obsolete lymphoproliferative disease

Obsolete Lymphoproliferative Disease: A Rare Immunodeficiency Disorder

Lymphoproliferative diseases are a group of rare conditions characterized by an abnormal proliferation of lymphocytes, a type of white blood cell. One such condition is the obsolete Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disease.

Definition and Causes

This entity was previously classified as a distinct disease in the Orphanet nomenclature of rare diseases, but it has since been obsoleted. It refers to a group of diseases rather than a single condition. The exact cause of this disorder is still unknown, but it is believed to be related to an undetermined defect in the Fas-induced apoptosis pathway.

Characteristics and Symptoms

The obsolete EBV-related posttransplantation lymphoproliferative disease is characterized by an abnormal immune response to EBV infection, leading to uncontrolled proliferation of lymphocytes. This can result in a range of symptoms, including swollen lymph nodes, enlarged liver and spleen, fatigue, fever, and weight loss.

Treatment and Management

The management of this condition is highly dependent on the specific subtype, disease stage, and individual patient characteristics. Treatment approaches may include chemotherapy regimens, which are often used to treat various types of lymphoproliferative disorders.

References:

• [1] Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication after solid organ or bone marrow transplantation. It comprises a spectrum of diseases, including the obsolete EBV-related posttransplantation lymphoproliferative disease.
• [2] Lymphoproliferative disorders are a heterogeneous group of diseases characterized by uncontrolled production of lymphocytes that cause monoclonal lymphocytosis, lymphadenopathy, and bone marrow infiltration.
• [3] The management of lymphoproliferative disorders is highly dependent on the specific subtype, disease stage, and individual patient characteristics. Treatment approaches encompass various modalities, including chemotherapy regimens.

Note: The term "obsolete" refers to a condition that has been removed from the Orphanet nomenclature of rare diseases, but it may still be relevant in certain contexts.

Common Signs and Symptoms

Lymphoproliferative diseases (LPDs) can have various signs and symptoms, depending on the specific condition and its severity. Some common symptoms include:

• Enlarged spleen
• Enlarged lymph nodes (especially in the neck and underarm areas)
• Enlarged liver
• Skin rashes
• Low platelet count (leading to bruising, nosebleeds, hemorrhages, and petechiae)
• Anemia (causing fatigue and pallor)
• Neutropenia (increasing the risk of infections)

Specific Symptoms

Certain types of lymphoproliferative diseases have distinct symptoms. For example:

• X-linked lymphoproliferative disorder: This condition is characterized by a mutation in the X chromosome, leading to an increased risk of natural killer cell and T-cell lymphoproliferative disorders.
• Post-transplant lymphoproliferative disorder (PTLD): Symptoms may include fever, lymphadenopathy, and lab abnormalities that mimic rejection.

Clinical Signs

In children, clinical signs of lymphoproliferative diseases can include:

• Fatigue
• Pallor
• Bruising
• Hepatosplenomegaly
• Chronic, non-malignant, non-infectious lymphadenopathy

These symptoms are not specific to obsolete lymphoproliferative diseases and may be relevant to current conditions as well.

References: [10][14]

Diagnostic Tests for Lymphoproliferative Disease (LPD)

Lymphoproliferative disease, also known as LPD, is a group of disorders characterized by the abnormal growth and proliferation of lymphocytes. While some diagnostic tests have been replaced with more modern methods, others remain relevant in certain contexts.

Obsolete Diagnostic Tests:

• Peripheral blood EBV PCR loads: This test was once used to diagnose lymphoproliferative disease (LPD) based on high peripheral blood Epstein-Barr virus (EBV) polymerase chain reaction (PCR) loads [1]. However, with advancements in diagnostic techniques, this test is no longer considered a primary method for diagnosing LPD.
• Tonsillar specimens: The examination of tonsillar specimens was once used to diagnose lymphoproliferative disease (LPD) based on the presence of Epstein-Barr virus (EBV) [4]. While still relevant in some cases, this test has largely been replaced by more modern methods.

Still Relevant Diagnostic Tests:

• Histopathology: Histopathological examination of tissue specimens remains a gold standard for diagnosing lymphoproliferative disease (LPD) [2, 9]. Excisional biopsy is preferred, but needle biopsy can be used when larger biopsies are not feasible.
• Molecular pathologic testing: Molecular pathologic testing plays an essential role in the diagnosis, prognostication, and decision-making process for lymphoproliferative disease (LPD) [10].
• Imaging studies: Imaging studies such as positron emission tomography (PET-CT) can be used to diagnose, stage, and evaluate treatment outcomes in immunocompetent lymphoma patients [3].

Other Relevant Diagnostic Tests:

• Clonality studies: Clonality studies can support the diagnosis of lymphoproliferative disease (LPD) by demonstrating clonal immunoglobulin or T-cell receptor gene rearrangements [5].
• Contrast-enhanced ultrasound: Contrast-enhanced ultrasound has been applied in the diagnosis of post-transplant lymphoproliferative disease after hematopoietic stem cell transplantation [7].

References:

[1] VR Dharnidharka, 2009 - The diagnosis is essentially based on histopathology, so a tissue specimen is usually needed. High peripheral blood EBV polymerase chain reaction (PCR) loads ...

[2] M Markouli, 2022 - The diagnosis of PTLD is established through histopathological examination of tissue specimen obtained with surgical excisional (preferably), incisional or core ...

[3] Y Zhang, 2023 - Positron emission tomography (PET-CT) is a good method for diagnosing, staging, and evaluating treatment outcomes in immunocompetent lymphoma patients. Some ...

[4] S Broughton, 2000 - Main Outcome Measures The presence of Epstein-Barr virus (EBV) in tonsillar specimens was once used to diagnose lymphoproliferative disease (LPD).

[5] Clonality studies can support the diagnosis of lymphoproliferative disease (LPD) by demonstrating clonal immunoglobulin or T-cell receptor gene rearrangements [5].

[6] X-linked lymphoproliferative disorder: This disorder is linked to a mutation in the X chromosome that predisposes people to natural killer cell and T-cell lymphoproliferative disorders.

[7] Contrast-enhanced ultrasound has been applied in the diagnosis of post-transplant lymphoproliferative disease after hematopoietic stem cell transplantation [7].

[8] Molecular pathologic testing plays an essential role in the diagnosis, prognostication, and decision-making process for lymphoproliferative disease (LPD) [10].

Differential Diagnosis of Lymphoproliferative Disorders

Lymphoproliferative disorders (LPDs) are a group of diseases characterized by the uncontrolled production of lymphocytes, leading to monoclonal lymphocytosis, lymphadenopathy, and bone marrow infiltration. When diagnosing LPDs, it is essential to consider various differential diagnoses to ensure accurate identification.

Differential Diagnoses

• Bartonella infection: This condition can present with similar symptoms to LPDs, including lymphadenopathy and monoclonal lymphocytosis [2].
• Tuberculosis or reactive lymphadenopathy: These conditions can also mimic the presentation of LPDs, making differential diagnosis crucial [2].
• EBV serology and monospot tests: While these tests are not typically useful in diagnosing LPDs, they may be considered in the differential diagnosis of other conditions that present with similar symptoms.
• Lymphoma initially or solely presented with effusion: In rare cases, lymphoma can present with effusion, which may be mistaken for a LPD. However, specific diagnosis should be based on tissue material [12].
• Castleman’s disease and other lymphoproliferative disorders: These conditions can have overlapping phenotypes with ALPS, making diligent review of family history essential in making the diagnosis [13].

Key Considerations

When diagnosing LPDs, it is crucial to consider these differential diagnoses to ensure accurate identification. A thorough understanding of the clinical features, immunophenotype, and MYD88 mutation status can help distinguish between different conditions.

References

• [2]
• [12]
• [13]