Background: Myocarditis is an inflammation of the myocardium diagnosed according to histological, immunological, and immunochemical criteria. The complexity of achieving a precise diagnosis and anatomopathological definition has necessitated updates to the classic Dallas histological criteria. Immunohistochemistry has improved diagnosis by allowing quantification of inflammatory infiltrate, though some degree of overdiagnosis remains. Study objective: To validate a new grading system for myocarditis diagnosis based on quantification of inflammatory infiltrate in endomyocardial biopsies (EMB), and to correlate clinical and histological data. Materials and methods: Optical microscope reevaluation of EMBs from patients clinically suspected of myocarditis was conducted to quantify CD3+ cell infiltrate and detect necrosis, fibrosis, cardiomyopathic changes, and potential PCR (Polymerase Chain Reaction) positivity. Clinical data including presentation mode, timing of EMB, follow-up with potential heart transplant or mortality, and cardiac magnetic resonance imaging (MRI) reports were collected. MRI provided information on edema, late gadolinium enhancement (LGE), and left ventricular ejection fraction (LVEF). Results: Applying the proposed new grading system to 106 cases, 43 (40.5%) EMBs were negative, 6 (5.7%) were non-lymphocytic myocarditis, 7 (6.6%) were mild myocarditis, 1 (0.9%) was moderate myocarditis, 13 (12%) were severe myocarditis, and 33 (31,1%) were classified as Lymphocytic Infiltrate of Undetermined Significance (LIUS). Additionally, 3 cases (2.8%) did not fit into any proposed diagnostic category. 14% of EMBs were positive for viral genome by PCR. Heart failure was the most common clinical presentation (58%), while shock was rare (2.8%). Most EMBs (43%) were performed more than a month after symptom onset. Myocarditis diagnosis was predominantly achieved within 4 weeks of EMB. CD3+ lymphocyte quantification among LIUS showed similar distribution across clinical presentations. There was no statistically significant correlation between LGE and histologically identified fibrosis, edema on MRI and myocarditis/LIUS diagnosis, or between LGE and cardiomyopathic changes. However, a significant relationship was found between LVEF values and cardiomyopathic changes (p=0.006). Follow-up biopsies of 3 patients diagnosed with severe myocarditis showed persistent myocarditis (2 severe, 1 mild) at 2 and 3 years. Among study participants, 1 patient died, and 8 underwent heart transplantation, though only 1 of these patients had myocarditis diagnosed. Myocarditis diagnosed by Dallas criteria accounted for 85.8%, significantly higher than diagnoses by the new criteria proposed by the Society for Cardiovascular Pathology (27.4%). Conclusions: The new grading system reduces myocarditis overdiagnosis through inflammatory infiltrate quantification and introduction of the LIUS category. EMB has greater diagnostic capability if performed within 4 weeks, especially within the first week of symptom onset. Further studies are needed to investigate statistical correlations, limited here by sample subgroup scarcity. Consistent with literature, despite MRI's growing importance, EMB remains the diagnostic gold standard for myocarditis.
Background:La miocardite è un’infiammazione del miocardio diagnosticata secondo criteri istologici, immunologici e immunoistochimici. La complessità di una diagnosi precisa e di una definizione anatomopatologica più accurata possibile ha portato alla necessità di aggiornare i criteri istologici di Dallas. L’immunoistochimica ha migliorato la diagnosi garantendo la possibilità di quantificare l’infiltrato infiammatorio, ma rimane ancora un grado di sovradiagnosi. Scopo:validare un nuovo sistema di grading per la diagnosi di miocardite basato sulla quantificazione dell’infiltrato infiammatorio alla biopsia endomiocardica(BEM) e correlare i dati clinici e istologici. Materiali e metodi:si sono rivalutate al microscopio ottico le BEM di pazienti con miocardite clinicamente sospetta per quantificare l’infiltrato infiammatorio di cellule CD3+ e ricercare la presenza di necrosi, fibrosi, alterazioni cardiomiopatiche e l’eventuale positività alla PCR. Per correlare i dati clinici e istologici, si sono ricercati i dati relativi alla modalità di presentazione clinica, il timing della BEM, il follow up con eventuale trapianto cardiaco o exitus; si sono raccolti anche i referti della risonanza magnetica cardiaca (RMC) per ottenere informazioni riguardanti la presenza di edema, di LGE, la frazione di eiezione del ventricolo sinistro. Risultati:applicando il nuovo sistema di grading proposto, in un totale di 106 casi analizzati, 43(40,5%) BEM sono risultate negative, 6(5,7%) miocarditi non linfocitarie, 7(6,6%) miocarditi lievi, 1(0,9%) miocardite moderata, 13(12%) miocarditi severe, e 33(31,1%) LIUS(Lymphocytic infiltrate of undetermined significance). Inoltre 3 casi(2,8%) non sono rientrati in nessuna categoria diagnostica proposta. Il 14% delle BEM è risultata positiva alla PCR per la ricerca del genoma virale. Considerando le presentazioni cliniche, lo scompenso cardiaco è stato l’esordio clinico più rappresentato(58%), lo shock quello più raro(2,8%). Il timing delle BEM è stato prevalentemente ritardato con solo il 2,8% delle BEM eseguite entro 48 ore, mentre la maggior parte(43%) oltre il mese. La diagnosi di miocardite si è avuta nella maggior parte con timing della BEM entro le 4 settimane. La quantificazione dei linfociti CD3+ tra le LIUS ha evidenziato una distribuzione abbastanza sovrapponibile tra le varie presentazioni cliniche. La correlazione tra la presenza del segnale LGE e la fibrosi identificata istologicamente, la corrispondenza tra l’edema alla RMC e la diagnosi di miocardite o di LIUS, e infine la relazione tra il segnale LGE e le alterazioni cardiomiopatiche non si sono dimostrate statisticamente significative. Una relazione significativa si è riscontrata invece tra i valori della FE e le alterazioni cardiomiopatiche(p=0,006). Analizzando le biopsie di follow up di 3 pazienti con diagnosi di miocardite severa, tutte presentavano ancora a distanza di 2 e 3 anni una miocardite(2 severe, 1 lieve). Dei pazienti inclusi nello studio, 1 è andato incontro ad exitus, mentre altri 8 sono andati in contro a trapianto cardiaco, sebbene solo in un paziente di questi vi fosse diagnosi di miocardite. Nei casi in studio, le miocarditi diagnosticate secondo Dallas sono 85,8%, nettamente superiori rispetto a quelle diagnosticate secondo i nuovi criteri proposti dalle SCVP-AECVP(27,4%).Conclusioni:il nuovo sistema consente di ridurre la sovradiagnosi di miocardite attraverso la quantificazione dell’infiltrato infiammatorio e l’aggiunta della categoria LIUS. La BEM ha maggior capacità diagnostica se eseguita entro le 4 settimane, o ancor di più entro la settimana dall’esordio. Sono necessari ulteriori studi per indagare il valore statistico delle correlazioni che nello studio sono state limitate dalla scarsità di alcune sottopopolazioni campionarie. Concordando con i dati in letteratura nonostante la crescente importanza della RMC, la BEM rimane il gold standard diagnostico per la miocardite.
Diagnosi istologica di miocardite: dai criteri di Dallas alla validazione di un nuovo sistema diagnostico
MUNARON, IRENE
2023/2024
Abstract
Background: Myocarditis is an inflammation of the myocardium diagnosed according to histological, immunological, and immunochemical criteria. The complexity of achieving a precise diagnosis and anatomopathological definition has necessitated updates to the classic Dallas histological criteria. Immunohistochemistry has improved diagnosis by allowing quantification of inflammatory infiltrate, though some degree of overdiagnosis remains. Study objective: To validate a new grading system for myocarditis diagnosis based on quantification of inflammatory infiltrate in endomyocardial biopsies (EMB), and to correlate clinical and histological data. Materials and methods: Optical microscope reevaluation of EMBs from patients clinically suspected of myocarditis was conducted to quantify CD3+ cell infiltrate and detect necrosis, fibrosis, cardiomyopathic changes, and potential PCR (Polymerase Chain Reaction) positivity. Clinical data including presentation mode, timing of EMB, follow-up with potential heart transplant or mortality, and cardiac magnetic resonance imaging (MRI) reports were collected. MRI provided information on edema, late gadolinium enhancement (LGE), and left ventricular ejection fraction (LVEF). Results: Applying the proposed new grading system to 106 cases, 43 (40.5%) EMBs were negative, 6 (5.7%) were non-lymphocytic myocarditis, 7 (6.6%) were mild myocarditis, 1 (0.9%) was moderate myocarditis, 13 (12%) were severe myocarditis, and 33 (31,1%) were classified as Lymphocytic Infiltrate of Undetermined Significance (LIUS). Additionally, 3 cases (2.8%) did not fit into any proposed diagnostic category. 14% of EMBs were positive for viral genome by PCR. Heart failure was the most common clinical presentation (58%), while shock was rare (2.8%). Most EMBs (43%) were performed more than a month after symptom onset. Myocarditis diagnosis was predominantly achieved within 4 weeks of EMB. CD3+ lymphocyte quantification among LIUS showed similar distribution across clinical presentations. There was no statistically significant correlation between LGE and histologically identified fibrosis, edema on MRI and myocarditis/LIUS diagnosis, or between LGE and cardiomyopathic changes. However, a significant relationship was found between LVEF values and cardiomyopathic changes (p=0.006). Follow-up biopsies of 3 patients diagnosed with severe myocarditis showed persistent myocarditis (2 severe, 1 mild) at 2 and 3 years. Among study participants, 1 patient died, and 8 underwent heart transplantation, though only 1 of these patients had myocarditis diagnosed. Myocarditis diagnosed by Dallas criteria accounted for 85.8%, significantly higher than diagnoses by the new criteria proposed by the Society for Cardiovascular Pathology (27.4%). Conclusions: The new grading system reduces myocarditis overdiagnosis through inflammatory infiltrate quantification and introduction of the LIUS category. EMB has greater diagnostic capability if performed within 4 weeks, especially within the first week of symptom onset. Further studies are needed to investigate statistical correlations, limited here by sample subgroup scarcity. Consistent with literature, despite MRI's growing importance, EMB remains the diagnostic gold standard for myocarditis.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/65755