Roman & Smith Histopathology 2011, 58, 4–14. Global Cancer Frequency
Definition: Hematological malignancies Group of cancers that affect the blood, lymph nodes, and bone marrow Account for ~9% of new cancer diagnoses in the US 3 major groups Leukemia: starts in bone marrow and spreads to blood/periphery Lymphoma: occurs in lymphoid tissue Plasma cell neoplasms (e.g. multiple myeloma)
All heme malignancies (100%) Leukemia (~40%) Acute Lymphocytic (ALL): most common childhood leukemia Chronic Lymphocytic (CLL): most common leukemia in elderly Acute Myeloid (AML) Chronic Myeloid (CML): more common in adults, rare in children Other leukemias Lymphoma (~50%) Non-Hodgkin lymphoma (NHL): many histological subtypes, more common than HL Hodgkin lymphoma (HL): morphologically distinct Reed-Sternberg cells Plasma Cell Neoplasm (~10%) Multiple myeloma (MM) Other
Acute vs. chronic Acute Elevated immature blood cells in the marrow and blood Rapid progression and accumulation of malignant cells Requires immediate treatment ALL is most common form of leukemia in children Chronic Elevated mature (or relatively mature) blood cells Takes months to years to progress Sometimes treated conservatively (esp. low-grade) Mostly occurs at older ages
Rates of Acute Leukemia (ALL & AML) by age and sex, US ALLAML
ALL Can involve B (~85%) or T (~15%) lymphocytes, rarely natural killer cells Risk factors largely unknown Ionizing radiation Higher rates found in more developed countries and families with higher SES 5-year survival 66% for all ages 91% for children under 5 yrs www.lls.org
AML Involves myeloid progenitor cells Potential risk factors: Chronic benzene exposure (found in cigarette smoke) Certain genetic disorders Down syndrome increased risk of AML Past chemo or radiation therapy History of other blood cancers or disorders 5-year survival 24% for all ages 61% for children under 15 yrs www.lls.org
Rates of Chronic Leukemia (CLL & CML) by age and sex, US CLLCML
CLL Most common type of leukemia in adults Begins in the bone marrow and can progress either slowly or quickly depending on subtype 95% are B lymphocyte origin, with remaining 5% either T cell or natural killer cell origin Risk factors Family history (1 st degree relatives of CLL cases are 3-4x more likely to develop CLL than people without family Hx) Vietnam veterans (agent orange exposure) 5-year survival: 80% for all ages
CML Involves proliferation of mature and immature myeloid cells, accumulate in bone marrow and blood Potential risk factors Ionizing radiation Radiation therapy from treatment of other cancers 5-year survival: 55% for all ages
CML and the Philadelphia chromosome Translocation between BCR and c-ABL BCR-ABL acts as a tyrosine kinase, and constitutive expression increases rate of mitosis and decreases apoptosis Treated with tyrosine kinase inhibitors (eg Gleevec) which has dramatically improved survival http://users.rcn.com/jkimball.ma.ultranet/Biology Pages/C/CML.html
Leukemia rates by race/ethnicity, US Source: SEER
Atomic bomb survivors J Radiat Res (Tokyo).J Radiat Res (Tokyo). 1991 Dec;32 Suppl 2:54-63.
Treatments for leukemia Depends on subtype and risk factors Multi-drug chemotherapy regimen Less common: radiation therapy or bone marrow transplant Consequence if untreated: disruption of normal blood production Anemia: caused by low levels of RBC production Neutropenia: more susceptible to infections due to low numbers of neutrophils (a type of WBC) Bleeding/bruising: caused by low platelet levels
Rates over time of NHL & HL by race/ethnicity, US NHLHL Source: SEER
Epstein-Barr Virus (EBV) Herpesvirus family Infects nasopharyngeal epithelial cells and B lymphocytes Promotes proliferation of infected cells Ubiquitous in human populations worldwide Childhood infections are generally mild Adolescent/adult infection can lead to mononucleosis
EBV & Burkitt lymphoma Rare, aggressive NHL with B-cell origin Endemic in regions of Africa where Epstein-Barr virus (EBV) and malaria are common Malaria causes T cell immunodeficiency Occurs typically in young children, beginning in the lymph nodes in the neck Nearly 100% of tumors from African Burkitt’s lymphoma carry the EBV genome and express EBV- encoded antigens Other types (weakly linked to EBV): sporadic (non-African) immunodeficiency-associated
EBV & HL ~1/3 of tumors positive for EBV in developed countries 2- to 3- fold increased HL risk with history of infectious mononucleosis Hygiene hypothesis Lower risk with daycare, higher birth order, larger sibship size Mueller & Grufferman. Hodgkin Lymphoma in Cancer Epidemiology and Prevention. 3 rd edition.
HTLV-1 & adult T-cell leukemia/lymphoma (ATLL) Human T-lymphotropic virus type 1 (HTLV-1) Endemic to Japan, Caribbean, & parts of Central Africa Immortalizes infected T-cells (similar to HIV) HTLV-1 is a necessary but not sufficient cause of ATLL ~3% of infected individuals develop ATLL
HIV & lymphoma HIV weakens the immune system More susceptible to other infectious agents (e.g. EBV) that increase lymphoma risk Introduction of antiretroviral therapy has reduced incidence of NHL among HIV- infected individuals Engels et al. Int J Cancer. 2008;123:187-94.
Treatment for lymphoma Primarily chemotherapy and radiation therapy In some cases: bone marrow transplant or immunotherapy 5-year survival rate in US NHL 1960-1963 (Caucasians only): 31% 1999-2006 (all races): 69% HL 1960-1963 (Caucasians only): 40% 1999-2006 (all races): 88% Persons <20 yrs old: 96%
MM Cancer of plasma cells (mature B lymphocytes), amass primarily in the bone marrow Risk factors Male gender African American race/ethnicity History of MGUS (monoclonal gammopathy of unknown significance) Environmental exposures (Agent Orange, smoking, radiation, pesticides) Obesity www.lls.org