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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 11  |  Issue : 1  |  Page : 47-50

The real burden of tuberculosis: Hidden cases diagnosed on autopsy at a tertiary care center of India


Department of Pathology, Dr. Baba Saheb Ambedkar College and Hospital, Delhi, India

Date of Submission12-Nov-2021
Date of Decision15-Dec-2021
Date of Acceptance10-Jan-2022
Date of Web Publication12-Mar-2022

Correspondence Address:
Zini Chaurasia
Department of Pathology, Dr. Baba Saheb Ambedkar College and Hospital, Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_227_21

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  Abstract 


Introduction: Developing nations have a huge burden of tuberculosis (TB), because of which many cases are undetected and diagnosed only on autopsies. The purpose of this study was to find these cases in a series of consecutive autopsies conducted at a tertiary care centers. Materials and Methods: This retrospective study of 7-year duration from 2014 to 2020 consisted of reviewing 767 autopsies. The records of cases where a diagnosis of TB were established on histopathology were noted and evaluated. Results: Of 767 autopsies, TB was the diagnosis on histopathology in 72 cases. Of the 72 cases, 53 cases were undiagnosed antemortem and incidentally detected on autopsy. The study showed a male predominance with a 1.52:1 male-to-female ratio. The most common age group involved was the second decade. The study constitutes 26 cases of isolated pulmonary TB, 23 cases of disseminated TB, three cases of solitary renal TB, and one case of hepatic TB. The liver was the most commonly involved organ along with the lung in cases of disseminated TB, followed by the spleen, kidney, pancreas, intestine, brain, and heart. Discussion: Epidemiology and research on TB may be affected by these hidden cases which are unraveled incidentally on autopsy. These cases must always be reported and brought to the attention of clinicians for nation's better public health.

Keywords: Autopsy, epithelioid cell granuloma, tuberculosis


How to cite this article:
Agarwal S, Chaurasia Z, Malik DK, Gupta R, Singh C, Jain S. The real burden of tuberculosis: Hidden cases diagnosed on autopsy at a tertiary care center of India. Int J Mycobacteriol 2022;11:47-50

How to cite this URL:
Agarwal S, Chaurasia Z, Malik DK, Gupta R, Singh C, Jain S. The real burden of tuberculosis: Hidden cases diagnosed on autopsy at a tertiary care center of India. Int J Mycobacteriol [serial online] 2022 [cited 2022 May 25];11:47-50. Available from: https://www.ijmyco.org/text.asp?2022/11/1/47/339507




  Introduction Top


Tuberculosis (TB) is one of the most ancient diseases of mankind. In spite of so much research work done on it for newer and better ways of its diagnosis and treatment, this infection still remains to be the leading cause of mortality and morbidity worldwide. India has the highest burden of TB accounting for 1/3rd of total cases annually.[1] The World Health Organization report further states that in 2017, 10 million people were diagnosed with TB and 4 million people remain undiagnosed and hence untreated.[1] India aims to eliminate TB from the country by 2025 through its National TB elimination program.[1]

The major hurdle in the diagnosis of TB is the social stigma associated with it. This leads to delay in the diagnosis, which in turn leads to increased transmission to the susceptible population, thus forming a vicious cycle. Another challenge for the accurate diagnosis is the vague clinical presentation, variable incubation period, and subclinical infection.

India has a high prevalence of TB; hence, many cases may remain undetected and only found on autopsy examination.[1]

This study aims to highlight such undetected cases of TB on autopsy.


  Methods Top


A retrospective, descriptive study was done over a 7-year duration from January 2014 to December 2020 in the Department of Pathology, Dr. Baba Saheb Ambedkar Medical College and Hospital, Delhi, India. Data were collected from the histopathological records of autopsy cases in the department. All the findings from 767 cases sent for autopsy during these 7 years were reviewed, and cases where a diagnosis of TB were given on histopathology undetected previously were included in our study. In all of the cases, the microscopic findings of all the representative organs were noted and reviewed by two histopathologists. The organs sent for histopathological analysis in all these cases included the heart, liver, spleen, kidneys, brain, lungs, and pancreas. However, in a few cases, parts of the intestine were also sent. These were received in 10% buffered formalin and subjected to processing in a routine manner. All the sections were then stained with hematoxylin and eosin (H and E) stain and special stains were used as and when required. The inclusion criterion for the case to be labeled as TB was the presence of epithelioid cell granulomas, caseous necrosis along with the presence of langhans giant cell. The cases where only granulomatous inflammation was observed were excluded from the study. The cases where a diagnosis of TB was already established were also excluded from the study. The cases were labeled as disseminated TB where TB involved organs other than lungs such as pleura, lymph node, liver spleen, pancreas, brain, genitourinary tract, skin, joints, and bone. Special stain for acid-fast bacilli – Ziehl–Neelsen stain was done in all the cases. The mycobacteria were examined with × 100 oil immersion objective, where the bacteria stained red with a light blue background. The histopathological findings pertaining to the presence of granuloma, giant cell, necrosis, and acid-fast bacilli were noted. After reviewing, we found 72 cases where a diagnosis of TB was made; however, 19 of them were already diagnosed cases. Hence, after applying the exclusion criterion, the undiagnosed cases came out to be 53. We tabulated the details noted for these 53 cases.


  Results Top


In the present study, a total of 72 cases had evidence of TB on histopathology. However, 19 cases were already diagnosed antemortem. Hence, making our undiagnosed cases as 53. Our study showed a male predominance with a male: female ratio of 1.52:1 [Table 1]. The most common age group involved was the third decade (20–30 years) followed by the second decade [Table 1]. Isolated pulmonary TB was seen in 26 cases [Figure 1]a. Solitary involvement of the kidney [Figure 1]b and liver [Figure 1]c was seen in three cases and one case, respectively. The remaining (23 cases) were labeled as disseminated TB [Table 2]. The most common organ involved in disseminated TB was the liver in 14 cases (26.4%), followed by the spleen [Figure 1]d in 11 cases (20.7%) and the kidney in 7 cases (13.2%). The less common organs involved were the pancreas [Figure 1]e and intestine [Figure 1]f with two cases each and a one case involving the heart [Figure 1]g and brain [Figure 1]h. The incidence of undiagnosed TB came out to be 6.91% (53/767) on autopsy. Fifty-three of total 72 cases of TB, 73.6% were incidentally diagnosed on autopsy. On microscopy, all cases showed caseating granulomatous inflammation [Figure 2]a. Eighteen cases of 53 showed the presence of epithelioid cell granulomas with langhans giant cell and 10 cases (14%) demonstrated acid-fast bacilli [Figure 2]b.
Table 1: Age and gender distribution

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Table 2: Organ involvement in disseminated tuberculosis

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Figure 1: (a) Pulmonary tuberculosis (H and E, ×4), (b) Renal tuberculosis (H and E, ×4), (c) Hepatic tuberculosis (H and E, ×10), (d) Splenic tuberculosis (H and E, ×4), (e) Pancreatic tuberculosis (H and E, ×10), (f) Intestinal tuberculosis (H and E, ×4), (g) tuberculosis pericarditis (H and E, ×4), (h) Cerebellar tuberculosis (H and E, ×4)

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Figure 2: (a) Epithelioid cell granuloma with giant cells (H and E, ×10), (b) Acid-fast bacilli seen as bright pink, beaded rod-like structure (Ziehl–Neelsen, ×100)

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  Discussion Top


TB is a chronic, infectious disease caused by Mycobacterium tuberculosis. It commonly affects the pulmonary system. Extrapulmonary TB has been reported in almost all organs except the enamel of teeth.[2] The heart, thyroid, pancreas, and skeletal muscle are considered to be relatively resistant to infection by tubercle bacilli.[2]

Human-to-human transmission occurs through droplet infection. After inhalation, the bacteria reach the alveoli. Alveolar macrophages are the first and foremost cells to be infected by M. tuberculosis where the microorganism replicates followed by helper T-cells response. The helper T-cells try to contain the bacteria and at the same time cause tissue damage. These macrophages get activated to form epithelioid histiocytes, and helper T cells coordinate the formation of granulomas and caseous necrosis, which marks the hallmark feature for the diagnosis of TB on histopathology.[3]

In the present study, the maximum incidence of TB was seen in the second to the third decade of life with a male predominance comparable to several previous studies.[3],[4]

The incidence of TB on autopsy in the present study came out to be 6.9% which was similar to the Indian study by Manmeet et al. [Table 3].[4] In the present postmortem study, undiagnosed cases of TB constituted a very high percentage (73.6%) as already reported by various authors from India and other countries, compared in [Table 3].[4],[5],[6],[7],[8] The large number of undetected or missed cases in general clinical practice may be due to various reasons. In a developing nation such as ours, the main cause is the taboo associated with TB. Furthermore, the clinical features of the disease are not specific and mimic several other infectious diseases such as viral infections, which are more commonly encountered by the clinicians. Hence, the cases may detected late causing multi-organ involvement leading to high mortality.
Table 3: Comparison of other studies with the present study

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The huge burden of disseminated TB (43%) was appreciated in the present study. Several other autopsy studies have shown that the percentage of disseminated TB ranges from 0.3% to 13.3%.[3] The high incidence of disseminated TB in our study can be explained by the fact that the patients are afraid and visit the clinician late because of attached social stigma with the disease.

The liver was the most common organ involved followed closely by the spleen and kidney in agreement with previous studies by Bhardwaj et al. and Shirvastava et al.[9],[10]

We report two cases of pancreatic involvement in disseminated TB, which is a very rare site. TB of the pancreas was first reported by Auerbach in 1944.[11] He identified 14 cases of pancreatic TB in a large series of 1656 autopsies. Various autopsy studies have shown involvement of the pancreas in 2.1%–4.7% of patients with miliary TB.[12],[13] Not much is known about the pathogenesis of pancreatic TB as it is very rare. It is postulated that the pancreas is rarely infected due to its retroperitoneal location and various pancreatic enzymes which inhibit the growth and replication of the Mycobacterium.[14] Pancreatic TB is mostly missed during the lifetime of the patient because of its low index of suspicion, symptomatology mimicking that of pancreatic carcinoma, and other potential diseases.[15]

The intestine was involved in one case as a part of disseminated TB. The ileocecal region is the most frequently associated part because of the presence of Peyer's patches and increased physiological stasis. Other sites that can be involved are ascending colon, jejunum, appendix, duodenum, and stomach. The gastrointestinal system gets involved by two ways. One way is the hematogenous spread from primary lung focus and the other way is the infection of Peyer's patches through ingestion of contaminated food and milk.[3]

Cardiac TB is rare, with a prevalence reported to be 0.14%–2% by Agarwal et al.[16] Infection can spread either: (i) directly to the heart from mediastinal lymph node, (ii) as a part of disseminated TB, and (iii) from the lymphohematogenous route. In 1664, Maurocord reported the first case of myocardial TB.[17] Antemortem diagnosis of TB is difficult due to nonspecific symptoms. We also diagnosed only one case where the heart was involved as a part of disseminated TB. It is hypothesized that the heart rarely gets affected due to its pumping activity which keeps it in motion always, which in turn makes it difficult for the bacterium to lodge itself in myocardium.[18]


  Conclusion Top


In spite of TB being a common disease in our country, we still face innumerable challenges in its diagnosis and treatment due to its varied clinical presentation. Through the results of the present study, we want to highlight the real magnitude of TB which may be much more than documented. The only way to prevent the increase in the number of cases and break the chain of transmission is its timely diagnosis and medical intervention. Hence, the clinicians need to be watchful for this possibility and always consider TB in the differential diagnosis of asymptomatic or mildly symptomatic cases as well as advise newer and rapid diagnostic modalities accordingly.

Limitations of the study

The retrospective study was done for only 7 years, thus limiting the number of cases. For a country such as India, where TB is prevalent, further studies need to be conducted for a longer duration of time.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
WHO. Global Tuberculosis Report 2018. Available from: http://www.who.int/tb/publications/global_report/en/. [Last accessed on 2021 Jun 10].  Back to cited text no. 1
    
2.
Lee JY. Diagnosis and treatment of extrapulmonary tuberculosis. Tuberc Respir Dis (Seoul) 2015;78:47-55.  Back to cited text no. 2
    
3.
Natarajan A, Beena PM, Devnikar AV, Mali S. A systemic review on tuberculosis. Indian J Tuberc 2020;67:295-311.  Back to cited text no. 3
    
4.
Kaur M, Tiwana KK, Niborhia S, Singla N. Incidental diagnosis of tuberculosis on histopathology: A 6 year autopsy study. Indian J Med Toxicol Forensic Med 2019;13:124-8.  Back to cited text no. 4
    
5.
Flavin RJ, Gibbons N, O'Briain DS. Mycobacterium tuberculosis at autopsy – Exposure and protection: An old adversary revisited. J Clin Pathol 2007;60:487-91.  Back to cited text no. 5
    
6.
Yamamoto A, Tsuchiya K, Kusajima K, Shimoide H, Nunomura M, Hebisawa A. Study on clinico-pathological features of active pulmonary tuberculosis found at autopsy in a general hospital. Kekkaku 2009;84:71-8.  Back to cited text no. 6
    
7.
Garg M, Aggarwal AD, Singh S, Kataria SP. Tuberculous lesions at autopsy. J Indian Acad Forensic Med 2011;33:116-9.  Back to cited text no. 7
    
8.
Bavikar R, Valand A, Kumar H, Gore C, Iqbal M B, et al. Tuberculosis at autopsy in inpatients at a tertiary referral centre in India: A prospective study. Indian J Pathol Oncol 2015;2:186-8.  Back to cited text no. 8
    
9.
Bhardwaj AK, Kumar D, Raina SK, Sharma S, Chander V. Assessment of Extra Pulmonary Tuberculosis (EPTB) cases from selected Tuberculosis Units (TUs) of Himachal Pradesh, India. Int J Health 2015;3:29-33.  Back to cited text no. 9
    
10.
Shirvastva AK, Brahmachari S, Pathak P, Kumar R, Patel U, Mandil A. Clinico- Epidemiological profile of extrapulmonary tuberculosis in central India. Int J Med Res Rev 2015;3:223-30.  Back to cited text no. 10
    
11.
Auerbach O. Acute generalized miliary tuberculosis. Am J Pathol 1944;20:121-36.  Back to cited text no. 11
    
12.
Tarvadi VP, Suares S, Permi SH, Manipady S, Shetty M. Miliart tuberculosis: An accidental finding at autopsy. Indian J Med Toxicol Forensic Med 2016;6:171-4.  Back to cited text no. 12
    
13.
Kwong JS, Carignan S, Kang EY, Müller NL, FitzGerald JM. Miliary tuberculosis. Diagnostic accuracy of chest radiography. Chest 1996;110:339-42.  Back to cited text no. 13
    
14.
Crook LD, Johnson FP Jr. Tuberculosis of the pancreas: A case report. Tubercle 1988;69:148-51.  Back to cited text no. 14
    
15.
Eyal AS, Karusseit VO. Tuberculosis of the pancreas mimicking carcinoma. Int J Infect Dis 2008;12:108-10.  Back to cited text no. 15
    
16.
Agarwal R, Malhotra P, Awasthi A, Kakkar N, Gupta D. Tuberculous dilated cardiomyopathy: An under-recognized entity? BMC Infect Dis 2005;5:29.  Back to cited text no. 16
    
17.
du Toit-Prinsloo L, Saayman G. “Death at the wheel” due to tuberculosis of the myocardium: A case report. Cardiovasc Pathol 2016;25:271-4.  Back to cited text no. 17
    
18.
Rose AG. Cardiac tuberculosis. A study of 19 patients. Arch Pathol Lab Med 1987;111:422-6.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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