Routine Pathology Research Articles

A new practical method of estimating tumoral microenvironment parameters of possible prognostic significance in patients with invasive breast carcinoma: Combined microenvironment score

Background and objectiveIn recent years, the tumor microenvironment has become increasingly recognized as an influential factor in breast cancer development and growth. The parameters that form the microenvironment are the tumor stroma ratio and tumor infiltrating lymphocytes. In addition, tumor budding, which shows the ability of the tumor to metastasize, gives information about the progression of the tumor. In this study, the combined microenvironment score (CMS) was determined with these parameters, and the relationship between CMS and prognostic parameters and survival was evaluated. Materials and methodsIn our study, tumor stroma ratio, tumor infiltrating lymphocytes, and tumor budding were evaluated in hematoxylin-eosin sections of 419 patients with invasive ductal carcinoma. Patients were scored separately for each of these parameters, and these scores were summed to determine the CMS. The patients were divided into 3 groups according to CMS and the relationship between CMS and prognostic parameters and the survival of the patients was studied. ResultsThe patients with CMS 3 had higher histological grade and Ki67 proliferation index compared to CMS 1 and 2. Additionally, lymphovascular invasion, axillary lymph node and distant metastasis were more common. Disease-free, and overall survival were significantly shortened in the CMS 3 group. CMS was found as an independent risk factor for DFS (HR: 2.144 (95 % CI: 1.219–3.77) p: 0.008), but not an independent risk factor for OS. ConclusionCMS is a prognostic parameter that can be easily evaluated and does not require extra time and cost. Evaluating the morphological parameters of the microenvironment with a single scoring system will contribute to routine pathology practice and predict patient prognosis.

CD8+ Cell Density Gradient across the Tumor Epithelium-Stromal Interface of Non-Muscle Invasive Papillary Urothelial Carcinoma Predicts Recurrence-Free Survival after BCG Immunotherapy.

Bacille Calmette-Guerin (BCG) immunotherapy is the first-line treatment in patients with high-risk non-muscle invasive papillary urothelial carcinoma (NMIPUC), the most common type of bladder cancer. The therapy outcomes are variable and may depend on the immune response within the tumor microenvironment. In our study, we explored the prognostic value of CD8+ cell density gradient indicators across the tumor epithelium-stroma interface of NMIPUC. Clinical and pathologic data were retrospectively collected from 157 NMIPUC patients treated with BCG immunotherapy after transurethral resection. Whole-slide digital image analysis of CD8 immunohistochemistry slides was used for tissue segmentation, CD8+ cell quantification, and the assessment of CD8+ cell densities within the epithelium-stroma interface. Subsequently, the gradient indicators (center of mass and immunodrop) were computed to represent the density gradient across the interface. By univariable analysis of the clinicopathologic factors, including the history of previous NMIPUC, poor tumor differentiation, and pT1 stage, were associated with shorter RFS (p < 0.05). In CD8+ analyses, only the gradient indicators but not the absolute CD8+ densities were predictive for RFS (p < 0.05). The best-performing cross-validated model included previous episodes of NMIPUC (HR = 4.4492, p = 0.0063), poor differentiation (HR = 2.3672, p = 0.0457), and immunodrop (HR = 5.5072, p = 0.0455). We found that gradient indicators of CD8+ cell densities across the tumor epithelium-stroma interface, along with routine clinical and pathology data, improve the prediction of RFS in NMIPUC.

Improving sarcoma classification by using RNA hybridisation capture sequencing in sarcomas of uncertain histogenesis of young individuals

Our aim was to utilise a 241-gene RNA hybridisation capture sequencing (CaptureSeq) gene panel to identify unexpected fusions in undifferentiated, unclassified or partly classified sarcomas of young individuals (<40 years). The purpose was to determine the utility and yield of a large, targeted fusion panel as a tool for classifying tumours that do not fit typical diagnostic entities at the time of the original diagnosis. RNA hybridisation capture sequencing was performed on 21 archival resection specimens. Successful sequencing was obtained in 12 of 21 samples (57%), two of which (16.6%) harboured translocations. A novel NEAT1::GLI1 fusion, not previously reported in the literature, presented in a young patient with a tumour in the retroperitoneum, which displayed low grade epithelioid cells. The second case, a localised lung metastasis in a young male, demonstrated a EWSR1::NFATC2 translocation. No targeted fusions were identified in the remaining 83.4% (n=10) of cases. Forty-three per cent of the samples failed sequencing as a result of RNA degradation. RNA-based sequencing is an important tool, which helps to redefine the classification of unclassified or partly classified sarcomas of young adults by identifying pathogenic gene fusions in up to 16.6% of the cases. Unfortunately, 43% of the samples underwent significant RNA degradation, falling below the sequencing threshold. As CaptureSeq is not yet available in routine pathology practice, increasing awareness of the yield, failure rate and possible aetiological factors for RNA degradation is fundamental to maximise laboratory procedures to improve RNA integrity, allowing the potential identification of significant gene alterations in solid tumours.

HER2 Expression in Bladder Cancer: A Focused View on Its Diagnostic, Prognostic, and Predictive Role.

Bladder cancer (BC) is a heterogeneous disease from a molecular, morphological, and clinical standpoint. HER2 is a known oncogene involved in bladder carcinogenesis. Assessing HER2 overexpression as a result of its molecular changes in a routine pathology practice using immunohistochemistry might be a useful adjunct in several scenarios, namely (1) to correctly identify flat urothelial lesions and inverted urothelial lesions in the diagnostic setting; (2) to provide prognostic hints in both non-muscle invasive (NMI) and muscle invasive (MI) tumors, thus supplementing risk stratification tools, especially when evaluating higher-risk tumors such as those with variant morphology; (3) to improve antibody panels as a surrogate marker of BC molecular subtyping. Furthermore, the potential of HER2 as a therapeutic target has been only partly explored so far, in light of the ongoing development of novel target therapies.

CCAD or eCRS: Defining Eosinophilic Subpopulations in Chronic Rhinosinusitis.

Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone. This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS. A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry. 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (τb = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm2, p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00-6.00] vs 6.00[6.00-6.75], p = 0.015). Other outcomes were similar. Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations.

Incomplete Intestinal Metaplasia Is Rare in Autoimmune Gastritis

Background: Incomplete intestinal metaplasia (IM) is reportedly associated with higher gastric cancer (GC) risk than its complete variant. AGA Guidelines recommend including IM subtyping in routine pathology reports. This study assesses the prevalence of complete versus incomplete IM in gastric conditions with different GC risks. Methods: IM subtyping (complete vs. incomplete) and grading (IM extension: G1: ≤30%; G2: >30%) were assessed in 386 patients with IM + ve gastric biopsy sets that included both antral and oxyntic samples. Cases were categorized as: (a) IM foci in otherwise normal mucosa (n = 59); (b) Helicobacter pylori gastritis (n = 138); (c) reactive gastropathy (141); and (d) autoimmune atrophic gastritis (AIG, n = 48). Odds ratios (OR) and their 95% CI were used in comparing the prevalence of incomplete IM and the correlation between subtype and IM extension. Results: Incomplete IM was present in 37.7% of patients with H. pylori gastritis, 8.3% of those with AIG 5.0% of those with reactive gastropathy, and none of those with otherwise normal mucosa. Incomplete IM was strongly associated with more extensive (G2-IM) mucosal intestinalization (OR = 6.69; 95% CI = 2.77–9.40). Conclusion: Incomplete IM is significantly more prevalent in conditions (H. pylori gastritis) known to carry a higher risk of GC and is strongly associated with its extension. The low prevalence of incomplete IM in AIG (8.3%) and reactive gastropathy (5.2%) is in keeping with the low GC risk associated with these conditions.

Altered MANF Expression in Pancreatic Acinar and Ductal Cells in Chronic Alcoholic Pancreatitis: A Cross-Sectional Study

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress response protein that plays an important role in pancreatic functions. As both alcohol and ER stress response proteins are involved in the pathogenesis of pancreatitis, we sought to investigate the expression of MANF in chronic alcoholic pancreatitis (CAP) and chronic non-alcoholic pancreatitis (CNP). A cohort of chronic pancreatitis tissues was gathered from routine surgical pathology (n = 77) and autopsy (n = 10) cases and tissue microarrays were created. Sampled tissues were reviewed and designated as representing CAP (n = 15), CNP (n = 58), or normal pancreatic tissue (NPT) (n = 27). MANF immunohistochemistry (IHC) and digital image analysis were performed to obtain an estimation of tissue fibrosis and an optical density (OD) of MANF IHC in ducts and acini for each case. The averaged values for these variables among histologic designations were compared. The amount of fibrous tissue of the combined CAP and CNP group (chronic alcoholic and non-alcoholic pancreatitis, CANP) exceeded that of the NPT group (70% vs. 34%, p < 0.0001). The MANF OD in ducts of CANP was significantly higher than that of NPT (0.19 vs. 0.10, p < 0.05). The MANF OD in ducts of CAP was significantly higher than that of CNP (0.27 vs. 0.17, p < 0.05). The MANF OD in acini of CAP was significantly lower than that in CNP (0.81 vs. 1.05, p < 0.05). Finally, there was a statistically significant positive relationship between the amount of fibrosis and MANF OD in ducts (p < 0.001). MANF expression was higher in ducts of CAP than CNP. In contrast, MANF expression in acini was lower in CAP than CNP and NPT. There was a positive correlation between fibrosis and MANF levels in the ducts.

Uniform Noting for International application of the Tumor-stroma ratio as Easy Diagnostic tool: The UNITED study - An update

Background: The UNITED study researches the tumor-stroma ratio (TSR) as prognostic parameter in colon cancer. A high amount of stroma has retrospectively been proven to lead to a worse overall and disease-free survival (OS and DFS, respectively), potentially influencing the choice for adjuvant therapy. The Union for International Cancer Control (UICC) and College of American Pathologists (CAP) supported the importance of this parameter, but indicated the necessity of a prospective international multicenter trial using a quality program for scoring. Hence, this study prepares the TSR for implementation in current routine pathology diagnostics in addition to the TNM classification.

The NeuroSAFE frozen section technique during radical prostatectomy - Implementation and optimization of technical aspects in a routine pathology workflow.

In prostate cancer patients, application of the NeuroSAFE frozen section technique during radical prostatectomy has been shown to increase the rate of nerve sparing surgery and to improve functional outcome for the patients. The aim of this study is to report on technical and organizational optimization opportunities of the procedure. All patients submitted to bilateral intraoperative frozen section from January 2018 until December 2020 (n=452) were retrospectively analyzed and parameters such as turnaround time, staff situation in the laboratory and histologic properties of the tumors were assessed. The median turnaround time per case was 40.3 (±10.5) min. In 2020 the average time needed from accessioning to diagnosis was 38.1min. Multivariate linear regression suggested that the number of technical assistants/cryotomes (46.1min vs. 39.13min; p<0.001), the place of microscopic examination (43.0min vs. 38.7min; p<0.001) and the presence of a positive margin (38.0 vs. 44.0min; p<0.001) were significant influential factors. The turnaround time was independent of the uropathological expertize of the consultant (39.84min vs. 40.7min; p=0.09), the tumor grade (42.3 vs 39.8min; p=0.493) and the presence of extraprostatic extension (44.0 vs 39.8min; p=0.099). The implementation of simple optimization measures in the workflow as well as structured training of all pathology staff involved in the examination leads to a significant increase in the efficiency of the examination while maintaining the same level of resources. The results could thus be a contribution to the broader application of the procedure.

P400 Identifying Nutritional targets in Crohn’s disease: INTICO1: a time-limited trial of exclusive enteral nutrition during adult CD remission

Abstract Background During clinical remission in adult Crohn’s disease (CD), impaired health reacted quality of life and fatigue is common, and the nutritional state may be affected by factors such as restrictive eating and altered anatomy from previous inflammation or surgeries. Adults with CD in clinical remission do not routinely undergo nutritional assessments or intervention. The INTICO1 study used a time-limited trial of exclusive enteral nutrition (EEN) to expose and explore nutritionally sensitive aspects of in adults with CD during remission. The extent to which the nutritional state relates to the quality of CD remission and the potential role for nutritional therapies is neither well described nor understood. Methods This was a single arm longitudinal observation study with a dietary intervention. 24 adults in CD remission (Harvey Bradshaw &amp;lt;5, faecal calprotectin &amp;lt;250) underwent assessment of nutritional state at 3 time points; after habitual diet (assessment 1), after 7 days of polymeric EEN (assessment 2) and after a 2-week gradual return to habitual diet (assessment3). Assessments comprised food diary analysis, anthropometry, bio-electrical impedance analysis, routine pathology measures of micronutrient concentration, and patient reported outcome measures (PROMs). Results Assessment 1 (habitual diet) identified individuals with multiple inadequacies of intake (7% (26/368)) micronutrients bloods below the normal laboratory range (see table for analytes) reduced lean mass, low phase angle (PhA) and excessive fatigue (reduced SF-36 vitality). At assessment 2 (post EEN), subjects had fewer deficiencies 4% (16/368), with significant increases seen in Vitamins A, D, E, B2, B6, B9 and the minerals Ca, Cu, Po4 and Se. At visit 3 (return to free diet), micronutrient concentrations reverted toward assessment 1 level, although B6 and B9 remained significantly higher (pairwise comparison visit 1 vs visit 3). BIA measures of nutritional status (PhA) and the SF36 physical function score improved 1 and 2 (5.2 vs 5.4 p&amp;lt;0.01 and 95 v100 p&amp;lt;0.05) and returned to baseline levels on return to free diet (Assessment 3). Conclusion A time-limited trial (7 days) of EEN, given in this setting of adults in CD remission led to changes in micronutrient biochemistry, objective improvement in the bioelectrical properties of the body (increased phase angle) and an improvement in fatigue among the subjects as captured by the SF36-PF. The study suggests that impaired nutritional state and excessive fatigue is likely to be prevalent among adults with CD during remission and may be sensitive to nutritional intervention.

HUBUNGAN KADAR ALBUMIN DAN INDEKS MASSA TUBUH PADA PASIEN HEMODIALISIS RUTIN DI RSUD ULIN BANJARMASIN

Malnutrition is most common risk in patients undergoing routine hemodialysis compared to other general popolation, malnutrition is a condition in which the body leses muscle and visceral protein reserves. Albumin levels and body mass index in routine hemodialysis patient, in this studi using a cross sectional study with Pearson product momment correlation test. This study used secondary data on routine hemodialysis patients and clinical pathology laboratory at Ulin Hospital Banjarmasin. The research method using random sampling, obtained as many 74 subjects with subject distribution of 92 peeople. The results of study obtained correlation value of albumin levels and body mass index with a value of p =0.7 and a value of r = -0.030

A standardized pathology report for gastric cancer: 2nd edition.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

A Standardized Pathology Report for Gastric Cancer: 2nd Edition.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

Deep learning based registration of serial whole-slide histopathology images in different stains

For routine pathology diagnosis and imaging-based biomedical research, Whole-slide image (WSI) analyses have been largely limited to a 2D tissue image space. For a more definitive tissue representation to support fine-resolution spatial and integrative analyses, it is critical to extend such tissue-based investigations to a 3D tissue space with spatially aligned serial tissue WSIs in different stains, such as Hematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) biomarkers. However, such WSI registration is technically challenged by the overwhelming image scale, the complex histology structure change, and the significant difference in tissue appearances in different stains. The goal of this study is to register serial sections from multi-stain histopathology whole-slide image blocks. We propose a novel translation-based deep learning registration network CGNReg that spatially aligns serial WSIs stained in H&E and by IHC biomarkers without prior deformation information for the model training. First, synthetic IHC images are produced from H&E slides through a robust image synthesis algorithm. Next, the synthetic and the real IHC images are registered through a Fully Convolutional Network with multi-scaled deformable vector fields and a joint loss optimization. We perform the registration at the full image resolution, retaining the tissue details in the results. Evaluated with a dataset of 76 breast cancer patients with 1 H&E and 2 IHC serial WSIs for each patient, CGNReg presents promising performance as compared with multiple state-of-the-art systems in our evaluation. Our results suggest that CGNReg can produce promising registration results with serial WSIs in different stains, enabling integrative 3D tissue-based biomedical investigations.

News in the classification of WHO 2022 bladder tumors.

The fifth-edition of World Health Organization (WHO) Classification of Tumors series for urinary and male genital tract tumors has been published, six years later the fourth-edition. In these years, new treatment approaches have been implemented and new molecular data on urological cancers are known. Morphology remains the groundwork for taxonomy of the urinary tract tumors. However, a molecular approach to classification of urothelial carcinomas and the management of selected neoplasms with new therapeutic modalities such as immunotherapy are emerging. More data are needed for the application of these advances in routine pathology practice and patient management. The 2022 World Health Organization (WHO) Classification of Tumors of the Urinary System and Male Genital Organs represents an update in classification on urinary tract tumors. It also offers new insights with regards to the grading of heterogeneous non-invasive urothelial neoplasms, the definition of inverted neoplasms, the grading of invasive urothelial carcinomas, the diversity of morphological appearance of urothelial carcinomas, the definition of precursor lesions and the lineage of differentiation of the tumors.

Development of Tier 2 LC-MRM-MS protein quantification methods for liquid biopsies

In the pursuit of personalized diagnostics and tailored treatments, quantitative protein tests contribute to a more precise definition of health and disease. The development of new quantitative protein tests should be driven by an unmet clinical need and performed in a collaborative effort that involves all stakeholders. With regard to the analytical part, mass spectrometry (MS)-based platforms are an excellent tool for quantification of specific proteins in body fluids, for example focused on cancer. The obtained readouts have great potential in determining tumor aggressiveness to facilitate treatment decisions, and can furthermore be used to monitor patient response. Internationally standardized TNM classifications of malignant tumors are beneficial for diagnosis, however treatment outcome and survival of cancer patients is poorly predicted. To this end, the importance of the tumor microenvironment has endorsed the introduction of the tumor-stroma ratio as a prognostic parameter in solid primary tumor types. Currently, the stromal content of tumor tissues is determined via routine diagnostic pathology slides. With the development of liquid chromatography (LC)-MS methods we aim at quantification of tumor-stroma specific proteins in body fluids. In this mini-review the analytical aspect of this developmental trajectory is further detailed.

Nerve Fiber Immunohistochemical Panel Discriminates between Nerve Sheath and Perivascular Wall Tumors.

Benign and malignant nerve sheath tumors (NST) pose a major challenge in routine diagnostic anatomic pathology because of shared histomorphological features with other soft-tissue tumors (STT). As a result, NST are often diagnosed as STT, a broad category that encompasses various entities including perivascular wall tumors (PWT) and that represents approximately 15% of all skin tumors in dogs. Immunohistochemistry (IHC) can assist the identification of histologic subtypes of STT. This IHC pilot study applies various markers largely expressed by peripheral nerves to twelve benign and six malignant NST and determines the intratumoral protein expression of laminin, periaxin-1, Sox-10 and S-100 in the NST subtypes. Furthermore, this study assesses the usefulness of peripheral nerve markers applied to diagnostic work cases and demonstrates the relevance of laminin expression patterns, periaxin-1 and Sox-10 in assisting the differentiation of NST from other STT, in particular from PWT.

Artificial intelligence for basal cell carcinoma: diagnosis and distinction from histological mimics

We trained an artificial intelligence (AI) algorithm to identify basal cell carcinoma (BCC), and to distinguish BCC from histological mimics. A total of 1061 glass slides were collected: 616 containing BCC and 445 without BCC. BCC slides were collected prospectively, reflecting the range of specimen types and morphological variety encountered in routine pathology practice. Benign and malignant histological mimics of BCC were selected prospectively and retrospectively, including cases considered diagnostically challenging for pathologists. Glass slides were digitally scanned to create a whole slide image (WSI), which was divided into patches representing a tissue area of 65,535 μm2. Pathologists annotated the data, yielding 87,205 patches labelled BCC present and 1,688,697 patches labelled BCC absent. The COMPASS model (COntext-aware Multi-scale tool for Pathologists Assessing SlideS) based on Convolutional Neural Networks, was trained to provide a probability of BCC being present at the patch level and the slide level. The test set comprised 246 slides, 147 of which contained BCC. The COMPASS AI model demonstrated high accuracy, classifying WSIs as containing BCC with a sensitivity of 98.0% and a specificity of 97.0%, representing 240 WSIs classified correctly, three false positives, and three false negatives. Using BCC as a proof of concept, we demonstrate how AI can account for morphological variation within an entity, and accurately distinguish from histologically similar entities. Our study highlights the potential for AI in routine pathology practice.

Artificial intelligence in breast cancer histopathology.

This is a review on the use of artificial intelligence for digital breast pathology. A systematic search on PubMed was conducted, identifying 17,324 research papers related to breast cancer pathology. Following a semimanual screening, 664 papers were retrieved and pursued. The papers are grouped into six major tasks performed by pathologists-namely, molecular and hormonal analysis, grading, mitotic figure counting, ki-67 indexing, tumour-infiltrating lymphocyte assessment, and lymph node metastases identification. Under each task, open-source datasets for research to build artificial intelligence (AI) tools are also listed. Many AI tools showed promise and demonstrated feasibility in the automation of routine pathology investigations. We expect continued growth of AI in this field as new algorithms mature.

Utility of anti-Mycobacterium tuberculosis antibody (ab905) for detection of mycobacterial antigens in formalin-fixed paraffin-embedded tissues from clinically and histologically suggestive extrapulmonary tuberculosis cases

BackgroundThe detection of acid-fast bacilli in extrapulmonary tissue samples is challenging due to its paucibacillary nature. The present study assessed the utility of immunohistochemistry (IHC) using anti-Mycobacterium tuberculosis antibody (ab905) for detecting the presence of mycobacterial antigens in archived formalin-fixed paraffin-embedded (FFPE) tissues. MethodsFFPE tissues [surgical biopsies (n = 32) and post-mortem tissues (n = 8)] from clinically and histologically suggestive extrapulmonary tuberculosis (EPTB) cases at the Korle Bu Teaching Hospital, Accra, Ghana from 2015 to 2020 were stained with IHC (anti-Mycobacterium tuberculosis antibody) and Ziehl-Neelsen (ZN) stain. The staining outcomes of IHC and ZN were compared, and their sensitivity and specificity determined against histopathology as reference standard. ResultsLymph nodes were about 40% (16/40) of the samples analyzed. IHC stained positive in 43.8% (7/16) biopsies and 87.5% (4/5) post-mortem samples ranging from 43.8% (7/16) in lymph nodes to 80% (4/5) in gastrointestinal organs. The overall sensitivity for IHC was 52.50% (95% CI: 36.13%–68.49%) and 0% (95% CI: 0.00%–8.81%) for ZN. Specificity was 72.50% (95% CI: 56.11%–85.40%) and 75% (95% CI: 58.80–87.31%) for IHC and ZN respectively. ConclusionsIHC using anti-Mycobacterium tuberculosis antibody (ab905) can detect mycobacterial antigens in diverse range of paucibacillary extrapulmonary tissue sections. It is potentially a useful tool for the diagnosis of EPTB in FFPE tissues in a routine pathology laboratory.