Keywords: Chapter 20b, Blood and Lymphoid Tissues II
Acute lymphoblastic lymphoma (ALL)
Clonal disorder arising from an aberrant lymphoid cell, with proliferation of lymphoblasts. ALL is the most common childhood malignancy, with approximately 3500 new cases diagnosed in 1995 in the USA. ALL has three subtypes in the FAB classification system. In childhood ALL, the patients usually present with hepatosplenomegaly, lymphadenapathy, anemia, thrombocytopenia, neutropenia and may have CNS involvement. A diagnosis is made when > 30% blasts are present in the bone marrow or peripheral blood. The two most important prognostic factors are age at diagnosis and the initial blood leukocyte count (unfavorable prognostic factors include: age 10 yr.; WBC > 50,000/ul; male sex; FAB subtype L2 or L3; black race; and prominent organ involvement.)
Acute myelogenous leukemia (AML)
Clonal disorder arising from an aberrant myeloid precursor cell, which includes myeloblasts, monoblasts, erythroblasts, and megakaryoblasts. AML is the most common acute leukemia in adults, and represents 4% of new adult cancers. AML is classified into 8 major subtypes in the FAB classification system (M0, M1-M7). A diagnosis is made when >30% blasts are present in the bone marrow or blood.
Agnogenic myeloid metaplasia
Agnogenic myeloid metaplasia is characterized by pancellular bone marrow hyperplasia, bone marrow fibrosis and extramedullary hematopoiesis with marked splenomegaly. Peripheral blood shows leukoerythroblastosis and anisopoikilocytosis with teardrop red blood cells. Leukemic conversion occurs in 15-20%, and the median 5 year survival is 3-4 years. CML is characterized by bone marrow granulocytic hyperplasia, marked leukocytosis with basophilia and the presence of the Philadelphia chromosome. The disease often has a stable (chronic) phase which progresses to an accelerated phase, and may then develop blast crisis. Leukemic conversion occurs in 70%, and the median 5 year survival is 3-4 years. The prognosis and outcome of CML is improving with the use of bone marrow transplantation.
Auer rod
Rod-shaped cytoplasmic inclusion observed in myeloblasts of some cases of AML and myelodysplastic disorders (RAEB-IT). The presence of an Auer rod helps to define myeloid lineage of the blast.
Bence-Jones protein
Immunoglobin light chains which are present in the urine. They are observed in the setting of patients with multiple myeloma, which may secrete a paraprotein.
Burkitt lymphoma (small non-cleaved cell lymphoma)
High grade non-Hodgkin lymphoma with a rapid doubling time. Histologic hallmark is the presence of sheets of blasts with cytoplasmic vacuoles and the presence of a "starry sky" appearance. The morphologic appearance is similar to the FAB subtype L3 of ALL. The characteristic chromosomal abnormality t(8,14) involving the c-myc gene is present in 80% of cases. Endemic African Burkitt lymphoma usually presents with a jaw or abdominal mass in children, and has EBV genome detectable in 95% of cases. In the United States, sporadic Burkitt lymphoma usually presents as an abdominal mass, and is associated with EBV in 15% of cases. Burkitt and Burkitt-like lymphoma is the most common type of lymphoma seen in the Aids population.
CD (cluster designation) number
Standardized designation for monoclonal antibodies that react with cell surface antigens. Currently, >125 CD numbers exist. The surface antigen expression of neoplastic cells is determined by reacting the cells with a panel of monoclonal antibodies. Analysis using a flow cytometer is often undertaken for determining the blast lineage in acute leukemia, and determining the immunophenotype of chronic leukemia and lymphoma. (Schlossman S., Boumsell L., Gilks W., et al, Leucocyte Typing V. Oxford Univ. Press, Oxford, 1994).
Cat scratch disease
Self-limited infection caused by Bartenella henselae. The bacteria are inoculated into the skin via a scratch from a cat, and may be carried to regional lymph nodes. Histopathology of the lymph node shows a necrotizing granulomatous inflammation. Diagnosis is aided by a serologic test as well as history of a cat scratch (usually from a kitten).
Chloroma (granulocytic sarcoma)
Tumor mass formed by neoplastic hemopoietic cells.
Chromosomal abnormality
The presence of a non-random cytogenetic abnormality. In hematogy, some subtypes of myelodysplasia, leukemia and lymphoma are associated with characteristic cytogenetic abnormalities, some of which are important for diagnosis as well as predicting the likelihood of achieving complete remission and survival. For example, 65% of cases of ALL have a cytogenetic abnormality, with hyperdiploidy being the most common and known to be a favorable prognostic indicator.
Chronic lymphocytic leukemia (CLL)
CLL is a clonal proliferation of immunologically incompetent small lymphocytes, which are almost always of B-cell phenotype. It is the most common leukemia in Western countries, occurs in the older population and has an indolent course, with a mean survival of 6 years. CLL involves the bone marrow and peripheral blood, with an absolute lymphocyte count above 5000 /µl, and may infiltrate the liver, spleen and lymph nodes as well as other organs. Associated hypogammaglobulinemia, Coomb-positive hemolytic anemia, thrombocytopenia and neutropenia may be present.
Diffuse large cell lymphoma
Diffuse large cell lymphoma is a heterogeneous group of malignant lymphoma which are placed in the intermediate grade category of the Working Formulation, although are considered fairly aggressive lymphomas. Up to 30% of these lymphomas present in an extranodal location.
Essential thrombocythemia
is characterized primarily by a persistent thrombocytosis (platelet count often >1 million/ul), with increased megakaryocytes in the bone marrow. Patients may have a thrombotic or bleeding tendency. Leukemic conversion occurs in 2-5% of patients, and the survival of most patients is 5-8 years.
Extramedullary plasmacytoma
Extramedullary soft tissue mass composed of neoplastic plasma cells, which most commonly occurs in the upper respiratory tract. In 20% of cases, progression to multiple myeloma occurs.
FAB (French American British) classification system
A classification system for acute leukemia and myelodysplasia, which was originally based on cytomorphology and cytochemical findings. This system was created to establish a universal system for nomenclature, diagnosis and classification of acute leukemia and myelodysplastic syndrome, and is currently widely utilized.
Follicular center cell lymphoma
Follicular center cell lymphoma refers to a group of lymphoma's which are composed of cells which resemble normal germinal center cells. Follicular center cell lymphoma's are classified by the growth pattern (nodular=follicular), and the cell type present. Follicular small cleaved and follicular mixed small and large cell type are placed in the low grade category, and follicular large cell is considered intermediate in grade. Most patients with follicular lymphoma present with stage III or IV disease and have generalized peripheral lymphadenapathy, splenomegaly and frequent bone marrow involvement. Follicular small cleaved lymphoma is an indolent disease most common in the elderly, with a median survival of 10 years, and is commonly associated with the t(14,18) involving the bcl-2 gene.
Hairy cell leukemia
Hairy cell leukemia is a low grade lymphoproliferative disorder of B-cell origin which primarily involves the spleen, bone marrow and peripheral blood. It is an uncommon disorder. The mean age is 50-60 years old, with a male predominance. Patients present with pancytopenia and splenomegaly, and usually have a diffuse infiltration of leukemic cells in the bone marrow and spleen. Diagnosis is based on the finding of "hairy" cells, due to cytoplasmic projections on the cell surface, and demonstration of characteristic tartrate-resistant acid phosphatase (TRAP) by cytochemistry. The recent use of 2-deoxycoformycin ( "2-CDA") has greatly improved the survival in these patients.
Hodgkin disease (HD)
HD is a malignant neoplasm which is diagnosed by the identification of a classic Reed Sternberg cell in the appropriate cellular background. HD has a bimodal age distribution, the first peak in the 20's and the second peak after the age of 50 years old. HD is unique in that it has a predictable pattern of spread along contiguous lymph node chains. There are 4 subtypes of HD: lymphocyte predominant, mixed cellularity, lymphocyte depletion, and nodular sclerosis. Nodular sclerosis HD is the most common subtype in the younger age group and has a very good prognosis. It is notable that the risk of therapy-related second malignancy is very high in patients treated for HD, and is reported in >15% of patients.
Immunoblastic lymphoma
Immunoblastic lymphoma is a high grade, aggressive non-Hodgkin lymphoma. The neoplastic cells morphologically resemble a benign immunoblast, and have a large centrally placed nucleolus. Immunoblastic lymphoma frequently occurs in the setting of patients who have disordered immune states and in the HIV-positive population. In most treatment protocols, this type of lymphoma is grouped with diffuse large cell lymphoma.
Immunophenotype
The antigens on the surface of a cell can be characterized by reacting the cell with a panel of monoclonal antibodies of known specificity. The cell lineage can be determined in this way. Methods to determine the immunophenotype of a cell include tissue immunoperoxidase staining and flow cytometry.
International working formulation
A classification for non-Hodgkin lymphoma, created in 1982, which places the different types of lymphoma into prognostic categories of low, intermediate and high grade. This system is based on morphologic diagnosis of the lymphoma, and was not originally created to represent a definitive classification for lymphoma, although it is now the most commonly used classification system in this country. The Working Formulation was originally intended for use with node-based B-cell lymphoma, and therefore does not easily categorize some of the extranodal and T-cell lymphoma's. (National Cancer Institute's Sponsored Study of Classifications of non-Hodgkin Lymphoma. Summary and Description of a Working Formulation for Clinical Usage. Cancer 1982; 49: 2112-2135. )
LAP score
Leukocyte alkaline phosphatase is an enzyme normally present in neutrophils. Cytochemical staining of a peripheral blood smear and visual quantitation of enzyme activity can be done, to arrive at an LAP score. In reactive leukocytosis and leukemoid reaction, the LAP score will be normal to high, and in CML, the LAP score is characteristically decreased.
Lacunar cell
A lacunar cell is a Reed-Sternberg cell variant which is observed in nodular sclerosis Hodgkin's disease. Lacunar cells are characterized by the presence of a clear space around the cell.
Leukemia
Malignant proliferation of hematopoietic cells, characterized by replacement of bone marrow by neoplastic cells. The leukemic cells usually are present in peripheral blood, and may infiltrate other organs of the reticuloendothelial system, such as liver, spleen and lymph nodes. Leukemia is broadly classified into acute and chronic leukemia, with multiple distinct clinicopathologic entities subclassified in each category.
Lymphadenopathy
Enlargement of lymph nodes, due to either a reactive or neoplastic process. In general, lymph nodes replaced by malignant cells are painless, firm, rubbery, and may be matted together. Reactive nodes are tender, may be fluctuant (soft), and generally are discrete.
Lymphoblast
Stem cell of committed lymphoid lineage. Lymphoblasts are usually positive for Tdt, and do not contain Auer rods. Lymphoblasts are usually positive for PAS and negative for myeloperoxidase, which is useful for their identification. Most cases of childhood ALL are of precursor B immunophenotype.
Lymphoblastic lymphoma
High grade non-Hodgkin lymphoma, which is the solid tissue counterpart of ALL. Most cases are of T-cell phenotype, and more than half of the patients present with a mediastinal mass (suggesting origin in the thymus). T lymphoblastic lymphoma is most common in adolescent and young adult males, often spreads to the bone marrow with subsequent leukemia and has an overall poor prognosis.
Lymphoid hyperplasia
Increase in cellular components of a lymph node or extranodal lymphoid tissue. This may create an increase in the size of the tissue, such as in a lymph node or tonsil. There are numerous etiologies for reactive lymphoid hyperplasia, which include host response to infections, foreign material, drugs, and chronic inflammatory diseases.
Monoclonal gammapathy of undetermined significance (MGUS)
Presence of a monoclonal spike in the serum or urine of a patient who does not have a demonstrable plasma cell dyscrasia or other disorder known to produce a monoclonal spike. In the longest follow-up study of this disorder, a series of 241 patients were followed for a mean of 22 years, and 24% developed myeloma, Macroglobulinemia or amyloidosis. (Kyle, RA. Mayo Clin Proc 1993; 68: 2636.)
Mucosal-associated lymphoid tissue (MALT)
Extranodal lymphoid tissue occurring in association with mucosa, such in the gastrointestinal tract, lung, and pharynx (Waldeyer ring). Malignant lymphoma arising from mucosa-associated lymphoid tissue is referred to as Maltoma.
Multiple myeloma
Neoplastic proliferation of plasma cells, with synthesis of monoclonal immunoglobin or immunoglobin fragment (M protein). Criteria for diagnosis involve meeting certain combinations of major and minor criteria (refer to standard texts). Multiple myeloma is usually a disease of the elderly, and radiographic studies often reveal multiple punched-out lytic lesions, commonly of the skull. Serum protein electrophoresis can detect the presence of monoclonal protein. Peripheral blood smears may show rouleaux, and bone marrow reveals an atypical plasma cell infiltrate.
Mycosis fungoides
T cell lymphoma primary to the skin, which is characterized by several clinical stages which include patch, plaque and tumor stage. If the disease manifests a leukemic phase, it produces generalized erythroderma, and is called Sezary syndrome. The cells of mycosis fungoides and Sezary syndrome are malignant T cells which have convoluted, cerebriform nuclei and hyperchromsia. In the skin, the malignant cells display epidermatropism (migration up into the epidermis), and form characteristic small epidermal aggregates termed Pautrier microabcesses.
Myeloblast
A stem cell committed to myeloid lineage. Normal bone marrow contains less than 1% myeloblasts. Myeloblasts give rise to granulocytes, monocytes, and megakaryocytes.
Myelodysplastic syndrome
Clonal stem cell disorder with heterogeneous clinical and hematologic presentations. Myelodysplastic syndromes are characterized by dysplastic changes present in the myeloid cells, with or without an increase in blasts. Myelodysplastic syndromes are classified in the FAB system by several different features, which include quantitation of blasts in peripheral blood and bone marrow. Patients with myelodysplastic syndrome typically present with pancytopenia, usually do not have organomegaly, and chromosomal abnormalities are found in up to 50% of cases. The treatment for MDS is generally supportive but may include chemotherapy and bone marrow transplant in some cases. Those cases which progress to acute leukemia have a worse prognosis that de novo acute leukemia.
Myeloproliferative disorder
Clonal stem cell disorder characterized by proliferation of one or more cell lines, which classically include 4 closely related disease entities which have overlapping clinical and morphologic features. Pancellular bone marrow hyperplasia, variable bone marrow fibrosis, leukocytosis, thrombocytosis and splenomegaly may be present, in variable degrees, in most patients. The four chronic myeloproliferative disorders are listed below, with a few notable features of each disease.
Non-Hodgkin lymphoma
Solid tumor composed of a proliferation of malignant lymphoid cells. Non-Hodgkin lymphoma can arise primarily in lymph nodes, or in extranodal sites, and represents a heterogeneous group of disease entities, both clinically and histologically.
Philadelphia chromosome
Characteristic cytogenetic abnormality associated with CML and some cases of acute leukemia. Philadelphia chromosome results from a reciprocal translocation between chromosomes 9 and 22 [ t(9;22)(q34;q11)]. The molecular changes involve the translocation of the abl oncogene on chromosome 9 to the major breakpoint cluster region on chromosome 22, with production of the bcr/abl hybrid gene. In CML, the Philadelphia chromosome is present in all cells of the myeloid lineage, including neutrophils, erythroblasts, megakaryocytes, monocytes, eosinophils and basophils.
Polycythemia vera
is characterized by an increase in total red cell mass, with an increase in hemoglobin, hematocrit and red blood cell count. The bone marrow usually shows pancellular hyperplasia with increased erythropoiesis. Major and minor criteria for diagnosis have been established by the polycythemia vera study group (please refer to standard texts). Leukemic conversion occurs in 1-3%, and the median survival is 13 years.
Reactive lymph node hyperplasia
Benign proliferation of lymphoid tissue. Histologically, the pattern may be follicular, interfollicular, sinusoidal or mixed. A wide variety of etiologies exist, including infection, drugs and systemic disease. Clinicopathologic correlation is usually required to determine the etiology, as the histologic findings alone are usually nonspecific. Some patterns are so characteristic that they suggest a specific underlying disease category, such as in dermatopathic lymphadenopathy, cat scratch disease, toxoplasmosis, and viral etiologies.
Reed-Sternberg cell
The pathognomonic malignant cell in Hodgkin disease is a Reed-Sternberg cell. The cell of origin remains controversial, but currently thought to most likely by an activated or progenitor lymphoid cell. The classic Reed-Sternberg cell is a large binucleate cell with mirror-image nuclei containing large, eosinophilic nucleoli ("owl's eye").
Revised European-American classification of lymphoid neoplasms (REAL)
A new classification system for lymphoid neoplasia was proposed recently. The original publication of this classification serves as an excellent reference as it includes a definition and specific characteristics of each currently accepted disease entity within the lymphoid system. The REAL system remains somewhat controversial because the diseases are not placed into prognostic groups, as they are in the Working Formulation. (Harris, et al. A Revised European-American Classification of Lymphoid Neoplasms: A Proposal From the International Lymphoma Study Group. Blood 1994; 84 (5): 1461-1392).
Small lymphocytic lymphoma
Small lymphocytic lymphoma is a low grade non-Hodgkin lymphoma which represents the solid tissue counterpart of chronic lymphocytic leukemia. Plasmacytoid-small lymphocytic lymphoma (lymphoplasmacytoid lymphoma) is often observed in conjunction with the clinicopathologic entity of Waldenstrom macroglobulinemia.
TDT (terminal deoxynucleotidyl transferase)
Nuclear enzyme present in most lymphoblasts. Useful in hematology to help identify blast lineage, as Tdt is positive in most cases of ALL and usually negative in AML.