Metabolic remodeling in cancer and senescence and its therapeutic implications.

Cellular metabolism is a flexible and plastic network that often dictates physiological and pathological states of the cell, including differentiation, cancer, and aging. Recent advances in cancer metabolism represent a tremendous opportunity to treat cancer by targeting its altered metabolism. Interestingly, despite their stable growth arrest, senescent cells - a critical component of the aging process - undergo metabolic changes similar to cancer metabolism. A deeper understanding of the similarities and differences between these disparate pathological conditions will help identify which metabolic reprogramming is most relevant to the therapeutic liabilities of senescence. Here, we compare and contrast cancer and senescence metabolism and discuss how metabolic therapies can be established as a new modality of senotherapy for healthy aging.

Chimeric Singleton Placenta Comprising Placental Mesenchymal Dysplasia and Complete Hydatidiform Mole with Live Birth and Postpartum Diagnosis of Gestational Trophoblastic Neoplasia.

INTRODUCTION: Placental mesenchymal dysplasia (PMD) is a benign lesion that is often misdiagnosed as complete (CHM) or partial hydatidiform mole. PMD usually results in live birth but can be associated with several fetal defects. Herein, we report PMD with CHM in a singleton placenta with live birth. CASE PRESENTATION: A 34-year-old gravida 2, para 1, living 1 (G2P1L1) woman was referred on suspicion of a molar pregnancy in the first trimester. Maternal serum human chorionic gonadotrophin levels were increased during early pregnancy, with multicystic lesions and placentomegaly observed on ultrasonography. Levels decreased to normal with no fetal structural abnormalities observed. A healthy male infant was delivered at 34 gestational weeks. Placental p57KIP2 immunostaining and short tandem repeat analysis revealed three distinct histologies and genetic features: normal infant and placenta, PMD, and CHM. Gestational trophoblastic neoplasia was diagnosed and up to fourth-line chemotherapy administered. CONCLUSION: Distinguishing PMD from hydatidiform moles is critical for avoiding unnecessary termination of pregnancy. CHM coexisting with a live fetus rarely occurs. This case is unique in that a healthy male infant was born from a singleton placenta with PMD and CHM.

A fatal case report of invasive pulmonary aspergillosis and mucormycosis coinfection in an immunocompetent patient with coronavirus disease 2019 in Korea.

Systemic glucocorticoid treatment is highly recommended in critically ill coronavirus disease 2019 (COVID-19) patients. However, secondary fungal infections are of concern in such patients. Here, we describe the first case of COVID-19-associated invasive pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) coinfection in a COVID-19 positive immunocompetent patient in Korea. A 69-year-old man was admitted to our hospital with COVID-19 pneumonia. He had no underlying comorbidities and was not taking medications. He received remdesivir, dexamethasone, and antibiotic therapy under mechanical ventilation. Although his condition improved temporarily, multiple cavities were observed on chest computed tomography, and Aspergillus fumigatus was cultured from tracheal aspiration culture. He was diagnosed with probable CAPA and received voriconazole therapy. However, his condition was not significantly improved despite having received voriconazole therapy for 4 weeks. After release from COVID-19 quarantine, he underwent bronchoscopy examination and was then finally diagnosed with CAPA and CAM coinfection on bronchoscopic biopsy. Antifungal treatment was changed to liposomal amphotericin B. However, his progress deteriorated, and he died 4 months after admission. This case highlights that clinical suspicion and active checkups are required to diagnose secondary fungal infections in immunocompetent COVID-19 patients who receive concurrent glucocorticoid therapy.

Prognostic significance of BLK expression in R-CHOP treated diffuse large B-cell lymphoma.

BACKGROUND: The aim of the present study was to evaluate the prognostic significance of B-cell lymphocyte kinase (BLK) expression for survival outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP. METHODS: We retrospectively analyzed the medical records of 89 patients from two tertiary referral hospitals. The expression of BLK, SYK, and CDK1 were evaluated in a semiquantitative method using an H-score, and the proportions of BCL2 and C-MYC were evaluated. RESULTS: A total of 89 patients received R-CHOP chemotherapy as a first-line chemotherapy. The expression rates of BLK in tumor cells was 39.2% (n = 34). BLK expression status was not significantly associated with clinical variables; however, BLK expression in tumor cells was significantly associated with the expression of both C-MYC and BCL2 (p = .003). With a median follow-up of 60.4 months, patients with BLK expression had significantly lower 5-year progression-free survival (PFS) and overall survival rates (49.8% and 60.9%, respectively) than patients without BLK expression (77.3% and 86.7%, respectively). In multivariate analysis for PFS, BLK positivity was an independent poor prognostic factor (hazard ratio, 2.208; p = .040). CONCLUSIONS: Here, we describe the clinicopathological features and survival outcome according to expression of BLK in DLBCL. Approximately 39% of DLBCL patients showed BLK positivity, which was associated as a predictive marker for poor prognosis in patients who received R-CHOP chemotherapy.

Outgrowing skin involvement in malakoplakia after kidney transplantation: A case report.

INTRODUCTION: Malakoplakia is a rare pseudotumor that arises in the context of recurrent infections, particularly in immunocompromised states. We report a case of renal allograft parenchymal malakoplakia. CASE REPORT: A 59-year-old woman successfully received a cadaveric renal transplant in June 2018. Two months after transplantation, she was treated for a urinary tract infection (UTI). In March 2019, she underwent allograft biopsy for increasing creatinine. The biopsy identified T cell mediated rejection and steroid pulse therapy was performed. In December 2019, she was hospitalized for right flank pain and pyuria, and her creatinine level was 1.9 mg/dL. Radiographic findings were suggestive of a hematoma or abscess in the perirenal area, and septated fluid collection was suspected. Biopsy results suggested malakoplakia, and von Kossa stain was positive for Michaelis- Gutmann bodies. Tissue culture demonstrated Escherichia coli, and this was treated with antibiotics. The dose of tacrolimus was reduced. The patient was discharged after 1 month of hospitalization and was maintained on oral antibiotics. Follow-up imaging revealed an increase in the extent of lesion into the adjacent abdominal wall. Assuming the case to be refractory, we performed surgical resection and abscess drainage. Although the renal parenchymal involvement persisted, the size showed a decreasing trend over 2 months of serial observation with ultrasonography. CONCLUSIONS: Malakoplakia should be considered as a differential diagnosis for recurrent UTI with graft dysfunction. Malakoplakia can be successfully treated with reduction in immunosuppression and medical therapy using long-term antibiotic treatment in most cases. However, early surgical treatment must be considered for refractory cases.

Amyloid Arthropathy and Pseudomyopathy Associated With Multiple Myeloma Detected by 18F-Florapronol Amyloid PET/CT.

ABSTRACT: We report a case of amyloid arthropathy and pseudomyopathy with multiple myeloma, detected by amyloid PET/CT using 18F-florapronol. Bone scintigraphy and 18F-FDG PET/CT in a multiple myeloma patient revealed uneven soft tissue uptakes, especially at periarticular areas. The joint capsule and intermuscular fascia showed enhancement on CT, whereas muscle enzymes were normal. These suggested amyloid arthropathy with pseudomyopathy. 18F-Florapronol amyloid PET/CT showed extensive soft tissue uptakes. Amyloid arthropathy and pseudomyopathy were confirmed after biopsy. This is the first report of amyloid PET/CT aiding in the diagnosis of unusual presentation of systemic amyloidosis.

Acute Abdominal Pain due to Accessory Splenic Infarction in an Adult: A Case Report.

Accessory spleens are common congenital anatomic variations that are usually asymptomatic. On the other hand, they can be clinically significant if complicated by hemorrhage, torsion, or infarction. This paper describes a case of an infarcted accessory spleen in a 30-year-old male who presented with abdominal pain. Abdominal CT and MRI revealed an isolated mass, 4.5 cm in size, in the perisplenic area. An infarcted accessory spleen was suspected. The patient underwent laparoscopic accessory splenectomy. Histopathology identified the mass as splenic tissue that had undergone ischemic necrosis. A definitive diagnosis of an infarcted accessory spleen was made, and the patient was discharged on day 5 after surgery symptom-free.

Targeting the stress support network regulated by autophagy and senescence for cancer treatment.

Autophagy and cellular senescence are two potent tumor suppressive mechanisms activated by various cellular stresses, including the expression of activated oncogenes. However, emerging evidence has also indicated their pro-tumorigenic activities, strengthening the case for the complexity of tumorigenesis. More specifically, tumorigenesis is a systemic process emanating from the combined accumulation of changes in the tumor support pathways, many of which cannot cause cancer on their own but might still provide excellent therapeutic targets for cancer treatment. In this review, we discuss the dual roles of autophagy and senescence during tumorigenesis, with a specific focus on the stress support networks in cancer cells modulated by these processes. A deeper understanding of such context-dependent roles may help to enhance the effectiveness of cancer therapies targeting autophagy and senescence, while limiting their potential side effects. This will steer and accelerate the pace of research and drug development for cancer treatment.

Primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), is one of the specific type of low-grade B-cell lymphoma not infrequently found worldwide. It typically involves mucosal sites such as stomach and conjunctiva; however, primary hepatic MALT lymphoma has been extremely rarely reported. We describe a case of hepatic MALT lymphoma in a 70-year-old male patient who underwent left hepatectomy due to the incidentally detected liver masses at a medical checkup. The resected specimen revealed multinodular masses consisting of small-to-intermediate-sized lymphoid cells with serpentine pattern and focal lymphoepithelial lesions. The tumor cells were diffusely positive for CD20 and Bcl-2 but negative for CD3, CD10, CD5, CD23, CD43, and cyclinD1. The Ki-67 labeling index was 10% and immunoglobulin heavy chain gene rearrangement study confirmed monoclonal proliferation. In this paper, we discuss several unique clinicopathologic characteristics which will be helpful to the differential diagnosis of hepatic MALT lymphoma.

Differential Associations of Circulating MicroRNAs With Pathogenic Factors in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disease driven by genetic and environmental factors. MicroRNAs (miRNAs) serve as pleiotropic post-transcriptional regulators of cellular pathways. Although several miRNAs have been associated with NAFLD and fibrosis, there are limited studies in humans examining their differential association with pathogenic factors or histological features of NAFLD. We examined the differential relationships of five of the best-described circulating microRNAs (miR-34a, miR-122, miR-191, miR-192, and miR-200a) with histological features and pathogenic factors of NAFLD. A cross-sectional study was conducted to examine the relationship between relative levels of circulating microRNAs standardized by z-scores and histological features of NAFLD, common NAFLD genetic polymorphisms, and insulin resistance measured by the enhanced lipoprotein insulin resistance index in 132 subjects with biopsy-proven NAFLD. We found that miR-34a, miR-122, miR-192, miR-200a, but not miR-191, strongly correlate with fibrosis in NAFLD by increases of 0.20 to 0.40 SD (P < 0.005) with each stage of fibrosis. In multivariate analysis, miR-34a, miR-122, and miR-192 levels are independently associated with hepatic steatosis and fibrosis, but not lobular inflammation or ballooning degeneration, whereas miR-200a is only associated with fibrosis. Among the four miRNAs, miR-34a, miR-122, and miR-192 are associated with pathogenic factors of NAFLD, including insulin resistance measured by eLP-IR, patatin-like phospholipase domain containing 3 I148M, and transmembrane 6 superfamily 2 (TM6SF2) E167K polymorphisms. In contrast, miR-200a is only associated with the TM6SF2 E167K variant. Finally, miR-34a has the strongest predictive value for various stages of fibrosis, with C-statistic approximates-combined predictive score for miRNAs. Conclusion: miR-34a, miR-122, miR-192, and miR-200a demonstrate strong associations with NAFLD severity by histology, but differential associations with pathogenic factors.

Pituitary Blastoma in a 19-Year-Old Woman: A Case Report and Review of Literature.

BACKGROUND: Pituitary blastoma is a malignant neoplasm of the pituitary gland that was recognized by the World Health Organization in 2017. It is commonly diagnosed in children before 24 months of age. Here, we report the first case of a young adult patient who was diagnosed with pituitary blastoma with increased levels of growth hormone instead of adrenocorticotropic hormone and provide a review of the literature. CASE DESCRIPTION: A 19-year-old woman presented to our hospital with visual disturbance. She had a medical history of Wilms' tumor and multinodular goiter. The brain imaging showed a 3.2 × 2.5 × 1.8-cm solid sellar and suprasellar cystic mass that upwardly displaced the optic chiasm. She had an elevated level of growth hormone but a normal level of adrenocorticotropic hormone, cortisol, and prolactin. The mass was subtotally removed through the left pterional craniotomy. The pathologic examination suggested a pituitary blastoma. Thereafter, the patient was treated with chemotherapy and radiotherapy. At 4-year follow-up postsurgery, her overall well-being is good. CONCLUSIONS: Although in this case the patient was a young adult, pituitary blastoma should be taken into consideration when children have an enhanced sellar and suprasellar mass with peripherally located cysts.

Programmed death-ligand 1 expression and its correlation with clinicopathological parameters in gallbladder cancer.

BACKGROUND: Immunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC). METHODS: We investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression- free survival (PFS) were analyzed. RESULTS: PD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05). CONCLUSIONS: The expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact.

Clinical Utility of 18F-Florbetaben PET for Detecting Amyloidosis Associated With Multiple Myeloma: A Prospective Case-Control Study.

PURPOSE: The aims of this study were to evaluate the diagnostic performance of F-florbetaben PET/CT for detecting amyloid deposits in patients with multiple myeloma (MM) and to identify the optimal PET analysis method. METHODS: Fourteen patients with MM were prospectively enrolled (6 with amyloidosis, 8 control subjects). Dynamic imaging of the kidneys was performed for 20 minutes, and the retention ratio was obtained. At 90 minutes after injection, PET was performed. All images were assessed qualitatively and quantitatively, and the SUVmax, SUVmean, and SUVratio were obtained. Variables were compared between the amyloidosis group and the control group. Amyloid deposition was confirmed according to international consensus guidelines. RESULTS: Tracer uptake was abnormal in all patients with amyloidosis. The visual detection rate was excellent (100%) in the heart, stomach, and tongue but limited in the kidneys (50%) and poor (0%) in the esophagus, liver, and colon. F-florbetaben PET/CT identified 13 unexpected cases of abnormal uptake, confirming further amyloid deposition. Both spherical and manual volumes of interest showed similar diagnostic performance when evaluating amyloidosis in target organs. There was no significant difference in diagnostic performance between the SUVmax, SUVmean, and SUVratio. CONCLUSIONS: F-florbetaben PET/CT can accurately detect systemic amyloid deposits in patients with MM. F-florbetaben PET/CT was particularly useful in the heart, stomach, and tongue but of limited value in the esophagus, liver, and colon. F-florbetaben PET/CT can provide clinical information on organ involvement and could replace pathologic examination for diagnosis of amyloidosis in the future.

Association of baseline histopathology and kidney donor risk index with graft outcomes in deceased donor kidney transplantation
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BACKGROUND: Donor organ quality is a key determinant of graft outcomes in deceased donor kidney transplantation (DDKT). The predictive values of baseline histopathology and several clinical scoring systems for long-term graft outcomes have been evaluated, but the results remain controversial. MATERIALS AND METHODS: We screened 167 patients who underwent DDKT at Ulsan University Hospital from April 2003 to June 2016. Among them, 66 patients who underwent baseline kidney biopsy and whose kidney donor risk index (KDRI) was available were included in this analysis. All baseline biopsies were rescored according to the updated Banff classification. RESULTS: Median follow-up was 22 months. Mean age of recipients and donors was 51.4 and 44.7 years, respectively. Mean KDRI was 1.40 ± 0.44. During follow-up, delayed graft function and biopsy-proven acute rejection (BPAR) developed in 7 and 11 patients, respectively. Graft failure occurred in 2 patients. In Cox regression analysis, interstitial fibrosis/tubular atrophy (IFTA) (hazard ratio (HR) = 3.59; p = 0.049) was a significant risk factor for BPAR. In multivariate linear regression, age (standardized ß (SB) = -0.282; p = 0.002), BPAR (SB = -0.406; p < 0.001), KDRI (SB = -0.277; p = 0.003), and IFTA (SB = -0.298; p = 0.001) were significant predictors of last-visit estimated glomerular filtration rate (eGFR). CONCLUSION: Several clinical and pathologic parameters, such as KDRI and IFTA, may be helpful for predicting long-term graft outcomes, including BPAR and last-visit eGFR, in DDKT.
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A Pathophysiologic Approach Combining Genetics and Insulin Resistance to Predict the Severity of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a complex disease dictated by both genetic and environmental factors. While insulin resistance (IR) is a key pathogenic driver, two common genetic variants in patatin-like phospholipase domain containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) also impart significant risk for disease progression. Traditional approaches to NAFLD risk stratification rely on biomarkers of fibrosis, an end result of disease progression. We hypothesized that by combining genetics and a novel measurement for IR we could predict disease progression by the NAFLD activity score (NAS) and histologic presence of significant fibrosis. A total of 177 patients with biopsy-proven NAFLD were enrolled in this cross-sectional study. PNPLA3 I148M and TM6SF2 E167K genotypes were determined by TaqMan assays. The enhanced lipoprotein IR index (eLP-IR) was calculated from serum biomarkers using nuclear magnetic resonance (NMR) spectroscopy. Multivariate regression models were used to study the relationships between genetics, IR, and histologic features of NAFLD. In the multivariate analysis, the eLP-IR was strongly associated with histologic features of NAFLD activity and hepatic fibrosis (P < 0.001 to 0.02) after adjustment for potential confounders. PNPLA3 148M and TM6SF2 E167K genotypes were significantly associated with steatosis (P = 0.003 and P = 0.02, respectively). A combination of the eLP-IR and genetic score was able to predict the presence of NAS ≥3 with an area under the receiver operating characteristic curve (AUROC) of 0.74. Adding age to this model predicted stages 3-4 liver fibrosis with an AUROC of 0.82. Conclusion: This proof-of-concept study supports the hypothesis that genetics and IR are major determinants of NAFLD severity and demonstrates the feasibility of a new risk stratification paradigm using exclusively pathogenic factors.

Activation of Nrf2 Is Required for Normal and ChREBPα-Augmented Glucose-Stimulated ß-Cell Proliferation.

Patients with both major forms of diabetes would benefit from therapies that increase ß-cell mass. Glucose, a natural mitogen, drives adaptive expansion of ß-cell mass by promoting ß-cell proliferation. We previously demonstrated that a carbohydrate response element-binding protein (ChREBPα) is required for glucose-stimulated ß-cell proliferation and that overexpression of ChREBPα amplifies the proliferative effect of glucose. Here we found that ChREBPα reprogrammed anabolic metabolism to promote proliferation. ChREBPα increased mitochondrial biogenesis, oxygen consumption rates, and ATP production. Proliferation augmentation by ChREBPα required the presence of ChREBPß. ChREBPα increased the expression and activity of Nrf2, initiating antioxidant and mitochondrial biogenic programs. The induction of Nrf2 was required for ChREBPα-mediated mitochondrial biogenesis and for glucose-stimulated and ChREBPα-augmented ß-cell proliferation. Overexpression of Nrf2 was sufficient to drive human ß-cell proliferation in vitro; this confirms the importance of this pathway. Our results reveal a novel pathway necessary for ß-cell proliferation that may be exploited for therapeutic ß-cell regeneration.

Clear Cell Hidradenoma: Characteristic Imaging Features on Ultrasonography, Computed Tomography, and Magnetic Resonance Imaging.

OBJECTIVES: The purpose of this study was to evaluate the imaging features of clear cell hidradenoma on ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI). METHODS: The radiologic and pathologic databases at 2 medical institutions were searched retrospectively from 2004 to 2016 to identify patients with a diagnosis of clear cell hidradenoma. Ultrasonographic, CT, and MRI features were described, and pathologic specimens were reviewed. RESULTS: There were 5 female and 4 male patients. The mean patient age was 48.9 years (range, 28-70 years). Five patients underwent only US; 2 patients underwent only CT; 1 patient underwent both US and CT; and 1 patient underwent US and MRI. Most of the tumors were located primarily in the subcutaneous fat layer. The mean tumor size was 18.4 mm. On US, 6 masses had a heterogeneous echo texture, including an anechoic portion with protruding echogenic portions. Two masses had multiple septa in the anechoic portion. On color Doppler US, blood flow was both central and peripheral in 5 patients. All 3 cases seen on CT presented as a low-attenuation mass with an enhanced solid internal nodule. On MRI, the mass showed heterogeneous signal intensity on T2-weighted images and enhancement of the peripheral wall and internal solid component on contrast-enhanced T1-weighted images. CONCLUSIONS: Clear cell hidradenoma is usually located in the subcutaneous fat layer, has a well-defined margin, appears as a cystic mass with an internal solid nodule, and occasionally has multiple septa on US, CT, and MRI.

Autophagy Is Pro-Senescence When Seen in Close-Up, but Anti-Senescence in Long-Shot.

When mammalian cells and animals face a variety of internal or external stresses, they need to make homeostatic changes so as to cope with various stresses. To this end, mammalian cells are equipped with two critical stress responses, autophagy and cellular senescence. Autophagy and cellular senescence share a number of stimuli including telomere shortening, DNA damage, oncogenic stress and oxidative stress, suggesting their intimate relationship. Autophagy is originally thought to suppress cellular senescence by removing damaged macromolecules or organelles, yet recent studies also indicated that autophagy promotes cellular senescence by facilitating the synthesis of senescence-associated secretory proteins. These seemingly opposite roles of autophagy may reflect a complex picture of autophagic regulation on cellular senescence, including different types of autophagy or a unique spatiotemporal activation of autophagy. Thus, a better understanding of autophagy process will lead us to not only elucidate the conundrum how autophagy plays dual roles in the regulation of cellular senescence but also helps the development of new therapeutic strategies for many human diseases associated with cellular senescence. We address the pro-senescence and anti-senescence roles of autophagy while focusing on the potential mechanistic aspects of this complex relationship between autophagy and cellular senescence.

Diagnostic clue of nodular fasciitis mimicking metastasis in papillary thyroid cancer, mismatching findings on 18F-FDG PET/CT and 123I whole body scan: A case report.

This study reports a case of nodular fasciitis incidentally detected in a patient with papillary thyroid cancer. A 47-year-old woman underwent a total thyroidectomy and radioactive iodine therapy for papillary thyroid cancer. On a follow-up fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) scan after 12 months, a focal 18F-FDG-avid lesion was incidentally detected in the paraspinal muscle. It was well-enhanced on CT and magnetic resonance imaging, indicating metastasis. However, the lesion was not iodine avid on the 123I whole body scan, which favored benign etiology over metastasis from thyroid cancer. For pathological confirmation, surgical excision was performed and the paraspinal lesion was finally confirmed as nodular fasciitis. Therefore, it was suggested that nodular fasciitis may be included in the differential diagnosis of a 18F-FDG avid/iodine non-avid soft tissue lesion in patients with thyroid cancer. In such circumstances, 123I whole body scans may serve a role in non-invasive work-up, and prevent unnecessary surgical procedures.

Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type.

Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are new therapeutic targets in cancer immunotherapy. The aim of this study was to investigate the clinicopathological characteristics of PD-1 and PD-L1 expression in extranodal natural killer/T­cell lymphoma, nasal type (ENKTL). We performed PD-1 and PD-L1 immunostaining in 79 ENKTL biopsy samples and retrospectively analyzed medical records of all 79 patients from four tertiary referral hospitals. The expression of PD-1 and PD-L1 by tumor cells and/or infiltrating immune cells was evaluated. The expression rates of PD-L1 in tumor cells and infiltrating immune cells were 79.7 and 78.5 %, respectively, whereas PD-1 in tumor cells and infiltrating immune cells were 1.3 and 11.4 %. The PD-L1 positivity in tumor cells and infiltrating immune cells was significantly associated with low international prognostic index (IPI) (P = 0.044 and 0.037, respectively). Patients with normal range of serum lactate dehydrogenase demonstrated a significantly higher PD-L1 positivity in tumor cells (P = 0.020). PD-L1-positive patients had a trend toward better overall survival compared with that in patients with PD-L1-negative in tumor cells and infiltrating immune cells (P = 0.498 and 0.435, respectively). The expression rate of PD-L1 was up to 79.7 % in ENKTL, while PD-1 expression rate was very low. This is the first report describing the clinicopathological features and survival outcome according to expression of PD-1 and PD-L1 in ENKTL.