Rubin's/Robbin's Flashcards
Chromosomal translocation involving 8q24 which harbors myc oncogene; most common childhood malignancy in Central Africa; may be induced by immunodeficiency; “starry sky” macrophage
Burkitt Lymphoma EBV caused
Fine needle aspirate of bone reveals numerous eosinophils; Otitis media is a common finding; scalp bone pain; Calvarial bone defects; Exopthalmous possible
Langerhans cell histiocytosis
Enlarged supraclavicular lymph node; common in HIV population; tumor cells express B-cell antigens and are EBV +
Large B-cell lymphoma/high-grade B-cell lymphoma ie Burkitt; bcl2 gene rearrangements often seen, as with follicular lymphoma
Pancytopenia; splenomegaly; peripheral blood smear reveals atypical lymphoid cells displaying tartare-resistant acid phophatase activity
Hairy cell leukemia; clonal B-cell proliferation of small to medium lymphocytes that exhibit lots of cytoplasm and hair-like protrusions on the cell membrane; bone marrow-spleen-liver; middle-aged to elderly, male:female ratio is 5:1
Biopsy, ie of stomach, reveals extranodal lymphocytic infiltrate invading glandular tissue; Cancer originates in mucosa-associated lymphoid tissue; H. Pylori-associated, commonly arise in the context of chronic inflammation or autoimmunity
MALT lymphoma/Marginal zone lymphoma cell proliferation of small to medium lymphocytes; appear to originate from marginal-zone B-cells
lymphocytic infiltrates at the dermal-epidermal junction; positive CD4+ immunohistochemical staining; scaly skin lesions/plaques
Mycosis fundoides - cutaneous T-cell lymphoma
enlarged lymph nodes; mild hepatosplenomegaly; small lymphocytes with plasmacytoid lymphotcytes containing Dutcher and Russell bodies; cytoplasmic accumulation of IgM; mainly affects the elderly
Waldenstrom disease - lymphoplasmacytic lymphoma; neoplastic proliferation of small lymphocytes; IgM secreting lymphocytes
Petechiae; Low platelets; bone marrow shows increased number of megakaryocytes; spontaneous recovery usually
Idiopathic thrombocytopenic purpura (ITP); acute ITP in children usually arises after a viral illness;
High peripheral reticulocyte count
Hemolytic anemia
Direct erythrocyte trauma due to an abnormal vascular surface ie graft or artificial valve; reticulocytes and schistocytes in peripheral blood smear Anemia is mild to moderate
Macroangiopathic (large vessels) hemolytic anemia
Uncontrolled prolifertion of megakaryocytes; increased platelets; episodes of thrombosis or hemorrhage; NO fibrosis in the bone marrow
Essential thrombocythemia
Dohle bodies or toxic granulation in mature neutrophils on peripheral blood smear
Leukemoid reaction Benign alk phos HIGH in leukemoidrxn, LOW in CML CML would not have mature neutrophils….
Hx of B-cell chronic lymphocytic leukemia; Hepatosplenomegaly; rapid onset of fever, abdominal pain, lymphadenopathy; Aggressive and refractory to therapy; High grade, large-cell lymphoma
Richter Syndrome
15% of patients with myasthenia gravis have ______
thymoma 1/3 pf patients with thymoma will develop MG
Posttransplant lymphoproliferative disorder (PTLD) is associated with immunosuppression and what virus?
EBV
sign of Leser-Trelat
sudden appearance of numerous seborrheic keratosis; sign of internal malignancy ie gastric adenocarcinoma
frequently pigmented, elevated papules or plaques; scales easily rubbed off; microscopic: broad, anastomosing cords of mature stratified squamous epithelium with small cysrs of keratin (horn cysts)
seborrheic keratoses
Genetic predisposition to melanoma
CDKN2A tumor suppressor gene (p16) mutation encodes an inhibitor of CDK that normally inhibits cell proliferation
actinic keratoses indicative of:
precursor to squamous cell carcinoma atypia in basal keratinocytes
tumor derived from endothelial cells; painful, purple nodules on hands and/or feet; neoplastic cells, poorly demarcated lesion
Kaposi’s sarcoma
Genetic (AD); mild hyperkeratosis and reduced or absent keratohyaline granules in the epidermis; scaly skin results from increased cohesiveness of the stratum corneum
Ichthyosis vulgaris
“Hutchinson melanotic freckle”; large pigmented macule; occurs on sun-damaged skin; fair-skinned, elderly, white people
Lentigo maligna melanoma
Most common form of melanoma in dark-skinned people; generally limited to palms, soles and subungual regions
Acral lentiginous melanoma
Persistent epidermal hyperplasia; chronic, runs in families; erythematous, scaly plaques, commonly on the dorsal extensor cutaneous surfaces; *Neutrophils* migrate into epidermis
Psoriasis
Tendency to form blisters at sites of minor trauma; Mutations of genes encoding cytokeratin IFs; can be minor, or widespread and life-threatening; blisters almost always noted at birth or shortly after; blister formation in *basement membrane* zone; no inflammatory cells in blisters, no antibody deposits
Epidermolysis Bullosa
Skin issue associated with gluten hypersensitivity
dermatitis herpetiformis
Blisters leave extensive denuded or crusted areas; separation of the stratum spinosum and basal layer; IgG on direct immunofluorescence; autoantibody to desmoglein-3; blister contains moderate #s of lymphocytes, macrophages, eosinophils and neutrophils
Pemphigus vulgaris
Most common malignant tumor in pale-skinned people; locally aggressive; metastases rare;
Basal cell carcinoma
Tumor that contains nests of deeply basophilic epithelial cells with narrow rims of cytoplasm that are attached to the epidermis and protrude into the subjacent papillary dermins
Basal cell carcinoma
Lesion on dorsal surfaces of hands or feet; 1 or multiple; no malignant potential; Papules bleed easily; Epithelial-lined fronds with fibrovascular cores
Verruca vulgaris - common wart; HPV-2, HPV-4, other HPVs
Common autoimmune blistering disease; Acantholysis (loss of intercellular connections) absent; IgG antibodies are directed against 2 basement membrane proteins, BPAG1 and BPAG2; immunofluorescent studies reveal linear deposition of C3 and IgG along epidermal BM zone
Bullous pemphigoid
Intensely pruritic cutaneous eruption; Wheal-like lesions with small vesicles Urticaria-like plaques and vesicles over extensor surfaces of the body; possible development of IgA antibodies to componenets of gluten
Dermatitis herpetiformis
Hypersensitivity reaction with lymphocytic infiltrates at the dermal-epidermal junction; results in hyperkeratosis; multiple, flat-topped, violaceous, polygonal papules
Lichen planus
The most important histologic feature of mycosis fungoides (a variant of cutaneous T-cell lymphoma) is:
lymphocytes in the epidermis (epidermotropism) CD4+ marker for T-lymphocytes
Sezary syndrome is disseminated _______
mycosis fungoides (a variant of cutaneous T-cell lymphoma)
Patient with chronic Hep B; numerous red lesions; purpuric small papules, do not blanch with pressure; necrotizing leukocytoclastic venulitis; immune complex deposition in vascular walls
Hypersensitivity Angiitis aka Cutaneous necrotizing vasculitis (CNV) C5a attracts neutrophils –> endothelial damage and fibrin disruption; can be primary or associated with something chronic
Fibrosis and tightening of the skin; dysphagia; structural and functional involvement of other organs is lungs and kidneys; Raynaud’s phenomenon common
Scleroderma
An autoimmune disease, most likely systemic lupus erythematosus (SLE), can be accompanied by what cell proliferation?
monocytosis. Cytopenias also can occur in SLE because of autoantibodies against blood elements, a form of type II hypersensitivity.
Toxic granulations, which are coarse and dark primary granules, and Döhle bodies, which are patches of dilated endoplasmic reticulum, represent:
reactive changes of neutrophils that are most indicative of overwhelming inflammatory conditions, such as bacterial sepsis.
Blood monocytes become tissue macrophages that evolve into epithelioid cells and giant cells of what kind of inflammation?
Granulomatous
T/F: Hodgkin lymphomas have no consistent peripheral blood findings and are not likely to produce solitary lung nodules.
True Hodgkin lymphoma is not characterized by an increased WBC count.
Marked leukocytosis and immature myeloid cells in the peripheral blood can represent an exaggerated response to infection (leukemoid reaction), or it can be a manifestation of ________.
CML Normal maturation of myeloid cells in the marrow rules out CML.
Lymph nodes draining from a cancer often show a reactive pattern, with dilated sinusoids that have endothelial hypertrophy and are filled with histiocytes (i.e., macrophages). Sinus histiocytosis represents:
an immunologic response to cancer antigens. Thus not all enlarged nodes are caused by metastatic disease in cancer patients.
CD3 is a:
T-cell marker
CD19 is a:
B-cell marker
CD68 is a:
macrophage (histiocyte) marker
__________ is a form of self-limited infectious lymphadenitis that most often is seen in children, typically “downstream” of lymphatic drainage from the site of an injury on a distal extremity.
cat-scratch disease from Bartonella henselae infection *stellate necrosis*
microthrombocytopenia; propensity to develop non-Hodgkin’s lymphoma; X-linked; many types of white blood cells, which are part of the immune system, to be abnormal or nonfunctional, leading to an increased risk of several immune and inflammatory disorders; eczema
Wiscott-Aldrich syndrome
“popcorn” cell
Reed-Sternberg cell aka lacunar histiocyte “crippled” B cell bc of mutations in Ig gene malignant B-cell; bi-nucleated does not stain with CD-20, CD45- NO immunoglobulin on its surface CD15+ CD30+
A chest CT scan shows a 10-cm mass in the anterior mediastinum; biopsy shows effacement by lymphoid cells with lobulated nuclei having delicate, finely stippled, nuclear chromatin; scant cytoplasm, many mitotic figures are seen; cells express deoxynucleotidyl transferase negative (TdT−), CD2, and CD7 antigens; point mutation in the NOTCH1 gene; seen in children
lymphoblastic lymphoma mediastinal location typical; chemotherapy is curative in most cases
The NOTCH1 gene encodes a transmembrane receptor required for:
T-cell development, and more than half of pre–T-cell tumors have activating point mutations.
TdT is a marker of:
pre–T cells and pre–B cells
Clonal rearrangement of immunoglobulin genes; CD19+, CD5+, and deoxynucleotidyl transferase negative (TdT−); blood smear shows monotonous population of small, round, mature-looking lymphocytes; elderly patient
chronic lymphocytic leukemia (CLL), a clonal B-cell neoplasm in which immunoglobulin genes are rearranged, and T-cell receptor genes are in germline configuration. There is typically a tissue component of small lymphocytic lymphoma (SLL).
The t(8;14) translocation is typical of:
Burkitt lymphoma MYC gene***
The t(14;18) translocation is a feature of:
follicular lymphomas, which are distinctive B-cell tumors that involve the nodes and produce a follicular pattern.
The CD30 antigen is a marker for:
activated T and B cells
bone pain and tenderness; most common malignancy seen in children; anemia; thrombocytopenia; presence of blasts in the peripheral blood and bone marrow that *have* nucleoli; petechial hemorrhages possible;
Acute lymphocytic leukemia
What are the poor prognostic markers for ALL?
Poor prognostic markers for acute lymphoblastic leukemia/lymphoma are: T-cell phenotype; patient age younger than 2 years; WBC count >100,000; presence of t(9;22) MLL gene mutations; presentation in adolescence and adulthood
__________ is the most common form of non-Hodgkin lymphoma among adults in Europe and North America.
Follicular lymphoma The neoplastic B cells mimic a population of follicular center cells and produce a nodular or follicular pattern. Nodal involvement is often generalized, but extranodal involvement is uncommon.
The t(14;18) translocation, which is characteristic of _______, causes overexpression of the BCL2 gene by juxtaposing it with the IgH locus; the cells are resistant to apoptosis.
Follicular lymphoma follicular lymphomas are indolent tumors that continue to accumulate cells for 7 to 9 years. IgH and bcl2 genes
t(11;14) translocation, in which the cyclin D1 gene (BCL1) is overexpressed, is seen in:
Mantle cell lymphoma B-cell lymphoma, more aggressive than follicular lymphoma
increased numbers of circulating small, round, mature lymphocytes with scant cytoplasm in the peripheral blood smear; cells express the CD5 marker and the pan B-cell markers CD19 and CD20; Most patients have a disease course of 4 to 6 years before death; symptoms appear as the leukemic cells begin to fill the marrow (thrombocytopenia)
Chronic lymphocytic leukemia (CLL)
Same small lymphocytes as CLL, but appearing in tissue and not blood; widespread lymphadenopathy; liver and spleen enlargement; lymphocytosis
Small lymphocytic lymphoma
BCL6 rearrangements or mutations in 30% of cases; staining pattern indicates a B-cell proliferation (CD19+, CD10+); T-cell (CD3) and monocytic (CD15) markers are negative; enlargement of the Waldeyer ring of oropharyngeal lymphoid tissue; **no hepatosplenomegaly
diffuse large B-cell lymphoma
T/F: Diffuse large-cell lymphoma of B cells often involve extranodal sites.
True aggressive but responsive to chemotherapy;
Multiple myeloma produces mass lesions of plasma cells that lead to bone lysis and pain; radiograph shows typical punched-out lytic lesions, produced by expanding masses of what kind of cells?
Plasma cells
The Ig genes in myeloma cells always show evidence of somatic hypermutation. Patients with myeloma often have infections with ____________ because of decreased production of IgG, required for opsonization.
encapsulated bacteria
visual disturbances; dizziness; headache; Raynaud phenomena; bone marrow is infiltrated with plasmacytoid lymphocytes that have stored immunoglobulins in their cytoplasm (Russell bodies)
Hyperviscosity syndrome associated with lymphoplasmacytic lymphoma (Waldenström macroglobulinemia). In this disorder, neoplastic B cells differentiate to IgM-producing cells; there is a monoclonal IgM spike in the serum. These IgM molecules aggregate and produce hyperviscosity, and some of them agglutinate at low temperatures and produce cold agglutinin disease.
Light chains in urine (Bence Jones proteins) are a feature of:
Multiple myeloma
Hypercalcemia occurs with myeloma because:
myeloma cells produce MIP1-α that up-regulates RANKL production and increased osteoclastic activity; punched-out lytic bone lesions are typical of multiple myeloma.
The most common sites for ___________ are the thyroid (in Hashimoto thyroiditis), the salivary glands (in Sjögren syndrome), or the stomach (in Helicobacter pylori infection).
MALT - marginal zone - lymphoma
Name the disease associated with the presence of hairy projections from neoplastic leukocytes in the peripheral blood smear and coexpression of B-cell (CD19, CD20) and monocyte (CD11c) markers.
Hairy cell leukemia B-cell leukemia
Auer rods are seen in myeloblasts in:
AML
A monoclonal IgM spike is a feature of:
lymphoplasmacytic lymphoma (Waldenström macroglobulinemia)
large cells, some of which contain horseshoe-shaped nuclei and voluminous cytoplasm; tumor cells cluster around venules and infiltrate sinuses; most often in children and young adults; characteristic gene rearrangement on chromosome 2p23 that results in production of anaplastic lymphoma kinase (ALK) with tyrosine kinase activity
anaplastic large-cell lymphoma
CD10 is what kind of cell marker?
B-cell
CD56 is a marker for
NK cells
HIV is best associated with what neoplasms?
HIV is best known to be associated with non-Hodgkin lymphomas and with Kaposi sarcoma
What is the action of Reed-Sternberg cells, for example in Hodgkin lymphoma?
Reed-Sternberg cells elaborate cytokines that promote an accompanying reactive cellular proliferation that forms the bulk of a neoplastic mass. Reed Sternberg cells are of B-cell origin, and in many cases, Epstein-Barr virus (EBV) infection can be demonstrated in these cells.
Subtype of Hodgkin Lymphoma; Seen in young adults, mainly women; thick bands of fibrosis; mediastinal involvement common
Nodular sclerosis
In all forms of HL except ____________ type, the Reed-Sternberg cells and variants stain with CD15.
lymphocyte predominance type
The lymphocyte depletion variant of Hodgkin lymphoma has what features?
an abundance of Reed-Sternberg cells and a paucity of lymphocytes.
JAK2 mutations are found in what cancers?
polycythemia vera and other myeloproliferative diseases
Atypical lymphocytes are characteristic in the peripheral blood of individuals with:
infectious mononucleosis
see lacunar cells, think….
Hodgkin Lymphoma seen with Reed-Sternberg cells
t(15;17) translocation seen in:
Acute promyelocytic leukemia (APL) it results in the fusion of the retinoic acid receptor gene on chromosome 17 with the promyelocytic leukemia gene on chromosome 15. The fusion gene results in elaboration of an abnormal retinoic acid receptor that blocks myeloid differentiation. Therapy with retinoic acid (vitamin A) can alleviate the block and induce remission in many patients.
the presence of peroxidase-positive blasts (myeloblasts) filling the marrow indicates what disease?
AML
Myelodysplasia is characterized by:
a cellular marrow in which there are maturation defects in multiple lineages; presence of ringed sideroblasts, megaloblasts, abnormal megakaryocytes, and myeloblasts in the marrow. Because these abnormal hematopoietic cells fail to mature normally, they are not released into the peripheral blood, leading to pancytopenia and susceptibility to infections. Myelodysplasias are clonal stem cell disorders that develop either de novo or after chemotherapy with alkylating agents
What disorders are in the differential when a high platelet count is given?
chronic myelogenous leukemia; myelofibrosis; polycythemia vera; essential thrombobyctosis (non-neoplastic)
What is the likely diagnosis? high blood pressure; NO hepatosplenomegaly or lymphadenopathy; high platelet count; occult blood in stool; high Hgb and Hct; afebrile
polycythemia vera (PCV), a myeloproliferative disorder characterized by an increased RBC mass, with hematocrit concentrations typically exceeding 60%. Although the increased RBC mass is responsible for most of the symptoms and signs, these patients also have thrombocytosis and granulocytosis. This occurs because, similar to other myeloproliferative disorders, PCV results from transformation of a multipotent stem cell.
The neoplastic erythroid progenitor cells require extremely small amounts of erythropoietin for survival and proliferation; the levels of erythropoietin are virtually undetectable in ________. When combined with abnormal platelet function, this condition predisposes the patient to bleeding. Abnormal platelet function also can predispose to thrombosis.
Polycythemia Vera
What are teardrop RBC’s?
Teardrop RBCs are misshapen RBCs that are seen when marrow undergoes fibrosis, as in myelofibrosis. Myelofibrosis with myeloid metaplasia is a myeloproliferative disorder that is also a stem cell disorder in which neoplastic megakaryocytes secrete fibrogenic factors leading to marrow fibrosis.
What is the likely diagnosis? skin eruptions; frequent recent ear infections; bone lesions with “Birbeck” granules in histiocytes; seen in children; exophthalmous sometimes seen, leading to diabetes insipidus from pressure on pituitary stalk
Langherhans cell histiocytosis
An elevated D-dimer level suggests:
a microangiopathic hemolytic anemia
Haptoglobin is:
a serum protein that binds to free hemoglobin. Ordinarily, circulating hemoglobin is contained within RBCs, but hemolysis can release free hemoglobin. The haptoglobin is used up as the amount of free hemoglobin increases.
Iron deficiency does not occur in hemolytic anemias because:
the iron that is released from hemolyzed cells is reused
Inheritance of three abnormal α-globin chains leads to:
hemoglobin H disease, with tetramers of β chains; survival to adulthood is possible
Mutations involving NADPH oxidase lead to immunodeficiency in what disease?
chronic granulomatous disease
What is the MOA of hydroxyurea that makes it effective for treatment of sickle cell disease?
hydroxyurea therapy can increase the concentration of hemoglobin F in RBCs, which interferes with the polymerization of hemoglobin S. However, the therapeutic response to hydroxyurea often precedes the increase in hemoglobin F levels. Hydroxyurea also has an anti-inflammatory effect, increases the mean RBC volume, and can be oxidized by heme groups to produce nitric oxide that promotes vasodilation.
Complement lysis is enhanced in paroxysmal nocturnal hemoglobinuria, which results from mutations in the _____ gene.
PIGA Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder that results from an acquired stem cell membrane defect produced by a PIGA gene mutation that prevents the membrane expression of certain proteins that require a glycolipid anchor. These include proteins that protect cells from lysis by spontaneously activated complement. As a result, RBCs, granulocytes, and platelets are exquisitely sensitive to the lytic activity of complement. The RBC lysis is intravascular, so patients can have hemoglobinuria (dark urine). Defects in platelet function are believed to be responsible for venous thrombosis. Recurrent infections can be caused by impaired leukocyte functions. Patients with PNH may develop acute leukemia or aplastic anemia as complications.
The direct antiglobulin (Coombs) test detects:
antibody bound to RBCs
The indirect antiglobulin (Coombs) test detects:
antibody in the plasma
__________ are the most frequent drugs implicated in drug-induced hemolytic anemias.
Cephalosporins
Anticardiolipin antibody often leads to a false-positive serologic test result for:
syphilis (Treponema pallidum infection) Antiphospholipid syndrome
Name the likely diagnosis: recurrent miscarriages; arterial and venous thromboses; anticardiolipin antobody +
Antiphospholipid syndrome (APS)
A deficiency of ADAMTS13, from an acquired antibody to this metalloproteinase or a genetic mutation in the encoding gene, can lead to accumulation of large von Willebrand multimers that promote platelet microaggregate formation, resulting in what disorder?
TTP that is marked by a pentad of: microangiopathic hemolytic anemia, fever, neurologic changes, thrombocytopenia, renal failure.
Acanthosis nigricans is an uncommon condition with hyperpigmented areas in skin folds; it may occur in association with:
endocrinopathies neoplasms
The most important gene in familial cases of _________ is that of cyclin-dependent kinase inhibitor 2 (CDKN2A), which encodes several tumor suppressors including p16/INK4A.
dysplastic nevus syndrome
pruritic, purple, polygonal papules indicate what disease?
lichen planus
Tinea versicolor is a common condition caused by a superficial fungal infection of:
Malassezia furfur The lesions can be lighter or darker than the surrounding skin.
Biopsy shows spindle-shaped cells and extravastated red cells. This indicates what neoplasm?
HHV8 - Kaposi’s sarcoma nodules can occur anywhere, not just skin
Acantholysis means:
loss of intercellular connections
The most important histologic feature of Mycosis Fungoides (CTCL) is:
the presence of lymphocytes in the epidermis aka epidermotropism
macrocytosis with hypersegmentation of neutrophils
pernicious anemia deficiency of B12 or folic acid
generally, megaloblastic anemias are caused by:
impaired DNA synthesis ie folic acid deficiency
Patients with sickle cell disease that undergo autosplenectomy are then at risk for what kind of sequelae?
Pneumonia, infections with encapsulated bacteria is strep pneumo; renal papillary necrosis due to low pH and low O2
Anemia of chronic disease is often mild to moderate, with what size RBCs?
Microcytic “poor utilization of iron stores” low serum iron LOW iron binding capacity
Associate acanthocytosis or “spur cells” (RBCs look like suns with multiple projections coming out of them) with:
chronic liver disease; free cholesterol is deposited in the RBC membrane
ring sideroblasts, elderly patient think:
myelodysplastic syndrome clonal stem cell defect
Fatty bone marrow, think:
aplastic anemia fatigue, severe pancytopenia, NO reticulocyte response to the anemia
Schilling test tests:
B12 normal - no B12 deficiency
Auer rods, think
Acute promyelocytic leukemia (APL)
translocation in PML/RAR (retinoic acid receptor)
APL 15;17
“smudge cells” think
CLL chronic lymphocytic leukemia
the most common subtype of Hodgkin lymphoma is:
nodular sclerosis
Lethal complication of multiple myeloma:
renal failure
Marrow fibrosis accompanied by megakaryocytosis and granulopoesis:
chronic idiopathic myelofibrosis 15% of cases transform to AML
version of Lagherhans Cell Histiocytosis seen in children 2-5; classic triad of: diabetes insipidus, proptosis, defects in membranous bones
Hand-Schuller-Christian disease typically multifocal and indolent otitis media is a common finding painful lytic bone lesions common
Acute, disseminated variant of Langherhans cell histiocytosis seen in children
Letterer-Siwe disease otitis media is a common finding painful lytic bone lesions common
Most lymphomas in patients who have AIDS are:
high grade B-cell lymphomas large grade B-cell lymhomas is Burkitts bcl2 gene usually EBV+
ITP can be seen in what autoimmune disorder?
SLE antibody-mediated platelet destruction
PAS + hyaline microthrombi in arterioles and capillaries, principally in the heart, brain and kidneys. This indicates what disorder?
TTP thrombotic thrombocytopenic purpura
Classic examples of microangiopathic hemolytic anemia:
DIC TTP both feature generalized thrombosis of capillary vessels
