The Leukemia's

The Leukemia's

A heterogeneous group of malignant neoplasms developing from hematopoietic (blood forming) cells. The cells of these neoplasms proliferate in bone marrow and lymphoid tissues and eventually involve peripheral blood and infiltrate other organ systems. These disorders are classified on the basis o the cell line involved as either myeloid or lymphoid and as acute or chronic depending on the course of progression of the illness.

In most cases, the etiology is not known. Congenital syndromes, radiation, and chemical exposure are important factors in some cases. The human T-cell leukemia virus (HTL V- І) is associated with adult T-cell leukemia.

The proliferating cell in acute leukemias is an immature clonal myeloid or lymphoid cell that may demonstrate varying degrees of differentiation. These proliferating cells accumulate in bone marrow primarily because they fail to mature past the myeloblast or promyelocyte level in acute myelogenous leukemia (AML) or the lymphoblast level in acute Lymphocytic leukemia (ALL). The neoplastic cells in many forms of acute and chronic leukemia demonstrate characteristic cytogenetic abnormalities. Many pts with leukemia demonstrate pancytopenia, which may result from bone marrow crowding by malignant cells or may be the result of direct effects of the leukemic cells or their interaction with the bone marrow microenvironment. Infiltration of leukemic cells into other organ system may produce the varied clinical manifestation of advanced leukemia.

Acute Leukemia

Bone marrow in acute leukemia is typically hypercellular and heavily infiltrated with a monomorphic population of leukemic blasts; numbers of normal bone marrow elements are markedly reduced. Prognostic and therapeutic considerations make it crucial to distinguish between AML and ALL. These disorders are classified on the basis of cellular morphology, cytochemical features, immunologic phenotype, and degree of differentiation. A collaborative French-American-British (FAB) group has divided ALL into 3 subtypes (L1, L2 and L3) and AML into subtypes (M1 through M7) based on morphologic features.

1.Initial symptoms of acute leukemia usually present for less  than  3 months; a preleukemic syndrome may be present in some 25 % of pts  with AML.
2.WBC may be low, normal or markedly elevated; circulating blast cells nay or may not be present; with WBC > 100,000 blasts//µL  leukostasis in lungs and brain may occur.
3.Thrombocytopenia and spontaneous bleeding, especially when platelet count < 20,000//µL
4.Bacterial and fungal infection common; risk is heightened when total neutrophil count < 500//µL; breakdown of mucosal and cutaneous  barriers aggravates susceptibility infections may be clinically occult in presence of severe leucopenia, and prompt recognition requires a  high degree of clinical suspicion.
5.Hepatosplenomegaly and lymphadenopathy are common in ALL, less so in AML; leukemic meningitis may present with headache, nausea, seizures, papilledema, cranial nerve palsies; testicular involvement in males with ALL.
6.Metabolic abnormalities may include hyponatremia, hypokalemia, elevated serum LDH, hyperuricemia, and (rarely) lactic acidosis.

Chronic Leukemia

CLL  is a neoplasm characterized by accumulation of mature-appearing lymphocytes in blood and bone marrow; 95 % of cases involves B lymphocytes; spleen and lymph nodes may be infiltrated; pts are usually over 50 years old. CLL is frequently an incidental finding on CBC.Complications include cytopenia, Coombs-positive hemolytic anemia, hypogammaglobulinemia, infection, evolution into lymphoma (Richter’s syndrome).Many pts require no therapy; some may need therapy with alkylating agents, glucocorticoids, immunoglobulin infusion.

CML is usually characterized by splenomegaly and production of increased numbers of granulocytes; course is initially indolent but eventuates in leukemic phase (blast crisis); rate of progression to blast crisis is variable; overall survival averages 3 ½ years from diagnosis. More than 95 % pts have characteristic chromosomal abnormality, Philadelphia chromosome. Blastic phase may involve cells of either lymphoid or myeloid origin. Treatment of chronic phase involves control of cell counts with alkylating agents or hydroxyurea; blast crisis is usually refractory to most regimens, but ALL or AML programs may be useful; bone marrow transplantation during chronic phase may improve prognosis in some pts. Hairy-Cell Leukemia Hairy-Cell Leukemia (HCL) is a lymphoid neoplasm marked by cytopenia, splenomegaly, and proliferation of typical cells (with characteristic cytoplasmic projections) in blood and bone marrow. Malignant cells are almost always B cells; T-cell variants are rare. Cells stain positively for tartrate-resistant acid phosphatase (TRAP). Complications include vasculitis and frequent infection.  

Definition-Malignant lymphomas are tumors characterized by malignant transformation of lymphoid or monocytoid cells. Two major variants are Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma. Diagnosis requires biopsy of affected tissue. Cellular Origins- Some 90 % of non-Hodgkin’s lymphomas are of B-cell origin; 10 % are T cell-derived. The derivation of the malignant cells in Hodgkin’s disease is unknown. Non-Hodgkin’s Lymphoma Etiology and Epidemiology- Etiology for most cases is unknown; EBV is associated with African Burkitt’s lymphoma; HTL V-1 is associated with adult T-cell lymphoma. There is increased incidence of non-Hodgkin’s lymphomas in HIV infection. Pts previously treated with chemotherapy ad radiation for malignancy are at higher risk.  Clinical Manifestations Two –third present with painless peripheral lymphadenopathy. Biopsy of affected node necessary for diagnosis. “B symptoms” (fever, sweats, weight loss) are less common than with Hodgkin’s disease. Mediastinal adenopathy is present in approximately 20 %. Superior vena cava syndrome may result. Involvement of retroperitoneal, mesenteric, pelvic nodes common. May arise in GI tract. Primary CNS site seen commonly in AIDS pts. Pathologic Classification- Classification schemes have evolved as histologic and immunologic methods of classifying tumors have improved.

Usually presents with asymptomatic lymph node enlargement or with adenopathy associated with fever, night sweats, weight loss and sometimes pruritus. Mediastinal adenopathy (common in nodular sclerosing HD) may produce cough. Visceral involvement of bone marrow, liver etc. may be seen, especially in advanced disease.

Breast cancer is a major disease. At particular risk are women whose mothers had breast cancer prior to menopause, women with first-degree relatives with postmenopausal breast cancer, nulliparous women above age 50, women whose first parity occurred after age 30, women with a history of chronic breast disease, women exposed to ionizing radiation, and obese women. Increased risk for breast carcinoma in men includes feminizing states (such as Klinefelter syndrome) and testicular atrophy from viral orchitis of injury.
Breast cancer is frequently multicentric (13 % of pts show microscopic foci in contra lateral breast). Size of primary tumor can be estimated by palpation combined with mammography. Tumor < 2 cm in size are associated with most favorable outcome. Another prognostic factor is presence or absence of estrogen receptor (ER) and progesterone receptor (PR), the degree of positivity being proportional to cellular differentiation and responsiveness of tumor to hormonal deprivation
Most breast masses are found by the pt either accidentally or during self-examination. Annual mammograms are recommended for all women over 50 and for high-risk women ages 40-49. disease usually presents with a hard, circumscribed mass in breast. Most lumps are benign, but if mass is fixed to skin or muscle or there is edema of skin or retraction of nipple, breast cancer is more likely. Once a  mass is detected, metastatic disease should be searched for, and the mass should then be biopsied.