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SBL Exam 1 > 13. WBCs, LNs, Spleen, Thymus > Flashcards

13. WBCs, LNs, Spleen, Thymus Flashcards

1
Q

What is the difference between serum and plasma?

A

Serum is the liquid part of blood AFTER coagulation; devoid of clotting factors like fibrinogen

[plasma - fibrinogen = serum]

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2
Q

Distribution of red vs. yellow marrow in adults

A

Adult red marrow = ~50% volume; skull, facial bones, vertebrae, clavicle, sternum, ribs, pelvix, proximal femur, hands, feet

Adult yellow marrow = ~50% volume, “long bones”; humerus, ulna, radius, femur, tibia, fibula

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3
Q

Definitive hematopoietic stem cells arise in the mesonephros. During the 3rd month of embryogenesis, HSCs migrate to the ____ which is the chief site of blood cell formation until shortly before birth. By the 4th month of embryogenesis, HSCs shift location again, taking up residence in the bone marrow.

A

Liver

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4
Q

Physiologic and pathologic implications of extramedullary hematopoiesis

A

Physiologic — hematopoiesis occuring in yolk sac, liver, or spleen as part of normal immune responses (i.e., APC and phagocyte production in spleen and liver)

Pathologic — conditions in which bone marrow becomes uninhabitable for stem and progenitor cells

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5
Q

Thin-walled vascular structures lined by single layer of endothelial cells which are underlaid by a discontinuous basement membrane and adventitial cells; function is to allow movement of cells from hematopoietic islands in bone marrow into the vascular space

A

Bone marrow sinusoids

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6
Q

Typical procedural location for bone marrow biopsy/aspiration in adults

A

PSIS

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7
Q

Cells of lymphoid lineage

A

NK cells
B cells
T cells

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8
Q

Cells of myeloid lineage

A 
Myeloblasts —> neutrophils
Monoblasts —> monocytes
Eosinophiloblasts —> eosinophils
Basophiloblasts —> basophils
Megakaryoblasts —> platelets
Erythroblasts —> RBCs
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9
Q

Agranulocytosis is a clinical significant reduction in neutrophils that increases susceptibility to infection. What is the MCC?

A

Drug toxicity

Examples: alkylating agents, anti-metabolites, aminopyrine, chloramphenicol, sulfonamides, chlorpromazine, thiouracil, phenylbutazone

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10
Q

Causes of acute lymphadenitis based on location in cervical, axillary or inguinal, or mesenteric LNs

A

In cervical region — d/t drainage of bacteria from infections of teeth or tonsils

In axillary or inguinal regions — d/t bacteria in extremities

In mesenteric LNs — d/t appendicitis

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11
Q

2 Causes of chronic lymphadenitis

A

H.pylori

Rheumatoid arthritis

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12
Q

Reactive condition marked by cytopenias and signs/symptoms of systemic inflammation related to macrophage and CD8 T cell activation

Most pts present with acute febrile illness associated with splenomegaly or hepatomegaly; hemophagocytosis usually seen on bone marrow exam, labs show anemia, thrombocytopenia, elevated plasma ferritin and IL-2R, elevated LFTs and triglycerides

A

Hemophagocytic lymphohistiocytosis

[can be sporadic or familial; most common trigger is infection with EBV]

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13
Q

Virus associated with adult T-cell leukemia/lymphoma

A

HTLV-1

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14
Q

Virus found in a subset of Burkitt lymphoma, Hodgkin lymphoma, B cell lymphomas arising in setting of T cell immunodeficiency, and NK cell lymphomas

A

EBV

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15
Q

Lifestyle risk factor commonly associated with AML

A

Smoking

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16
Q

Immunostaining for _______ is present in 95% of cases of precursor B and T cell lymphomas

A

TdT

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17
Q

95% of precursor B and T cell lymphomas achieve complete remission w/ aggresive chemotherapy, but are still the leading cause of cancer death in children. What are factors associated with a FAVORABLE prognosis in this type of lymphoma?

A 
Age between 2-10
Low white cell count
Hyperdiploidy (seen in B-ALL)
Trisomy of Chr 4, 7, 10
Presence of a t(12;21)
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

[Note: worse px associated w/ age <2 (associated with MLL translocations), presentation in adolescence or adulthood, peripheral blood blast counts >100,000]

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18
Q

Gene mutations and cell markers associated with B-ALL

A

Genes: PAX5, E2A, EBF, or balanced t(12;21) involving ETV6 and RUNX1

Cell markers: CD19, CD10, PAX5

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19
Q

70% of T-ALL presents with gain of function mutations in _______, and cell markers include ____________

A

NOTCH1

CD1, CD2, CD5, CD7

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20
Q

Most common leukemia of adults in western world

A

CLL/SLL

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21
Q

Clinical features of CLL/SLL include nonspecific sxs like fatigue, weight loss, anorexia, and mild HSM. Median age of dx is 60, affecting M>F. Hypogammaglobulinemia is common —> increased susceptibility to infection. The prognosis depends on clinical stage and median survival is 4-6 years.

What are features of a WORSE prognosis with CLL/SLL?

A

Deletions of 11q and 17p
Lack of somatic hypermutation
Expression of ZAP-70
Presence of NOTCH1 mutation

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22
Q

What is Richter syndrome?

A

When CLL/SLL transforms into a DLBCL, characterized by rapidly enlarging mass within LN or spleen; poor prognosis of <1 year

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23
Q

Proliferation centers with architectural effacement as well as presence of smudge cells

CD markers of CD19, CD20, CD23, CD5

A

CLL/SLL

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24
Q

Memory B cell lymphoma associated with t(11;18), t(1;14), or t(14;18) [MALT1 or BCL10 translocations], seen in extranodal locations in adults with chronic inflammatory diseases

A

Extranodal marginal zone lymphoma

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25
Q

Naive B cell lymphoma associated with t(11;14) —> increased levels of cyclin D1. Most express Ig with monoclonality and are CD5+, CD23-. Presents with painless generalized LAD and occasional lymphomatoid polyposis of colon.

A

Mantle cell lymphoma

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26
Q

Germinal center B cell lymphoma characterized by t(14;18) in which BCL2 is expressed in 90%; presents with painless generalized LAD and often invovles splenic white pulp and hepatic portal triads

A

Follicular lymphoma

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27
Q

Memory B cell malignancy characterized by activating BRAF mutation; usually presents in older caucasian males with pancytopenia and massive splenomegaly; associated with increased incidence of MYCOBACTERIUM and immunophenotype that includes CD11c

A

Hairy cell leukemia

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28
Q

Presents in older adults with lytic bone lesions, hypercalcemia, and renal failure secondary to chronic bence jones proteinuria (d/t tubular depositions of kappa or gamma light chains); rouleaux formation on PB smear, immunophenotype CD138 and sometimes CD56

A

Multiple myeloma

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29
Q

What are the consequences of bone marrow involvement in multiple myeloma pts?

A

Normocytic normochromic anemia, sometimes accompanied by leukopenia and thrombocytopenia

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30
Q

What causes lytic bone lesions in multiple myeloma?

A

Myeloma-derived MIP1-alpha regulates expression of receptor activator of NFkB ligand (RANKL) by bone marrow stromal cells, which in turn activates osteoclasts

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31
Q

Multiple myeloma has a variable prognosis, with worse prognosis associated with deletions of 17p or 13q, t(4;14), and high serum IL-6. A better prognosis is associated with translocations involving _____

A

Cyclin D1

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32
Q

Plasmacytomas are isolated plasma cell masses in bone or soft tissues (lungs, oronasopharynx, nasal sinuses). Solitary osseous plasmacytomas inevitably progresses to _____ ____ but can take up to 10-20+ years

A

Multiple myeloma

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33
Q

Clinical manifestations of waldenstrom macroglobulinemia (high levels of IgM leading to blood hyperviscosity)

A

Visual impairment d/t venous congestion, HA, dizziness, deafness, stupor, bleeding, and cryoglobulinemia (presents as Raynaud)

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34
Q

Most common plasma cell dyscrasia, particularly of elderly pts in US

A

Monoclonal gammopathy of undetermined significance (MGUS) — characterized by small to moderately large M components in blood

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35
Q

Most common form of NHL

A

DLBCL

36
Q

Germinal center or postgerminal center B cell malignancy most often characterized by BCL6 genotype, usually affecting males age ~60 who commonly present with involvement of Waldeyer ring (oropharyngeal lymphoid tissue)

A

DLBCL

37
Q

DLBCLs usually involve BCL6 genotype and 60-80% achieve remission with chemo. What other potential translocation denotes a worse prognosis?

A

MYC

38
Q

Subtypes of DLBCL include immunodeficiency-associated large B-cell lymphoma, which is seen in the setting of T-cell deficiency in which neoplastic B cells are usually infected with _____.

Another subtype is primary effusion lymphoma, presenting with malignant pleural or ascitic effusion, and tumor cells are usually infected with ________ and have clonal IgH rearrangements

A

EBV

KSHV/HHV-8

39
Q

Germinal center B cell malignancy associated with translocations involving MYC and Ig loci, usually t(8;14); morphologically identified by “starry sky” pattern and failure to express antiapoptotic protein BCL2; also associated with warburg effect

A

Burkitt lymphoma

40
Q

Burkitt lymphoma clinically presents in adolescents or young adults with extranodal masses. What is the difference in presentation in endemic/African BL vs. sporadic BL?

A

Endemic/african: often presents as a mass involving mandible; predilection for abdominal viscera including kidneys, ovaries, and adrenal glands

Sporadic: often presents as mass involving ileocecum and peritoneum

41
Q

B-cell neoplasm of older adults that usually presents in 6-7th decade of life; associated with acquired mutation in MYD88. 10% will have autoimmune hemolysis d/t cold agglutinins and subset of tumor cells undergo terminal differentiation to plasma cells, usually IgM leading to hyperviscosity (neuro symptoms)

A

Lymphoplasmacytic lymphoma

42
Q

CTL and NK cell neoplasm associated with point mutations in STAT3; morphology shows large lymphocytes w/abundant blue cytoplasm and a few coarse azurophilic granules

A

Large granular lymphocytic leukemia

43
Q

Large granular lymphocytic leukemia presents with splenomegaly, neutropenia, and anemia d/t autoimmune and cytokine effects. T-cell disease tends to be more indolent while NK disease is more aggressive. How is cell type determined based on immunophenotype?

A

T-cell variants are CD3+

NK cell variants are CD3- and CD56+

44
Q

Neoplasm in which epidermis and upper dermis are infiltrated by CD4+ T cells, often with cerebriform appearance

A

Mycosis fungoides

45
Q

CD4+ T cell neoplasm in which skin involvement is manifested as generalized exfoliative erythroderma and also shows characteristic cerebriform appearance

A

Sezary syndrome

46
Q

Immunophenotype associated with mycosis fungoides/sezary syndrome

A

CLA, CCR4, CCR10 — markers that contribute to homing T cells to skin

47
Q

Helper T or CTL neoplasm without associated chromosomal abnormality that is characterized by diffuse effacement of LNs and is typically composed of pleomorphic mixture of variably sized malignant T cells; mainly affects older adults, usually presenting with generalized LAD, sometimes with eosinophilia, pruritis, fever, and weight loss. Immunophenotype includes CD2, CD3, CD5, and either alpha/beta or gamma/delta TCRs; sometimes CD4 or CD8; px relatively poor

A

Peripheral T cell lymphoma, unspecified

48
Q

CTL neoplasm with associated ALK rearrangements and CD30 cell marker, usually presenting in children and young adults with LN and soft-tissue disease. Aggressively behaving but very good px with chemotherapy (substantially worse px in adults). Morphology shows “hallmark cells” — horseshoe shaped nuclei and voluminous cytoplasm

A

Anaplastic large-cell lymphoma (ALK positive)

49
Q

Helper T cell neoplasm associated wtih HTLV-1 provirus in tumor cells; occurs mainly in Japan, West Africa, and Caribbean with cutaneous lesions, marrow involvement, and hypercalcemia, and results in death w/i 1 year unless confined to the skin; morphology shows “cloverleaf” or “flower” cells with multilobated nuclei

A

Adult T-cell leukemia/lymphoma

50
Q

Complication of HTLV-1 infection associated with adult T-cell leukemia/lymphoma

A

Progressive demyelinating disease of the CNS and spinal cord

51
Q

EBV-associated neoplasm that invades small vessels leading to ischemic necrosis. Most commonly presents with destructive nasopharyngeal mass; more common in Asia. Morphology is large azurophilic granules in tumor cells

A

Extranodal NK/T-Cell lymphoma

Note: NK-cell is more common than CTL as origin cell

52
Q

Neoplasm that arises in single node or chain of nodes and spreads in a predictable fashion; characterized by presence of neoplastic giant cells called Reed-Sternberg cells and is one of the most common cancers of young adults and adolescents with avg age at dx = 32

A

Hodgkin lymphoma

53
Q

Classical subtypes of hodgkins lymphoma originate from a GC or post-GC (have undergone V(D)J recomb and somatic hypermutation) and have genetic signature of B cell but lack most B-cell specific genes including Ig genes.

What is the general/common pathogenesis of classical subtypes?

A

Common event is activation of NFkB by several mechanisms:

Activation of NFkB by EBV infection or other mechanism and turns on genes that promote survival/prolif

EBV+ tumor cells express LMP-1, which upregulates NFkB

Acquired loss of function mutations in IkB or A20, which are negative regulators of NFkB

54
Q

Most common subtype of HL

A

Nodular sclerosis HL

55
Q

HL subtype characterized by frequent mononuclear and diagnostic RS cells with a background infiltrate rich in T cells, eosinophils, macrophages, and plasma cells. Has biphasic incidence, peaking in young adults and adults >55 (M>F). Immunophenotype is RS cells CD15+, CD30+, 70% EBV+

A

Mixed cellularity HL

56
Q

Subtype of HL characterized by frequent lacunar cells and occasional RS cells on background of T cells, eosinophils, macrophages, and plasma cells as well as fibrous bands that divide cellular areas. Often presents with mediastinal involvement in young adults (M=F). Immunophenotype is CD15+, CD30+, and usually EBV-

A

Nodular sclerosis HL

57
Q

Uncommon HL subtype characterized by frequent mononuclear and diagnostic RS cells on background infiltrate rich in CD3+ T cells; tends to be seen in older adults (M>F). Immunophenotype CD15+, CD30+, and 40% EBV+

A

Lymphocyte-rich HL

58
Q

Reticular variant of HL with frequent diagnostic RS cells and variants and a paucity of background reactive cells; more common in older males, HIV-infected pts, and developing countries. Immunophenotype CD15+, CD30+, 90% EBV+

A

Lymphocyte-depleted HL

59
Q

Prognoses for classical subtypes of HL

A

Nodular sclerosis — excellent px
Mixed cellularity — very good overall px
Lymphocyte-rich — ?
Lymphocyte-depletion — worst overall px

60
Q

While classical subtype RS cells have similar immunophenotype, lymphocyte-predominant cells have distinct B cell immunophenotype. Describe morphology, immunophenotype, and clinical features of lymphocyte predominance HL

A

Morph: lymphohistiocytic RC cells (popcorn cells) in background of follicular DCs and reactive B-cells

Immunophenotype: RS cells CD20+, CD15-, CD30-, and EBV-

Clinically: Uncommon, affects young males with cervical or axillary LAD; px is excellent

61
Q

Category of myeloid neoplasms characterized by accumulation o immature myeloid forms in bone marrow which suppresses hematopoiesis leading to marrow failure, anemia, thrombocytopenia, and neutropenia; Dx is based on presence of 20% myeloid blasts in bone marrow

A

Acute myeloid leukemias

62
Q

Clinical features of AML

A

Fatigue, fever, and spontaneous mucosal and cutaneous bleeding

Infections are frequent — esp oral cavity, skin, lungs, kidneys, urinary bladder, and colon; usually d/t opportunistic infxn

63
Q

4 types of AML include AML with genetic aberrations, AML with MDS-like features, therapy-related AML, and AML not otherwise specified.

In AML with genetic aberrations, what aberrations are considered to have a more favorable prognosis?

A

AML with t(8;21)(q22;q22) — RUNX1/E10 fusion; full range of myelocytic maturation; auer rods easily found, abnormal cytoplasmic granules

AML with inv(16)(p13q22) — myelocytic and monocytic differentiation; abnormal eosinophilic precursors w/abnormal basophilic granules, mucosal bleeding more common w/monocytic diff

AML with t(15;17)(q22;11-12) — RARA/PML fusion; this is acute promyelocytic leukemia and the one most likely to exhibit early significant bleeding; numerous auer rods and high incidence of DIC

AML with normal cytogenetics and mutated NPM

64
Q

AML with MDS-like features — including AML w/prior MDS, AML with multilineage dysplasia, AML with MDS-like cytogenetic aberrations associated with 5q, 7q, and 20q — are all known to have a _____ prognosis

A

Poor

65
Q

Describe therapy-related AML and its px

A

If following alkylator therapy or radiation therapy, there is a 2-8 yr latency period followed by MDS-like aberrations

If following topoisomerase II inhibitor, there is a 1-3 yr latency period followed by translocations involving MLL

66
Q

Subtype of “AML, not otherwise specified” with antibodies to GPIIb-IIIa or vWF, often associated with marrow fibrosis, and the most common type in Down syndrome

A

AML w/megakaryocytic maturation

67
Q

Myelodysplastic syndromes involve defective maturation of progenitors leading to ineffective hematopoiesis and cytopenias. Bone marrow is eventually replaced by clonal progeny of a neoplastic multipotent stem cell. These syndromes have a high risk of ____ transformation

A

AML

68
Q

Causes of myelodysplastic syndromes

A

Primary (idiopathic) — predominantly older adults with mean age of 70, may be discovered incidentally or present w/ weakness, infection, and hemorrhage d/t pancytopenia

Secondary to previous genotoxic drug/radiation therapy

69
Q

The following are chromosomal abnormalities associated with what category of myeloid neoplasm?

Monosomies 5 and 7
Deletions of 5q, 7q, and 20q
Trisomy 8

A

Myelodysplastic syndromes

70
Q

Pluripotent HSC neoplasm characterized by BCR-ABL fusion in 100% of cases, usually d/t reciprocal (9;22) translocation, aka the philadelphia chromosome

A

CML

71
Q

BCR-ABL fusion in CML preferentially drives proliferation of ____ and ____ precursors

A

Granulocytic; megakaryocyte

72
Q

Clinical features of CML

A

Primarily adults w/ peak incidence in 5-6th decade

Insidious onset w/ mild to moderate anemia and hypermetabolism leading to fatigueability, weakness, weight loss, and anorexia

HUGE splenomegaly — may lead to acute onset LUQ pain d/t splenic infarct

PB smear shows leukocytosis, often exceeding 100,000

73
Q

Myeloproliferative disorder characterized by increased marrow production of red cells, granulocytes, and platelets; Other features include JAK2 point mutation, low serum EPO, Hb 14-28, and Hct 60+%

A

Polycythemia vera

74
Q

Clinical features of polycythemia vera

A

Plethora, cyanosis, headaches, dizziness, HTN, pruritis, peptic ulceration, GI sxs, gout

Increased risk of major bleeding and thrombotic episodes (budd chiari if in hepatic veins)

Possible transformation to AML (transformation to ALL is rare)

75
Q

Myeloproliferative disorder characterized by elevated platelet count, JAK2 or MPL point mutations, and occurs in the absence of polycythemia or marrow fibrosis

A

Essential thrombocythemia

76
Q

Essential thrombocythemia shows mildly increased BM cellularity w/ markedly increased megakaryocytes that are abnormally large. What are some clinical features of this d/o?

A

Uncommon, usually occurs past age 60

Platelet dysfunction may lead to thrombosis and hemorrhage

Characteristic sx is erythromelalgia — throbbing and burning of hands and feet d/t occlusion of small arterioles (may also be found in PCV)

77
Q

Myeloproliferative disorder for which the hallmark is develoment of marrow fibrosis resulting in cytopenias and extensive extramedullary hematopoiesis particularly in the spleen; chief pathologic feature is extensive deposition of collagen in marrow by non-neoplastic fibroblasts d/t PDGF and TGF-beta released by megakaryocytes

A

Primary myelofibrosis

78
Q

Most common mutation associated with langerhans cell histiocytosis

A

Activating mutation of BRAF (also implicated in hairy cell leukemia)

Less common mutations: TP53, RAS, and tyrosine kinase MET

79
Q

Appearance of B cell germinal centers in thymus; usually associated with myasthenia gravis or other autoimmune condition; not clinically significant but may be mistaken for a neoplasm

A

Thymic follicular hyperplasia

80
Q

Tumors of thymic epithelial cells, typically containing benign immature T cells (thymocytes)

A

Thymoma

81
Q

Clinical features of thymoma

A

Occur in adults >40; M=F

Most arise in anterior mediastinum and may present with sxs relating to impingement of mediastinal structures

82
Q

3 histologic subtypes of thymoma and which of these is EBV-related

A
  1. Cytologically benign and noninvasive — composed of medullary-type epithelial cells or mix of medullary w/cortical; sparse thymocyte infiltrate
  2. Cytologically benign but invasive — composed of cortical epithelial cells; numerous thymocytes and invades into surrounding structures
  3. Cytologically malignant (thymic carcinoma) — most are SCC, followed by lymphoepithelioma-like carcinoma ** EBV related **
83
Q

5 Conditions that may evolve to DLBCL

A 
CLL
Follicular lymphoma
T cell immunodeficiency w/EBV
Marginal zone lymphoma
Lymphoplasmacytic lymphoma
84
Q

LN biopsy showing exuberant sinus histiocytosis w/intracellular pigment deposition is defined as a ______ rxn

A

Leukamoid

85
Q

Condition characterized by elevated CRP and LDL, mild leukocytosis, possible bone lytic lesions, mononuclear cells, dense core bodies, and birbeck granules, S-100, CCR7, and CD1a

A

Eosinophilic granuloma

86
Q

Condition characterized by initially hypercellular and later hypocellular and diffusely fibrotic bone marrow w/ teardrop shaped cells called dacrocytes

A

Primary myelofibrosis

87
Q

Clinical features of primary myelofibrosis

A

Individuals older than 60

Usually presents with progressive anemia and splenomegaly; fatigue, weight loss, night sweats, gout

Complications: intercurrent infections, thrombosis, bleeding, and transformation to AML

SBL Exam 1 (8 decks)

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