Characterization of unique pattern of immune cell profile in patients with nasopharyngeal carcinoma through flow cytometry and machine learning.

In patients with nasopharyngeal carcinoma (NPC), the alteration of immune responses in peripheral blood remains unclear. In this study, we established an immune cell profile for patients with NPC and used flow cytometry and machine learning (ML) to identify the characteristics of this profile. After isolation of circulating leukocytes, the proportions of 104 immune cell subsets were compared between NPC group and the healthy control group (HC). Data obtained from the immune cell profile were subjected to ML training to differentiate between the immune cell profiles of the NPC and HC groups. We observed that subjects in the NPC group presented higher proportions of T cells, memory B cells, short-lived plasma cells, IgG-positive B cells, regulatory T cells, MHC II+ T cells, CTLA4+ T cells and PD-1+ T cells than subjects in the HC group, indicating weaker and compromised cellular and humoral immune responses. ML revealed that monocytes, PD-1+ CD4 T cells, memory B cells, CTLA4+ CD4 Treg cells and PD-1+ CD8 T cells were strongly contributed to the difference in immune cell profiles between the NPC and HC groups. This alteration can be fundamental in developing novel immunotherapies for NPC.

Magnifying Endoscopy With Narrow Band Imaging for Graft Failure and Disease Recurrence in Patients With Crohn Disease After Intestinal Transplantation: 2 Case Reports.

Crohn disease (CD) is one of the most common causes of short bowel syndrome and intestinal failure. Intestinal transplantation (IT) is sometimes needed for patients with CD who develop intestinal failure after multiple intestinal resections resulting from CD-related complications, such as uncontrollable bleeding and penetrating diseases. However, there have been few case reports concerning the endoscopic surveillance of patients with CD after IT. In this article, we present 2 patients with CD who underwent IT because of short bowel syndrome with intestinal failure. We administered posttransplantation immunosuppressants and conducted regular follow-up magnifying endoscopy with narrow-band imaging (ME-NBI). Both cases demonstrated favorable outcomes after surveillance with ME-NBI. In this report, we outline our post-IT follow-up strategies applying the VENCH scoring system, which is based on endoscopic features using ME-NBI to predict graft rejection. Our approach could effectively distinguish between acute cellular rejection and non-rejection, particularly disease recurrence of underlying CD. This study was approved by the institutional review board of Far Eastern Memorial Hospital (FEMH-105023-F). The patients provided written informed consent for publication.

Newly-diagnosed immunoglobulin A nephropathy with increased plasma galactose-deficient-IgA1 antibody associated with mRNA COVID-19 vaccination: a case report.

Newly-diagnosed or relapses of immunoglobulin A nephropathy (IgAN) have been associated with COVID-19 vaccination in the literature. Most reported cases were mild clinical diseases characterized by microscopic haematuria and do not require dialysis treatment. This current case report describes a 55-year-old male patient that presented to the emergency department with acute kidney injury after receiving the first dose of the mRNA-1273 COVID-19 vaccine. After admission, his renal function deteriorated rapidly, and then he developed uraemic encephalopathy. He underwent emergency haemodialysis with a rapid improvement in his mental status. Renal biopsy showed newly-diagnosed IgA nephropathy along with markedly elevated plasma level of galactose-deficient-IgA1 (Gd-IgA1) antibody. The patient did not receive immunosuppressive treatment and is now dialysis-free. Immune activation is considered an essential factor in developing or exacerbating IgAN following COVID-19 vaccination. This current case report demonstrates that elevated Gd-IgA1 antibody may be the potential mechanistic link between COVID-19 vaccination and IgAN.

Surveillance of Rejection After Intestinal Transplantation Using an Image Enhanced Endoscopy "VENCH" Scoring System.

BACKGROUND: Graft rejection after intestinal transplantation remains challenging. We aimed to use endoscopy for rejection prediction. MATERIALS AND METHODS: Patients ≥7 years old who underwent intestinal transplantation between November 2016 and September 2019 were prospectively enrolled. Magnifying endoscopy under narrow-band imaging was performed through ileostomy. Endoscopic findings were reported as five components (each graded from 0-2): "V" (villi appearance), "E" (erythema), "N" (capillary network), "C" (crypt widening), and "H" (heterogeneity). The correlation between histological severity and endoscopic score was analyzed. RESULTS: Ninety-nine endoscopic biopsies from three female and one male patient were analyzed. The mean ± SD age was of 41.25±13.77 (range 29-58) years. Three short bowel syndrome patients after multiple intestinal resections and one with chronic intestinal pseudo-obstruction were indicated for intestinal transplantation. Sensitivity, specificity, and accuracy of V, E, N, C, and H scores for predicting rejection were 97.4%, 45.9%, 65.7%; 94.7%, 70.5%, 79.8%; 97.4%, 52.5%, 69.7%; 94.7%, 54.1%, 69.7%; and 97.4%, 62.3%, 75.8%, respectively. Pearson's correlation coefficients between total and individual V, E, N, C, H scores and histological rejection were 0.79, 0.64, 0.70, 0.71, 0.73, and 0.66, respectively (P < .001). To predict mild and moderate/severe rejection, total scores more than 4 and 6 had the sensitivity/specificity of 87.50%/57.38% and 96.67%/85.25%, respectively (area under the ROC 0.791 and 0.987). CONCLUSION: Endoscopic VENCH scoring is promising for predicting rejection after IT. More studies are warranted to validate such results. (ClinicalTrials.gov number, NCT03616548.).

Mutation analysis and copy number changes of KRAS and BRAF genes in Taiwanese cases of biliary tract cholangiocarcinoma.

BACKGROUND/PURPOSE: Cholangiocarcinoma (CC) is a fatal malignancy originating from biliary tracts and constitutes approximately 10-20% of hepatobiliary cancers. CC is characterized by a very poor prognosis. The definite molecular mechanisms leading to oncogenesis remain unclear. This study aimed to perform mutation analysis and copy number changes of KRAS and BRAF genes of CC in Taiwan. METHODS: A total of 182 cases of biliary tact CC were studied for point mutation and quantitative real-time polymerase chain reaction analysis of KRAS and BRAF genes. The obtained data were analyzed with clinical and histopathological variables and survival. RESULTS: KRAS point mutations were detected in intrahepatic CC (7.6%), common bile duct cancer (13.3%), and gallbladder carcinoma (3.3%). BRAF gene amplifications were demonstrated in intrahepatic CC (4.3%), common bile duct cancer (3.3%), and gallbladder cancer (5%). No association was observed between mutation patterns and histopathological features. The analyses of risk factors for overall survival in patients with CC revealed no significant association in age, tumor site, genetic mutation, or amplifications. The tumor stage was the significant prognostic factor. CONCLUSION: Unlike other studies from American, European, or Japanese groups which showed certain levels of gene mutations in CC, our data revealed a rather low frequency of KRAS mutations and BRAF gene amplifications in CC in Taiwan. Tumor TNM stage was the only significant prognostic parameter in this analysis. It is crucial to gain more information of carcinogenesis, molecular mechanisms and therapeutic strategy in biliary tract cholangiocarcinoma.

ALK-positive large B-cell lymphoma: identification of EML4-ALK and a review of the literature focusing on the ALK immunohistochemical staining pattern.

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+LBCL) is a rare, aggressive B-cell lymphoma with ALK fusion genes. Histopathologically, the ALK immunohistochemical staining pattern is suggestive of the fusion partner of ALK. Here, we examined an ALK+LBCL case showing a unique diffuse cytoplasmic ALK staining pattern and identified EML4-ALK, which has not previously been reported in ALK+LBCL. Furthermore, to clarify whether the prognosis differs depending on the staining pattern, we reviewed 112 previously reported cases, and analyzed immunohistochemical markers and clinical data stratified by the staining pattern. We found that ALK staining can be classified into a granular cytoplasmic staining (GCS) or a non-GCS patterns. Sixty-four adult cases for which both the ALK staining pattern and survival time were reported were further analyzed for survival trends. The non-GCS pattern was significantly associated with inferior overall survival (P = 0.031). This difference remained significant after adjusting for age and clinical stage (hazard ratio 5.08, 95 % CI 1.88-13.7, P = 0.0013). Given that the ALK immunohistochemical staining pattern is associated with the ALK fusion partner, the present results suggest that the prognosis for ALK+LBCL differs depending on the ALK fusion partner.

Central granular cell odontogenic tumor: the first reported case in Oriental people and literature review.

The central granular cell odontogenic tumor (CGCOT) is a rare odontogenic neoplasm, usually occurring in the mandible of middle-aged women. Previous studies have reported only 34 cases, all of whom were white or black individuals. The present study reports an additional case of CGCOT, occurring in the posterior mandible of a 69-year-old Taiwanese man. To the authors' knowledge, this is the first reported case in Oriental people. The odontogenic epithelium exhibited strong positive immunoreactivity for pan-cytokeratin, and focal weak staining for bcl-2. The granular cells showed strong positivity for vimentin and α1-antichymotrypsin, and focal weak staining for carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and CD68. These features indicated a mesenchymal origin and possible histiocytic lineage for the granular cells. This study also presents a literature review and describes immunohistochemical features of the tumor.

Mutation analysis of papillary tubal hyperplasia associated with ovarian atypical proliferative serous tumor and low-grade serous carcinoma.

We present a patient with ovarian atypical proliferative serous tumor and low-grade serous carcinoma, related to KRAS mutation. Bilateral fallopian tubes had papillary tubal hyperplasia, providing additional evidence that it is the putative precursor of low-grade serous tumors. Mutation analysis of papillary tubal hyperplasia has not been done in previous literature.

Tic douloureux as a presenting feature of facial leprosy: diagnostic enigma in Taiwan.

PURPOSE: Leprosy is rarely seen in Taiwan. We herein report a foreign worker concomitantly with facial borderline tuberculoid leprosy presenting with trigeminal neuralgia. CASE REPORT: A 26-year-old male foreign labor from Indonesia, presented with 1 year history of a hypoanaesthetic erythematous plaque of right face and subsequent 6 months constant, severe pain in the right side of his face over the nasolabial groove. Biopsies and histopathological examination confirmed the diagnosis of leprosy. We treated the patient with a multidrug regimen including dapsone, clofazimine, and rifampine since April of 2012 with a good response. CONCLUSIONS: We report a rare case of new-onset leprosy presenting with trigeminal neuralgia in Taiwan and suggest leprosy should be listed in the differential diagnosis of unusual skin manifestations and neuralgia.

Polyvinylpyrrolidone storage disease presenting as pathologic fracture and anemia: report of a case with imprint cytology.

Polyvinylpyrrolidone (PVP) storage disease can be caused by local injection and systemic parenteral administration of PVP-containing solutions. PVP has been used as plasma expander, a retardant in certain medicines, components of food additive, and hair care products. High-molecular-weight PVP polymers are prevented from renal excretion and are retained in the reticuloendothelial system. The clinical manifestations include skin lesions and hematologic and orthopedic complications because of bone marrow failure and bony destruction with infiltration of PVP storage histiocytes. Herein, we report a 65-year-old female patient with PVP storage disease presenting as femoral fracture and anemia. In our case, some gelatinous material was noted atthe fracture site, and the initial clinical impression was bony tumor or metastatic lesion. Imprint cytology showed some atypical cells exhibiting foamy cytoplasm and vacuoles. The biopsy specimen revealed that some blue-grayish, vacuolated cells infiltrate in the bone marrow spaces and regional soft tissue near fracture site. The unusual morphology caused a diagnostic dilemma, with the differential diagnosis, including metastatic carcinoma, chordoma, liposarcoma, and hereditary storage disease. The vacuolated cells were positive for CD68, mucicarmine, and Congo red stains, but negative for CK (AE1/AE3) and S-100 protein. Combing the patient's history with long-term intravenous supplement of PVP-containing blood solutions, PVP storage disease involving the bone and regional soft tissue was diagnosed.

A possible rare cause of renal failure in streptococcal infection.

To the best of our knowledge, this is the first biopsy-proven case of streptococcal infection-associated acute interstitial nephritis (AIN) with existence of streptococcal pyrogenic exotoxin B (SPE B) by a controlled immunohistochemical method. Both the intact tubular epithelial cells and oedematous interstitium had strong positive signals, whereas only interstitial inflammation was dominant without tubular necrosis. Reflective of the nature of AIN is that the injury from the hypersensitivity reaction was specific for renal interstitium instead of tubules. SPE B is potentially allergenic and may confuse the clinicians due to its clinical mimicry of drug-induced AIN. Although very rare, AIN might be included into the differential diagnosis of patients with streptococcal sepsis and acute renal failure.

Imprint cytology in diagnosing-primary non-Hodgkin's lymphoma of the breast during intraoperative frozen consultation: a case report.

UNLABELLED: BACKGROUND; Primary non-Hodgkin's lymphoma of the breast is uncommon among primary malignant breast tumors. Here we present a case diagnosed as primary breast lymphoma with imprint cytology during intraoperative frozen consultation. CASE: A 67-year-old woman presented with a palpable, non-tender mass in her left breast that she had had for 2 weeks. The mammogram and ultrasound studies revealed 1 lobular mass in the left breast without axillary lymphadenopathy. Imprint cytology helped diagnose malignant lymphoma of the breast, preventing radical surgery. CONCLUSION: Frozen artifact may obscure the evaluation of cytomorphology during intraoperative consultation. Imprint cytology may help due to less artifact with the cytologic details. Primary breast lymphomas should be considered in the differential diagnosis of breast tumors. The current literature recommendation of intermediate to high grade lymphoma is combined partial mastectomy followed by chemotherapy with local radiotherapy.