LITERATURE UPDATE


A new artificial intelligence-based method for identifying Mycobacterium tuberculosis in Ziehl-Neelsen stain on tissue


Zurac S, Mogodici C, Poncu T et al. Diagnostics (Basel) 2022; 12 (6): 1484. doi: 10.3390/diagnostics12061484.


Mycobacteria identification is crucial to diagnose tuberculosis. As the bacillus is very small, finding it in Ziehl-Neelsen (ZN)-stained slides is a long task requiring significant pathologist effort. The authors developed an automated (AI-based) method of identification of mycobacteria. They prepared a training dataset of over 260,000 positive and over 700,000,000 negative patches annotated on scans of 510 whole-slide images (WSI) of ZN-stained slides (110 positive and 400 negative).


Several image augmentation techniques coupled with different custom computer vision architectures were used. Automatic analysis of WSIs was followed by a report indicating areas more likely to present mycobacteria. The model performs AI-based diagnosis (the final decision of the diagnosis of WSI belongs to the pathologist). The results were validated internally on a dataset of 286,000 patches and tested in pathology laboratory settings on 60 ZN slides (23 positive and 37 negative). The authors compared the pathologists’ results obtained by separately evaluating slides and WSIs with the results given by a pathologist aided by automatic analysis of WSIs. The architecture showed 0.977 area under the receiver operating characteristic curve. The clinical test presented 98.33% accuracy, 95.65% sensitivity, and 100% specificity for the AI-assisted method, outperforming any other AI-based proposed methods for AFB detection.


Comparative diagnostic utility of metagenomic next-generation sequencing, GeneXpert, modified Ziehl-Neelsen staining, and culture using cerebrospinal fluid for tuberculous meningitis: A multi-center, retrospective study in China. Chen Y, Wang Y, Liu X et al. J Clin Lab Anal 2022; 36 (4): e24307. doi: 10.1002/ jcla.24307.


Early diagnosis of tuberculosis meningitis (TBM) remains a great challenge during clinical practice. The diagnostic efficacies of cerebrospinal fluid (CSF)-based mycobacterial growth indicator tube (MGIT) culture, modified Ziehl-Neelsen (ZN) staining, Xpert MTB/RIF, and metagenomic next-generation sequencing (mNGS) for TBM remained elusive.


A total of 216 adult patients with suspicious TBM were retrospectively enrolled in this multi-cohort study. The diagnostic performances for MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS using CSF samples were evaluated. Uniform clinical case definition classified 88 (40.7%) out of 216 patients as definite TBM, five (2.3%) patients as probable TBM cases, and 24 (11.1%) patients as possible TBM cases. The sensitivities of MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS for TBM diagnosis against consensus uniform case definition for definite TBM were 25.0%, 76.1%, 73.9% and 84.1%, respectively. Negative predictive values (NPVs) were 66.0%, 85.9%, 84.8% and 90.1%, respectively. The sensitivities of MGIT, modified ZN staining, Xpert MTB/ RIF, and mNGS for TBM diagnosis against consensus uniform case definition for definite, probable, and possible TBM were 18.8%, 57.3%, 55.5% and 63.2%, respectively. Negative predictive values (NPVs) were 51.0%, 66.4%, 65.6% and 69.7%, respectively. mNGS combined with modified ZN stain and Xpert could cover TBM cases against a composite microbiological reference standard, yielding 100% specificity and 100% NPV. Metagenomic next-generation sequencing detected TBM with higher sensitivity than Xpert, ZN staining and MGIT culture, but mNGS cannot be used as a rule-out test. mNGS combined with Xpert or modified ZN staining could enhance the sensitivity of diagnostic tests for TBM.


Clinical performance of mycobacterial immunohistochemistry in anatomic pathology specimens Crothers JW, Laga AC, Solomon IH. Am J Clin Pathol 2021; 155 (1): 97–105. doi: 10.1093/ajcp/aqaa119.


Diagnosis of mycobacterial infections poses significant challenges in anatomic pathology. This study described the use of antimycobacteria immunohistochemistry (IHC) as a sensitive, efficient diagnostic tool and now reports the clinical performance of this assay among general, noninfectious disease pathology-trained anatomic pathologists.


Over a two-year period, all cases


were retrospectively identified in which mycobacterial IHC was performed during routine diagnostic workup. From October 2017 to September 2019, mycobacterial IHC was evaluated for 267 cases, resulting in 58 (22%) positive stains. Compared with culture and molecular results, the sensitivity and specificity of IHC were 52% and 80%,


WWW.PATHOLOGYINPRACTICE.COM SEPTEMBER 2022


Evaluation of polymerase chain reaction in nerve biopsy specimens of patients with Hansen’s disease Tiwari V, Malhotra K, Khan K et al. J Neurol Sci 2017; 380: 187–190. doi: 10.1016/j.jns.2017.07.038.


The pure neuritic variety of leprosy (PNL) presents as peripheral neuropathy with


61


respectively. Immunohistochemistry performed significantly better than acid- fast bacilli (AFB) staining (Ziehl-Neelsen; P<0.0001; sensitivity 21%, specificity 92%) but similarly to modified AFB staining (mAFB, Fite-Faraco; P=0.90; sensitivity 61%, specificity 84%). In cases with discordant IHC and mAFB staining, there were no differences in rates of culture or polymerase chain reaction-confirmed positivity.


Mycobacterial IHC was well adopted with superior clinical performance to AFB and comparable performance to mAFB. These results support the use of IHC as an adjunctive tool in the diagnosis of mycobacterial infections and suggests its potential role as a rapid screening test for molecular testing.


Challenge of a false-positive acid-fast bacilli: a diagnostic conundrum Kumar A, Gupta K. J R Coll Physicians Edinb 2021; 51 (4):369–72. doi: 10.4997/ JRCPE.2021.411.


Infectious and autoimmune diseases are distinct entities that require opposite therapeutic approaches. However, differentiating between the two can be a challenge, especially when the histopathology misguides the clinician. This study highlights the case of a


66-year-old female who presented with fever, shortness of breath and cough for three months’ duration. She had raised inflammatory markers, and imaging revealed bilateral cavitating nodules. Histopathology revealed necrotising granulomatous inflammation along with acid-fast bacilli on Ziehl-Neelsen staining. The patient was diagnosed with tuberculosis and started on anti-tubercular therapy.


When no response was seen, a rheumatologist was consulted, and a suspected diagnosis of granulomatosis with polyangiitis was made on the basis of clinical and laboratory features. Dramatic response to steroids and a negative mycobacteria culture confirmed the diagnosis. The patient responded to a combination of steroids and cyclophosphamide.


This case highlights the importance


of recognising the possibility of a false- positive acid-fast bacilli report.


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64