Sporadic Intradural Extramedullary Hemangioblastoma Not Associated with von Hippel-Lindau Syndrome: A Case Report and Literature Review

Hemangioblastomas are low-grade, highly vascular tumors that are usually associated with von Hippel-Lindau syndrome. Hemangioblastomas most commonly occur in the cerebellum, and intradural extramedullary hemangioblastoma of the cauda equina is very rare, especially in patients without von Hippel-Lindau syndrome. Herein, we report a case of intradural extramedullary hemangioblastoma of the cauda equina that was not associated with von HippelLindau syndrome, with a focus on its imaging characteristics and differential diagnoses. We compared the clinical presentation and imaging features of our case with those of previously reported cases in the review of the literature.

Programmed cell death-ligand 1 assessment in urothelial carcinoma: prospect and limitation

Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.

ARCO Consensus on the Pathogenesis of Non-traumatic Osteonecrosis of the Femoral Head

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

Effects of low-level laser therapy and adipose-derived stem cells on the viability of autologous fat grafts: a preliminary study

Background@#Autologous fat grafts are commonly used in cosmetic and reconstructive surgery, and various methods are used to improve their viability. Low-level laser therapy (LLLT) can enhance the proliferation, growth, and differentiation of various cell lines, including stem cells. Our study investigated and compared the effects of LLLT and the addition of adipose-derived stem cells (ADSCs) on the viability of fat grafts. @*Methods@#Twenty nude mice were divided into four groups: control (group 1), LLLT irradiation (group 2), ADSC addition (group 3), and LLLT irradiation+ADSC addition (group 4). ADSCs were combined with the fat tissue. LLLT irradiation was performed once daily for 1 week from the day of grafting. After 8 weeks, the weight, volume, histology, and Western blot findings of the grafted fat tissues were evaluated. @*Results@#The retention rate and volume of the fat tissue in groups 2, 3, and 4 were higher than that of group 1, but the difference was not statistically significant. The number of capillaries, histological parameters, and immunofluorescence staining analyses for CD68, CD31, fibroblast growth factor, and vascular endothelial growth factor (VEGF) showed no significant differences among the four groups. The expression level of VEGF was higher in group 2 than in the other groups, but not to a statistically significant level. @*Conclusions@#LLLT and ADSCs did not significantly improve the viability of autologous fat grafts. Therefore, further study is necessary to develop safe and effective methods to improve the viability of these grafts for clinical application.

Sporadic Intradural Extramedullary Hemangioblastoma Not Associated with von Hippel-Lindau Syndrome: A Case Report and Literature Review

Hemangioblastomas are low-grade, highly vascular tumors that are usually associated with von Hippel-Lindau syndrome. Hemangioblastomas most commonly occur in the cerebellum, and intradural extramedullary hemangioblastoma of the cauda equina is very rare, especially in patients without von Hippel-Lindau syndrome. Herein, we report a case of intradural extramedullary hemangioblastoma of the cauda equina that was not associated with von HippelLindau syndrome, with a focus on its imaging characteristics and differential diagnoses. We compared the clinical presentation and imaging features of our case with those of previously reported cases in the review of the literature.

Programmed cell death-ligand 1 assessment in urothelial carcinoma: prospect and limitation

Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.

ARCO Consensus on the Pathogenesis of Non-traumatic Osteonecrosis of the Femoral Head

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

Effects of low-level laser therapy and adipose-derived stem cells on the viability of autologous fat grafts: a preliminary study

Background@#Autologous fat grafts are commonly used in cosmetic and reconstructive surgery, and various methods are used to improve their viability. Low-level laser therapy (LLLT) can enhance the proliferation, growth, and differentiation of various cell lines, including stem cells. Our study investigated and compared the effects of LLLT and the addition of adipose-derived stem cells (ADSCs) on the viability of fat grafts. @*Methods@#Twenty nude mice were divided into four groups: control (group 1), LLLT irradiation (group 2), ADSC addition (group 3), and LLLT irradiation+ADSC addition (group 4). ADSCs were combined with the fat tissue. LLLT irradiation was performed once daily for 1 week from the day of grafting. After 8 weeks, the weight, volume, histology, and Western blot findings of the grafted fat tissues were evaluated. @*Results@#The retention rate and volume of the fat tissue in groups 2, 3, and 4 were higher than that of group 1, but the difference was not statistically significant. The number of capillaries, histological parameters, and immunofluorescence staining analyses for CD68, CD31, fibroblast growth factor, and vascular endothelial growth factor (VEGF) showed no significant differences among the four groups. The expression level of VEGF was higher in group 2 than in the other groups, but not to a statistically significant level. @*Conclusions@#LLLT and ADSCs did not significantly improve the viability of autologous fat grafts. Therefore, further study is necessary to develop safe and effective methods to improve the viability of these grafts for clinical application.

Spinal Intraosseous Hibernoma: A Case Report and Review of Literature

Hibernoma is a rare benign tumor that arises from vestiges of brown fat. Spinal intraosseous hibernoma has only recently been described in the literature, and only 12 cases have been reported to date due to its extreme rarity. Here, we report the case of a patient who was incidentally diagnosed with an intraosseous hibernoma in the thoracic spine, following a diverse imaging work-up and pathologic confirmation. We correlate the clinical presentation and imaging features of our case with those of previously reported cases during our review of the literature.

Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications. MATERIALS AND METHODS: We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival. RESULTS: The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival. CONCLUSION: Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

Rare Case of Nerve Sheath Myxoma of the Eyelid Misdiagnosed as Mucocele

No abstract available.

A Rare Case of Dystrophic Calcification in the Masseter Muscle / 대한피부과학회지

No abstract available.

Pediatric Ewing's Sarcoma/Primitive Neuroectodermal Tumor (ES/PNET) Developed in the Small Intestine: A Case Report / 임상소아혈액종양

Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are a group of malignant tumors with varying degrees of neuroectodermal differentiation. Although it may develop in any organs, ES/PNET originating from small intestine is exceedingly rare. We experienced a 9-year-old girl presenting with abdominal pain, melena, and iron deficiency anemia. Imaging work-up showed multiple masses in the small bowel and omentum with disseminated peritoneal seeding nodules, indicating lymphoma as the most likely diagnosis. Pathological reports from explorative diagnostic laparoscopic biopsy showed tumors comprising small round cells with CD99 expression and EWS-FLI1 translocation leading to the diagnosis of ES/PNET. Tumor burden decreased gradually during five consecutive cycles of systemic chemotherapy. The patient received segmental resection of jejunum, followed by adjuvant chemotherapy. This is the first pediatric case of ES/PNET found in small intestine in Korea.

Pediatric Ewing's Sarcoma/Primitive Neuroectodermal Tumor (ES/PNET) Developed in the Small Intestine: A Case Report / 임상소아혈액종양

Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are a group of malignant tumors with varying degrees of neuroectodermal differentiation. Although it may develop in any organs, ES/PNET originating from small intestine is exceedingly rare. We experienced a 9-year-old girl presenting with abdominal pain, melena, and iron deficiency anemia. Imaging work-up showed multiple masses in the small bowel and omentum with disseminated peritoneal seeding nodules, indicating lymphoma as the most likely diagnosis. Pathological reports from explorative diagnostic laparoscopic biopsy showed tumors comprising small round cells with CD99 expression and EWS-FLI1 translocation leading to the diagnosis of ES/PNET. Tumor burden decreased gradually during five consecutive cycles of systemic chemotherapy. The patient received segmental resection of jejunum, followed by adjuvant chemotherapy. This is the first pediatric case of ES/PNET found in small intestine in Korea.

Bullous hemorrhagic dermatosis due to enoxaparin use in a bullous pemphigoid patient

Adverse reactions of subcutaneous low molecular weight heparin or unfractionated heparin could be complications by bleeding, heparin-induced thrombocytopenia, drug-induced liver injury, osteoporosis, and cutaneous reactions. Heparin-induced skin lesions vary from allergic reactions like erythema, urticaria, eczema to intradermal microvascular thrombosis associated with heparin-induced thrombocytopenia. There is a rare cutaneous complication, called bullous hemorrhagic dermatosis. We experienced this rare case of the cutaneous complication caused by enoxaparin. Several tense bullous hemorrhagic lesions occurred after 3 days of enoxaparin in a known bullous pemphigoid patient who had aortic valve replacement surgery with a mechanical prosthesis. The bullous hemorrhagic lesions were regressed after the discontinuation of enoxaparin but recurred after re-administration. The lesions were controlled by the administration of systemic corticosteroid and alternative anticoagulant. To date, less than 20 cases have been reported worldwide. This is the first case of bullous hemorrhagic dermatosis induced by enoxaparin, a low-molecular-weight heparin in Korea. This is also the first case of bullous hemorrhagic dermatosis in a known bullous pemphigoid patient.

Stromal Expression of MicroRNA-21 in Advanced Colorectal Cancer Patients with Distant Metastases

BACKGROUND: The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis. METHODS: miR-21 expression was investigated by using locked nucleic acid- fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry. RESULTS: The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1-4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041). CONCLUSIONS: miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.

The role of pathologists in multidisciplinary cancer care

In recent years there has been significant growth in multidisciplinary cancer treatment. In cancer patient management, multidisciplinary cancer treatment is essential for evaluation of treatment response and proper decision making. Multidisciplinary cancer treatment has some systematic problems in Korea; however, it is expected to be increasingly activated in tertiary medical institutions. Pathologists are core members of multidisciplinary cancer treatment teams. We reviewed the pathologist's role in multidisciplinary cancer treatment. The days of precision medicine have arrived with remarkable development in molecular pathology. Pathologists not only histologically confirm the cancer diagnosis and pathologic stage but also evaluate both prognostic factors and predictive factors determining targeted therapy. Pathologists' participation in multidisciplinary cancer treatment and explanation of pathologic results can draw good curative effect and improve patient satisfaction. The only caveat is that pathologists need to be brought down to the patient's level while describing pathologic findings. We suspect that pathologists' role will expand as pathologists participate in multidisciplinary cancer treatment in the era of precision medicine.

The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 microl) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

Potential Prognostic Value of Histone Deacetylase 6 and Acetylated Heat-Shock Protein 90 in Early-Stage Breast Cancer / 한국유방암학회지

PURPOSE: Histone deacetylase 6 (HDAC6) is an enzyme that deacetylates heat-shock protein 90 (HSP90). Many studies have investigated the role of HDAC6 and HSP90 in tumorigenesis and in the prognosis of cancer patients. This study aimed to evaluate the prognostic value of HDAC6 and acetylated HSP90 (acetyl-HSP90) in a cohort of breast cancer patients. METHODS: Immunohistochemical analysis of 314 surgical specimens obtained from patients with invasive breast cancer was carried out to assess standard pathologic factors and the expression of HDAC6 and acetyl-HSP90. Statistical analyses were performed to determine the association between HDAC6, acetyl-HSP90, and conventional clinicopathological factors, and the prognostic values of these factors were evaluated. RESULTS: HDAC6 expression did not show any correlation with other clinicopathological factors, but acetyl-HSP90 was significantly correlated with histologic grade (p=0.001) and the Ki-67 index (p=0.015). HDAC6 and acetyl-HSP90 expression were significantly associated with each other (p=0.047). Although HDAC6 was not prognostic for disease-free survival (DFS), some patients with high expression of HDAC6 experienced recurrence 5 years after diagnosis, while there was no recurrent disease after 5 years in those with low expression. Acetyl-HSP90 was significantly associated with the DFS of all patients (p=0.016) and with high HDAC6 expression (p=0.017), but not with low expression. CONCLUSION: Expression of HDAC6 and acetyl-HSP90 are correlated. HDAC6 is proposed to be a possible predictive marker of late recurrence, and acetyl-HSP90 has prognostic value in predicting the DFS of breast cancer patients.

Expression of c-MET in Invasive Meningioma

BACKGROUND: Meningiomas show high recurrence rates even after curative tumor removal. The invasiveness of meningiomas may contribute to their high recurrence rates. Recently, c-MET and hepatocyte growth factor (HGF) have been reported to be involved in cancer invasion. METHODS: We examined the immunohistochemical expression of c-MET and HGF in 100 cases of patients with meningiomas who have undergone complete tumor removal. RESULTS: c-MET(-High) and HGF(-High) were found in 17% and 13% of meningiomas, respectively. Brain invasion was observed in 17.6% of c-MET(-High) meningiomas, but in only 2.4% of c-MET(-Low) meningiomas (p=.033). Bone/soft tissue invasion was observed in 23.5% of c-MET(-High) meningiomas and in 9.6% of c-MET(-Low) meningiomas (p=.119). HGF(-High) did not show statistical association with brain invasion or bone/soft tissue invasion. c-MET(-High) demonstrated shorter recurrence-free survival (RFS, 93.5+/-8.2 months vs 96.1+/-1.9 months); however, this difference was not statistically significant (p=.139). There was no association of HGF(-High) with RFS. CONCLUSIONS: This study demonstrates that c-MET(-High) is associated with brain invasion of meningiomas, and that c-MET expression may be a useful predictive marker for meningioma recurrence. Patients with invasive meningiomas with high expressions of c-MET may be good candidates for targeted therapy using c-MET inhibitors.