Leukemia/Lymphoma

Question 1

CML genetic disorder

Answer 1

Philidelphia chromosome, reciprocal translocation between 9,22 → t(9;22)(q34;q11) → BCR-ABL 1 fusion gene.  
Blasts >20% in BM, -> blast crisis
Low LAP (leukocyte alkaline phosphatase)

Question 2

CMML

Answer 2

(Chronic myelomonocytic leukemia) – MDS/MP neoplasm characterized by overproduction of maturing monocytic cells and sometimes dysplastic neutrophils, often accompanied by anemia and/or thrombocytopenia
WHO criteria
- Persistent peripheral blood monocytosis, absolute monocyte count > 1000/mL
- Ph chromosome or BCR ABL fusion gene absent
- 1500/mL
Note: Both Atypical CML and CMML can be Ph (-)ve

Question 3

Richter’s transformation

Answer 3

CLL transformation to diffuse large B cell lymphoma
- Sudden clinical deterioration, marked increase in lymphadenopathy at one more sites (abdominal), splenomegaly, worsening constitutional sx. Elevated LDH, anemia in 50%

Question 4

CLL complications

Answer 4

Hypogammaglobulinemia, anemia (AIHA drug induced)

Question 5

MM diagnostic criteria

Answer 5

meet all 3 criteria

• Presence of a serum or urinary monoclonal protein
• Presence of clonal plasma cells in the BM or plasmacytoma
• Presence of end organ damage felt related to plasma cell dyscrasia → increased calcium concentration, lytic bone lesion, anemia, or renal failure

Question 6

AL Amyloidosis diagnosis

Answer 6

o Diagnostic criteria for AL amyloidosis require the presence of all of the following:
• Presence of an amyloid-related systemic syndrome (eg, renal, liver, heart, gastrointestinal tract or peripheral nerve involvement).
• Positive amyloid staining by Congo red in any tissue (eg, fat aspirate, bone marrow or organ biopsy).
• Evidence that the amyloid is light chain-related established by direct examination of the amyloid (eg, using mass spectrometry based proteomic analysis; note that immunohistochemistry results to type amyloid may be unreliable).
• Evidence of a monoclonal plasma cell proliferative disorder (eg, presence of a serum or urine M protein, abnormal serum free light chain ratio, or clonal plasma cells in the bone marrow).

Question 7

Hodgkin’s lymphoma staging

Answer 7

Stage 1 – Involvement of single LN region or of a single extralymphatic organ or site
Stage 2 – Involvement of 2 or more LN regions on the same side of the diaphragm alone or with involvement of limited, contiguous extralymphatic organ or tissue.
Stage 3 – Involvement of LN regions or lymphoid structures on both sides of the diaphragm, which may include spleen or limited, a contiguous extralymphatic organ or site.
Stage 4 – Diffuse or disseminated foci of involvement of one ore more extralymphatic organs or tissues, with or without associated lymphatic involvement

Question 8

MGUS diagnosis

Answer 8

1) M protein

Question 9

MGUS complication

Answer 9

Progress to more advanced disease at a rate of 1% per year → develop MM, macroglobulinemia, amyloidosis

Question 10

Waldenstrom macroglobulinemia

Answer 10

distinct clinicopathological entity demonstrating lymphoplasmacytic lymphoma (B cell) in the BM with IgM monoclonal gammopathy in the blood: IgM >3g/dL
MYD88 L265P somatic mutation found in 91% with WM, used to distinguish from MM
No evidence of bone lesions, (otherwise it’s IgM myeloma)

Question 11

MM diagnostic tests

Answer 11

SPEP quantitate M components
UPEP for light chains only
Immunofixation identifies Ig type
Serum-free light chain assay for dx and follow up response to Rx
Beta-microglobulin and LDH for tutor burden

BM bx cytogenetics: high risk vs. standard risk karyotype
Skeletal survey (bone scan not helpful!)

Question 12

MM treatment

Answer 12

Smoldering MM, asx stage 1 MM: no treatment
Treatment decision dictated by Risk stratification and transplant eligibility
Not transplant eligible: induction chemo, not curative, but increase survival
Transplant eligible: induction chemo + high dose chemo + auto-HSCT, not curative, increase further survival, only if

Question 13

WM clinical manifestations

Answer 13

Fatigue from anemia most common sx
Tumor infiltration: BM cytopenia, hepatomegaly, splenomegaly, lymphadenopathy
Circulating monoclonal IgM: hyperviscosity syndrome (neurological, cardiopulmonary: CHF, pulmonary infiltrates), type 1 cryo - Raynaud’s phenomenon, platelet dysfunction, IgM deposits -> amyloidosis, glomerulopathy, Autoantibody activity of IgM -chronic AIHA, peripheral neuropathy

Question 14

WM treatment

Answer 14

Hyperviscosity: plasmapheresis
Symptoms: rituximab for anemia +/- chemo