Case Report
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Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: A rare case report Harpal Singh, Ramesh Kundal Department of Pathology, Government Medical College Patiala, Patiala, Punjab, India Address for correspondence: Dr. Harpal Singh, Department of Pathology, Government Medical College Patiala, # 835/13 Ghuman Nagar A, Sirhind Road, Patiala - 147 001, Punjab, India. E-mail: [email protected]
ABSTRACT
Access this article online
Idiopathic granulomatous myocarditis is extremely rare, particularly since the introduction of drugs effective against tuberculosis (TB), viruses, fungi and the effective treatment of sarcoidosis. Here is a case of a 65-year-old female prisoner having history of sudden collapse and ultimately death. Autopsy findings of various viscera on histopathological examination show granulomatous pathology, that is, in spleen, liver and in the left ventricular wall of heart. Ziehl-Neelsen staining of the sections show the absence of acid fast bacilli, negative for fungal staining as most of the granulomas are noncaseating type with presence of giant cells having no asteroid body and Schuamann body, real-time polymerase chain reaction for TB is negative. Idiopathic giant cell myocarditis is a disease of relatively young adults, that is, between 3rd and 4th decade of life. So, this case is strongly considered to be a case of sudden death due to myocarditis as a result of idiopathic systemic granulomatous pathology, a rare case in in literature. KEY WORDS: Endomyocardial biopsy, idiopathic giant cell myocarditis, idiopathic granulomatous myocarditis
INTRODUCTION Myocarditis or inflammatory cardiomyopathy is inflammation of heart muscle diagnosed on endomyocardial biopsy (EMB) established by histological, immunological, and immunohistochemical criteria. Myocarditis is most often due to infection by common viruses.[1] Systemic miliary tuberculosis (TB) occurs when bacteria disseminate through the systemic arterial system marked by a characteristic granulomatous inflammatory reaction that forms both caseating and noncaseating tubercles.[2] Lymphocytic and giant cell myocarditis are presumed idiopathic or autoimmune if no viruses are identified in EMB and other known causes are excluded.[3] Recent prospective post-mortem data had shown sudden cardiac death of young adults at rates of 8.6-12% due to myocarditis.[4] CASE REPORT The viscera, that is, whole heart, part of spleen, part of liver and parts of both the kidneys of a 65-year-old female prisoner received in the Department of Pathology to know the cause of death, who died in hospital admitted with complaints of urinary incontinency, lower back ache, prolapsed inter-vertebral disc and fracture of L1 vertebra recorded in post-mortem report. Her post-mortem was done in the Department of Forensic Medicine. On gross examination, heart is enlarged weighing 460 g with pericardial fat and on cutting hypertrophied left ventricle wall of thickness of 1.9 cm with white grey area, INDIAN JOURNAL
OF
PATHOLOGY
AND
Website: www.ijpmonline.org PMID: xxxxxxxxx DOI: 10.4103/0377-4929.151201 Quick Response Code:
but with normal interventricular septum and patent coronary arteries [Figure 1]. Grossly part of liver looks grey brown with somewhat greasy touch, measuring 12 cm × 10 cm × 8 cm and weighing 450 g and cut section looks normal. Part of spleen measuring 10 cm × 8 cm × 4 cm and weighing 172 g looks enlarged with rounded light grey areas on cut surface are identified [Figure 2]. Parts from both the kidneys show dilated pelves and on cutting both parts show small cystic areas with one large cystic area studded with white single stone in its center. Microscopically, sections from the light colored area of the left ventricle wall show well-formed noncaseating granulomas with presence of numerous Langhans’ type and foreign body type of giant cells, lymphocytes and macrophages. Most of the granulomas are started near the wall of the blood vessel surrounded by pericardial fat towards the periphery. Bundles of normal looking cardiac myocytes also encircles the granulomas with evidence of cardiomyolysis in the center and toward the periphery [Figures 3 and 4]. Sections from the leaflets, aorta and coronaries look normal and patent.
MICROBIOLOGY - 58(1), JANUARY-MARCH 2015
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[Downloaded free from http://www.ijpmonline.org on Friday, May 15, 2015, IP: 61.12.101.178] Singh and Kundal: Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: A rare case repot
Sections from the part of spleen and liver again show similar type of granulomas, with addition of fatty change in the liver [Figures 5 and 6]. Microscopic examination of the parts
of kidneys show lymphocytic infiltration and degenerated tubules.
Figure 1: Gross examina on of heart shows pathological light colored area on the hypertrophied le ventricle
Figure 2: Cut surface of spleen show light colored pathological rounded areas
Figure 3: H and E sec on from light colored area of le ventricle heart under ×10
Figure 4: H and E section of left ventricle under ×40 showing noncasea ng granuloma
Figure 5: H and E sec on of spleen under ×10 shows noncasea ng granulomas
Figure 6: H and E sec on of liver under ×5 showing fa y infiltra on and noncasea ng granulomas
100
INDIAN JOURNAL
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PATHOLOGY
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Final diagnosis of idiopathic granulomatous myocarditis with systemic granulomatous pathology as a cause of sudden death was
MICROBIOLOGY - 58(1), JANUARY-MARCH 2015
[Downloaded free from http://www.ijpmonline.org on Friday, May 15, 2015, IP: 61.12.101.178] Singh and Kundal: Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: A rare case repot
made after considering noncaseating granulomas by excluding sarcoidosis with absence of asteroid and Schaumann body, negative for special stains of fungi, acid fast bacilli (AFB) not detected on Ziehl-Neelsen (ZN) staining and real-time polymerase chain reaction (RT-PCR). No record of any EMB is available. DISCUSSION Myocarditis is a group of pathologic entities in which infectious micro-organisms and/or inflammatory processes cause myocardial injury. A rare type of this disease is idiopathic giant cell myocarditis.[5] Tuberculous myocarditis is very rare and was at one time found most frequently in children and young adults, invariably co-existing with tuberculous disease elsewhere.[6] The diagnosis is usually established on post-mortem and the incidence may therefore be greater than currently reported.[7] Major symptom is rapid progressive heart failure or concomitant ventricular arrhythmias. Its high morbidity and mortality are due to its refractory response to all forms of treatment.[8] However, the granulomas in sarcoidosis do have a characteristic appearance with concentric fibrosis, suggestive of the diagnosis on histology.[9] A retrospective study of 112 consecutive patients with biopsy-confirmed myocarditis at the Massachusetts General Hospital demonstrated the following pathological distribution: Lymphocytic 55%, borderline 22%, granulomatous 10%, and eosinophilic 6%.[10] In this case scattered, small granulomas without caseous necrosis can also be seen, but absence of the hallmark of tertiary syphilis such as the presence of arteritis and phlebitis with hyperplasia of the endothelium and a perivascular cuffing of lymphocytes and plasma cells, rules out to be a case of syphilis. Another strong evidence favoring TB in this case was the presence of hydronephrosis, nephrolithiasis and pyonephrosis with clinical features of urinary incontinence, pain in the flank, pathological fracture of lumbar vertebra in the absence of any history of trauma, but AFB were not detected on ZN staining and RT-PCR,
INDIAN JOURNAL
OF
PATHOLOGY
AND
thus rules out to be a case of systemic TB. Asteroid bodies in giant cells, Schuamann bodies which are characteristics although not pathognomonic and concentric fibrosis in the granulomas are absent, thus rules out to be a definite case of sarcoidosis. This case thus emphasizes the importance of a careful search for similar type of granulomas in each organ excluding all other causes of granulomas leading to sudden death due to ventricular arrhythmias. Keeping all these conditions in mind along with prevailing living conditions in the prisons, strong possibility of idiopathic systemic granulomatous pathology causing myocarditis needs to be investigated before death and thus giving proper treatment. REFERENCES 1. 2. 3. 4. 5.
6.
7.
8. 9.
10.
Subiksha PS. Myocarditis pathology. Int J Pharm Sci Invent 2014;3:1-4. Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 8th ed. New Delhi: Elsevier; 2010. p. 370-1. Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet 2012;379:738-47. Doolan A, Langlois N, Semsarian C. Causes of sudden cardiac death in young Australians. Med J Aust 2004;180:110-2. Momin YA, Raghuvanshi SR, Lanjewar DN. Idiopathic giant cell myocarditis leading to sudden death – A rare case report. Bombay Hosp J 2008;50:288-9. Horn H, Saphir O. The involvement of the myocardium in tuberculosis: A review of the literature and report of three cases. Am Rev Tuberc 1935;32:492-506. Agarwal R, Malhotra P, Awasthi A, Kakkar N, Gupta D. Tuberculous dilated cardiomyopathy: An under-recognized entity? BMC Infect Dis 2005;5:29. Blauwet LA, Cooper LT. Myocarditis. Prog Cardiovasc Dis 2010;52:274-88. Sarno M, Hasleton PS, Spiteri MA. Sarcoidosis. In: Haselton PS, editor. Spencer’ Pathology of the Lung. 5th ed. New York: McGraw-Hill; 1996. p. 507-35. Magnani JW, Danik HJ, Dec GW Jr, DiSalvo TG. Survival in biopsy-proven myocarditis: A long-term retrospective analysis of the histopathologic, clinical, and hemodynamic predictors. Am Heart J 2006;151:463-70.
How to cite this article: Singh H, Kundal R. Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: A rare case report. Indian J Pathol Microbiol 2015;58:99-101. Source of Support: Nil, Conflict of Interest: None declared.
MICROBIOLOGY - 58(1), JANUARY-MARCH 2015
101
[Downloaded free from http://www.ijpmonline.org on Friday, May 15, 2015, IP: 61.12.101.178]
Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: A rare case report Harpal Singh, Ramesh Kundal Department of Pathology, Government Medical College Patiala, Patiala, Punjab, India Address for correspondence: Dr. Harpal Singh, Department of Pathology, Government Medical College Patiala, # 835/13 Ghuman Nagar A, Sirhind Road, Patiala - 147 001, Punjab, India. E-mail: [email protected]
ABSTRACT
Access this article online
Idiopathic granulomatous myocarditis is extremely rare, particularly since the introduction of drugs effective against tuberculosis (TB), viruses, fungi and the effective treatment of sarcoidosis. Here is a case of a 65-year-old female prisoner having history of sudden collapse and ultimately death. Autopsy findings of various viscera on histopathological examination show granulomatous pathology, that is, in spleen, liver and in the left ventricular wall of heart. Ziehl-Neelsen staining of the sections show the absence of acid fast bacilli, negative for fungal staining as most of the granulomas are noncaseating type with presence of giant cells having no asteroid body and Schuamann body, real-time polymerase chain reaction for TB is negative. Idiopathic giant cell myocarditis is a disease of relatively young adults, that is, between 3rd and 4th decade of life. So, this case is strongly considered to be a case of sudden death due to myocarditis as a result of idiopathic systemic granulomatous pathology, a rare case in in literature. KEY WORDS: Endomyocardial biopsy, idiopathic giant cell myocarditis, idiopathic granulomatous myocarditis
INTRODUCTION Myocarditis or inflammatory cardiomyopathy is inflammation of heart muscle diagnosed on endomyocardial biopsy (EMB) established by histological, immunological, and immunohistochemical criteria. Myocarditis is most often due to infection by common viruses.[1] Systemic miliary tuberculosis (TB) occurs when bacteria disseminate through the systemic arterial system marked by a characteristic granulomatous inflammatory reaction that forms both caseating and noncaseating tubercles.[2] Lymphocytic and giant cell myocarditis are presumed idiopathic or autoimmune if no viruses are identified in EMB and other known causes are excluded.[3] Recent prospective post-mortem data had shown sudden cardiac death of young adults at rates of 8.6-12% due to myocarditis.[4] CASE REPORT The viscera, that is, whole heart, part of spleen, part of liver and parts of both the kidneys of a 65-year-old female prisoner received in the Department of Pathology to know the cause of death, who died in hospital admitted with complaints of urinary incontinency, lower back ache, prolapsed inter-vertebral disc and fracture of L1 vertebra recorded in post-mortem report. Her post-mortem was done in the Department of Forensic Medicine. On gross examination, heart is enlarged weighing 460 g with pericardial fat and on cutting hypertrophied left ventricle wall of thickness of 1.9 cm with white grey area, INDIAN JOURNAL
OF
PATHOLOGY
AND
Website: www.ijpmonline.org PMID: xxxxxxxxx DOI: 10.4103/0377-4929.151201 Quick Response Code:
but with normal interventricular septum and patent coronary arteries [Figure 1]. Grossly part of liver looks grey brown with somewhat greasy touch, measuring 12 cm × 10 cm × 8 cm and weighing 450 g and cut section looks normal. Part of spleen measuring 10 cm × 8 cm × 4 cm and weighing 172 g looks enlarged with rounded light grey areas on cut surface are identified [Figure 2]. Parts from both the kidneys show dilated pelves and on cutting both parts show small cystic areas with one large cystic area studded with white single stone in its center. Microscopically, sections from the light colored area of the left ventricle wall show well-formed noncaseating granulomas with presence of numerous Langhans’ type and foreign body type of giant cells, lymphocytes and macrophages. Most of the granulomas are started near the wall of the blood vessel surrounded by pericardial fat towards the periphery. Bundles of normal looking cardiac myocytes also encircles the granulomas with evidence of cardiomyolysis in the center and toward the periphery [Figures 3 and 4]. Sections from the leaflets, aorta and coronaries look normal and patent.
MICROBIOLOGY - 58(1), JANUARY-MARCH 2015
99
[Downloaded free from http://www.ijpmonline.org on Friday, May 15, 2015, IP: 61.12.101.178] Singh and Kundal: Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: A rare case repot
Sections from the part of spleen and liver again show similar type of granulomas, with addition of fatty change in the liver [Figures 5 and 6]. Microscopic examination of the parts
of kidneys show lymphocytic infiltration and degenerated tubules.
Figure 1: Gross examina on of heart shows pathological light colored area on the hypertrophied le ventricle
Figure 2: Cut surface of spleen show light colored pathological rounded areas
Figure 3: H and E sec on from light colored area of le ventricle heart under ×10
Figure 4: H and E section of left ventricle under ×40 showing noncasea ng granuloma
Figure 5: H and E sec on of spleen under ×10 shows noncasea ng granulomas
Figure 6: H and E sec on of liver under ×5 showing fa y infiltra on and noncasea ng granulomas
100
INDIAN JOURNAL
OF
PATHOLOGY
AND
Final diagnosis of idiopathic granulomatous myocarditis with systemic granulomatous pathology as a cause of sudden death was
MICROBIOLOGY - 58(1), JANUARY-MARCH 2015
[Downloaded free from http://www.ijpmonline.org on Friday, May 15, 2015, IP: 61.12.101.178] Singh and Kundal: Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: A rare case repot
made after considering noncaseating granulomas by excluding sarcoidosis with absence of asteroid and Schaumann body, negative for special stains of fungi, acid fast bacilli (AFB) not detected on Ziehl-Neelsen (ZN) staining and real-time polymerase chain reaction (RT-PCR). No record of any EMB is available. DISCUSSION Myocarditis is a group of pathologic entities in which infectious micro-organisms and/or inflammatory processes cause myocardial injury. A rare type of this disease is idiopathic giant cell myocarditis.[5] Tuberculous myocarditis is very rare and was at one time found most frequently in children and young adults, invariably co-existing with tuberculous disease elsewhere.[6] The diagnosis is usually established on post-mortem and the incidence may therefore be greater than currently reported.[7] Major symptom is rapid progressive heart failure or concomitant ventricular arrhythmias. Its high morbidity and mortality are due to its refractory response to all forms of treatment.[8] However, the granulomas in sarcoidosis do have a characteristic appearance with concentric fibrosis, suggestive of the diagnosis on histology.[9] A retrospective study of 112 consecutive patients with biopsy-confirmed myocarditis at the Massachusetts General Hospital demonstrated the following pathological distribution: Lymphocytic 55%, borderline 22%, granulomatous 10%, and eosinophilic 6%.[10] In this case scattered, small granulomas without caseous necrosis can also be seen, but absence of the hallmark of tertiary syphilis such as the presence of arteritis and phlebitis with hyperplasia of the endothelium and a perivascular cuffing of lymphocytes and plasma cells, rules out to be a case of syphilis. Another strong evidence favoring TB in this case was the presence of hydronephrosis, nephrolithiasis and pyonephrosis with clinical features of urinary incontinence, pain in the flank, pathological fracture of lumbar vertebra in the absence of any history of trauma, but AFB were not detected on ZN staining and RT-PCR,
INDIAN JOURNAL
OF
PATHOLOGY
AND
thus rules out to be a case of systemic TB. Asteroid bodies in giant cells, Schuamann bodies which are characteristics although not pathognomonic and concentric fibrosis in the granulomas are absent, thus rules out to be a definite case of sarcoidosis. This case thus emphasizes the importance of a careful search for similar type of granulomas in each organ excluding all other causes of granulomas leading to sudden death due to ventricular arrhythmias. Keeping all these conditions in mind along with prevailing living conditions in the prisons, strong possibility of idiopathic systemic granulomatous pathology causing myocarditis needs to be investigated before death and thus giving proper treatment. REFERENCES 1. 2. 3. 4. 5.
6.
7.
8. 9.
10.
Subiksha PS. Myocarditis pathology. Int J Pharm Sci Invent 2014;3:1-4. Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 8th ed. New Delhi: Elsevier; 2010. p. 370-1. Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet 2012;379:738-47. Doolan A, Langlois N, Semsarian C. Causes of sudden cardiac death in young Australians. Med J Aust 2004;180:110-2. Momin YA, Raghuvanshi SR, Lanjewar DN. Idiopathic giant cell myocarditis leading to sudden death – A rare case report. Bombay Hosp J 2008;50:288-9. Horn H, Saphir O. The involvement of the myocardium in tuberculosis: A review of the literature and report of three cases. Am Rev Tuberc 1935;32:492-506. Agarwal R, Malhotra P, Awasthi A, Kakkar N, Gupta D. Tuberculous dilated cardiomyopathy: An under-recognized entity? BMC Infect Dis 2005;5:29. Blauwet LA, Cooper LT. Myocarditis. Prog Cardiovasc Dis 2010;52:274-88. Sarno M, Hasleton PS, Spiteri MA. Sarcoidosis. In: Haselton PS, editor. Spencer’ Pathology of the Lung. 5th ed. New York: McGraw-Hill; 1996. p. 507-35. Magnani JW, Danik HJ, Dec GW Jr, DiSalvo TG. Survival in biopsy-proven myocarditis: A long-term retrospective analysis of the histopathologic, clinical, and hemodynamic predictors. Am Heart J 2006;151:463-70.
How to cite this article: Singh H, Kundal R. Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: A rare case report. Indian J Pathol Microbiol 2015;58:99-101. Source of Support: Nil, Conflict of Interest: None declared.
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