Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B-cell proliferation due to therapeutic immunosuppression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia. Some of these B-cells may undergo mutations which will render them malignant, giving rise to a lymphoma.

In some patients, the malignant cell clone can become the dominant proliferating cell type, leading to frank lymphoma, a group of B cell lymphomas occurring in immunosuppressed patients following organ transplant.

XMEN patients have splenomegaly, chronic Epstein Barr Virus (EBV) infection, and are developmentally normal. They have an increased susceptibility for developing EBV+ lymphoma. Additionally, XMEN patients have excessive infections consistent with the underlying immunodeficiency. These infections included recurrent otitis media, sinusitis, viral pneumonia, diarrhea, upper respiratory infections, epiglottitis, and pertussis. Although autoimmune symptoms do not feature prominently in XMEN autoimmune cytopenias were observed in two unrelated patients.

In the figure to the left, major features are present in all XMEN patients, while minor features are found only in some.

The disease is believed to be induced by a combination of Epstein Barr virus infection and immunosuppression through; immunosuppressive drugs (with case reports of methotrexate and azathioprine), infections such as HIV or chronic viral hepatitis or endogenous T-cell defects.

Lymphomatoid granulomatosis (LYG or LG) is a very rare lymphoproliferative disorder first characterized in 1972 with lymphomatoid meaning lymphoma-like and granulomatosis denoting one of its microscopic characteristics, polymorphic lymphoid infiltrates and focal necrosis within it. While most commonly found in middle age patients, it has been observed in young people with a study identifying 47 cases of patients aged 0–18 years in the literature. Males are found to be affected twice as often as females.

A primary CNS lymphoma usually presents with seizure, headache, cranial nerve findings, altered mental status, or other focal neurological deficits typical of a mass effect. Systemic symptoms may include fever, night sweats, or weight loss.Other symptoms include

- diplopia

- dysphagia

- vertigo

- monocular vision loss

- progressive dementia or stupor in patients with a nonfocal neurologic exam and minimal abnormalities on MRI (more common in AIDS patients)

- facial hypoesthesia

Patients with this disease usually present at an advanced stage and show systemic involvement. The clinical findings typically include a pruritic skin rash and possibly edema, ascites, pleural effusions, and arthritis.

Patients usually present with constitutional symptoms (malaise, weight loss, fatigue), and hepatosplenomegaly is commonly found on physical exam. Lymphadenopathy is also found to a lesser extent. Due to the aggressive nature of the disease, patients may initially present at a more advanced stage, with coagulopathies, hemophagocytic syndrome, and multi-organ failure.

This disease is known for an indolent clinical course and incidental discovery. The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to the associated neutropenia are seen in almost half of cases.

Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Felty's syndrome. Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia.

The leukemic cells of T-LGLL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.

XMEN disease is a rare genetic disorder of the immune system that illustrates the role of Mg2+ in cell signaling. XMEN stands for “X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia.” It is characterized by CD4 lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation. Investigators in the laboratory of Dr. Michael Lenardo, National Institute of Allergy and Infectious Diseases at the National Institutes of Health first described this condition in 2011.

LCH provokes a non-specific inflammatory response, which includes fever, lethargy, and weight loss. Organ involvement can also cause more specific symptoms.

- Bone: The most-frequently seen symptom in both unifocal and multifocal disease is painful bone swelling. The skull is most frequently affected, followed by the long bones of the upper extremities and flat bones. Infiltration in hands and feet is unusual. Osteolytic lesions can lead to pathological fractures.

- Skin: Commonly seen are a rash which varies from scaly erythematous lesions to red papules pronounced in intertriginous areas. Up to 80% of LCH patients have extensive eruptions on the scalp.

- Bone marrow: Pancytopenia with superadded infection usually implies a poor prognosis. Anemia can be due to a number of factors and does not necessarily imply bone marrow infiltration.

- Lymph node: Enlargement of the liver in 20%, spleen in 30% and lymph nodes in 50% of Histiocytosis cases.

- Endocrine glands: Hypothalamic pituitary axis commonly involved. Diabetes insipidus is most common. Anterior pituitary hormone deficiency is usually permanent.

- Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others suffer from chronic cough and shortness of breath.

- Less frequently gastrointestinal tract, central nervous system, and oral cavity.

Due to the systemic nature of this disease, neoplastic cells can be found in lymph nodes, liver, spleen, skin, and bone marrow.

The most common clinical finding is hepatosplenomegaly. Pruritus, gout, and mucocutaneous bleeding are occasionally seen.

The disease is an uncontrolled proliferation of B cell lymphocytes latently infected with Epstein-Barr virus. Production of an interleukin-10, an endogenous, pro-regulatory cytokine, has also been implicated.

In immunocompetent patients, Epstein-Barr virus can cause infectious mononucleosis in adolescents, which is otherwise asymptomatic in children during their childhood. However, in immunosuppressed transplant patients, the lack of T-cell immunosurveillance can lead to the proliferation of these EBV-infected of B-lymphocytes.

However, calcineurin inhibitors (tacrolimus and ciclosporin), used as immunosuppressants in organ transplantation inhibit T cell function, and can prevent the control of the B cell proliferation.

Depletion of T cells by use of anti-T cell antibodies in the prevention or treatment of transplant rejection further increases the risk of developing post-transplant lymphoproliferative disorder. Such antibodies include ATG, ALG and OKT3.

Polyclonal PTLD may form tumor masses and present with symptoms due to a mass effect, e.g. symptoms of bowel obstruction. Monoclonal forms of PTLD tend to form a disseminated malignant lymphoma.

PEL most commonly arises in patients with underlying immunodeficiency, such as AIDS. PEL is caused by Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). In most cases, the lymphoma cells are also infected with Epstein Barr virus (EBV).

The condition can exist in the absence of HHV-8 and HIV, though this is rare.

The symptoms of AIDS-related lymphoma can include: weight loss, fever, and night sweats.

The typical clinical finding in a patient with hepatosplenic T-cell lymphoma is hepatosplenomegaly.

Hepatosplenic T-cell lymphoma is a rare and generally incurable form of lymphoma.

Hepatosplenic T-cell lymphoma is a systemic neoplasm comprising medium-sized cytotoxic T-cells that show a significant sinusoidal infiltration in the liver, spleen, and bone marrow.

The most common symptoms of CAEBV include:

- Fever

- Hepatitis

- Pancytopenia

- Spleen enlargement

- Hypersensitivity to mosquito bites

Complications include:

- Interstitial pneumonia

- Lymphoma, including B-cell, T-cell and NK-cell lymphomas

- Haemophagocytic syndrome

- Coronary artery aneurysms

- Liver failure

- Nasopharyngeal carcinoma

- Gastric adenocarcinoma

- CNS

- Intestinal perforation

- Myocarditis

- Peripheral neuropathy

Primary effusion lymphoma (PEL) is a B-cell lymphoma, presenting with a malignant effusion without a tumor mass.

Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells (NK cells) and a rapidly declining clinical course.

It is also called "aggressive NK-cell lymphoma".

Multifocal multisystem LCH, also called "Letterer-Siwe disease", is a rapidly progressing disease in which Langerhans Cell cells proliferate in many tissues. It is mostly seen in children under age 2, and the prognosis is poor: even with aggressive chemotherapy, the five-year survival is only 50%.

A primary central nervous system lymphoma (PCNSL), also known as microglioma and primary brain lymphoma, is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency (typically patients with AIDS). PCNSLs represent around 20% of all cases of lymphomas in HIV infections (other types are Burkitt's lymphomas and immunoblastic lymphomas). Primary CNS lymphoma is highly associated with Epstein-Barr virus (EBV) infection (> 90%) in immunodeficient patients (such as those with AIDS and those immunosuppressed), and does not have a predilection for any particular age group. Mean CD4+ count at time of diagnosis is ~50/uL. In immunocompromised patients, prognosis is usually poor. In immunocompetent patients (that is, patients who do not have AIDS or some other immunodeficiency), there is rarely an association with EBV infection or other DNA viruses. In the immunocompetent population, PCNSLs typically appear in older patients in their 50's and 60's. Importantly, the incidence of PCNSL in the immunocompetent population has been reported to have increased more than 10-fold from 2.5 cases to 30 cases per 10 million population. The cause for the increase in incidence of this disease in the immunocompetent population is unknown.

AIDS-related lymphoma describes lymphomas occurring in patients with acquired immunodeficiency syndrome (AIDS).

A lymphoma is a type of cancer arising from lymphoid cells. In AIDS, the incidences of non-Hodgkin's lymphoma, primary cerebral lymphoma and Hodgkin's disease are all increased. There are three different varieties of AIDS-related lymphoma: Diffuse large B-cell lymphoma, B-cell immunoblastic lymphoma, and Burkitt's lymphoma (small non-cleaved cell lymphoma).

Clinically, PASLI disease is characterized by recurrent sinopulmonary infections that can lead to progressive airway damage. Patients also suffer from lymphoproliferation (large lymph nodes and spleen), chronic viremia due to EBV or CMV, distinctive lymphoid nodules at mucosal surfaces, autoimmune cytopenias, and EBV-driven B cell lymphoma. Importantly, the clinical presentations and disease courses are variable with some individuals severely affected, whereas others show little manifestation of disease. This “variable expressivity,” even within the same family, can be striking and may be explained by differences in lifestyle, exposure to pathogens, treatment efficacy, or other genetic modifiers.