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Septic pulmonary embolism: Is it an underestimated diagnosis?


1 Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
2 Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College Mumbai, Maharashtra, India

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Date of Submission21-Jun-2022
Date of Decision17-Jul-2022
Date of Acceptance17-Jul-2022
Date of Web Publication18-Oct-2022
 

   Abstract 


Background: Non-thrombotic pulmonary embolism, an uncommon entity, is defined as the embolization of tissues, microorganisms, air, or foreign material. One subset in this non-thrombotic category is septic pulmonary embolism (SPE) that refers to embolism of microorganisms with or without a thrombotic mantle into the pulmonary vasculature. This condition is often recognized on the basis of imaging with a clinical correlation. Unfortunately, data regarding the pathological features are meager. This has prompted to review such cases at autopsy. Aims: To study the pathological features of SPE at autopsy. Materials and Methods: Ten-year (2012 to 2021) autopsy records of the hospital were retrospectively reviewed. The diagnosis was based on the identification of acute necrotizing pulmonary arteritis with peri-bronchoarterial consolidation. These cases were analyzed with reference to the demographics, clinical characteristics, and pulmonary/extrapulmonary findings at autopsy. Statistical Analysis: Nil. Results: According to the inclusion criterion, 19 cases demonstrated the presence of SPE. There were 11 men and 8 women with a mean age of 32.1 years. The major source of infection included infection arising from skin and musculo-skeletal system (11 patients, 59.7%). The common clinical presentation included fever, dyspnea, chest pain, hemoptysis, and altered sensorium. The cause of death was mainly due to septicemia and/or confluent lung consolidations. A large number of bacterial colonies were seen in all; Candida species were also identified in two cases. Other lung findings included diffuse alveolar damage, fresh arterial thrombosis, infarction, arterial pseudo-aneurysms, abscess formation, and pyogenic pleuritis. Conclusion: Presence of an extrapulmonary infection with persistent fever, bacteremia, and pulmonary complaints should raise suspicion for this entity, particularly in resource-poor settings, to prevent grave pulmonary complications.

Keywords: Non-thrombotic pulmonary embolism, pulmonary necrotizing arteritis, pulmonary pathology, septic pulmonary embolism


How to cite this URL:
Kolhe S, Vaideeswar P. Septic pulmonary embolism: Is it an underestimated diagnosis?. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Sep 30]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=358854





   Introdcution Top


In comparison to pulmonary thromboembolism (the third most frequent cause of cardiovascular disorder-related mortality), non-thrombotic pulmonary embolism is uncommon and is defined as embolization of tissues, microorganisms, air, or foreign material.[1] Since the nature and size of the embolic material are diverse in nature, it not only produces mechanical obstruction but also triggers a pulmonary parenchymal inflammatory reaction. One subset in this non-thrombotic category is septic pulmonary embolism (SPE) that refers to embolism of microorganisms with or without a thrombotic mantle into the pulmonary vasculature;[2] it is a common sequel of right-sided infective endocarditis (RSIE).[3] Specific radiological findings combined with the presence of significant extrapulmonary infective foci and amelioration of the lung lesions under appropriate anti-microbial therapy are the important criteria for a clinical diagnosis of SPE.[4] But the data regarding the pathological features are scarce since such moribund patients seldom undergo lung biopsies. This has prompted to review such cases at autopsy.


   Materials and Methods Top


Cases that had been indexed as “SPE,” “bronchopneumonia,” “hemorrhagic pneumonia,” “lung abscess,” “pulmonary thrombosis,” and “pulmonary infarction” were reviewed from a ten-year (2012 to 2021) autopsy records maintained in the cardiovascular and thoracic pathology subspecialty of a tertiary-care center. The main histopathological criterion for the diagnosis of SPE was the presence of acute necrotizing pulmonary arteritis [Figure 1]a and [Figure 1]b with peri-bronchoarterial consolidation (hemorrhage or fibrino-purulent exudates). The cases showing these findings were analyzed with reference to the demographics, clinical presentations, risk factors—exogenous or endogenous (cardiac or non-cardiac) infections, and investigations. Other associated lung and extrapulmonary lesions at autopsy were also noted. SPE in pediatric patients or those secondary to RSIE were excluded in this study.
Figure 1: (a) Granular basophilic bacterial colonies adherent to the intimal surface of the muscular arteries. Edema is present in the adjoining parenchyma (H and E ×100); (b) A muscular artery shows bacterial colonies in its lumen and over the intima. Focal destruction (white arrow) of the wall is present. There is a thick circumferential cuff of neutrophils around the adventitia (H and E ×100)

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   Results Top


In the study period, 19 cases satisfied the histopathologic criterion for SPE. There were 11 men and 8 women; 5 women had been pregnant (molar pregnancy in one of them). The age ranged from 13 to 70 years with a mean age of 32.1 years. One patient had been declared dead on arrival; the remaining patients had been admitted for a period of 2 hrs for 35 days. Smoking, alcoholism, hypertension, and/or diabetes mellitus had been noted in two patients, while four had hematological disorders, Non-Hodgkin's lymphoma and aplastic anemia in one patient each, and post-hemorrhagic anemia in two other patients. Suppurative inflammation involving the skin and/or the musculo-skeletal system had been the source of SPE in 11 patients (57.9%). Fever, symptoms related to the lung involvement (such as dyspnea, chest pain, and hemoptysis) and/or altered sensorium had been noted in 12 patients (63.2%). Most common laboratory findings were anemia and neutrophilic leukocytosis. Majority of patients were transferred to intensive care unit and treatment included combination of antibiotics, anti-viral agents, corticosteroids, and mechanical ventilation. Radiological imaging (X-ray or computed tomography (CT)) had been performed in only four patients and had revealed multifocal consolidation, cavitations, and/or pleural effusions. Wound scrapings in one patient had shown gram-negative bacilli, while blood culture in another patient had no growth. All the patients had succumbed to dominant lung involvement [Figure 2]a to [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e or septicemia. A large number of bacterial colonies [Figure 1]a and [Figure 1]b were seen in all; Candida species [Figure 3]a were also identified in two cases. Apart from necrotizing arteritis and consolidation, other lung findings included diffuse alveolar damage [Figure 3]b, fresh arterial thrombosis [Figure 3]c, infarction, arterial pseudo-aneurysms [Figure 3]d, abscess formation [Figure 2]e, and pyogenic pleuritis [Figure 2]d. The non-pulmonary autopsy findings included pyogenic meningitis, myocardial, or renal micro-abscesses.
Figure 2: (a) Cut surface of the right lung in case of right forearm cellulitis showing subpleural foci of congestion (black arrows) with larger foci of red-brown consolidation; Case of non-Hodgkin's lymphoma under chemotherapy; (b) Wrinkled and patchily opacified pleural surfaces of both lungs with multiple elevated congested foci (white arrows); (c) Cut surface of the right lung showing acute cavitations with foci of consolidation and hemorrhagic infarction; Young lady treated for molar pregnancy with methotrexate;- (d) Left lung with diffuse pleural opacification and a layer of fibrino-purulent exudate over the lower lobe; (e) The cut surface showing large red-brown foci of consolidation with peripheral areas of abscess formation

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Figure 3: (a) Yeast and pseudo-hyphal forms of Candida species (Gomori methenamine silver × 400); (b) Diffuse alveolar damage with hyaline membrane formation and edema fluid with neutrophils within the alveoli (H and E × 100); (c) Segmental necrosis and inflammation of the arterial wall with nonocclusive fresh thrombus (black arrow, H and E × 100); (d) Discontinuity (black arrows) of the wall of a muscular artery with bacterial colonies embedded in fibrinous material (H and E × 100)

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   Discussion Top


Many of the studies on SPE are based mainly on clinicoradiological data, but even then there have been only a few case series since SPE is considered an infrequent phenomenon.[2] Due to prevailing morbid conditions of the patients (often critically ill), lung biopsy is hardly resorted to for confirmation of the disease, and hence correlation with characteristic imaging features is lacking. Herein, the pathological features of SPE at autopsy have been outlined. The rates of clinical or medical autopsies are dwindling worldwide due to multiple reasons.[5] This study, as a corollary, reiterates the fact that autopsies continue to be the “gold” standard for disease diagnosis. However, the data of 19 patients over ten years does reflect the true incidence of SPE at autopsy as the cases were retrieved from the specialty of cardio-pulmonary pathology.

In the past, apart from RSIE, causes of SPE were attributed to puerperal sepsis, Lemierre's disease, and intra-venous drug abuse; the etiology was, therefore, cardiac, peripheral endogenous, or exogenous, respectively.[6] However, recent data draw attention to a change in the clinical setting such as indwelling catheters/devices and pyogenic infections of the skin, deep soft tissues and bones, which is potentiated by the presence of common and uncommon immunocompromised or immunosuppressed states.[2],[7],[8],[9] There was a similar experience, wherein most of the patients had skin or deep-seated soft tissue infections. Unfortunately, there was not a mention of positive blood cultures in any of these patients. Bacterial colonies had been abundant in the affected lung parenchyma; Candida species were identified in 2 of the 19 cases. The type of microbes would depend on the primary site of suppuration, and even on the geographic distribution, for example, gram-positive bacteria are the usual pathogens isolated (especially Staphyococcus. aureus), anaerobes in oropharyngeal infections and K. pneumoniae in some Southeast Asian countries.[2],[8]

Contiguous septic thrombo-phlebitis triggered by bacterial toxins or inflammatory cytokines are said to embolize and produce features of SPE.[7] But, it has to be emphasized that in most of cases, the morphological changes of SPE had been produced by mere embolism of the organisms, which were often found clinging to the arterial intima. There was segmental or circumferential arteritis and even pseudo-aneurysms. Subsequent thrombosis can then occur, leading to consolidation or infarctions with secondary breakdown of the parenchyma; these consolidations are usually hemorrhagic. Plain chest X-rays may not be particularly useful, but CT usually reveals bilateral, peripheral multifocal nodular opacities, or wedge-shaped lesions, all in the vicinity of the obstructed arteries.[8] A characteristic “feeding vessel” or “fruits on the branch” is produced that indicates an obstructed vessel leading to a mass or nodule.[10] Radiological findings were available in only four patients in this study.

The main clinical manifestation of SPE is an acute febrile illness, which is often accompanied by dyspnea, cough, chest pain, or hemoptysis.[2],[8],[9] All these were present in most of the patients. Early diagnosis and therapy aimed at primary and pulmonary infections are essential in reducing morbidity and mortality. Antibiotic therapy should be appropriate and extended to cover both gram-positive and gram-negative organisms (unless proven by blood cultures), similar to the recommendation for patients with sepsis.[8],[9] Antifungal agents may also be required. Surgical intervention may be indicated to curb the primary infection.[8],[9] Delayed diagnosis and/or inappropriate drug therapy can lead to grave pulmonary complications like diffuse alveolar damage and respiratory failure or multi-organ suppuration and septic shock as noted in some of the patients. Since SPE is a rare disease with nonspecific and insidious clinical manifestations, the presence of an extrapulmonary infection with persistent fever, bacteremia, and pulmonary complaints should raise suspicion for this entity and be considered in the differential diagnosis. This becomes important as in many centers CT scans cannot always be performed, and hence it is possible that many such cases may not be clinically diagnosed. Since the overall autopsy study data are sparse, this study can help in arriving at a proper diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Jorens PG, Van Marck E, Snoeckx A, Parizel PM. Non-thrombotic pulmonary embolism. Eur Respir J 2009;34:452-74.  Back to cited text no. 1
    
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Song XY, Li S, Cao J, Xu K, Huang H, Xu ZJ. Cardiac septic pulmonary embolism: A retrospective analysis of 20 cases in a Chinese population. Medicine 2016;95:e3846.  Back to cited text no. 3
    
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Cook RJ, Ashtom RW, Aughenbau GL, Ryu RH. Septic pulmonary embolism: Presenting features and clinical course of 14 patients. Chest 2005;128:162-6.  Back to cited text no. 4
    
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van den Tweel JG, Wittekind C. The medical autopsy as quality assurance tool in clinical medicine: Dreams and realities. Virchows Arch 2016;468:75-81.  Back to cited text no. 5
    
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MacMillan JC, Milstein SH, Samson PC. Clinical spectrum of septic pulmonary embolism and infarction. J Thorac Cardiovasc Surg 1978;75:670-9.  Back to cited text no. 6
    
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Goswami U, Brenes JA, Punjabi GV, LeClaire MM, Williams DN. Associations and outcomes of septic pulmonary embolism. Open Respir Med J 2014;8:28-33.  Back to cited text no. 7
    
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Chou DW, Wu SL, Chung KM, Han SC, Cheung BM. Septic pulmonary embolism requiring critical care: Clinicoradiological spectrum, causative pathogens and outcomes. Clinics 2016;71:562-9.  Back to cited text no. 8
    
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Jiang J, Liang Q, Liu L, Cai S, Du Z, Kong J, et al. Septic pulmonary embolism in China: Clinical features and analysis of prognostic factors for mortality in 98 cases. BMC Infect Dis 2019;19:1082.  Back to cited text no. 9
    
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Dodd JD, Souza CA, Müller NL. High-resolution MDCT of pulmonary septic embolism: Evaluation of the feeding vessel sign. Am J Roentgenol 2006;187:623-9.  Back to cited text no. 10
    

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Correspondence Address:
Pradeep Vaideeswar,
Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_528_22



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