Tumors of the hematopoietic and lymphoid tissues

Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making aplasia, myeloproliferation and lymphoproliferation (and thus the leukemias and the lymphomas) closely related and often overlapping problems. While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of hematological malignancies. Hematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "hematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions (there are also surgical and radiation oncologists). Not all hematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.

Hematological malignancies may derive from either of the two major blood cell lineages: myeloid and lymphoid cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B, T, NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin.

A subgroup of them are more severe and are known as haematological malignancies (British English)/hematological malignancies (American English) or blood cancer. They may also be referred to as liquid tumors.

Diagnosis
For the analysis of a suspected hematological malignancy, a complete blood count and blood film are essential, as malignant cells can show in characteristic ways on light microscopy. When there is lymphadenopathy, a biopsy from a lymph node is generally undertaken surgically. In general, a bone marrow biopsy is part of the "work up" for the analysis of these diseases. All specimens are examined microscopically to determine the nature of the malignancy. A number of these diseases can now be classified by cytogenetics (AML, CML) or immunophenotyping (lymphoma, myeloma, CLL) of the malignant cells.

Classification
Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia) or in lymph nodes (lymphomas).

Relative proportions of hematological malignancies in the United States

World Health Organization
4th Edition

NOS = "Not otherwise specified"

• Myeloid neoplasms

Myeloproliferative neoplasms

Chronic myeloid leukaemia, BCR-ABL1-positive

Chronic neutrophilic leukaemia

Polycythamemia vera

Primary myelofibrosis

Essential thrombocythemia

Chronic eosinophilic leukaemia, NOS

Myeloproliferative neoplasm, unclassifiable

Mastocytosis

Cutaneous mastocytosis

Indolent systemic mastocytosis

Systemic mastocytosis with an associated hematological neoplasm

Aggressive systemic mastocytosis

Mast cell leukaemia

Mast cell sarcoma

Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement

Myeloid/lymphoid neoplasms with PDGFRA rearrangement

Myeloid/lymphoid neoplasms with PDGFRB rearrangement

Myeloid/lymphoid neoplasms with FGFR1 rearrangement

Myeloid/lymphoid neoplasms with PCM1―JAK2

Myelodysplastic/myeloproliferative neoplasms

Chronic myelomonocytic leukaemia

Atypical chronic myeloid leukaemia, BCR-ABL1―negative

Juvenile myelomonocytic leukaemia

Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis

Myelodysplastic/myeloproliferative neoplasm, unclassifiable

Myelodysplastic syndromes

Myelodysplastic syndrome with single lineage dysplasia

Myelodysplastic syndrome with ring sideroblasts and single lineage dysplasia

Myelodysplastic syndrome with ring sideroblasts and multilineage dysplasia

Myelodysplastic syndrome with multilineage dysplasia

Myelodysplastic syndrome with excess blasts

Myelodysplastic syndrome with isolated del(5q)

Myelodysplastic syndrome, unclassifiable

Refractory cytopenia of childhood

Myeloid neoplasms with germline predisposition

Acute myeloid leukaemia with germline CEBPA mutation

Myeloid neoplasms with germline DDX41 mutation

Myeloid neoplasms with germline RUNX1 mutation

Myeloid neoplasms with germline ANKRD26 mutation

Myeloid neoplasms with germline ETV6 mutation

Myeloid neoplasms with germline GATA2 mutation

Acute myeloid leukaemia (AML) and related precursor neoplasms

AML with recurrent genetic abnormalities

AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1

AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

Acute promyelocytic leukaemia with PML-RARA

AML with t(9;11)(p21.3;q23.3); KMT2A-MLLT3

AML with t(6;9)(p23;q34.1); DEK-NUP214

AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM

AML (megakaryoblastic) with t(1;22)(p13.3;q13.1); RBM15-MKL1

AML with BCR-ABL1

AML with mutated NPM1

AML with biallelic mutation of CEBPA

AML with mutated RUNX1

AML with myelodysplasia-related changes

Therapy-related myeloid neoplasms

Acute myeloid leukaemia, NOS

AML with minimal differentiation

AML without maturation

AML with maturation

Acute myelomonocytic leukaemia

Acute monoblastic and monocytic leukaemia

Pure erythroid leukaemia

Acute megakaryoblastic leukaemia

Acute basophilic leukaemia

Acute panmyelosis with myelofibrosis

Myeloid sarcoma

Myeloid proliferations associated with Down syndrome

Transient abnormal myelopoiesis associated with Down syndrome

Myeloid leukaemia associated with Down syndrome

Blastic plasmacytoid dendritic cell neoplasm

Acute leukaemias of ambiguous lineage

Acute undifferentiated leukaemia

Mixed-phenotype acute leukaemia with t(9;22)(q34.1;q11.2); BCR-ABL1

Mixed-phenotype acute leukaemia with t(v;11q23.3); KMT2A-rearranged

Mixed-phenotype acute leukaemia, B/myeloid, NOS

Mixed-phenotype acute leukaemia, T/myeloid, NOS

Mixed-phenotype acute leukaemia, NOS, rare types

Acute leukaemias of ambiguous lineage, NOS

• Lymphoid neoplasms

Precursor lymphoid neoplasms

B-lymphoblastic leukaemia/lymphoma, NOS

B-lymphoblastic leukaemia/lymphoma with t(9;22)(q34.1;q11.2); BCR-ABL1

B-lymphoblastic leukaemia/lymphoma with t(v;11q23.3); KMT2A-rearranged

B-lymphoblastic leukaemia/lymphoma with t(12;21)(p13.2;q22.1); ETV6-RUNX1

B-lymphoblastic leukaemia/lymphoma with hyperdiploidy

B-lymphoblastic leukaemia/lymphoma with hypodiploidy (hypodiploid ALL)

B-lymphoblastic leukaemia/lymphoma with t(5;14)(q31.1;q32.1); IGH/IL3

B-lymphoblastic leukaemia/lymphoma with t(1;19)(q23;p13.3); TCF3-PBX1

B-lymphoblastic leukaemia/lymphoma, BCR-ABL 1―like

B-lymphoblastic leukaemia/lymphoma with iAMP21

T-lymphoblastic leukaemia/lymphoma

Early T-cell precursor lymphoblastic leukaemia

NK-lymphoblastic leukaemia/lymphoma

Mature B-cell neoplasms

Chronic lymphocytic leukaemia (CLL)/ small lymphocytic lymphoma

Monoclonal B-cell lymphocytosis, CLL-type

Monoclonal B-cell lymphocytosis, non-CLL-type

B-cell prolymphocytic leukaemia

Splenic marginal zone lymphoma

Hairy cell leukaemia

Splenic B-cell lymphoma/leukaemia, unclassifiable

Splenic diffuse red pulp small B-cell lymphoma

Hairy cell leukaemia variant

Lymphoplasmacytic lymphoma

Waldentrom macroglobulinemia

IgM monoclonal gammopathy of undetermined significance

Heavy chain diseases

Mu heavy chain disease

Gamma heavy chain disease

Alpha heavy chain disease

Plasma cell neoplasms

Non-IgM monoclonal gammopathy of undetermined significance

Plasma cell myeloma

Solitary plasmacytoma of bone

Extraosseous plasmacytoma

Monoclonal immunoglobulin deposition diseases

Primary amyloidosis

Light chain and heavy chain deposition diseases

Extranodal marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma)

Nodal marginal zone lymphoma

Paediatric nodal marginal zone lymphoma

Follicular lymphoma

In situ follicular neoplasia

Duodenal-type follicular lymphoma

Testicular follicular lymphoma

Paediatric-type follicular lymphoma

Large B-cell lymphoma with IRF4 rearrangement

Primary cutaneous follicle centre lymphoma

Mantle cell lymphoma

In situ mantle cell neoplasia

Diffuse large B-cell lymphoma (DLBCL), NOS

Germinal centre B-cell subtype

Activated B-cell subtype

T-cell/histiocyte-rich large B-cell lymphoma

Primary DLBCL of the CNS

Primary cutaneous DLBCL, leg type

EBV-positive DLBCL, NOS

EBV-positive mucocutaneous ulcer

DLBCL associated with chronic inflammation

Fibrin-associated diffuse large B-cell lymphoma

Lymphomatoid granulomatosis, grade 1,2

Lymphomatoid granulomatosis, grade 3

Primary mediastinal (thymic) large B-cell lymphoma

Intravascular large B-cell lymphoma

ALK-positive large B-cell lymphoma

Plasmablastic lymphoma

Primary effusion lymphoma

Multicentric Castleman disease

HHV8-positive DLBCL, NOS

HHV8-positive germinotropic lymphoproliferative disorder

Burkitt lymphoma

Burkitt-like lymphoma with 11q aberration

High-grade B-cell lymphoma

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements

High-grade B-cell lymphoma, NOS

B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma

Mature T- and NK-cell neoplasms

T-cell prolymphocytic leukaemia

T-cell large granular lymphocytic leukaemia

Chronic lymphoproliferative disorder of NK cells

Aggressive NK-cell leukaemia

Systemic EBV-positive T-cell lymphoma of childhood

Chronic active EBV infection of T- and NK-cell type, systemic form

Hydroa vacciniforme-like lymphoproliferative disorder

Severe mosquito bite allergy

Adult T-cell leukaemia/lymphoma

Extranodal NK/T-cell lymphoma, nasal type

Enteropathy-associated T-cell lymphoma

Monomorphic epitheliotropic intestinal T-cell lymphoma

Intestinal T-cell lymphoma, NOS

Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract

Hepatosplenic T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma

Mycosis fungoides

Sézary syndrome

Primary cutaneous CD30-positive T-cell lymphoproliferative disorders

Lymphomatoid papulosis

Primary cutaneous anaplastic large cell lymphoma

Primary cutaneous gamma delta T-cell lymphoma

Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma

Primary cutaneous acral CD8-positive T-cell lymphoma

Primary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorder

Peripheral T-cell lymphoma, NOS

Angioimmunoblastic T-cell lymphoma

Follicular T-cell lymphoma

Nodal peripheral T-cell lymphoma with T follicular helper phenotype

Anaplastic large cell lymphoma, ALK-positive

Anaplastic large cell lymphoma, ALK-negative

Breast implant-associated anaplastic large cell lymphoma

Hodgkin lymphomas

Nodular lymphocyte predominant Hodgkin lymphoma

Classic Hodgkin lymphoma

Nodular sclerosis classic Hodgkin lymphoma

Lymphocyte-rich classic Hodgkin lymphoma

Mixed cellularity classic Hodgkin lymphoma

Lymphocyte-depleted classic Hodgkin lymphoma

Immunodeficiency-associated lymphoproliferative disorders

Post-transplant lymphoproliferative disorders (PTLD)

Non-destructive PTLD

Plasmacytic hyperplasia PTLD

Infectious mononucleosis PTLD

Florid follicular hyperplasia

Polymorphic PTLD

Monomorphic PTLD

Classic Hodgkin Lymphoma PTLD

Other iatrogenic immunodeficiency- associated lymphoproliferative disorders

• Histiocytic and dendritic cell neoplasms

Histiocytic sarcoma

Langerhans cell histiocytosis, NOS

Langerhans cell histiocytosis, monostotic

Langerhans cell histiocytosis, polystotic

Langerhans cell histiocytosis, disseminated

Langerhans cell sarcoma

Indeterminate dendritic cell tumour

Interdigitating dendritic cell sarcoma

Follicular dendritic cell sarcoma

Fibroblastic reticular cell tumour

Disseminated juvenile xanthogranuloma

Erdheim–Chester disease

Treatment
Treatment can occasionally consist of "watchful waiting" (e.g., in CLL) or symptomatic treatment (e.g., blood transfusions in MDS). The more aggressive forms of disease require treatment with chemotherapy, radiotherapy, immunotherapy and—in some cases—a bone marrow transplant. The use of rituximab has been established for the treatment of B-cell–derived hematologic malignancies, including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).

In addition to cure-directed treatment, people can benefit from self-care to manage symptoms. For example, aerobic exercise, such as walking, can reduce fatigue and feelings of depression in people with hematological malignancies.

Follow-up
If treatment has been successful ("complete" or "partial remission"), a person is generally followed up at regular intervals to detect recurrence and monitor for "secondary malignancy" (an uncommon side-effect of some chemotherapy and radiotherapy regimens—the appearance of another form of cancer). In the follow-up, which should be done at pre-determined regular intervals, general anamnesis is combined with complete blood count and determination of lactate dehydrogenase or thymidine kinase in serum. Hematological malignancies as well as their treatments are associated with complications affecting many organs, with the lungs being frequently affected.

Etiology
Chromosomal translocations are a major etiologic factor in hematologic malignancies. Such translocations usually arise in cells as the result of aberrant DNA double-strand break repair by an imprecise processes such as non-homologous end joining. Chromosome instability in chronic myeloid leukemia may be due to oxidative damage to DNA along with impairments of genetic surveillance leading to imprecise error prone DNA repair.

Epidemiology
Taken together, haematological malignancies account for 9.5% of new cancer diagnoses in the United States and 30,000 patients in the UK are diagnosed each year. Within this category, lymphomas are more common than leukemias.