Fibrosarcoma of Great Toe Shown with Multimodality Radiologic Imaging Features.

INTRODUCTION: Fibrosarcoma of bone is a rare malignant spindle cell tumor. CASE STUDY: Herein, we present a case of fibrosarcoma in a 40-year-old male who was presented to the clinic with left-sided great toe pain for 20 years. Simple radiographs showed acrolysis at the distal phalanx of great toe. Magnetic resonance imaging (MRI) revealed a 1.5 cm sized heterogenous high signal intensity mass on T2-weighted images and iso signal intensity on T1- weighted images. Dorsal and distal portion of the mass showed markedly dark signal intensity on T1 and T2-weighted images. CONCLUSION: In an enhanced image, the mass showed heterogenous enhancement. Surgical removal was performed and pathologic analysis revealed fibrosarcoma. Although extremely rare, fibrosarcoma of the bone should be kept in mind as a possibility when a lesion exhibits a black signal intensity component on an MRI with acrolysis.

The significance of programed cell death-ligand 1 expression in vestibular schwannoma.

BACKGROUND: The association between programed cell death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in vestibular schwannoma (VS) has been investigated in a few studies. These published studies report a difference in the PD-L1 positivity rate in malignant peripheral nerve sheath tumors. We examined PD-L1 expression and lymphocyte infiltration in patients with VS who had undergone surgical resection and investigated the association between PD-L1 expression and clinicopathological features. METHODS: The expression of PD-L1, CD8, and Ki-67 in 40 VS tissue specimens was investigated using immunohistochemistry, and a clinical review of the patients was performed. RESULTS: Of the 40 VS samples, 23 (57.5%) were positive for PD-L1 and 22 (55%) were positive for CD8. No significant differences in age, tumor size, pure-tone audiometry, speech discrimination, or Ki-67 expression were observed between patients in the PD-L1-positive and PD-L1-negative groups. A higher level of CD8-positive cell infiltration was observed in PD-L1-positive tumors than in PD-L1-negative tumors. CONCLUSION: We demonstrated that PD-L1 was expressed in VS tissues. Although no correlation was identified between clinical characteristics and PD-L1 expression, the association between PD-L1 and CD8 was confirmed. Thus, additional research on targeting PD-L1 is necessary to improve immunotherapy for VS in the future.

Rare case of hepatocellular carcinoma metastasis to urinary bladder: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver cancer with high prevalence and mortality. There are many cases of advanced HCC at the time of diagnosis. Treatment methods and prognosis are different depends on whether metastasis is present. Thus, it is necessary to make an accurate evaluation at the time of diagnosis. Extrahepatic metastases of HCC usually occur through hematogenous spread or through adjacent organs such as the peritoneum. Metastasis to the urinary bladder alone is rare. Here, we report a rare case of biopsy-proven solitary metastasis of HCC to the bladder in a 60-year-old woman. CASE SUMMARY: A 60-year-old female patient was found to be positive for hepatitis B surface antigen by chance after abdominal ultrasonography showed abnormal findings. Thus, liver dynamic computed tomography (CT) was performed. The patient visited the hospital for further examination. Ultrasound and CT showed 3.6 cm sized arterial enhancing mass in segment 5 and an infiltrative mass in segment 8. The patient was diagnosed with HCC through liver dynamic magnetic resonance imaging and liver biopsy. Afterwards, she underwent two transcatheter arterial chemoembolizations within five months for HCC. During follow-up, a newly appeared bladder tumor was found on liver dynamic CT. She underwent transurethral resection of the bladder tumor for diagnosis and treatment. The tissue was confirmed as metastatic HCC. CONCLUSION: Although rare, metastasis to urinary bladder from HCC can occur without evidence of other distant metastases. Thus, regular follow-up imaging examination and clinical attention are required.

Acute Hepatitis A-Induced Autoimmune Hepatitis: A Case Report and Literature Review.

INTRODUCTION: The pathogenesis of autoimmune hepatitis (AIH) is little known. Previous case reports suggest that several viral hepatitis, including hepatitis A, can trigger AIH. PATIENT: A 55-year-old female showed general weakness and jaundice. The patient was diagnosed with acute hepatitis A and discharged after 14 days of hospitalization with improving liver function. However, blood tests performed 6 days after discharge revealed an increase in liver enzymes and high serum titers of an anti-nuclear antibody and immunoglobulin G. She was readmitted for liver biopsy. DIAGNOSIS: Liver biopsy showed acute hepatitis A along with AIH. According to the revised international autoimmune hepatitis group scoring system, her score was 14 and she was diagnosed as AIH induced by acute hepatitis A. INTERVENTION: Conservative treatments with crystalloid (Lactated Ringer's Solution), ursodeoxycholic acid, and silymarin were administered. OUTCOMES: The patient has been followed up on an outpatient basis and neither symptom recurrence nor an increase in liver enzymes has been reported thus far. LESSONS: After the treatment of acute hepatitis A, liver function needs to be carefully monitored over time, and the possibility of autoimmune hepatitis should be considered when liver enzymes increases.

Biopsy-confirmed fenofibrate-induced severe jaundice: A case report.

BACKGROUND: Drug-induced liver injury (DILI) is the leading cause of acute liver failure in the United States. DILI is mainly caused by painkillers and fever reducers, and it is often characterized by the type of hepatic injury (hepatocellular or cholestatic). This report presents a case of fenofibrate-induced severe jaundice in a 65-year-old Korean male with no prior history of liver disease. We offer a strategy for patients who present signs of severe liver injury with jaundice and high elevations in serum transaminases. CASE SUMMARY: A 65-year-old male visited the gastroenterology outpatient clinic of a tertiary hospital due to increased levels of liver enzyme and total bilirubin which were incidentally detected through a preoperative screening test. Abdominal ultrasound and computed tomography showed no biliary obstruction or non-specific findings in the liver. Liver biopsy was performed and the patient was finally diagnosed with acute cholestatic hepatitis. Following the biopsy, steroid therapy was initiated and after 3 wk of treatment, the total bilirubin level was reduced to 7.22 mg/dL. CONCLUSION: In patients with hyperlipidemia, treatment including fenofibric acid induces rare complications such as severe jaundice and acute cholestatic hepatitis, warranting clinical attention.

Pazopanib-induced severe acute liver injury: A case report.

RATIONALE: Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United States. Painkillers and fever antipyretics are the most common cause of DILI. Hepatic injury can be provoked by DILI as hepatocellular or cholestatic type. PATIENT CONCERNS: A 48-year-old woman presented jaundice accompanied by nausea and vomiting. The patient was an inactive hepatitis B carrier with low viral titer and was diagnosed renal cell carcinoma (RCC) with hepatic metastasis requiring pazopanib treatment. Prior to administration of pazopanib, tenofovir administration was started to prevent exacerbation of hepatitis B. The patient was referred to clinic of gastroenterology department due to sudden elevation of bilirubin after 5 weeks of pazopanib treatment. DIAGNOSES: Abdominal ultrasound and computed tomography showed non-specific finding other than metastatic nodule in the liver and liver cirrhosis. After then, the patient was performed liver biopsy, and the biopsy result was acute cholestatic hepatitis with centrilobular area necrosis and portal inflammation. Therefore, considering the clinical history and biopsy results, the patient was diagnosed as DILI due to pazopanib. INTERVENTIONS: After the biopsy, empirical steroid therapy was initiated and after 7 weeks of pazopanib discontinuation. OUTCOMES: The total bilirubin level returned to normal from peak level of 24.61 to 1.52 mg/dL. LESSONS: In patients with renal cell carcinoma, pazopanib treatment requires clinical caution as it causes rare complications such as severe jaundice and acute cholestatic hepatitis.

Pyoderma Gangrenosum Mimicking Wound Infection after Breast Cancer Surgery.

Postoperative pyoderma gangrenosum (PPG) is rare, and its diagnosis is often delayed because of its wound infection-mimicking course. A 53-year-old breast cancer patient who underwent breast-conserving surgery of the right breast presented with fever, leukocytosis, C-reactive protein elevation, and redness of the right breast on postoperative day (POD) 3. The breast wound showed desquamation with painful ulcerative changes from POD 6, and fever was sustained under antibiotic administration. Wound irrigation was attempted; however, inflammatory skin damage progressed to involvement of the entire skin overlying the breast. With clinical suspicion of PPG, skin biopsy and systemic corticosteroid initiation were performed on POD 12. Wound damage progression ceased, and the systemic inflammation subsided. The patient underwent split-thickness skin grafting under intravenous corticosteroid administration, and the wound healed after 30 days. PPG is a rare clinical scenario. Early diagnosis is critical to avoid unnecessary treatment and aggravation of the surgical wound.

Malignant rhabdoid tumor of the kidney in an adult with loss of INI1 expression and mutation in the SMARCB1 gene.

A 57-year-old man with left flank pain was referred to our institute. Computed tomography scans revealed two enhancing masses in the left kidney. The clinical diagnosis was renal cell carcinoma (RCC). He underwent a radical nephrectomy with an adrenalectomy. Two well-circumscribed solid masses in the hilum and the lower pole (4.5 × 3.5 cm and 7.0 × 4.1 cm) were present. Poorly cohesive uniform round to polygonal epithelioid cells making solid sheets accounted for most of the tumor area. The initial diagnosis was RCC, undifferentiated with rhabdoid features. As the tumor showed loss of INI1 expression and a mutation in the SMARCB1 gene on chromosome 22, the revised diagnosis was a malignant rhabdoid tumor (MRT) of the kidney. To date, only a few cases of renal MRT in adults have been reported. To the best of our knowledge, this is the first report of MRT in the native kidney of an adult demonstrating a SMARCB1 gene mutation, a hallmark of MRT.

ERG and nestin: useful markers of immature vessels and novel prognostic markers in renal cell carcinoma.

OBJECTIVES: Renal cell carcinoma (RCC) accounts for approximately 90% of all renal malignancy. Because a rich vasculature is an outstanding feature of RCC, information on the blood vessels of RCC might explain its tumor characteristics. Several researchers have noted the effects of tumor vessels on the clinicopathologic characteristics and prognosis of tumors; however, a clear association has not been established. We hypothesized that the immaturity of the neovasculature may be an important clinicopathologic characteristic forprognosis of RCC patients. ERG and nestin are new vascular markers that regulate vascular homeostasis and angiogenesis. Therefore, in the present study, we investigated how ERG and nestin were expressed with respect to tumor characteristics. MATERIALS AND METHODS: IHC staining for ERG, nestin, CD31, and CD34 was performed for 217 renal tumors, including clear-cell RCC (ccRCC; n = 184), papillary RCC (pRCC; n = 14), chromophobe RCC (chRCC; n = 14), and oncocytoma (n = 5). RESULTS: Vascular endothelial cells from normal kidney consistently showed strong nuclear expression of ERG and nestin. Conversely, a loss of ERG and nestin expression was observed in endothelial cells of some tumor blood vessels, which was associated with tumor progression. In particular, the loss of ERG expression was significantly associated with progression-free survival and overall survival (univariate analyses: P = 0.027 and P = 0.004, respectively; multivariate analyses: P = 0.030 and P = 0.046, respectively). CONCLUSION: A loss of ERG and nestin expression is associated with tumor progression, and loss of ERG is a powerful prognostic marker for ccRCC.

Upregulation of receptor tyrosine kinase-like orphan receptor 2 in idiopathic pulmonary fibrosis.

BACKGROUND/AIMS: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a major regulator of Wnt signaling, which is involved in fibroblast dysfunction. Because its role has not been evaluated in idiopathic pulmonary fibrosis (IPF), we examined the clinical implications of ROR2 expression. METHODS: ROR2 mRNA expression was measured using reverse transcription polymerase chain reaction in lung tissue-derived fibroblasts from IPF patients (n = 14) and from controls (n = 10). ROR2 protein was measured using enzyme-linked immunosorbent assay in primary fibroblasts from IPF patients (n = 14) and controls (n = 10), and in bronchoalveolar lavage (BAL) fluids obtained from normal controls (NC; n = 30). IPF patients (n = 84), and other patients with interstitial lung diseases, including nonspecific interstitial pneumonia (NSIP; n = 10), hypersensitivity pneumonitis (HP; n = 10), and sarcoidosis (n = 10). RESULTS: ROR2 mRNA and protein levels were significantly higher in IPF fibroblasts than in controls (p = 0.003, p = 0.0017, respectively). ROR2 protein levels in BAL fluids from patients with IPF were significantly higher than in those from NC (p < 0.001), and from patients with NSIP (p = 0.006), HP (p = 0.004), or sarcoidosis (p = 0.004). Receiver operating characteristic curves showed a clear difference between IPF and NC in ROR2 protein level (area under the curve, 0.890; confidence interval, 0.829 to 0.950; p < 0.001). ROR2 protein levels were significantly higher in GAP stage III than in GAP stages I and II (p = 0.016). CONCLUSION: ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF.

Spontaneous rupture of immature gastric teratoma with hemoperitoneum in a newborn with 3-year follow-up.

Among the subtypes of germ cell tumors, teratomas are the most frequent in the pediatric population and commonly occur in the sacrococcygeal region and the gonads. Less than 1% of all teratoma are found in abdominal organs including the stomach, liver, and kidney. Gastric teratomas are very rare tumors predominantly found in infants. Moreover, an immature gastric teratoma is exceptionally rare. Here, we present a case of immature gastric teratoma with spontaneous rupture in a newborn who was preoperatively diagnosed with neuroblastoma. On the first day after birth, the neonate presented with progressive abdominal distension accompanying respiratory distress. A firm mass was detected during a physical examination of the abdomen. An emergency exploratory laparotomy revealed hemoperitoneum resulting from a rupture of the tumor located in the posterior wall of the gastric antrum. Complete resection of the tumor and gastroduodenostomy were performed. The pathology evaluation revealed a grade 3 immature gastric teratoma with no malignant components. The patient was treated with adjuvant chemotherapy to prevent recurrence, since the tumor was ruptured in the abdominal cavity and the level of alpha-fetoprotein was decreased but still remained high above the normal range after surgery. In conclusion, physicians should be aware of the existence of gastric teratoma as the differential diagnosis of a huge abdominal mass in infants, especially neonates. Complete surgical removal of the tumor and long-term follow-up has been adopted as the standard management for immature gastric teratoma, although there has been controversy with adjuvant chemotherapy.

Intramuscular composite hemangioendothelioma: case report of an unusual tumor in an unusual location.

Composite hemangioendothelioma (CHE) is an extremely rare locally aggressive vascular neoplasm comprising various benign, intermediate, and malignant vascular components. It is usually located superficially, in the dermis and subcutis of the extremities. Herein, we report a first case of CHE arising from the skeletal muscle in a 67-year-old woman who presented with a palpable mass on her right forearm. Magnetic resonance imaging revealed a 3.0 × 2.7-cm intramuscular mass with high-signal intensity on contrast-enhanced T2-weighted images. Excision was performed, and microscopic examination revealed a heterogeneous mixture of vascular components, consisting of arteriovenous malformation, spindle cell hemangioma, retiform hemangioendothelioma, and angiosarcoma-like areas. Moreover, we present a brief review of previously reported cases of CHE arising from the extremities.

Intralobar pulmonary sequestration with cystic degeneration mimicking a bronchogenic cyst in an elderly patient: A case report and literature review.

INTRODUCTION: Pulmonary sequestration (PS) is a rare congenital malformation defined as nonfunctioning lung tissue supplied by systemic circulation. It is uncommonly diagnosed in adults. Herein, we describe a clinical case of PS with cystic degeneration mimicking a bronchogenic cyst in an elderly patient. PATIENT CONCERNS: A huge cystic mass was incidentally found in a 65-year-old man on chest computed tomography (CT) scans during preoperative workup for a hand laceration. A 15-cm-sized round cystic mass was detected in the right lower lobe. DIAGNOSIS: After reviewing the chest CT scan, we decided to perform contrast-enhanced chest magnetic resonance imaging (MRI) and CT-guided lung aspiration biopsy. On MRI, the lesion had the appearance of a cystic mass with hemorrhagic clots, such as an intrapulmonary bronchogenic cyst. The aspirated specimen was nondiagnostic; thus, we decided to surgically remove the mass. INTERVENTIONS: Upon right lower lobectomy, the mass was diagnosed as a PS. A thin systemic artery supplying the cystic mass was visualized during surgery. OUTCOMES: The patient is undergoing regular follow-up at the outpatient clinic. CONCLUSIONS: PS should be considered as a differential diagnosis in patients with a cystic lung mass. Identification of a systemic artery on radiologic imaging is important in the diagnosis of PS before preoperative workup to prevent unpredicted massive bleeding during surgery.

Distribution of Adrenergic Receptor Subtypes and Responses to Topical 0.5% Apraclonidine in Patients With Blepharoptosis.

PURPOSE: To determine the relationship between the distribution of adrenergic receptors in the human eyelid and the eyelid elevation after topically instilling 0.5% apraclonidine in blepharoptosis patients. METHODS: A total of 26 blepharoptotic patients (30 eyelids) were included in the experimental study. Marginal reflex distance 1 was measured before and after topical instillation of 0.5% apraclonidine. Eyelids were divided into 2 groups according to the responses to topical 0.5% apraclonidine. Patients who positively responded to apraclonidine were classified as group A and those that negatively responded to it were classified as group B. Müller's muscle was obtained during the blepharoptotic surgery, followed by immunohistochemical staining and scoring. This study was approved by the Institutional Review Board of Kim's Eye Hospital and the study protocol adhered to the tenets of the Declaration of Helsinki. RESULTS: α-1D staining intensity was significantly higher in group A than in B (p < 0.001) and α-2C and ß-1 staining intensities were significantly higher in group B than in A (p < 0.001 and p < 0.05, respectively). The difference in ß-2 staining intensity between groups A and B was not statistically significant. CONCLUSIONS: α-1D adrenoceptor was predominant in patients showing a positive response to topical 0.5% apraclonidine. Because apraclonidine has an α-1 agonistic effect, α-1D adrenoceptor may contribute to apraclonidine's elevating effect in patients with blepharoptosis.

Gene copy number variation and protein overexpression of EGFR and HER2 in distal extrahepatic cholangiocarcinoma.

EGFR and HER2 are among the most promising therapeutic targets in solid cancers. The expression status of EGFR and HER2 are associated with the prognosis, and with a number of clinicopathological factors, in many cancers. However, few studies have examined this association in distal extrahepatic cholangiocarcinoma (EHCC). Therefore, we investigated EGFR and HER2 protein expression and gene copy number variation (CNV) in distal EHCC. We also studied the association of these factors with clinicopathological parameters and prognosis. Immunostaining, using antibodies against EGFR and HER2, was performed on 84 cases of distal EHCC. All positive (3+) and equivocal (2+) EGFR and HER2 expression cases, together with randomly selected negative (1+ and 0) cases, were evaluated for EGFR and HER2 CNV. Among distal EHCC samples, 6.0% (n=5) were positive (3+) for EGFR expression and 6.0% (n=5) were equivocal (2+). HER2 expression was positively identified in 2.4% of samples (n=2), and was equivocal in 1.2% of samples (n=1). All cases of positive EGFR expression showed amplification (n=1) or high polysomy (n=4) involving the EGFR gene; three cases (60%) of equivocal EGFR expression showed high polysomy of the EGFR gene. All cases of positive or equivocal HER2 expression (n=3, 3.6%) showed amplification of the HER2 gene. In univariate analysis, EGFR expression and CNV were associated with shorter cancer-specific overall survival (p=0.003 and p=0.018, respectively). Multivariate analysis also showed that EGFR CNV was a significant prognostic factor in distal EHCC (p=0.015). Although further study is warranted, our findings suggest that EGFR expression and CNV are factors associated with poor prognosis, and that anticancer therapeutics against EGFR and HER2 receptors may be promising therapeutic options for patients with distal EHCC.

Clear cell neuroendocrine tumor of the pancreas in von Hippel-Lindau disease: a case report and literature review.

Clear cell neuroendocrine tumor (NET) of the pancreas is found in von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type I (MEN I), and sporadic form. Clear cell NETs are often misdiagnosed as metastatic renal cell carcinoma. A 47-year-old woman with VHL was found to have a mass in the pancreatic tail and two masses in the right kidney with two cysts. A distal pancreatectomy and right radical nephrectomy were performed. The pancreatic lesion was a well-circumscribed, golden-yellow solid mass, which was lobulated by septal fibrosis. Microscopically, the tumor consisted of entirely of clear cells with prominent nucleoli. The tumor cell nests were separated by collagen fibrosis. Immunohistochemical studies were positive for the neuroendocrine markers and vimentin. Synchronous kidney tumors were clear cell renal cell carcinoma and cystic renal cell carcinoma. Those with syndrome are younger than those without syndrome. Sporadic tumors have larger size and higher grade than those of VHL and MEN I. Stromal sclerosis is frequently observed in VHL, compared with the other two groups. In the absence of a documented genetic profile and family history, awareness of these features should help us to diagnose clear cell pancreatic NETs resembling metastatic renal cell carcinoma.

Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis. RESULTS: The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034). CONCLUSION: The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.

Primary Pleural Synovial Sarcoma with Metastatic Cardiac Involvement: A Case Report.

Primary pleuropulmonary synovial sarcomas are rare soft tissue malignancies; combined metastatic involvement of the heart is extremely rare. In this case report, a 17-year-old female presented with a history of chest pain. Chest radiographs revealed a round mass in the left upper hemithorax, and computed tomography (CT) showed a well-defined heterogeneous enhancing mass abutting the pleura. A core needle biopsy revealed malignant spindle cells. Surgical resection was performed, and a final diagnosis of primary pleural synovial sarcoma, monophasic fibrous type, was made. The patient underwent radical irradiation and chemotherapy and remained stable for 28 months until a follow-up chest CT showed a poorly enhancing nodule in the left pericardial region that enlarged after 5 months. Surgical resection was performed. Histological examination confirmed metastatic cardiac involvement from a primary pleural synovial sarcoma. We report this unusual case of a primary pleural synovial sarcoma metastasis to the heart.