Journal of Pathology and Translational Medicine

Original Article

Indirect pathological indicators for cardiac sarcoidosis on endomyocardial biopsy: Myung-Jin Cha, Jeong-Wook Seo, Seil Oh, Eun-Ah Park, Sang-Han Lee, Moon Young Kim, Jae-Young Park; J Pathol Transl Med. 2020;54(5):396-410. Published online July 29, 2020; DOI: https://doi.org/10.4132/jptm.2020.06.10

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Background
The definitive pathologic diagnosis of cardiac sarcoidosis requires observation of a granuloma in the myocardial tissue. It is common, however, to receive a “negative” report for a clinically probable case. We would like to advise pathologists and clinicians on how to interpret “negative” biopsies.
Methods
Our study samples were 27 endomyocardial biopsies from 25 patients, three cardiac transplantation and an autopsied heart with suspected cardiac sarcoidosis. Pathologic, radiologic, and clinical features were compared.
Results
The presence of micro-granulomas or increased histiocytic infiltration was always (6/6 or 100%) associated with fatty infiltration and confluent fibrosis, and they showed radiological features of sarcoidosis. Three of five cases (60%) with fatty change and confluent fibrosis were probable for cardiac sarcoidosis on radiology. When either confluent fibrosis or fatty change was present, one-third (3/9) were radiologically probable for cardiac sarcoidosis. We interpreted cases with micro-granuloma as positive for cardiac sarcoidosis (five of 25, 20%). Cases with both confluent fibrosis and fatty change were interpreted as probable for cardiac sarcoidosis (seven of 25, 28%). Another 13 cases, including eight cases with either confluent fibrosis or fatty change, were interpreted as low probability based on endomyocardial biopsy.
Conclusions
The presence of micro-granuloma could be an evidence for positive diagnosis of cardiac sarcoidosis. Presence of both confluent fibrosis and fatty change is necessary for probable cardiac sarcoidosis in the absence of granuloma. Either of confluent fibrosis or fatty change may be an indirect pathological evidence but they are interpreted as nonspecific findings.

Citations

Citations to this article as recorded by

Diagnostic Value of Comprehensive Echocardiographic Assessment Including Speckle-Tracking in Patients with Sarcoidosis Versus Healthy Controls: A Systematic Review and Meta-Analysis
Hritvik Jain, Maryam Shahzad, Muneeba Ahsan, Rahul Patel, Jagjot Singh, Ramez M. Odat, Aman Goyal, Raveena Kelkar, Nishad Barve, Hina Farrukh, Raheel Ahmed
Diagnostics.2025; 15(6): 708. CrossRef
Advances in cellular and tissue-based imaging techniques for sarcoid granulomas
Junwoo Kim, Girish Dwivedi, Berin A. Boughton, Ankur Sharma, Silvia Lee
American Journal of Physiology-Cell Physiology.2024; 326(1): C10. CrossRef
Lipomatous Metaplasia Is Associated With Ventricular Tachycardia Recurrence Following Ablation in Patients With Nonischemic Cardiomyopathy
Lingyu Xu, Mirmilad Khoshknab, Juwann Moss, Ronald D. Berger, Jonathan Chrispin, David Callans, Francis E. Marchlinski, Stefan L. Zimmerman, Yuchi Han, Natalia Trayanova, Benoit Desjardins, Saman Nazarian
JACC: Clinical Electrophysiology.2024; 10(6): 1135. CrossRef
Cardiac Sarcoidosis: A Comprehensive Clinical Review
András Vereckei, Zsuzsanna Besenyi, Viktória Nagy, Bence Radics, Hajnalka Vágó, Zsigmond Jenei, Gábor Katona, Róbert Sepp
Reviews in Cardiovascular Medicine.2024;[Epub] CrossRef
Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis
Jukka Lehtonen, Valtteri Uusitalo, Pauli Pöyhönen, Mikko I Mäyränpää, Markku Kupari
European Heart Journal.2023; 44(17): 1495. CrossRef
Cardiac sarcoidosis: a comprehensive review of risk factors, pathogenesis, diagnosis, clinical manifestations, and treatment strategies
Hussain Haider Shah, Syeda Alishah Zehra, Aliza Shahrukh, Radeyah Waseem, Tooba Hussain, Muhammad Sheheryar Hussain, Fareeha Batool, Muhammad Jaffer
Frontiers in Cardiovascular Medicine.2023;[Epub] CrossRef
Histology of Cardiac Sarcoidosis with Novel Considerations Arranged upon a Pathologic Basis
Shu Kato, Yasuhiro Sakai, Asako Okabe, Yoshiaki Kawashima, Kazuhiko Kuwahara, Kazuya Shiogama, Masato Abe, Hiroyasu Ito, Shin’ichiro Morimoto
Journal of Clinical Medicine.2022; 11(1): 251. CrossRef
Cardiac sarcoidosis: A multimodal approach to reach the diagnosis
Nicolas Piriou, Patrick Bruneval
International Journal of Cardiology.2021; 323: 264. CrossRef
Value of 3D mapping‐guided endomyocardial biopsy in cardiac sarcoidosis
Danielle M. Haanschoten, Ahmet Adiyaman, Nils A. ‘t Hart, Piet L. Jager, Arif Elvan
European Journal of Clinical Investigation.2021;[Epub] CrossRef
Cardiac Sarcoidosis: A Clinical Overview
Ana Carolina Alba, Shyla Gupta, Lakshmi Kugathasan, Andrew Ha, Alejandro Ochoa, Meyer Balter, Alvaro Sosa Liprandi, Maria Inés Sosa Liprandi
Current Problems in Cardiology.2021; 46(10): 100936. CrossRef

Case Reports

Cardiac Sarcoidosis Treated by Cardiac Transplantation: A Case Report.: Jaejung Jang, Kwangseon Min, Gyeong cheon Jung, Jaejung Kim, Inchul Lee; Korean J Pathol. 2001;35(1):71-75.

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Abstract PDF: Sarcoidosis, in general, has a low mortality rate. But cardiac sarcoidosis (CS) is a serious condition which may lead to death. Here, we report a rare case of CS that was treated by heart transplantation. A 47-year-old male had occasional syncopes and atypical chest pain. Ventricular tachycardia with right bundle branch block was noted by electrocardiogram. Multiple fixed myocardial perfusion defects in the interventricular septum and both the inferior-posterior ventricular walls were observed by thallium scan. Coronary angiography was unremarkable. Neither perihilar nor mediastinal lymphadenopathy was noted. The patient also suffered three times from tonic-clonic generalized seizures in 3 years, but no neurologic abnormalities were detected. The explanted heart displayed multiple white patches on the endomyocardial surface, measuring up to 8x7 cm. On microscopic examination, the lesion consisted of multiple well-formed and confluent granulomas with numerous scattered multinucleated giant cells, CD68-positive epithelioid histiocytes, and T-lymphocytes. Neither microorganisms nor foreign material was identified on special stain and culture study. It has been six months since the heart transplant, and the patient has been doing well.

Sarcoidosis Associated with Adenocarcinoma of the Lung: A Case Report.: Joon Seon Song, Seungkoo Lee, Yong Hee Kim, Se Jin Jang; Korean J Pathol. 2008;42(2):108-112.

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Abstract PDF: Sarcoidosis and malignant neoplasm are frequently encountered pulmonary diseases, but their combined existence in the same patient is rare. As sarcoidosis usually presents as mediastinal lymphadenopathy, its concurrence in lung cancer patient radiologically mimics mediastinal metastasis and this can be possibly interpreted as unresectable disease. We report here on a case of lung adenocarcinoma associated with sarcoidosis that developed in a 64 year-old male who underwent surgical resection. Radiological examinations revealed 5.7 cm-sized mass in the right upper lobe with an enlargement of the bilateral supraclavicular, highest mediastinal, subcarinal and the upper and lower paratracheal lymph nodes. Histologic examination showed a well differentiated adenocarcinoma with non-caseating epithelioid granulomas in the lung. The enlarged peribronchial and mediastinal lymph nodes also revealed sarcoid granulomas without cancer metastasis. A good prognosis may be expected for those cases of lung cancers with non-caseating granulomas in the regional lymph nodes. The patient presently has no symptoms or signs of tumor, without further treatment since his surgery.

Sudden Death from Cardiac Sarcoidosis: A Case Report.: Soo Kyoung Lee, Sun Zoo Kim, Yoon Seup Kum, Tae In Park, Sang Han Lee, Jong Min Chae, Jung Sik Kwak; Korean J Pathol. 2003;37(5):358-361.

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Abstract PDF: Sarcoidosis is a systemic granulomatous inflammation with an unknown cause. The commonly involved sites are the lymph nodes, lungs, skin, eyes, and heart. Although cardiac involvement in sarcoidosis is rarely detected clinically, it is reported in 20-50% of autopsied sarcoidosis patients. Cardiac involvement is one of the most severe conditions of sarcoidosis and may cause sudden death. We report a case of a sudden death due to a massive cardiac sarcoidosis in a 43-year-old man. The microscopic examination revealed an extensive noncaseating granulomatous inflammation in the mediastinal lymph nodes and the heart with no evidence of myocyte necrosis. A special stain and molecular study excluded the possibility of other causes such as fungi or mycobacterium. The authors concluded that the cause of death was attributed to arrhythmia due to a cardiac sarcoidosis with massive involvement of the conduction system.

Original Articles

An Analysis for Angiotensin Converting Enzyme Gene Polymorphism in Formalin-fixed, Paraffin-embedded Tissues from Patients with Sarcoidosis.: Tae Sook Kim, Hee Yeon Hong, In chul Lee; Korean J Pathol. 2003;37(4):225-231.

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Abstract PDF: BACKGROUND
Sarcoidosis is a systemic disease characterized by nonnecrotizing granulomas involving the lung and hilar lymph nodes. Serum angiotensin converting enzyme (sACE) levelsin patients with sarcoidosis have been implicated as an indicator of granuloma burden.Recently, it has been found that ACE gene insertion/deletion (ID) polymorphism affects sACE levels in healthy individuals. Moreover, reported sACE levels were highest in the deletion/deletion(DD) genotype. Previous studies to investigate the distribution of ACE genotypes accordingto ethnic groups have revealed various results and have caused controversy.
METHODS
Polymerase chain reactions were performed to determine the ACE genotypes in fifteen formalinfixed, paraffin-embedded tissues from patients with sarcoidosis.
RESULTS
The distribution of ACE gene (I/D) polymorphism in patients with sarcoidosis was significantly different from that in normal controls. The DD genotype was more frequent in patients with sarcoidosis than in thenormal controls. The D allele frequency was also higher in patients with sarcoidosis than in thenormal controls. The relative risk of sarcoidosis was higher in DD homozygotes.
CONCLUSIONS
These results suggested the ACE gene I/D polymorphism may play an important rolein the pathogenesis and progression of sarcoidosis.

Sarcoidosis Involving the Spinal Dura.: Young Shin Kim, Ki Hwa Yang, Byoung Kee Kim, Sun Moo Kim; Korean J Pathol. 1991;25(2):158-163.

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Abstract PDF: Neurosarcoidosis without systemic manifestation is vary unusual condition. Solitary lesion in the spinal dura is exceptional. The diagnosis of the neurosarcoidosis is very difficult, because the efficacy of Kveim test is low in neurosarcoidosis. The histologic examination is considered as confirmative diagnostic tool. The authors reported a case of neurosarcoidosis involving the dura of the cervical spine, in a fifty-nine year old female who had suffered from mid-back pain for six months and paraparesis for two weeks. There was a dumbbell shaped mass in the D4-5 dura. It showed tan gray color with rubbery consistency. With histological examination, it revealed diffuse non-caseating granuloma. Occasionally asteroid bodies were observed within the cytoplasm of the multinucleated giant cells. After operation, she was treated with steroid, and she has been well about nine month period.

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