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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 31  |  Issue : 1  |  Page : 56-58

Postmortem diagnosis of fulminant infectious mononucleosis


Department of Molecular Medicine and Laboratory Sciences, Army Hospital Research and Referral, New Delhi, India

Date of Web Publication17-Jan-2017

Correspondence Address:
Khushboo Dewan
26, Amit Apartments, Sector-13, Rohini, New Delhi - 110 085
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-4958.198467

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  Abstract 

Fulminant infectious mononucleosis (FIM) is a rare but life-threatening complication of Epstein-Barr virus infection that usually affects immunodeficient individuals. It is a hyperinflammatory syndrome caused due to release of massive amount of various cytokines, leading to hemophagocytic lymphohistiocytosis on histopathology, and a plethora of clinical manifestations due to simultaneous involvement of multiple organs of the body. The case of a young male who presented with fever and dyspnea and died within 12 h of presentation to the hospital was taken for autopsy. The postmortem evidence of hemophagocytic lymphohistiocytosis in the spleen, bone marrow, lymph nodes, liver, and lungs and the presence of large, basophilic intranuclear inclusions that stained latent membrane protein-1 positive on immunohistochemistry led to the diagnosis of FIM.

Keywords: Epstein-Barr virus, fulminant infectious mononucleosis, hemophagocytic lymphohistiocytosis


How to cite this article:
Dewan K, Chatterjee T, Bharadwaj R. Postmortem diagnosis of fulminant infectious mononucleosis. J Med Soc 2017;31:56-8

How to cite this URL:
Dewan K, Chatterjee T, Bharadwaj R. Postmortem diagnosis of fulminant infectious mononucleosis. J Med Soc [serial online] 2017 [cited 2020 May 25];31:56-8. Available from: http://www.jmedsoc.org/text.asp?2017/31/1/56/198467


  Introduction Top


Fulminant infectious mononucleosis (FIM) is the most severe form of infectious mononucleosis that usually affects young boys having X-linked lymphoproliferative disease and has a survival rate of only about 4%. [1] It commonly manifests with hepatic dysfunction, anemia, thrombocytopenia, and meningoencephalitis. Both B- and T-cells infiltrate and destroy multiple organs causing multiorgan dysfunction syndrome. Ninety percent of patients with FIM have hemophagocytic lymphohistiocytosis due to massive release of tumor necrosis factor-α by activated T-cells. We present the autopsy findings of a young male whose immune status was unknown but who succumbed to FIM within 12 h of presentation to the hospital.


  Case Report Top


A 26-year-old male patient presented with a 1-week history of high-grade fever associated with malaise and recent onset of breathlessness and reduced urine output. On examination, the patient had tachycardia, tachypnea, hypotension, periorbital puffiness, and erythematous blanchable rash on the chest and back. Air entry was reduced in the right infrascapular region, and fine crackles over the bilateral infra-axillary regions were present. On preliminary investigations, the patient had lymphocytosis with the presence of numerous atypical lymphocytes on peripheral smear, thrombocytopenia, elevated liver transaminases, and deranged coagulation profile. Serological tests for various viruses including hepatitis A, B, and C, HIV, dengue, and chikungunya were negative. Weil-Felix test for rickettsial infection and immunochromatography for malaria was negative. The patient was offered symptomatic treatment and put on ventilator due to reducing oxygen saturation; however, within 12 h of presentation to the hospital, he had a sudden cardiac arrest and was declared dead. The body was sent for autopsy. On gross examination, the patient had enlarged, congested liver (weight 2000 g) and an enlarged spleen with hematoma formation (weight 500 g) that on cut section was congested. On opening the thoracic cavity, hemothorax with congested pleura and bilateral heavy (weight: right lung 900 g; left lung 850 g), congested and boggy lungs with petechiae on the external surface were present. Similar petechiae were present on external surface of the heart that was otherwise normal in weight and on cut section. Multiple pre- and para-tracheal, hilar, retroperitoneal, mesenteric, and para-aortic lymph nodes were enlarged and congested. On opening the cranial cavity, meninges were congested and a right-sided subdural hematoma measuring 4 cm × 3 cm was present. Histopathological examination of both lungs revealed widespread edema and infiltration by mononuclear cells in the thickened alveolar septae. There was congestion and presence of numerous Type II pneumocytes, many containing large, basophilic intranuclear inclusion bodies within these septae. In addition, many cytologically benign histiocytes having vesicular nuclei and abundant cytoplasm containing engulfed erythrocytes, platelets, and lymphocytes were seen. Sections from the multiple thoracic and abdominal lymph nodes examined showed hyperplastic follicles and proliferation of interfollicular immunoblasts, plasma cells, and tingible body macrophages. In addition, infiltration of nodal sinuses by bland histiocytes showing hemophagocytosis and similar intranuclear inclusions was seen [Figure 1]. Sections from the spleen showed expansion of the red pulp with the presence of mature histiocytes showing hemophagocytosis and intranuclear inclusions in the splenic sinusoids. A similar infiltration of the bone marrow by hemophagocytic cells with intranuclear inclusions was seen. The bone marrow cellularity, composition, and maturation were otherwise normal. On immunohistochemistry, the intranuclear inclusions were strongly positive for latent membrane protein-1 (LMP-1) [Figure 2]. Sections from the liver also showed congestion of the hepatic sinusoids, portal triaditis with extensive infiltration by lymphocytes, and hyperplasia of Kupffer cells showing hemophagocytosis. Meningeal lymphohistiocytic infiltration was noted. Sections from the heart showed lymphocytic myocarditis. Sections from the kidney showed hypoperfusion injury with acute tubular necrosis. A final diagnosis of FIM with disseminated intravascular coagulation was made on autopsy. In retrospect, the history of recurrent infections since childhood in the patients or other family members was found to be negative.
Figure 1: Section from lymph node shows the presence of numerous benign histiocytes showing hemophagocytosis) (Hematoxylin and Eosin, ×1000)

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Figure 2: Section from lymph node shows histiocytes with large intranuclear inclusions and membranous staining with latent membrane protein-1 (immunohistochemical staining for latent membrane protein-1, ×1000)

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  Discussion Top


Infectious mononucleosis is a disease characterized by fever, pharyngitis, and lymphadenopathy and is caused by Epstein-Barr virus (EBV). [5] Complications of infectious mononucleosis include hepatitis, myocarditis, pericarditis, pneumonia, thrombocytopenia, splenic rupture, encephalitis, and cranial palsies. [2] FIM is a rare, life-threatening complication of infectious mononucleosis and has been mostly described in the patients with immunodeficiency, but a few cases without any known preexisting immune deficiency are also reported. [1],[3],[4]

We report the findings in a case of FIM diagnosed postmortem. The patient did not have an acquired cause of immunodeficiency, and a negative history of recurrent infections since childhood suggested the absence of inherited immunodeficiency syndrome. This patient presented with nonspecific symptoms of a viral infection causing pneumonia and quickly progressed to develop a constellation of complications in the form of hepatitis, pancytopenia, splenic hematoma, hemothorax, subdural hematoma, lymphocytic myocarditis, and widespread lymphadenopathy. Due to simultaneous derangement and dysfunction of multiple organs, the patient did not survive beyond 12 h of presentation to the hospital. The diagnosis of FIM causing hemophagocytic lymphohistiocytosis could only be made on postmortem when an extensive infiltrate of hemophagocytic cells in all the reticuloendothelial organs of the body including liver, spleen, bone marrow, and multiple lymph nodes was found. The presence of intranuclear inclusion bodies and intense positive staining of hemophagocytic cells for LMP-1 provided the final clue to the etiological diagnosis of EBV that had led to hemophagocytic lymphohistiocytosis.

Infection-associated hemophagocytic lymphohistiocytosis most commonly occurs due to EBV infection. The EBV causes proliferation and activation of numerous cytotoxic T-lymphocytes and causes massive production of cytokines, mainly interferon γ, tumor necrosis factor-α, interleukin-1 and -6, granulocyte monocyte colony stimulation factor that cause fever and persistent inflammation and promote the activation of macrophages on a large scale. The activated macrophages to begin with occur in the spleen causing splenomegaly and have high rates of hemophagocytosis, leading to pancytopenia, release ferritin, increase plasmin activity causing fibrinolysis and disseminated intravascular coagulation, hepatomegaly and altered liver function tests, inhibit lipoprotein lipase causing hypertriglyceridemia. The hyperproliferative immune cell dysfunction is further reinforced by inadequate apoptosis of immunogenic cells.

Clinically, fever, splenomegaly, hepatomegaly, lymphadenopathy, maculopapular rash, and neurological signs occur in decreasing order of frequency. The patient in discussion had most of these clinical manifestations. In addition, cytopenia, hypertriglyceridemia, hypofibrinogenemia, hyperbilirubinemia, and elevated ferritin levels may be present due to causes explained above. Histopathologically, the reticuloendothelial organs including bone marrow, spleen, and lymph nodes show hemophagocytosis that is ingestion of erythrocytes, leukocytes, and platelets by histiocytes. In addition, lymphocytic infiltration of the hepatic portal tracts is present. The patient in discussion had pancytopenia and evidence of extensive hemophagocytosis in various organs of the body.

The clinicopathological picture of FIM, a rare but life-threatening condition, is described to highlight the significance of timely identification and vigorous management of such cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Ochs HD, Smith CI, Puck JM. Primary Immunodeficiency Diseases - A Molecular and Genetic Approach. 3 rd ed. New York: Oxford University Press; 2014.  Back to cited text no. 1
    
2.
Katsanos KH, Christodoulou D, Kitsanou M, Economides CA, Patsouras D, Goudevenos I, et al. Epstein-Barr virus multi-organ attack in a twenty-year-old boy: Myocarditis, pneumonia and hepatitis. Ann Gastroenterol 2003;16:377-80.  Back to cited text no. 2
    
3.
Busch D, Hilswicht S, Schöb DS, von Trotha KT, Junge K, Gassler N, et al. Fulminant Epstein-Barr virus - Infectious mononucleosis in an adult with liver failure, splenic rupture, and spontaneous esophageal bleeding with ensuing esophageal necrosis: A case report. J Med Case Rep 2014;8:35.  Back to cited text no. 3
    
4.
Nourse JP, Jones K, Dua U, Runnegar N, Looke D, Schmidt C, et al. Fulminant infectious mononucleosis and recurrent Epstein-Barr virus reactivation in an adolescent. Clin Infect Dis 2010;50:e34-7.  Back to cited text no. 4
    
5.
 Fisman DN. Hemophagocytic syndromes and infection. Emerg Infect Dis 2000;6:601-8.  Back to cited text no. 5
    


    Figures

  [Figure 1], [Figure 2]



 

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