Page 371 - Textbook of Pathology, 6th Edition

i) Identical twins: There is high concordance rate among i) Immunodeficiency diseases. Various inherited and 355
identical twins if acute leukaemia develops in the first year acquired immunodeficiency diseases including AIDS and
of life. Hodgkin’s disease is 99 times more common in iatrogenic immunosuppression induced by chemotherapy or
identical twin of an affected case compared with general radiation, are associated with subsequent development of
population, implicating genetic origin strongly. lymphomatous transformation.
ii) Family history. Families with excessive incidence of ii) Autoimmune disease association. A few autoimmune
leukaemia have been identified. diseases such as Sjögren’s syndrome, nontropical sprue,
iii) Genetic disease association. Acute leukaemia occurs with rheumatoid arthritis and SLE are associated with higher
increased frequency with a variety of congenital disorders incidence of NHL.
such as Down’s, Bloom’s, Klinefelter’s and Wiskott-Aldrich’s
syndromes, Fanconi’s anaemia and ataxia telangiectasia. PATHOGENESIS
Hodgkin’s disease has familial incidence and with certain It needs to be emphasised that since haematopoietic cells
HLA type. have a rapid turnover, they are more vulnerable to
2. INFECTIONS. There is evidence to suggest that certain chromosomal damages and cytogenetic changes under
infections, particularly viruses, are involved in development influence of various etiologic factors listed above. CHAPTER 14
of lymphomas and leukaemias (Chapter 8): 1. Genetic damage to single clone of target cells. Leukaemias
i) Human T cell leukaemia-lymphoma virus I (HTLV-I) and lymphomas arise following malignant transformation
implicated in etiology of adult T cell leukaemia-lymphoma of a single clone of cells belonging to myeloid or lymphoid
(ATLL). series, followed by proliferation of the transformed clone.
ii) HTLV II for T cell variant of hairy cell leukaemia. Basic mechanism of malignant transformation is genetic
iii) Epstein-Barr virus (EBV) implicated in the etiology of damage to the DNA of the target white cells followed by
Hodgkin’s disease (mixed cellularity type and nodular proliferation, disrupting normal growth and differentiation.
sclerosis type), endemic variety of Burkitt’s lymphoma, post- The heritable genetic damage may be induced by various
transplant lymphoma, etiologic agents listed above (e.g. RNA viruses HTLV-I, EBV
iv) HIV in diffuse large B-cell lymphoma and Burkitt’s etc) and causes insertional mutagenesis for which oncogenes
may play a role (Chapter 8). The evolution of leukaemia is
lymphoma. multi-step process, and in many cases, acute leukaemia may
v) Hepatitis C virus (HCV) in lymphoplasmacytic lymphoma. develop after a pre-existing myelodysplastic or
vi) Human herpes virus 8 (HHV-8) in primary effusion myeloproliferative disorder.
lymphoma.
vii) Helicobacter pylori bacterial infection of gastric mucosa 2. Chromosomal translocations. A number of cytogenetic
abnormalities have been detected in cases of leukaemias-
in MALT lymphoma of the stomach.
lymphomas, most consistent of which are chromosomal Disorders of Leucocytes and Lymphoreticular Tissues
3. ENVIRONMENTAL FACTORS. Certain environmental translocations. In NHL, translocation involving antigen
factors are known to play a role in the etiology of leukaemias receptor genes, immunoglobulin genes, or overexpression
and lymphomas: of BCL-2 protein may be seen. The most consistent
i) Ionising radiation. Damage due to radiation exposure chromosomal abnormality in various forms of acute and
has been linked to development of leukaemias and chronic leukaemias is Philadelphia (Ph) chromosome seen
lymphomas. Individuals exposed to occupational radiation in 70-90% cases with CML, involving reciprocal translocation
exposure, patients receiving radiation therapy, and Japanese of parts of long arm of chromosome 22 to the long arm of
survivors of the atomic bomb explosions have been found to chromosome 9 i.e. t(9;22) (Fig. 14.11).
be at higher risk of developing haematopoietic malignancies, 3. Maturation defect. In acute leukaemia, the single most
particularly prone to development of CML, AML and ALL prominent characteristic of the leukaemic cells is a defect in
but not to CLL or hairy cell leukaemia. maturation beyond the myeloblast or promyelocyte level in
ii) Chemical carcinogens. Benzene, tobacco smoking, AML, and the lymphoblast level in ALL. It needs to be
alcohol, use of certain hair dyes and exposure to agriculture emphasised that it is the maturation defect in leukaemic
chemicals are associated with increased risk of development blasts rather than rapid proliferation of leukaemic cells
of haematopoietic malignancies. responsible for causing acute leukaemia. In fact, the
iii) Certain drugs. Long-term exposure to certain drugs such generation time of leukaemic blasts is somewhat prolonged
as phenytoin, alkylating agents and other chemotherapeutic rather than shortened.
agents is associated with increased incidence of leukaemias 4. Myelosuppression. As the leukaemic cells accumulate
and lymphomas. Patients treated for Hodgkin’s disease can in the bone marrow, there is suppression of normal
develop NHL.
haematopoietic stem cells, partly by physically replacing the
4. ASSOCIATION WITH DISEASES OF IMMUNITY. normal marrow precursors, and partly by inhibiting normal
Since lymphoid cells are the immune cells of the body, haematopoiesis via cell-mediated or humoral mechanisms.
diseases with derangements of the immune system have This is based on the observation that some patients with acute
higher incidence of haematopoietic malignancies: leukaemia have a hypocellular marrow indicating that