ABSTRACT
Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.
Subject(s)
Cystadenocarcinoma, Serous , Deep Learning , Ovarian Neoplasms , Platinum , Female , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/genetics , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/diagnostic imaging , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/genetics , Platinum/therapeutic use , Middle Aged , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Treatment Outcome , Neoplasm Grading , Cohort Studies , Adult , Reproducibility of ResultsABSTRACT
We investigated frequencies of HER2-low breast cancer (BC) (immunohistochemistry [IHC] 1+ or 2+ without gene amplification) before and after IHC conditions were modified in order to understand the impact of IHC staining conditions on frequencies of HER2-low BC. Primary BC cases diagnosed at the Yeungnam University Hospital (YUH, n = 728) or Keimyung University Dongsan Hospital (KUDH, n = 290) in 2022 were reviewed, and data on HER2 status and IHC conditions were collected (cohort 1). Both institutions used the 4B5 antibody for HER2 IHC but had different staining protocols. After modifications of the IHC conditions at both institutions, primary BC cases (YUH, n = 324 and KUDH, n = 135) diagnosed from April to July 2023 (cohort 2) were reviewed to assess any changes in the frequency of HER2 status. In cohort 1, of the 728 cases diagnosed at YUH, 556 (76.4%) were HER2-zero, 76 (10.4%) were HER2-low, and 96 (13.2%) were HER2-positive, and of the 290 cases diagnosed at KUDH, 135 (46.6%) were HER2-zero, 82 (28.3%) were HER2-low, and 73 (25.2%) were HER2-positive. Modifications in HER2 IHC staining conditions dramatically increased the frequencies of HER2-low BC in cohort 2 (YUH 38.9% and KUDH 49.6%), but they did not result in significant changes in the HER2-positive rates (YUH 15.4% and KUDH 25.2%) compared to cohort 1. In conclusion, minor modifications in HER2 IHC staining conditions significantly affected the frequency of HER2-low BC but had little impact on the HER2-positivity rate. Each pathology laboratory should verify IHC conditions using control slides (including 1+) to enable the accurate identification of HER2-low BC.
ABSTRACT
Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.
Subject(s)
Iron , Lipocalin-2 , Liver Cirrhosis , Mice, Knockout , Non-alcoholic Fatty Liver Disease , Sterol Regulatory Element Binding Protein 1 , Animals , Humans , Male , Mice , Carbon Tetrachloride/pharmacology , Disease Models, Animal , Gene Expression Regulation , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Hepatocytes/metabolism , Hepatocytes/pathology , Iron/metabolism , Lipocalin-2/metabolism , Lipocalin-2/genetics , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/etiology , Liver Cirrhosis/genetics , Liver Cirrhosis/chemically induced , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/geneticsABSTRACT
Friend Leukemia Virus Integration 1 (FLI-1) is a member of E26 transformation-specific family of transcription factors that participates in hematopoietic and vascular endothelial cell development. Immunohistochemical detection of FLI-1 has been widely used to diagnose vascular tumors or, more evidently, Ewing's sarcoma. However, the expression pattern of FLI-1 in hematolymphoid neoplasms remains unclear. Therefore, in this study, we aimed to investigate the expression of FLI-1 in these tumors, focusing on high-grade lesions, which presents a diagnostic challenge by mimicking Ewing's sarcoma. We evaluated the expression FLI-1 in various types of lymphoid and plasmacytic tumors, including 27 plasmablastic lymphomas, 229 diffuse large B-cell lymphomas, 22 precursor T- or B-lymphoblastic lymphomas, 24 angioimmunoblastic-type nodal T-follicular helper cell lymphomas, 52 peripheral T-cell lymphomas, NOS, 18 Burkitt lymphomas, 18 non-gastric lymphomas of mucosa-associated lymphoid tissue, 38 chronic lymphocytic leukemia/small lymphocytic lymphomas, 15 mantle cell lymphomas, 23 gastric MALT lymphomas, 50 plasma cell myelomas, and 38 follicular lymphomas. We calculated the H-scores of FLI-1 immunostaining, ranging from 0 to 200, and used the scores to analyze the clinicopathological significance of FLI-1 statistically. FLI-1 was expressed to varying degrees in all types of hematological tumors. FLI-1 expression was detected in 84.1% of patients (466/554). FLI-1 was highly expressed in precursor T- or B-lymphoblastic lymphomas. Follicular lymphomas exhibited low FLI-1 expression. In plasmablastic lymphoma, 85.2% of the patients were focally positive for FLI-1. FLI-1 expression did not correlate with clinicopathological variables, such as demographic data or disease stage, in patients with plasmablastic lymphoma and diffuse large B-cell lymphoma. However, FLI-1 overexpression was associated with poorer overall survival in patients with plasmablastic lymphoma. This study demonstrates that FLI-1 is expressed in various hematolymphoid neoplasms. FLI-1 expression can lead to diagnostic confusion, especially in small blue round cell tumors, such as lymphoblastic lymphoma, plasmablastic lymphoma, and plasma cell myeloma, when distinguishing tumors positive for CD99 and CD56 without CD3, CD20, or CD45. Our findings also suggested the possibility of FLI-1 as a potential prognostic biomarker for plasmablastic lymphoma.
Subject(s)
Lymphoma, Follicular , Lymphoma, Large B-Cell, Diffuse , Multiple Myeloma , Plasmablastic Lymphoma , Sarcoma, Ewing , Humans , Diagnosis, Differential , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Plasmablastic Lymphoma/diagnosis , Sarcoma, Ewing/diagnosisABSTRACT
The currently available coronavirus disease 2019 (COVID-19) vaccines in South Korea include mRNA (Moderna® and Pfizer®) and adenoviral vector (AstraZeneca® and Janssen®) vaccines. Dermatologic side effects of COVID-19 vaccines range from local injection site reactions to systemic eruptions, including morbilliform rashes or erythema multiforme. Pernio-like lesions, one of the most common cutaneous manifestations of COVID-19, have been rarely reported post-vaccination. Herein, we report four cases of pernio-like lesions, which were detected in a single tertiary hospital within 2 months, after the first dose of mRNA-1273 (Moderna®) vaccination was administered. In this study, we discuss the clinical and pathological features of our cases and compare them with those of previously reported cases of pernio-like lesions after COVID-19 vaccination. It is pivotal to realize that perniolike lesions can be a possible side effect of COVID-19 vaccination and that the number of patients experiencing this side effect is bound to be quite high in real-world clinical settings.
ABSTRACT
Objectives: This study aimed to determine whether GCSB-5 has anti-inflammatory and antinociceptive effects in mice with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis (RA), and investigate the influence of GCSB-5 on the mitogen-activated protein kinase (MAPK) pathway. Materials and methods: The experimental animal study was designed to include five groups: CIA mice treated with GCSB-5 (300 mg/kg), GCSB-5 (600 mg/kg), celecoxib (60 mg/kg), or saline for four weeks, and nontreated control mice. The clinical severity of arthritis was scored. Nociceptive thresholds were measured by using a von Frey dynamic plantar analgesimeter. The MAPK pathway was evaluated in mouse synovium. The expression of channels associated with pain signaling was assessed by western blot and immunohistochemical staining. Results: GCSB-5 treatment diminished the severity of clinical arthritis and increased the nociceptive threshold in mice with CIA. Celecoxib, a positive control drug, also showed comparable changes. Clinical arthritis scores were inversely related to mechanical thresholds. GCSB-5 administration decreased the levels of anti-type II collagen antibody and inflammatory cytokines in the sera of mice with CIA. Furthermore, ERK, p38 MAPK, and JNK phosphorylation were downregulated and TRPV1 and ASIC3 expression were decreased in the synovium of GCSB-5-treated mice compared to salinetreated mice. Interleukin-6-induced TRPV1 and ASIC3 upregulation were also inhibited by GCSB-5 in human RA fibroblast-like synoviocytes in vitro. Conclusion: GCSB-5 decreased inflammatory arthritis and pain in a murine model of RA. The results present evidence that GCSB-5 may be beneficial for relieving pain as well as decreasing inflammation in autoimmune arthritis, such as RA.
ABSTRACT
RATIONALE: Colonic mucosa-associated lymphoid tissue (MALT) lymphoma is an unusual subtype comprising only 2.5% of all MALT lymphomas. Most cases of colonic MALT lymphoma are diagnosed at an early stage. Therefore, the clinical features of advanced-stage colonic MALT lymphoma have seldom been reported, and the endoscopic findings are not well established. In this study, we report the clinical and endoscopic characteristics of stage IV colonic MALT lymphoma and highlight the importance of repeat biopsy to figure out this rare disease. PATIENT CONCERNS: The patient was a 68-year-old male complaining of hematochezia and lower left quadrant abdominal pain for the past 3 days. DIAGNOSES: The patient had 3 masses and friable mucosal lesions in the colon. With the first colonoscopy and biopsy, he was initially diagnosed as having eosinophilic colitis. However, the first treatment with steroids did not show any response. Because of atypical clinical features and colonoscopic findings, a second colonoscopy and a repeat biopsy were performed, and the results were consistent with colonic MALT lymphoma arising in the colon. The patient was finally diagnosed with stage IV colonic MALT lymphoma accompanied by multiple distant metastases. INTERVENTIONS AND OUTCOMES: The patient started to receive chemotherapy with a combination regimen of cyclophosphamide, vincristine, and prednisolone. The follow-up study after 3 months showed stable disease status based on response evaluation criteria in solid tumors. LESSONS: This case report presents atypical clinical characteristics and colonoscopic findings of stage IV colonic MALT lymphoma. Clinical suspicion and repeat biopsy should be considered to diagnose this rare and diagnostically challenging cancer.
Subject(s)
Abdominal Abscess , Lung Neoplasms , Lymphoma, B-Cell, Marginal Zone , Male , Humans , Aged , Lymphoma, B-Cell, Marginal Zone/complications , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/drug therapy , Follow-Up Studies , Colon/pathology , Lung Neoplasms/complications , Abdominal Abscess/complicationsABSTRACT
BACKGROUND: The Helicobacter pylori eradication rate with standard triple therapy (STT) is continuously decreasing due to clarithromycin resistance. This study aimed to investigate the eradication rate of empirical and tailored therapy and explore various factors affecting this eradication rate using clarithromycin resistance test data for the last 4 years at a single institution in Daegu. METHODS: From August 2018 to July 2021, a total of 1,395 patients diagnosed with H. pylori infection based on rapid urea testing and histology at Keimyung University Dongsan Hospital were retrospectively examined. Participants were classified into the empirical and tailored therapy groups according to the results of the clarithromycin resistance test using the polymerase chain reaction. RESULTS: The overall eradication rate of empirical STT was 72.8%, and the eradication rate by year was 71.6% in 2018, 77.4% in 2019, 70.3% in 2020, and 70.6% in 2021; the differences were not statistically significant (p = 0.173). No significant difference was noted in the eradication rate according to gender, age, type of proton pump inhibitors, and use of probiotics. Significant differences were noted in the eradication rate according to the treat-ment period: 69.7% in the 7-day, 67.3% in the 10-day, and 81.4% in the 14-day group (p = 0.001). The eradication rate with STT was 87.4% in the non-resistant group. In the case of clarithromycin resistance, treatment was mainly with bismuth quadruple therapy (BQT), and the eradication rate was 86.1%. The eradication rate was higher with administration of BQT for 10 days or 14 days than for administration of BQT for 7 days, but with no statistical significance (p = 0.364). CONCLUSIONS: Extending the treatment period of STT helped in improving the eradication rate, and tailored therapy through clarithromycin resistance testing showed superior results when compared to empirical therapy.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , Clarithromycin/therapeutic use , Clarithromycin/pharmacology , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , Drug Therapy, Combination , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Bismuth/therapeutic use , Treatment OutcomeABSTRACT
(1) Background: Differential diagnosis using immunohistochemistry (IHC) panels is a crucial step in the pathological diagnosis of hematolymphoid neoplasms. In this study, we evaluated the prediction accuracy of the ImmunoGenius software using nationwide data to validate its clinical utility. (2) Methods: We collected pathologically confirmed lymphoid neoplasms and their corresponding IHC results from 25 major university hospitals in Korea between 2015 and 2016. We tested ImmunoGenius using these real IHC panel data and compared the precision hit rate with previously reported diagnoses. (3) Results: We enrolled 3052 cases of lymphoid neoplasms with an average of 8.3 IHC results. The precision hit rate was 84.5% for these cases, whereas it was 95.0% for 984 in-house cases. (4) Discussion: ImmunoGenius showed excellent results in most B-cell lymphomas and generally showed equivalent performance in T-cell lymphomas. The primary reasons for inaccurate precision were atypical IHC profiles of certain cases, lack of disease-specific markers, and overlapping IHC profiles of similar diseases. We verified that the machine-learning algorithm could be applied for diagnosis precision with a generally acceptable hit rate in a nationwide dataset. Clinical and histological features should also be taken into account for the proper use of this system in the decision-making process.
Subject(s)
Hematologic Diseases , Thrombocytopenia , Vestibular Diseases , Child , Humans , Sirolimus , Republic of KoreaABSTRACT
A four-year-old female patient visited the pediatric hematologic clinic due to periodic generalized edema and eosinophilia. Laboratory assessment showed an eosinophil count of 40.02×109/L (73.6% of white blood cells). A bone marrow aspirate smear film showed no signs of malignant cells but had hypercellular marrow particles with eosinophilia (45% of all nucleated cells) and 52% of eosinophils were immature. Other laboratory tests showed an increased IgM level of 827 mg/dL, and lymphocyte phenotyping by flow cytometry revealed an aberrant CD3-CD4+ T-cell population of 27-53×109/L (1.9-3.6% of lymphocytes). Polymerase chain reaction analysis for the T-cell receptor gamma gene rearrangement showed a T-cell clonality peak. At the age of 13, allogeneic stem cell transplantation was performed, but with primary rejection. From the age of 17, she has continued receiving 3 mg/kg of reslizumab intravenously every 4 weeks for 21 months. Since reslizumab treatment was initiated, her eosinophil count remained consistently within the normal range. This is the first report describing the effective use of reslizumab in a Korean adolescent patient for the management of lymphocytic-variant hypereosinophilic syndrome (L-HES). Since the patient showed clinical manifestations of L-HES as well as episodic angioedema with eosinophilia (EAE), a continuous periodic examination is required given the higher risk of developing lymphoma or leukemia.
Subject(s)
Angioedema , Hypereosinophilic Syndrome , Adolescent , Angioedema/diagnosis , Angioedema/drug therapy , Antibodies, Monoclonal, Humanized , Child , Child, Preschool , Eosinophils/pathology , Female , Humans , Hypereosinophilic Syndrome/diagnosis , Hypereosinophilic Syndrome/drug therapy , Infant, Newborn , Republic of KoreaABSTRACT
Keratoacanthoma (KA) is a common cutaneous neoplasm which often resembles typical squamous cell carcinoma (SCC) in both its clinical and historical presentation. Several studies have attempted to identify methods for distinguishing between KA and SCC, however, none of these have proven to play any obvious roles in these tumors. Given this we went on to evaluate mitochondrial microsatellite instability (mtMSI) in KA and SCC in an effort to understand these tumors better. DNA was isolated from paired normal and tumoral tissues donated by 57 KA patients and 43 SCC patients. MtMSI was then analyzed using eight microsatellite markers and was observed in 2 (3.5%) of the 57 KA patients and 8 (18.6%) of the 43 SCC patients, respectively. MtMSI was also shown to affect different locations depending on tumor type. In KA patients, mtMSI was detected at mitochondrial D514 D-loop and presented with (CA) n repeats, in contrast, all of the SCC patient experienced mtMSI at the D310 with (C)n repeats of the D-loop region. These differences in location were found to be significant, which may support the hypothesis that KA and SCC have different pathogenetic pathways. Our results also suggest that mtMSI may be a candidate for developing novel differential diagnostic methods for KA and SCC.
Subject(s)
Carcinoma, Squamous Cell/genetics , Keratoacanthoma/genetics , Microsatellite Instability , Mitochondria/genetics , Skin Neoplasms/genetics , Base Sequence , DNA, Mitochondrial/genetics , Genetic Markers , HumansABSTRACT
Neurolymphomatosis (NL) is defined as the involvement of the peripheral nervous system in lymphocytic invasion. It is a very rare form of lymphoma that may occur as an initial presentation or recurrence. It affects various peripheral nervous structures and can therefore mimic disc-related nerve root pathology or compressive mononeuropathy. NL often occurs in malignant B-cell non-Hodgkin lymphomas. Notwithstanding its aggressiveness or intractability, NL should be discriminated from other neurologic complications of lymphoma. Herein, we present a case of primary NL as the initial presentation of diffuse large B-cell lymphoma (DLBCL) of the sciatic nerve. The patient presented with weakness and pain in his left leg but had no obvious lesion explaining the neurologic deficit on initial lumbosacral and knee magnetic resonance imaging (MRI). NL of the left sciatic nerve at the greater sciatic foramen was diagnosed based on subsequent hip MRI, electrodiagnostic test, positron emission tomography/computed tomography, and nerve biopsy findings. Leg weakness slightly improved after chemotherapy and radiotherapy. We report a case wherein NL, a rare cause of leg weakness, manifested as the initial presentation of primary DLBCL involving the sciatic nerve at the greater sciatic foramen.
ABSTRACT
Actinomycosis is an inflammatory disease with various clinical presentations including inflammation and formation of masses. There are several reports suggesting the infiltrative mass-like nature of actinomycosis that is misunderstood as a tumor. A 39-year-old male clinically presented with a fungating mass-like lesion during colonoscopy for healthcare screening. Biopsy was performed for the lesion, and chronic inflammation was diagnosed. Abdominal computed tomography (CT) suggested severe edematous changes in the appendix with an appendicolith, suspected chronic inflammation, and wall thickening of the cecal base, but malignancy could not be definitively ruled out. The patient underwent a laparoscopic single-port cecectomy based on the possibility of cecal cancer. The final biopsy was diagnosed as actinomycosis, and the patient was prescribed antibiotics and showed no recurrence in the follow-up CT scan. We present this rare case of mass-like appendiceal actinomycosis treated with the single-port laparoscopic method.
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PURPOSE: The sonographic differential diagnosis of umbilical polyps and granulomas in children based on correlations with pathologic findings. METHODS: We retrospectively analyzed the ultrasonographic findings of twenty-two umbilical masses in children that were pathologically confirmed as umbilical polyps or umbilical granulomas by surgery. We analyzed size, depth, echogenicity, internal content, intralesional vascularity, and the presence of unobliterated medial umbilical ligament. Pathologic correlation was performed for all of the umbilical masses. RESULTS: Twenty-two masses consisted of eight umbilical polyps and fourteen umbilical granulomas. The mean age of the children with umbilical polyps was 30.13 months (range, 2 to 108 months) and it was 1.33 months (range, 0.6 to 3 months) for the children with umbilical granulomas. The average mass sizes were 10.25 mm (range, 5 to 35 mm) for umbilical polyps and 6.21 mm (range, 3 to 10 mm) for umbilical granulomas. The umbilical polyps were manifested as cystic lesions with thick echogenic walls in five patients (62.5%), which were associated with the intestinal mucosa (four lesions) and ectopic pancreatic tissue (one lesion) on pathology. Umbilical granulomas were superficially located in 13 (92.9%) and solid in thirteen (92.9%), which correlated with prominent granulation tissues on pathology. Seven (87.5%) of the eight umbilical granulomas were hypervascular and correlated with neovascularization on pathologic examination. CONCLUSION: The umbilical polyps revealed deep-seated, hypovascular nodules with cyst formation surrounded by thick echogenic walls. In contrast, the umbilical granulomas revealed superficially located hypervascular hypoechoic solid nodules in young infants.
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BACKGROUND: Lymph node fine-needle aspiration (LN FNA) cytology indicates necrosis in various diseases. Dominant necrotic features make the diagnosis of underlying conditions very difficult. METHODS: We retrospectively reviewed 460 patients who underwent cervical LN aspiration cytology that revealed necrotic findings at Keimyung University Dongsan Hospital in Daegu, Korea, from 2003-2017. Each specimen was evaluated and analyzed in association with the clinical findings, biopsy findings, and/or other ancillary tests, including acid-fast bacilli staining and molecular testing for Mycobacterium tuberculosis. RESULTS: When necrotic features were noted upon cervical LN FNA cytology, the most common pathologic LN FNA category was necrosis alone (31.5%). The second most common category was granulomatous inflammation (31.3%), followed by Kikuchi disease (20.0%) and malignant neoplasm (8.7%). In cases where the cervical LN FNA revealed necrosis alone, the most common final diagnosis was tuberculosis. In young patients, Kikuchi disease should be considered as one cervical LN FNA category, while metastatic carcinoma should be suspected in older patients. CONCLUSIONS: Even when necrosis alone is observed in LN FNA cytology, it is important to determine the cause through further evaluation.
ABSTRACT
AIMS: Kikuchi-Fujimoto disease (KFD) is a self-limited disease characterised by destruction of the lymph node parenchyma. Few studies have assessed the immunohistological features of KFD, and most employed limited antibody panels that lacked many of the novel immunohistochemistry markers currently available. METHODS AND RESULTS: We used immunohistochemistry to reappraise the microanatomical distribution of plasmacytoid dendritic cells (pDCs), follicular helper T cells and cytotoxic T cells, B cells, follicular dendritic cell (FDC) meshworks, and histiocytes in lymph nodes involved by KFD. The study group consisted of 138 KFD patients (89 women; 64.5%) with a median age of 27 years (range, 3-50 years). Cervical lymph nodes were most commonly involved, in 108 (78.3%) patients. The numbers of pDCs were increased, predominantly around and within apoptotic areas and the paracortex, and tapering off within xanthomatous areas. pDCs formed sizeable tight clusters, most notably around apoptotic/necrotic areas. T cells consisted mostly of CD8-positive cells with predominant expression of T-cell receptor-ß. There were notable increases in the numbers of CD8-positive T cells within lymphoid follicles, and their numbers correlated with alterations in FDC meshworks (P < 0.001). The number of follicular helper T cells was decreased within distorted FDC meshworks. CD21 highlighted frequent distortion of FDC meshworks, even in lymph node tissue that was distant from apoptotic/necrotic areas. Distorted FDC meshworks spanned all morphological patterns, and FDC meshwork characteristics (intact; distorted; remnant/nearly absent) correlated with morphological patterns (P < 0.01). CONCLUSIONS: The immunohistological landscape of KFD is complex and characterised by increased numbers of pDCs that frequently cluster around apoptotic/necrotic foci, increased numbers of cytotoxic T cells, and substantial distortion of FDC meshworks.
Subject(s)
Biomarkers/metabolism , Histiocytic Necrotizing Lymphadenitis/pathology , Immunohistochemistry/methods , Adolescent , Adult , B-Lymphocytes/pathology , Child , Child, Preschool , Dendritic Cells/pathology , Female , Histiocytes/pathology , Humans , Lymph Nodes/pathology , Male , Middle Aged , T-Lymphocytes, Helper-Inducer/pathology , Young AdultABSTRACT
BACKGROUND: Pilocytic astrocytoma (PA) is a brain tumor that is relatively more common in children and young adults. METHODS: We retrospectively reviewed the medical records of patients with PA treated at a single center between 1988 and 2018. RESULTS: We included 31 subjects with PA. The median age at diagnosis was 13.4 years, and the median follow-up duration was 9.9 years. The total PA group had a 10-year disease-specific survival (DSS) rate of 92.6% [95% confidence interval (CI), 82.6-100] and 10-year progression-free survival (PFS) rate of 52.8% (95% CI, 32.0-73.6). In patients aged <20 years, tumors were more likely to be located in sites in which gross total tumor resection (GTR) was impossible. No statistically significant difference in 10-year DSS was found between the GTR (100%) and non-GTR (89.7%; 95% CI, 76.2-100; p=0.374) groups. However, a statistically significant difference in 10-year PFS was found between the GTR (100%) and non-GTR groups (30.7%; 95% CI, 8.6-52.8; p=0.012). In the non-GTR group, no statistically significant difference in 10-year DSS was found between the patients who received immediate additional chemotherapy and/or radiotherapy (Add-Tx group, 92.9%; 95% CI, 79.4-100) and the non-Add-Tx group (83.3%; 95% CI, 53.5-100; p=0.577). No statistically significant difference in 10-year PFS was found between the Add-Tx group (28.9%; 95% CI, 1.7-56.1) and non-Add-Tx group (33.3%; 95% CI, 0-70.9; p=0.706). CONCLUSION: The PFS of the patients with PA in our study depended only on the degree of surgical excision associated with tumor location. This study is limited by its small number of patients and retrospective nature. A multicenter and prospective study is necessary to confirm these findings.
ABSTRACT
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 World Health Organization classifications. To further elucidate the clinicopathologic features of this new disease, we carried out a retrospective, multicenter analysis of 42 patients with MEITL. The median age of the patients was 59 years (range, 20-84 years), and 27 patients (64 %) were male. Thirty-two patients (76 %) were Ann-Arbor stages I-II and 28 (67 %) were Lugano stages I-II1&2. The most frequent site of involvement was the jejunum (N = 21). Most cases expressed CD8 (79 %) and CD56 (95 %) and did not express CD30 (5 %) or EBER (0 %). The median progression-free survival was 6.9 months (95 % CI 4.3-9.6); the median OS was 14.8 months (2.4-27.2). Thirty-two patients (76 %) underwent surgery and 37 (88 %) received chemotherapy. A complete response (CR) rate was 38 %. Sixteen patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 24 cases, most frequently in the primary site (N = 23). Four cases showed central nervous system relapse. Age over 55 years, poor performance scale, advanced Lugano stage (IIE-IV), not achieving CR, and not receiving ASCT were associated with inferior OS. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem essential. As CHOP might be insufficient for achieving CR, more efficient combinations should be investigated. Additionally, considering the frequent local failure and CNS relapse, novel therapeutic approaches are required to improve survival.