, and comorbidities including diabetes, renal disease, obesity, malignancy, rheumatoid arthritis, immunodeficiency virus infection, autoimmune disease not elsewhere classified, mixed connective tissue disease, or vasculitis with 4 participants from the general population who did not have a history of HZ (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between DM or PM and the risk of subsequent HZ. The incidence of HZ in the exposure and control cohorts was 35.8 and 7.01 per 1000 person-years, respectively. The exposure cohort had a significantly higher overall risk of subsequent HZ than did the control cohort (adjusted hazard ratio [HR] = 3.90, 95% confidence interval [CI] = 3.18-4.77). The risk of HZ in patients with DM or PM in whichever stratification (including sex, age, and comorbidity) was also higher than that of the control cohort. The findings from this population-based retrospective cohort study suggest that DM or PM is associated with an increased risk of subsequent HZ. A synergistic effect was observed between DM or PM and one of the comorbidities.

A rare but potentially lethal case of tuberculous aortic aneurysm presenting with repeated attacks of abdominal pain.

Tuberculous aortic aneurysm is an extremely rare disease with a high mortality rate. The clinical features of this condition are highly variable, ranging from asymptomatic with or without constitutional symptoms, abdominal pain to frank rupture, bleeding and shock. We herein report the case of a 56-year-old man with a large tuberculous mycotic aneurysm in the abdominal aorta with an initial presentation of repeated attacks of abdominal pain lasting for several months. Due to the vague nature of the initial symptoms, tuberculous aortic aneurysms may take several months to diagnose. This case highlights the importance of having a high index of suspicion and providing timely surgery for this rare but potentially lethal disease.

Recurrent Hypokalemic Periodic Paralysis Unmasks Sjogren Syndrome without Sicca Symptoms.

Hypokalemic Periodic Paralysis (HPP) may occur as a rare complication of Sjogren Syndrome (SS) and Renal Tubular Acidosis (RTA). A 64-year male patient came with HPP, and was later diagnosed with distal RTA. The patient, who had no xerostomia and xerophthalmia, was diagnosed with primary SS from serologic and histologic findings of minor salivary gland biopsy. The patient recovered after potassium replacement therapy. Renal biopsy was also performed and revealed evidence of tubulointerstitial nephritis. Corticosteroids were administered and there was no recurrence of HPP during a 4-year follow-up period. The case highlights the significance of acute hypokalemia management in emergency department as it can unmask SS even if the SS is not associated with sicca symptoms. Hypokalemic paralysis associated with normal anion gap metabolic acidosis should prompt toward the diagnosis of SS.