Current Issue : January - March Volume : 2017 Issue Number : 1 Articles : 8 Articles
Background: The tumor suppressor gene CDC73 was found to be associated with hyperparathyroidism-jaw tumor\nsyndrome (HPT-JT), which is characterized by parathyroid adenoma or carcinoma, ossifying fibroma (OF) of the\njaws, and renal and uterine lesions. Mutations in CDC73 have also been frequently detected in sporadic parathyroid\ncarcinomas and renal tumors. However, the prevalence and range of CDC73 mutations in sporadic OFs have not\nbeen established.\nMethods: We directly sequenced coding and flanking splice junctional regions of CDC73 in 40 cases of sporadic\nOF of the jaws. We also used immunohistochemistry to detect parafibromin, the protein product of CDC73, in\nthose cases.\nResults: Two novel CDC73 mutations were identified in 2 of the 40 cases (5 %). Both were somatic mutations\nlocated in exon 1 of the coding region. Strong parafibromin expression was detected in all 40 cases, irrespective\nof the presence of CDC73 mutations.\nConclusions: Mutations inCDC73 were rare in sporadic OF of the jaws, but may affect the pathogenesis of a small\nsubset of tumors of this type....
Background: Isolated hypothalamic-pituitary Langerhans cell histiocytosis (HPLCH) is very rare. We investigated the\nclinicopathological characteristics, endocrine function changes, BRAFV600E mutations and treatments of isolated\nHPLCH.\nMethods: We identified seven patients with isolated HPLCH by reviewing the clinical and pathological files in our\nhospital from 2007 to 2015. The clinical characteristics of the seven patients were retrospectively reviewed,\nespecially the endocrine function changes. Immunostaining and mutation profiling of BRAFV600E were performed.\nResults: The seven HPLCH patients included three men and four women, aged 9ââ?¬â??47 years. All patients presented\nwith symptoms of central diabetes insipidus (CDI), and four displayed anterior pituitary hypofunction as well.\nMagnetic resonance imaging showed hypothalamic-pituitary axis involvement in all patients. There was no\nevidence for the involvement of other organs in all seven patients. Langerhans cell histiocytosis was confirmed by\nneuroendoscopic procedures, and immunohistochemical staining showed that all cases (7/7) were positive for\nCD68, CD1a, Langerin, and S-100. The BRAFV600E mutation was detected in three of the six cases (3/6). Six patients\nhad follow-up information; all received desmopressin acetate and high-dose corticosteroid therapy, and two\npatients received radiotherapy.\nConclusions: Our study indicated that all patients with isolated HPLCH had CDI as the earliest symptom, and more\nthan half of the patients had anterior pituitary deficiencies. The BRAFV600E mutation is a common genetic change in\nHPLCH patients. Treatment of HPLCH patients is difficult, and the progressive loss of endocrine function is\nirreversible in most cases....
Background: The concomitant presence of idiopathic membranous nephropathy and IgA nephropathy is rare.\nHere, we report 9 cases of phospholipase-A2-receptor (PLA2R) positive idiopathic membranous nephritis combined\nwith IgA nephropathy, while reviewing publications regarding the pathological characteristics of this\nglomerolonephritis complication.\nCase presentation: Nine cases of renal biopsy tissues were retrospectively reviewed, including the clinicopathological\nfeatures, the results of the immunofluorescence assays, and the electron microscopic examination. The patients mainly\npresented proteinuria and microscopic hematuria, and the serum anti-PLA2R was detected as positive in all of\nthe patients. Histologically, a wide thickening of the glomerular basement membrane was observed in each of\nthe 9 cases. Additionally, there existed mild hyperplasia in the mesangial cell and the matrix of the mesangial\narea. Immunofluorescence assays showed prominent glomerular granular staining on the glomerular capillary\nloops for IgG (++/+++), IgG4 (++/++++), and PLA2R (+/++). In addition, moderate IgA positive stains were\nfocally or sparsely limited to the mesangial areas. Electron microscopy revealed subepithelial and mesangial\nelectron-dense deposits.\nConclusions: The results from the case analyses indicated that idiopathic membranous nephropathy combined\nwith IgA nephropathy possess the clinicopathological features found in both components. It is suggested that\nserum anti-PLA2R and tissue PLA2R are important biomarkers that can assist in the diagnosis of idiopathic\nmembranous nephropathy associated with IgA nephropathy...
Background: Increased expression of DEF6 is correlated with the malignant behavior of various cancers. Both DEF6 and\np16 contribute to the regulation of cell cycle progression, and p53 plays important role in the cell cycle checkpoints. This\nstudy was designed to elucidate the prognostic significance of DEF6, p53 and p16 immunoexpressions in different\nhistology subtypes of ovarian carcinoma.\nMethods: Immunohistochemistry results of DEF6, p53 and p16 on ovarian carcinoma were compared with histology\nsubtypes, clinical data, overall survival (OS) and disease-free survival (DFS) by Cox regression and Kaplan-Meier analysis.\nResults: We studied 180 cases of ovarian carcinomas (75 high-grade serous, 41 clear cell, 36 mucinous and 28\nendometrioid), including 109 FIGO stage I-II cases and 71 FIGO stage III-IV cases. Ovarian carcinomas positive for both\nDEF6 and p16 expression were associated with the worst OS (P = 0.027) and DFS (P = 0.023), whereas those negative for\nboth DEF6 and p16 had the best OS and DFS. Aberrant p53 expression combined with positive DEF6 was associated with\nworst OS (P = 0.031) and DFS (P = 0.028). Kaplan-Meier analysis showed that significantly shorter survival rates were seen\nin patients with high expressions of DEF6 (P = 0.008) and p16 (P = 0.022). Patients with aberrant p53 expression in highgrade\nserous carcinoma (P = 0.012) and patients with high DEF6 expression in clear cell carcinoma (P = 0.001) were also\nassociated with shorter overall survival. In univariate analysis, FIGO stage, DEF6 and p16 were associated with poor\nprognosis. DEF6 expression was the only independent prognostic factor correlated with shorted OS (HR 2.115; P= 0.025)\nand DFS (HR 2.248; P = 0.016) upon multivariate analysis.\nConclusions: DEF6 expression may serve as an independent prognostic factor, and interacted positively with p16 toward\nhigh tumor stage and shorter survival....
Background: Inhibition of the oncogenic fusion-gene EML4-ALK is a current first-line approach for patients with\nstage IV non-small cell lung cancer. While FISH was established as the gold standard for identifying these patients,\nthere is accumulating evidence that other methods of detection, i.e., immunohistochemistry and next-generation\nsequencing (NGS), exist that may be equally successful. However, the concordance of these methods is under\ninvestigation.\nCase presentation: Adding to the current literature, we here report a 56 year old female never-smoker with stage\nIV lung adenocarcinoma whose biopsy was IHC and FISH inconclusive but positive in NGS. Retroactive profiling of\nthe resection specimen corroborated fusion reads obtained by NGS, FISH-positivity and showed weak ALK-positivity\nby IHC. Consequently, we diagnosed the case as ALK-positive rendering the patient eligible to crizotinib treatment.\nConclusions: With IHC on biopsy material only, this case would have been overlooked withholding effective\ntherapy....
Background: Signet ring cells (SRCs) often accompany gastrointestinal carcinoma, referred to as SRC carcinoma;\nhowever, breast cancers containing SRCs have not been well characterized, leaving the prognostic significance of\nSRCs undetermined. We have described clinicopathological characteristics of patients with breast cancer containing\nSRCs in relation to the expression levels of MUC1, MUC2, MUC4, MUC5AC, and MUC6.\nMethods: Twenty-two breast cancer cases with variable degrees of SRC population were retrospectively studied.\nEach case was categorized as high (>31 %) or low (<30 %) SRC tumor. The SRCs were morphologically classified\ninto the intra-cytoplasmic lumen (ICL) type, or the non-ICL type. The expression levels of MUC1, MUC2, MUC4,\nMUC5AC and MUC6 were determined immunohistochemically. Depending on its subcellular localization, MUC1\nwas categorized as the luminal and cytoplasmic (LC) type, or the cytoplasmic with circumferential membranous\naccentuation (CM) type. These histological findings were compared with other clinicopathological parameters.\nResults: The series consisted of invasive ductal carcinoma (n = 9), invasive lobular carcinoma (n = 9), and mucinous\ncarcinoma (n = 4) cases. The SRC population accounted for 8ââ?¬â??81 % of the tumor cells. Eight cases had ICL type\nSRCs, and the remaining 14 had non-ICL type SRCs. Neither the high (n = 12) and low (n = 10) percentage of SRCs,\nnor the SRC types affected the clinicopathological parameters. In the low MUC1 group (n = 11), larger tumors,\nhigher nuclear grade, lymph node metastasis, and negativity for estrogen receptor was more frequently identified\ncompared to the high MUC1 group (n = 11; p = 0.01, p = 0.002, p = 0.008, and p = 0.02, respectively). The CM group\n(n = 7) had more patients with large-sized tumors, lymph node metastasis, lymphovascular invasion, and higher Ki67\nindices than the LC group (n = 15; p = 0.04, p = 0.001, p = 0.006, and p = 0.03, respectively). The expression levels of\nMUC2, MUC4, MUC5AC, and MUC6 showed no clinicopathological significance. Two patients with low MUC1\nexpression and CM patterns had tumor recurrence, resulting in death, while all the other patients survived without\nrecurrence.\nConclusion: Our results demonstrate that in breast cancers containing SRCs, low MUC1 expression and/or its CM\nsubcellular localization patterns are associated with unfavorable clinicopathological factors. The utility of MUC1\nexpression as a prognostic marker remains to be verified in future studies....
Background: Understanding the role of alternative complement pathway dysregulation in membranoproliferative\nglomerulonephritis (MPGN) has led to a dramatic shift in its classification into two subgroups: immune complexmediated\nMPGN and complement-mediated MPGN, consisting of dense deposit disease and C3 glomerulonephritis\n(C3GN). A limited number of C3GN cases have been published to date with not yet conclusive results since the\nnovel therapeutic approach with eculizumab was introduced.\nCase presentation: We report the clinical follow-up of a 16-year-old patient in whom a diagnosis of C3GN was\nconfirmed by immunofluorescence and electron microscopy in second and third kidney biopsies, while the first\nbiopsy revealed idiopathic immune complex-mediated MPGN type III, Anders and Strife variant, which failed to\nimprove after several attempts at conventional immunosuppression therapy. Although applied late in an already\nfairly advanced stage of the severe active form of MPGN, the efficacy of eculizumab on C3GN was evidenced\nclinically and pathohistologically. Its beneficial influence on pathomorphogenesis was demonstrated by a unique\nfollow-up in the last three biopsies, despite the recent observation, confirmed in this study, of eculizumab binding\nwithin the kidney tissue.\nConclusions: Clinicians and pathologists should be aware that, in some patients, an underlying genetic or acquired\ncomplement alternative pathway abnormality can be masked by an initial immune complex-mediated mechanism,\nwhich subsequently triggers an unbalanced excessive continual driving of complement terminal pathway activation\nand the development of C3GN. In such a patient, supplementary steroids in addition to eculizumab appear\nnecessary to achieve an adequate response....
Background: As the World Health Organization grading system for gastroenteropancreatic-neuroendocrine tumors\n(GEP-NETs) may not always correlate with tumor progression, it is imperative that other independent predictors of\ntumor progression be established. To identify such predictors, we conducted a retrospective histopathological study\nof hindgut NETs, obtained from endoscopic procedures, and used statistical analyses to evaluate predictive factors.\nMethods: We first obtained clinicopathological data of cases of hindgut NETs. Tissue sections from tumor samples\nwere prepared and subjected to pathological examination. In particular, we calculated the microvessel density\n(MVD) and lymphatic microvessel density (LMVD) values, and performed appropriate statistical analyses.\nResults: A total of 42 cases of hindgut NETs were selected for the study, 41 from the rectum and 1 from the\nsigmoid colon. Based on the Ki-67 labeling index, 34 cases were classified as NET G1 tumors and 8 as NET G2\ntumors. MVD values ranged from 1.4/mm2 to 73.9/mm2 and LMVD values from 0/mm2 to 22.9/mm2. MVD and\nLMVD were identified as risk factors for venous and lymphatic invasion of hindgut NETs. Moreover, MVD positively\ncorrelated with the maximum diameter of the tumor.\nConclusions: Tumor progression of NETs may cause angiogenesis and lymphangiogenesis, via an unknown\nmechanism, as well as lymphovascular invasion. Angiogenesis likely plays an important role in occurrence and\nprogression in the initial phase of hindgut NETs....
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