Symptoms 09: Weight Loss & Fatigue (Hem/onc)

Front 1

How common is clinically significant weight loss?

Back 1

~4%

Front 2

In an elderly patient with weight loss, what are the most common causes?

Back 2

- Cancer
- Psychiatric problems
- GI disorders
- Med effects

Front 3

What is considered clinically significant unintentional weight loss?

Back 3

Loss of 10 pounds or >5% of baseline body weight in 6-12 months

Front 4

What do you need to establish first in a patient who has unintentional weight loss?

Back 4

- Is it intentional (dieting?)
- Is the patient's food intake less (weight loss due to reduced caloric intake) or the same/increased (implies hypermetabolic state or absorption problem)

Front 5

What is the differential for weight loss?

Back 5

DECREASED BODY MASS:
- Depression
- Endocrinopathy (thyroid, adrenal insufficiency)
- Cancer
- Renal failure
- Enteric (Crohn’s, chronic mesenteric ischemia)
- Access to food (financial, transportation)
- Systemic inflammatory dz (SLE, temporal arteritis)
- Eating difficulty (tremor, dentures, dysphagia)
- Diabetes Mellitus

- Bulimia & Anorexia
- Opportunistic Infection (HIV, TB, helminths)
- Dementia
- Yucky food (low salt, low fat, institutionalized)

- Medication side effects/Substance Induced
- Aging
- Systemic chronic disease (CHF, COPD, cirrhosis)
- Schizophrenia/Psychosis

Front 6

What is the most common medication to cause decreased eating? Why?

Back 6

Digitalis / Digoxin - gives weird taste in mouth

Front 7

Case 1:
Mrs. Twiggy Gaunt, a 45 y/o F presents to her PCP with 20 pound weight loss and fatigue for about a year. She states she was not intentionally attempting to lose weight. What is the next question that you should ask to begin to develop your differential?
a) Whether her appetite has been diminished or if her food intake has been the same/increased
b) If she is a member of NutriSystem, Jenny Craig or WeightWatchers
c) If you can have that super cute dress she was wearing at her last visit since it is probably too big for her now
d) If she wants to drink Boost or Ensure in chocolate, vanilla or strawberry

Back 7

Whether her appetite has been diminished or if her food intake has been the same/increased

Front 8

Case 1:
- Mrs. Gaunt reports appetite and food intake hasn't changed - although maybe she gets full more quickly when eating
- Feeling tired, denies other symptoms including depression, change in bowel habits, polyuria, or joint pains
- She has enlarged spleen

What should you consider first?

Back 8

Hematologic malignancy: lymphoma or leukemia
- She has no signs of liver disease and prevalence of EBV is low among married middle aged women

Front 9

What is a lymphoma? Types?

Back 9

Malignancy of white blood cells arising in the lymph nodes
- Hodgkin's or Non-Hodgkin's Lymphoma

Front 10

What is a leukemia? Types?

Back 10

Lymphoid neoplasms with widespread involvement of bone marrow. Tumor cells are usually found in peripheral blood.
• Acute Myelogenous Leukemia (AML)
• Acute Lymphoblastic Leukemia (ALL)
• Chronic Lymphocytic Leukemia (CLL)
• Chronic Myeloid Leukemia (CML)
• (Other) Hairy Cell Leukemia

Front 11

What should you think of if you see an African patient with a jaw mass?

Back 11

Burkitt's (Non-Hodgkin) Lymphoma

Front 12

What translocation is seen in Mantle Cell (Non-Hodgkin) Lymphoma? Cell marker? Prognosis?

Back 12

t(11;14) - deactivation of cyclin D regulatory gene, CD5+,
- Poor prognosis

Front 13

What translocation is seen in Follicular (Non-Hodgkin) Lymphoma? Cell marker? Prognosis?

Back 13

t(14;18) - bcl-2 expression, which inhibits apoptosis
- Indolent course, but difficult to cure

Front 14

What should you think of when you see a child with a mediastinal mass?

Back 14

Lymphoblastic T cell (ALL)

Front 15

Which non-Hodgkin Lymphoma is associated with mycosis fungoides?

Back 15

Cutaneous T cell Lymphoma

Front 16

Which non-Hodgkin Lymphoma is associated with HTLV-1 infection?

Back 16

Adult T cell Lymphoma

Front 17

Which non-Hodgkin Lymphoma is associated with H. pylori infection?

Back 17

Marginal Cell MALToma

Front 18

Which cancer has a "starry sky" histology? What is this?

Back 18

Highly aggressive B cell non-Hodgkin lymhoma
- Sheets of lymphocytes with interspersed macrophages

Front 19

Who gets Burkitt's Lymphoma?

Back 19

- Children and young adults, sporadically or associated with HIV
- In Africa, associated with EBV and presents as maxillary/mandibular mass

Front 20

What is the translocation associated with Burkitt's Lymphoma? Implications? Markers?

Back 20

t(8;14) - c-MYC gene originally on chr 8
- Places c-MYC proto-oncogene adjacent to Ig heavy chain locus on 14w over-expression of the transcription factor c-MYC that leads to increased cell growth
- CD20, CD10, and BCL-6 positive

Front 21

What are the complications of treating Burkitt's Lymphoma?

Back 21

Treatment may lead to tumor lysis syndrome low phos, low calcium, increased uric acid, increased potassium and AKI, preventable w hydration and allopurinol

Front 22

What are the symptoms that occur in Hodgkin's Lymphoma?

Back 22

- B symptoms: weight loss, fevers, night sweats
- Patients sometimes itch
- Node doesn't hurt

Front 23

What is the histologic sign of Hodgkin's Lymphoma?

Back 23

Reed-Sternberg cells = cells are formed from germinal B cell centers

Front 24

What are the markers positive in Hodgkin's Lymphoma?

Back 24

CD15+ and CD30+

Front 25

How do you treat Hodgkin's Lymphoma? Prognosis?

Back 25

- Curable
- Excision
- +XRT or advanced ABVD chemo: Adriamycin (doxorubicin), Bleomycin, Vinblastine, Dacarbazine)

Front 26

What are the subtypes (which are most common) of Hodgkin's Lymphoma?

Back 26

- Nodular sclerosis (most common - 70%)
- Lymphocyte predominance (6% - popcorn cells)
- Lymphocyte rich (40% - assoc. with EBV)
- Lymphocyte depleted (HIV)
- Mixed cellularity (25% - older patients with EBV)

Front 27

Which subtype of Hodgkin's Lymphoma is the most common version?

Back 27

Nodular Sclerosis (70%)

Front 28

Which subtype of Hodgkin's Lymphoma is described as having "popcorn cells"?

Back 28

Lymphocyte Predominant (6%)

Front 29

Which subtype of Hodgkin's Lymphoma is associated with EBV?

Back 29

- Lymphocyte rich (40%)
- Mixed cellularity (older patients with EBV - 25%)

Front 30

Which subtype of Hodgkin's Lymphoma is associated with HIV?

Back 30

Lymphocyte depleted

Front 31

What is this?

Back 31

Reed-Sternberg Cells looks like Owl's eyes
- Sign of Hodgkin's Lymphoma

Front 32

What is the mechanism of Vincristine? Most important side effect?

Back 32

- M phase specific, blocks polymerization of microtubules so mitotic spindle cannot form
** Causes neuropathy (peripheral neuritis, areflexia, paralytic ileus)

Front 33

What is Vincristine used for? Most important side effect?

Back 33

- Used in acute leukemia, Hodgkin's , Wilms tumor, choriocarcinoma
- Part of MOPP regimen for Hodgkin lymphoma

** Causes neuropathy (peripheral neuritis, areflexia, paralytic ileus)

Front 34

Case 1:
- Your preceptor tells you to go back and do a thorough lymph node exam
- You cannot find a painlessly, enlarged submental, submandibular, anterior or posterior cervical, pre or post auricular, suboccipital, supraclavicular, axillary, epitrochelear, or even a medistinal node using your x ray vision and Twiggy refuses a groin exam

What should you consider / do next?

Back 34

- Consider Leukemia
- Order a CBC

Front 35

What are the signs and symptoms of leukemia?

Back 35

Unregulated growth of leukocytes in BM
- Bone pain
- Decreasing working WBC → infections, especially cellulitis
- Decreased Hgb & HCT → fatigue, dyspnea on exertion, pallor on exam
- Decreased platelets → bleeding gums, epistaxis, petechiae
- Hepatosplenomegaly (d/t leukemic infiltrates in liver, spleen, or lymph nodes)

Front 36

What are the signs of decreasing working WBCs in leukemia?

Back 36

Infections, especially cellulitis

Front 37

What are the signs of decreasing Hgb and HCT in leukemia?

Back 37

- Fatigue
- Dyspnea on exertion
- Pallor on exam

Front 38

What are the signs of decreasing platelets in leukemia?

Back 38

- Bleeding gums
- Epistaxis
- Petechiae

Front 39

Case 1:
Initial blood tests:
• CBC: WBC 167,000; Hgb 11.5, HCT 33, MCV 99; Platelets 625,000 (Leukocytosis, normocytic/macrocytic anemia, thrombocytosis)
• Blood smear many late granulocytic precursor cells, eosinophils and basophils, few metamyelocytes
• Very low LAP leukocyte alkaline phosphatase (due to immature granulocytes)

What additional testing should she get?

Back 39

Philadelphia chromosome testing

Front 40

What is the translocation in the Philadelphia Chromosome? What disease is it seen in?

Back 40

CML: Chronic Myelogenous Leukemia
- t(9;22) - forms BCR-ABL fusion gene, translocation of ABL proto-oncogene to BCR
- BCR-ABL fusion protein results in constitutively active Abl tyrosine kinase in the Ras/Raf/MEK/MAPK pathway
- Leads to apoptosis and unregulated cell division

Front 41

What translocation is responsible for CML (Chronic Myelogenous Leukemia)?

Back 41

- t(9;22) - forms BCR-ABL fusion gene, translocation of ABL proto-oncogene to BCR
- BCR-ABL fusion protein results in constitutively active Abl tyrosine kinase in the Ras/Raf/MEK/MAPK pathway
- Leads to apoptosis and unregulated cell division

Front 42

What is the average age of onset of Chronic Myelogenous Leukemia (CML) and symptoms?

Back 42

- 35-55 years
- Splenomegaly, hepatomegaly, and lymphadenopathy
- Leukocytosis and normocytic to macrocytic anemia
- Platelet derangement either thrombocytosis during active phase or thrombocytopenia in spent phase
- BM is hypercellular

Front 43

What is the histologic appearance of Chronic Myelogenous Leukemia (CML)?

Back 43

Promyelocytes
- Big cells and big nuclei
- Coarse grains in cytoplasm
- Basophilic

Front 44

Twiggy Gaunt your 45 y/o F patient presenting with weight loss, fatigue and splenomegaly tests positive for the Philadelphia chromosome. What is her most likely diagnosis?
a) Polycythemia vera
b) Chronic myelogenous leukemia
c) Acute myeloblastic leukemia
d) Pernicious anemia
e) Chronic lymphocytic leukemia

Back 44

Chronic myelogenous leukemia

Front 45

What drug is used for CML? Significant side effects?

Back 45

- Hydroxyurea
- Busalfan (Pulmonary Fibrosis)
- Imatinib / Gleevac

Front 46

What is the mechanism of Imatinib / Gleevac?

Back 46

Highly specific Bcr-Abl tyrosine kinase competitive inhibitor
- Blocks proliferation, induces apoptosis in Bcr-Abl positive cell lines and fresh leukemic cells

Front 47

30

Back 47

30