WBC Diseases PDF

White Blood Cells Disorders Karen Gil MD, MHSN Non Neoplastic disorders Leukopenia Leukocytosis NV: White blood cell count (3,400 to 9,600 cells/mcL) Neoplastic disorders Lymphomas Leukemias Non-Neoplasic Disorders Leukopenia Decrease in peripheral WBC (granulocytes) Associated to : Immunodeficiency...

White Blood Cells Disorders Karen Gil MD, MHSN Non Neoplastic disorders Leukopenia Leukocytosis NV: White blood cell count (3,400 to 9,600 cells/mcL) Neoplastic disorders Lymphomas Leukemias Non-Neoplasic Disorders Leukopenia Decrease in peripheral WBC (granulocytes) Associated to : Immunodeficiency disorders (HIV) Corticosteroid treatment Neutropenia Inadequate production (aplastic anemia) Accelerated removal or increase utilization Major risk is susceptibility of infections Complete Blood Count – CBC with differential Non-Neoplasic Disorders Leukocytosis Increase in the absolute number of WBC Causes Surgery Infection Illness Stress Pregnancy Non-Neoplasic Disorders Neutrophilia Increase in the absolute numbers of neutrophils Causes Stress Exercise, pain, fear Infections (especially bacterial) Infectious Mononucleosis Self limited diseases caused by EBV (Epstein Barr virus) Direct oral contact “kissing disease” Fever, sore throat (pharyngitis), generalized lymphadenopathy, rash 1-4 weeks CBC leukocytosis, lymphocytosis Ab against EBV Dx: MONOSPOT TEST (+) Enlarged spleen liver function abnormalities (elevated enzymes) leukocytosis Heterophile Ab Monospot Test Commercially available test kits are 70–92% sensitive and 96–100% specific Rx: Support (hydration, bed rest) Reactive lymphadenitis Acute nonspecific Follows systemic bacterial or viral or infections Lymph nodes will be swollen and tender May undergo abscess formation with eventual scarring Chronic nonspecific Three patterns: 1. Follicular hyperplasia B cell region Follows chronic infections 2. Paracortical lymphoid hyperplasia T cell region Follows viral infections 3. Sinus Hitiocytosis Distention of lymphatic channels Cat-Scratch Disease Self-limited lymphadenitis Cause Bartonella henselae Disease of childhood - 90% younger than 18 y/o Regional lymphadenopathy Most frequent axilla and the neck Nodal enlargement approximately 2 weeks after feline scratch Nodal inflammation could last 2-4 months Nodule vesicle or eschar at the site of injury Complications Encephalitis, osteomyelitis, thrombocytopenia Cat-Scratch Disease Cat-Scratch Disease Parinaud oculoglandular syndrome conjunctival disease characterized by a unilateral granulomatous follicular conjunctivitis associated with ipsilateral regional lymphadenopathy Cat Scratch Disease is the most common cause, but other organism can cause this syndrome Cat Scratch Disease generally self-limited treatment is usually supportive Broad-spectrum ophthalmic drops (Fluroquinolones) Systemic antibiotics are recommended for moderate to severe disease Treat immunocompromised patients doxycycline, azithromycin, trimethoprim/sulfamethoxazole DS, ciprofloxacin MALIGNANT DISORDERS OF WHITE BLOOD CELLS Lymphomas Plasma Cell dyscrasias Leukemias Neoplastic Proliferations of White Blood Cells Three board categories based on the origin of the tumor cells: 1. Lymphoid Phenotype of neoplastic cell resembles a frozen stage of normal lymphocyte differentiation non-Hodgkin lymphomas (NHLs) Hodgkin lymphomas Lymphocytic leukemias 2. Myeloid Arise from hematopoietic stem cells Acute Myeloid leukemia (AML) Myelodysplastic disorders 3. Hystiocytosis Proliferation of macrophages and dendritic cells Langerhans cell hystiocytosis WBC Neoplasms Classification Previously, lymphoid neoplasms were classified as Bone marrow/blood = Leukemias Solid LN neoplasm = Lymphomas Actually, WHO classifies lymphoid neoplasm based on the cell origin, not anatomic location A leukemia can evolve in lymphoma and vice versa Leukemia and lymphoma are malignant proliferative diseases involving leukocytes early cell growth and maturation are inhibited – malignant clones Classification of the Lymphoid Neoplasms Non Hodgkin’s Lymphoma Precursors B–Cell Neoplasms Peripheral B-cell neoplasms (neoplasms of mature B cells) Precursor T-cell neoplasms (neoplasms of immature T cells) Peripheral T-cell and NK-cell neoplasms (neoplasms of mature T cells and natural killer cells) Hodgkin lymphoma (neoplasms of Reed-Sternberg cells and variants). Non-Hodgkin’s Lymphoma Epidemiology: Increases with age (peak > 50 years) Etiology: - Infections (HIV, EN, HTLV-1, HCV, H. Pylori) - Autoimmune diseases (e.g., Hashimoto thyroiditis, rheumatic disease) - Chromosomal translocation (abnormalities) Types: Classification based on: - Cell type Precursors cells : B cell, T cells Mature cells: natural killer (NK) cells - Location (nodal or extranodal) - Tumor grade Adenopathy + Extranodal (Multiple lymph node groups) - Lymph nodes throughout the body, but can also arise in normal organs - Noncontiguous spread Clinical features: - Nodal disease: B symptoms 20-50% lymphadenopathy, mass, Hepatosplenomegaly, cytopenias (decrease RBC, WBC, platelets) - Extranodal disease: GI 15% inflammation can evolve to ulcer and perforation of stomach or small intestine Liver/ spleen – diffuse hepatosplenomegaly Skin – rash Bone – pathologic fractures (pain-swelling) CNS – epidural SCC, peripheral nerve infiltration, CNS lymphoma (1%) Non-Hodgking in children (more frequently between the ages of 10 – 20) Small noncleaved cell lymphoma (Burkitt's and non-Burkitt's): B-cell origin 40-50% of childhood NHLs. Lymphoblastic Predominantly `B-cell origin, sometimes is hard to distinguish from leukemia; 30% of childhood NHLs. Large cell lymphoma both T and B; 20-25% of childhood NHLs. Non-Hodgkin Lymphomas in adults B cells ( more common ) 20% DLBCL (Diffuse Large B Cell lymphoma) of all NHL and 60% to 70% of aggressive lymphoid neoplasms 45% Follicular Prognosis measured in months Most common form of NHL in the United States Is a middle age disease and afflicts males and females equally Usually indolent Prognosis measured in years (7-9) 10% marginal zone Mucosal sites Driven by chronic antigen stimulation (inflammation) as Sjogren's, HCV, H. Pylori T-cells ( less common) < 15% Peripheral T-cell Generally aggressive Diagnose Physical exam- lymphadenopathies (neck, axillar, inguinal), hepatosplenomegaly CBC with diff Imaging tests. CT, MRI and positron emission tomography (PET) Lymph node test- lymph node biopsy Bone marrow test Lumbar puncture (spinal tap) Treatment Bone Marrow transplant Chemotherapy CHOP-Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone Radiotherapy immunotherapy Hodgkin’s Lymphoma Epidemiology: two peaks young adults 15-30, older 50-70 Malignant lymphoma that is typically of B-cell origin Etiology: Immunosuppression (e.g., HIV, EBV infection, Autoimmune diseases) Clinical features: - Adenopathy (painless)-localized above the diaphragm - Contiguous spread - Lymph nodes in upper portion of the body (the neck, underarms, or chest) - B symptoms fever, night sweats, decrease weight - Pruritus: (focal or generalized) Usually no hepatosplenomegaly (Rare but might occur if the spleen or liver are involved) No leukemic phase Hodgkin’s lymphoma in children are rare under five years of age; in children under age 10, it is more common in boys than girls Currently, Hodgkin's lymphoma is more curable than nonHodgkin’s Develops at a single site and spreads in a predictable fashion to contiguous lymph node groups For this reason, early in its course, local therapy may be Indicated HL accounts for 0.7% of all new cancers in the United States, It is one of the most common forms of malignancy in young adults, with an average age at diagnosis of 32 years. Curable in most cases Cotswold Modification of Ann Arbor Staging of Hodgkin Lymphoma and Non-Hodgkin Lymphoma Stage* Criteria I In 1 lymph region only II In ≥ 2 lymph regions on the same side of the diaphragm III In the lymph nodes, spleen, or both and on both sides of the diaphragm IV Extranodal involvement (eg, bone marrow, lung, liver) *Subclassification E indicates extranodal involvement adjacent to an involved lymph node (eg, disease of mediastinal nodes and hilar adenopathy with adjacent lung infiltration is classified as stage IIE). Stages can be further classified by A to indicate the absence or B to indicate the presence of constitutional symptoms (weight loss, fever, or night sweats). Constitutional symptoms generally occur with stages III and IV (20 to 30% of patients); the suffix X is used to denote bulky disease, which is > 10 cm in maximum dimension or > 1/3 the chest diameter on chest x-ray. Hodgkin’s lymphoma Reed Sternberg cell characteristic histological finding (owl eyes nuclei) Prognosis: Good Treatment: Chemotherapy ABVD (Adriamycin-bleomycinvinblastine-decarbazine) BEACOPP (bleomycin-etoposide phosphate-Adriamycincyclophosphamide-oncovinprocarbazine hydrochlorideprednisone Leukemias Classification Four general types Acute lymphoblastic leukemia (ALL) Acute myeloblastic leukemia (AML) Chronic lymphiod leukemia (CLL) Chronic myeliod leukemia (CML) Acute Leukemias Principal pathogenetic problem block in differentiation Abrupt stormy onset Laboratory findings: Absolute leukocytosis (>100,00 WBC/ul but >50% is 25% of marrow population. Acute Leukemias The disease usually affects all ages, but usually occurs in younger patients The predominate cell type is BLAST cells 30% of the bone marrow are blast cells (immature cells) Leading cause of cancer death in children under 15 years of age and the seventh most common form of cancer death overall Acute Leukemias Two Mayor Types 1. Acute Myeloblastic Leukemia (AML) Common in infants and middle age or older Mean age 50 y/o Characterized by normal WBC count with excessive myeloblasts Auer Rods may be seen within leukemic cells in the blood Acute Leukemias 2. Acute Lymphoblastic Leukemia (ALL) Peak age is 2-10 years (4 years old) Disease of the children 80% Normal WBC count with excessive lymphoblasts With treatment – 75% children remain free of the disease in > 5 years ALL AML Clinical Manifestations Bone marrow Replacement of normal parenchyma by neoplastic cells Alteration of stem cell: differentiated cell Symptoms fatigue leukopenia anemia thrombocytopenia bleeding diathesis Skin rash Systemic alteration Decrease immunologic functions Hepatomegaly Splenomegaly Infiltration of the gums Nonspecific symptoms fever weigh loss petechia echymosis purpura Chronic Leukemias Usually affects older adults Median age of onset 65 y/o Represents 1/3 of all Leukemias Male predominance 2:1 Predominant cells are mature cells of the bone marrow “Well differentiated” lymphocytes Characterized by the accumulation lymphocytes in the blood and lymphocytic organs Often patients are asymptomatic and can have anemia Two main types Myelocytic Lymphocytic Chronic Leukemias 1. Chronic Myelocytic Leukemia (CML) Age of onset 25-60 y/o Poor prognosis, only 3 years of survival rate Characterized by WBC count of 50,000 to 300,000 with increased (normal – 4,000 – 10,000) granulocytes in all states of maturation 90% have Philadelphia chromosome Chronic Leukemias 2. Chronic Lymphocytic Leukemia Age of onset is greater than 50 y/o Male/female ratio 2:1 Characterized by WBC count 20,000 to 200,000 with a predominance of mature small lymphocytes 5-10 years of survival rate Ocular Manifestations of Leukemias Ocular involvement is relatively common may be the first indication of manifestation, relapse, or early worsening of the condition In particular Leukemic Retinopathy is the most common ocular manifestation Both acute and chronic could present Leukostasis Retinopathy: Prolonged leukocytosis increased number of circulating platelets --> Increased whole blood viscosity --> Reduced blood flow and vascular stagnation --> Peripheral capillary dropout and microaneurysm formation --> Proliferative retinopathy Ocular Manifestations of Leukemias ROTH SPOTS White centered hemorrhages known as ‘Roth spots’ result from retinal capillary rupture and extrusion of whole blood Cotton wool spots Dilated and Tortuous veins Retinal hemorrhages Flame Dot and blot Preretinal, superficial, sub-hyaloid, vitreal Plasma cell disorders Multiple myeloma Proliferation of malignant clone of plasma cells in the bone marrow Often results in extensive skeletal bone destruction, unexpected anemia, hypercalcemia and acute renal failure MULTIPLE MYELOMA Multiple Melyoma 80% of pt. produce complete Ig Constitutive alteration in IgG locus Chr. 14 IgG 60% 20 – 25% IgA IgM, IgE or IgD Rarely Peak age incidence is 5th – 6th decade Bone pain Pathologic fractures Hypercalcemia Neurologic manifestations Anemia Renal insufficiency Recurrent bacterial infections (encapsulated organisms) VISUAL IMPAIRMENT Tortuosity and distention of retinal veins Retinal hemorrhages and exudates Ocular Manifestations in Multiple Myeloma Ophthalmic Symptoms: Ocular symptoms may include diplopia, pain or pressure in the eye, ptosis, proptosis, or loss of vision Ophthalmic signs: Proptosis – orbital tumors Iris cysts or tumors Crystalline corneal deposits Retinal microaneurysms Hyperviscosity Retinopathy CRVO Bone Marrow Transplant Defective marrow must be destroyed by drugs (chemotherapy) or radiation. Cord blood cells High number of stem cells Less commonly cause GVH disease Less likely to transmit infection Can be stored instantly