4am and I can't sleep. 3 weeks of night shift has screwed up my clock for when I actually COULD sleep at night. 🙁
So for some idiot reason this thread was on my mind and I felt compelled to look up my old objectives from fall 1998 Clinical Medicine class. Found the Heme/Onc folder and my notes from the anemias/leukemias/lymphomas lecture (can't believe I didn't get some kind of repetitive motion disorder from all that handwriting) but didn't find the objectives which I wanted...must be another folder.
So instead I decided to post the brief notes from the powerpoint presentation on Leukocyte Disorders which I gave last fall to the PA students at Pacific U. in Forest Grove, OR (my alma mater). Of course medicine evolves and we know more than we knew 8 years ago, but the conceptual knowledge expected of us was the same.
FWIW, this type of lecture is typical of the PA didactic year.
Trail Pass made some compelling arguments that NPs shouldn't be expected to know the ins & outs of cancer, just to recognize that some cancers have telltale signs and these "Red flags" should tip off the NP that there may be a problem and s/he should refer. I disagree: especially as primary care providers I think the NP is at a distinct disadvantage not to know as much pathology as s/he can. Yes, "common things are common", but some uncommon things are not so uncommon that they shouldn't be taught. I myself knew the basics of Hodgkin's as a student, and certainly would consider it as a possibility in a patient with painless lymphadenopathy. To be fair, I didn't REALLY know and understand Hodgkin's well until I had a 17 yo softball player who came in with an unresolving cervical node for 3 weeks. She flunked the trial of antibiotics so she went to ENT. Even the ENT thought it was benign but sure enough, the FNA proved Hodgkin's. She (the patient) got the full workup and sure enough, she had Stage 3 disease with nodes in the pelvis. BUT because Hodgkin's is so responsive to treatment in most young'uns she did well and is about 3yr out from treatment and in college.
I interviewed 2 years ago for a teaching job in a PA program here in SC (um, the only PA program in SC). I didn't get the job but I did have a delightful interview with the medical director who taught me something valuable: his mantra to his students who continually asked "What should we know for the test?" He would just smile and say, "Know all you can." I loved that and have incorporated it into my own educational philosophy.
Being a PA is an exercise in lifelong learning. I expect it is the same for an NP. My educational bent is of course toward PAs because that's what I know best and that's how I was trained, and I think we as PAs benefit from a thorough exposure to pathophys. I agree we don't learn it to the cellular and biochemical level of the physician, a fact which has frustrated me as a practitioner and has spurred my own desire to go back to med school, but I do believe there is still a lot of good in what we do and how we train PAs to step in to the provider role in conjunction with other providers and our supervising physicians.
Now, happy reading:
Objectives: Disorders of Leukocytes
 Review normal WBC values and morphology:
 Neutrophil
 Lymphocyte
 Monocyte
 Eosinophil
 Basophil
Objectives
 2. Recognize the clinical presentation and laboratory findings of the following leukocyte disorders:
 Chronic Myelogenous Leukemia (CML)
 Acute Lymphocytic (Lymphoblastic) Leukemia (ALL)
 Chronic Lymphocytic Leukemia (CLL)
Objectives
 3. Recognize the clinical presentation and laboratory findings of the following lymphomas:
 Non-Hodgkins Lymphoma
 Hodgkins Disease
 Multiple Myeloma
Lymphomas: Non-Hodgkins
 Non-Hodgkins Lymphomas
 B-cell Lymphomas
 Precursor B cell lymphoblastic lymphoma
 Small lymphocytic lymphoma/ CLL
 Marginal zone lymphomas
 Nodal marginal zone lymphoma
 Extranodal MALT
 Splenic
 Hairy cell leukemia
 Follicular lymphoma
 Mantle cell lymphoma
 Diffuse large B cell lymphoma
 Burkitts lymphoma
 T-cell Lymphomas
 Anaplastic large cell lymphoma
 Peripheral T cell lymphoma
 Mycosis fungoides
Other Lymphomas
 Hodgkins Disease
 Multiple Myeloma
 Waldenstroms Macroglobulinemia
Hodgkins Disease: Overview
 Painless lymphadenopathy and lymphoid enlargement of liver and spleen
 Presence of Reed-Sternberg cells
 Related to EBV
 Bimodal age distribution
 Most common between 15-45 yo and after age 60
 More common in men between 15-45 yo
 4 major subtypes:
 Nodular lymphocyte predominant
 Nodular Sclerosis
 Mixed Cellularity
 Lymphocyte Depleted
Distinguish from other malignant lymphomas by pathology
Also consider: infectious mononucleosis, cat-scratch disease, drug reactions
Hodgkins Disease: Presentation
 Begins in a lymph node area, and progresses along the chain to contiguous areas of lymph nodes
 Cervical, supraclavicular, and mediastinal lymphadenopathy
 Stage A lack of constitutional symptoms
 Stage B 1/3 of patients present with constitutional symptoms
Hodgkins Disease:
Laboratory Findings
 Ann Arbor staging system
 Includes CT scans of neck, chest, abdomen, and pelvis
 Biopsy of bone marrow
 Presence of Reed-Sternberg cells confirm diagnosis
Reed-Sternberg Cell
Hodgkins Disease: Treatment
 Chemotherapy cures > 50%, even with advanced stage disease
 Radiation therapy cures 90% of stage IA and IIA disease
Non-Hodgkins Lymphoma
 Group of malignancies arising from cells in the lymphoid tissue
 90% of cases are from B-lymphocytes
 Higher incidence in patients with HIV and other immunodeficiencies
 Incidence has been rising 1-2% since the 1950s
 Peak incidence 20-40 y/o
Non-Hodgkins Lymphoma
 Lymphomas divided into two categories
 Indolent
 Aggressive
 Clinical Features
 Diffuse, painless, persistent lymphadenopathy is most common
 Common extralymphatic sites
 Constitutional symptoms less common than in Hodgkins
 Laboratory
 Persistent, unexplained nodes should be biopsied
Non-Hodgkins Lymphoma
 Treatment
 Radiation therapy may cure indolent lymphomas, but usually limited role
 Aggressive lymphomas require aggressive combination chemotherapy
 Prognosis
 6-8 years in indolent lymphomas
Multiple Myeloma
 Bone marrow is replaced by malignant plasma cells
 Monoclonal protein in serum
 Proteinuria
 Lytic lesions in bones
 May be caused by a new herpes virus
 Older adults median age is 65 (rare under age 40)
 Equal incidence in men and women
Multiple Myeloma
 Signs and symptoms
 Normochromic normocytic anemia
 Normoblasts may be present in blood
 Leukocyte count slightly decreased, normal, or slightly increased
 Elevated ESR
 Striking feature: Rouleaux formation
 Bone pain, back and ribs, sternum
 Infection (esp. encapsulated organisms e.g. S. pneumoniae; H. influenzae)
 Rouleaux
Multiple Myeloma
 Physical Exam
 Pallor
 Bone tenderness
 Soft tissue masses
 May have neuro symptoms if spinal cord is compressed
Multiple Myeloma
 Labs
 Anemia (normochromic normocytic)
 Neutrophils and platelets are normal at onset
 HALLMARK: paraprotein on serum protein electrophoresis (SPEP) (M spot)
 Bone marrow with plasma cell infiltration
 Bone x-ray
 Hypercalcemia
 Renal failure
 Amyloidosis in 10-15% of MM contributes to RF
MM: Bone Marrow Aspiration
Multiple Myeloma
 Treatment
 Palliative for bone pain
 Autologous stem cell transplantation for patients < 60 y/o
 Prognosis is poor
 Median survival 3 years
And finally
 A few more that were not listed on your objectives, but are mentioned in Current, so I suppose theyre fair game
 (Bonus questions anyone??)
Waldenstroms Macroglobulinemia
 Nonspecific symptoms
 Splenomegaly common
 Monoclonal IgM paraprotein
 Plasmacytic lymphocytes infiltrate bone marrow
 Absence of lytic bone disease
 Malignant B cell disease; hybrid of lymphocytes and plasma cells
 Insidious onset in 60s & 70s
 Fatigue related to anemia
 Mucosal & GI bleeding secondary to engorged blood vessels, platelet dysfunction
 +/- HSM, LAD; retinal veins engorged; purpura may be present; no bone tenderness
 Anemia universal; Rouleaux formation common
 Monoclonal IgM spike on SPEP in beta or gamma globulin region
 Serum viscosity sometimes significantly increased (4-6x H2O)
 Treatment and survival rates variable; median survival 3-5 years
Myelofibrosis
 Bone marrow becomes fibrotic
 Platelet-derived growth factor (PDGF)
 Extramedullary hematopoiesis in liver, spleen, lymph nodes
 Dry tap
 Teardrop poikilocytosis on peripheral smear
 Myeloproliferative, toxin, infection
 Adults over age 50; insidious onset
 Fatigue due to anemia; abdominal tenderness due to splenomegaly (often massive)
 Uncommon: bleeding, bone pain
 WBC count is variable
Myelofibrosis
 No specific treatment
 Transfusion for anemia
 Androgens may boost blood counts (poorly tolerated in women)
 Allogeneic bone marrow transplantation
 Median survival from time of diagnosis: 5 years
 End-stage: generalized debility, liver failure, bleeding from thrombocytopenia
 Some cases terminate in AML
Myelodysplastic Syndromes
 Cytopenias with hypercellular bone marrow
 2 or more hematopoietic cell lines have morphologic abnormalities
 Acquired clonal disorders of hematopoeitic stem cell
 Usually idiopathic
 May be seen after cytotoxic chemotherapy
 Ineffective hematopoeisis occurs
 Ultimately may evolve into AML; preleukemia
 Usually over age 60; may be asymptomatic
 Ultimately fatal disease (infections, bleeding)
Hairy Cell Leukemia
 Pancytopenia
 Splenomegaly, often massive
 Hairy cells on blood smear and esp. in bone marrow biopsy
 Uncommon indolent B-cell lymphocytic cancer
 Middle-aged men (median age 55)
 Striking 5:1 male predominance
 Anemia universal; 75% thrombocytopenia and neutropenia
 Dry tap on bone marrow
Hairy Cell Leukemia
 Distinguish from other lymphoproliferative diseases (Waldenstroms macroglobulinemia, non-Hodgkins lymphomas)
 Treatment: cladribine (2-chlorodeoxyadenosine; CdA); relatively nontoxic with benefit in 95%; complete remission > 80%
 Long-lasting response with most patients surviving > 10 years with current treatment modalities
Review and Questions
