A research report submitted to the Faculty of Health Sciences, University of Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Medicine in the branch of Diagnostic Radiology Johannesburg 2018. / INTRODUCTION: Tuberculosis (TB) is an important public health issue, but diagnosis in children can be challenging. The radiological hallmark of pulmonary TB (PTB) in children is mediastinal lymphadenopathy, however there is inter-observer variability in detecting this. The value of the lateral CXR in addition to the frontal view to detect lymphadenopathy has not been well studied. OBJECTIVES: To investigate the prevalence of lymphadenopathy in children with confirmed PTB detected on frontal compared to frontal-lateral CXRs. METHODS: This was a secondary analysis of a study from Red Cross Children’s Hospital in Cape Town. Children with definite TB and a control group (Lower respiratory tract infection other than TB) who had frontal and lateral CXRs were included in this study. Three radiologists independently read the CXRs in 2 separate sittings (frontal CXR and ‘combination frontallateral’ CXR). A 3 reader consensus reading was used during data analysis. Odds ratios and 95% confidence intervals were calculated to determine the presence of lymphadenopathy. Kappa statistics were calculated to determine inter reader agreement. RESULTS: Of 172 children (88 confirmed TB and 84 control children), with a median age of 29 months, lymphadenopathy was reported in 86 (50%) patients on the frontal CXR alone and in 143 (83%) on the frontal-lateral CXR combination, p= 0.00. Amongst confirmed PTB cases, 52 (60%) had lymphadenopathy on the frontal CXR alone while 72 (82%) had lymphadenopathy on the frontal-lateral CXR combination, p= 0.00. Amongst the control group, 34 (40%) had lymphadenopathy on the frontal CXR alone while 71 (85%) had lymphadenopathy on the frontal-lateral CXR combination, p= 0.00. The consensus reading using a frontal-lateral CXR combination resulted in a 5 fold increase (OR 4,9; 95% CI 2,9-8,4) in diagnosis of lymphadenopathy compared to a frontal CXR only. Overall inter reader agreement for all 3 readers was fair on both the frontal CXR (Kappa= 0,21) and the frontal-lateral CXR (Kappa= 0,23) combination. CONCLUSION: The addition of a lateral view to the frontal CXR increased detection of lymphadenopathy, however, the prevalence of lymphadenopathy was similar in children with PTB and those in the control group, with fair inter reader agreement. / LG2018

Histoplasmosis involving mediastinum is very rare which can present as a mediastinal mass or fibrosing mediastinitis. Fibrosing mediastinitis can be life-threatening if left untreated due to the involvement of the surrounding visceral and vascular structures. We present an interesting case of fibrosing mediastinitis due to histoplasmosis presented with palpitations, chest pain and dyspnea. The patient had mediastinal and hilar lymphadenopathy with calcification on chest imaging. The patient was diagnosed on lymph node biopsy and treated with antifungals.

A research report submitted to the Faculty of Health Sciences, University of Witwatersrand, in fulfillment of the requirements for the degree of Master of Medicine in the branch of Internal Medicine Johannesburg, 2015 / Lymphadenopathy is a common clinical presentation of disease in South Africa (SA), particularly in the era of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) coinfection. Methods Data from 560 lymph node biopsy reports of specimens from patients older than 12 years at Chris Hani Baragwanath Academic Hospital (CHBAH) between 1 January 2010 and 31 December 2012 was extracted from the National Health Laboratory Service (NHLS), division of Anatomical Pathology. Cytology reports of lymph node fine needle aspirates (FNAs) performed prior to lymph node biopsy in 203 patients were also extracted from the NHLS. Consent was not obtained from participants for their records to be used as patient information was anonymized and de-identified prior to analysis. Results The majority of patients were female (55%) and of the African/black racial group (90%). The median age of patients was 40 years (range12-94). The most common indication for biopsy was an uncertain diagnosis (more than two differential diagnoses entertained), followed by a suspicion for lymphoma, carcinoma and TB. Overall, malignancy constituted the largest biopsy pathology group (39%), with 36% of this group being carcinoma and 27% non-Hodgkin lymphoma. 22% of the total sampled nodes displayed necrotizing granulomatous inflammation (including histopathology and cytology demonstrating definite, and suspicious for mycobacterial infection), 8% comprised HIV reactive nodes; in the remainder no specific pathology was identified (nonspecific reactive lymphoid hyperplasia). Kaposi sarcoma (KS) accounted for 3% of lymph node pathology in this sample. Concomitant lymph node pathology was diagnosed in four cases of nodal KS (29% of the subset). The co-existing pathologies were TB and Castleman disease. HIV-positive patients constituted 49% of this study sample and the majority (64%) of this subset had CD4 counts less than 350 cells/ul. 27% were HIVnegative and in the remaining nodes, the HIV status of patients was unknown. The most common lymph node pathologies in HIV-positive patients were Mycobacterial infection (31%), HIV reactive nodes (15%), non-Hodgkin lymphoma (15%) and nonspecific reactive lymphoid hyperplasia (15%). Only 9% were of Hodgkin lymphoma. In contrast, the most common lymph node pathologies in HIV-negative patients were nonspecific reactive lymphoid hyperplasia (45%), carcinoma (25%) and Mycobacterial infection (11%). In this group, non-Hodgkin lymphoma and Hodgkin lymphoma constituted 9% and 8%, respectively. There were more cases of high-grade non-Hodgkin lymphoma in the HIV-positive group compared to the HIV-negative group. FNA and lymph node biopsy had excellent agreement with regard to Hodgkin lymphoma (K 0.774, SE 0.07, 95% CI 0.606-0.882, p=0.001), and good agreement with regard to non-Hodgkin lymphoma (K 0.640, SE 0.07, 95% CI 0.472-0.807, p=0.001), carcinoma (K 0.723, SE 0.069, 95% CI 0.528-0.918, p=0.001), and mycobacterial infection (K 0.726, SE 0.07, 95% CI 0.618-0.833, p=0.001). Conclusions The most common lymph node pathologies in CHBAH are malignancies, nonspecific reactive lymphoid hyperplasia, necrotizing granulomatous inflammation and HIV reactive nodes. The distribution of disease differed in HIV-positive patients. Overall, adequate FNA samples of lymph nodes have been found to have good correlation with lymph node biopsy findings in our setting.

Histoplasmosis is an endemic infection of the Ohio and Mississippi River valleys. Clinical presentation of infection in immunocompetent hosts ranges from asymptomatic to minor flu-like symptoms; however, disseminated infection can occur in immunocompromised patients. Esophageal involvement in the form of dysphagia secondary to mediastinal histoplasmosis is rarely reported in the literature. We present a young female who complained of dysphagia and was found to have an esophageal stricture on barium esophagogram. Endoscopy revealed a submucosal nodule stricture situated 29 cm from the incisors. She underwent thoracotomy for lymph node removal. Histologic findings of the removed lymph node showed caseating granuloma with macrophages. The clinical findings together with the laboratory evaluation and biopsy features were suggestive of mediastinal histoplasmosis as the cause of the dysphagia.

Histoplasmosis is an endemic infection of the Ohio and Mississippi River valleys. Clinical presentation of infection in immunocompetent hosts ranges from asymptomatic to minor flu-like symptoms; however, disseminated infection can occur in immunocompromised patients. Esophageal involvement in the form of dysphagia secondary to mediastinal histoplasmosis is rarely reported in the literature. We present a young female who complained of dysphagia and was found to have an esophageal stricture on barium esophagogram. Endoscopy revealed a submucosal nodule stricture situated 29 cm from the incisors. She underwent thoracotomy for lymph node removal. Histologic findings of the removed lymph node showed caseating granuloma with macrophages. The clinical findings together with the laboratory evaluation and biopsy features were suggestive of mediastinal histoplasmosis as the cause of the dysphagia.

Thesis (PhD (Pathology. Anatomical Pathology))--University of Stellenbosch, 2009. / Dissertation presented for a PhD degree in anatomical pathology at Stellenbosch University. / ENGLISH ABSTRACT: Expediting a diagnosis of tuberculosis in children, particularly those who are immunocompromised due to HIV/AIDS, is essential, as they are vulnerable to develop severe forms of disease due to their immature or compromised immune systems. A significant percentage of children (8 to 10%) with TB have TB lymphadenitis, in isolation, or in combination with other disease manifestations. Fine needle aspiration biopsy (FNAB) is a simple and minimally invasive procedure well tolerated by children. It may be performed as an outpatient procedure by clinicians as well as nurses, and excellent results can be achieved with training in the correct procedure. The aim of this dissertation was to demonstrate that FNAB may contribute significantly to the diagnosis of mycobacterial lymphadenitis, with particular reference to children TB suspects. We first established that TB lymphadenitis is a common clinical problem in children in TB endemic areas and that FNAB is an efficient simple and effective diagnostic modality in children with peripheral lymphadenopathy. We then proceeded to document the diagnostic yield and time to diagnosis of FNAB compared to conventional laboratory specimens collected in children. We investigated the value of additional diagnostic modalities such as autofluorescence in improving the ability of cytology to make a definitive diagnosis of mycobacterial infection based on cytomorphology and identification of the organism. In countries where organisms such as Mycobacterium bovis BCG and nontuberculous mycobacteria are prevalent, culture with subsequent speciation is essential. The amount of material harvested during FNAB is minuscule, and requires immediate bedside inoculation for optimal yields. We developed an inexpensive and effective transport medium to facilitate mycobacterial culture from FNAB, even if this is collected at an outside facility. It is ideally suited for use in clinics and rural hospitals as it is stable at room temperature, maintains viability of the organism for seven days, and the closed lid format reduces contamination. Mycobacterial culture even using liquid-based media, takes up to 6 weeks, and this delay is unacceptable particularly in children. We developed a Nucleic Acid Amplification Technique (NAAT) using High Resolution Melt Analysis and applied this novel technique to FNAB specimens submitted in transport medium. Although sensitivity remained suboptimal, the technique is highly specific, simple and rapid. Its use could be incorporated into routine microbiology laboratories, to assist with rapid diagnosis while cultures are pending. We collected a solid body of evidence, which will promote the use of FNAB in suspected mycobacterial lymphadenopathy, particularly in children in resource-limited countries. The utilisation of the diagnostic methods identified will expedite speciation and allow early and appropriate initiation of therapy. This is in keeping with Millennium Development Goal 6: to combat TB by early detection of new cases and effective treatment. / AFRIKAANSE OPSOMMING: Kinders met tuberkulose (TB), en veral diegene met gekompromiteerde immuniteit as gevolg van MIV/VIGS, het ‘n verhoogde neiging om ernstige siektebeelde te ontwikkel vanweë hul onvolwasse of gekompromiteerde immuunsisteme. ‘n Spoedige diagnose van TB in kinders is dus noodsaaklik. ‘n Betekenisvolle persentasie van kinders (8 tot 10%) met TB het TB limfadenitis met of sonder meegaande ander siekteverskynsels. Fynnaaldaspirasiebiopsie (FNAB) is ‘n eenvoudige en minimale indringende prosedure wat geredelik deur kinders aanvaar word. Geneeshere en verpleegkundiges wie toepaslike opleiding in die uitvoering van FNAB ontvang het, kan die prosedure op buitepasiënte uitvoer en uitstekende resultate behaal. Die doel van hierdie studie was om aan te toon dat FNAB betekenisvol kan bydra tot die diagnose van mikobakteriële limfadenitis in veral kinders met vermoedelike TB. Daar was eerstens bevestig dat TB limfadenitis ‘n algemene kliniese probleem is in kinders in TB endemiese areas en dat FNAB ‘n doeltreffende, eenvoudige en effektiewe diagnostiese modaliteit is in kinders met perifere limfadenopatie. Vervolgens was FNAB se diagnostiese opbrengs en die tydsverloop tot diagnose vergelyk met dié van konvensionele laboratoriummonsters wat in kinders verkry word. Die bydrae van verdere diagnostiese modaliteite soos outofluoressensie tot ‘n verbetering in sitologie se rol in die diagnose van mikobakteriële infeksie, soos gebaseer op sitomorfologie en identifisering van organismes, is ondersoek. In lande waar organismes soos Mycobacterium bovis BCG en nie-tuberkuleuse mikobakterië heersend is, is kultuur en spesiebepaling noodsaaklik. Die hoeveelheid materiaal wat met FNAB verkry word is baie min en vereis onmiddellike okulasie vir die beste resultate. Tydens hierdie studie is ‘n goedkoop en effektiewe vervoermedium ontwikkel om mikobakteriële kultuur van FNAB verkreë monsters te fasiliteer, selfs al is die monster vanaf ‘n buite fasiliteit bekom. Die vervoermedium is baie geskik vir gebruik in klinieke en plattelandse hospitale. Dit is stabiel by kamertemperatuur, handhaaf lewensvatbaarheid van organismes vir sewe dae, en die geslote dekselformaat verminder kontaminasie. Mikobakteriële kultuur neem tot ses weke, selfs met die gebruik van vloeistofgebaseerde mediums. Sodanige vertraging in die diagnose is veral in kinders onaanvaarbaar. Tydens hierdie studie is ‘n Nukleïnsuur Amplifikasietegniek ontwikkel deur die aanwending van Hoë Resolusie Smeltanalise en is hierdie nuwe tegniek toegepas op FNAB verkreë monsters wat in die vermelde vervoermedium versamel was. Alhoewel sensitiwiteit nie optimaal was nie, is die tegniek baie spesifiek, eenvoudig en vinnig. Dit kan in roetine mikrobiologie laboratoriums gebruik word om vinnige diagnose te bewerkstellig terwyl daar gewag word vir die kultuur se resultaat. Hierdie studie bied omvattende bewys ter ondersteuning van die gebruik van FNAB in veral kinders met vermoedelike mikobakteriële limfadenopatie in lande met beperkte hulpbronne. Die toepassing van die diagnostiese metodes wat in hierdie studie identifiseer is sal spesiebepaling bespoedig en vroegtydige en toepaslike behandeling verseker. Dit stem ooreen met Millennium Ontwikkelingsdoelwit 6: om TB te beveg deur vroeë opsporing van nuwe gevalle en effektiewe behandeling.

Cat scratch disease (CSD) is a self limited zoonotic disease that presents most commonly as a regional lymphadenopathy. We are reporting a case of a 25-year-old male patient who presented with fever and large right inguinal lymphadenopathy. The diagnosis of cat scratch disease was confirmed based on the characteristic cytopathological features on aspirate smears from the lymph node and the serological titers for Bartonella henselae. This case report emphasizes the importance of combining Bartonella serology, and cytopathology in the diagnostic work-up of febrile lymphadenopathy and suspected CSD since the culture of this organism is arduous.

Linfadenopatia pode estar presente em qualquer fase da infecção pelo HIV a apresenta uma variedade de diagnósticos diferenciais possíveis, desde manifestações secundárias ao próprio HIV até doenças oportunistas ou neoplasias. Foi realizado um estudo de corte transversal de pacientes que realizaram biópsias de linfonodo periférico no Hospital de Clínicas de Porto Alegre entre Janeiro de 2004 a Dezembro de 2008. Foram realizadas 210 biópsias, 131 (61,9%) pacientes eram do sexo masculino, a mediana da idade foi 36 (18-74) anos e da contagem de CD4 149 (1-756) cels/mm3. Cento e seis (50,5%) biópsias foram realizadas na região cervical. Os diagnósticos mais prevalentes incluíram micobacteriose 105 casos (50,2%) sendo que mais de 90% dos casos foram tuberculose; hiperplasia reacional (HR) 48 casos (22,7%), linfoma 19 casos (9,0%) e micoses sistêmicas 12 casos (5,7%) que incluíram a histoplasmose, paracoccidioidomicose e criptococose. Esse estudo demonstra que a biópsia de linfonodos periféricos em pacientes com infecção pelo HIV é uma importante ferramenta no diagnóstico de doenças oportunistas no nosso meio. / Peripheral lymphadenopathy is commonly present in HIV- infected patients and has a wide spectrum of differential diagnoses. We performed a cross-sectional study of peripheral lymph node biopsies performed from 2004 to 2008 in HIV patients assisted in a public hospital in Southern Brazil. Two hundred and ten biopsies were performed, 131(61.9%) patients were male, median of age was 36 years old with a mean of lymphocyte CD4 count of 149 (1-756) cells/mm3. Most of biopsies were performed in the cervical site 106 (50.5%). The most prevalent diagnosis were mycobacteriosis 105 (50.2%), more than 90% was tuberculosis; reactive follicular hyperplasia 48 (22.7%); lymphoma 19 (9.0%); systemic mycosis 12 (5.7%), including histoplasmosis, paracoccidioidomycosis and cryptococcosis. Peripheral lymph node biopsy is a useful tool to diagnose opportunistic diseases such as mycobacteriosis, HIV related malignancies and invasive fungal infections in HIV-infected patients.

Linfadenopatia pode estar presente em qualquer fase da infecção pelo HIV a apresenta uma variedade de diagnósticos diferenciais possíveis, desde manifestações secundárias ao próprio HIV até doenças oportunistas ou neoplasias. Foi realizado um estudo de corte transversal de pacientes que realizaram biópsias de linfonodo periférico no Hospital de Clínicas de Porto Alegre entre Janeiro de 2004 a Dezembro de 2008. Foram realizadas 210 biópsias, 131 (61,9%) pacientes eram do sexo masculino, a mediana da idade foi 36 (18-74) anos e da contagem de CD4 149 (1-756) cels/mm3. Cento e seis (50,5%) biópsias foram realizadas na região cervical. Os diagnósticos mais prevalentes incluíram micobacteriose 105 casos (50,2%) sendo que mais de 90% dos casos foram tuberculose; hiperplasia reacional (HR) 48 casos (22,7%), linfoma 19 casos (9,0%) e micoses sistêmicas 12 casos (5,7%) que incluíram a histoplasmose, paracoccidioidomicose e criptococose. Esse estudo demonstra que a biópsia de linfonodos periféricos em pacientes com infecção pelo HIV é uma importante ferramenta no diagnóstico de doenças oportunistas no nosso meio. / Peripheral lymphadenopathy is commonly present in HIV- infected patients and has a wide spectrum of differential diagnoses. We performed a cross-sectional study of peripheral lymph node biopsies performed from 2004 to 2008 in HIV patients assisted in a public hospital in Southern Brazil. Two hundred and ten biopsies were performed, 131(61.9%) patients were male, median of age was 36 years old with a mean of lymphocyte CD4 count of 149 (1-756) cells/mm3. Most of biopsies were performed in the cervical site 106 (50.5%). The most prevalent diagnosis were mycobacteriosis 105 (50.2%), more than 90% was tuberculosis; reactive follicular hyperplasia 48 (22.7%); lymphoma 19 (9.0%); systemic mycosis 12 (5.7%), including histoplasmosis, paracoccidioidomycosis and cryptococcosis. Peripheral lymph node biopsy is a useful tool to diagnose opportunistic diseases such as mycobacteriosis, HIV related malignancies and invasive fungal infections in HIV-infected patients.

Linfadenopatia pode estar presente em qualquer fase da infecção pelo HIV a apresenta uma variedade de diagnósticos diferenciais possíveis, desde manifestações secundárias ao próprio HIV até doenças oportunistas ou neoplasias. Foi realizado um estudo de corte transversal de pacientes que realizaram biópsias de linfonodo periférico no Hospital de Clínicas de Porto Alegre entre Janeiro de 2004 a Dezembro de 2008. Foram realizadas 210 biópsias, 131 (61,9%) pacientes eram do sexo masculino, a mediana da idade foi 36 (18-74) anos e da contagem de CD4 149 (1-756) cels/mm3. Cento e seis (50,5%) biópsias foram realizadas na região cervical. Os diagnósticos mais prevalentes incluíram micobacteriose 105 casos (50,2%) sendo que mais de 90% dos casos foram tuberculose; hiperplasia reacional (HR) 48 casos (22,7%), linfoma 19 casos (9,0%) e micoses sistêmicas 12 casos (5,7%) que incluíram a histoplasmose, paracoccidioidomicose e criptococose. Esse estudo demonstra que a biópsia de linfonodos periféricos em pacientes com infecção pelo HIV é uma importante ferramenta no diagnóstico de doenças oportunistas no nosso meio. / Peripheral lymphadenopathy is commonly present in HIV- infected patients and has a wide spectrum of differential diagnoses. We performed a cross-sectional study of peripheral lymph node biopsies performed from 2004 to 2008 in HIV patients assisted in a public hospital in Southern Brazil. Two hundred and ten biopsies were performed, 131(61.9%) patients were male, median of age was 36 years old with a mean of lymphocyte CD4 count of 149 (1-756) cells/mm3. Most of biopsies were performed in the cervical site 106 (50.5%). The most prevalent diagnosis were mycobacteriosis 105 (50.2%), more than 90% was tuberculosis; reactive follicular hyperplasia 48 (22.7%); lymphoma 19 (9.0%); systemic mycosis 12 (5.7%), including histoplasmosis, paracoccidioidomycosis and cryptococcosis. Peripheral lymph node biopsy is a useful tool to diagnose opportunistic diseases such as mycobacteriosis, HIV related malignancies and invasive fungal infections in HIV-infected patients.