Flashcards in EXAM #3: REVIEW Deck (70):
Describe the clinical presentation of MDS.
1) Many patients are asymptomatic at diagnosis and come to their physician for an abnormality on a CDC i.e.
2) Other patients present with symptoms relating to the above, of which, anemia is the most common
What are the specific physical exam findings that may present with MDS?
- Pallor (anemia)
- Petechiae/ purpura (thrombocytopenia)
- Sweet's Syndrome i.e. Acute Febrile Neutrophilic Dermatosis
- Hepatomegaly/Splenomegaly (relatively uncommon)
What are some of the differential diagnoses to MDS?
1) Vitamin B12 and Folate Deficiency
2) Viral infection e.g. HIV
5) Pb toxicity
7) Erythropoietic agents e.g. EPO or GM-CSF
What is 5q Syndrome?
MDS associated with a deletion of the long arm of chromosome 5
What are the clinical features of 5q Syndrome>
This is a syndrome seen almost exclusively in older women; it is characterized by:
1) Severe macrocytic anemia
3) Normal to elevated platelet counts
4) Lack of neutropenia
What is CMML?
Chornic Myelomonocytic Leukemia; the overproduction of maturing monocytic cells and sometimes dysplastic neutrophils with:
What does low intensity treatment entail for MDS?
1) Supportive care
3) Growth Factor Support
What is CML?
Neoplastic hyperproliferation of mature myeloid cells, especially granulocytes and their precursors
Describe the presentation of CML.
Symptomatic presentations of CML present most frequently with:
2) Bleeding episodes from platelet dysfunction
3) Weight loss
4) Night sweats
5) Abdominal pain/ fullness (LUQ radiating to left shoulder)
What CBC findings are characteristic of CML?
Dramatically increased WBC count with BASOPHILIA being the most specific elevation associated with CML
What are the characteristic features of the chronic phase of CML?
1) Basophilic on WBC diff.
2) Myeloblasts less than 10%
3) Presence of BCR-ABL fusion protein
How is CML diagnosed?
1) CBC/ PBS showing leukocytosis w/ basophilia
2) Bone marrow biopsy showing granulocytic hyperplasia
3) Confirmation with FISH or RT-PCR for BCR/ABL
List the MAJOR criteria for PV.
1) Hb greater than 18.5 and 16.5 for men and women
2) JAK2 mutation
List the MINOR criteria for PV.
1) Bone marrow hypercellularity
2) Low serum EPO
What are the clinical manifestations of ET?
Either increased risk of thrombosis or bleeding events depending on if the overproduced platelets are functional vs. non-functional
What are the diagnostic criteria for ET?
1) Platelet count greater than 450,000
2) BM biopsy showing hyperproliferation of megakaryocyte lineage
3) JAK2 mutation present or rule out reactive thrombocytosis
How is ET treated?
What cell line undergoes hyperprolifeation in Primary Myelofibrosis? What factor causes fibrosis?
- Mature myeloid cells i.e. megakaryocytes
- PDGF causes fibrosis of the bone marrow
What are the clinical features of Primary Myelofibrosis?
1) Splenomegaly due to extramedullary myelofibrosis
2) Leukoerythroblastic PBS i.e. tear drop RBCs, nucleated RBCs, immature granulocytes
3) Increased risk of infection, bleeding, and thrombosis
What are the supportive measures used as treatment for Primary Myelofibrosis?
1) Recombinant EPO
2) Iron chelation
4) JAK2 inhibitors
5) Allogenic Stem Cell Transplant*
Note that this is the only treatment currently available that has curative potential.
Generally, how is Multiple Myeloma treated?
4) Bone marrow transplant
5) Bisphosphates/ radiation
How are Plasmacytomas diagnosed?
1) Biopsy proven lesion of the bone or soft tissue WITH:
- Normal bone survey
- No evidence of end organ damage
- Bone marrow with no evidence of plasma cells
Thus, a) demonstrate presence of tumor, b) rule out Multiple Myeloma
What are indications of poor prognosis with Amyloidosis?
1) Cardiac involvement
2) ANS neuropathy
3) Liver involvement with hyperbilirubinemia
4) Lack of suppression of underlying clonal disease
What is the key symptom of Waldenstrom's Macroglobulinemia?
What is the treatment for Waldenstrom's Macroglobulinemia?
Chemotherapy and plasmapharesis if symptomatic
What are the major categories of disease that are associated with a higher prevalence of childhood cancer?
2) Metabolic disorders
3) Chromosome instability
When a child presents with unexplained petechiae, what are the two disorders that should be high on your differential diagnosis?
When a child presents with lymphadenopathy that is unresponsive to antibiotics, what are the two disorders that should be high on your differential diagnosis?
When a child presents with a pharyngeal mass, what are the three disorders that should be high on your differential diagnosis?
3) Nasopharyngeal carcinoma
When a child presents with a periodontal mass or loose teeth, what are the four disorders that should be high on your differential diagnosis?
1) Langhans Cell Histiocytosis
2) Burkitt's Lymphoma
When a child presents with a GU mass, what are the two disorders that should be high on your differential diagnosis?
1) Germ cell tumor
In a child, what are the six signs and symptoms that are red flags for Leukemia?
1) Unexplained fever ( greater than 101F) for more than 7 days
2) Petechiae, especially in the wasitline or sockline
3) Unexplained anemia/ pallor
6) Bone/joint pain that is a) not controlled with NSAIDs, or b) wakes from sleep
What are red flags concerning isolated lymphadenopathy that would prompt you to order a lymph node biopsy?
1) Worsening lymadenopathy after 2-3 weeks of treatment
2) Any lymphadenopathy seen on CXR
3) Lymphadenopathy with concerning constitutional symptoms
4) Any lymphadenopathy in an uncommon area
Describe the presentation of ALL.
Most common in male children and hallmarked by the constellation of symptoms surrounding:
AND bone pain that causes a limp/ decreased walking
What are the CBC/PBS findings that are characteristic of ALL?
1) Increased WBC count
2) 2+ cytopenias
3) Lymphoblasts on PBS (+TdT)
What four disorders should be considered on the differential for ALL?
1) EBV (Mononucleosis)
2) Acute anemia
3) Parvovirus B19
Aside from a mediastinal mass, what accompanies the typical presentation of T-ALL in adolescents?
1) High WBC mass
2) Lymhadenopathy that resembles Mumps
What are the long term adverse effects of radiation therapy for CNS tumors?
1) Impaired neurocognitive development
2) Hearing changes
3) Development of a secondary cancer
4) Endocrine abnormalities
5) Skeletal growth abnormalities
What are the three most common presenting symptoms of a Wilm's Tumor?
What are six common signs/symptoms of a neuroblastoma?
1) Proptosis/ exopthalmous or anterior bulging of the eye in the orbit
2) Periorbital ecchymosis i.e. "Raccoon eyes"
3) Bone lesions
4) Abdominal mass that crosses the midline
5) Lower extremity weakness
6) Horner's Syndrome from high thoracic or cervical masses
What tumor involving the head and neck may cause proptosis and periorbital swelling?
What are the signs/symptoms of a parameningeal rhabdomyosarcoma?
1) CN palsy
2) Hearing loss
3) Chronic aural or sinus drainage
Describe the etiology of signs/symptoms seen in acute leukemia.
- Increased lymphoblasts or myeloblasts crowd out normal hematopoiesis
- Results in the "acute" presentation of:
1) Anemia (Fatigue)
2) Thrombocytopenia (Bleeding)
3) Neutropenia (Infection)
- Blasts enter the blood stream to result in an abnormally high WBC count
What is APL?
Acute Promyelocytic Leukemia i.e. a subclass of AML
What is the major adverse event/ risk factor associated with APL?
What is the major adverse event that is associated with APL treatment?
APL Differentiation Syndrome, formerly "Retinoic Acid Syndrome," which is:
- Treatment with ATRA
- ATRA treatment leads to differentiation of promyelocytes
- Differentiation of promyelocytes results in cytokine storm
Essentially, ATRA-->differentiation and cytokine release-->sepsis/shock
List the differential diagnosis for a patient with a macrocytic anemia.
1) Vitamin B12/ Folate deficiency*
3) Liver Failure
4) Drugs (e.g. methotrexate/ hydroxyurea)
6) Myelodysplastic Syndrome
What are the common labs associated with Myelodysplastic Syndrome?
1) Macrocytic anemia
What is the typical age of onset of a Follicular Lymphoma?
What are the typical clinical findings associated with Follicular Lymphoma?
1) Painless lymphadenopathy
What is the typical presentation of Mantle Cell Lymphoma?
Painless lymphadenopathy in late adulthood (5th - 6th decade)
What is the translocation associated with Mantle Cell Lymphoma?
What protein is overexpressed in Mantle Cell Lymphoma?
Cyclin D1, which mediates G1-->S-phase transition
What is the immunophenotype of Mantle Cell Lymphoma?
What are the characteristics of Burkitt's Lymphoma on microscopy?
High mitotic index and starry sky appearance
What is the clinical presentation of Adult T-Cell Leukemia/ Lymphoma?
2) Generalized LAD
4) Lytic bone lesions
What drug is used to treat Adult T-Cell Leukemia/Lymphoma?
What is Mycosis Fungoides?
Neoplastic proliferation of CD4+ T-cells that infiltrate the skin
What are the characteristics of malignant cells in MF?
1) Cerebriform nuclei
2) Highly folded nuclear membrane
What are the two principle manifestations of Seazry Syndrome?
This is when the neoplasic CD4+ T-cells of MF infiltrate the blood. Results in:
2) Exfoliative Erythroderma
What is the immunophenotype of T-ALL?
1) TdT positive (all lymphoblasts)
3) NO CD10
Describe the morphology of T-ALL.
Forms sheets of blasts
What factors indicate a poor prognosis for T-ALL?
1) Patient under 2 years-old
2) Presentation in adolescence or adulthood
3) t(9:22) or translocation involving MLL gene on chromosome 11
4) WBC count greater than 100,000
What Lymphoma are "hallmark" cells associated with?
What are the two immunohistochemistry markers for RS cells in HL?
What is the translocation seen in DLCL?
What protein is overproduced in DLCL?
Describe the presentation of DLCL?
- Enlarging mass in a nodal or extra-nodal site accompanied by B-symptoms
- More common in the elderly
List the three most common HIV associated Lymphomas.
2) Burkitt's Lymphoma