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.

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.

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.

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.

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.

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.

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.

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.).

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.

Estrogen replacement in female lung cancer during gefitinib therapy.

Estrogen receptor (ER) has been detected in some specimens of lung cancer. Estrogen has an effect on the growth of lung cancer cell lines. An inverse relationship between ER and epithelial growth factor receptor (EGFR) was reported in pre-clinical data. A 70-year-old female with lung adenocarcinoma, who achieved a partial response by gefitinib, underwent estrogen replacement for menopause-associated symptoms during gefinitib therapy. Lung nodules enlarged with 1-month estrogen use and regressed 6 weeks after the end of estrogen therapy. To our knowledge, this is the first case report regarding the interaction between estrogen and EGFR inhibitors.

Hoarseness in asthmatic patients: the side effect of inhaled steroid or not?

Hoarseness is one of the possible side effects of inhaled steroid in asthmatic patients as well as a common presenting feature of laryngeal tuberculosis. We report an asthmatic patient on inhaled corticosteroid treatment who presented with a 3-month history of hoarseness. Laryngeal tuberculosis without pulmonary involvement was diagnosed by laryngeal biopsy and microbiologic studies. Laryngeal tuberculosis should be considered in asthmatic patients who present with hoarseness, at least in regions in which tuberculosis is prevalent.

Pulmonary tuberculosis with delayed tuberculosis infection of total knee arthroplasty.

Tuberculous prosthetic joint infection is rare. While early diagnosis is critical for treatment, it is usually delayed. Here, we present the case of a 72-year-old patient who underwent total knee arthroplasty for his right knee due to degenerative arthritis 4 years ago. Three years after arthroplasty, pulmonary tuberculosis was found and he hesitated on starting antituberculosis chemotherapy. He suffered from progressive pain and swelling of the right prosthetic knee for 2 months before this admission. The pathologic report of the debridement of the right prosthetic knee was caseous granulomatous inflammation with positive acid-fast staining bacilli. The culture of the debridement also yielded Mycobacterium tuberculosis. He died due to aspiration pneumonia with multiorgan dysfunction. This case is a reminder of the possibility of tuberculosis while dealing with prosthetic joint infection.

Disseminated Mycobacterium kansasii infection in an HIV-negative patient presenting with mimicking multiple bone metastases.

We report a patient with disseminated Mycobacterium kansasii infection, but with no underlying disease, presenting with mimicking multiple bone metastases with cancer of unknown primary site. Disseminated M. kansasii infection is rare in HIV-negative patients without underlying diseases. This patient had disseminated M. kansasii infection manifested with vertebral osteomyelitis, sacroiliitis, psoas abscess, bone marrow granuloma, liver granuloma, and possible spleen abscesses. The clinical manifestations are described and discussed in details.

TGF-beta1 immobilized tri-co-polymer for articular cartilage tissue engineering.

Tri-co-polymer with composition of gelatin, hyaluronic acid and chondroitin-6-sulfate has been used to mimic the cartilage extracellular matrix as scaffold for cartilage tissue engineering. In this study, we try to immobilize TGF-beta1 onto the surface of the tri-co-polymer sponge to suppress the undesired differentiation during the cartilage growth in vitro. The scaffold was synthesized with a pore size in a range of 300-500 microm. TGF-beta1 was immobilized on the surface of the tri-co-polymer scaffold with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) as a crosslinking agent. Tri-co-polymer scaffolds with and without TGF-beta1 were seeded with porcine chondrocytes and cultured in a spinner flask for 2, 4, and 6 weeks. The chondrocytes were characterized by the methods of immunohistochemical staining with anti-type II collagen and anti-S-100 protein monoclonal antibody, and RT-PCR. After culturing for 4 weeks, chondrocytes showed positive in S-100 protein, Alcian blue, and type II collagen for the scaffold with TGF-beta1 immobilization. There is no observed type I and type X collagen expression in the scaffolds from the observation of RT-PCR. In addition, the scaffold without TGF-beta1 immobilization, type X collagen, can be detected after cultured for 2 weeks. Type I collagen was progressively expressed after 4 weeks. These results can conclude that TGF-beta1 immobilized scaffold can suppress chondrocytes toward prehypertrophic chondrocytes and osteolineage cells. The tri-co-polymer sponge with TGF-beta1 immobilization should have a great potential in cartilage tissue engineering in the future.

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.