Diagnostic Pathology - Latest Articles

Immunohistochemical detection of S100A1 in the postmortem diagnosis of acute myocardial infarction

Haitao Bi — 2013-05-17T00:00:00Z

Background: Sudden cardiac death resulting from acute myocardial infarction (AMI) constitutes a significant percentage of the caseload for forensic and clinical pathologists. When sudden death occurs at an early stage (<6 h), pathologists experience difficulty in the postmortem diagnosis of AMI. Because of the specific tissue distribution of S100A1 and its relationship with acute ischemic heart disease, this study aimed to evaluate the performance of S100A1 in the postmortem diagnosis of AMI. Methods: We constructed a rat model of AMI through permanent ligation of the left anterior descending coronary artery (LAD) to investigate the depletion of S100A1 from ischemic cardiomyocytes by immunohistochemistry and measuring S100A1 plasma concentrations by enzyme-linked immunosorbent assay at varying post-infarction intervals. In addition, immunohistochemical staining of S100A1 for definite infarction, suspected early infarction, and in normal human hearts, was also performed to test its practical feasibility for postmortem diagnosis of AMI at an early stage. Results: As early as 15 min after ligation of the LAD, depletion of S100A1 was observed in ischemic cardiomyocytes, and S100A1 plasma concentration was also significantly higher than that of the sham-operated group (P < 0.001). With continuation of the occlusion time, the depleted areas of S100A1 further expanded and S100A1 plasma concentrations further increased. For autopsy material, all human cases of definite myocardial infarction and suspected early infarction showed well-defined areas without S100A1 staining. None of the normal human cases showed diffuse depletion of S100A1. Conclusion: Our results suggest that immunohistochemical detection of S100A1 is useful for the postmortem diagnosis of AMI at an early stage.

RTEL1 tagging SNPs and haplotypes were associated with glioma development

Gang Li — 2013-05-17T00:00:00Z

As glioma ranks as the first most prevalent solid tumors in primary central nervous system, certain single-nucleotide polymorphisms (SNPs) may be related to increased glioma risk, and have implications in carcinogenesis. The present case-control study was carried out to elucidate how common variants contribute to glioma susceptibility. Ten candidate tagging SNPs (tSNPs) were selected from seven genes whose polymorphisms have been proven by classical literatures and reliable databases to be tended to relate with gliomas, and with the minor allele frequency (MAF) > 5% in the HapMap Asian population. The selected tSNPs were genotyped in 629 glioma patients and 645 controls from a Han Chinese population using the multiplexed SNP MassEXTEND assay calibrated. Two significant tSNPs inRTEL1 gene were observed to be associated with glioma risk (rs6010620, P = 0.0016, OR: 1.32, 95% CI: 1.11-1.56; rs2297440, P = 0.001, OR: 1.33, 95% CI: 1.12-1.58) by chi2 test. It was identified the genotype "GG" of rs6010620 acted as the protective genotype for glioma (OR, 0.46; 95% CI, 0.31-0.7;P = 0.0002), while the genotype "CC" of rs2297440 as the protective genotype in glioma (OR, 0.47; 95% CI, 0.31-0.71;P = 0.0003). Furthermore, haplotype "GCT" in RTEL1gene was found to be associated with risk of glioma (OR, 0.7; 95% CI, 0.57-0.86; Fisher's P = 0.0005; Pearson'sP = 0.0005), and haplotype "ATT" was detected tobe associated with risk of glioma (OR, 1.32; 95% CI, 1.12-1.57; Fisher's P = 0.0013; Pearson's P = 0.0013). Two single variants, the genotypes of "GG" of rs6010620 and "CC"of rs2297440 (rs6010620 and rs2297440) in the RTEL1gene, together with two haplotypes ofGCT and ATT, were identified to be associated with glioma development. And it might be used to evaluate the glioma development risks to screen the above RTEL1 tagging SNPs and haplotypes.Virtual slidesThe virtual slides for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1993021136961998

Pathophysiological implication of reversed CT halo sign in invasive pulmonary mucormycosis: a rare case report

Yoichiro Okubo — 2013-05-17T00:00:00Z

Background: It has been accepted that reversed halo sign (RHS) appeared on a computed tomography (CT) image in immunocompromised patients indicates an invasive fungal infection, but its pathophysiology remains obscure as to what this image implies. Therefore, the present reportdescribes detailed radiological and histopathological findings of a case of invasive pulmonary mucormycosis (IPM) presenting RHS with comparison to those from a lesion of discrete nodule caused by invasive pulmonary aspergillosis (IPA), and discusses the pathophysiological implications of this characteristic image.Case presentationRHS had been clinically noted at the time of recovering of bone marrow function of a 64-year-old Japanese man who had chemotherapy for his acute lymphoblastic leukemia.Histological examination of the surgically removed lung revealed a lesion of IPM. This was composed of coagulation necrosis of septa at the center of lesion with preservation of aircontent which was encompassed outer rim comprising triplet structure; liquefaction, consolidation, and organization from the inner to the outer layer. In addition, Micro-CTexamination confirmed reticular structure and monotonous high density at the central coagulation necrosis preserving air content and surrounding consolidation, and organizationlesion of the IPM lesion. Conclusion: Our investigations suggest that RHS might be understood as a kind of immune reconstitution syndrome and be the initial and prior status of air crescent sign.Virtual SlidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/3480054198968132

De novo CD5-positive diffuse large B-cell lymphomas show high specificity for cyclin D2 expression

Takuro Igawa — 2013-05-15T00:00:00Z

D cyclins positively regulate the cell cycle and mediate the pathogenesis of some lymphomas.Cyclin D1 overexpression is the hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 are reportedly not as specific to certain lymphomas as cyclin D1. In this study, cyclin D2 was found to be overexpressed in 98% of de novoCD5-positive diffuse large B-cell lymphomas (DLBCLs) (50/51) and in 28% of CD5-negative DLBCLs (14/51). Astatistically significant difference was observed between these two groups (p<0.0001). In contrast, no statistical difference was found in the cyclin D3 expression between CD5-positive (18/51) and CD5-negative (24/51) DLBCLs (p=0.23). Based on these findings, cyclin D2 is therefore considered to be closely associated with de novo CD5-positive DLBCLs. This insight may be useful for overcoming the inferior survival of this aggressive lymphoma.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1382856320966453

Expression of thyroid transcription factor-1 is associated with a basal-like phenotype in breast carcinomas

Tor Klingen — 2013-05-15T00:00:00Z

Background: The differential diagnosis between primary and secondary breast cancers might be difficult, especially in poorly differentiated tumors. Thyroid Transcription Factor-1 (TTF-1) has been regarded as a reliable marker for lung or thyroid origin, with only occasional positive staining in other tumors. However, positive cases have recently been reported among primary breast carcinomas.Methods and results: Here, we analyzed expression of TTF-1 protein (clone SPT24) by immunohistochemical staining of sections from paraffin embedded tumor samples in 247 primary breast cancers from the population-based Norwegian Breast Cancer Screening Program. Positive staining (weak or strong)was observed in 7 cases (2,8%). As novel observations, positivity was demonstrated more frequently in estrogen receptor negative cases (14,0% vs. 1,4%; p = 0,004), highly proliferative tumors (8,8% vs. 1,1%; p = 0,008), tumors with a basal-like phenotype by showing expression of CK5/6 and/or P-cadherin (11,1% vs. 1,4%; p = 0,01), and tumors with blood vessel invasion (9,7% vs. 1,9%; p = 0,04). Also, TTF-1 was associated with histological grade 3 tumors compared with grade 1 or 2 tumors (7,7% vs. 1,5%; p = 0,04) as well as lymph node positive cases (5,2% vs. 1,8%; p = 0,03). Conclusions: Our population-based findings indicate that TTF-1 may be positive in approximately 3% of primary breast cancers, and positivity indicates an association with adverse prognostic factors.Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8313753509421182

Necrotizing sarcoid granulomatosis with hemoptysis: a case report and literature review

Haidong Huang — 2013-05-13T00:00:00Z

We present a case of 39-year-old male with the symptoms of fever, cough, chest pain and bloody phlegm, whose chest CT showed multiple subpleural nodules and inflammatoryinfiltration. Video-Assisted Thoracic Surgery ( VATS ) for rightsubplural nodule was performed and confirmed the diagnosis of necrotizing sarcoid granulomatosis. Prednisolonewas administered and the symptoms were under control untill the occurrence of intermittent hemoptysis after 10 months. Chest CT and bronchoscope revealed the right lower lobe nodule with intraluminal necrotic tissue in the right lower lobe posterior basal segment respectively.Fatal hemoptysis happened during endobronchial biopsy by flexible bronchoscope forcep.Based on this case, we reviewed the relevant literature and discussed the clinical features, pathological changes and prognosis of the disease.Virtual SlidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1955868163936338

Deletion mutation in BSCL2 gene underlies congenital generalized lipodystrophy in a Pakistani family

Obaid Rahman — 2013-05-09T00:00:00Z

Background: Congenital generalized lipodystrophy (CGL) also known as Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a genetically heterogeneous disorder characterized by loss of adipose tissues, Acanthosis nigricans, diabetes mellitus, muscular hypertrophy, hepatomegaly and hypertriglyceridemia. There are four subclinical phenotypes of CGL (CGL1-4) and mutations in four genes AGPAT2, BSCL2, CAV1 and PTRF have been assigned to each type. Methods: The study included clinical and molecular investigations of CGL disease in a consanguineous Pakistani family. For mutation screening all the coding exons including splice junctions of AGPAT2, BSCL2, CAV1 and PTRF genes were PCR amplified and sequenced directly using an automated DNA sequencer ABI3730. Results: Sequence analysis revealed a single base pair deletion mutation (c.636delC; p.Tyr213ThrfsX20) in exon 5 of BSCL2 gene causing a frame shift and premature termination codon. Conclusion: Mutation identified here in BSCL2 gene causing congenital generalized lipodystrophy is the first report in Pakistani population. The patients exhibited characteristic features of generalized lipodystrophy, Acanthosis nigricans, diabetes mellitus and hypertrophic cardiomyopathy.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1913913076864247.

Clinico- pathological profile of patients with breast diseases

Hafiz Aslam — 2013-05-09T00:00:00Z

Background: To evaluate the spectrum of breast diseases and their association with presenting complains of patients.MethodologyIt was a cross sectional study conducted from 1st January 2010 – 30th December 2012. A total of 254 breast specimens of patients, who were admitted in Civil Hospital Karachi with breast complaints, were included. Specimens were collected either from mastectomy, lumpectomy or needle biopsy from the admitted patients. Informed written consent was taken from all the patients. All patients with primary breast diseases were included. Patients undergoing chemotherapy or with secondary breast disease and slides with insufficient specimen were excluded. All data was entered and analyzed through SPSS 19.ResultThere were 254 breast lesions, histologically diagnosed in 3 year review period. The overall mean age of patients with breast lesion was 25.18, SD ± 11.73 with a wide age range of 12–74 years. Most common cases identified are benign 191(75.3%), followed by inflammatory 30(11.8%) and malignant lesions 30(11.8%). Most patients presenting with the complain of pain have diagnosis of fibroadenoma 24 (63.2%) while patient with complain of lump also have the most common diagnosis of fibroadenoma 147 (72.8%). Conclusions: Study shows that in Pakistani females, mostly encountered breast lesion was fibroadenoma. Due to lack of awareness breast diseases present lately. Awareness must be created among women to reduce the mortality and morbidity with breast lesions.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1037059088969395.

HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population

Ling Shan — 2013-05-09T00:00:00Z

Background: With varied immunohistochemistry scoring criteria and patient cohorts, HER2-positivity rates in gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma have been reported with a wide range. Recently standardized scoring criteria for GC and GEJ cancer has been established and recommended. In this study, the frequency of HER2 expression and the relationship between HER2 expression and clinicopathological features were examined in a large cohort of Chinese GC and GEJ cancer patients. Methods: A total of 1463 patients, including 929 primary GCs and 534 primary GEJ adenocarcinomas, was retrospectively analyzed for HER2 overexpression by immunohistochemistry (IHC). Fluorescence in situ hybridization (FISH) analysis was used in 308 GCs and GEJ adenocarcinoma cases to assess HER2 gene amplification. Results: HER2 overexpression (3+) was detected in 9.8% of carcinomas and more frequently observed in GEJ cancer cases, in the intestinal type, and in the well or moderately differentiated type (P=0.003, 0.000, and 0.000, respectively). HER2 equivocal (2+) was detected in 14.4% of cases. As for the 308 cases analyzed by FISH, 39 (of 40, 97.5%) IHC 3+ cases, 11 (of 38, 28.9%) IHC 2+ cases, and 3 (of 230, 1.3%) IHC 1+/0 cases showed HER2 gene amplification. A high concordance rate (98.5%) between IHC and FISH was demonstrated. Conclusions: Approximately 10% of Chinese patients with primary GC and GEJ adenocarcinoma were HER2-positive on IHC. HER2 overexpression was associated with GEJ site, intestinal cancer subtype, and well or moderately differentiated carcinomas.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1935951199941072.

Pleomorphic carcinoma of the breast associated with cyst formation: a unique surgical case focusing on cytological and immunohistochemical findings. Cystic breast PC

Sohsuke Yamada — 2013-05-07T00:00:00Z

A mammary nodular lesion was recognized one month before the surgeryin the right upperbreast of a 55-year-old female. The fine needle aspiration cytology specimens containedmany individual bizarre, multi-nucleated, and/or giant cells havinghyperchromaticpleomorphic nuclei, prominent nucleoli, and relatively abundant cytoplasm, admixed withnumerous mitotic figures in a hemorrhagic or inflammatory background. A small amount ofsheet-like or three-dimensional clusters of malignant cells coexisted. We first interpreted it ashigh-grade malignancy, such as invasive carcinoma, not otherwise specified. A right breast-conserving surgery was performed, and gross examination revealed acystic cavity-formedand solid tumor lesion, measuring 35 x 35 x 25 mm and looking gray-yellowish to -whitish.On microscopic examination, the tumor was composed of a diffuse proliferation of highlyatypical cells devoid of adhesive characteristics, including manymulti-nucleated giant bizarrecells, in a haphazard fashion with stromal invasion, alternating withsarcomatoid features ofspindle tumor cells. The cystic cavity was surrounded by hemorrhagic and inflammatorygranulation tissue and lined by mostly denuded but atypical tumor cells or bland-lookingflattened epithelial cells. Immunohistochemically, these tumor cells are specifically positivefor all epithelial markers. Therefore, we made a conclusive diagnosis of pleomorphiccarcinoma of the breast with cyst formation. We should be aware that, owing to itscharacteristic findings, cytopathologists can diagnose correctly,based on careful cytologicalexamination of adequate samplings.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9290689448998782