Retrospective cohort evaluation of non-HIV Castleman disease from a single academic center in Beijing, China.

The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).

Multimodality imaging of spleen involvement in Erdheim-Chester disease mimicking splenic hemangioma: a unique case report.

Erdheim-Chester disease (ECD) is a rare and clinically heterogeneous non-Langerhans cell histiocytosis, and its diagnosis relies on established clinical, radiologic, histopathological criteria. ECD can be evaluated by whole-body preoperative imaging methods. Although 18F-FDG PET/CT shows negative findings in some splenic benign or borderline lesions, such as splenic inflammatory myofibroblastic tumors and hemangioendotheliomas, it can provide value in differentiating some malignant diseases, such as hemangiosarcoma and metastases. Here, we report the CT, MRI, and 18F-FDG PET/CT imaging performance of an ECD patient who presented with only spleen involvement. Even though some clinical and radiological descriptions can be found in the literature, ECD reports with only splenic involvement mimicking splenic hemangioma as the first presentation are rare, to the best of our knowledge. Histopathology and molecular analysis of this case confirmed the diagnosis of ECD. Clinicians should pay attention to the possibility of ECD occurrence in the spleen, while negative findings on 18F-FDG PET/CT of the spleen indicated a low risk for high-grade malignant splenic tumors and metastases.

Value of High-Frequency Ultrasonography in the Qualitative and Semi-Quantitative Assessment of Immunoglobulin G4-Related Submandibular Sialadenitis.

OBJECTIVE: To assess the value of high-frequency ultrasonography in the evaluation of immunoglobulin G4-related submandibular sialadenitis (IgG4-SS). METHODS: Thirty-four submandibular glands in 17 patients with IgG4-SS were retrospectively enrolled, as well as 34 submandibular glands in 17 healthy control subjects. Qualitative ultrasonic features including submandibular gland size, border, echogenicity, and vascularity were reviewed. Two different scoring systems (0-16 and 0-48, respectively) were used for semi-quantitative analysis of imaging features. Comparison of both qualitative and semi-quantitative ultrasonic analysis were made between patients with IgG4-SS and healthy controls. Spearman correlation was used to explore relationships between variables. RESULTS: The submandibular glands with IgG4-SS presented with enlarged size, rough border, increased vascularity, and abnormal echogenicity (All P < .05). The most common echogenicity pattern for IgG-SS was diffuse hypoechoic foci pattern (44.1%), followed by superficial hypoechoic pattern (20.6%), tumor-like pattern (14.7%), and diffuse hypoechogenicity pattern (11.8%). Most IgG4-SS glands presented linear hyperechogenicity in parenchyma (91.2%). Based on both scoring system, scores of IgG4-SS were significantly higher than those of the controls (All P < .05). Association analysis of both scoring systems showed positive correlation of scores with vascularity in the gland parenchyma (All P < .05). CONCLUSION: The ultrasonic features of IgG4-SS comprise enlarged gland, rough border, increased vascularity, and abnormal echogenicity, which correlate with its pathological characteristics. The most common echogenicity pattern for IgG4-SS was diffuse hypoechoic foci pattern. Semi-quantitative analysis systems could be useful in the assessment of IgG4-SS. Ultrasound is a potential, valuable, and non-invasive tool for the diagnosis and evaluation of IgG4-SS.

A rectal gastrointestinal stromal tumor case accompanied by elevated CEA mimicking rectal carcinoma on 18F-FDG PET/CT.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm arising from gastrointestinal tract and can be benign or malignant. Rectal GISTs are rare and have poor prognosis. We here reported an older male who presented with features of distending discomfort in the rectum and pain in the anus due to a large rectal tumor. Physical examinations detected a mass in the rectum without blood staining on the gloved finger. Carcinoembryonic antigen (CEA) was found to be slightly elevated and the prostate-specific antigen level was normal. 18F-FDG PET/CT showed a soft tissue density mass at the bottom of the pelvic, with an unclear boundary to the surroundings with the significantly increased FDG uptake (SUVmax 17.5). Although a rectal carcinoma was suspected based on the finding of PET/CT and CEA, the histopathological examination confirmed the diagnosis of the malignant GIST of the rectum. The patient was then treated with imatinib and on follow-up regularly. In this case, 18F-FDG PET/CT shows the advantage of visualizing both primary and metastatic lesions and provides valuable information for the diagnosis, staging, evaluation, and prognosis of GIST.

An innovative single-base extension method for synchronous detection of point mutations and MSI status in colorectal cancer.

BACKGROUND: An accurate genotyping analysis is one of the critical prerequisites for patients with colorectal cancer receiving matched therapies. Conventional genotyping analysis is currently used to detect either gene mutations or MSI status, delaying the detection of critical tumor biomarkers and thus the optimal time for treatment. An assay that analyzes both biomarkers in a streamlined process is eagerly needed. METHODS: We developed an assay combining Multiplex PCR Amplification, Single-base Extension and capillary electrophoresis (CE) analysis (MASE-CE) for synchronous detection of KRAS/NRAS/BRAF mutations and MSI status. In a 190 colorectal cancer cohort, we identified seven somatic mutations in KRAS, NRAS and BRAF as well as five MSI loci (D2S123/D5S346/D17S250/BAT-25/BAT-26) simultaneously. KRAS/NRAS/BRAF mutations were detected by NGS and MASE-CE, and MSI status were detected by PCR-CE and MASE-CE methods. RESULTS: The MASE-CE method showed high consistency with NGS for mutation detection (Kappa value ≥0.8) and PCR-CE (Kappa value = 0.79). In addition, the limits of detection (LOD) of MASE-CE assay for MSI and somatic mutation were 5% and 2%, respectively. CONCLUSIONS: In somatic mutation detection and MSI detection, the LOD of MASE-CE assay was superior to that of qPCR and NGS. MASE-CE assay is a highly sensitive, time-saving and specimen-saving method, which can greatly avoid the cumbersome testing process and provide clinical decision for doctors in time.

Clinicopathologic Analysis of Kikuchi-Fujimoto Disease and Etiologic Exploration Using Metagenomic Next-Generation Sequencing.

CONTEXT.­: Kikuchi-Fujimoto lymphadenitis, also known as Kikuchi-Fujimoto disease (KFD), is a self-limited lymphoproliferative disease, with no definitive causative agent confirmed by traditional methods. OBJECTIVES.­: To further explore the clinicopathologic features of KFD and clarify related pathogenic factors. DESIGN.­: A retrospective analysis was performed in a collection of KFD cases to review the clinical and histopathologic features, and metagenomic next-generation sequencing (mNGS) was used in 64 formalin-fixed, paraffin-embedded (FFPE) tissues from patients with KFD. RESULTS.­: One hundred five of the 170 patients with KFD (61.8%) were female; 10 patients had autoimmune diseases. Four pathologic subtypes were classified: necrotic (45.9%, 78 of 170), phagocytic (32.4%, 55 of 170), proliferative (17.1%, 29 of 170), and xanthomatous (4.7%, 8 of 170). Patients younger than 40 years with unilateral cervical lymphadenopathy and small vessel fibrinous degeneration accounted for significant differences among the 4 pathologic subtypes (P < .05). Among 64 patients with KFD, 9 had detectable bacterial or viral DNA-of 6 bacterial cases, 1 involved Chlamydia psittaci; while of 3 viral cases, 1 involved human beta herpesvirus 6B and 2 involved Epstein-Barr virus. No significant relationships were found between the pathologic subtypes and specific pathogens. CONCLUSIONS.­: Only a small proportion of patients with KFD had autoimmune diseases or infections from specific pathogens, suggesting that KFD is likely a reactive lesion of lymph nodes to various circumstances. To our knowledge, this is the first and the largest study to detect pathogens with the use of mNGS on FFPE samples in KFD. Our study also further confirms that mNGS can be used on FFPE samples to detect potentially infectious agents in clinical settings.

To diagnose primary and secondary squamous cell carcinoma of the thyroid with ultrasound malignancy risk stratification.

Objectives: This study aimed to investigate the clinico-ultrasound features of primary squamous cell carcinoma of the thyroid (PSCCT) and secondary SCCT (SSCCT) and evaluate the accuracy of fine needle aspiration (FNA) recommendation for SCCT with American College of Radiology-Thyroid Imaging and Reporting Data System (ACR-TIRADS) and Chinese-TIRADS (C-TIRADS). Materials and methods: We retrieved 26 SCCT patients (11 PSCCT, 15 SSCCT) from our hospital's pathology database (5,718 patients with thyroid malignancy) over 23 years. Medical records and ultrasound data of the 26 patients with 27 SCCTs were analyzed retrospectively, and each SCCT focus was categorized based on the two TIRADSs. Results: For 26 patients (21 males, 5 females) with an age range of 42-81 years, rapidly enlarging thyroid/neck nodules (18/26, 69.2%), dysphagia (7/26, 26.9%), hoarseness (6/26, 23.1%), dyspnea (5/26, 19.6%), cough (4/26, 15.4%), neck pain (2/26, 7.7%), B symptoms (2/26, 7.7%), and blood in sputum (1/26, 3.8%) were presented at diagnosis. Five asymptomatic patients (5/26, 19.2%) were detected by ultrasound. Hoarseness was more common in PSCCT (5/11, 45.5%) than in SSCCT (1/15, 6.7%) (P=0.032). For 27 SCCTs with a mean size of 3.7 ± 1.3 cm, the ultrasound features consisted of solid (25/27, 92.6%) or almost completely solid composition (2/27, 7.4%), hypoechoic (17/27, 63%) and very hypoechoic echogenicity (10/27, 37%), irregular/lobulated margin with extra-thyroidal extension (27/27, 100%), taller-than-wide shape (13/27, 48.1%), punctate echogenic foci (6/27, 22.2%), hypervascularity (23/27, 85.2%) and involved neck lymph (13/26, 50.0%). A total of 27 SCCTs were evaluated as high malignancy risk stratification (≥TR4 and 4B) by the two TIRADSs and recommended FNA in 96.3-100% (26/27, 27/27). Pathologically, more than half of PSCCTs (7/12, 58.3%) and a quarter of SSCCTs (4/15, 26.7%) were poorly differentiated, while moderately and well-differentiated grades were observed in 5 PSCCTs and 11 SSCCTs (P=0.007). Thirteen patients (50.0%) underwent surgery with radical operation in 5 cases (5/13, 38.5%). Conclusion: SCCT is an extremely rare and aggressive malignancy with a male predominance. PSCCT and SSCCT had similar clinical and ultrasound features except for tumor differentiation and the symptom of hoarseness. SCCT showed a high malignancy risk stratification in ACR-TIRADS and C-TIRADS, with a high rate of FNA recommendation.

Plasmacytic Pleural Effusion as a Major Presentation of Angioimmunoblastic T-Cell Lymphoma: A Case Report.

Angioimmunoblastic T-cell lymphoma is one of the peripheral T-cell lymphomas. Reactive plasma cells can occasionally be observed in AITL patients' peripheral blood and bone marrow. Plasmacytic pleural effusion as the presentation of AITL has not been reported before. The mechanisms of plasmacytic pleural effusion are not fully understood. Here we present an 82-year-old male with exuberant plasma cells in his pleural effusion in addition to his peripheral blood and bone marrow aspiration. By presenting this case, we would like to expand the spectrum of disease presentations in AITL and discuss the significance of flow cytometry in the differential diagnosis of pleural effusion. To our knowledge, this is the first case report in the literature, which will be crucial to assist the hematopathologist in accurate diagnosis and treatment.

A rare B-cell type chronic active Epstein-Barr virus infection patient mimicking lymphoma on 18F-FDG PET/CT and literature review.

A 13-year-old girl suffered from worsen snoring and persistent bilateral nasal congestion for one year. Paranasal sinus computed tomography (CT) and magnetic resonance imaging (MRI) found nasopharyngeal passages and sinus were occupied with soft tissues and bilateral neck enlarged lymph nodes 6 months ago. Tumor markers were normal. The titers of anti-Epstein-Barr virus (EBV) IgM, anti-EBV IgG, early antigen (EA) IgG, and Epstein-Barr nuclear antigen (EBNA) IgG increased. 2-Deoxy-2-[fluorine-18]-fluoro-D-glucose (18F-FDG) positron emission tomography combined with CT (PET/CT) revealed thickened soft tissues in nasopharynx and oropharynx, enlarged multiple lymph nodes in the neck, bilateral armpits, abdominal cavity and retroperitoneum, and pelvic cavity, diffuse thickening of the gastric wall of the antrum with hypermetabolism. According to the age, situation, regions, and abnormal FDG uptake, an initial diagnosis of EBV-related lymphoma was made. However, the pathological results of the nasopharyngeal mass and the abdominal lymph node confirmed the final diagnosis of a B-cell type chronic active Epstein-Barr virus disease (CAEBV), a rare type of EBV associated lymphoproliferative disorder (LPD). After receiving adoptive immune cells therapy, the EBV load decreased. At present, the patient is being followed up.

Expression of SASP, DNA Damage Response, and Cell Proliferation Factors in Early Gastric Neoplastic Lesions: Correlations and Clinical Significance.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated senescence-associated secretory phenotype (SASP) pathway has recently been identified in the suppression and promotion of cancers. However, its practical role in carcinogenesis remains to be comprehensively elucidated. Here, we describe an investigation analysing SASP activity and its correlations with DNA damage response (DDR), genomic mutations, and cell proliferation in gastric carcinogenesis among 30 cases with available endoscopic submucosal dissection (ESD) specimens of early neoplastic lesions (including low-grade dysplasia [LGD], high-grade dysplasia [HGD], and intramucosal carcinoma). The positive cells of senescence-associated ß-galactosidase staining and cGAS, STING, interferon-regulatory factor 3 (IRF3), and signal transducer and activator of transcription 6 (STAT6) expression levels using immunostaining were elevated in HGD and in cancers. Similarly, increased expression of the Fanconi anemia group D2 (FANCD2) protein, tumour suppressor p53 binding protein 1 (TP53BP1), and replication protein A (RPA2) (i.e., primary DDR factors) was detected in HGD and in cancers; these increased expression levels were closely correlated with high expression of Ki67 and minichromosome maintenance complex component 7 (MCM7) proteins. Moreover, genomic mutations in TP53 gene were detected in 56.67% of the evaluated cases (17/30) using next-generation sequencing, and positive staining was verified in HGD and in cancers. Statistical analysis revealed that cell proliferation closely correlated with the expression of DDR factors, of which TP53BP1 was positively associated with SASP factors and IRF3 was positively correlated with cell proliferation. In addition, an analysis evaluating clinical features demonstrated that STAT6-positive cases showed a longer progression-free survival time than STAT6-negative cases. Our evaluation, conducted using a limited number of specimens, suggests SASP may be prevalent in early gastric neoplastic lesions and could be activated by accelerated cell proliferation-induced DDR. The clinical significance of SASP still needs to be determined.

Primary Epstein-Barr Virus-Positive Mucocutaneous Ulcer of Esophagus: A Rare Case Report.

Primary EBV-positive mucocutaneous ulcer (EBVMCU) is a rare and indolent disorder occurring in the oropharynx, skin, and gastrointestinal tract, with remission after removal of the immunosuppressive causes. We present a 69-year-old woman with heartburn, regurgitation of gastric acid, enlarged lymph nodes, and parotid glands. The endoscopic examination showed a circumscribed ulcer in the lower esophagus. A biopsy pathology indicated an esophageal EBV-associated lymphoproliferative disorder and a parotid gland/lymph node indolent B-cell lymphoma. Interestingly, the patient did not undergo any treatment, but the endoscopic ulcer improved significantly after more than 2 months. The last pathology showed EBV negativity, and EBVMCU was considered in combination with clinical and endoscopic manifestations. We followed up with the patient at 6 months, and the symptoms of acid reflux and heartburn had disappeared. Our case demonstrates that EBVMCU may occur in the esophagus with spontaneous regression.

Case Report: Systemic Amyloidosis Involving the Heart and Skeletal Muscle.

Background: Amyloidosis refers to an etiologically heterogeneous group of protein misfolding diseases characterized by extracellular deposition in organs and tissues of amyloid fibers, leading to severe organ dysfunction and death. Systemic amyloidosis often involves multiple organs. Heart and kidney are the most commonly affected organs, whereas skeletal muscle involvement is rare and often accompanied by other organs' involvement. Case Summary: We reported a 70-year-old man manifested with myopathy followed by heart failure who was suspected of transthyretin amyloidosis clinically, after the pathological results and the 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, light-chain (AL) amyloidosis involving the heart and skeletal muscle was confirmed. Conclusion: The patient's unique presentation gives insight into a rare but debilitating disorder and the potential link between various types of amyloidosis. In addition, myopathy in amyloidosis should be recognized.

The genetic deletion and protein expression of PRDM1 and its clinical implications in diffuse large B cell lymphoma: A retrospective cohort study in China.

OBJECT: To investigate the clinical implications of the PRDM1 deletion and PRDM1 protein expression in Chinese diffuse large B cell lymphoma (DLBCL). MATERIALS AND METHODS: Tumor samples of 199 patients with DLBCL were obtained from the Department of Pathology of Peking University First Hospital between 2008 and 2015. The PRDM1 expression was detected by immunohistochemistry (IHC) in all samples. Among them, the PRDM1 deletion was detected in 60 samples by fluorescence in situ hybridization (FISH). The correlations between PRDM1 protein expression and PRDM1 molecular status and clinicopathological features were analyzed. RESULTS: Immunohistochemically, 58 (29.1%) patients were classified as the germinal center B-cell (GCB) subtype, and 141 (70.9%) patients were non-GCB subtype. PRDM1 protein was strongly expressed in 15 (7.5%) patients, weakly expressed in 67 (33.7%) patients, and negative in 117 (26.6%) patients. Heterozygous and homozygous PRDM1 deletions were observed in 28.3% (17/60) and 8.3% (5/60) of cases, respectively. The PRDM1 deletion was not significantly correlated with PRDM1 protein expression. Neither the PRDM1 protein expression nor the PRDM1 deletion was significantly associated with most clinicopathological features, including their immunophenotypes according to the Han's algorithm. However, Kaplan-Meier survival analysis showed that heterozygous and/or homozygous PRDM1 deletion but not PRDM1 expression was a poor prognostic factor in the non-GCB group. In addition, there was a positive correlation between PRDM1 and c-Myc expression. CONCLUSIONS: Our results suggested that homozygous or heterozygous PRDM1 deletion is a poor prognostic factor for non-GCB DLBCL.

Diffuse large B-cell lymphoma presenting as reversible intrapulmonary arteriovenous shunts with hypoxia, fever and progressive jaundice: a case report and literature review.

BACKGROUND: Intrapulmonary arteriovenous shunts is rare seen in a patient without lung involvement. CASE PRESENTATION: This is the first report of reversible intrapulmonary arteriovenous shunts secondary to extrapulmonary lymphoma as one initial symptom. The patient presented as fever of unknown origin and dyspnea, and examinations of infection were negative. Diagnosis of DLBCL was finally confirmed through bone marrow and splenic biopsies. Intrapulmonary arteriovenous shunts were diagnosed through 100% oxygen inhalation test and transthoracic contrast echocardiography (TTCE). After the treatment of lymphoma, his respiratory failure was relieved. We rechecked the 100% oxygen inhalation test and TTCE, which both indicated that his intrapulmonary arteriovenous shunts had resolved. CONCLUSIONS: We speculated the prominent inflammation from active DLBCL was the most possible mechanism associated with the reversible intrapulmonary shunt in this patient. These findings will assist us to better understand the mechanism of intrapulmonary shunts.

Ultrasonic Characterization of Primary Squamous Cell Carcinoma of the Thyroid.

OBJECTIVES: To identify the ultrasonographic characteristics of primary squamous cell carcinoma of the thyroid (PSCCT), and to assess the value of the 2015 American Thyroid Association (ATA) guideline and 2017 American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) in the evaluation of this disease. METHODS: Eight patients with 9 PSCCTs over a 20-year study period were enrolled. Ultrasonic characteristics including nodule echogenicity, composition, shape, margin, calcification, size, vascularity, and cervical lymphadenopathy were reviewed. All nodules were then evaluated by 2017 ACR TI-RADS and 2015 ATA guidelines. RESULTS: The average size of PSCCTs was 3.87 ± 1.41 cm. All PSCCTs were hypoechoic or very hypoechoic, solid nodules with intranodular vascularity. The average resistive index (RI) was 0.84 ± 0.18. Near half of PSCCTs (44.4%) demonstrated extrathyroidal extension. Taller-than-wide signs and cervical lymphadenopathy were observed in 33.3% of PSCCTs, and microcalcification was observed in 11.1% of them. All PSCCTs were classified as high suspicion patterns by 2015 ATA and recommended for fine-needle aspiration (FNA). Six PSCCTs (66.7%) were classified as grade 5 by 2017 ACR TI-RADS, while the remaining were grade 4. 88.9% of PSCCTs were recommended for FNA based on 2017 ACR TI-RADS. CONCLUSION: PSCCT has certain ultrasonic features, including relatively large, hypoechoic, or very hypoechoic solid nodules with intranodular vascularity and extrathyroidal extension. Both 2015 ATA and 2017 ACR TI-RADS could identify PSCCT as suspicious for malignancy.

The usefulness of serial ultrasound in thyroid mucosa-associated lymphoid tissue lymphoma.

Background: Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal lymphoma with an indolent natural course. The thyroid gland is an uncommon site of involvement. We aimed to investigate serial ultrasound features and the disease progression during the clinical course of thyroid MALT lymphoma. Methods: We searched our hospital's pathology database (5,418 patients with thyroid malignancy) between January 2000 and July 2022. The medical records and serial ultrasounds of 11 patients with 12 thyroid MALT lymphoma foci were analyzed retrospectively. Results: An enlarging neck mass, dyspnea, B symptoms, and neck lymphadenopathy were seen at diagnosis in 9 (9/11, 81.8%), 3 (3/11, 27.3%), 2 (2/11, 18.2%), and 9 (9/11, 81.8%) cases, respectively. Eleven cases were concomitant Hashimoto thyroiditis. Common ultrasound features included bilateral or unilateral asymmetric goiter or large, solid, and very hypoechoic nodules (11/12, 91.7%) interspersed with linear, reticular hyperechoic, and enhanced posterior echoes (11/12, 91.7%), and neck lymph node involvement (10/11, 90.9%). The Thyroid Imaging and Reporting Data System (TIRADS) categories showed higher diagnostic accuracy (11/12, 91.7%) than real-time ultrasound (2/12, 16.7%) in evaluating thyroid lesions for recommendation of fine-needle aspiration (FNA). Serial ultrasound showed self-limiting changes in three cases, relapse in three cases after subtotal thyroidectomy and chemotherapy, large cell transformation (LCT) in one case after left lobectomy, partial remission in one case, and complete remission after chemo/radiation in four cases; progression to enlarged thyroid nodules occurred in three cases without treatment, with no obvious change observed after diagnosis. Three patients died during follow-up. Conclusion: On sonograms, solid large thyroid nodules or goiter with very hypoechoic and enhanced posterior echoes in the setting of Hashimoto thyroiditis should raise suspicion for MALT lymphoma. TIRADS categories can improve the ultrasound diagnostic efficacy for malignancy. Serial ultrasound examinations demonstrated self-limiting and indolent natures of thyroid MALT lymphoma.

Eyelid erythema as the first manifestation of subcutaneous panniculitis-like T-cell lymphoma mimicking dermatomyositis: a case-based review.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) which preferentially infiltrates into subcutaneous adipose tissue is rare, however may mimic autoimmune diseases from the aspect of clinical manifestations. Here, we describe a 16-year-old young man, who initially presented with eyelid erythema and swelling, accompanied by fever and muscle and bone marrow involvement. He was preliminarily considered as a patient with classical dermatomyositis (DM), but finally diagnosed as SPTCL concomitant with paraneoplastic inflammatory myositis, confirmed by in total 8 times repeated biopsies at different sites. After systematically reviewing the literatures, we summarized the main features of SPTCL mimicking DM with eyelid edema as the presenting manifestation. The cautionary tale reminds rheumatologists of considering mimickers in patients with atypical autoimmune-like manifestations. Suitable biopsy is critical for diagnosis and improving prognosis.

Hemophagocytic lymphohistiocytosis secondary to composite lymphoma: Two case reports.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disease caused by inherited pathogenic mutations and acquired dysregulations of the immune system. Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphomas that occur in a single patient. Here, we report two cases of HLH secondary to composite lymphoma with mixed lineage features of T- and B-cell marker expression both in the bone marrow and lymph nodes in adult patients. CASE SUMMARY: Two patients were diagnosed with HLH based on the occurrence of fever, pancytopenia, lymphadenopathy, splenomegaly, hemophagocytosis and hyperferritinemia. Immunohistochemical staining of the axillary lymph node and bone marrow in case 1 showed typical features of combined B-cell and T-cell lymphoma. In addition, a lymph node gene study revealed rearrangement of the T-cell receptor chain and the immunoglobulin gene. Morphology and immunohistochemistry studies of a lymph node biopsy in case 2 showed typical features of T cell lymphoma, but immunophenotyping by flow cytometry analysis of bone marrow aspirate showed B cell lymphoma involvement. The patients were treated with high-dose methylprednisolone combined with etoposide to control aggressive HLH progression. The patients also received immunochemotherapy with the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen immediately after diagnosis. Both patients presented with highly aggressive lymphoma, and died of severe infection or uncontrolled HLH. CONCLUSION: We present two rare cases with overwhelming hemophagocytosis along with composite T- and B-cell lymphoma, which posed a diagnostic dilemma. HLH caused by composite lymphoma was characterized by poor clinical outcomes.

Potential Role of Pleural Fluid Cytokine Profile in Myelomatous Pleural Effusions.

BACKGROUND: Myelomatous pleural effusion (MPE), as a presentation of extramedullary infiltration of multiple myeloma (MM), is rare and currently associated with poor outcomes without effective therapy. The potential value of cytokine detection in pleural effusion to MPE has not been reported to date. CASE PRESENTATION: We herein report a case of refractory and relapsed multiple myeloma that developed bilateral MPE due to disease progression caused by intolerance to various chemotherapy regimens. Cytomorphology and flow cytometry were adopted for diagnosis confirmation. Chemotherapy containing immunomodulators combined with thoracic catheterization drainage was applied to the patient, showing a certain therapeutic effect. During the course of disease, the change of cytokine profile in pleural effusion was monitored by cytometric bead array (CBA) technology, revealing that cytokines related to tumor load such as interleukin 6 (IL-6) and interleukin 10 (IL-10) in pleural effusion decreased with the improvement of disease, while other cytokines such as interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 17A (IL-17A), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), granzyme A, granzyme B, perforin and granulysin increased with the improvement of disease. CONCLUSION: There is a prospect that cytokine level in pleural effusion may indicate treatment response of MPE, and in light of this case, immunomodulators may be utilized in treating patients suffering MPE. Due to limitations of our single case, we urge more groups to evaluate the potential role of cytokine profile in MPE.

Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Protects the Growth and Survival of Cancer Cells.

The cGAS (GMP-AMP synthase)-mediated senescence-associated secretory phenotype (SASP) and DNA-induced autophagy (DNA autophagy) have been extensively investigated in recent years. However, cGAS-mediated autophagy has not been elucidated in cancer cells. The described investigation revealed that active DNA autophagy but not SASP activity could be detected in the BT-549 breast cancer cell line with high micronucleus (MN) formation. DNA autophagy was identified as selective autophagy of free genomic DNA in the cytoplasm but not nucleophagy. The process of DNA autophagy in the cytosol could be initiate by cGAS and usually cooperates with SQSTM1-mediated autophagy of ubiquitinated histones. Cytoplasmic DNA, together with nuclear proteins such as histones, could be derived from DNA replication-induced nuclear damage and MN collapse. The inhibition of autophagy through chemical inhibitors as well as the genomic silencing of cGAS or SQSTM1 could suppress the growth and survival of cancer cells, and induced DNA damage could increase the sensitivity to these inhibitors. Furthermore, expanded observations of several other kinds of human cancer cells indicated that high relative DNA autophagy or enhancement of DNA damage could also increase or sensitize these cells to inhibition of DNA autophagy.