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).

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.

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.

Predictors of treatment failure after top-hat procedure in squamous intraepithelial lesion.

AIM: The value of top-hat procedure during loop electrosurgical excision procedure (LEEP) for squamous intraepithelial lesions had remained controversial. This study aimed to evaluate whether top-hat specimens positive for cervical intraepithelial neoplasia (CIN) on histopathology can serve as an independent risk factor to predict treatment failure. METHODS: We reviewed the medical records of patients who underwent LEEP and top-hat procedures in Peking University First Hospital between 2011 and 2016 and collected their follow-up data until January 2019. We compared the pathological risk factor of treatment failure. Multivariate analysis was carried out to clarify the independent determinant of treatment failure. A Cox model was used to assess the influence of different variables on cumulative treatment failure rates. RESULTS: This study included 295 cases for short-term treatment failure, and among them, 178 cases were used to study the long-term. The presence of CIN in top-hat was relevant to short-term treatment failure (OR = 9.64, 95% CI 2.55-36.4) despite a clear margin. On multivariate analysis, top-hat result (OR = 3.58, 95% CI 1.30-9.89), age ≥ 50 (OR = 10.2, 95%CI 3.64-28.3) and post-treatment HPV 16/18 infection (OR = 2.35, 95%CI 1.19-4.63) were independent risk factors in predicting short-term failure. In the Cox model, these factors were also associated with higher cumulative failure rates. CONCLUSION: The current study supported the predictive value of top-hat procedure in short-term failure after LEEP. Typically, women with positive top-hat need closer follow-up despite their negative margin status. Older women with positive top-hat findings and HPV 16/18 infections after the treatment suffer a higher risk of short-term failure.

PSMP/MSMP promotes hepatic fibrosis through CCR2 and represents a novel therapeutic target.

BACKGROUND & AIMS: C-C motif chemokine receptor 2 (CCR2) has been recognized as a promising target for the treatment of liver fibrosis. PC3-secreted microprotein (PSMP)/microseminoprotein (MSMP) is a novel chemotactic cytokine and its receptor is CCR2. In the present study we investigated the expression and role of PSMP in liver fibrosis/cirrhosis. METHODS: PSMP expression was studied in patients with fibrosis/cirrhosis and in 3 murine models of liver fibrosis, including mice treated with carbon tetrachloride (CCl4), bile-duct ligation, or a 5-diethoxycarbonyl-1,4-dihydrocollidine diet. The role of PSMP was evaluated in Psmp-/- mice and after treatment with a PSMP antibody in wild-type mice. The direct effects of PSMP on macrophages and hepatic stellate cells were studied in vitro. RESULTS: In this study, we found that PSMP was highly expressed in fibrotic/cirrhotic tissues from patients with different etiologies of liver disease and in the 3 experimental mouse models of fibrosis. Damage-associated molecular pattern molecules HMGB-1 and IL-33 induced hepatocytes to produce PSMP. PSMP deficiency resulted in a marked amelioration of hepatic injury and fibrosis. In CCl4-induced hepatic injury, the infiltration of macrophages and CCR2+ monocytes into the liver was significantly decreased in Psmp-/- mice. Consistent with the decreased levels of intrahepatic macrophages, proinflammatory cytokines were significantly reduced. Moreover, adeno-associated virus-8 vectors successfully overexpressing human PSMP in Psmp-/- mouse livers could reverse the attenuation of liver injury and fibrosis induced by CCl4 in a CCR2-dependent manner. Treatment with a specific PSMP-neutralizing antibody, 3D5, prevented liver injury and fibrosis induced by CCl4 in mice. At the cellular level, PSMP directly promoted M1 polarization of macrophages and activation of LX-2 cells. CONCLUSION: PSMP enhances liver fibrosis through its receptor, CCR2. PSMP is a potentially attractive therapeutic target for the treatment of patients with liver fibrosis. LAY SUMMARY: Our present study identifies the essential role of the protein PSMP for the development and progression of liver fibrosis in humans and mice. PSMP promotes liver fibrosis through inflammatory macrophage infiltration, polarization and production of proinflammatory cytokines, as well as direct activation of hepatic stellate cells via its receptor CCR2. A PSMP antibody can significantly reduce liver fibrosis development in vivo. These findings indicate that PSMP is a potential therapeutic target and its antibody is a potential therapeutic agent for the treatment of liver fibrosis.

Cutaneous composite lymphoma of mycosis fungoides and Hodgkin lymphoma: Response to sequential therapy.

Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphoma clones that occur in the same tissue site. The occurrence of cutaneous composite lymphoma (CCL) is extremely rare. Here we report a unique case of CCL consisting of Hodgkin lymphoma (HL) and mycosis fungoides (MF). Our patient presented with longstanding erythematous plaques on the skin and later developed axillary lymph node enlargement. Histopathologically, the skin lesions were characterized by a dense dermal lymphocytic infiltrate with prominent epidermotropism of pleomorphic T-cells, consistent with typical MF. Nonetheless, scattered large atypical cells resembling Reed-Sternberg (R-S) cells were interspersed among these atypical T-cells in the deep dermis. Immunophenotyping suggested a HL origin of these R-S cells. Monoclonality of T-cell receptor beta gene was detected in the skin, monoclonal immunoglobulin heavy chain gene rearrangement was identified in these R-S cells microdissected from the deep dermis, confirming the origin from HL. The lymph node biopsy showed nodular sclerosis classic Hodgkin lymphoma. Therefore, CCL of HL and MF, with lymph node HL was diagnosed. The lesions of this patient responded to a sequential treatment to HL and MF. Being aware of this rare CCL facilitates correct diagnosis and proper clinical management.

Eosinophilic peritonitis and nephrotic syndrome in Kimura's disease: a case report and literature review : Eosinophilic peritonitis in Kimura's disease.

BACKGROUND: Eosinophilic peritonitis is a relatively rare entity. Kimura's disease is a rare chronic inflammatory disorder of unknown etiology, characterized by subcutaneous nodules mainly in the head and neck region, regional lymphadenopathy and occasional involvement of kidney. There is currently no report of eosinophilic peritonitis in Kimura's disease. CASE PRESENTATION: A 44-year-old Chinese man presented with abdominal distention, nausea, vomiting and edema in lower limbs for 1 month. Laboratory data showed elevated eosinophils in peripheral blood and ascites, nephrotic syndrome with progressively renal dysfunction, and elevated IgE. Ultrasonography of lymph nodes showed multiple lymphadenopathy in bilateral inguinal regions. Surgical excision was performed for one of the enlarged lymph nodes and histopathology revealed diagnosis of Kimura's disease. Renal biopsy indicated focal segmental glomerulosclerosis (FSGS) and acute tubulointerstitial nephritis with infiltration of eosinophils in renal interstitium. The patient was prescribed with oral prednisolone therapy (30 mg/day), and underwent continuous ambulatory peritoneal dialysis (CAPD). The peripheral and peritoneal eosinophil count decreased rapidly and normalized within 2 days. Forty-five days after prednisolone therapy, partial remission of nephrotic syndrome and decrease of serum creatinine were achieved while peritoneal dialysis dosage had decreased. Inguinal lymph nodes gradually shrunk in size. The overall conditions remain stable afterwards. CONCLUSIONS: This rare case highlighted the clinical conundrum of a patient presenting with eosinophilic peritonitis, lymphadenopathy, nephrotic syndrome and renal failure associated with Kimura's disease. The remarkable eosinophilia, pathology of lymph node and kidney, as well as significant response to steroids should guide towards the diagnosis.

Value of top-hat procedure in management of squamous intraepithelial lesion.

AIM: To investigate the features of skip lesions and evaluate value of top-hat procedure in management of squamous intraepithelial lesion. METHODS: We reviewed the records of patients who underwent loop electrosurgical excision procedure (LEEP) in Peking University First Hospital between 2011 and 2016. Patients were confirmed to have CIN1-3. The term 'skip lesion' refers to lesion lying deep in cervical canal discontiguous with other lesions in transformation zone and was confirmed by top-hat. We compared their lesion grade in patients with or without skip lesion using logistic regression. We further reviewed patients who underwent subsequent hysterectomy within 6 months following LEEP and evaluated if top-hat procedure led to less residual lesions or was able to predict residual lesions. RESULTS: A total of 2260 patients were included and 595 underwent top-hat procedure. Thirty-nine out of 595 patients had skip lesions (6.5%), among whom two patients had CIN1 (5.1%), eight had CIN2 (20.5%) and 29 had CIN3 (74.4%). Logistical regression showed CIN3 was associated with higher risk of skip lesions compared to CIN1 (OR = 4.433, 95%CI: 1.036-18.964), while CIN2 was not (OR = 1.762, 95%CI: 0.366-8.471). Sixty-two patients underwent hysterectomy within 6 months following LEEP (CIN1-3), 24 underwent top-hat. Analysis revealed top-hat procedure did not result in less residual lesions. Colposcopy impression or prior HPV test was unable to predict skip lesions. CONCLUSION: About 9.4% patients with CIN3 had skip lesions in the study, which is associated with elevated risk for residual lesion. Top-hat procedure is able to detect skip lesions, but should not be performed on routinely because its prognostic value is not proved.

Effectiveness of rituximab-containing treatment regimens in idiopathic multicentric Castleman disease.

Human herpes virus type 8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disease often involving constitutional symptoms, cytopenias, and multiple organ system dysfunction. In China, the majority of MCD cases are HHV-8 negative. Given that siltuximab, the only FDA-approved treatment for iMCD is not available in China; rituximab- and cyclophosphamide-containing regimens are often used in the treatment of Chinese iMCD patients. To evaluate the efficacy of rituximab in this rare and heterogeneous disease, clinical and pathological data from 27 cases of iMCD were retrospectively analyzed from two large medical centers in China. The novel diagnostic criteria for iMCD were applied, and POEMS syndrome, IgG4-related diseases, and follicular dendritic cell sarcomas cases were excluded from analyses. Total response rate of rituximab- and cyclophosphamide-containing regimens was 55.5%, with 33.3% (9/27) of the cases reaching CR and 22.2% (6/27) PR. In the 14 cases of R-R iMCD, total response rate was only 42.9% (CR 14.3% [2/14], PR 28.6% [4/14]). The 5-year OS of these 27 iMCD cases was 81% (95% CI 64-98; 27 total patients, 4 events, 23 censored) after receiving these regimens, but the 5-year PFS was 43% (95% CI 19-66; 25 total patients, 11 events, 14 censored). Thus, rituximab-based regimens should be considered for the treatment of iMCD patients when siltuximab is not available and potentially in siltuximab-refractory cases.

Frequent immunoglobulin G4 expression in a common variant of primary cutaneous marginal zone B-cell lymphoma.

Immunoglobulin (Ig)G4 expression was recently observed in a proportion of primary cutaneous marginal zone B-cell lymphoma (PCMZL) with plasmacytic differentiation. IgG4-related disease is characterised by polyclonal lymphoplasmacytic infiltration with IgG4 expression, storiform fibrosis and obliterative phlebitis in histopathology. Here we report three cases of common variants of PCMZL with predominant and varied IgG4 expression, suggesting there is an underlying clonal progression between these two entities.

Hypermethylation of PRDM1/Blimp-1 promoter in extranodal NK/T-cell lymphoma, nasal type: an evidence of predominant role in its downregulation.

The loss of PRDM1 expression is common in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT), but the role of promoter methylation in silencing PRDM1 expression remains unclear. Hence, we performed pyrosequencing analysis to evaluate the promoter methylation of PRDM1 gene in vivo and in vitro, to analyze the association between methylation and its expression, and to assess cellular effects of PRDM1 reexpression. The promoter hypermethylation of PRDM1 gene was detected in 11 of 25 EN-NK/T-NT cases (44.0%) and NK92 and NKL cells. The promoter hypermethylation of PRDM1 was significantly correlated with PRDM1 expression in vivo and in vitro, predominantly contributing to the loss of PRDM1 expression compared with genetic deletion and aberrant expression of miR-223 in EN-NK/T-NT. PRDM1 expression was significantly restored by demethylation treatment, which induced cell proliferation suppression, cell cycle arrest, and apoptosis increase. We also found that PRDM1 reexpression could downregulate the expression of Ets-1, T-bet, granzyme B, and c-myc. Our findings demonstrated that the promoter hypermethylation of PRDM1 harbored a predominant role in the downregulation of PRDM1 expression, significantly affecting the biological behavior of tumor cells in EN-NK/T-NT.

Primary cutaneous anaplastic large cell lymphoma with intralymphatic involvement associated with chronic lymphedema.

Chronic lymphedema predisposes to develop malignant cutaneous tumors, including angiosarcoma, Kaposi's sarcoma and B-cell lymphoma. T-cell malignancy has rarely been associated with chronic lymph stasis. Here, we report a case of primary cutaneous anaplastic large cell lymphoma (pcALCL) with lymphatic spread associated with chronic lymphedema. The patient is a 56-year-old man who received orchiectomy and right inguinal lymphadenectomy for malignant seminoma 10 years ago, which led to prominent lymphedema of the right leg. He developed extensive skin nodules on the lymphedematous area for 3 months. Histopathology findings confirmed a diagnosis of pcALCL, which is a subtype of cutaneous T-cell lymphoma characterized by the presence of CD30+ T cells. Intralymphatic infiltration of malignant cells is prominent. The pathogenesis of intralymphatic cutaneous anaplastic large cell lymphoma is largely unknown. Our case suggests that chronic lymphedema resulted in persistent CD4+ T-cell inflammation, which then may contribute to the development of pcALCL.

Clinical and laboratory characterization of 114 cases of Castleman disease patients from a single centre: paraneoplastic pemphigus is an unfavourable prognostic factor.

This study retrospectively collected the clinical and laboratory data of 114 patients with Castleman disease (CD) from a single medical centre. Clinical classification identified 62 patients (54·4%) with unicentric Castleman disease and 52 (45·6%) with multi-centric Castleman disease. Pathological classification revealed 68 cases (59·6%) of hyaline vascular variant, 16 (14·1%) mixed cellular variant (Mix) and 30 (26·3%) plasmacytic variant. Clinical complications occurred in 69 CD patients, including 37 cases of paraneoplastic pemphigus (PNP) and 25 cases with renal complications. Haematological involvement, pleural effusion and/or ascites and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) were also found. Univariate analysis showed that presence of clinical complications and PNP were both risk factors relating to CD patient survival. Prognostic factors showing P < 0·15 in univariate analysis and those with clinical significance were subjected to multivariate analysis using a Cox regression model. PNP presence and age over 40 years both significantly adversely affected survival. Thus, only presence of PNP was identified as an independent unfavourable survival risk factor in both univariate and multivariate analyses. Overall, the present data provide a panoramic description of CD cases and emphasize that the presence of PNP is an adverse prognostic factor.

[Children primary intestinal inflammatory myofibroblastic tumor: a case report].

Children intestinal inflammatory myofibroblastic tumor (IMT) is rare, and its clinical differential is very difficult to the malignant tumor. Its diagnosis depends on pathology, and operation is the most effective therapy method. We preset here a case of a 5-year-old girl who was admitted to the hospital for intestinal obstruction. A malignant tumor in the intestinal wall showed on the enhanced CT. Exploratory laparotory found the tumor and then it was resected. Postoperative pathology and immunohistochemistry proved that it was an intestinal IMT. Three months' follow-up found no tumor recurrence and metastasis.

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.

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.

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.

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.