Diseases of the White Blood Cells, Lymph Nodes, Spleen and Thymus

Question 1

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.

Answer 1

Leukopenia

Question 2

Clinically significant neutropenia (<500/mm3); highly susceptible to infections (Candida and Aspergillus); most common cause: drug toxicity

Answer 2

Agranulocytosis

Question 3

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.

Answer 3

Reactive leukocytosis, Leukemoid reaction (high leukocyte alkaline phosphatase, a product of normal WBCs; used to differentiate it from leukemias)

Question 4

Enlargement of a lymph node as immune response to foreign antigens; histology usually nonspecific; depends on duration of disease and type of offending agent.

Answer 4

Reactive lymphadenitis

Question 5

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).

Answer 5

Acute lymphoblastic leukemia (ALL)

Question 6

Clinical differences between B- and T-cell ALL.

Answer 6

B-cell ALL typically occurs in younger children presenting with BM failure T-cell ALL typically occurs in adolescent males presenting with thymic masses

Question 7

Good prognostic factors in ALL.

Answer 7

Children 2-10 years old; t(12;21) and hyperdiploidy

Question 8

Poor prognostic factors in ALL.

Answer 8

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

Question 9

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).

Answer 9

Chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL) SLL: <5000 lymphocytes/mm3

Question 10

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.

Answer 10

Follicular lymphoma

Question 11

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.

Answer 11

Diffuse Large B-cell lymphoma (DLBCL)

Question 12

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.

Answer 12

Burkitt lymphoma

Question 13

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.

Answer 13

Multiple myeloma

Question 14

Most common M protein in myeloma cells.

Answer 14

IgG

Question 15

Excess light or heavy chains along with complete Igs synthesized by neoplastic plasma cells.

Answer 15

Bence-Jones protein

Question 16

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.

Answer 16

Lymphoplasmacytic lymphoma

Question 17

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

Answer 17

Marginal zone lymphoma

Question 18

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.

Answer 18

Mycosis fungoides (Cutaneous T-cell lymphoma)

Question 19

Diagnostic cells in HL; large, multiple nuclei or single with multiple lobes; each with nucleolus about a size of a small lymphocyte, CD15(+), CD30(+).

Answer 19

Reed-Sternberg (RS) cells

Question 20

Classical HL types; CD15 and CD30(+).

Answer 20

NSHL, MCHL, LRHL, LDHL

Question 21

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.

Answer 21

Nodular sclerosis HL (NSHL)

Question 22

Mononuclear and diagnostic RS cells with heterogenous cellular infiltrate; associated with EBV in 70% of cases; >50% of cases diagnosed at Stage III/IV .

Answer 22

Mixed cellularity HL (MCHL)

Question 23

Mononuclear and diagnostic RS cells with lymphocytic infiltrate; not associated with EBV; excellent prognosis.

Answer 23

Lymphocyte-rich HL (LRHL)

Question 24

Lymphocytes are scarce with relative abundance of diagnostic RS cells; associated with EBV in 90% of cases; associated with PLHIV; worst prognosis.

Answer 24

Lymphocyte-depleted HL (LDHL)

Question 25

Lymphohistiocytic “popcorn” RS cells with nodular infiltrate of small lymphocytes admixed with macrophages; excellent prognosis; CD15 and 30 (-), CD20(+).

Answer 25

Lymphocyte-predominant (LPHL)

Question 26

Staging system used for HL.

Answer 26

Ann-Arbor classification

Question 27

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.

Answer 27

Acute myeloid leukemia (AML)

Question 28

Stains used to differentiate Myeloblasts from Monoblasts.

Answer 28

Myeloblasts: Myeloperoxidase (MPO)(+) Non-specific esterase (NSE)(-) Monoblasts: MPO(-), NSE(+)

Question 29

Stains used to differentiate Myeloblasts from lymphoblasts.

Answer 29

Lymphoblasts: MPO(-) PAS(+)

Question 30

Main differences between AML and ALL.

Answer 30

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

Question 31

An AML type that usually presents with DIC; associated with t(15;17) translocations; highly responsive to all-trans retinoic acid.

Answer 31

Acute promyelocytic leukemia

Question 32

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.

Answer 32

Myelodysplastic syndrome

Question 33

Common features of chronic myeloproliferative disorders.

Answer 33

Increased proliferative drive in BM, extramedullary hematopoiesis, spent phase, and variable transformation to AML

Question 34

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.

Answer 34

Chronic myelogenous leukemia (CML)

Question 35

Increase in all cell lines, but erythroid lines are more increased; associated with JAK2 mutations in most cases; 2% chance of transformation to AML.

Answer 35

Polycythemia vera (PV)

Question 36

Increase in megakaryotic lines; associated with JAK2 mutations in 50% of case; transformation to AML is uncommon.

Answer 36

Essential thrombocytosis

Question 37

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.

Answer 37

Primary myelofibrosis