Pathology 1 - Block 3 - Part 3

davidwurbel7's version from 2016-03-22 19:54

White Blood Cells and Lymph Nodes 4

Question Answer
Group of ‘clonal stem cell’ disorders characterized by maturation defects associated with ineffective hematopoiesis. Increased risk of cytopenias, and transformation to AML. Incidence: older age group (exception: following chemotherapy/associated with Down’s Synd) chemicals: benzene, alkylating agents. radiationMyelodysplastic Syndrome
Labs values show pancytopenia, neutropenia, thrombocytopenia. Peripheral blood smear show hypogranular granulocytes and Pelger-Huet cellsMyelodysplastic Syndrome
Bone Marrow Morphology shows dysplastic maturation affecting all non lymphoid lineage - erythroid, granulocytic, monocytic, megakaryocyctic. Erythroid series: ringed sideroblasts, megaloblastoid cells. Myeloid series: pseudo Pelger-Huet cells; neutrophils with 2 nuclear lobes. Megakaryocyte: pawn ball megakaryocytes (single nuclear lobes). Myeloblasts less than 20% in bone marrowMyelodysplastic Syndrome
Neutrophil with bilobed nucleusPelger-Huet Cell
Clinical course - older age group (> 60 years). Weakness, infections, hemorrhages. Progression to AML in 10 to 40%. T- MDS has very poor prognosisMyelodysplastic Syndrome
Common Features of these conditions include association with JAK-2 mutation, increased cell turnover (exception ET), marrow fibrosis (exception ET), transformation to acute leukemias, mostly AML, but some end with ALL (transformation to acute leukemia not seen with ET)Myeloproliferative Disorders
Chronic Myeloid Leukemia (CML), Polycythemia vera, Essential thrombocytosis and Primary myelofibrosis are examples of this class of conditionsMyeloproliferative Disorders
Incidence: adults between 25 to 60 yrs with a peak: 45 to 55 yrs. The pathophysiology presence of a distinctive molecular abnormality. Translocation involving ABL gene on chromosome 9 and BCR gene on chromosome 22. Activates multiple downstream pathways examples: RAS, JAK/STAT, AKT. AKT enhances cell survivalChronic Myeloid Leukemia
Philadelphia chromosome is associated with increased cell division through non-receptor tyrosine kinase and inhibition of apoptosis. Affects granulocytic progenitors. Lab diagnosis - Total WBC: more than 100,000 cells/mm3 (many cases have counts around 200,000 cells/mm3). Platelet count: increased initially, later thrombocytopenia. Peripheral blood smear: moderate anemia may be seen. Myeloid series in all stages of development majority of cells being myelocytes, metamyelocytes, and band forms eosinophils, and basophils. Bone Marrow: marked hypercellularity. Myeloid & megakaryocytic lineage. Eosinophils & basophils are increased. Myeloblasts are less than 5% (increase over 10% signifies onset of accelerated phase). Later stages show collagen proliferation. Biochemistry: hyperuricemia. LAP score is low (differential diagnosis with Leukemoid reaction). Molecular diagnosis - Philadelphia chromosome (95%)Chronic Myeloid Leukemia
This drug blocks the effects of the BCR-ABL fusion product normalization of white cell count is seen by two months of therapy, and bone marrow normalization by 8 monthsImatinib
Incidence - adult age group, mostly males. Neoplasm arising in a multipotent myeloid stem cell. Pathogenesis - characterized by increased marrow production of erythroid, granulocytic and megakaryocytic elements. Erythroid proliferation is not regulated by erythropoietin. There is decreased erythropoietin levelsPolycythemia Vera
The mutation in chromosome 9, seen in 97% of the cases of polycythemia veraJAK2
Lab Diagnosis - increased red cell count, increased Hb, increased Hematocrit, leukocytosis, thrombocytosis. Peripheral blood - increased basophils, large platelets. Bone marrow - hypercellular. Late stages - marrow fibrosis. Biochemical - hyperuricemiaPolycythemia Vera
Clinical features include headache, dizziness, tinnitus, visual disturbances. “ruddy” color of skin, especially face. deep vein thrombosis, infarcts, & bleeding. pruritus. ‘aquagenic pruritus’. Peptic ulceration. Hyperuricemia. Complications: myelofibrosis, acute leukemiaPolycythemia Vera
The clinical features of this condition is mostly due to expanded total blood volume and slowing of blood flow due to increased viscosityPolycythemia Vera
Condition seen in adults (over 50 yrs), presents with anemia. Rapid development of obliterative marrow fibrosis. There is suppression of hematopoiesis resulting in extra medullary hematopoiesis (shifts to spleen). Pathogenesis - extensive deposition of collagen. Fibrogenic factors: PDGF and TGF-β released from neoplastic megakaryocytes with a JAK-2 mutationPrimary Myelofibrosis
Lab diagnosis - Total WBC count: mild elevation in early stages. Hemoglobin: reduced. Peripheral blood smear: nucleated rbc, ‘tear drop’ rbc (dacrocytes), early granulocytes“leukoerythroblastosis” (leukoerythroblastic reaction). Bone Marrow- initially hypercellular, but becomes hypocellular with disease progression diffusely fibrotic (classically, increase in reticulin fibers) atypical megakaryocytes. Biochemistry- hyperuricemiaPrimary Myelofibrosis
Clinical course is anemia, splenomegaly, fatigue, night sweats, hyperuricemia (gout). Survival rate 3 to 5 yearsPrimary Myelofibrosis
A clonal hematopoietic stem cell disorder characterized by an isolated thrombocytosis and associated with thrombotic and hemorrhagic complications. patients may present at any age, most cases seen in later life with a peak incidence between the ages of 50 and 70 years. Slightly more common in females. Pathogenesis - JAK2 mutation which leads to proliferation of plateletsEssential Thrombocytosis
Lab finding - Total WBC count: elevated. Total platelet count: elevated. Peripheral smear: anemia, basophilia, leukocytosis, thrombocytosis (increased number), platelets are larger. Bone marrow - increased cellularity, megakaryocytic hyperplasia. Bleeding time: may be abnormal. Platelet defect: presentEssential Thrombocytosis
Clinical features include deep vein thrombosis, portal & hepatic vein thrombosis (Budd Chiari Syndrome), myocardial infarction, tendency to bleed, GI bleed, splenomegaly. Erythromyalgia ( intense burning or throbbing pain of hand and feet) associated with warmth, duskiness, & mottled erythemia induced by exerciseEssential Thrombocytosis

WBC & Lymph Nodes Part 5

Question Answer
Follicular Lymphoma, Diffuse Large B-cell Lymphoma (DLBCL), Burkitt Lymphoma, Mantle cell Lymphoma and Marginal zone Lymphoma are examples of this lymphomaNon- Hodgkin Lymphoma (NHL) B-cell Lymphomas
Anaplastic Large-cell Lymphoma is an examples of this lymphomaNon- Hodgkin Lymphoma (NHL) T-cell lymphomas
Incidence - common type of lymphoma middle aged, males and females. Pathogenesis - translocation 14; 18 (seen in 90%) leads to overexpression of bcl-2 inhibition of apoptosis, therefore these abnormal cells continue to proliferateNHL Follicular Lymphoma
Labs/Investigations - Complete Blood Counts: within normal limits. Lymph node biopsy - loss of architecture, “follicle-like” pattern, stain positive for bcl-2 (immunohistochemistry). Bone Marrow: involvement seen in 85% of cases. Spleen/Liver: involved. Immunophenotype: tumor expresses CD19, CD20, CD10. CD 5 is not expressed bcl-2 positive. Others investigations: CT scan (to see about other node involvement)NHL Follicular Lymphoma
Clinical features - painless generalized lymphadenopathy about 10% of patients present with B symptoms (fever, drenching night sweats, or loss of 10% of the body weight). Disease usually is widespread at presentation, with involvement of multiple lymph node, liver, and spleen bone marrow is involvement seen incurable, but has an indolent course median survival: 7 to 9 yearsNHL Follicular Lymphoma
NHL Follicular lymphoma may transform into this conditionDiffuse Large B Cell Lymphoma
Incidence - any age group, but mostly middle-age. Common type of non-Hodgkin lymphoma. Aggressive (related to being poorly differentiated) and may involve ‘extra-nodal’ sites (example: GIT, liver, brain)NHL: Diffuse Large B Cell Lymphoma
Subtype of NHL: Diffuse large B cell lymphoma seen mostly in advanced HIV infectionPrimary Effusion Lymphoma (PEL)
This gene is normally required for the formation of normal germinal centersBCL-6
Deregulation of BCL-6 is seen in this conditionNHL: Diffuse Large B Cell Lymphoma
Investigations - Complete blood counts: normal. Bone marrow: involved late in disease. Serology: HIV. Elevated LDH: due to increased tumor burden. CT scan: organ involvement, abdominal lymph nodes. Diagnosis is based on tissue biopsy. Lymph node/tissue morphology. presence of large lymphoid cells. immunophenotype: CD19, CD20. surface Ig is seen. negative for TdTNHL: Diffuse large B cell lymphoma
Clinical course - rapidly enlarging lymph nodes at single nodal site or extra nodal site. Aggressive tumors, but show response to therapy. Adjuvant therapy with anti-CD20 antibody. extra nodal: GIT, skin, brain. Bone marrow involvement is lateNHL: Diffuse Large B Cell Lymphoma
An eastern equatorial Africa, with a peak age incidence at 4 to 7 years, and is nearly twice as frequent in boys as in girls. There is also an association with malariaAfrican (Endemic) NHL: Burkitt Lymphoma
Clinical features include extra-nodal common location: mandible, abdominal viscera (kidney, ovaries, adrenal) aggressive, but responds to chemotherapy. Immunophenotype: CD19, CD20, B-cell expression of IgM. Translocation t(8; 14): myc gene on chromosome 8NHL: Burkitt Lymphoma
Labs - Complete Blood Counts: normal. Bone marrow: very rarely involved. Diagnosis: based on tissue biopsy and karyotyping. Morphology - involved tissues show diffuse infiltrate of intermediate-sized lymphoid cells. High mitotic index, extensive apoptotic cell death. Benign macrophages are scattered within the tumor tissue forming, “starry sky” patternNHL: Burkitt Lymphoma
Incidence seen more in Europe. 5th to 6th decade of life. more in males. widespread disease at the time of diagnosis. Pathology - tumor cells resemble the mantle zone B lymphocytes. Associated with t(11,14)NHL: Mantle cell lymphoma
Lab Diagnosis - CBC: normal Bone marrow: frequently involved. Lymph node biopsy: loss of architecture. few reactive germinal centers. These are surrounded by tumor cells. Immunophenotype: CD19, CD20, CD5, are positive CD23 negativeNHL: Mantle cell lymphoma
Clinical features - painless lymphadenopathy, splenomegaly. Extranodal involvement: Waldeyer ring, and GIT. GIT: present as lymphmatoid polypNHL: Mantle cell lymphoma
A distinct B-cell neoplasms with variable clinical features. Seen arising from areas involved in chronic inflammation by autoimmune or infectious etiology (Sjörgen syndrome, Hashimoto’s thyroiditis, Helicobacter pylori) may regress, if inciting agent is eradicatedNHL: Marginal zone Lymphomas
Inflammation and lymphoma - MALTomas begin as polyclonal immune reactions and later acquire an initiating mutation in the B-cell clone. NF-kB activation promotes growth and survival of these transformed B-cells. MALTomas are indolent and tends to remain localized at the site of origin for yearsNHL: Marginal zone Lymphomas
Uncommon, children and young adults, characterized by re-arrangement in ALK gene (2p23) in mostAnaplastic Large-cell Lymphoma
Lab Diagnosis - CBC: normal. Skin biopsy: infiltrates of large anaplastic cells, horseshoe nuclei (hallmark cells), Lymph node: loss of architecture. large anaplastic cells, “hallmark” or “doughnut” cells. positive for CD30 (Ki-1). Prognosis: good considering that it is a T-cell malignancyAnaplastic Large-cell Lymphoma
Characterized by: Reed-Sternberg cell: residing in a mixed infiltrate of non-neoplastic cells. Incidence: mostly young adults, bimodal distribution, 15 to 34 years. second peak after 50 yearsHodgkin Lymphoma
Pathogenesis - IgG genes of RS have undergone V(D)J recombination and somatic hypermutation. this phenomenon thus establish that the RS cell taken origin from the germinal/post-germinal center B-cell. however, RS cell fail to express most B-cell specific markers. NF-kB activation is seen. NF-kB helps these abnormal RS from being removed through apoptosis. RS cells produces cytokines (IL-5, IL-10, 1L-13, and TGF-β), which creates a reactive response in the surrounding cellsHodgkin lymphoma
Most common form (65%) of Hodgkin Lymphoma. frequent involvement of the lower cervical, supraclavicular, and mediastinal lymph nodes in adolescents and young adults, particularly femalesNodular sclerosis, HL
Morphology - presence of RS cell variant: ‘lacunar cell’, fibrous bands, circumscribing the lymph node into nodular areas. ‘lacunar RS cells’ are seen in a reactive background composed of T-cells, eosinophils, plasma cells, macrophages. Immunophenotype: CD15, CD30 positive. mostly involve lower cervical, supra clavicular and mediastinal lymph nodesNodular sclerosis, HL
Clinical course: painless lymph node enlargement neck, supraclavicular, axilla mediastinal lymph nodes in 50% at the time of diagnosis. one-third of patients present with fevers, night sweats, and/or weight loss: B symptoms. fever: Pel-Epstein feverHodgkin lymphoma
Fevers persist for days to weeks, followed by afebrile intervals and then recurrence of the feverPel-Epstein Ffver
Clinical course patients with are cured >90% of the time association of ‘anemia of chronic disease’ (ACD) with normocytic normochromic anemia. long term survivors of chemotherapy, and radiotherapy have an increased risk for second malignancy: AML in the setting of MDS, lung cancers, and breast cancersHodgkin lymphoma

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