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.

All people with ALPS have signs of lymphoproliferation, which makes it the most common clinical manifestation of the disease. The increased proliferation of lymphoid cells can cause the size of lymphoid organs such as the lymph nodes and spleen to increase (lymphadenopathy and splenomegaly, present in respectively over 90% and over 80% of patients). The liver is enlarged (hepatomegaly in 30 - 40% of patients).

Autoimmune disease is the second most common clinical manifestation and one that most often requires treatment. Autoimmune cytopenias: Most common. Can be mild to very severe. Can be intermittent or chronic. These include: Autoimmune hemolytic anemia, Autoimmune neutropenia, Autoimmune thrombocytopenia.

Other signs can affect organ systems similar to systemic lupus erythematosus (least common, affecting <5% of patients) Symptoms of the nervous system include: Autoimmune cerebellar ataxia; Guillain–Barré syndrome; transverse myelitis. Gastrointestinal signs like Autoimmune esophagitis, gastritis, colitis, hepatitis, pancreatitis can be found or (Dermatologic) Urticaria, (Pulmonary) bronchiolitis obliterans, (Renal) Autoimmune glomerulonephritis, nephrotic syndrome.

Another sign are cancers such as Hodgkin and non-Hodgkin lymphomas which appear to be increased, possibly due to Epstein–Barr virus-encoded RNA-positivity. Some carcinomas may occur. Unaffected family members with genetic mutations are also at an increased risk of developing cancer.

Clinically, RALD is characterized by splenomegaly, a relatively mild degree of peripheral lymphadenopathy, and autoimmunity. The autoimmune phenotype can present in childhood or adulthood and primarily includes autoimmune hemolytic anemia, ITP, and neutropenia. Some patients have a history of recurrent respiratory tract infections. It is unclear if increased risk for malignancy is part of RALD.

Importantly, however, the clinical and laboratory phenotype resembles juvenile myelomonocytic leukemia. The high fatality rate of this childhood blood cancer puts it in sharp contrast when compared to the relatively benign and chronic course of RALD. Approximately 15-30% of patients diagnosed with JMML have somatic, activating RAS mutations. However, due to the difficulty in distinguishing JMML from RALD, it is possible a subset of patients treated for JMML actually have RALD and could therefore avoid the aggressive JMML treatment. This distinction is under investigation.

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.

Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in people who have a compromised immune system. They are sometimes equated with "immunoproliferative disorders", but technically lymphoproliferative disorders are a subset of immunoproliferative disorders, along with hypergammaglobulinemia and paraproteinemias.

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.

RAS-associated autoimmune leukoproliferative disorder (RALD) is a rare genetic disorder of the immune system. RALD is characterized by lymphadenopathy, splenomegaly, autoimmunity, and elevation in granulocytes and monocytes. It shares many features with autoimmune lymphoproliferative syndrome and is caused by somatic mutations in NRAS or KRAS. This was first described by investigators João Oliveira and Michael Lenardo from the National Institutes of Health.

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.

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.

Lymphoproliferative disorders are a set of disorders characterized by the abnormal proliferation of lymphocytes into a monoclonal lymphocytosis. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoetic stem cells in the bone marrow. Individuals who have some sort of dysfunction with their immune system are susceptible to develop a lymphoproliferative disorder because when any of the numerous control points of the immune system become dysfunctional, immunodeficiency or deregulation of lymphocytes is more likely to occur. There are several inherited gene mutations that have been identified to cause lymphoproliferative disorders; however, there are also acquired and iatrogenic causes.

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.

Lymphoid leukemias — also called lymphocytic, lymphogenous, or lymphoblastic leukemias — are a group of leukemias affecting circulating lymphocytes, a type of white blood cells. The lymphocytic leukemias are closely related to lymphomas of the lymphocytes, to the point that some of them are unitary disease entities that can be called by either name (for example, adult T-cell leukemia/lymphoma). Such diseases are all lymphoproliferative disorders. Most lymphoid leukemias involve a particular subtype of lymphocytes, the B cells.

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

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.

Historically, they have been most commonly divided by the stage of maturation at which the clonal (neoplastic) lymphoid population stopped maturing:

- Acute lymphoblastic leukemia

- Chronic lymphocytic leukemia

However, the influential WHO Classification (published in 2001) emphasized a greater emphasis on cell lineage. To this end, lymphoid leukemias can also be divided by the type of cells affected:

- B-cell leukemia

- T-cell leukemia

- NK-cell leukemia

The most common type of lymphoid leukemia is B-cell chronic lymphocytic leukemia.

2003 nomenclature

- IA - Fas

- IB - Fas ligand

- IIA - Caspase 10

- IIB - Caspase 8

- III - unknown

- IV - Neuroblastoma RAS viral oncogene homolog

Revised nomenclature (2010)

- ALPS-FAS: Fas. Germline FAS mutations. 70% of patients. Autosomal dominant. Dominant negative and haploinsufficient mutations described.

- ALPS-sFAS: Fas. Somatic FAS mutations in DNT compartment. 10% of patients

- ALPS-FASL: Fas ligand. Germline FASL mutations. 3 reported cases

- ALPS-CASP10: Caspase 10. Germline CASP10 mutation. 2% of patients

- ALPS-U: Undefined. 20% of patients

- CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder

- RALD: NRAS, KRAS. Somatic mutations in NRAS and KRAS in lympocyte compartment. No longer considered a subtype of ALPS but distinct disesase

Although not a malignant neoplasm like other cancers, MPNs are classified within the hematological neoplasms. There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome:

In 2008, the World Health Organization listed these diagnoses as types of MPD:

- Chronic myelogenous leukemia (BCR-ABL1–positive)

- Chronic neutrophilic leukemia

- Polycythemia vera

- Primary myelofibrosis

- Essential thrombocythemia

- Chronic eosinophilic leukemia (not otherwise specified)

- Mastocytosis

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

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

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

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".

The myeloproliferative neoplasms (MPNs), previously myeloproliferative diseases (MPDs), are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek. In the most recent World Health Organization classification of hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms". This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.

The increased numbers of blood cells may not cause any symptoms, but a number of medical problems or symptoms may occur. The risk of thrombosis is increased in some types of MPN.

Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is sometimes called the plasmablastic form of multicentric Castleman disease. It has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. It has variable CD20 expression and unmutated immunoglobulin variable region genes.

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).