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, myelomas, 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 also used for the analysis of these diseases.[citation needed] 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.[citation needed]

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-positiveChronic neutrophilic leukaemiaPolycythamemia veraPrimary myelofibrosisEssential thrombocythemiaChronic eosinophilic leukaemia, NOSMyeloproliferative neoplasm, unclassifiableMastocytosis Cutaneous mastocytosisIndolent systemic mastocytosisSystemic mastocytosis with an associated hematological neoplasmAggressive systemic mastocytosisMast cell leukaemiaMast cell sarcomaMyeloid/lymphoid neoplasms with eosinophilia and gene rearrangement Myeloid/lymphoid neoplasms with PDGFRA rearrangementMyeloid/lymphoid neoplasms with PDGFRB rearrangementMyeloid/lymphoid neoplasms with FGFR1 rearrangementMyeloid/lymphoid neoplasms with PCM1―JAK2Myelodysplastic/myeloproliferative neoplasms Chronic myelomonocytic leukaemiaAtypical chronic myeloid leukaemia, BCR-ABL1―negativeJuvenile myelomonocytic leukaemiaMyelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosisMyelodysplastic/myeloproliferative neoplasm, unclassifiableMyelodysplastic syndromes Myelodysplastic syndrome with single lineage dysplasiaMyelodysplastic syndrome with ring sideroblasts and single lineage dysplasiaMyelodysplastic syndrome with ring sideroblasts and multilineage dysplasiaMyelodysplastic syndrome with multilineage dysplasiaMyelodysplastic syndrome with excess blastsMyelodysplastic syndrome with isolated del(5q)Myelodysplastic syndrome, unclassifiableRefractory cytopenia of childhoodMyeloid neoplasms with germline predisposition Acute myeloid leukaemia with germline CEBPA mutationMyeloid neoplasms with germline DDX41 mutationMyeloid neoplasms with germline RUNX1 mutationMyeloid neoplasms with germline ANKRD26 mutationMyeloid neoplasms with germline ETV6 mutationMyeloid neoplasms with germline GATA2 mutationAcute myeloid leukaemia (AML) and related precursor neoplasms AML with recurrent genetic abnormalities AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11Acute promyelocytic leukaemia with PML-RARAAML with t(9;11)(p21.3;q23.3); KMT2A-MLLT3AML with t(6;9)(p23;q34.1); DEK-NUP214AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOMAML (megakaryoblastic) with t(1;22)(p13.3;q13.1); RBM15-MKL1AML with BCR-ABL1AML with mutated NPM1AML with biallelic mutation of CEBPAAML with mutated RUNX1AML with myelodysplasia-related changesTherapy-related myeloid neoplasmsAcute myeloid leukaemia, NOS AML with minimal differentiationAML without maturationAML with maturationAcute myelomonocytic leukaemiaAcute monoblastic and monocytic leukaemiaPure erythroid leukaemiaAcute megakaryoblastic leukaemiaAcute basophilic leukaemiaAcute panmyelosis with myelofibrosisMyeloid sarcomaMyeloid proliferations associated with Down syndrome Transient abnormal myelopoiesis associated with Down syndromeMyeloid leukaemia associated with Down syndromeBlastic plasmacytoid dendritic cell neoplasmAcute leukaemias of ambiguous lineage Acute undifferentiated leukaemiaMixed-phenotype acute leukaemia with t(9;22)(q34.1;q11.2); BCR-ABL1Mixed-phenotype acute leukaemia with t(v;11q23.3); KMT2A-rearrangedMixed-phenotype acute leukaemia, B/myeloid, NOSMixed-phenotype acute leukaemia, T/myeloid, NOSMixed-phenotype acute leukaemia, NOS, rare typesAcute leukaemias of ambiguous lineage, NOS
• Lymphoid neoplasms Precursor lymphoid neoplasms B-lymphoblastic leukaemia/lymphoma, NOSB-lymphoblastic leukaemia/lymphoma with t(9;22)(q34.1;q11.2); BCR-ABL1B-lymphoblastic leukaemia/lymphoma with t(v;11q23.3); KMT2A-rearrangedB-lymphoblastic leukaemia/lymphoma with t(12;21)(p13.2;q22.1); ETV6-RUNX1B-lymphoblastic leukaemia/lymphoma with hyperdiploidyB-lymphoblastic leukaemia/lymphoma with hypodiploidy (hypodiploid ALL)B-lymphoblastic leukaemia/lymphoma with t(5;14)(q31.1;q32.1); IGH/IL3B-lymphoblastic leukaemia/lymphoma with t(1;19)(q23;p13.3); TCF3-PBX1B-lymphoblastic leukaemia/lymphoma, BCR-ABL 1―likeB-lymphoblastic leukaemia/lymphoma with iAMP21T-lymphoblastic leukaemia/lymphomaEarly T-cell precursor lymphoblastic leukaemiaNK-lymphoblastic leukaemia/lymphomaMature B-cell neoplasms Chronic lymphocytic leukaemia (CLL)/ small lymphocytic lymphomaMonoclonal B-cell lymphocytosis, CLL-typeMonoclonal B-cell lymphocytosis, non-CLL-typeB-cell prolymphocytic leukaemiaSplenic marginal zone lymphomaHairy cell leukaemiaSplenic B-cell lymphoma/leukaemia, unclassifiable Splenic diffuse red pulp small B-cell lymphomaHairy cell leukaemia variantLymphoplasmacytic lymphoma Waldentrom macroglobulinemiaIgM monoclonal gammopathy of undetermined significanceHeavy chain diseases Mu heavy chain diseaseGamma heavy chain diseaseAlpha heavy chain diseasePlasma cell neoplasms Non-IgM monoclonal gammopathy of undetermined significancePlasma cell myelomaSolitary plasmacytoma of boneExtraosseous plasmacytomaMonoclonal immunoglobulin deposition diseases Primary amyloidosisLight chain and heavy chain deposition diseasesExtranodal marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma)Nodal marginal zone lymphoma Paediatric nodal marginal zone lymphomaFollicular lymphoma In situ follicular neoplasiaDuodenal-type follicular lymphomaTesticular follicular lymphomaPaediatric-type follicular lymphomaLarge B-cell lymphoma with IRF4 rearrangementPrimary cutaneous follicle centre lymphomaMantle cell lymphoma In situ mantle cell neoplasiaDiffuse large B-cell lymphoma (DLBCL), NOS Germinal centre B-cell subtypeActivated B-cell subtypeT-cell/histiocyte-rich large B-cell lymphomaPrimary DLBCL of the CNSPrimary cutaneous DLBCL, leg typeEBV-positive DLBCL, NOSEBV-positive mucocutaneous ulcerDLBCL associated with chronic inflammation Fibrin-associated diffuse large B-cell lymphomaLymphomatoid granulomatosis, grade 1,2Lymphomatoid granulomatosis, grade 3Primary mediastinal (thymic) large B-cell lymphomaIntravascular large B-cell lymphomaALK-positive large B-cell lymphomaPlasmablastic lymphomaPrimary effusion lymphomaMulticentric Castleman diseaseHHV8-positive DLBCL, NOSHHV8-positive germinotropic lymphoproliferative disorderBurkitt lymphomaBurkitt-like lymphoma with 11q aberrationHigh-grade B-cell lymphoma High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangementsHigh-grade B-cell lymphoma, NOSB-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphomaMature T- and NK-cell neoplasms T-cell prolymphocytic leukaemiaT-cell large granular lymphocytic leukaemiaChronic lymphoproliferative disorder of NK cellsAggressive NK-cell leukaemiaSystemic EBV-positive T-cell lymphoma of childhoodChronic active EBV infection of T- and NK-cell type, systemic formHydroa vacciniforme-like lymphoproliferative disorderSevere mosquito bite allergyAdult T-cell leukaemia/lymphomaExtranodal NK/T-cell lymphoma, nasal typeEnteropathy-associated T-cell lymphomaMonomorphic epitheliotropic intestinal T-cell lymphomaIntestinal T-cell lymphoma, NOSIndolent T-cell lymphoproliferative disorder of the gastrointestinal tractHepatosplenic T-cell lymphomaSubcutaneous panniculitis-like T-cell lymphomaMycosis fungoidesSézary syndromePrimary cutaneous CD30-positive T-cell lymphoproliferative disorders Lymphomatoid papulosisPrimary cutaneous anaplastic large cell lymphomaPrimary cutaneous gamma delta T-cell lymphomaPrimary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphomaPrimary cutaneous acral CD8-positive T-cell lymphomaPrimary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorderPeripheral T-cell lymphoma, NOSAngioimmunoblastic T-cell lymphomaFollicular T-cell lymphomaNodal peripheral T-cell lymphoma with T follicular helper phenotypeAnaplastic large cell lymphoma, ALK-positiveAnaplastic large cell lymphoma, ALK-negativeBreast implant-associated anaplastic large cell lymphomaHodgkin lymphomas Nodular lymphocyte predominant Hodgkin lymphomaClassic Hodgkin lymphoma Nodular sclerosis classic Hodgkin lymphomaLymphocyte-rich classic Hodgkin lymphomaMixed cellularity classic Hodgkin lymphomaLymphocyte-depleted classic Hodgkin lymphomaImmunodeficiency-associated lymphoproliferative disorders Post-transplant lymphoproliferative disorders (PTLD) Non-destructive PTLD Plasmacytic hyperplasia PTLDInfectious mononucleosis PTLDFlorid follicular hyperplasiaPolymorphic PTLDMonomorphic PTLDClassic Hodgkin Lymphoma PTLDOther iatrogenic immunodeficiency- associated lymphoproliferative disorders
• Histiocytic and dendritic cell neoplasms Histiocytic sarcomaLangerhans cell histiocytosis, NOSLangerhans cell histiocytosis, monostoticLangerhans cell histiocytosis, polystoticLangerhans cell histiocytosis, disseminatedLangerhans cell sarcomaIndeterminate dendritic cell tumourInterdigitating dendritic cell sarcomaFollicular dendritic cell sarcomaFibroblastic reticular cell tumourDisseminated juvenile xanthogranulomaErdheim–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.[citation needed]

See also

• Myelodysplastic–myeloproliferative diseases