Gastric tuberculosis. Endoscopic cytology as a diagnostic tool

OBJECTIVE: To highlight the utility of endoscopic brush smears in the diagnosis of gastric tuberculosis in clinically unsuspected cases. STUDY DESIGN: A retrospective analysis of endoscopic brush smears from 210 patients with gastric symptoms. In seven of these patients (3.3%) the possibility of gastric tuberculosis was suggested in Giemsa-stained smears. Biopsy was available in all cases. Ziehl-Neelsen stain to demonstrate tubercle bacilli was used in brush smears and biopsies in seven and three cases, respectively. RESULTS: Endoscopically the sites involved were antrum (two), pylorus (two), pylorus and duodenum (three). One patient had an ulcerative lesion, and six had growths. Granulomas and/or epithelioid cells were seen in brush smears in all cases. Tubercle bacilli could be demonstrated in cytologic smears in four cases. Endoscopic biopsy showed granulomas in five cases and non-specific gastritis in two. Tubercle bacilli could not be demonstrated in any of the biopsy sections. On further clinicoradiologic investigation, two patients were found to be follow-up cases of pulmonary and nodal tuberculosis. Enzyme-linked immunosorbent assay for HIV, done in three cases, was negative. A final diagnosis of primary gastric tuberculosis in five patients and secondary in two was considered. Six patients responded to antituberculosis treatment and showed healing of the lesions on repeat endoscopy after six months of therapy, while one was a recent case with four weeks' follow-up. CONCLUSION: Endoscopic brush cytology is a reliable modality for the diagnosis of gastric tuberculosis.     

Circulating nucleic acids as a new diagnostic tool

The discovery of circulating nucleic acids in the 1940s opened up new possibilities for the non-invasive detection, monitoring and screening of various human disorders. Several tumour markers that enable early cancer detection or tumour behaviour prediction have been detected in the plasma of cancer patients. Maternal plasma analysis can be used to detect certain fetal abnormalities, with the quantification of cell-free nucleic acids used to screen for several pregnancy-associated disorders. Some other applications are in transplant monitoring and graft rejection assessment, and in certain medical emergencies such as trauma and burn severity stratification. Many studies have yielded promising results in this field, but the techniques have yet to be applied in routine clinical practice. Large-scale studies using similar technologies and a broad spectrum of patients are still needed to verify the results of the various studies.     

Tubercular dactylitis: Fine needle aspiration cytology as a diagnostic modality

OBJECTIVE: To evaluate the efficacy of aspiration cytology in the early diagnosis of tuberculous dactylitis and describe the spectrum of cytomorphologic features in these cases. STUDY DESIGN: We studied 12 cases of dactylitis diagnosed as of tubercular etiology by fine needle aspiration cytology (FNAC) over a period of 6 years and assessed the clinicoradiologic features. The stained slides were reviewed and the spectrum of features noted. RESULTS: The most common clinical presentation was an indurated swelling of the involved digit (100%). On radiography, most often an expansile, lytic lesion along with soft tissue swelling was noted in 83% of cases. However, the clinical diagnosis did not consider a tubercular (TB) etiology. FNAC of these cases showed variable features; the most common was granulomas with or without necrosis (75% in total). Two cases showed acute suppurative cytology, and 1 revealed only fibroblasts and afew neutrophils. On the basis of suspicion, staining for acid-fast bacilli (AFB) was done in all cases, and bacilli were identified in all of them after a thorough search. These patients were soon started on antituberculous therapy, with significant improvements. CONCLUSION: FNAC can serve as an inexpensive and comparatively less invasive procedure for early diagnosis of TB dactylitis, permitting timely initiation of specific therapy. This study also highlighted the unusual cytomorphology in some cases. Clinicians and pathologists should maintain a high index of suspicion in cases of dactylitis and stain for AFB in all cases.     

Segmental motion of forefoot and hindfoot as a diagnostic tool

Segmental motions derived from non-invasive motion analysis are being used to investigate the intrinsic functional behavior of the foot and ankle in health and disease. The goal of this research was to examine the ability of a generic segmented model of the foot to capture and differentiate changes in internal skeletal kinematics due to neuromuscular disease and/or trauma. A robotic apparatus that reproduces the kinematics and kinetics of gait in cadaver lower extremities was employed to produce motion under normal and aberrant neuromuscular activation patterns of tibialis posterior and/or tibialis anterior. Stance phase simulations were conducted on 10 donor limbs while recording three-dimensional kinematic trajectories of (1) skin-mounted markers used clinically to construct segmented foot models, and (2) bone-mounted marker clusters to capture actual internal bone motion as the gold standard for comparison. The models constructed from external marker data were able to differentiate the kinematic behaviors elicited by different neuromuscular conditions in a manner similar to that using the bone-derived data. Measurable differences between internal and externally measured kinematics were small, variable and random across the three axes of rotation and neuromuscular conditions, with a tendency toward more differences noted during early and late stance. Albeit slightly different, three-dimensional motion profiles of the hindfoot and forefoot segments correlated well with internal skeletal motion under all neuromuscular conditions, thereby confirming the utility of measuring segmental motions as a valid means of clinical assessment.     

Effectiveness of the Quick Medical Reference as a diagnostic tool

A number of computer-based systems with diagnostic capabilities have been developed for internal medicine. Quick Medical Reference (QMR) is one such program. The authors describe key features of QMR and report on their study of its effectiveness as a diagnostic tool. They investigated how frequently the correct diagnosis would appear among the 5 highest ranked diagnoses generated by QMR. The charts of 1144 consecutive patients admitted to a teaching unit were retrospectively screened. Eligible cases included those referred for investigation of an undiagnosed illness with an objectively proven final diagnosis (n = 154). Two physicians familiar with, but not experts in, the use of QMR entered clinical information abstracted from the patients'' charts into the program. Physician A obtained the correct diagnosis in 62 (40%) of the 154 cases, and physician B was successful in 56 (36%) of the cases. The authors use study cases to illustrate QMR''s strengths and weaknesses.     

Metagenomic next-generation sequencing as a diagnostic tool for toxoplasmic encephalitis

Background

More than 100 different pathogens can cause encephalitis. Testing of all the neurological pathogens by conventional methods can be difficult. Metagenomic next-generation sequencing (NGS) could identify the infectious agents in a target-independent manner. The role of this novel method in clinical diagnostic microbiology still needs to be evaluated. In present study, we used metagenomic NGS to search for an infectious etiology in a human immunodeficiency virus (HIV)-infected patient with lethally diffuse brain lesions. Sequences mapping to Toxoplasma gondii were unexpectedly detected.

Case presentation

A 31-year-old HIV-infected patient presented to hospital in a critical ill condition with a Glasgow coma scale score of 3. Brain magnetic resonance imaging showed diffuse brain abnormalities with contrast enhancement. Metagenomic NGS was performed on DNA extract from 300 μL patient’s cerebrospinal fluid (CSF) with the BGISEQ-50 platform. The sequencing detection identified 65,357 sequence reads uniquely aligned to the Toxoplasma gondii genome. Presence of Toxoplasma gondii genome in CSF was further verified by Toxoplasma gondii-specific polymerase chain reaction and Sanger sequencing. Altogether, those results confirmed the diagnosis of toxoplasmic encephalitis.

Conclusions

This study suggests that metagenomic NGS may be a useful diagnostic tool for toxoplasmic encephalitis. As metagenomic NGS is able to identify all pathogens in a single run, it may be a promising strategy to explore the clinical causative pathogens in central nervous system infections with atypical features.

     

Imprint cytology of vacuum-assisted breast biopsy specimens: a rapid diagnostic tool in non-palpable solid lesions

Objective:  Imprint cytology provides a rapid preliminary diagnosis shortly after the completion of breast biopsy. This study aims to assess the validity of imprint cytology for the pre-operative diagnosis of non-palpable mammographic solid lesions excised by vacuum-assisted breast biopsy (VABB).
Methods:  Seventy-two women with non-palpable Breast Imaging Reporting and Data System 3 and 4 mammographic solid lesions without microcalcifications underwent VABB on the stereotactic Fischer's table with 11-G Mammotome vacuum probes. Imprint samples were examined (Diff-Quick stain, modified Papanicolaou stain and May-Grünwald–Giemsa). The cores were dipped into a CytoRich Red Collection fluid for a few seconds in order to obtain samples with the use of the specimen wash. After the completion of cytological procedures, the core was prepared for routine pathological study. The pathologist was blind to the preliminary cytological results. The cytological and pathological diagnoses were comparatively evaluated.
Results:  The sensitivity of the cytological imprints for cancer was 90%. The specificity of the method for cancer diagnosis was 100%. Two precursor lesions were present in the material: one case of atypical ductal hyperplasia, which was successfully detected, and one case of lobular neoplasia, which escaped detection. The cytological imprints were inadequate in four out of 72 cases (5.6%), but none of them were included within the malignant subgroup.
Conclusions:  Imprint cytology seems to be an important adjunctive tool in the management of patients with non-palpable mammographic solid lesions. Its very satisfactory sensitivity and optimal specificity could establish its use in general clinical practice.     

Efficacy and pattern of use of sputum cytology as a diagnostic test

Sputum cytology is regarded by many clinicians as a noninvasive, cheap and simple test for the diagnosis of bronchogenic carcinoma. Since the introduction of fibre-optic bronchoscopy and more easily obtained bronchial biopsies reliance on sputum cytology has diminished. However, in Edinburgh it was perceived that sputum samples were still being sent as well as, rather than instead of, bronchoscopic specimens. This retrospective study was undertaken to determine whether or not cytological examination of sputum is an efficient and sensitive test in the investigation of patients with suspected bronchogenic carcinoma. It demonstrated that the Lothian University Hospitals NHS Trust Pathology Directorate receives many sputa from departments not specializing in respiratory disease when there is no indication for the test. In addition, we have shown that the absolute sensitivity of the test is only 5% and that when there is a strong clinical suspicion of bronchogenic carcinoma the results of sputum cytology do not play a significant role in the management of the patient. We recommend that sputum cytology is restricted to those patients under the care of Respiratory Units in whom bronchoscopy is inappropriate or unsuccessful.     

Medical image processing as a necessary tool for a medical diagnostic process

The authors provide a rationale for mathematically processing medical images for the progression of a medical diagnostic process. The tools made by the real-time conveyor 2D processing and visualization technology are proposed for work with medical images. The results of conveyor 2D processing of medical images as graphical presentations are given.     

Pilomatrixoma as a diagnostic pitfall in fine needle aspiration cytology: a case report

BACKGROUND: Pilomatrixoma (pilomatrixoma, calcifying epithelioma of Malherbe) is a relatively uncommon, benign neoplasm arising from the skin adnexa. The tumor can cause diagnostic difficulty not only for the clinician but also for the cytologist. CASE: A 62-year-old woman presented with a right submandibular swelling of 4 months' duration. The clinical findings were highly suspicious for malignancy. A fine needle aspiration biopsy was performed. Three preliminary differential diagnoses were offered: mucoepidermoid carcinoma of the submandibular salivary gland, squamous cell carcinomatous deposit in a submandibular lymph node and calcifying odontogenic tumor. Computed tomography demonstrated no bony lesion. No primary site of squamous cell carcinoma could be identified. An excisional biopsy of the swelling was performed, and the histologic diagnosis of pilomatrixoma was made. CONCLUSION: The cytologic presentation of pilomatrixoma of the right submandibular region can masquerade as that of a malignant tumor, in this case mucoepidermoid carcinoma, squamous cell carcinoma or odontogenic tumor. This case delineates the cytomorphologic features of pilomatrixoma that may mimic carcinoma.     

Minimalist protein model as a diagnostic tool for misfolding and aggregation

We propose a realistic coarse-grained protein model and a technique to "anchor" the model to available experimental data. We apply this procedure to characterize the effect of multiple mutations on the folding mechanism of protein S6. We show that the mutation of a few "gatekeeper" residues triggers significant changes on the folding landscape of S6. These results suggest that gatekeeper residues control the flexibility of critical regions of S6, that in turn regulates the delicate balance between folding and aggregation. Although obtained with a minimalist protein model, these results are fully consistent with experimental evidence and offer a clue to understand the interplay between folding and aggregation in protein S6.     

Periodic assessment of urine and serum by cytology and molecular biology as a diagnostic tool for BK virus nephropathy in renal transplant patients

OBJECTIVE: To investigate the significance of polyomavirus (PV) viruria and viremia by morphologic, immunohistochemical and molecular analysis (multiplex nested-polymerase chain reaction) in renal transplant patients. STUDY DESIGN: Urine (n=328), serum (n= 53) and renal biopsies (n=24) from renal transplant patients (n=106) were studied. RESULTS: Decoy cells were found in 53 samples (16%) from 19 patients (18%); viral DNA was amplified in all urinary samples and disclosed BK virus (BKV) (n=24), JC virus (JCV) (n=16), and JCV and BKV DNA (n=13). BKV was the prevailing genotype in patients with a high frequency of decoy cell excretion (p = 0.001). JCV excretion correlated with a low number (p = 0.01) and BKV with a high number of decoy cells (p=0.003). PV DNA was amplified from 30/53 serum samples (56.6%); BKV was the prevailing genotype (p = 0.04). On 24 renal biopsies (18 from the decoy cell-negative and 6 from the decoy cell-positive group) PV nephropathy (PVN) was identified and BKV DNA amplified in 4 biopsies, all from the group with a high frequency of decoy cell excretion. PVN was not identified in renal biopsies from the decoy cell-negative group. CONCLUSION: PV infection is frequent in renal transplant patients. The BKV genotype in urine and serum is significantly related to a high frequency and high number of decoy cells. PVN occurs only in patients with BKV viremia and a high number and frequency of decoy cell excretion in urine. In the absence of decoy cells, PVN can be excluded. Cytologic analysis of urine is an important diagnostic tool for screening renal transplant patients at risk of PVN.     

A new diagnostic tool for rapid and accurate detection of Mycobacterium tuberculosis

Mycobacterium tuberculosis, acid fast bacilli from the family of Mycobacteriaceae, is the causative agent of most cases of tuberculosis. Tuberculosis, as a communicable disease, remains a serious public health threat, killing more than one million people globally every year. Primary diagnosis of tuberculosis bacilli (TB) relies mainly on microscopic detection of acid fast bacilli (AFB), but the method suffers from low sensitivity and the results largely depend on the technician’s skill. New diagnostic tools are necessary to be introduced for rapid and accurate detection of the bacilli in sputum samples. We, in collaboration with Anda Biologicals, have developed a new platform, named as “Patho-tb”, for rapid detection of AFB with high sensitivity and with low dependence on human skills. Evaluation of Patho-tb test performance was done in two settings: (1) primary field study conducted using 38 sputa from high TB prevalence area of Iran (Zabol city near to the Afghanistan border), and (2) main study conducted using 476 sputa from Tehran, capital of Iran. Patho-tb was applied for processed sputum samples in parallel with routine diagnostic methods (including AFB microscopy, culture and PCR). All test results were compared to final clinical diagnostic state of an individual and diagnostic sensitivity (DSe), specificity, positive predictive value, negative predictive value and accuracy of each test results were calculated using standard formulations. Analytical sensitivity and specificity of the Patho-tb test were also determined. Calculated values for five above mentioned parameters are as follows: for field study: AFB (DSe: 29.6, DSp: 81.8, PPV: 80, NPV: 23.1, AC: 44.7), Patho-tb (DSe: 63, DSp: 72.7, PPV: 85, NPV: 44.4, AC: 65.8), and for main study: AFB (DSe: 86.1, DSp: 99.4, PPV: 98.5, NPV: 93.9, AC: 95.2), Patho-tb (DSe: 97.4, DSp: 92.9, PPV: 86.5, NPV: 98.7, AC: 94.3). Reproducibility of Patho-tb test results were near to 100% (Cohen’s kappa value between 0.85 and 1). The detection limit of Patho-tb test with 100% positivity rate was 3 × 10³ cells/ml of sputum. In the field study, Patho-tb test was 33.4% more sensitive than AFB microscopy, while the improvement was only 11.3% during the main study. Patho-tb results are easy to interpret and the test can be merged with other screening tests, like AFB. Totally, Patho-tb test alone or in conjunction with AFB microscopy is a useful screening tool for TB detection especially in poor geographical lab conditions.     

Protein S-100 immunostaining as a diagnostic tool for DMBA-induced melanotic lesions

In the present study we demonstrate immunohistochemically the presence of S-100 protein in numerous melanotic and amelanotic lesions (benign, premalignant and malignant) induced in albino guinea-pigs on topical application of the carcinogen. Positive staining was also present in all their amelanotic metastases. We reiterate the value of this stain in the diagnosis of melanomas, in particular amelanotic melanomas.     

Esophageal exfoliative cytology samplers. A comparison of three types

OBJECTIVE: To compare three types of esophageal exfoliative cytology samplers in terms of patient acceptability, ease of use, final destination of the sampler tip in the gastrointestinal tract and cellular yield. STUDY DESIGN: A controlled, single-blind, cross-over study was undertaken to compare the balloon, sponge and sponge-mesh samplers in healthy volunteers. After completing the three procedures in random order, participants were asked about their preferred method. Ease of use was defined as the technician's ability to perform the intubation successfully. Final destination of the samplers was assessed fluoroscopically. Cytopathologists determined the cellular yield of each sampler using the Bethesda System. RESULTS: Sixty-two volunteers participated. The two encapsulated samplers were significantly preferred over the balloon (P < .0001). There was no significant difference in ease of use, final destination or cellular yield of the three techniques. All three samplers were successfully intubated on the first attempt and retrieved adequate numbers of squamous and glandular cells in > 78% of cases. CONCLUSION: All three samplers obtained satisfactory yields of squamous and glandular cells, but the encapsulated samplers were more patient acceptable. The sponge-mesh sampler may be the least complicated sampler for field screening use. Larger-scale studies will be required to test the accuracy of these three samplers for detecting esophageal dysplasia and carcinoma.