Diseases of the White Blood Cells, Lymph Nodes, Spleen and Thymus Flashcards
Decreased number of circulating leukocytes; most commonly neutrophils (neutropenia); deficiency of lymphocytes (lymphopenia) is less common, and is commonly seen in advanced HIV and other diseases.
Leukopenia
Clinically significant neutropenia (<500/mm3); highly susceptible to infections (Candida and Aspergillus); most common cause: drug toxicity
Agranulocytosis
An increase in the number of white cells in the blood in a variety of inflammatory states caused by microbial and nonmicrobial stimuli that may mimic leukemia.
Reactive leukocytosis, Leukemoid reaction (high leukocyte alkaline phosphatase, a product of normal WBCs; used to differentiate it from leukemias)
Enlargement of a lymph node as immune response to foreign antigens; histology usually nonspecific; depends on duration of disease and type of offending agent.
Reactive lymphadenitis
Most common type of cancer in children; highly aggressive tumors manifesting with signs and symptoms of bone marrow failure, marrow expansion, dissemination of leukemic cells, and CNS manifestations; lymphoblasts with irregular nuclear contours, condensed chromatin, small nucleoli and scant agranular cytoplasm on BMA; blasts compose >25% of marrow cellularity; TdT(+) in 95% of cases; most responsive to chemotherapy (Asparaginase).
Acute lymphoblastic leukemia (ALL)
Clinical differences between B- and T-cell ALL.
B-cell ALL typically occurs in younger children presenting with BM failure T-cell ALL typically occurs in adolescent males presenting with thymic masses
Good prognostic factors in ALL.
Children 2-10 years old; t(12;21) and hyperdiploidy
Poor prognostic factors in ALL.
Male gender; age younger than 2 or older than 10 years; a high leukocyte count at diagnosis; and molecular evidence of persistent disease on day 28 of treatment, t(9;22) and MLL rearrangements
Most common leukemia of adults in Western world; chronic leukemia associated with BCL2, an antiapoptotic molecule; patient presents with increased susceptibility to infections due to hypogammaglobulinemia; CBC showed >5000 lymphocytes/mm3; histologically, foci of mitotically active cells (proliferation centers) are present; also, smudge cells (due to fragility of circulating tumor cells) are also evident; can transform into DLBCL (Richter syndrome).
Chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL) SLL: <5000 lymphocytes/mm3
Most common indolent lymphoma of adults; frequent small “cleaved” cells mixed with large cells, growth pattern is nodular, centroblasts present; occurs in older adults, usually involves nodes, marrow, spleen; associated with t(14;18) that results in overexpression of cyclin D1.
Follicular lymphoma
Most common lymphoma of adults; most common form of NHL; tumor cells have large nuclei with open chromatin and prominent nucleoli; most important type of lymphoma in adults, accounting to ~50% of adult NHLs.
Diffuse Large B-cell lymphoma (DLBCL)
17/M presented with a short history of fever, tonsillitis and unilateral enlarged cervical lymph nodes. PE revealed enlargement of right cervical lymph node, 3 cm in diameter, hard, and pharyngeal hyperemia. Histologically, there was intermediate-sized round lymphoid cells with 2-5 prominent nucleoli. High rates of proliferation and apoptosis are characteristic. Nuclear remnants phagocytosed by interspersed macrophages with abundant clear cytoplasm, “starry sky pattern”. Also, it is associated with cMYC oncogene [t(8;14)]. The most likely diagnosis is? Clue: it is also the fastest growing human tumor.
Burkitt lymphoma
Disease that presents as multifocal destructive bone lesions seen as punched-out defects on imaging. Renal involvement is also prominent, causing production of proteinaceous casts in the DCT and collecting ducts (that can cause renal insufficiency); can also present with immunodeficiency due to impaired normal plasma cell function.
Multiple myeloma
Most common M protein in myeloma cells.
IgG
Excess light or heavy chains along with complete Igs synthesized by neoplastic plasma cells.
Bence-Jones protein
Basically, CLL/SLL with plasmacytic differentiation; usually present with hyperviscosity syndrome (Waldenstrom macroglobulinemia (IgM)): visual changes, neurologic problems, bleeding diathesis and cryoglobulinemia; no bone manifestations; renal manifestations rare.
Lymphoplasmacytic lymphoma
Lymphomas of memory B-cell origin; usually arises on tissues on chronic inflammation; regresses when inciting agent is removed, but once it progresses to DLBCL, regression may not be possible; examples: salivary glands: Sjogren syndrome, thyroid gland: Hashimoto thyroiditis, stomach: H. pylori gastritis
Marginal zone lymphoma
These tumors of neoplastic CD4+ T cells home to the skin; usually manifests as a nonspecific erythrodermic rash that progresses over time to a plaque phase and then to a tumor phase; histologically, neoplastic T cells, often with a cerebriform appearance produced by marked infolding of the nuclear membranes, infiltrate the epidermis and upper dermis.
Mycosis fungoides (Cutaneous T-cell lymphoma)
Diagnostic cells in HL; large, multiple nuclei or single with multiple lobes; each with nucleolus about a size of a small lymphocyte, CD15(+), CD30(+).
Reed-Sternberg (RS) cells
Classical HL types; CD15 and CD30(+).
NSHL, MCHL, LRHL, LDHL
Most common variant of HL; with lacunar Reed-Sternberg (RS) cells; with deposition of collage bands that divide lymph node into nodules; not associated with EBV; excellent prognosis; usually diagnosed at early stage (Stage I/II) with frequent mediastinal involvement.
Nodular sclerosis HL (NSHL)
Mononuclear and diagnostic RS cells with heterogenous cellular infiltrate; associated with EBV in 70% of cases; >50% of cases diagnosed at Stage III/IV .
Mixed cellularity HL (MCHL)
Mononuclear and diagnostic RS cells with lymphocytic infiltrate; not associated with EBV; excellent prognosis.
Lymphocyte-rich HL (LRHL)
Lymphocytes are scarce with relative abundance of diagnostic RS cells; associated with EBV in 90% of cases; associated with PLHIV; worst prognosis.
Lymphocyte-depleted HL (LDHL)
Lymphohistiocytic “popcorn” RS cells with nodular infiltrate of small lymphocytes admixed with macrophages; excellent prognosis; CD15 and 30 (-), CD20(+).
Lymphocyte-predominant (LPHL)
Staging system used for HL.
Ann-Arbor classification
BMA shows hypercellular marrow packed with _20% myeloblasts (and azurophilic needle-like material called Auer rods (faggot cells)); clinically presents with pancytopenia and bleeding; poor prognosis because it is difficult to treat.
Acute myeloid leukemia (AML)
Stains used to differentiate Myeloblasts from Monoblasts.
Myeloblasts: Myeloperoxidase (MPO)(+) Non-specific esterase (NSE)(-) Monoblasts: MPO(-), NSE(+)
Stains used to differentiate Myeloblasts from lymphoblasts.
Lymphoblasts: MPO(-) PAS(+)
Main differences between AML and ALL.
AML occurs in adults, CNS spread is rare, and is more difficult to treat; ALL occurs in children, CNS spread is common and is generally responsive to chemotherapy
An AML type that usually presents with DIC; associated with t(15;17) translocations; highly responsive to all-trans retinoic acid.
Acute promyelocytic leukemia
Disorder of defective hematopoietic maturation that results in ineffective hematopoiesis (cytopenias); more common in the elderly; clinically present as bone marrow failure; associated with increased risk of transformation to AML; poor prognosis.
Myelodysplastic syndrome
Common features of chronic myeloproliferative disorders.
Increased proliferative drive in BM, extramedullary hematopoiesis, spent phase, and variable transformation to AML
Chronic leukemia associated with BCR-ABL fusion gene (Philadelphia chromosome, t(9;22)); clinically presents with nonspecific symptoms and splenomegaly; BMA shows hypercellular marrow packed with less than 10% myeloblasts with more mature forms; CBC shows leukocytosis >100,000/mm3 with low leukocyte alkaline phosphatase; and scattered macrophages with abundant, wrinkled, green-blue cytoplasm (sea-blue histiocytes); can proceed to a blast crisis if neglected.
Chronic myelogenous leukemia (CML)
Increase in all cell lines, but erythroid lines are more increased; associated with JAK2 mutations in most cases; 2% chance of transformation to AML.
Polycythemia vera (PV)
Increase in megakaryotic lines; associated with JAK2 mutations in 50% of case; transformation to AML is uncommon.
Essential thrombocytosis
Extensive deposition of collagen in marrow by non-neoplastic fibroblasts; associated with JAK2 mutations in 50-60% of cases; 5-20% chance of transformation to AML.
Primary myelofibrosis
