LGR5 and Downstream Intracellular Signaling Proteins Play Critical Roles in the Cell Proliferation of Neuroblastoma, Meningioma and Pituitary Adenoma

Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream signaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.

A Case of Large Cell Neuroendocrine Carcinoma of the Maxillary Sinus / 대한두경부종양학회지

Large cell neuroendocrine carcinoma is a rare epithelial neuroendocrine malignancy and is preferentially located in gastrointestinal tract and pancreas. Cases of large cell neuroendocrine carcinoma have been reported in many other locations, including the thymus, gallbladder, prostate, larynx, salivary glands, nasopharynx, tonsil and mastoid. However, primary sinonasal large cell neuroendocrine carcinoma never have been reported in Korea. We experienced a case of primary large cell neuroendocrine carcinoma arising from left maxillary sinus recently. A 82-year-old male patient presented with nasal obstruction and epistaxis. The biopsy revealed large cell neuroendocrine carcinoma with poor differentiation. After a general evaluation, the patient was staged as cT3N0M0. The patient was treated by combined radiotherapy and chemotherapy. We report this rare case with literature review.

The submucosal fibrosis: what does it mean for colorectal endoscopic submucosal dissection?

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) allows removal of colorectal epithelial neoplasms en bloc regardless of size. Colorectal ESD is a difficult procedure because of technical difficulties and risks of complications. This study aimed to assess the relationship between ESD outcome and degree of submucosal fibrosis. METHODS: Patients with colorectal tumors undergoing ESD and their medical records were reviewed retrospectively. The degree of submucosal fibrosis was classified into three types. The relationship between ESD outcome and degree of submucosal fibrosis was analyzed. RESULTS: ESD was performed in 158 patients. Thirty-eight cases of F0 (no) fibrosis (24.1%) and 46 cases of F2 (severe) fibrosis (29.1%) were observed. Complete resection was achieved for 138 lesions (87.3%). Multivariate analysis demonstrated that submucosal invasion of tumor and histology of carcinoma were independent risk factors for F2 fibrosis. Severe fibrosis was an independent risk factor for incomplete resection. CONCLUSIONS: Severe fibrosis is an important factor related to incomplete resection during colorectal ESD. In cases of severe fibrosis, the rate of complete resection was low even when ESD was performed by an experienced operator. Evaluation of submucosal fibrosis may be helpful to predict the submucosal invasion of tumors and technical difficulties in ESD.

The submucosal fibrosis: what does it mean for colorectal endoscopic submucosal dissection?

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) allows removal of colorectal epithelial neoplasms en bloc regardless of size. Colorectal ESD is a difficult procedure because of technical difficulties and risks of complications. This study aimed to assess the relationship between ESD outcome and degree of submucosal fibrosis. METHODS: Patients with colorectal tumors undergoing ESD and their medical records were reviewed retrospectively. The degree of submucosal fibrosis was classified into three types. The relationship between ESD outcome and degree of submucosal fibrosis was analyzed. RESULTS: ESD was performed in 158 patients. Thirty-eight cases of F0 (no) fibrosis (24.1%) and 46 cases of F2 (severe) fibrosis (29.1%) were observed. Complete resection was achieved for 138 lesions (87.3%). Multivariate analysis demonstrated that submucosal invasion of tumor and histology of carcinoma were independent risk factors for F2 fibrosis. Severe fibrosis was an independent risk factor for incomplete resection. CONCLUSIONS: Severe fibrosis is an important factor related to incomplete resection during colorectal ESD. In cases of severe fibrosis, the rate of complete resection was low even when ESD was performed by an experienced operator. Evaluation of submucosal fibrosis may be helpful to predict the submucosal invasion of tumors and technical difficulties in ESD.

Bioballs Causing Asymptomatic or Recurrent Acute Rhinosinusitis: Two Cases

A variety of intrinsic and extrinsic factors have been studied to explain the pathogenesis of rhinosinusitis. Recently biofilms are emerging as an important cause. Biofilms are highly organized structures composed of a protective extracellular matrix and bacterial colonies, and provide the means for bacterial survival and virulence. Biofilms are known to be associated with intractable cases of rhinosinusitis and antibiotic resistance. Patients diagnosed with biofilm-related rhinosinusitis tend to suffer more severe disease that those without biofilms. Biofilm severity can also influence the prognosis of rhinosinusitis. We present two cases of pseudomonas-induced macroscopic biofilms (bioballs) of the maxillary sinuses. These bioballs cause intractable chronic rhinosinusitis as well, but unlike traditional biofilms, they can be surgically removed by endoscopy, and thus have a better prognosis than traditional biofilms. This is the first report of visible biofilms (bioballs) found in the maxillary sinuses.

Histiocytic Sarcoma of the Cervical Spinal Cord with Secondary Involvement of the Skin / 대한피부과학회지

Histiocytic sarcoma is a rare, lymphohematopoietic malignant tumor comprised of tumor cells with the morphological and immunophenotypic features of mature histiocytes. A 35-year-old man presented with a disseminated histiocytic sarcoma that first occurred in the spinal cord and metastasized to the skin and lymph nodes. The tumor cells of the primary histiocytic sarcoma of the spinal cord were very large epithelioid cells with abundant eosinophilic cytoplasms and large, round-to-oval nuclei. In contrast, the metastatic histiocytic sarcoma of the skin was composed of relatively small polygonal cells with well-defined cell borders and high N/C (nucleus/cytoplasm) ratios. Immunohistochemically, both tumors were diffusely positive for histiocyte-associated antigens; but negative for epithelial, melanocyte, lymphoid, and dendritic cell antigens. It is important to recognize the morphological features and immunohistochemical characteristics of metastatic cells in order to ensure accurate diagnoses.

Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma

BACKGROUND: Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown. METHODS: Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated. RESULTS: E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p 40%) were independent prognostic factors for shorter overall survival. CONCLUSIONS: Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.

Increased Expression of Forkhead Box M1 Is Associated with Aggressive Phenotype and Poor Prognosis in Estrogen Receptor-Positive Breast Cancer

Fox transcription factors play a critical role in the regulation of a variety of biological processes. While FoxM1 behaves like the oncogenic transcription factor, FoxO3a is known as a tumor suppressor by inhibiting FoxM1. This study aimed to investigate the clinicopathological significance of FoxM1 and FoxO3a expression in breast cancer. Expression of FoxM1 and FoxO3a were analyzed by immunohistochemical staining on tissue microarray sections from 236 breast cancer patients, and correlated with various clinicopathological characteristics. Overexpression of FoxM1 correlated with adverse clinicopathological features, such as larger tumor size, lymph node metastasis, advanced tumor stage, and lymphovascular invasion. The Kaplan-Meier survival curves revealed no prognostic significance of FoxM1 expression. However, in subgroup analyses with patients of estrogen receptor (ER) positive breast cancers, FoxM1 overexpression associated with poor disease free and overall survival. No association was found between FoxO3a and FoxM1 expression. Regarding clinicopathological variables, the only association between histologic grade and FoxO3a was observed. In conclusion, FoxM1 overexpression was significantly associated with aggressive phenotypes and poor prognosis of ER-positive breast cancer. These findings suggest the possible role of FoxM1 as a prognostic biomarker and putative target of anti-cancer therapy.

Intrathoracic Desmoid Tumor Presenting as Multiple Lung Nodules 13 Years after Previous Resection of Abdominal Wall Desmoid Tumor / 결핵및호흡기질환

Desmoid tumors are rare soft tissue tumors considered to have locally infiltrative features without distant metastasis until now. Although they are most commonly intraabdominal, very few cases have extra-abdominal locations. The origin of intrathoracic desmoid tumors is predominantly the chest wall with occasional involvement of pleura. True intrathoracic primary desmoid tumors with no involvement of the chest wall or pleura are extremely rare. We recently experienced a case of true intrathoracic desmoid tumor presenting as multiple lung nodules at 13 years after resection of a previous intraabdominal desmoid tumor.

Concurrent Ruptured Pseudoaneurysm of the Internal Carotid Artery and Cerebral Infarction as an Initial Manifestation of Polycythemia Vera

The most common neurologic manifestations of polycythemia vera (PV) are cerebral infarction and transient ischemic attacks, while cerebral hemorrhage or intracranial dissection has been rarely associated with PV. Here we report the first case of a 59-year-old patient with intracranial supraclinoid internal carotid artery (ICA) dissection causing cerebral infarction and concomitant subarachnoid hemorrhage due to pseudoaneurysm rupture as clinical onset of PV. This case report discusses the possible mechanism and treatment of this extremely rare condition.

A Case of Significant Endobronchial Injury due to Recurrent Iron Pill Aspiration / 결핵및호흡기질환

Gastric mucosal damage by iron pills is often reported. However, iron pill aspiration is uncommon. Oxidation of the impacted iron pill causes bronchial mucosal damage that progresses to chronic bronchial inflammation, necrosis, endobronchial stenosis and rarely, perforation. We reported a case of a 92-year-old woman with chronic productive cough and significant left-sided atelectasis. Bronchoscopy revealed substantial luminal narrowing with exudative inflammation of the left main bronchus. Bronchial washing cytology showed necroinflammatory exudate and a small amount of brown material. Mucosal biopsy showed diffuse brown pigments indicative of ferrous pigments, crystal deposition, and marked tissue degeneration. After vigorous coughing, she expectorated dark sediments and her symptoms and radiological abnormalities improved. There are a few such reports worldwide; however, this was the first case reported in Korea. Careful observation of aspiration-prone patients and early detection of iron pill aspiration may prevent iron pill-induced bronchial injury.

Pulmonary Foreign Body Granulomatosis in Dental Technician / 결핵및호흡기질환

Occupational lung diseases are caused by several toxic substances including heavy metals; however, the exact pathologic mechanisms remain unknown. In the workplace, dental technicians are often exposed to heavy metals such as cobalt, nickel, or beryllium and occasionally develop occupational lung diseases. We described a case of occupational lung disease in a patient who was employed as a dental technician for over a decade. A 31-year-old, non-smoking woman presented with productive cough and shortness of breath of several weeks duration. Chest computed tomography revealed a large number of scattered, bilateral small pulmonary nodules throughout the lung field, and multiple mediastinal lymph nodes enlargement. Percutaneous needle biopsy showed multifocal small granulomas with foreign body type giant cells suggestive of heavy metals inhalation. The patient's condition improved on simple avoidance strategy for several months. This case highlighted the importance of proper workplace safety.

Gastric Syphilis and Membranous Glomerulonephritis

Syphilis is a chronic systemic infectious disease caused by the bacterium Treponema pallidum. Gastric involvement and nephrotic syndrome are uncommon but well documented complications of syphilis, but the co-occurrence of these two complications in the same patient is extremely rare. Thus, because of their nonspecific presentation, suspicion of gastric syphilis (GS) and nephrotic syndrome is essential for diagnosis. Patients should be investigated thoroughly and a diagnosis made based on clinical, endoscopic, and histological findings, in order to initiate appropriate therapy. We report of a 34-year-old male patient with a history of epigastric pain and a diagnosis of GS and syphilis-associated membranous glomerulonephritis confirmed by gastroscopy and kidney biopsy, who was treated successfully with penicillin G benzathine. This case report provides information on the typical features of GS that should help raise awareness of this rare disease entity among clinicians, resulting in earlier diagnosis and administration of appropriate therapy.

IgG4-related Sclerosing Cholangitis Presented as a Mass in the Liver / 대한췌담도학회지

Autoimmune pancreatitis or IgG4-related sclerosing cholangitis often involves the liver. Most common lesion involving the liver is shown as mass or masses often referred as inflammatory pseudotumor. Inflammatory pseudotumor usually needs to be discriminated with malignancy. Here we report a case of IgG4-related sclerosing cholangitis with liver involvement presented as a mass. It was proven by biopsy and did not show any evidence of autoimmune pancreatitis. The mass infiltrated around the portal tract and portal vein thrombosis was also present.

Hepatocellular Carcinoma Arising from Non-Cirrhotic Non-Alcoholic Steatohepatitis / 이화의대지

The major risk factors of hepatocellular carcinoma include hepatitis B or C virus infection and alcohol consumption in Korea which lead to liver cirrhosis development and progression. However, prevalence of non-alcoholic fatty liver disease related hepatocellular carcinoma is rising worldwide and hepatocellular carcinoma cases in patients with non-cirrhotic non-alcoholic steatohepatitis are increasing. A hypoechoic nodule was incidentally detected in a 52-year-old woman, with no evidence of liver cirrhosis or specific hepatocellular carcinoma findings on radiological examination. Non-cirrhotic non-alcoholic steatohepatitis-associated hepatocellular carcinoma was diagnosed based on clinical, laboratory, and histopathological findings of liver biopsy. To our knowledge, this is the first such case report in Korea.

Characteristics of Cutaneous Lymphomas in Korea According to the New WHO-EORTC Classification: Report of a Nationwide Study

BACKGROUND: Previously, cutaneous lymphomas were classified according to either the European Organization for the Research and Treatment of Cancer (EORTC) or the World Health Organization (WHO) classification paradigms. The aim of this study was to determine the relative frequency of Korean cutaneous lymphoma according to the new WHO-EORTC classification system. METHODS: A total of 517 patients were recruited during a recent 5 year-period (2006-2010) from 21 institutes and classified according to the WHO-EORTC criteria. RESULTS: The patients included 298 males and 219 females, and the mean age at diagnosis was 49 years. The lesions preferentially affected the trunk area (40.2%). The most frequent subtypes in order of decreasing prevalence were mycosis fungoides (22.2%), peripheral T-cell lymphoma (17.2%), CD30+ T-cell lymphoproliferative disorder (13.7%), and extranodal natural killer/T (NK/T) cell lymphoma, nasal type (12.0%). Diffuse large B-cell lymphoma accounted for 11.2% of cases, half of which were secondary cutaneous involvement; other types of B-cell lymphoma accounted for less than 1% of cases. CONCLUSIONS: In comparison with data from Western countries, this study revealed relatively lower rates of mycosis fungoides and B-cell lymphoma in Korean patients, as well as higher rates of subcutaneous panniculitis-like T-cell lymphoma and NK/T cell lymphoma.

Sequestrated Intradural Disc Herniation Around Couns Medullaris: A Case Report

STUDY DESIGN: A case report. OBJECTIVES: To report a rare case of intradural disc herniation (IDH) around conus medullaris. SUMMARY OF LITERATURE REVIEW: IDH is rare with an incidence of less than 1% of all lumbar disc herniations. It is important to differentiate IDH from other condition with accurate diagnosis and subsequent surgical treatment. IDH has a higher risk of neurologic deficit, like conus medullaris syndrome and cauda equina syndrome. MATERIALS AND METHODS: A 62 year-old male was affected by lumbar back pain radiating to the anterolateral aspect of the right thigh for 5 days. MRI showed a mass that existed on the anterior portion of the conus medullaris. We performed partial laminectomy at the L1-L2level. The mass located anteriorly in the intradural space was eliminated after durotomy by a posterior approach. RESULTS: We confirmed the IDH for histopathology. CONCLUSIONS: IDH usually needs accurate differential diagnosis. Preoperative MRI scans are necessary to differentiate IDH from other intradural lesions. The confirmative diagnosis can be done only in the operative field.

Brain and Skin Metastasis From Urothelial Carcinoma of the Bladder

Brain and skin metastasis from urothelial carcinoma of the bladder is rare. There have been few case reports of the clinical course of patients with metastatic urothelial carcinoma of the brain and skin. In the present case, a 60-year-old man had undergone radical cystectomy with an ileal conduit owing to urothelial carcinoma (T1N0M0). The patient developed dizziness 9 years later and a solitary brain tumor was discovered in his left cerebellar hemisphere. The tumor was totally resected and the mass was verified to be metastatic urothelial carcinoma. One year after the metastasectomy of the brain lesion, multiple erythematous nodular lesions developed on his abdominal skin. The skin lesions were excised and verified to be metastatic urothelial carcinoma. This report describes this case of urothelial carcinoma of the bladder that metastasized to the brain and abdominal skin.

Hepatocellular carcinoma composed of two different histologic types: imaging features on gadoxetic acid-enhanced liver MRI

No abstract available.

Merkel Cell Carcinoma Concurrent with Bowen's Disease

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy of the elderly and immunocompromised patients. It is occasionally found coexisting with other diseases, such as squamous cell carcinoma, basal cell carcinoma, actinic keratosis, miscellaneous adnexal tumors, and rarely Bowen disease. A 75-year-old woman presented with a 6-month history of an irregularly shaped erythematous patch on the left mandibular angle. Three months later, a 1.5x1.0 cm sized painless and rapidly growing erythematous nodule developed on the patch. Microscopically, the patch lesion was consistent with that of Bowen disease. The nodular lesion showed a number of small uniform hyperchromatic cells with scanty cytoplasm. It showed dense small-cell like nodular infiltration in the dermis. Immunohistochemical staining for cytokeratin 20 showed a positive result with a dot-like perinuclear pattern. Additionally, the result for thyroid transcription factor-1 was negative, which is positive in small cell neuroendocrine carcinoma. From these findings, we diagnosed this lesion as MCC concurrent with Bowen disease.