Differentiated vulvar intraepithelial neoplasia (dVIN) is a non-human papilloma virus (HPV)-related high-grade precursor lesion to vulvar squamous cell carcinoma (vSCCa). Although TP53 gene mutations ...have been identified in 80% of dVIN, its role in dVIN pathogenesis as well as malignant transformation is still being poorly understood. Poor reproducible diagnostic criteria and ambiguous p53 immunostaining patterns, along with morphologic discordance still pose a diagnostic challenge.
A series of 60 cases of dVIN-related vSCCa along with adjacent dVIN were evaluated. Clinicopathological features as well as immunohistochemical results were recorded on the resection-confirmed dVIN-related vSCCa.
The average age of the patients was 71 years. Thirty-five cases (58.4%) of dVIN-related vSCCa were moderately differentiated, fourteen cases (23.3%) were poorly differentiated, and the remaining eleven cases (18.3%) were well-differentiated. Twenty-nine cases (48.3%) were found to have lichen sclerosus adjacent to dVIN. In terms of p53 and p16 expression in dVIN-related vSCCa and the adjacent dVIN, fifty-five (91.7%) dVIN showed mutant p53 immunostaining pattern with strong positive expression in 80% cases (basal/para-basal expression) and null pattern expression in 11.7% cases. Five (8.3%) dVIN showed p53 wild-type staining pattern. The wild-type pattern were seen in 5% of vSCCa and p53 null pattern were seen in 13.3% vSCCa. Six cases demonstrated atypical staining patterns: two cases showed p53 null expression in dVIN but p53 overexpression in invasive carcinoma; three cases exhibited p53 null expression in invasive carcinoma, with the adjacent dVIN showing basal and para-basal mutant (2 cases) and wild-type (1 case) p53 expression patterns. A single case demonstrated p53 wild-type pattern in dVIN and overexpression in invasive carcinoma. In addition, 65% dVIN were p16 negative and 31.7% dVIN had patchy p16 staining.
Clinical and prognostic value of the ambiguous/inconsistent patterns are uncertain and molecular studies are needed for further characterization.
•p53 expression patterns are concordant in dVIN and the subsequent dVIN related vSCCa. However, there is a need for additional studies addressing the mutational profiles of dVIN and dVIN-related vSCCa with discordant or discrepant p53 expression patterns, especially in cases with unusual morphologic features.•An immunohistochemical panel including p53, Ki-67, and p16 should be utilized for a diagnosis of dVIN-related vSCCa.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA David L. Murray & Mindy C. Kohlhagen 4. Department of Pathology, Anatomy and Laboratory Medicine, West Virginia ...University, Morgantown, WV, USA Jeffrey A. Vos 5. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
The pancreatobiliary carcinomas are characterized by presence of desmoplastic stroma. Overexpression of secreted protein acid and rich in cysteine (SPARC), a matrix producing agent has been ...documented in pancreatic ductal adenocarcinomas, with survival benefits. This study was targeted to see if SPARC expression in pancreatobiliary carcinomas is responsible for stromal desmoplasia and its prognostic significance.
In this retrospective study 48 cases of pancreatic cancer and 27 cases of cholangiocarcinoma were analyzed. The expression pattern of SPARC and vascular endothelial growth factor (VEGF) (angiogenic factors) was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. Immunoreactivity was scored semi quantitatively based on stain intensity and stain distribution. SPARC expression was correlated with tumor histology, stromal desmoplasia, VEGF expression, various histological parameters and overall survival in patients. Real time polymerase chain reaction was performed in few cases to validate the immunohistochemistry expression pattern.
SPARC expression was high in peritumoral stroma in pancreatic carcinoma than in pancreatic controls; however, SPARC expression pattern was not grossly different in desmoplastic and non-desmoplastic pancreatobiliary carcinomas and in cholangiocarcinomas. No definite correlation was noted between SPARC expression and histological markers of severity and overall survival data.
The relevance of SPARC expression in pancreato-biliary carcinomas though may still be important for therapeutic decision making, it is not responsible for peritumoral stromal desmoplasia in these tumors and it does not have any significant prognostic implication.
Abstract
Background
Mu heavy chain disease is a rare lymphoid neoplasm characterized by vacuolated bone marrow plasma cells and secretion of defective mu immunoglobulin heavy chains. The biological ...basis of mu heavy chain disease is poorly understood.
Case presentation
We report a case of mu heavy chain disease with
MYD88
L265P mutation and deletion of 6q, genetic aberrations that are both strongly associated with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Identification of the truncated mu immunoglobulin was facilitated by mass spectrometric analysis of the patient’s serum.
Conclusions
Mu heavy chain disease has been described as similar to chronic lymphocytic leukemia; however, the frequency of lymphocytosis in mu heavy chain disease has not been previously reported. We reviewed all previously published mu heavy chain disease reports and found that lymphocytosis is uncommon in the entity. This finding, along with the emerging genetic feature of recurrent
MYD88
mutation in mu heavy chain disease, argues that at least a significant subset of cases are more similar to lymphoplasmacytic lymphoma than to chronic lymphocytic leukemia.
Background: Both noncirrhotic portal fibrosis (NCPF) and extrahepatic portal venous obstruction (EHPVO) are important causes of noncirrhotic portal hypertension (PH) in the Asian region. In this ...study, we analyzed the histopathological changes of liver needle-core biopsies from patients with NCPF and EHPVO. Patients and Methods: The patients were diagnosed as per the Asia Pacific Association for the Study of Liver (APASL) criteria. Minimum adequacy criteria for liver core biopsies were defined, and finally, 69 liver biopsies from patients with NCPF and 100 liver biopsies from patients with EHPVO were analyzed. All histological parameters were predefined, and three experienced pathologists analyzed the biopsies after reaching consensus. Institute ethics committee clearance was taken. Results: Although some histological features were overlapping, phlebosclerosis of intra-hepatic branches of the portal vein (PV), periportal aberrant vascular channels, remnant portal tracts, and hepatic fibrosis beyond the portal tracts without the formation of complete hepatic nodules (P < 0.001 for all) were common histological characteristics of NCPF on core-needle liver biopsies; while maintained lobular architecture, nonspecific dilatation of PV branches, absence of intra-hepatic PV phlebosclerosis, aberrant vascular channels, and significant fibrosis were characteristics of EHPVO. Conclusions: Despite the considerable histological overlap between NCPF and EHPVO, careful histological evaluation, supplemented by clinical features, radiological and biochemical findings can help in making a conclusive diagnosis. Patients with NCPF and EHPVO with clinical jaundice show transaminitis, high serum alkaline phosphatase level, more variceal bleed, and histological evidences of nodular regenerative hyperplasia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Aggressive pancreatobiliary tumors often require oxaliplatin-based therapies, instead of standard gemcitabine-based therapy and biomarker studies at diagnosis to decide the appropriate ...therapeutic regimen. The ribonucleotide Reductase catalytic subunit M1 (RRM1) and excision repair cross-complementing gene-1 (ERCC1) are related to DNA synthesis and repair and essential in this regard. However, apart from the therapeutic benefit, their prognostic implication is controversial. Methods: In this retrospective study, paraffin-embedded tissue from 51 cases of pancreatic cancer and 29 cases of cholangiocarcinoma were evaluated for RRM1 and ERCC1 expression by immunohistochemical technique along with 18 control pancreatic and biliary tissues. The semiquantitatively H score was calculated based on stain distribution and stain intensities. Results: Both RRM1 and ERCC1 expression were high in tumor epithelium than in controls (RRM1: the difference was statistically significant in cholangiocarcinoma (P = 0.008); ERCC1: the difference was statistically significant both in pancreatic and cholangiocarcinoma (P < 0.05). However, no correlation was noted between RRM1 and ERCC1-low and high tumors with histological markers of prognosis and overall survival in these patients. Conclusions: The present study adds further evidence against the controversy that if RRM1 and ERCC1 expression in pancreatic and biliary carcinomas have any prognostic significance apart from their proven therapeutic benefits in these tumors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Thyroid tuberculosis is uncommon even in countries like India where prevalence of tuberculosis is high. Bactericidal actions of colloid, excess iodine stores and high vascularity of the gland have ...been implicated for the very rare occurrence of thyroid tuberculosis. We present a case of a 16-year-old male with thyroid involvement as a part of disseminated tuberculosis. The clinical presentation of thyroid tuberculosis is varied and may be missed if not kept in the differential diagnosis of goitre. This case also highlights the role of fine needle aspiration cytology in management of goitre. It is an important diagnostic test as it avoids unnecessary surgical intervention.
Background: It is hypothesized that the duodenal mucosal damage in patients with celiac disease (CeD) is caused by the mucosa-infiltrating lymphoid cells. This study aimed to analyze the immune ...effective and regulatory T (Treg) cells in duodenal biopsies from treatment-naive adult patients with CeD having different histological grades and controls. Patients and Methods: Dual-color immunohistochemical staining was done in a total of 234 duodenal biopsies, including 132 controls and 102 adult patients with CeD using CD20, CD3:CD4, CD3:CD8, CD4:FoxP3, CD8:FoxP3, and TCRαβ:TCRγδ antibodies. The density of these lymphoid cells in lamina propria and mucosal epithelium was compared between controls and CeD, with different modified Marsh grades. Results: Densities of CD4+ T cells in lamina propria and CD8+γδ intraepithelial lymphocytes (IELs) were significantly more in biopsies from patients with CeD, than in controls. An increasing linear pattern of IELs, CD3+ T cells, and CD20+ B cells was observed with increasing grades of villous abnormalities. Although CD8+ FoxP3+ Treg cells were significantly more in biopsies from patients with CeD, there was no significant difference in CD4+ FoxP3+ Treg cell infiltrate between both the groups. Conclusion: Our finding in this observational study generates interest to study the local intestinal mucosal immunity in CeD in detail. A study to prove the failure of CD4+ FoxP3+ Treg cell recruitment in CeD and its direct functional impact may yield valuable information regarding loss of mucosal tolerance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intra-abdominal thrombosis is a complication of paroxysmal nocturnal hemoglobinuria (PNH). There is scarcity of data on cases presenting with thrombosis in whom PNH is the predisposing factor. We ...assessed the role of PNH defect in 81 patients with intra-abdominal thrombosis, 44 patients of Budd Chiari syndrome and 37 patients of extra hepatic venous obstruction. Flowcytometry with glycosylphosphatidyl inositol-anchored proteins (GPI-AP)-CD55, -CD59, and -CD16 was performed on all patients and controls to assess the prevalence of deficiencies and PNH-type phenotype clone size. Deficiencies of individual GPI-AP were seen in 17.3% cases versus 3.4% controls. This was due to CD55 deficiency on red blood cells and CD16 deficiency on the granulocytes. Deficiency of multiple GPI-APs was less frequent (3.7% cases). Data of this study indicate that the PNH defect as detected with CD55, CD59, and CD16 is not an important cause of intra-abdominal thrombosis in northwestern India.
The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have ...developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies.
We performed a computer-assisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists.
Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%-85.03%) and interobserver (24.6%-71.5%) agreements.
Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD. (Intest Res, Published online).
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