Pathology Flashcards
Differential diagnosis of Reactive lymphadenopathy?
- Infections: bacteria and viruses
- Immune or connective tissue disorders: rheumatoid arthritis, systemic lupus erythematosus
- Iatrogenic causes (drugs…)
- Idiopathic (but often specific pattern): progressive transformation of germinal centers, Kikuchi-Fujimoto lymphadenopathy
Origin of leukemia (derived from which cells)?
Mostly myeloid cells and lymphoid cells, less erythroid cells or megakaryocytes
Origin of lymphoma (derived from which cells)?
–Precursor B- or T-lymphoblasts
–Mature B- or T- lymphoid cells
Those symptomes are suggestive of what ?
–Effects due to replacement of marrow
- Anemia: fatigue, weakness, dyspnea
- Neutropenia: infections
- Thrombocytopenia: bleeding…
- Bone pain
–Abdominal pain (splenomegaly)
–Systemic symptoms: fever, night sweats…
Leukemia
Those symptoms are suggestive of what?
–Enlarged lymph nodes, mass, pain, bleeding, organ-related symptoms
–Abdominal pain (splenomegaly or other)
–Systemic effects: “B” symptoms (fever, night sweats, weight loss), fatigue…
Lymphomas
Diffuse large B-cell lymphoma (DLBCL)?
–Aggressive B-cell lymphoma with large cells in a diffuse pattern
–Most common NHL in adults
Immunoprofile
- CD20+
- High Ki67 proliferation rate
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)?
- Prognosis: indolent
- Therapy is specific, so need a specific diagnosis!
Follicular lymphoma (FL)?
- Neoplasm of B-cells of germinal center origin: centrocytes + centroblasts in follicular pattern
- 2nd most common NHL, ~40% in West
- Grading (correlates with prognosis)
–Low grades 1, 2: ≤ 15 centroblasts per high power field
–High grade, 3A, B: >15 centroblasts/HPF
Plasma cell neoplasms?
Diagnosis based on
- Clinical: pathological fractures, bone pain, anemia, low immunity, renal failure, hypercalcemia
- Radiological: Iifiltration of bone and marrow (always) by neoplastic plasma cells
- Pathological findings: paranuclear Golgi, CD138
Mature T- and NK-cell lymphomas’ general features?
- Prognosis generally poorer than B-cell lymphomas, more difficult to treat
- T-cell markers positive (or loss): CD2, CD3, CD5…
General features of Hodgkin lymphoma?
A clinically and pathologically distinctive lymphoma derived from germinal center B-cells composed of a small population of malignant cells, the Reed-Sternberg or other “Hodgkin” cells, admixed with numerous reactive cells
- Principally a nodal disease
- Orderly spread by contiguity
- Often a single group of lymph nodes (esp. cervical)
- Mesenteric nodes & Waldeyer ring rarely involved
- Extra-nodal involvement rare
- Leukemic phase extremely rare
- Prognosis very good to excellent with Rx
- Two main types each with distinctive features and immunohistochemical profile
Types of Hodgkin lymphoma (HL)?
- Nodular lymphocyte predominant: mostly males, age 30-50, cervical, axillary, inguinal nodes
- Classical: M ~ F, 15-35 + peak in older persons, cervical, mediastinal, axillary, para-aortic
- Nodular sclerosis
- Mixed cellularity
- Lymphocytes-depleted
- Lymphocytes-predominant
Popcorn cells is a pathologic feature of?
Nodular lymphocyte predominant HL
Reed-Sternberg cell are a pathological feature of?
Classical Hodgkin lymphoma
What are the B cell markers (mature)?
CD20, CD19: very specific
T cell markers?
–CD3 very specific
–CD4: helper T-cells; CD8: cytotoxic T-cells
BCL6, CD10 are markers for?
follicular center cells
CD138, k, l light chains are markers of?
plasma cells myeloma
CD45 is a marker for?
lymphoid cells, some myeloid
CD8 is a marker for?
cytotoxic T-cells
CD5 is a marker for?
mostly T-cells, but present and diagnostic of some B-cell lymphomas (CLL/SLL, mantle cell)
BCL2 is a marker for?
anti-apoptotic protein: follicular lymphomas (B-cells)
Ki67 is a marker for?
proliferation
What are the Primary B Cell Deficiencies?
- Agammaglobulinemia (X-linked [XLA], AR)
- Hyper IgM immunodeficiency (HIGMS)
- Common variable immunodeficiency (CVID)
- Selective IgA deficiency
- Anti-polysaccharide antibody deficiency
- Transient hypogammaglobulinemia of infancy (THI)
What are the Primary T Cell deficiencies?
- Severe combined immunodeficiency (SCID)
- DiGeorge syndrome
- Wiskott-Aldrich syndrome
- Ataxia-Telangiectasia
- Miscellaneous CID
Clinical presentation of XLA?
- Infections begin at 4-6 months when maternal immunity wanes
- Absent circulating mature B cells
- All major classes of immunoglobulin affected (IgG, IgM, IgA)
- No antibody responses to antigen
- Sino-oto-pulmonary infections with encapsulated bacteria
- Bacteremia, meningitis, septic arthritis, etc
- Chronic infections with enteroviruses
Clinical presentation of SCID?
- Lymphopenia is an early clue
- Also severe antibody deficiency
- Extreme susceptibility to infection since birth to high-grade or low-grade pathogens
- Protracted diarrhea, failure to thrive
- Ommen Syndrome: desquamating erythroderma, fever, hepatosplenomegaly, lymphadenopathy, eosinophilia, high IgE, diarrhea, FTT
Molecular mechanism of XLA?
- Arrest of B cell development at pre-B cell stage
- Mutation in btk gene (Bruton tyrosine kinase)
- Autosomal recessive: µ, Ig-α, λ-5 chains
Molecular mechanism of SCID?
- Severe defect in T cell development: EMPTY THYMUS
- No T cells, +/- B cells or NK cells
- Many genetic variants: γ-common chain (XL) is the most frequent
Treatment od XLA?
IVIG: antibody replacement
Treatment of SCID?
Bone marrow transplant before 1 unless death
What are the 2 main classes of HLA?
- MHC class I aka HLA A, B, C, found on all nucleated cells
- MHC class II aka HLA DR, DQ, DP, found on APC
What are the 3 structures of the MHC complexe?
- Class I: 3 different gene sections for the protein that become ONE class I molecule
- Class III: contains a lot of the HLA-like proteins & some genes for proteins for other parts of immune system (ex: complement)
- Class II: the structure of class II on surface of cell = alpha chain + beta chain
–> Great variability
What are the characteristics of HLA?
- Polymorphic: many shapes
- Polygenic: come from many different genes
- Linkage disequilibrium: genes are inherited are preferentially in blocks / as a group –> 1/4 match with sibling
- Co-dominantly expressed: genes on BOTH chromosomes are expressed (ABC from mom + ABC from dad = 6 class I proteins on one cell)
What are the HLA tissue typing and their characteristics?
- Serology: gives you the type (gets you 80% out of the way)
- Genetic: used to better define the allele carried by the patient, ideal tool
- Functional typing: MLR (mixed lymphocyte rxn), can be evaluated in lab, may be done with patients with previous solid organ transplant
What is the limitation with cord blood donner?
Higher possibility of FAILURE TO ENGRAFT + repopulating from such a naive pool means time for symptoms to show up is slower (while infection risks are higher because your patient is immunosuppressed)
What is the limitation with Haplo-identival transplant?
When a parent gives a transplant to their child, there’s an extra HLA-Y: girls into boys OK, boys into girls might be a problem
For what type of transplant we don’t have to do HLA match?
- Blood ***but does have to match for ABO
- Corneal
What type of match is essential for kidney grafts and solid organts?
Class I
What type of match has to be done with bone marrow transplants?
Class II
