Exam 3 Flashcards
(219 cards)
1
Q
Key feature in bone marrow for myelodysplastic syndromes (MDS)
A
- Normocellular or hypercellular bone marrow
2
Q
What type of cancer(s) does MDS have a high risk of transformation to?
A
- Acute leukemias. When this occurs, prognosis is poor.
3
Q
Etiology of MDS
A
- Vast majority occur de novo with unclear cause
- Secondary: genetic, environment, antineoplastic drugs
o Alkylating agents almost always cause MDS prior to AML. Latency 3-7 years.
o Topoinhibitors present with AML rather than MDS. Latency 1-2 years.
4
Q
Are blast cells present in MDS?
A
- Yes, but not sufficient % as in leukemia.
5
Q
Signs and symptoms of MDS
A
- Note, MDS can present with cytopenias from any / all cell lines
- Anemia (SOB, pallor, tiredness, weakness etc.)
- Infections (neutropenia)
- Bleeding manifestations (thrombocytopenia – if low ~ 5, 10, 20, not 120)
- Organomegaly, lymphadenopathy
- Sweet’s syndrome: skin papules d/t neutrophil infiltration
6
Q
Lab features of MDS
A
- Bone marrow: dyspoeisis of any / all of cell lineages (abnml WBC, RBC or platelet precursors), excess BM blasts, fibrosis (different to myelofibrosis)
- Peripheral blood: cytopenias, iron studies to confirm anemia not d/t ACD, IDA etc., can see giant platelet, pseudo-Pelger Huet anomaly in neutrophil, ringed sideroblasts (last three items on list unimportant to memorize)
7
Q
Differential diagnosis of MDS
A
- Vit b12 and folate deficiency – if severe, can drop platelets and neutrophils
- Viral infections (esp HIV, hep can cause cytopenias)
- Chemo agents
- Etoh exposure (if chronic and heavy)
- Lead
- Benzene
- EPO agents and G-CSF can induce marrow hyperplasia and hypergranularity
8
Q
Antineoplastic agent class that more commonly leads to MDS
A
- Alkylating agents. Latency period of 3-7 years.
9
Q
Screening of MDS
A
- Based on # of blasts, karyotype of abnormal cells in BM and how many cytopenias.
- This is the IPSS (international prognostic scoring system). This determines medial survival and 25% AML progression
10
Q
What is 5q- syndrome? Lab findings? Prognosis? Treatment?
A
- Predominant in females
- Lab Abnormalities = typically elevated platelets (can be normal), macrocytic anemia and leukopenia
- Key per Hughes = females, elevated platelets
- Prognosis: favorable, transformation to AML less common than other MDS subtypes.
- Treatment: non-standard MDS, treat iron overload, volume
11
Q
Is MDS a disease of youth?
A
- No. Almost always in 60-70 age group
12
Q
What is CMML? Lab findings?Treatment?
A
- Form of MDS/MPD
- Lab: increased monocytes in BM and peripheral smear with varying degree of myelocyte dysplasia.
- Tx: can tx with imatinib (Gleevec), a CML treatment. Otherwise, use MDS tx.
13
Q
MDS subtypes
A
- Majority = normocellular or hypercellular bone marrow
- 5q- syndrome: platelets high
- CMML: + monocytes
- Hypocellular MDS: resembles aplastic anemia
14
Q
What is hypocellular MDS?
A
- Small % of MDS patients. Symptoms are same as hypercellular MDS, resembles aplastic anemia except for presence of dysplasia, abnormal karyotype and immature precursors.
15
Q
Did Hughes say not to remember any treatments?
A
Did Hughes say not to remember any treatments?
16
Q
What are myeloproliferative disorders? Compare with MDS?
A
- MPD: overproduction of one or more cell line, normal maturation
- MDS: normocellular / hypercellular bone marrow with cytopenia or one or more cell line, abnormal dyspoiesis (with abnml maturation)
- Both have risk for acute leukemia transformation
17
Q
Types of MPD disorders. Describe the genetic defect in each?
A
- CML: translocation b/w 9 and 22 = Philadelphia c/s with BCR-ABL formation, a constitutively active tyrosine kinase
- Polcythemia vera: JAK2 mutation >90% of the time
- Essential thrombocytosis: JAK2 mutation ~40-50% of the time
- Primary myelofibrosis
18
Q
CML. Pathogenesis, symptoms, labs, phases, diagnosis, treatment
A
- Pathogenesis: MPD; translocation b/w 9 & 22 = Philadelphia c/s w/ BCR-ABL formation, a constitutively active tyrosine kinase
- Sx: fatigue, nightsweats, weight loss, splenomegaly, anemia and / or platelet dysfunction. If hyperleukocytosis: dizziness, light-headedness
- Labs: If elevated WBCs and basophilia, think CML. Officially: neutrophilia, immature circulating myeloid cells, absolute basophilia, eosinophilia common, elevated LDH/uric acid
- Phases:
a. Chronic phase: blast cells 10%, progressive splnomegaly, weight loss, fevers, bone pain, increasing counts unresponsive to therapy
c. Blast phase: blood or BM blasts > 20% - Dx: BCR-ABL mutation critical for dx, check BM for increased myeloid:erythroid ratio and basophilia
- Tx: TKIs such as imatinib (Gleevec)
19
Q
Polycythemia vera. Pathogenesis, symptoms/signs, diagnosis, treatment
A
- Pathogenesis: MPD; JAK2 mutation (90% of the time) leads to elevated RBC mass. Also concomitant increase in WBC and platelets. Hyperviscosity.
- SSx: pruritis, erythromelagia (redness, burning pain) typical to hands and feet, venous/arterial thrombosis, GI complaints, headaches/dizziness and vision change d/t hyperviscosity. Signs = HTN, splenomegaly, hepatomegaly, cutaneous ulcers, gouty features, pulmonary HTN.
- Dx:
a. Major: Hgb > 18.5 men, > 16.5 women; presence of JAK2 mutation
b. Minor: BM with hypercellularity and trilineage growth; serum EPO below ref range
c. Requires both major + 1 minor OR 1st major with 2 minor - Tx: phlebotomy + low dose ASA; then risk-adjusted therapy which may include cytoreductive therapy such as hydroxyurea or IFN-alpha (not commonly used). If childbearing, don’t give hydroxyurea
20
Q
How does polycythemia vera and essential thrombocytosis differ?
A
In ET, more so just elevated in platelets.
- Men > women for PV
- Women > men for ET
21
Q
Essential thrombocytosis. Pathogenesis, symptoms/signs, diagnosis, treatment
A
- Pathogenesis: MPD; JAK2 mutation leads to isolated increase in platelets. Other cell lines normal.
- SSx: vasomotor (visual disturbance, dizziness, headaches, erythromelagia, cutaneous ulcers); thrombotic (arterial or venous); hemorrhage (commonly GI tract) although platelets high; first TM spontaneous abortion
- Diagnosis: sustained platelet count >= 450 K, BM biopsy showing increase mature large megakaryocytes, no WHO for PV, JAK2 or if absent, no evidence of reactive thrombocytosis
- Tx: hydroxyurea, IFN-alpha (pregnant)
22
Q
Differential diagnosis for essential thrombocytosis
A
- IDeficiency, infection, inflammation, surgery, trauma, tissue injury/infarct, malignancy, post-splenectomy
23
Q
Which MPD has the worse prognosis?
A
- Primary myelofibrosis, no therapies found to prolong survival
24
Q
What is primary myelofibrosis?
A
- Marrow fibrosis and extramedullary hematopoiesis
25
Primary myelofibrosis. Pathogenesis, symptoms/signs, diagnosis, treatment
- Pathogenesis: worst of all MPD; ? pathogenesis (JAK2?) – hallmarks = marrow fibrosis and extramedullarly hematopoiesis
- SSx: fatigue, hyperuricemia, splenomegaly, portal HTN, anemia, secondary iron overload
- Diagnosis: BM, CBC
- Tx: no therapies found to prolong survival – supportive/palliative tx: epo, iron chelation, splenectomy/irradiation, JAK2 inhibitors, allo stem cell transplant (rare to do this d/t age)
26
Name the plasma cell dyscrasias
- MGUS
- Multiple myeloma
- Plasmacytoma
- Amyloidosis
- Waldenstroms macroglobulinemia
27
What is the pre-cursor disease to multiple myeloma?
- MGUS
28
What is multiple myeloma?
- Cancer of plasma cells – there is an overgrowth of abnormal plasma cells leading to overproduction of immunoglobulins (M protein).
29
In what population(s) is multiple myeloma more common?
- Men, AA, avg age ~ 65
30
Which is the most common Ig produced in multiple myeloma?
- IgG > IgA > light chain only (kappa, lambda)
31
What is MGUS?
- Monoclonal gammopathy of undetermined significance
| - It is a pre-cancerous condition w/o symptoms that has a 1% chance per year of developing into a myeloma
32
Multiple myeloma symptoms?
- Bone pain/fractures d/t lytic lesions (seen only on skeletal survey, not bone scane)
- Numbness / tingling lower back / legs
- Weight loss
- Weakness, N, V, AMS
- SOB, fatigue
- Urinary issues
33
Diagnostic criteria for multiple myeloma
1. Multiple myeloma (requires all three criteria)
- Presence of M protein in serum or urine
- Presence of clonal plasma cells in BM or a plasmacytoma
- Presence of end organ damage (increased calcium, lytic bone lesion, anemia, renal failure)
2. Smoldering (asymptomatic) multiple myeloma (both must be met)
- Serum M protein >= 3 g/dL and / or >= 10% to
34
Is multiple myeloma curable?
- No. Patients live with it given treatment.
- Allogeneic transplant shown in past to cure. Not commonly done as drugs prolong life span quite well. Complication and death rate with transplant is high.
35
Tx of multiple myeloma?
- Smoldering: watch and wait – observe Igs, CBC etc.
- Mostly steroids, immunomodulators, chemo (is later line of tx if necessary), bisphosphonates, radiation. BM transplant not common (usually auto if any).
- Note: tx dependent on risk. Also role for maintenance therapy.
36
What is a plasmacytoma?
- Plasma cell cancer that is isolated into a discrete mass. Can be bone or soft tissue.
- Bone: in humerus > femur > pelvis > vertebra
- Soft tissue: upper respiratory site (most common), also in GI, CNS, bladder, thyroid, breast, testes, parathyroid or LNs
37
Lab diagnosis for plasmacytoma?
- No or low levels of M protein (monoclonal Igs) in serum or urine. Rarely are heavy chains elevated. Serum free light chains may be elevated.
- Biopsy with clonal plasma cells
- Absence of end organ damage
- Bone marrow with no evidence of plasma cells
38
Tx of plasmacytoma
- Radiation therapy for both bone or soft tissue
| - Surgical removal of plasmacytoma if extramedullary
39
What is amyloidosis?
- Protein conformation disorder associated with clonal plasma cell disorder. Result = deposition of light chain fragments in insoluble form leading to impaired organ function.
- ~ 10% of patients with myeloma have concurred amyloidosis
40
Most common symptoms with amyloidosis?
- Nephrotic syndrome
- Restrictive cardiomyopathy (associated with the worst prognosis ~ 6 mos)
- Peripheral neuropathy, hepatomegaly, macroglossia, purpura (supposed to be a classic sign, but almost never shows up)
41
Diagnosis of amyloidosis
- +ve Congo stain of biopsy w/red-green birefringence under polarized light
- note, this isn’t very sensitive
42
Tx of amyloidosis
- No optimal treatment. Tx aimed to retard further deposition of protein.
43
What is Waldenstroms macroglobulinemia?
- Plasma cell disorder with macroglobulinemia, ie. excess IgM production in bone / blood + lymphoplasmacytic lymphoma in marrow
44
Symptoms of Waldenstroms macroglobulinemia?
- Related to IgM (very large molecule): neuropathy, Coombs pos hemolytic anemia (autoimmune mediated), GI bleed, hyperviscosity (dizziness, light headedness, CVA), cytopenias, LA, hepatosplenomegaly
45
Diagnosis of Waldenstroms macroglobulinemia?
- IgM monoclonal gammopathy
| - Bone marrow > 10% monoclonal lymphocytes and plasma cell differentiation
46
Tx of Waldenstroms macroglobulinemia?
- Asymptomatic = observation
- Symptomatic = chemo, plasmapharesis
- Incurable
- Does not convert to multiple myeloma (low yield I think)
47
Most common childhood cancers
- Leukemia (ALL) 0-14 years; 15-19 (Hodgkin lymphoma)
- CNS
- Soft tissue
- Other: non-Hodgkin, kidney, bone, Hodgkin
48
Known causes of cancer in children
- Neurofibromatosis (optic pathway gliomas)
- Familial polyposis (FAP gene – common cause of hepatoblastoma in children) – in adults causes Lynch syndrome (colon cancer)
- Li-Fraumeni syndrome (p53 mutation)
* most we don't know what causes them
49
Hypertension in child leads you to think about what cancer (s)?
- Renal (Wilms) or abdominal tumor (adrenal tumor d/t NBL)
50
Weight loss, sudden onset in child leads you to suspect what cancer(s)?
- Any malignancy
51
Petechiae in child leads you to suspect what cancer(s)?
- Leukemia, NBL
52
Adenopathy unresponsive to abx in child leads you to suspect what cancer(s)?
- Leukemia, lymphoma
53
Endocrine abnormalities in child leads you to suspect what cancer(s)?
- Pituitary tumors, hypothalamic tumors, gonadal tumors, adrenal tumors
54
Eye symptoms/signs (white spot, proptosis, blindness, wandering eye, intraorbital hemorrhage) in child leads you to suspect what cancer(s)?
- Retinoblastoma, metastatic neuroblastoma, rhabdomyosarcoma (or other soft tissue sarcoma)
55
Ear symptoms/signs (bulging mass external canal, mastoid tenderness/swelling) in child leads you to suspect what cancer (s)?
- Langerhan cell histiocytosis, rhabdomyosarcoma
56
Puffy face and neck in child leads you to suspect what cancer(s)?
- Mediastinal tumors leading to SVC syndrome
57
Pharyngeal mass in child leads you to suspect what cancer(s)?
- Rhabdomyosarcoma, lymphoma, nasopharyngeal cancer
58
Periodontal mass and loose teeth in child leads you to suspect what cancer(s)?
- Langerhan cell histiocytosis, Burkitt’s lymphoma, neuroblastoma, osteosarcoma
59
Thoracic findings (mass, cough, SOB w/o fever or no hx of asthma, allergies) in child leads you to suspect what cancer(s)?
- Soft tissue tumors, mediastinal tumors, metastatic tumors
60
Abdominal/pelvic masses in child leads you to suspect what cancer(s)?
- Wilms’ tumor, soft tissue sarcoma, neuroblastoma, hepatoblastoma, hepatocellular carcinoma
61
GU findings (testicular/vaginal mass, masculinization/feminization) in child leads you to suspect what cancer(s)?
- Germ cell tumor, rhabdomyosarcoma, adrenal tumor
62
Musculoskeletal findings (soft tissue/bone marrow) in child leads you to suspect what cancer(s)?
- Osteosarcoma, Ewings sarcoma, leukemia, neuroblastoma, soft tissue sarcoma
63
CNS symptoms/signs concerning for brain tumors in children
- Seizures, weakness, difficulties with coordination. If interfere with CSF circulation = increased ICP = HA (esp morning or with wake) and vomiting
- Signs: papilledema, optic atrophy, loss of vision, head circumference increase, bulging fontanelles, spreading sutures, setting sun (Parinaud syndrome), increased BP, low pulse
64
Abnormal lymphadenopathy in children
- Generalized
- Regional non-head and neck = more likely malignant
- Posterior auricular, epitrochlear or supraclavicular = abnormal. Also mediastinal.
65
Bone pain in children leads to suspicion for what cancer(s)
- Ewing’s sarcoma, osteosarcoma, ALL (30% of patients)
66
What is the most common malignancy in childhood? Which populations are at risk?
- ALL, peak age 2-5 years of age
- Caucasian > AA; highest in Hispanics; males > females; trisomy 21; pre-natal exposure to x-rays and post-natal high dose radiation
67
Pathogenesis of ALL
- Lymphoid progenitor cell is genetically altered and undergoes dysregulated proliferation and expansion. Occurs in B and T cells. More commonly B cells (85%).
- Thought to arise in bone marrow, but blasts at presentation can be in liver, spleen, lymph nodes, testes and CNS
68
Signs/symptoms for ALL in children
- Bone marrow infiltration = anemia (pallor, lethargy, dyspnea, murmur), thrombocytopenia (bleeding, petechiae, purpura), neutropenia (fevers, infections), bone pain (limp, less walking regression to crawling, irritability) - ~30% of time
- Extramedullary: lymphadenopathy, hepatosplenomegaly, lung (orthopnea, cough, mediastinal mass, trach compression), facial never palsy, testicular enlargement, skin lesions, gingival hypetrophy
69
How is ALL diagnosed in children?
- CBC shows lymphocytosis in ~ 50% of cases. ~80% have lymphoblasts on peripheral smear. 95% will have >=2 cytopenias. Small percentage have only 1 cytopenia and smaller proportion have a normal CBC and diff.
70
Differential diagnosis for leukemia
- Mono (EBV)
- Acute anemia
- Parvovirus B19
- ITP
71
How does B-cell ALL differ to T-cell ALL presentation?
- B-cell ALL: BM involvement primarily w/ extramedullary involvement frequent – see other flash cards for Ssx.
- T-cell ALL: mediastinal mass common, also extramedullary involvement
72
High risk B-cell ALL patient
- WBC > 50 K
| - > 10 years of age or
73
Outcomes/prognosis of ALL
- >95% attain remission w/75-85% 5 years survival
| - Tx effects = osteonecrosis/osteopenia, neuropathies, neuropsych, obesity
74
What tumors are the most common solid tumor of childhood?
- Brain tumors
75
Most common brain tumor
- Astrocytoma (associated with NF-1 in 50-80% of cases)
76
Posterior fossa brain tumor signs/symptoms in children
- Ataxia, tremors, dysarthria, stiff neck, papilledema
77
Brainstem brain tumor signs/symptoms in children
- Extremity weakness, CN signs (double vision, facial weakness, swallowing dysfunction)
78
Clinical features of hemispheric tumor
- Hemiparesis, hemianopsia, aphasia, seizures
79
Risk factor of brain tumors in children
- Radiation to head/neck (survivors of childhood leukemias)
80
Brain tumors with best prognosis in children? Worst?
- Low-grade astrocytoma and medulloblastoma (in std risk pt) = best prognosis
- Brain stem gliomas
81
Which cancer is a leading cause of morbidity and mortality in pediatric cancers?
- Brain tumors
82
What is the 2nd most common abdominal malignancy in children?
- Wilms’ tumor
83
What is a Wilms’ tumor? What mutation has occurred?
- 2nd most common abdominal malignancy in children. This is a renal tumor.
- Mutation in WT1 (tumor suppressor gene) predisposes to embryonal tumor formation.
84
Population at risk for Wilms’ tumor
- AA, peak age 2-3 (rare > 5)
85
Clinical associations of Wilms’ tumor
- Hemihypertrophy
- Aniridia: absence of iris
- Denys-Drash syndrome: GU anomalies and renal failure
- Beckwith-Wiedemann syndrome: overabundance of IGF2, leads to kidney, adrenal and liver problems, resulting in severe hypoglycemia. Characterized by microcephaly, macroglossia and umbilical hernia.
86
Physical exam findings for Wilms’ tumor
- Large palpable abdominal mass. Be careful you don’t rupture the tumor.
87
SSx of Wilms’ tumor presentation
- HTN, gross hematuria and fever. If hemorrhaged into tumor, present with signs of anemia, hypotension and fever.
88
Prognosis for Wilms’ tumor
- 80-90% survival with current tx scheme.
89
Location of neuroblastomas
- Any neural crest derived tissue (from ectoderm): adrenal, paraspinal SNS tissue.
- Mets to: bone, BM, LNs, skin, liver
90
Signs and symptoms of neuroblastomas
- Irritability, weight loss, bone pain, fever, pallor, proptosis, bone lesions, periorbital ecchymoses (raccoon eyes)
- Large abdominal masses, LE weakness (d/t spinal cord compression), high thoracic/cervical mass presents with Horner’s syndrome (miosis, ptosis, anhydrosis)
91
What is the most common extra-cranial solid tumor in children?
- Neuroblastoma
92
Age presentation of neuroblastoma in children?
- 75%
93
What are poor prognostic indicators for neuroblastoma in children?
- Age > 18 months, myc-N amplification, unfavorable histology
94
What tests are useful in diagnosis of neuroblastoma?
- Urine catecholamines: HVA, VMA
- Imaging
- BM biopsies
- LN evaluation
95
What is the most common soft tissue sarcoma in children?
- Rhabdomyosarcoma (from mesenchymal original)
96
Signs and symptoms of rhabdomyosarcoma
- Depend on age and site
- Head neck: proptosis, periorbital swelling, CN palsies, hearing loss, chronic aural/sinus drainage
- GU: hematuria, urinary obstruction, painless mass (paratesticular), abdominal pass, vaginal mass, vaginal bleeding/discharge
97
What is Ewing’s sarcoma? Presentation?
- Soft tissue sarcoma more common in males. Aka small round blue cell tumor (PNET).
- Presents with pain, swelling, frequently after a sport-related injury
98
Presentation of Hodgkin’s disease in children
- More common in adolescents than young child
- Location of cancer: painless LA (cervical, supraclavicular, below diaphragm / spleen), mediastinal mass, LNs, liver lung and bone marrow.
- Sx: painless LA (see above), fevers, night sweats, weight loss, pruritus
99
Types of leukemias
- Divided by cell types involved
1. Myeloid line: granulocytes, monocytes, erythrocytes, megakaryocytes
2. Lymphoid line: B-cells, T-cells
100
Incidence of AML?
- + 65 years old: 12.2 per 100K
| - males > females
101
Which disease has better survivorship: ALL or AML?
- ALL (65 vs 25% 5 year survival)
102
Genetic abnormalities that predispose to acute leukemia
- Trisomy 21 (1 in 700)
- Klinefelter’s (1 in 750)
- Others = Fanconi’s anemia, Bloom’s syndrome, Familial RUNX1 mutations, Turners, NF
103
Cancers that can predispose to acute leukemia
- MDS (pre-leukemia), myeloproliferative syndrome (PV)
104
Environmental exposures that can predispose to acute leukemia
- Chemicals: eg. benzene
- Radiation
- Tobacco
- Chemotherapy
105
What is the most common leukemia in adults?
- CLL
- 4.2 per 100K – under reported!
- 5 year survival = ~80%
106
Acute leukemia presentation
- General fatigue (weeks to months)
- Pallor
- Weakness
- Bone pain
- Fever/infection
- Petechiae, ecchymoses, infiltration of skin (AMML)
- Sweet’s syndrome: red nodules and plaques on skin (d/t infiltration of neutrophils)
- Retinal hemorrhage or white plaques
- If CNS involvement: HA, CN palsy, visual changes
- Oral: wet purpura, gum infiltration (excess of monocyte deposition)
- Organomegaly not common
- Joint arthralgia
- Myeloid sarcoma (
107
Auer rods think…
- AML. These are cellular inclusions
108
Leukemia cutis skin findings is shown in what disease
- AML
109
Most common site for bone marrow biopsy to diagnose acute leukemia
- Posterior iliac crest
| - Ant iliac crest more dangerous, sternum not recommended at all!
110
We had adequate therapy to treat leukemias, does that mean that every leukemia patient should be treated?
- No. It is important to remember a few things, one of them being the mortality rate during the induction of chemo in the first 28 days. Depending on the patients performance status (ECOG), death rate can be high. Patient needs to be advised of this.
- 69 with poor performance status (>=3) = ~60% chance of dying in the first 28 days
- 5 year survival based on molecular risk factors needs to be taken into account and that information provided to the patient
111
William Damesheck and AML tx
- Must give big enough dose of chemo to get rid of leukemia in the bone marrow.
112
Describe general tx for AML
1. Standard induction: 7+3
- 7 days of ara-C + 3 days of anthracycline (dauno- or idarubicin)
2. Consolidation: high dose ara-C
3. Bone marrow transplant (to salvage bone marrow)
4. If Ph+ (Philadelphia c/s), then add TKI
113
What is important to remember about blood products that AML patients receive?
- Must irradiate them all to prevent GVHD
114
What is tumor lysis in AML?
- Side effect of induction therapy. Leads to hyperuricemia = kidney stones, renal failure.
115
How is APL (acute promyelocytic leukemia) treated? Same as AML?
- Not standard: induction + consolidation + transplant
- First give all trans-retinoic acid (ATRA), a maturation agent prior to starting 7+3 tx
- Observe for APL differentiation syndrome: edema, pleural effusion, lung infiltrates. Tx with steroids
116
What is a fairly common presentation with APL (acute promyelocytic leukemia) in addition to the other more common signs/symptoms?
- DIC. If patient presents with leukemia w/DIC, it is likely APL
117
Factors for which ALL has worse prognosis
- Age > 35
- Leukocytosis > 30 K for B-cells or > 100 K for T-cells
- Certain karyotypes
- Time to remission > 4 weeks: usually remits pretty quickly w/tx
118
Does AML require maintenance therapy?
- No. ALL does
119
Pathogenesis of CML
- Philadelphia c/s resulting from switch bw 9 and 22 = extra-short 22 and extra-long 9. BCR-ABL on 22 produces excess tyrosine kinase promoting cell growth
120
Tx for CML
- TKIs (example: imatinib (Gleevec), dasatinib, nilotinib)
121
Review L32 case
Review L32 case
122
Identify structural red cell abnormalities on a peripheral blood smear and describe clinical association. Review powerpoint.
Identify structural red cell abnormalities on a peripheral blood smear and describe clinical association. Review powerpoint.
123
Lab values for iron deficiency anemia
- Low H&H
| - MCV low
124
Differential diagnosis for microcytic anemia
- IDA
- Thalassemia
- Anemia of chronic dz
- Hemoglobinopathy
- Sideroblastic anemia
125
What is the most common anemia in the world?
- Iron deficiency anemia
126
Tx plan for iron deficiency anemia
- Tx the cause
- Replace the blood (transfuse,
a. Transfuse: upper GI bleed w/ or w/o portal HTN, should only receive blood when Hb drops below 7 g / dL
b. Oral iron / parenteral iron
- Retic count should rise in 1 week, Hb rises by week 2. Continue iron therapy until stores are replete
127
Lab values for B12 deficiency anemia
- Low H&H
- MCV high > 100
- Retic count low
- B12 low
- Folate nml
- High methylmalonic acid, high total homocysteine
128
Differential diagnosis for macrocytic anemia
1. Megaloblastic: B12/folate deficiency, meds (metformin, triamterene, valproic acid, TMP-SMX)
2. Non-megaloblastic: MDS, liver dz, hypothyroidism, etoh
129
Causes of vit B12 deficiency
- Most common: pernicious anemia
- Malabsorption
- Atrophic gastritis
130
Tx plan for B12 deficiency
- Parenteral injection/enteral dosing
- Response: retic count increases by end of week 1, megaloblastic anemia corrects in 6-8 weeks.
- Pernicious anemia/malabsorption is life-long tx
131
Lab values for G6PDH deficiency anemia
- Low Hb
- MCV nml
- Ferritin nml, serum iron nml, TIBC nml, transferring sat nml
- Retic count high
- Direct coombs neg
- Lactate DH high
- Total bili high
- Indirect bili high
- Direct bilin ml
- Serum haptoglobin low
132
Differential diagnosis for normocytic anemia
1. Hemolytic:
a. Intrinsic: membrane defect (spherocytosis), enzyme deficiencies (G6PDH), hemoglobinopathies (SC dz)
b. Extrinsic: autoimmune, alloimmune, non-immune (splenomegaly, physical trauma, infections)
2. Non-hemolytic: acute blood loss, aplastic anemia, anemia of chronic disease, chronic renal insufficiency
133
Is anemia of chronic disease microcytic or normocytic?
- Both
134
Bite cells, Heinz bodies indicates what?
- Hemolytic anemia, bite cells = G6PDH deficiency
135
What is the most common enzymatic disorder of RBCs in humans?
- G6PDH deficiency
136
Triggers of acute hemolytic anemia in G6PDH deficiency
- Fava beans, infections, drugs (many sulfa, antimalarials)
137
Tx of G6PDH deficiency
- Prevention of exposure (fava beans, infection, drugs)
- If stable, no specific tx
- If anemia severe – transfuse
- If acute renal failure – hemodialysis
138
Review cases L33 by O’Shea
Review cases L33 by O’Shea
139
Over 90% of the lymphoid neoplasms in the world are of what cell type?
- B-cell lymphomas
140
Lymphomas that originate the in the germinal center
- Follicular lymphoma, Burkitt lymphoma, large cell lymphoma
141
Lymphomas that originate in the mantle zone
- Mantle cell lymphoma
142
Follicular lymphoma. What is it? Common in what age group? Clinical findings? Immunophenotype?
- B cell lymphoma in the germinal center of lymph node. Low grade = mostly centrocytes, high grade mostly centroblasts
- Common in: middle age
- Clinical: peripheral and central LA, slenomegaly, BM findings (up to 70%), peripheral blood findings (up to 10% of time)
- Immunophenotype: B cell (CD19/20), CD10 (germinal center marker), Bcl-2. Note: neg for CD5 and 3
143
What is bcl-2?
- Anti-apoptotic protein. Pos in follicular lymphoma
144
Mantle cell lymphoma. What is it? Common what in what group? Clinical findings? Immunophenotype?
- B cell lymphoma in the mantle zone of the lymph node.
- Presents in 5th/6th decade of life, male predominant
- Clinical: generalized LA, BM involvement, liver involvement commonly, lymphocytosis (~30% of patients), splenomegaly (~50%), small bowel involvement (not key)
- Immunophenotype: B cell (CD19/20), CD5, cyclin D1. Neg for CD23 and CD3
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What is cyclin D1?
- Pro-proliferative marker, pos in mantle cell lymphoma
146
Burkitt lymphoma. What is it? 3 types – epidemiology and clinical findings? Pathology findings and Immunophenotype? Prognosis?
- B cell lymphoma in the germinal center
- 3 types
a. Endemic (African): equatorial Africa, commonly childhood malignancy (4-7 yo group), EBV+ majority of time
- Presentation: 50% jaw/facial bone involvement, also ovaries, kidneys and breast frequently.
b. Sporadic (non-African, non-endemic): worldwide, children/young adults – median = 30 yo
- Presentation: abdominal masses in ileo-cecal region w/involvement of ovaries, kidneys and breast frequently. Rarely jaw involvement
c. Immunodeficiency: commonly with HIV infection (often first manifestation of AIDS)
- Presentation: nodular localization and involvement of BM frequent
- Pathology: DIFFUSE MONOMORPHIC INFILTRATE, TINGIBLE BODY MACROPHAGES (STARRY-SKY PATTERN)
- Immunophenotype: B cells (CD19/20) and CD10 (germinal center). Neg for Bcl-2. Pos for c-myc overexpression.
- Prognosis: aggressive (med emergency), responds well to therapy. Cure rates 70-90% depending on stage.
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CD10, CD19 and CD20 positive is what lymphoma
- Burkitt lymphoma
| - If Bcl-2 positive with above = follicular lymphoma
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Adult T-cell leukemia/lymphoma. What is it? Cause? Where is it seen? Clinical findings? Immunophenotype/pathology findings? Prognosis?
- Mature T cell lymphoma
- HTLV-1 virus
- Central Africa, Caribbean, SW Japan, uncommon in US (if seen – cities, FL)
- Clinical: LA, skin lesions, hepatosplenomegaly, lymphocytosis, hypercalcemia
- Immunophenotype: CD4+, flower cells w/HTLV-1 provirus in tumor
- Prognosis: death in 1 year despite chemo
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Mycosis fungoides (Sezary syndrome). What it is? Clinical findings? Pathology/Immunophenotype?
- Mature T-cell lymphoma, indolent dz
- Clinical: one dz with two manifestations that overlap. Skin always involved. Lesions start with premycotic (plaque/patch) phase with a few neoplastic lymphoid cells in epidermis. Tumor phase occurs with tumor masses predominantly in the dermis. Involvement in LN and BM as disease progresses. Also seen is exfoliative erythroderma.
- Pathology: folded nuclear membrane
- Immunophenotype: CD4+
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T lymphoblastic leukemia/lymphoma. What is it? Clinical findings? Pathology/immunophenotype?
- Immature T-cell lymphoma/leukemia
- Clinical: 85% presents as mas (lymphoma) on mediastinum w/cervical LNs. 15% present as leukemia w/symptoms similar to B-ALL. Sx between the two are similar except T-ALL presents with anterior mediastinal mass. Note: T-ALL is a medical emergency.
- Pathology: sheet of blasts in LNs, soft tissue or BM
- Immunophenotype: CD34, TdT, CD1a and cytoplasmic CD3 positive
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Anaplastic large (T) cell lymphoma (ALCL). What is it? Clinical findings? Pathology/immunophenotype?
- Immature T cell, non-Hodgkin lymphoma
- Clinical: LN and extranodal site involvement, less commonly mediastinal mass.
- Pathology: pleomorphic with characteristic “Hallmark” cells (medium, abundant cytoplasm, kidney sized nuclei, paranuclear eosinophilic region
- Immunophenotype: ALK-1 +ve in children/young adults w/better prognosis; ALK-1 –ve in elder adults w/poorer prognosis. CD30+, EMA+ and CD3 neg.
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Hodgkin’s lymphoma risk groups
- 2nd/3rd decades and > 50 years
- Caucasians, males
- Family hx 3-5 x
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Majority of lymphoma’s are Hodgkin’s or NH?
- Non-Hodgkin’s
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Is Hodgkin’s Lymphoma B or T cell neoplasm?
- B cell
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Infectious agents associated with Hodgkin’s dz
- EBV and HIV. Usually Hodgkin’s is spontaneous though
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Clinical presentation of Hodgkin’s disease
1. B symptoms: fevers, chills, night sweats are key, pruritus, etoh-induced LN pain, weight loss
2. Non-tender lymphadenopathy: 70% in cervical, 60% mediastinal – contiguous
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How does the lymphadenopathy between Hodgkin’s and Non-H differ?
- Contiguous in Hodgkin’s
| - Sporadic in Non-H
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Staging for Hodgkin’s lymphoma
I: 1 nodal region or lymphoid structure
II: 2 or more nodal region (same side of diaphragm)
III: both sides of diaphragm
IV: > 1 extranodal site (including BM)
A: asymptomatic
B: B symptoms
X: bulky dz (>10 cm or 1/3rd width of mediastinum)
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Characteristic cell type in Hodgkin’s lymphoma. Describe pathology/histology findings.
- Reed-Sternberg cell: malignant large multi-nucleated (owl eyes) B cell
- CD15+ CD30+
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Adverse prognostic factors for Hodgkin’s lymphoma
- Large mediastinal mass, extranodal dz, advanced stage, albumin 45, Hb 15 K
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Is Hodgkin’s dz curable?
- Yes – high survival rate esp I and II stages
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Tx of Hodgkin’s dz?
- Non surgical
| - Chemo + radiation (it is radiosensitive) typically.
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Which non-Hodgkin’s lymphoma are more aggressive?
- T-cell versions.
| - Non-H can be B or T cell neoplasms
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Sx of Non-Hodgkin’s lymphoma
- B-symptoms = fever, chills, night sweats and weight loss only. More common in aggressive lymphomas
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Which Non-Hodgkin’s lymphomas more commonly involved the CNS?
- Burkitt’s, lymphoblastic, HIV-lymphoma
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Non-Hodgkin’s lymphomas typical involve a translocation with what chromosome?
- 14
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Oncogene involved in mantle cell lymphoma?
- Bcl-1
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Oncogene involved in small lymphocytic lymphoma?
- Bcl-3
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Oncogene involved in Burkitt’s lymphoma?
- cMyc
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Oncogene involved in diffuse large cell lymphoma?
- Bcl-6
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Most common Non-Hodgkin lymphomas?
- Diffuse large cell lymphoma
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Classification of Non-Hodgkin lymphoma
1. Indolent (low grade): follicular, mantle cell, small lymphocytic, splenic, MALT, hairy cell leukemia
2. Aggressive (intermediate grade): diffuse large cell, anaplastic large cell, immunoblastic
3. Very aggressive (high grade): Burkitt’s (small, non-cleaved), lymphoblastic/T cell lymphoma/leukemia
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What is the least aggressive Non-H lymphoma? Most?
- Least: Follicular
| - Most aggressive: Burkitt’s, T-cell lymphoma / leukemia
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What is diffuse large-cell lymphoma? Presentation? Cure rate?
- Most common Non-H lymphoma presenting with enlarging mass in nodal or extranodal site. It is intermediate grade (aggressive)
- Sx: B-symptoms: fever, chills, night sweats and weight loss. Other symptoms depending on extranodal site.
- Cure rate? 45%
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DLCL treatment
- I think this is low yield
| - CHOP therapy + rituximab (anti-CD20 drug)
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Is follicular lymphoma curable?
- Typical not curable in late stages when it presents, although indolent.
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What is follicular lymphoma? Clinical presentation?
- Non-H lymphoma presenting with enlarging LNs overs months to year intermittent.
- Sx: usually asymptomatic. B symptoms uncommon. Most present with stage III or IV as a result.
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What is Richter’s transformation?
- Occurs in ~40% of follicular lymphomas where they transform into DLCL at ~ 10 years of disease. Can be more favorable to treat.
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Tx for follicular lymphoma
- Early stage, goal = cure
- Late stage, goal = palliate, promote longevity
- Use radiation, chemo (CHOP-like + rituxan, fludarabine)
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What age groups are the very aggressive non-H lymphomas common in? Are these curable?
- These include: Lymphoblastic lymphoma, Burkitt’s and any T-cell lymphoma/leukemia
- Peds patients and young adults.
- Curable, but aggressive. Use intense IV chemo regimens (Hyper CVAD) + CNS prophylaxis with intrathecal methotrexate.
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Are bone marrow/stem cell transplants useful in non-H lymphomas?
- In DLCL (aggressive) and very aggressive lymphomas it has utility after relapse. Use auto SCT.
- No utility in indolent lymphomas such as follicular
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What is MALT lymphoma?
- Indolent (or very) Non-H lymphoma of the MALT tissue (GI, lung, breast, salivary glands, thyroid, skin).
- Many live with these and don’t die from them
- Example = Gastric MALT lymphoma which are mostly H.pylori pos.
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Which lymphomas are HIV associated? What sites in the body are these found at? Survival and tx?
- DLCL, Burkitt’s or CNS lymphoma. Many associated with HHV-8 and EBV.
- Sites: anus, rectum, soft tissues, pleural fluid
- Median survival is 6 months. Tx w/ HAART + CHOP (w/rituximab)
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What is the most common leukemia in adults? Age group where these is seen mostly? Etiology?
- CLL (a non-H lymphoma)
- Median age of diagnosis = 72 yo
- Etiology: sporadic mostly, immune deficiencies (eg. RA)
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Pathology of CLL. What cells are implicated?
- Clonal proliferation of incompetent B cells. Therefore always involves bone marrow and peripheral blood.
- CD5+, CD20+ (B cell), CD23+
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Symptoms of CLL. PE findings?
- Usually asymptomatic. Can be infectious symptoms, fever and weakness
- PE findings: LA (diffuse), splenomegaly
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Lab findings for CLL
- CBC: high WBC w/lymphocyte count > 5K
- Low IgG, A and M (late stage)
- Peripheral blood shows CD5, 20 and 23 + B cells
- Often times the above is sufficient to make diagnosis. Can do BM biopsy to look for > 40% mature lymphocytes
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Causes of malignant lymphocytosis in adult
- CLL
- Mantle cell lymphoma
- Hairy cell leukemia
- Splenic lymphoma with villous lymphs
- Prolymphocytic leukemia
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Staging of CLL
0: lymphocytosis = low = 10 year median survival
1: lymphadenopathy = intermediate = 7 year
2: splenomegaly = intermediate = 7 year
3: anemia (Hb
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Is CLL curable? Tx?
- Not curable
- Tx with chemo when stage 3 or 4, persistent symptoms, LA is causing medical problems or cosmetic deformities or immune-related hemolytic anemia or thrombocytopenia
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Examples of oncologic emergencies.
- SVC syndrome
- Neutropenic fever
- Pericardial tamponade
- Malignant spinal cord compression
- Tumor lysis syndrome
- Pulmonary embolus
- Not spoken about: metabolic (hyponatremia, hypercalcemia, hypoglycemia), AMS, DVT, severe pain, symptomatic thrombocytopenia, GI obstruction, urinary obstruction, adrenal insufficiency, increased ICP
192
What is SVC syndrome?
- Benign or malignant condition that is caused by obstruction of blood flow through SVC
193
Signs and symptoms of SVC syndrome?
- Venous collaterals / dilatation (JVD)
- Edema of head, neck, arms, upper chest, larynx (stridor, unable to talk) and brain
- SOB, head fullness, cyanosis, cough, chest pain, headaches, confusion, coma
194
Etiology of SVC syndrome
- ~70% d/t malignancy such as lung cancer and non-H lymphoma
| - Benign etiologies = SVC stenosis, SVC thrombosis d/t intravascular devices, fibrosing mediastinitis d/t H. capsulatum
195
Diagnostic studies for SVC syndrome. What is the test of choice?
- CXR, CT (contrast), venography, MR, histologic diagnosis (if malignancy)
- Test of choice: CT chest w/contrast (esp if malignant obstruction suspected). If thrombosis d/t indwelling catheter, then venography necessary.
196
Tx of SVC syndrome
- Alleviate symptoms: SVC endovascular stent
| - Treat underlying disease: Malignant tx with radiation, chemo
197
What is a neutropenic fever.?
- Temperature > 38.3 (101 F) sustained for greater than 1 hour occurring in patients who are neutropenic (absolute neutrophil count =
198
Etiology of neutropenic fever
- Cytotoxic chemo, which suppresses myelopoiesis and affects integrity of GI mucosa allow for infection
- Infectious source only identified 20-30% of the time. 80% of infections identified believed to arise from endogenous gut flora.
- Pathogens:
a. Gram pos: Staph (incl epidermidis account for half), Strep
b. Gram neg: E.coli, pseudomonas
c. Fungal: candida, aspergillus (rare, if fever persists 1 week after abx tx, this is likely cause)
d. Viral: HSV, HZ, CMV, EBV
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Tx for neutropenic fever
- Broad-spectrum empiric antibiotics to all patients w/in 60 mins of presentation is std of care. Typically give 3rd generation cephalosporin.
- Antifungals as needed
- Remove infected indwelling devices
- ? G-CSF
200
Describe evaluation for neutropenic fever
- Meticulous hx and PE daily – avoid rectal exam
- Lab studies: CBC w/diff, LFTs, CMP, cultures
- Rad: CXR***, CT chest ?
201
Most common cause of central venous catheter-associated infections
- Candida
202
Etiology of malignant pericardial tamponade
- Lung cancer, breast cancer, leukemia, lymphoma or previous chemo/radiation therapy.
203
Signs and symptoms of pericardial tamponade
- Cough, chest pain, SOB, weakness, tachycardia, JVD, peripheral edema, diminished heart sounds, pulsus paradoxus, reduced pule pressure, pericardial friction rub, electrical alternans on ECG
204
How to diagnose pericardial tamponade?
- Clinical suspicion based on hx and PE
| - Echo is test of choice. CXR insensitive. CT not usually.
205
Tx of pericardial tamponade
- Drainage via percutaneous US-guided pericardiocentesis = tx of choice in most patients.
- If recurrent effusions, pericardial window surgery
206
What is malignant spinal cord compression? Etiology?
- Malignant spinal cord compression: compression of spinal cord of cauda equina by tumors. Injury occurs through compression leading to compromised blood flow = ischemia and infarct leading to paralysis.
- Cancer etiologies = lung, breast, prostate and multiple myeloma.
- ~90% d/t tumor growing into epidural space and compressing. Most common site = thoracic spine > l-spine > c-spine
207
Signs and symptoms of malignant spinal cord compression
- Localized back pain (worse by coughing, movement and supine)
- Radicular component (radiation to limb)
- Lhermitte’s sign (electrical shock down spine with neck flexion)
- Weakness, spasticity, reflexes
- Numbness, paresthesias
- Bladder/bowel dysfunction
208
Signs and symptoms of cauda equina syndrome d/t cord compression
- LBP, decreased sensation over buttocks and saddle distribution, bladder/bowel dysfunction, decreased patellar/Achilles reflex, LE weakness
209
Test of choice to diagnose malignant spinal cord compression?
- MRI. CT myelogram for those unsuitable for MRI (if pacemaker)
210
Tx of malignant spinal cord compression
- Glucocorticoids, radiation, surgery, chemo, radiofrequency ablation w/vertebroplasty
211
What is tumor lysis syndrome? Signs and symptoms?
- Rapid death/turnover of rapidly proliferating cancer cells following chemo. High potential for this in high grade lymphomas, acute leukemias and any rapidly proliferating tumor. Is reported in solid tumors.
- Signs: hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia (d/t hyperphosphatemia?), metabolic acidosis, acute kidney injury (crystal deposits in renal tubule). Can lead to renal failure (uric acid precipitates readily in presence of CaPO4 and vice verse), cardiac arrhythmias, seizures and death. Organ failure d/t massive release of cytokines from tumor cells.
- Will he want us to remember the Cairo-Bishop definition of TLS?
212
What is the most common disease related emergency in patients with hematologic malignancies?
- Tumor lysis syndrome
213
High risk group for tumor lysis syndrome?
- Pre-existing chronic renal insufficiency
- Oliguria
- Volume depletion
- Hypotension
- Acidic urine
214
Management of tumor lysis syndrome
- Hydration (mainstay for prevention of TLS)
- Allpurinol (xanthine oxidase inhibitor): blocks conversion of xanthine and hypoxanthine to uric acid. No utility once uric acid is made.
- Rasburicase (urate oxidase): oxidation of uric acid to water-soluble allantoin
- Dialysis
215
Signs and symptoms of pulmonary embolus?
- Dyspnea with exertion or at rest, pleuritic chest pain, cough, calf/thigh pain or swelling. Most common signs: tachypnea, tachycardia, rales, JVD.
216
Why is cancer a risk factor for PE?
- Thrombogenic effects of malignancy and hypercoagulability caused by chemo
217
Risk factors for PE
- Malignancy
- Hospitalization
- Immobility
- Trauma
- Surgery
- Central catheter
- Obesity
- More…
218
How are PEs diagnosed?
- CT pulmonary angiography: utility great in patients with a high pre-test probability for PE. Good test for excluding.
- CXR has poor sensitivity and specificity
- VQ scan: used when absolute contraindication to IV contrast
219
Tx of PEs
- Resuscitation: respiratory and hemodynamic support
- Anti-coag with LMWH if no contraindication to anticoagulation. Use in patients that are hemodynamically stable. This prevents further growth of embolus.
- If hemodynamically unstable, use tPA.
