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Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report.

Ameli F, Ghafourian F, Masir N - J Med Case Rep (2014)

Bottom Line: Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate.He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure.A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak 56000, Cheras, Kuala Lumpur, Malaysia. noraidah@ppukm.ukm.edu.my.

ABSTRACT

Introduction: Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The clinical and pathological features of the disease overlap with other conditions including infectious mononucleosis, chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis and natural killer cell malignancies. We describe the rare case of systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease in a 16-year-old Malay boy.

Case presentation: He presented with a six-month history of fever and cough, with pulmonary and mediastinal lymphadenopathy and severe pancytopenia. Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate. He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure.

Conclusions: Although systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is a disorder which is rarely encountered in clinical practice, our case report underlines the importance of a comprehensive diagnostic approach in the management of this disease. A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease.

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Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease: bone marrow biopsy. A: Hematoxylin and eosin (H&E) sections illustrate the medium-sized lymphoid cells replacing the normal hematopoietic elements and exhibiting moderate atypia with irregular kidney-shaped nuclei, dispersed chromatin and distinct nucleoli (100x, 400x and 600x respectively left to right). Hemophagocytosis is also easily seen (inset). B: An immunohistochemical study shows that the majority of infiltrated atypical lymphocytes expressed CD2+ and CD4+ with scattered positivity to CD8. C. The atypical lymphoid cells are not immunoreactive to CD20 and there is a paucity of B cells in the bone marrow. Ki-67 immunostaining shows a high proliferative index and EBV-encoded RNA (EBER) by in situ hybridization demonstrates a strong reactivity of atypical lymphoid cells.
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Figure 1: Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease: bone marrow biopsy. A: Hematoxylin and eosin (H&E) sections illustrate the medium-sized lymphoid cells replacing the normal hematopoietic elements and exhibiting moderate atypia with irregular kidney-shaped nuclei, dispersed chromatin and distinct nucleoli (100x, 400x and 600x respectively left to right). Hemophagocytosis is also easily seen (inset). B: An immunohistochemical study shows that the majority of infiltrated atypical lymphocytes expressed CD2+ and CD4+ with scattered positivity to CD8. C. The atypical lymphoid cells are not immunoreactive to CD20 and there is a paucity of B cells in the bone marrow. Ki-67 immunostaining shows a high proliferative index and EBV-encoded RNA (EBER) by in situ hybridization demonstrates a strong reactivity of atypical lymphoid cells.

Mentions: A bone marrow biopsy was performed. The aspirate showed several clusters of abnormal lymphoid cells and hemophagocytic activity but assessment was limited due to hemodilution. Accordingly, he underwent treatment for hemophagocytic lymphohistiocytosis (HLH) (with unknown cause) based on the HLH-2004 protocol. This protocole was developed by the treatment protocol of the second international HLH study 2004 [5]. Immunophenotyping of the atypical lymphoid cells by flow cytometry was inconclusive due to suboptimum aspirate sampling. The trephine biopsy was hypocellular with a marked reduction of normal hematopoietic elements. This was replaced by scattered medium- to large-sized malignant lymphoid cells. The cells were moderately pleomorphic with a kidney-shaped nuclei, irregular nuclear membrane and prominent nucleoli (Figure 1). Occasional mitotic figures, including abnormal forms and hemophagocytosis, were also noted. It was revealed upon immunohistochemistry that the atypical lymphoid cells expressed CD3, CD2 and CD4 positivity (Figure 1). A few atypical cells were also positive for CD8. The malignant cells were negative for CD20, CD56 and ALK1 (Figure 1). Ki-67 immunostaining highlighted an increased proliferative rate in the malignant cells. In situ hybridization for EBV encoded RNA (EBER) demonstrated EBV-positive atypical lymphoid cells (Figure 1). Therefore a diagnosis of systemic EBV-positive T-cell lymphoproliferative childhood disease was made.


Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report.

Ameli F, Ghafourian F, Masir N - J Med Case Rep (2014)

Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease: bone marrow biopsy. A: Hematoxylin and eosin (H&E) sections illustrate the medium-sized lymphoid cells replacing the normal hematopoietic elements and exhibiting moderate atypia with irregular kidney-shaped nuclei, dispersed chromatin and distinct nucleoli (100x, 400x and 600x respectively left to right). Hemophagocytosis is also easily seen (inset). B: An immunohistochemical study shows that the majority of infiltrated atypical lymphocytes expressed CD2+ and CD4+ with scattered positivity to CD8. C. The atypical lymphoid cells are not immunoreactive to CD20 and there is a paucity of B cells in the bone marrow. Ki-67 immunostaining shows a high proliferative index and EBV-encoded RNA (EBER) by in situ hybridization demonstrates a strong reactivity of atypical lymphoid cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150421&req=5

Figure 1: Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease: bone marrow biopsy. A: Hematoxylin and eosin (H&E) sections illustrate the medium-sized lymphoid cells replacing the normal hematopoietic elements and exhibiting moderate atypia with irregular kidney-shaped nuclei, dispersed chromatin and distinct nucleoli (100x, 400x and 600x respectively left to right). Hemophagocytosis is also easily seen (inset). B: An immunohistochemical study shows that the majority of infiltrated atypical lymphocytes expressed CD2+ and CD4+ with scattered positivity to CD8. C. The atypical lymphoid cells are not immunoreactive to CD20 and there is a paucity of B cells in the bone marrow. Ki-67 immunostaining shows a high proliferative index and EBV-encoded RNA (EBER) by in situ hybridization demonstrates a strong reactivity of atypical lymphoid cells.
Mentions: A bone marrow biopsy was performed. The aspirate showed several clusters of abnormal lymphoid cells and hemophagocytic activity but assessment was limited due to hemodilution. Accordingly, he underwent treatment for hemophagocytic lymphohistiocytosis (HLH) (with unknown cause) based on the HLH-2004 protocol. This protocole was developed by the treatment protocol of the second international HLH study 2004 [5]. Immunophenotyping of the atypical lymphoid cells by flow cytometry was inconclusive due to suboptimum aspirate sampling. The trephine biopsy was hypocellular with a marked reduction of normal hematopoietic elements. This was replaced by scattered medium- to large-sized malignant lymphoid cells. The cells were moderately pleomorphic with a kidney-shaped nuclei, irregular nuclear membrane and prominent nucleoli (Figure 1). Occasional mitotic figures, including abnormal forms and hemophagocytosis, were also noted. It was revealed upon immunohistochemistry that the atypical lymphoid cells expressed CD3, CD2 and CD4 positivity (Figure 1). A few atypical cells were also positive for CD8. The malignant cells were negative for CD20, CD56 and ALK1 (Figure 1). Ki-67 immunostaining highlighted an increased proliferative rate in the malignant cells. In situ hybridization for EBV encoded RNA (EBER) demonstrated EBV-positive atypical lymphoid cells (Figure 1). Therefore a diagnosis of systemic EBV-positive T-cell lymphoproliferative childhood disease was made.

Bottom Line: Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate.He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure.A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak 56000, Cheras, Kuala Lumpur, Malaysia. noraidah@ppukm.ukm.edu.my.

ABSTRACT

Introduction: Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The clinical and pathological features of the disease overlap with other conditions including infectious mononucleosis, chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis and natural killer cell malignancies. We describe the rare case of systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease in a 16-year-old Malay boy.

Case presentation: He presented with a six-month history of fever and cough, with pulmonary and mediastinal lymphadenopathy and severe pancytopenia. Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate. He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure.

Conclusions: Although systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is a disorder which is rarely encountered in clinical practice, our case report underlines the importance of a comprehensive diagnostic approach in the management of this disease. A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease.

Show MeSH
Related in: MedlinePlus