Granulomatous Pericarditis in a Sudden Death: The Critical Role of Forensic Histopathology in Diagnosing Latent Tuberculosis

Granulomatous Pericarditis in a Sudden Death: The Critical Role of Forensic Histopathology in Diagnosing Latent Tuberculosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Granulomatous Pericarditis in a Sudden Death: The Critical Role of Forensic Histopathology in Diagnosing Latent Tuberculosis Ahlam Elbedwi, Hoda M Tawel, Marwah Ikdeewish This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8229831/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Disseminated tuberculosis, specifically tuberculous pericarditis, represents a diagnostically challenging yet critical contributor to sudden death. The condition frequently progresses without overt symptoms, evading clinical detection especially among young migrants from endemic regions. Forensic histopathologist is often the first and only person to identify this reportable disease. Without a systematic forensic autopsy including histology, this death would have been certified as "undetermined". The present case emphasizes the necessity of improved TB screening initiatives for high-risk populations, such as recent immigrants from endemic nations. Case presentation A 24-year-old male immigrant of Black ethnicity was received a case of sudden death. The person had been declared deceased upon arrival at the hospital, and resuscitation attempts were unsuccessful. Neither previous clinical history nor reviewable medical data were accessible. The deceased's exterior examination revealed a slim physique, cachexic, with a slumped posture. The autopsy examination showed granulomatous pericarditis and purulent lung abnormalities, but no signs of trauma or toxication. A histopathological analysis of the pericardium showed multinucleated giant cells, lymphocytes, epithelioid cells, and central necrosis—all of which are indicative of tuberculous pericarditis. Additionally, lung tissue examination revealed military TB. The cause of death was determined to be disseminated tuberculosis, which resulted in respiratory and circulatory collapse, even though no premortem symptoms or medical history were recorded. Conclusion This case highlights the indispensable role of systematic autopsy and histopathological examination in identifying occult tuberculosis in medicolegal investigations, especially in high-risk populations. Forensic pathology enhances mortality data quality, enables contact tracing to avoid transmission, and informs targeted screening programs to strengthen TB control in the country. Sudden cardiac death granulomatous pericarditis Mycobacterium tuberculosis miliary tuberculosis postmortem diagnosis global health Figures Figure 1 Figure 2 Figure 3 Background Tuberculosis (TB) remains a critical public health challenge worldwide, with 10.6 million new cases reported in 2022 (133 cases per 100,000 population) and 1.3 million deaths, making it the leading infectious cause of mortality worldwide (Global Tuberculosis Report 2023, 2023). While 75% of the cases are concentrated in 12 high-burden countries (such as India, Indonesia, and Nigeria), Sub-Saharan Africa follows in the footsteps with 45% of HIV/TB coinfections (Wondmeneh and Mekonnen, 2023 ). Libya, a nation with a moderate burden of TB, had an annual prevalence of 59 cases per 100,000 people (about 4,000 cases) in 2022. Nonetheless, underdiagnosis is still a problem, with only 53% of cases being identified, reflecting gaps in the diagnostic capacity of the country (Global Tuberculosis Report 2023, 2023). The escalating TB burden in Libya is caused by two interrelated factors: first, the ongoing migration from sub-Saharan African regions, and second, the significant deterioration of healthcare facilities during the COVID-19 epidemic (Dheda et al., 2022 ; McKay et al., 2024 ). Although pulmonary TB accounts for approximately 70% of the cases, disseminated TB can spread to other organs such as the lymph nodes, pleura, kidneys, spine, brain, abdomen, liver, and heart with various percentages (Khan, 2019 ). Tuberculous pericarditis occurs in 1–2% of pulmonary TB cases and is discovered in roughly 1% of TB-related autopsies (Lucero et al., 2022 ). This granulomatous condition poses diagnostic and forensic challenges, particularly when it leads to sudden unexpected death in individuals without preceding cardiac symptoms (Basso et al., 2017 ). There are two primary ways that Mycobacterium tuberculosis usually infects the pericardium: either through retrograde lymphatic spread from adjacent infected lymph nodes or through hematogenous dissemination. Less frequently, the infection spreads through the blood from distant focus or directly from adjacent lung tissue (Lucero et al., 2022 ). The disease advances in four stages: early inflammation with fibrin deposition, then bloody fluid accumulation, fibrous tissue creation, and lastly scarring that stiffens the pericardium (Naicker and Ntsekhe, 2020 ). Without treatment, 30–60% of cases develop constrictive pericarditis, which causes serious consequences and increases mortality (Al-Anbagi et al., 2025 ). Invasive sample is often necessary for the conclusive confirmation of the diagnosis of tuberculous pericarditis through the microbiological or histological detection of M. tuberculosis (Naicker and Ntsekhe, 2020 ); nevertheless, in endemic regions, clinical diagnosis often relies on supportive radiological and biochemical findings due to limited access to confirmatory testing. Granulomatous inflammation sometimes is the only observable symptom in postmortem investigations, requiring thorough histopathological analysis in addition to specialized methods like PCR and immunohistochemistry to distinguish tuberculosis from other granulomatous diseases (Basso et al., 2017 ). This diagnostic approach not only establishes causation in sudden deaths but also reveals systemic gaps in antemortem tuberculosis detection, particularly among vulnerable populations. In the current case presentation, we highlight the crucial role of forensic pathology in identifying undetected tuberculosis through postmortem histological analysis, linking clinical medicine and public health efforts. Additionally, this instance emphasizes the need for standardized procedures for assessing granulomatous inflammation in sudden, unexpected deaths in order to enhance tuberculosis surveillance and improve mortality statistics. Case Presentation A 24-year-old male immigrant of Black ethnicity was received by the Forensic Medicine Department in Tripoli, Libya, in January 2024 as a case of sudden death. The person had been declared deceased upon arrival at the hospital, and resuscitation attempts were unsuccessful. Furthermore, neither previous clinical history nor reviewable medical data were accessible. The deceased's exterior examination revealed a slim physique, cachexic, standing 160 cm tall with a slumped posture. The head, neck, torso, and upper extremities showed no indications of trauma or fractures; however, the posterolateral region of the right thigh and upper lateral aspect of the left thigh had pressure ulcers, or bedsores. The autopsy examination revealed no anomalies in the scalp or skull, and the thoracic cavity contained no indications of bleeding or rib fractures. However, both lungs and the pericardium showed purulent pathological alterations, whereas the rest of the organs appeared normal (Fig. 1 A). Postmortem blood samples were collected for toxicology screening, while representative tissue biopsies from various organs were taken for histopathological examination. The Toxicology analysis revealed negative results for alcohol, drugs, and common poisons, thereby ruling out intoxication as a contributing cause. Histopathological examination of the submitted myocardium and coronary arteries samples were found to be unremarkable. The pericardium, on the other hand, showed dense yellowish deposition on the external surface, thickened, opaque, with fibrinous exudate and possible adhesions (Fig. 1 B). Microscopically showed granulomatous lesions with multinucleated giant cells, lymphocytes, and epithelioid cells surrounding a core necrosis, consistent with tuberculous pericarditis (Fig. 2 ). Additionally, the lung tissue sections displayed partial architectural damage and comparable granulomatous infiltrates (Fig. 3 ), supporting a diagnosis of miliary tuberculosis in this case. Acid-fast bacilli (AFB) staining was indicated for conclusive evidence of tuberculosis. Postmortem examination, supported by histopathological findings, confirmed disseminated tuberculosis as the primary cause of death. The disease progression resulted in subsequent respiratory and circulatory failure, and eventually leading to death in this instance. Discussion Tuberculous pericarditis is a particularly severe form of extrapulmonary tuberculosis, with mortality rates estimated between 17% and 40%, despite ongoing treatment efforts. The primary causes of death are often complications such as cardiac tamponade and constrictive pericarditis (Mayosi et al., 2008 ). This case involves a 24-year-old male migrant who died suddenly from disseminated tuberculosis. Autopsy findings confirmed tuberculous pericarditis and miliary TB as the causes of death. External causes such as trauma or toxicological factors were excluded. Histopathology revealed granulomatous inflammation with caseous necrosis in both the pericardium and lungs, characteristic of TB. The presence of miliary dissemination indicates hematogenous spread, likely due to delayed diagnosis and advanced disease, culminating in respiratory and circulatory failure. The patient’s cachexia, pressure ulcers, and lack of accessible medical history suggest chronic illness and neglect, highlighting vulnerabilities commonly faced by underprivileged migrant groups. It is not unusual for vulnerable groups like refugees, criminals, and the socioeconomically disadvantaged to experience the deadly course of their disease, even in the absence of documented symptoms or medical assistance (Kimbrough et al., 2012 ; Dhavan et al., 2017 ; Knipper et al., 2021 ). Delays or missed diagnoses are caused by a number of factors, including stigma around infectious diseases, underdiagnosis, a failure to seek medical attention, and restricted access to healthcare (Dhavan et al., 2017 ). Socioeconomic status significantly affects disease diagnosis and outcomes. Low-income people are more vulnerable to tuberculosis due to overcrowded living conditions (Mucheleng’anga et al., 2022 ). Studies indicate that men, face a higher risk of unexpected or violent death as a result of advanced disease complications, possibly due to poor health-seeking behavior (Himwaze et al., 2020 ; Mucheleng’anga et al., 2022 ). Many of these deaths occur outside healthcare facilities. For example, an autopsy research conducted in South Africa revealed a high prevalence of pulmonary TB in sudden at-home deaths, and was often linked to undetected HIV coinfection (Omar et al., 2015 ). Similarly, 31% of forensic autopsy cases in Lusaka were found to be HIV-positive (Himwaze et al., 2020 ). Given these reasons, targeted TB screening is essential for high-risk groups, including migrants, inhabitants of high-density/low-income areas, and HIV-positive individuals. This is especially relevant in Libya, which has become a major migratory hub in recent years. The histological features observed in this case—granulomatous inflammation with caseous necrosis, multinucleated giant cells, and epithelioid cell infiltrates—are hallmarks of tuberculosis and provide final diagnostic evidence. While diagnostic procedures such as PCR and culture are important, they can produce false negatives due to low bacillary load or prior medication (Karimi et al., 2014 ). Histopathology, on the other hand, reliably detects tuberculosis even in paucibacillary or extrapulmonary instances, such as tuberculous pericarditis and miliary TB (Karimi et al., 2014 ). This indicates its crucial importance, especially in situations with limited resources where modern diagnostics are unavailable. Histopathology continues to play an important role in lowering TB-related morbidity and death, particularly in high-risk and immunocompromised patients. In addition, the likelihood of HIV coinfection, while not investigated in this case, is clinically significant given Libya's increasing HIV prevalence, and its reported link with disseminated and extrapulmonary TB presentations (Hamidi, Regmi and van Teijlingen, 2021 ). Future forensic investigations into similar instances should include multiplex disease screening to identify multifactorial contributors to mortality. Diagnosis of TB in living patients usually involves clinical evaluation and lab/radiographic tests. Though, TB often goes undiagnosed until forensic autopsy. Postmortem TB detection is an important epidemiological indicator, and forensic autopsies are critical for TB mortality surveillance, exposing the burden of unreported TB mortality. The prevalence of TB at forensic autopsies varies by region, as revealed in studies worldwide. Research in India reported a 5.1% TB rate at forensic autopsies, with 84.6% of cases undiagnosed before death (Punia et al., 2012 ). In New Zealand, TB was shown to be the cause of death in 0.2% of autopsies and a large proportion (70%) was undiagnosed before death (Lum and Koelmeyer, 2005 ). Another study in Cape Town, South Africa, discovered a TB prevalence of 6.2% in cases of sudden unexpected death (Osman et al., 2021 ). This variation may allude to regional differences in the prevalence of the infection. However, the burden of undiagnosed TB in community deaths has not been estimated in Libya yet. This case highlights the public health vulnerabilities in Libya, due to the political instability and fragmented healthcare system contributing to TB underdiagnosis, especially among migrants and detainees (Ismael Almlyan et al., 2025 ). Undetected TB, worsened by overcrowding settings where migrant populations are disproportionately affected, as demonstrated in this case. Given Libya's critical high-risk settings could reduce unnecessary mortality. In conclusion, this case illustrates how forensic pathology, infectious disease trends, and health disparities intersect. To avoid repeat incidents, public health initiatives must enhance early TB detection and healthcare access for vulnerable groups. Forensic institutions also play a critical role by identifying and reporting such cases to guide interventions. Declarations Ethics approval and consent to participate: Ethical approval for this study was granted by the Libyan National Medical Centre Bioethics Committee (Approval No.: NBC:018.H.24.69). The committee waived the requirement for informed consent. Clinical trial number: not applicable. Consent for publication : it has been approved by the Scientific Committee of the Forensic Histopathology Department at Tripoli Medical Centre, Libya, which waived the need for further consent. Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article. Author Contribution - **Ahlam Elbedwi:** Conceptualized the study, performed the autopsy, supervised the histopathological processing and analysis, provided the photomicrographs, and drafted the initial manuscript- **Hoda Tawel:** Conceptualized the study, Supervised the histopathological processing and analysis, interpreted the microscopic findings, analyzed the clinical and autopsy data, and critically revised the manuscript for important intellectual content.- **Marwah Ikdeewish:** Collected and analyzed the clinical and autopsy data, contributed to the literature review, assisted in data curation and interpretation, and participated in editing the final manuscript. Acknowledgement The authors thank MOHAMED F. MAHMUD ELMOAKET (Head of Pathology Department, Consultant Pathologist, Ministry of Justice Judicial Expertise & Research Center, Tripoli Forensic & Analysis Management) for his support and for providing essential data for this study. Data Availability The datasets supporting the findings of this case report are not publicly available due to patient privacy concerns but are available from the corresponding author upon reasonable request. References Al-Anbagi U et al (2025) ‘Disseminated Tuberculosis with Pericardial Effusion and Early Tamponade: A Case Report’, Cureus , 17(4), p. e82632. Available at: https://doi.org/10.7759/cureus.82632 Basso C et al (2017) ‘Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology’, An International Journal of Pathology , 471(6), pp. 691–705. Available at: https://doi.org/10.1007/s00428-017-2221-0 Dhavan P et al (2017) ‘An overview of tuberculosis and migration’, The International Journal of Tuberculosis and Lung Disease , 21(6), pp. 610–623. 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Available at: https://doi.org/10.1258/td.2011.110314 Wondmeneh TG, Mekonnen AT (2023) ‘The incidence rate of tuberculosis and its associated factors among HIV-positive persons in Sub-Saharan Africa: a systematic review and meta-analysis’, BMC Infectious Diseases , 23, p. 613. Available at: https://doi.org/10.1186/s12879-023-08533-0 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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01:07:00","extension":"html","order_by":28,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":58305,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8229831/v1/38283e36b39911fdaeab7884.html"},{"id":98269196,"identity":"1dda5cfe-5df1-4486-84bb-1b70dda02e46","added_by":"auto","created_at":"2025-12-16 01:06:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":920696,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAutopsy examination:\u003c/strong\u003e The deceased's exterior examination revealed a slim physique, cachexic, and both lungs and the pericardium showed purulent pathological alterations \u003cstrong\u003e(A).\u003c/strong\u003e The pericardium showed dense yellowish deposition on the external surface (\u003cstrong\u003eB)\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8229831/v1/544f78d63549da119da5c1e5.png"},{"id":98435551,"identity":"e9c726b4-c56b-4633-848c-142f6bd0743b","added_by":"auto","created_at":"2025-12-17 16:54:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1209849,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTuberculous pericarditis.\u003c/strong\u003eCaseating granulomas with fibrin deposition in tuberculous pericarditis (A) (H\u0026amp;E, ×20), featuring Langhans giant cells and chronic inflammation diagnostic for TB (B)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8229831/v1/8bfb2bf456c6982a75f094e8.png"},{"id":98269200,"identity":"2c778b05-c409-4cc0-9f7d-7bc5d0d5c620","added_by":"auto","created_at":"2025-12-16 01:06:59","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1481408,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistopathology of pulmonary tuberculosis:\u003c/strong\u003e(A) necrotizing granulomatous inflammation with central caseous necrosis (pink amorphous debris), surrounded by epithelioid macrophages, lymphocytes, and Langhans giant cells (H\u0026amp;E stain, ×20). (B) The granuloma is bordered by a fibrous cuff with chronic inflammatory infiltrates, characteristic of Mycobacterium tuberculosis infection\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8229831/v1/cad8ec494b68d060db2a0649.png"},{"id":100548207,"identity":"b9941b85-abbc-425b-8710-ea8ee7aaca69","added_by":"auto","created_at":"2026-01-19 08:17:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4651716,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8229831/v1/6952461e-94be-49db-aaa3-34311d0283b9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Granulomatous Pericarditis in a Sudden Death: The Critical Role of Forensic Histopathology in Diagnosing Latent Tuberculosis","fulltext":[{"header":"Background","content":"\u003cp\u003eTuberculosis (TB) remains a critical public health challenge worldwide, with 10.6\u0026nbsp;million new cases reported in 2022 (133 cases per 100,000 population) and 1.3\u0026nbsp;million deaths, making it the leading infectious cause of mortality worldwide (Global Tuberculosis Report 2023, 2023). While 75% of the cases are concentrated in 12 high-burden countries (such as India, Indonesia, and Nigeria), Sub-Saharan Africa follows in the footsteps with 45% of HIV/TB coinfections (Wondmeneh and Mekonnen, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eLibya, a nation with a moderate burden of TB, had an annual prevalence of 59 cases per 100,000 people (about 4,000 cases) in 2022. Nonetheless, underdiagnosis is still a problem, with only 53% of cases being identified, reflecting gaps in the diagnostic capacity of the country (Global Tuberculosis Report 2023, 2023). The escalating TB burden in Libya is caused by two interrelated factors: first, the ongoing migration from sub-Saharan African regions, and second, the significant deterioration of healthcare facilities during the COVID-19 epidemic (Dheda et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; McKay et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAlthough pulmonary TB accounts for approximately 70% of the cases, disseminated TB can spread to other organs such as the lymph nodes, pleura, kidneys, spine, brain, abdomen, liver, and heart with various percentages (Khan, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Tuberculous pericarditis occurs in 1\u0026ndash;2% of pulmonary TB cases and is discovered in roughly 1% of TB-related autopsies (Lucero et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). This granulomatous condition poses diagnostic and forensic challenges, particularly when it leads to sudden unexpected death in individuals without preceding cardiac symptoms (Basso et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere are two primary ways that Mycobacterium tuberculosis usually infects the pericardium: either through retrograde lymphatic spread from adjacent infected lymph nodes or through hematogenous dissemination. Less frequently, the infection spreads through the blood from distant focus or directly from adjacent lung tissue (Lucero et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). The disease advances in four stages: early inflammation with fibrin deposition, then bloody fluid accumulation, fibrous tissue creation, and lastly scarring that stiffens the pericardium (Naicker and Ntsekhe, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Without treatment, 30\u0026ndash;60% of cases develop constrictive pericarditis, which causes serious consequences and increases mortality (Al-Anbagi et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eInvasive sample is often necessary for the conclusive confirmation of the diagnosis of tuberculous pericarditis through the microbiological or histological detection of M. tuberculosis (Naicker and Ntsekhe, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2020\u003c/span\u003e); nevertheless, in endemic regions, clinical diagnosis often relies on supportive radiological and biochemical findings due to limited access to confirmatory testing. Granulomatous inflammation sometimes is the only observable symptom in postmortem investigations, requiring thorough histopathological analysis in addition to specialized methods like PCR and immunohistochemistry to distinguish tuberculosis from other granulomatous diseases (Basso et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). This diagnostic approach not only establishes causation in sudden deaths but also reveals systemic gaps in antemortem tuberculosis detection, particularly among vulnerable populations.\u003c/p\u003e\u003cp\u003eIn the current case presentation, we highlight the crucial role of forensic pathology in identifying undetected tuberculosis through postmortem histological analysis, linking clinical medicine and public health efforts. Additionally, this instance emphasizes the need for standardized procedures for assessing granulomatous inflammation in sudden, unexpected deaths in order to enhance tuberculosis surveillance and improve mortality statistics.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 24-year-old male immigrant of Black ethnicity was received by the Forensic Medicine Department in Tripoli, Libya, in January 2024 as a case of sudden death. The person had been declared deceased upon arrival at the hospital, and resuscitation attempts were unsuccessful. Furthermore, neither previous clinical history nor reviewable medical data were accessible. The deceased's exterior examination revealed a slim physique, cachexic, standing 160 cm tall with a slumped posture. The head, neck, torso, and upper extremities showed no indications of trauma or fractures; however, the posterolateral region of the right thigh and upper lateral aspect of the left thigh had pressure ulcers, or bedsores.\u003c/p\u003e\u003cp\u003eThe autopsy examination revealed no anomalies in the scalp or skull, and the thoracic cavity contained no indications of bleeding or rib fractures. However, both lungs and the pericardium showed purulent pathological alterations, whereas the rest of the organs appeared normal (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Postmortem blood samples were collected for toxicology screening, while representative tissue biopsies from various organs were taken for histopathological examination. The Toxicology analysis revealed negative results for alcohol, drugs, and common poisons, thereby ruling out intoxication as a contributing cause.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eHistopathological examination of the submitted myocardium and coronary arteries samples were found to be unremarkable. The pericardium, on the other hand, showed dense yellowish deposition on the external surface, thickened, opaque, with fibrinous exudate and possible adhesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Microscopically showed granulomatous lesions with multinucleated giant cells, lymphocytes, and epithelioid cells surrounding a core necrosis, consistent with tuberculous pericarditis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAdditionally, the lung tissue sections displayed partial architectural damage and comparable granulomatous infiltrates (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), supporting a diagnosis of miliary tuberculosis in this case. Acid-fast bacilli (AFB) staining was indicated for conclusive evidence of tuberculosis. Postmortem examination, supported by histopathological findings, confirmed disseminated tuberculosis as the primary cause of death. The disease progression resulted in subsequent respiratory and circulatory failure, and eventually leading to death in this instance.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTuberculous pericarditis is a particularly severe form of extrapulmonary tuberculosis, with mortality rates estimated between 17% and 40%, despite ongoing treatment efforts. The primary causes of death are often complications such as cardiac tamponade and constrictive pericarditis (Mayosi et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). This case involves a 24-year-old male migrant who died suddenly from disseminated tuberculosis. Autopsy findings confirmed tuberculous pericarditis and miliary TB as the causes of death. External causes such as trauma or toxicological factors were excluded. Histopathology revealed granulomatous inflammation with caseous necrosis in both the pericardium and lungs, characteristic of TB. The presence of miliary dissemination indicates hematogenous spread, likely due to delayed diagnosis and advanced disease, culminating in respiratory and circulatory failure.\u003c/p\u003e\u003cp\u003eThe patient\u0026rsquo;s cachexia, pressure ulcers, and lack of accessible medical history suggest chronic illness and neglect, highlighting vulnerabilities commonly faced by underprivileged migrant groups. It is not unusual for vulnerable groups like refugees, criminals, and the socioeconomically disadvantaged to experience the deadly course of their disease, even in the absence of documented symptoms or medical assistance (Kimbrough et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Dhavan et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Knipper et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Delays or missed diagnoses are caused by a number of factors, including stigma around infectious diseases, underdiagnosis, a failure to seek medical attention, and restricted access to healthcare (Dhavan et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSocioeconomic status significantly affects disease diagnosis and outcomes. Low-income people are more vulnerable to tuberculosis due to overcrowded living conditions (Mucheleng\u0026rsquo;anga et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Studies indicate that men, face a higher risk of unexpected or violent death as a result of advanced disease complications, possibly due to poor health-seeking behavior (Himwaze et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Mucheleng\u0026rsquo;anga et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Many of these deaths occur outside healthcare facilities. For example, an autopsy research conducted in South Africa revealed a high prevalence of pulmonary TB in sudden at-home deaths, and was often linked to undetected HIV coinfection (Omar et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Similarly, 31% of forensic autopsy cases in Lusaka were found to be HIV-positive (Himwaze et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Given these reasons, targeted TB screening is essential for high-risk groups, including migrants, inhabitants of high-density/low-income areas, and HIV-positive individuals. This is especially relevant in Libya, which has become a major migratory hub in recent years.\u003c/p\u003e\u003cp\u003eThe histological features observed in this case\u0026mdash;granulomatous inflammation with caseous necrosis, multinucleated giant cells, and epithelioid cell infiltrates\u0026mdash;are hallmarks of tuberculosis and provide final diagnostic evidence. While diagnostic procedures such as PCR and culture are important, they can produce false negatives due to low bacillary load or prior medication (Karimi et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Histopathology, on the other hand, reliably detects tuberculosis even in paucibacillary or extrapulmonary instances, such as tuberculous pericarditis and miliary TB (Karimi et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). This indicates its crucial importance, especially in situations with limited resources where modern diagnostics are unavailable. Histopathology continues to play an important role in lowering TB-related morbidity and death, particularly in high-risk and immunocompromised patients. In addition, the likelihood of HIV coinfection, while not investigated in this case, is clinically significant given Libya's increasing HIV prevalence, and its reported link with disseminated and extrapulmonary TB presentations (Hamidi, Regmi and van Teijlingen, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Future forensic investigations into similar instances should include multiplex disease screening to identify multifactorial contributors to mortality.\u003c/p\u003e\u003cp\u003eDiagnosis of TB in living patients usually involves clinical evaluation and lab/radiographic tests. Though, TB often goes undiagnosed until forensic autopsy. Postmortem TB detection is an important epidemiological indicator, and forensic autopsies are critical for TB mortality surveillance, exposing the burden of unreported TB mortality. The prevalence of TB at forensic autopsies varies by region, as revealed in studies worldwide. Research in India reported a 5.1% TB rate at forensic autopsies, with 84.6% of cases undiagnosed before death (Punia et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). In New Zealand, TB was shown to be the cause of death in 0.2% of autopsies and a large proportion (70%) was undiagnosed before death (Lum and Koelmeyer, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). Another study in Cape Town, South Africa, discovered a TB prevalence of 6.2% in cases of sudden unexpected death (Osman et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). This variation may allude to regional differences in the prevalence of the infection. However, the burden of undiagnosed TB in community deaths has not been estimated in Libya yet.\u003c/p\u003e\u003cp\u003eThis case highlights the public health vulnerabilities in Libya, due to the political instability and fragmented healthcare system contributing to TB underdiagnosis, especially among migrants and detainees (Ismael Almlyan et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Undetected TB, worsened by overcrowding settings where migrant populations are disproportionately affected, as demonstrated in this case. Given Libya's critical high-risk settings could reduce unnecessary mortality.\u003c/p\u003e\u003cp\u003eIn conclusion, this case illustrates how forensic pathology, infectious disease trends, and health disparities intersect. To avoid repeat incidents, public health initiatives must enhance early TB detection and healthcare access for vulnerable groups. Forensic institutions also play a critical role by identifying and reporting such cases to guide interventions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for this study was granted by the Libyan National Medical Centre Bioethics Committee (Approval No.: NBC:018.H.24.69). The committee waived the requirement for informed consent. Clinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eit has been approved by the Scientific Committee of the Forensic Histopathology Department at Tripoli Medical Centre, Libya, which waived the need for further consent.\u003c/p\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eThe author(s) received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003e- **Ahlam Elbedwi:** Conceptualized the study, performed the autopsy, supervised the histopathological processing and analysis, provided the photomicrographs, and drafted the initial manuscript- **Hoda Tawel:** Conceptualized the study, Supervised the histopathological processing and analysis, interpreted the microscopic findings, analyzed the clinical and autopsy data, and critically revised the manuscript for important intellectual content.- **Marwah Ikdeewish:** Collected and analyzed the clinical and autopsy data, contributed to the literature review, assisted in data curation and interpretation, and participated in editing the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe authors thank MOHAMED F. MAHMUD ELMOAKET (Head of Pathology Department, Consultant Pathologist, Ministry of Justice Judicial Expertise \u0026amp; Research Center, Tripoli Forensic \u0026amp; Analysis Management) for his support and for providing essential data for this study.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe datasets supporting the findings of this case report are not publicly available due to patient privacy concerns but are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAl-Anbagi U et al (2025) \u0026lsquo;Disseminated Tuberculosis with Pericardial Effusion and Early Tamponade: A Case Report\u0026rsquo;, \u003cem\u003eCureus\u003c/em\u003e, 17(4), p. e82632. 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N Z Med J 118(1211):U1356\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMayosi BM et al (2008) \u0026lsquo;Mortality in patients treated for tuberculous pericarditis in sub-Saharan Africa\u0026rsquo;, \u003cem\u003eSouth African Medical Journal\u003c/em\u003e, 98(1), pp. 36\u0026ndash;40. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.scopus.com/inward/record.url?scp=39749093269\u0026amp;partnerID=8YFLogxK\u003c/span\u003e\u003cspan address=\"http://www.scopus.com/inward/record.url?scp=39749093269\u0026amp;partnerID=8YFLogxK\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (Accessed: 26 June 2025)\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcKay T et al (2024) \u0026lsquo;The Missing Millions: Uncovering the Burden of Covid-19 Cases and Deaths in the African Region\u0026rsquo;, \u003cem\u003ePopulation and Development Review\u003c/em\u003e, 50(1), pp. 7\u0026ndash;58. 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Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5588/ijtld.15.0222\u003c/span\u003e\u003cspan address=\"10.5588/ijtld.15.0222\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOsman M et al (2021) \u0026lsquo;Tuberculosis in persons with sudden unexpected death, in Cape Town, South Africa\u0026rsquo;, \u003cem\u003eInternational journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases\u003c/em\u003e, 105, pp. 75\u0026ndash;82. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ijid.2021.02.036\u003c/span\u003e\u003cspan address=\"10.1016/j.ijid.2021.02.036\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePunia RS et al (2012) \u0026lsquo;Tuberculosis prevalence at autopsy: a study from North India\u0026rsquo;, \u003cem\u003eTropical Doctor\u003c/em\u003e, 42(1), pp. 46\u0026ndash;47. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1258/td.2011.110314\u003c/span\u003e\u003cspan address=\"10.1258/td.2011.110314\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWondmeneh TG, Mekonnen AT (2023) \u0026lsquo;The incidence rate of tuberculosis and its associated factors among HIV-positive persons in Sub-Saharan Africa: a systematic review and meta-analysis\u0026rsquo;, \u003cem\u003eBMC Infectious Diseases\u003c/em\u003e, 23, p. 613. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12879-023-08533-0\u003c/span\u003e\u003cspan address=\"10.1186/s12879-023-08533-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Sudden cardiac death, granulomatous pericarditis, Mycobacterium tuberculosis, miliary tuberculosis, postmortem diagnosis, global health","lastPublishedDoi":"10.21203/rs.3.rs-8229831/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8229831/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDisseminated tuberculosis, specifically tuberculous pericarditis, represents a diagnostically challenging yet critical contributor to sudden death. The condition frequently progresses without overt symptoms, evading clinical detection especially among young migrants from endemic regions. Forensic histopathologist is often the first and only person to identify this reportable disease. Without a systematic forensic autopsy including histology, this death would have been certified as \"undetermined\". The present case emphasizes the necessity of improved TB screening initiatives for high-risk populations, such as recent immigrants from endemic nations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 24-year-old male immigrant of Black ethnicity was received a case of sudden death. The person had been declared deceased upon arrival at the hospital, and resuscitation attempts were unsuccessful. Neither previous clinical history nor reviewable medical data were accessible. The deceased's exterior examination revealed a slim physique, cachexic, with a slumped posture. The autopsy examination showed granulomatous pericarditis and purulent lung abnormalities, but no signs of trauma or toxication. A histopathological analysis of the pericardium showed multinucleated giant cells, lymphocytes, epithelioid cells, and central necrosis—all of which are indicative of tuberculous pericarditis. Additionally, lung tissue examination revealed military TB. The cause of death was determined to be disseminated tuberculosis, which resulted in respiratory and circulatory collapse, even though no premortem symptoms or medical history were recorded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case highlights the indispensable role of systematic autopsy and histopathological examination in identifying occult tuberculosis in medicolegal investigations, especially in high-risk populations. Forensic pathology enhances mortality data quality, enables contact tracing to avoid transmission, and informs targeted screening programs to strengthen TB control in the country.\u003c/p\u003e","manuscriptTitle":"Granulomatous Pericarditis in a Sudden Death: The Critical Role of Forensic Histopathology in Diagnosing Latent Tuberculosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-16 01:06:55","doi":"10.21203/rs.3.rs-8229831/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3c9072bf-abaa-489b-9c3d-f8c5a08460ad","owner":[],"postedDate":"December 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-17T20:38:28+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-16 01:06:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8229831","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8229831","identity":"rs-8229831","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}