Diagnostic Pathology - Most accessed articles

Antinuclear antibodies and their detection methods in diagnosis of connective tissue diseases: a journey revisited

Yashwant Kumar — 2009-01-02T00:00:00Z

It has been more than 50 years since antinuclear antibodies were first discovered and found to be associated with connective tissue diseases. Since then different methods have been described and used for their detection or confirmation. For many decades immunofluorescent antinuclear antibody test has been the "gold standard" in the diagnosis of these disorders. However to increase the sensitivity and specificity of antinuclear antibody detection further approaches were explored. Today a battery of newer techniques are available some of which are now considered better and are competing with the older methods. This article provides an overview on advancement in antinuclear antibody detection methods, their future prospects, advantages, disadvantages and guidelines for use of these tests.

Breast spindle cell tumours: about eight cases

Howayda Abd El All — 2006-07-22T00:00:00Z

Background: Breast spindle cell tumours (BSCTs), although rare, represent a heterogeneous group with different treatment modalities. This work was undertaken to evaluate the utility of fine needle aspiration cytology (FNAC), histopathology and immunohistochemistry (IHC) in differentiating BSCTs. Methods: FNAC of eight breast masses diagnosed cytologically as BSCTs was followed by wide excision biopsy. IHC using a panel of antibodies against vimentin, pan-cytokeratin, s100, desmin, smooth muscle actin, CD34, and CD10 was evaluated to define their nature. Results: FNAC defined the tumors as benign (n = 4), suspicious (n = 2) and malignant (n = 3), based on the cytopathological criteria of malignancy. Following wide excision biopsy, the tumors were reclassified into benign (n = 5) and malignant (n = 3). In the benign group, the diagnosis was raised histologically and confirmed by IHC for 3 cases (one spindle cell lipoma, one myofibroblastoma and one leiomyoma). For the remaining two cases, the diagnosis was set up after IHC (one fibromatosis and one spindle cell variant of adenomyoepithelioma). In the malignant group, a leiomyosarcoma was diagnosed histologically, while IHC was crucial to set up the diagnosis of one case of spindle cell carcinoma and one malignant myoepithelioma. Conclusion: FNAC in BSCTs is an insufficient tool and should be followed by wide excision biopsy. The latter technique differentiate benign from malignant BSCTs and is able in 50% of the cases to set up the definite diagnosis. IHC is of value to define the nature of different benign lesions and is mandatory in the malignant ones for optimal treatment. Awareness of the different types of BSCTs prevents unnecessary extensive therapeutic regimes.

Malignant perivascular epithelioid cell tumor (PEComa) of the uterus with late renal and pulmonary metastases: a case report with review of the literature

Henry Armah — 2007-12-03T00:00:00Z

Background: Perivascular epithelioid cell tumor (PEComa), other than angiomyolipoma (AML), clear cell sugar tumor (CCST), and lymphangioleiomyomatosis (LAM), is a very rare mesenchymal tumor with an unpredictable natural history. The uterus is the most prevalent reported site of involvement of PEComa-not otherwise specified (PEComa-NOS). To the best of our knowledge, about 100 PEComa-NOS have been reported in the English Language medical literature, of which 38 were uterine PEComa-NOS. These reported cases of uterine PEComa-NOS have usually shown clinically benign behavior, but 13 tumors, three of them associated with tuberous sclerosis complex (TSC), exhibited local aggressive behavior and four of them showed distant metastases.Case presentationWe report the case of a 59-year-old woman, who presented with renal and pulmonary lesions seven years after the initial diagnosis of uterine leiomyosarcoma. Left nephrectomy and right middle lobe wedge resection were performed. Histological and immunohistochemical analysis of the renal and pulmonary lesions, in addition to retrospective re-evaluation of the previous uterine tumor, led to the final diagnosis of malignant uterine PEComa with late renal and pulmonary metastases. All three lesions had the typical histological appearance of PEComa-NOS showing a biphasic growth pattern with continuous transition between spindle cells and epithelioid cells, often arranged around vascular spaces. Immunohistochemically, the tumor cells of both phenotypes in all three lesions stained for melanocytic (HMB-45 and Melan-A/MART-1) and myoid (desmin, smooth muscle actin, and muscle-specific actin/all muscle actin/HHF-35) markers. Conclusion: The findings indicate that despite the small number of reported cases, PEComas-NOS should be considered tumors of uncertain malignant potential, and metastases to other organs might become evident even several years after the primary diagnosis.

Sporadic Hemangioblastoma of the Kidney: a rare renal tumor

Yang Liu — 2012-05-01T00:00:00Z

Hemangioblastoma is a benign and morphologically distinctive tumor that can occursporadically or in association with von Hippel-Lindau disease in approximately 25 % of thecases, and which involves the central nervous system in the majority of the cases. Rareoccurrences of hemangioblastoma in peripheral nerves and extraneural tissues have beenreported. This report describes one case of sporadic renal hemangioblastoma happened in a16-year-old Chinese female patient, presenting with hematuria, and low back pain.Histologically, the tumors were circumscribed, and composed of sheets of large polygonalcells traversed by arborizing thin-walled blood vessels. The diagnosis of hemangioblastomawas confirmed by negative immunostaining for cytokeratin, and positive staining for alpha-inhibin, S100 and neuron-specific enolase (NSE). This benign neoplasm which can bemistaken for various malignancies such as renal cell carcinoma, epithelioidhemangiopericytoma and epithelioid angiomyolipoma, deserves wider recognition for itsoccurrence as a primary renal tumor.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/5445834246942699

Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring

Anthony Rizzardi — 2012-04-19T00:00:00Z

Immunohistochemical (IHC) assays performed on formalin-fixed paraffin-embedded (FFPE)tissue sections traditionally have been semi-quantified by pathologist visual scoring ofstaining. IHC is useful for validating biomarkers discovered through genomics methods aslarge clinical repositories of FFPE specimens support the construction of tissue microarrays(TMAs) for high throughput studies. Due to the ubiquitous availability of IHC techniques inclinical laboratories, validated IHC biomarkers may be translated readily into clinical use.However, the method of pathologist semi-quantification is costly, inherently subjective, andproduces ordinal rather than continuous variable data. Computer-aided analysis of digitizedwhole slide images may overcome these limitations. Using TMAs representing 215 ovarianserous carcinoma specimens stained for S100A1, we assessed the degree to which dataobtained using computer-aided methods correlated with data obtained by pathologist visualscoring. To evaluate computer-aided image classification, IHC staining within pathologistannotated and software-classified areas of carcinoma were compared for each case. Twometrics for IHC staining were used: the percentage of carcinoma with S100A1 staining(%Pos), and the product of the staining intensity (optical density [OD] of staining) multipliedby the percentage of carcinoma with S100A1 staining (OD*%Pos). A comparison of the IHCstaining data obtained from manual annotations and software-derived annotations showedstrong agreement, indicating that software efficiently classifies carcinomatous areas withinIHC slide images. Comparisons of IHC intensity data derived using pixel analysis softwareversus pathologist visual scoring demonstrated high Spearman correlations of 0.88 for %Pos(p < 0.0001) and 0.90 for OD*%Pos (p < 0.0001). This study demonstrated that computeraidedmethods to classify image areas of interest (e.g., carcinomatous areas of tissuespecimens) and quantify IHC staining intensity within those areas can produce highly similardata to visual evaluation by a pathologist.Virtual SlidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1649068103671302

Expression features of SOX9 associate with tumor progression and poor prognosis of hepatocellular carcinoma

Xiaodong Guo — 2012-04-19T00:00:00Z

Background: SOX9 as a member of the SOX (SRY [sex determining region Y] box) gene superfamily hasbeen previously demonstrated to be a proto-oncogene in a variety of malignancies. However,the clinical significance of SOX9 expression in hepatocellular carcinoma (HCC) remainsunclear. The aim of this study was to investigate the expression of SOX9 in HCC anddetermine its correlation with tumor progression and prognosis. Methods: One-hundred and thirty HCC patients who had undergone curative liver resection wereselected and immunohistochemistry, Western blotting, and quantitative real time polymerasechain reaction (Q-PCR) were performed to analyze SOX9 expression in the respectivetumors. Results: Immunohistochemistry, Western blotting, and Q-PCR consistently confirmed SOX9overexpression in HCC tissues compared with their adjacent nonneoplastic tissues (P < 0.01).Additionally, immunostaining showed more SOX9 positive cells in the higher tumor stage(T3 ~ 4) and tumor grade (G3) than in the lower tumor stage (T1 ~ 2, P = 0.03) and tumorgrade (G1 ~ 2, P = 0.01), respectively. Moreover, HCC patients with high SOX9 expressionwere significantly associated with lower 5-year overall survival (P < 0.01) and lower 5-yeardisease-free survival (P < 0.01), respectively. The Cox proportional hazards model furthershowed that SOX9 over-expression was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR] = 2.621, 95% confidence interval [CI] = 1.548-5.829, P = 0.01) and 5-year overall survival (HR = 3.825, CI = 1.638-7.612, P = 0.003) inHCC. Conclusion: Our data suggest for the first time that the overexpression of SOX9 protein in HCC tissues isof predictive value on tumor progression and poor prognosis.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9029740396926377

p16 as a diagnostic marker of cervical neoplasia: a tissue microarray study of 796 archival specimens

Iana Lesnikova — 2009-07-09T00:00:00Z

Background: To evaluate the usefulness of this biomarker in the diagnosis of cases of cervical neoplasia we studied the immunohistochemical expression of p16INK4a in a large series of archival cervical biopsies arranged into tissue microarray format. Methods: TMAs were constructed with tissue cores from archival formalin fixed, paraffin-embedded donor tissues from 796 patients, and included cases of cervical intraepithelial neoplasia (CIN)1 (n = 249), CIN2 (n = 233), CIN3 (n = 181), and invasive cervical carcinoma (n = 133). p16INK4a expression was scored using two different protocols: 1) positive vs negative p16INK4a staining; 2) a semi-quantitative immunohistochemical score (0 to 8 points) according to the intensity of staining and the proportion of stained cells Results: p16INK4A expression was not seen in normal cervix tissue, but was found with increasing frequency in the sequence: CIN1 (180/249; 72.3%) – CIN2 (212/233; 91.0%) – CIN3 (178/181; 98.3%) – invasive carcinoma (131/133; 98.5%). Using semi-quantitative scoring, all normal cervical samples had low scores (from 0 to 2 points), whilst the number of specimens with high scores was proportional to the degree of cervical dysplasia or the presence of invasive carcinoma. Conclusion: Immunohistochemical analysis of p16INK4a expression is a useful diagnostic tool. Expression is related to the degree of histological dysplasia, suggesting that it may have prognostic and predicative value in the management of cervical neoplasia.

Introduction of virtual microscopy in routine surgical pathology - a hypothesis and personal view from Europe

Klaus Kayser — 2012-04-30T00:00:00Z

The technology of whole image acquisition from histological glass slides (Virtual slides,(VS)) and its associated software such as image storage, viewers, and virtual microscopy(VM), has matured in the recent years. There is an ongoing discussion whether to introduceVM into routine diagnostic surgical pathology (tissue-based diagnosis) or not, and if these areto be introduced how best to do this. The discussion also centres around how to substantiallydefine the mandatory standards and working conditions related to introducing VM. Thisarticle briefly describes some hypotheses alongside our perspective and that of several of ourEuropean colleagues who have experienced VS and VM either in research or routine praxis.After consideration of the different opinions and published data the following statements canbe derived: 1. Experiences from static and remote telepathology as well as from daily routinediagnoses, confirm that VM is a diagnostic tool that can be handled with the same diagnosticaccuracy as conventional microscopy; at least no statistically significant differences (p >0.05) exist. 2. VM possesses several practical advantages in comparison to conventionalmicroscopy; such as digital image storage and retrieval and contemporary display of multipleimages (acquired from different stains, and/or different cases). 3. VM enables fast andefficient feedback between the pathologist and the laboratory in terms of ordered additionalstains, automated access to the latest research for references, and fast consultation withoutstanding telepathology experts. 4. Industry has already invested "big money" into thistechnology which certainly will be of influence in its future development. The mainconstraints against VM include the questionable reimbursement of the initial investment, themissing direct and short term financial benefit, and the loss of potential biological identitybetween the patient and the examined tissue. This article tries to analyze and evaluate thefactors that influence the implementation of VM into routine tissue-based diagnosis, forexample in combination with predictive diagnosis. It focuses on describing the advantages ofmodern and innovative electronically based communication technology.Virtual SlidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1245603103708547

A diagnostic dilemma in breast pathology - benign fibroadenoma with multinucleated stromal giant cells

Helen Heneghan — 2008-08-01T00:00:00Z

Fibroadenomas are common benign breast tumours that display a characteristic pathological morphology, although several epithelial and stromal variations exist. A very rare histological finding is the presence of multinucleated giant cells throughout the stroma of a benign fibroadenoma. Cells of this type, which are more commonly found incidentally within the interlobular stroma of breast tissue, are benign and should not be mistaken for malignant cells on microscopic examination. Unfortunately a lack of awareness of this pathological entity can lead to diagnostic confusion amongst pathologists resulting in the multinucleate giant cells being mistaken for highly mitotic cells and consequently the fibroadenoma being mistaken for a malignant lesion. This may have serious implications for the subsequent management of the patient. The presence of this unusual cell type in the stroma does not alter the prognosis of otherwise benign lesion. We encountered two such cases at our institution in a six month period recently. We present their histories along with relevant radiological, microscopic and immunohistochemical features, followed by a discussion of this unusual pathological entity.

Histological variants of cutaneous Kaposi sarcoma

Liron Pantanowitz — 2008-07-25T00:00:00Z

This review provides a comprehensive overview of the broad clinicopathologic spectrum of cutaneous Kaposi sarcoma (KS) lesions. Variants discussed include: usual KS lesions associated with disease progression (i.e. patch, plaque and nodular stage); morphologic subtypes alluded to in the older literature such as anaplastic and telangiectatic KS, as well as several lymphedematous variants; and numerous recently described variants including hyperkeratotic, keloidal, micronodular, pyogenic granuloma-like, ecchymotic, and intravascular KS. Involuting lesions as a result of treatment related regression are also presented.