Hemosiderin induced acute kidney injury requiring hemodialysis in patients with paroxysmal nocturnal hemoglobinuria: A case report.

RATIONALE: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disease with features of hemolytic anemia, thrombosis, and bone marrow failure. Due to intravascular hemolysis and hemoglobinuria, renal dysfunction is often accompanied in PNH patients. PATIENT CONCERNS: A 25-year old woman presenting gross hematuria after coronavirus disease 2019 infection was admitted to our medical center. She had mild nausea and headache. She was diagnosed with iron deficiency anemia few years ago and had no other underlying disease. Her laboratory findings showed acute kidney injury (AKI) and severe anemia, with evidences of hemolysis. DIAGNOSIS: Renal biopsy was done to determine the cause of renal failure and the result was acute tubular necrosis with deposition of golden pigments, hemosiderin. With pathologic result and laboratory finding of hemolysis, we did flow cytometry for PNH, and the patient was finally diagnosed with PNH. INTERVENTIONS: With AKI and oliguria, the patient started to take hemodialysis. OUTCOMES: After taking 5 sessions of hemodialysis, the patient's renal function was recovered from AKI. With diagnosis of PNH, the patient is now being treated with complement C5 inhibitor. LESSONS: This challenging case tells us that we should consider the first manifestation of PNH as a cause of severe AKI requiring hemodialysis in a patient with anemia and evidence of hemolysis.

Elevated expression of TLR2 and its correlation with disease activity and clinical manifestations in adult-onset Still's disease.

This study investigated the role of Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR7, and TLR9 in patients with adult-onset Still's disease (AOSD). This study included 20 patients with AOSD and 15 healthy controls (HCs). TLR expression in the peripheral blood was quantified using flow cytometry; TLR expression pattern, in the skin lesions and lymph nodes (LNs) of patients with AOSD, was evaluated immunohistochemically. Significantly higher mean intensities of cells presenting TLR2 and TLR7 from whole blood were observed in patients with AOSD than in HCs. TLR2 expression in whole cells correlated with systemic scores, levels of lactate dehydrogenase and ferritin and serum levels of interleukin-1ß (IL-1ß), IL-6, and IL-18. The percentage of TLR2-positive inflammatory cells was higher in skin biopsy samples from patients with AOSD than those in HCs. TLR9-expressing positive inflammatory cell counts were higher in skin lesions from patients with AOSD than those in the HC, eczema, and psoriasis groups. The expression levels of TLR1, TLR4, TLR7, and TLR9 were higher in LNs of patients with AOSD than in those with T cell lymphoma and reactive lymphadenopathy. Circulating TLR2- and TLR7-positive cells may contribute to the pathogenesis of AOSD. Furthermore, immunohistochemical staining for TLRs in skin lesions and LNs may aid in differentiating AOSD from similar conditions.

Lymphopenia as a Potential Predictor of Ipsilateral Breast Tumor Recurrence in Early Breast Cancer.

BACKGROUND/AIM: The aim of this study was to investigate the association between lymphopenia after breast conserving therapy (BCT) and ipsilateral breast tumor recurrence (IBTR) in early breast cancer (EBC). PATIENTS AND METHODS: We examined 216 EBC patients treated with partial mastectomy followed by radiotherapy (RT), none of whom received chemotherapy. Absolute lymphocyte counts (ALCs) during the two years after RT were collected from each patient: pretreatment ALC, ALC at 3-5 months (ALC1), ALC at 9-11 months, ALC at 15-17 months, and ALC at 21-23 months. RESULTS: The 102 patients with ALC1 ≤1,479 cells/µl (defined as lymphopenia) had significantly higher 10-year IBTR rate than the 102 patients with ALC1 >1,479 cells/µl (16.2% vs. 1%, p=0.0034). The multivariate analysis showed that age, resection margins, human epidermal growth factor receptor, and lymphopenia were significant predictors of IBTR. CONCLUSION: Lymphopenia is a potential predictor for IBTR in EBC patients treated with BCT.

The levels of CXCL12 and its receptor, CXCR4, as a biomarker of disease activity and cutaneous manifestation in adult-onset Still's disease.

OBJECTIVES: This study evaluated the SDF-1/CXCL12 and soluble CXCR4 (sCXCR4) levels, and investigated their clinical relevance in adult-onset Still's disease (AOSD). METHODS: Forty-two AOSD patients and 30 healthy controls (HC) were enrolled for serum sampling. Expression levels of CXCL12 and CXCR4 in skin biopsy materials of 40 AOSD patients, 10 patients with eczema, or 10 psoriasis, and 10 HC skin were evaluated with immunohistochemistry. RESULTS: The serum CXCL12 levels in patients with AOSD (2,452±1,531 pg/mL) were higher than those in HC (1,708±1,322 pg/mL, p=0.017). The serum sCXCR4 levels in patients with AOSD (14,449±16,627 pg/mL) were higher than those in HC (3,046±2,554 pg/mL, p<0.001). Serum CXCL12 levels correlated positively with counts of leukocytes and neutrophils, erythrocyte sedimentation rate, ferritin, and C-reactive protein (CRP). Serum sCXCR4 levels correlated positively with systemic scores, platelet counts, and CRP levels. The serum levels of CXCL12 and sCXCR4 were decreased significantly in the patients with AOSD followed after resolution of disease activity. On immunohistochemical stain, the mean percentage of CXCR4-positive inflammatory cells was 51.4±27.5% and that of CXCL12-positive inflammatory cells was 16.7±13.3% in AOSD patients. CXCR4 was more frequently expressed in inflammatory cells from AOSD patients than in those with eczema or psoriasis and HC skin. CONCLUSIONS: These results provide that sCXCR4 could be a clinical biomarker of evaluation for disease activity in AOSD, and show that CXCR4/CXCL12 may influence the inflammatory condition and skin manifestations of AOSD.

The loss of succinate dehydrogenase B expression is frequently identified in hemangioblastoma of the central nervous system.

Succinate dehydrogenase (SDH) is a mitochondrial enzyme that plays an important role in both the Krebs cycle and the electron transport chain. SDH inactivation is associated with tumorigenesis in certain types of tumor. SDH consists of subunits A, B, C and D (SDHA, SDHB, SDHC, and SDHD, respectively). Immunohistochemistry for SDHB is a reliable method for detecting the inactivation of SDH by mutations in SDHA, SDHB, SDHC, SDHD and SDH complex assembly factor 2 (SDHAF2) genes with high sensitivity and specificity. SDHB immunohistochemistry has been used to examine the inactivation of SDH in various types of tumors. However, data on central nervous system (CNS) tumors are very limited. In the present study, we investigated the loss of SDHB immunoexpression in 90 cases of CNS tumors. Among the 90 cases of CNS tumors, only three cases of hemangioblastoma showed loss of SDHB immunoexpression. We further investigated SDHB immunoexpression in 35 cases of hemangioblastoma and found that 28 (80%) showed either negative or weak-diffuse pattern of SDHB immunoexpression, which suggests the inactivation of SDH. Our results suggest that SDH inactivation may represent an alternative pathway in the tumorigenesis of hemangioblastoma.

Change in microcalcifications on mammography after neoadjuvant chemotherapy in breast cancer patients: correlation with tumor response grade and comparison with lesion extent.

BACKGROUND: After neoadjuvant chemotherapy (NAC), persistent microcalcifications are often observed in spite of a decrease in the primary tumor size. PURPOSE: To analyze the changes in microcalcifications after NAC and to evaluate the accuracy of residual microcalcifications in predicting the extent of residual cancer. MATERIAL AND METHODS: Eighty patients who received NAC and underwent both mammography and magnetic resonance imaging (MRI) before and after the completion of NAC were included. The location of microcalcifications was classified into two types: inside the mass and outside the mass. RESULTS: The extent of the residual calcifications was larger than the pathologic residual lesion in 14 (74%) of 19 patients with complete response (CR) on MRI, but the discrepancy was <1 cm in eight (42%) patients. The median value of the discrepancy was significantly higher in patients showing CR with outside calcifications compared to CR with inside calcifications (2.0 cm vs. 0.7 cm, P = 0.008). After NAC, the decrease of calcifications was more frequently observed in cancers showing CR on MRI or Miller-Payne grade 5 and the increase of calcifications more frequently occurred in cancers showing progress disease on MRI or Miller-Payne grade 1 ( P < 0.001 and P = 0.044). CONCLUSION: The change in microcalcifications after NAC was correlated with the tumor response to NAC. The discrepancy was highest in the group showing CR on MRI with outside calcifications. In tumors with inside calcifications, the discrepancy was relatively low within an acceptable range.

Small bowel obstruction from distant metastasis of primary breast cancer: a case report.

Gastrointestinal (GI) tract metastasis of primary breast cancer is very rare. We present a patient with small bowel obstruction from distant metastasis of primary breast cancer. Each characteristic features of concern of GI tract distant metastasis from many pervious studies has been reported differently. We should remember that GI tract metastasis may coexist when patients with breast cancer have intermittent or recurrent abdominal pain with or without obstructive symptoms.

Serum Levels of Interleukin 33 and Soluble ST2 Are Associated with the Extent of Disease Activity and Cutaneous Manifestations in Patients with Active Adult-onset Still's Disease.

OBJECTIVE: Interleukin 33 (IL-33), a member of the IL-1 family and a ligand of the orphan receptor ST2, plays key roles in innate and adaptive immunity. We examined the associations between IL-33/ST2 levels and clinical manifestations of patients with active adult-onset Still's disease (AOSD). METHODS: Blood samples were collected from 40 patients with active AOSD, 28 patients with rheumatoid arthritis (RA), and 27 healthy controls (HC). The serum levels of IL-33 and soluble ST2 were determined using ELISA. Expression levels of IL-33 and ST2 in biopsy specimens obtained from 34 AOSD patients with rash were immunohistochemically investigated. RESULTS: IL-33 levels of patients with AOSD were higher than those of patients with RA and HC. Soluble ST2 levels of patients with AOSD were higher than those of HC, but not of patients with RA. Serum IL-33 levels correlated with systemic score, erythrocyte sedimentation rate, ferritin levels, and aspartate transaminase levels. However, serum soluble ST2 levels correlated only with ferritin levels. The numbers of inflammatory cells expressing IL-33 and ST2 were elevated in skin lesions of patients with AOSD compared to HC, but did not differ from those of the skin lesions of eczema or psoriasis. CONCLUSION: We found significantly higher serum IL-33 and soluble ST2 levels in patients with active AOSD. Results indicate that the IL-33/ST2 signaling pathway may play a role in the pathogenesis of the acute inflammation and skin manifestations associated with AOSD.

Elevated circulating levels of the interferon-γ-induced chemokines are associated with disease activity and cutaneous manifestations in adult-onset Still's disease.

C-X-C motif chemokine 9 (CXCL9), CXCL10, and CXCL11 are produced in response to interferon-γ (IFN-γ) and trigger inflammation with the accumulation of activated lymphocytes. It appears that these chemokines could play a role in the pathogenesis of adult-onset Still's disease (AOSD). Therefore, we investigated the associations between the levels of these chemokine and clinical manifestations in patients with active AOSD. Serum levels of IFN-γ, CXCL9, CXCL10 and CXCL11 were determined using enzyme-linked immunosorbent assays. IFN-γ levels were higher in AOSD patients than in rheumatoid arthritis (RA) patients (p = 0.001) or healthy controls (HCs) (p = 0.032). AOSD patients also exhibited higher levels of CXCL9, CXCL10, and CXCL11 compared with RA patients (p < 0.001) and HCs (p < 0.001). In follow-up AOSD patients after treatment with corticosteroid, the levels of CXCL9, CXCL10 and CXCL11 fell significantly, whereas IFN-γ levels were not significantly different. On immunohistochemistry, the percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples from AOSD patients than in those from normal control (p = 0.012), eczema (p = 0.019), and psoriasis (p = 0.009) groups. Levels of the IFN-γ-induced chemokines, CXCL9, CXCL10 and CXCL11, were elevated and correlated with several disease activity markers. These interferon-γ-induced chemokines may contribute to inflammatory responses and skin manifestations in AOSD.

Prognostic utility of FDG PET/CT and bone scintigraphy in breast cancer patients with bone-only metastasis.

We performed this retrospective clinical study to examine the prognostic power of bone scintigraphy (BS) and F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in terms of overall survival (OS) of breast cancer with bone-only metastasis.We retrospectively evaluated 100 female invasive ductal breast cancer patients (mean age 48.1 years) with bone-only metastasis. Twenty-five patients had human epidermal growth factor receptor 2 (HER2)-positive tumors, 65 were estrogen receptor (ER) and/or progesterone receptor (PR)-positive, HER2-negative tumors, and 10 were triple negative tumors. The patients were treated properly with various treatments, including chemotherapy, radiotherapy, hormone, and bisphosphonate therapy, based on their clinical status. All patients underwent BS and FDG PET/CT at baseline and 1 year after treatment. The baseline and follow images were visually compared, and the patients were grouped as responders or nonresponders based on their images. OS was compared between the groups.The mean OS after the diagnosis of bone-only metastasis was 57.6 months. Fifty-one patients (51%) died within 5 years after diagnosis of metastasis. No difference in survival was evident between responders and nonresponders based on BS imaging data (P = .090). The response status based on PET imaging data waste only significant independent prognostic factor on multivariate analysis (P = .001). Survival was lower in nonresponders than in responders based on PET imaging (32.7% vs 66.4%; P < .001).Our findings suggest that the response status according to FDG PET imaging can be used to predict OS in breast cancer patients with bone-only metastasis.

Young Age Is Associated with Increased Locoregional Recurrence in Node-Positive Breast Cancer with Luminal Subtypes.

PURPOSE: The effects of biological subtypes within breast cancer on prognosis are influenced by age at diagnosis. We investigated the association of young age with locoregional recurrence (LRR) between patients with luminal subtypes versus those with nonluminal subtypes. MATERIALS AND METHODS: Medical records of 524 breast cancer patients with positive lymph nodes between 1999 and 2010 were reviewed retrospectively. All patients received curative surgery and adjuvant chemotherapy based on contemporary guidelines. Radiation was delivered for patients who underwent breast conserving surgery or those who had four or more positive lymph nodes after mastectomy. Adjuvant hormone therapy was administered to 413 patients with positive hormone receptors according to their menstrual status. RESULTS: During median follow-up of 84 months, the 10-year locoregional recurrence-free survival rate (LRRFS) was 84.3% for all patients. Patients < 40 years showed significantly worse 10-year LRRFS than those ≥ 40 years (73.2% vs. 89.0%, respectively; p=0.01). The negative effect of young age on LRRFS was only observed in luminal subtypes (69.7% for < 40 years vs. 90.8% for ≥ 40 years; p < 0.01). Multivariate analysis using luminal subtypes ≥ 40 years as a reference revealed luminal subtypes < 40 years were significantly associated with increased risk of LRR (hazard ratio, 2.33; p < 0.01). CONCLUSION: Young breast cancer patients with positive lymph nodes had a higher risk of LRR than those aged ≥ 40 years. This detrimental effect of young age on LRR was confined in luminal subtypes.

Value of volume-based metabolic parameters for predicting survival in breast cancer patients treated with neoadjuvant chemotherapy.

We evaluated the role of metabolic parameters in the prediction of disease recurrence in operable invasive ductal breast cancer patients treated with neoadjuvant chemotherapy (NAC).We retrospectively evaluated 139 female patients (mean age, 46.5 years; range: 27-72 years) with invasive ductal breast cancer, treated with NAC followed by surgery. All patients underwent F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging at baseline and after completion of NAC before surgery. The prognostic significance of clinicopathological and imaging parameters for disease-free survival (DFS) was evaluated.Recurrence of cancer was detected in 31 of 139 patients (22.3%; follow-up period: 6-82 months). Baseline maximum standardized uptake value, metabolic tumor volume (MTV), and reduction rate (RR) of MTV after NAC were significant independent prognostic factors for DFS in a multivariate analysis (all P < 0.05). The survival functions differed significantly between low and high histological grades (P < 0.001). DFS of the patients with high baseline MTV (≥5.23 cm) was significantly poorer than that of low MTV patients (P = 0.019). The survival function of the group with low RR of MTV after NAC (≤90.72%) was poorer than the higher RR of the MTV group (P = 0.008).Our findings suggest that breast cancer patients who have a high histological grade, large baseline MTV, or a small RR of MTV after NAC should receive great attention to check for possible recurrence.

TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-Onset Still's Disease and Their Association with Disease Activity and Clinical Manifestations.

S100A8/A9 has been suggested as a marker of disease activity in patients with adult-onset Still's disease (AOSD). We evaluated the clinical significance of S100A8/A9 as a biomarker and its pathogenic role in AOSD. Blood samples were collected prospectively from 20 AOSD patients and 20 healthy controls (HCs). Furthermore, skin and lymph node biopsy specimens of AOSD patients were investigated for S100A8/A9 expression levels via immunohistochemistry. Peripheral blood mononuclear cells (PBMCs) of active AOSD patients and HCs were investigated for S100A8/A9 cell signals. S100A8/A9, interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) levels in active AOSD patients were higher than those of HCs. S100A8/A9 levels correlated positively with IL-1ß, TNF-α and C-reactive protein. The inflammatory cells expressing S100A8/A9 were graded from one to three in skin and lymph node biopsies of AOSD patients. The grading for S100A8/A9 was more intense in the skin lesions with karyorrhexis, mucin deposition, and neutrophil infiltration. Like lipopolysaccharide (LPS), S100A8/A9 induced phosphorylation of p38 and c-Jun amino-terminal kinase (JNK) in PBMCs, suggesting that S100A8/A9 activates Toll-like receptor 4 signaling pathways. These findings suggest that S100A8/A9 may be involved in the inflammatory response with induction of proinflammatory cytokines and may serve as a clinicopathological marker for disease activity in AOSD.

Evaluation of the VE1 Antibody in Thyroid Cytology Using Ex Vivo Papillary Thyroid Carcinoma Specimens.

BACKGROUND: Recently, VE1, a monoclonal antibody against the BRAFV600E mutant protein, has been investigated in terms of its detection of the BRAFV600E mutation. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in thyroid cytology samples is rarely performed, and its diagnostic value in cytology has not been well established. In present study, we explored VE1 immunoexpression in cytology samples from ex vivo papillary thyroid carcinoma specimens in order to minimize limitations of low cellularity and sampling/targeting errors originated from thyroid fineneedle aspiration and compared our results with those obtained using the corresponding papillary thyroid carcinoma tissues. METHODS: The VE1 antibody was evaluated in 21 cases of thyroid cytology obtained directly from ex vivo thyroid specimens. VE1 immunostaining was performed using liquid-based cytology, and the results were compared with those obtained using the corresponding tissues. RESULTS: Of 21 cases, 19 classic papillary thyroid carcinomas had BRAFV600E mutations, whereas two follicular variants expressed wild-type BRAF. VE1 immunoexpression varied according to specimen type. In detection of the BRAFV600E mutation, VE1 immunostaining of the surgical specimen exhibited 100% sensitivity and 100% specificity, whereas VE1 immunostaining of the cytology specimen exhibited only 94.7% sensitivity and 0% specificity. CONCLUSIONS: Our data suggest that VE1 immunostaining of a cytology specimen is less specific than that of a surgical specimen for detection of the BRAFV600E mutation, and that VE1 immunostaining of a cytology specimen should be further evaluated and optimized for clinical use.

Analysis of kinetic curve and model-based perfusion parameters on dynamic contrast enhanced MRI in breast cancer patients: Correlations with dominant stroma type.

OBJECTIVE: Our purpose was to evaluate imaging findings of breast cancers according to the dominant stroma type by using kinetic curve analysis and model-based perfusion parameters from dynamic contrast-enhanced magnetic resonance imaging. METHODS: From March 2011 to September 2011, 64 cancers in 64 patients were included for data analysis. Kinetic curve analysis and model based perfusion parameters (Ktrans, Kep and Ve) were obtained using dynamic contrast-enhanced magnetic resonance imaging and post-processing software. Imaging characteristics were analyzed according to the tumor-stroma ratio and dominant stroma type. RESULTS: Ve values were significantly lower in tumors with more than 50% cellularity (0.44 vs. 0.29, p=0.008). Histologic grade, estrogen receptor status and subtype of cancer (triple negative versus non-triple negative) were significantly different (p=0.009, p=0.019 and p=0.03, respectively). Median Kep values were different between collagen dominant, fibroblast dominant and lymphocyte dominant groups. By post hoc comparisons, mean Kep values were significantly higher in lymphocyte dominant group than collagen dominant group (p=0.003). Ktrans and Ve values were not significantly different according to dominant stroma type (p=0.351 and p=0.257, respectively). In multivariate regression analysis, nuclear grade (p=0.021) and dominant stroma type (collagen dominant, p=0.017) were independently correlated with Kep values. In terms of the dominant stroma type, the collagen dominant type showed a decrease of 0.247 in Kep values, compared with the fibroblast-dominant type (p=0.017). CONCLUSIONS: Ve values were significantly lower in tumors with high tumor-stroma ratio. Kep values were significantly lower in breast cancers with dominant collagen type and higher in cancers with high nuclear grade.

Endoscopic ultrasound-guided sampling of solid pancreatic masses: 22-gauge aspiration versus 25-gauge biopsy needles.

BACKGROUND: Biopsy needles have recently been developed to obtain both cytological and histological specimens during endoscopic ultrasound (EUS). We conducted this study to compare 22-gauge (G) fine needle aspiration (FNA) needles, which have been the most frequently used, and new 25G fine needle biopsy (FNB) needles for EUS-guided sampling of solid pancreatic masses. METHODS: We conducted a retrospective cohort study of all EUS-guided sampling performed between June 2010 and October 2013. During the study period, 76 patients with pancreatic masses underwent EUS-guided sampling with a 22G FNA needle (n = 38) or a 25G FNB needle (n = 38) for diagnosis. An on-site cytopathologist was not present during the procedure. Technical success, the number of needle passes, cytological diagnostic accuracy, cytological sample quality (conventional smear and liquid-based preparation), histological diagnostic accuracy, and complications were reviewed and compared. RESULTS: There were no significant differences in technical success (100% for both), the mean number of needle passes (5.05 vs. 5.55, P = 0.132), or complications (0% for both) between the 22G FNA group and the 25G FNB group. The 22G FNA and 25G FNB groups exhibited comparable outcomes with respect to cytological diagnostic accuracy (97.4% vs. 89.5%, P = 0.358) and histological diagnostic accuracy (34.2% vs. 52.6%, P = 0.105). In the cytological sample quality analysis, the 25G FNB group exhibited higher scores for the amount of diagnostic cellular material present (22G FNA: 0.92 vs. 25G FNB: 1.32, P = 0.030) and the retention of appropriate architecture (22G FNA: 0.97 vs. 25G FNB: 1.42, P = 0.010) in the liquid-based preparation. The 25G FNB group showed a better histological diagnostic yield for specific tumor discrimination compared with the 22G FNA group (60 % vs. 32.4%, P = 0.018). CONCLUSIONS: Use of the 25G FNB needle was technically feasible, safe, efficient, and comparable to use of the standard 22G FNA needle in patients with solid pancreatic masses in the absence of an on-site cytopathologist. The cytological sample quality in the liquid-based preparation and the histological diagnostic yield for specific tumor discrimination of EUS-guided sampling using a 25G FNB needle were significantly higher than those using a 22G FNA needle.

Association of CXCL10 and CXCL13 levels with disease activity and cutaneous manifestation in active adult-onset Still's disease.

INTRODUCTION: C-X-C motif chemokine 10 (CXCL10) is produced in response to interferon-γ, and tumor necrosis factor-α (TNF-α) triggers the accumulation of activated lymphocytes. CXCL13 is constitutively expressed in secondary lymphoid tissues, and the expression is upregulated by TNF-α, via T cell stimulation. It appears that CXCL10 and CXCL13 could play a potential role in the pathogenesis of adult-onset Still's disease (AOSD), therefore, we investigated the associations between CXCL10 and CXCL13 levels and clinical manifestations in patients with active AOSD. METHODS: Blood samples were collected from 39 active AOSD patients, 32 rheumatoid arthritis (RA) patients and 40 healthy controls (HC). Of the AOSD patients, follow-up samples were collected from 15 9.6 ± 9.2 months later. Serum levels of CXCL10 and CXCL13 were determined using enzyme-linked immunosorbent assay. CXCL10, CXCL13, and C-X-C chemokine receptor type 3 (CXCR3) expression levels in biopsy specimens obtained from 26 AOSD patients with skin rashes were investigated via immunohistochemistry. RESULTS: The CXCL10 levels in AOSD patients (1,031.3 ± 2,019.6 pg/mL) were higher than in RA (146.3 ± 91.4 pg/mL, p = 0.008) and HC (104.4 ± 47.9 pg/mL, p = 0.006). Also, the CXCL13 levels of AOSD patients (158.8 ± 151.2 pg/mL) were higher than those of RA (54.4 ± 61.1 pg/mL, p < 0.001) and HC (23.5 ± 18.1 pg/mL, p < 0.001). Serum CXCL10 levels correlated with ferritin and systemic scores. Serum CXCL13 levels correlated with those of hemoglobin, C-reactive protein, ferritin, and albumin, and systemic scores. In follow-up AOSD patients, the levels of CXCL10 and CXCL13 fell significantly (153.7 ± 130.1 pg/mL, p = 0.002, and 89.1 ± 117.4 pg/mL, p = 0.001, respectively). On immunohistochemistry, the percentages of inflammatory cells expressing CXCL10 ranged from 1 to 85%, CXCL13 from 1 to 72%, and CXCR3 from 2 to 65%. The percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples exhibiting mucin deposition than in those that did not (p = 0.01). CXCL13 levels were correlated with those of CD4 and CD68. CONCLUSIONS: Serum CXCL10 and CXCL13 levels may serve as clinical markers for assessment of disease activity in AOSD. CXCL10/CXCR3 and CXCL13 may contribute to the inflammatory response, especially skin manifestations thereof, in AOSD.

The pathologic findings of skin, lymph node, liver, and bone marrow in patients with adult-onset still disease: a comprehensive analysis of 40 cases.

Adult-onset Still disease (AOSD) is characterized by fever, skin rash, and lymphadenopathy with leukocytosis and anemia as common laboratory findings. We investigated the characteristic pathologic findings of skin, lymph node, liver, and bone marrow to assist in proper diagnosis of AOSD.Forty AOSD patients were included in the study. The skin (26 patients), lymph node (8 patients), liver (8 patients), or bone marrow biopsies (22 patients) between 1998 and 2013 were retrospectively analyzed. AOSD patients were diagnosed according to the Yamaguchi criteria after excluding common infections, hematological and autoimmune diseases. Immunohistochemistry, immunofluorescence, and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization were performed.Most skin biopsies revealed mild lymphocytic or histiocytic infiltration in the upper dermis. Nuclear debris was frequently found in the dermis in 14 cases (53.8%). More than half of the cases (n = 14, 53.8%) showed interstitial mucin deposition. Some cases showed interface dermatitis with keratinocyte necrosis or basal vacuolization (n = 10; 38.5%). The lymph node biopsies showed a paracortical or diffuse hyperplasia pattern with immunoblastic and vascular proliferation. The liver biopsies showed sparse portal and sinusoidal inflammatory cell infiltration. All cases showed various degrees of Kupffer cell hyperplasia. The cellularity of bone marrow varied from 20% to 80%. Myeloid cell hyperplasia was found in 14 out of the 22 cases (63.6%). On immunohistochemistry, the number of CD8-positive lymphocytes was greater than that of CD4-positive lymphocytes in the skin, liver, and bone marrow, but the number of CD4-positive lymphocytes was greater than that of CD8-positive lymphocytes in the lymph nodes.The relatively specific findings with respect to the cutaneous manifestation of AOSD were mild inflammatory cell infiltration in the upper dermis, basal vacuolization, keratinocyte necrosis, presence of karyorrhexis, and mucin in the dermis. In all cases, pathologic findings in the lymph nodes included paracortical hyperplasia with vascular and immunoblastic proliferation. Skin and lymph node pathology in addition to clinical findings can aid in the diagnosis of AOSD.