She had been diagnosed as acute leukemia on basis of FNAC from an enlarged lymph node in an outside medical facility and referred to us for further management. Examination revealed, pallor, generalized lymphadenopathy, hepatomegaly 6 cm below the right costal margin and splenomegaly 4 cm below the right costal margin. She had a maculopapular rash over the trunk and both upper limbs which developed after patient was given cefixime in the outpatient department.
Investigations at presentation revealed pancytopenia with a hemoglobin of 9. Considering the diagnosis of Febrile Neutropenia, she was started on injection ciprofloxacin and amikacin.
Because of the persistence of high grade fever, cytopenias and splenomegaly she was worked up for Hemophagocytic syndrome. Bone marrow revealed hemophagocytosis Fig. Blood and urine cultures were sterile. As the patient continued to have high grade fever and no identifiable focus of infection, she was started empirically on amphotericin B following which she became afebrile. A work up for hemophagocytosis revealed IgG anti viral capsid antigen to be positive.
It was decided to start the patient on etoposide, cyclosporine and dexamethasone as per HLH protocol however, as the patient had clinically improved, this was deferred. At discharge patient had regression of hepatosplenomegaly and lymph nodes. At the time of discharge, investigations revealed hemoglobin of 9. The patient was followed up on an outpatient basis after 4 weeks and showed sustained clinical and hematological recovery.
Epstein—Barr virus associated infectious mononucleosis is a benign syndrome characterized by proliferation of lymphomononuclear cells. These cells are also observed in other viral illnesses as well conditions such as toxoplasmosis [ 6 ]. Hemophagocytic lymphohistiocytosis is a syndrome characterized by proliferation of the histiocytes and dysfunction of the natural killer and cytotoxic T cells commonly presenting as multiorgan failure due to infiltration of various organs of the body by mononuclear cells.
The disease manifests as fever, pancytopenia and hepatosplenomegaly. Investigations reveal hypertriglyceridemia, hyperferritinemia, increased CD25 and hypofibrinogenemia.
Some congenital syndromes linked with HLH like Chediak-Higashi syndrome, Griscelli syndrome-2 and X-linked lymphoproliferative disease etc. It is secondarily associated with variety of bacterial, viral and fungal infections. It is called macrophage activation syndrome when it is associated with autoimmune diseases. EBV associated hemophagocytic syndrome is seen most commonly between 1 and 2 years of age, however presentation in young adulthood is also reported.
HLH is highly fatal if left untreated. According to HLH protocol , patients with persistent or familial HLH should be treated with 8 weeks of cyclosporine, dexamethasone and etoposide [ 7 ]. Lymphoproliferative diseases are a close mimicker of EBV associated syndromes, as the primary target of this virus are B cells but it also leads to proliferation of T cells as well.
T cell lymphoproliferative disorders show down regulation of CD 7 as well as CD3 and CD4 on immunophenotyping but this can be seen in a lot of other conditions too [ 8 , 9 ]. A quite good number of infectious mononucleosis patients show T cell clones which express HLA DR however this may also be seen in some T cell lymphoproliferative conditions.
So to make a definitive diagnosis of EBV associated syndromes requires a comprehensive battery of tests like peripheral smear examination, viral serologic markers, detection of viral DNA through PCR and careful interpretation of flow cytometry. Epstein—Barr virus associated disorders may mimic haematological malignancies. EBV associated syndromes should always be considered in the differential diagnosis of patients presenting with fever, jaundice, hepatosplenomegaly and cytopenias.
If at all there is a strong clinical suspicion of EBV associated condition, a detailed work up should be done before labelling the patient with a diagnosis of a lymphoproliferative neoplasm to avoid erroneous administration of hazardous chemotherapy.
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Patients with benign breast diseases were used as a comparison group for both immunohistochemical and serological analysis. Results: 58 cases of malignant breast disease and 63 of benign breast disease controls were included in the study.
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