Oncology Flashcards

Question

Non-Hodgkin Lymphoma staging: Ann Arbor System

Answer 1

Ann Arbor: - A or - B= "B symptoms": fever (> 38C), weight loss (> 10%), night sweats Stage I: Involves single lymph node/region or single extralymphatic site Stage II: 2+ lymph nodes on same side of diaphragm (could have localized extralymphatic involvement) Stage III: involves lymph nodes on both sides of diaphragm, spleen, localized extranodal disease Stage IV: diffuse extra-lymphatic disease (liver, bone marrow, lung, skin)

Answer 2

APLES (apples): 1. Age > 60 2. Performance status (>= 2) 3. LDH elevated 4. Extra-nodal sites (> 1) 5. Stage (Ann arbor stage III or IV) ``` Risk: Low= 0-1 Low-Intermediate= 2 factors High-intermediate= 3 factors High= 4-5 factors ```

Answer 3

aka Small Cell Lymphocytic Lymphoma: Diagnosis: - Malignant clone (small, mature) with lymphocytes > 5000/uL - Frequent bone marrow involvement Immunophenotype/genetics: - CD5+, CD19+, CD20+/- - 40% have v-region mutations in H chain gene Prognosis based on genetics/immuno: BAD= CD38+, trisomy 12, Bcl-1 Good= abnormal 13q

Answer 4

Presentation: - May be on routine labs - Seen in elderly - Male > Female - Lymphadenopathy - Splenomegaly/hepatomegaly - Fatigue Labs: - Smudge cells - Lymphocytosis - Cytopenia - Monoclonal protein - Hypogammaglobulinemia - Autoimmune cytopenias Complications: - Autoimmune hemolytic anemia (tx: corticosteroids) - Immune thrombocytopenia (tx: corticosteroids) - Red cell aplasia (tx: corticosteroids) - Infections - Hypogammaglobulinemia - Transformation to large cell lymphoma (Richter's transformation)- poor prognosis

Answer 5

``` Rai classification: Stage 0 -- lymphocytes >15,000/ml and >40% marrow Stage 1 -- enlarged lymph nodes Stage 2 -- enlarged liver and/or spleen Stage 3 -- anemia (< 100,000/l) ```

Answer 6

Combination: - monoclonal antibody (Rituximab) - Purine analog (fluarabine, pentostain) + Allogenic stem cell transplant (curative) Prognosis: - Only curative with stem cell transplant - Can live many years without transplant

Answer 7

Often related to chronic infections/inflammatory states Presentation= Extranodal; May be associated with: - h. pylori - Chronic lung infections - autoimmune disease (thyroid, Sjogren's) - 1/3 multifocal Pathology: - Tumors derived from cells surrounding germinal centers (B memory cells) - Larger than small lymphocytes, have more cytoplasm - Admixed with plasma cells- can be benign (reactive) or derived from tumor cells

Answer 8

Immunophenotype (not specific): - sig+ (M>G or A) - IgD- some cig + - CD19+, CD20+, CD22+, CD79+, CD5-, CD10-, CD23-, CD43-/+, CD11c +/- Genetics: - bcl-2 and bcl-1 negative

Answer 9

1. Triple antibiotic therapy for H. Pylori 2. Cyclophosamide-based therapy with Rituximab 3. Radiotherapy for early stage disease Prognosis: good; may recur - Response to therapy (antibiotics) less likely with deeper invasion, lymph node metastases, or t(11;18) found Complications: related to organ involved/therapy

Answer 10

One of most common indolent lymphomas (22% non-HL) Presentation: enlarged lymph node; asymptomatic. Common marrow involvement Pathology: - Tumor enlarges, fills entire lymph node with neoplastic follicles, obliterates normal architecture - Recapitulates nodal germinal center arrangement, germinal center cells - May transform into larger, more aggressive lymphoma - Involvement: lymph nodes, neoplastic follicles in extranodal soft tissue - Stains for Bcl-2

Answer 11

Immunophenotype: - sig+ = IgM+/-, IgD > IgG > IgA - CD10+ CD25-, CD2-/+, CD42-, CD11c- - *** Bcl-2** Genetics: - t(14;18)(q32;q21): bcl-2 rearrangment--> IgH control--> overexpression of anti-apoptotic Bcl-2

Answer 12

Therapy: Chemo, rituximab - ONLY cure is allogeneic stem cell transplant - Remission with autologous stem cell transplant Prognosis: FLIPI score - Localized disease: 50% 10-year disease free survival; overall 60-70% survival - Advanced disease: over 10-year median survival - Elderly patients: watch and wait Complications: infections, complication of chemo; can have normal life w/o therapy for several years

Answer 13

Seen in Adults only (more common in males): frequently involves extranodal spaces Presentation: presents SICK: can be v. aggressive with tumor lysis syndrome; not cured with standard therapy - Usually seen in advanced disease - Bone marrow, Waldeyer's ring (tonsillar) and GI tract involvement - Found in peripheral blood Pathology: - Most aggressive small cell lymphoma; - Derives from pre-germinal center (antigen-naive) B lymphocytes in zone around germinal center (mantle zone) - Cells small to medium - Irregular nuclei (larger= more aggressive) - Widespread involvement at diagnosis (bone marrow, GI tract) - Colon involvement--> polypoid lesions (lymphomatous polyposis coli)

Answer 14

Immunophenotype: - slgM+, IgD+, - CD 19+. 20+, 22+, 5+, 10-, 23-, 43+, 11c- - Nuclear Bcl-1+ * Like B-CLL this B-cell tumor expresses a T-cell marker Genetics: - t(11;14) involving Bcl-1--> cyclin D1 overexpression - Mutation drives cell cycling

Answer 15

Therapy: multiple options: - Chemo, rituximab - ONLY cure is allogeneic stem cell transplant Prognosis: - Poor without allogeneic transplant - High M&M with transplant Complications: - Infection - Complications of chemo - Tumor lysis syndrome - Rare visceral perforation

Answer 16

Most common aggressive lymphoma (31% non-HL) - Variant= mediastinal large cell (younger women with good prognosis) Presentation: - Presents sick; aggressive in tumor lysis syndrome at diagnosis Often has splenogmegaly

Answer 17

Pathology: - Arise de novo (most common) - derive from lower grade tumor (less common) - Nodal/extra-nodal - Large cells - Bizarre nuclei, big nucleoli Immuno: slg+, Cig +/-, CD19, 20, 22, 79a, 5+ Genetics: - Some positive for bcl-2 rearrangement (follicular cell lymphomas) - some c-myc positive (gene rearrangment) - bcl-6 rearrangment

Answer 18

``` Rituximab Cyclophosphamide Doxorubicin Vincristine, prednisone (R-CHOP)--> nothing better to date - Autologous HSC transplantation with relapse ``` Prognosis: based on IPI Complications: infections, complications of chemo, tumor lysis syndrome

Answer 19

``` Caused by Epstein Barr Virus HIV= risk factor More common in men Endemic variant in West Africa with jaw involvement Non-endemic may have abdominal disease - Involve kidneys, ovaries, breasts - 1/3 bone marrow involvement ``` Presentation: - Presents sick - Aggressive tumor lysis

Answer 20

Pathology: - Small, primitive B-cells - High mitotic rate - Basophilic cytoplasm with lipid vacuoles - Starry sky pattern (=> macrophages ingesting apoptotic debris) Immuno: slg+, Cig +/-, CD19, 20, 22, 79a, 5+ Genetics: * t(8;14)(q24;q32)--> MYC, IgH* t(8;22)(q24;q11)--> MYC IgL t(2;8)(p12;q24)--> IgK, MYC

Answer 21

CNS prophylaxis with intrathecal chemo/high dose methotrexate ``` 2nd line: Rituximab Cyclophosphamide Doxorubicin Vincristine, prednisone (R-CHOP) ``` Prognosis: based on IPI - Children do better than adults Complications: infections, complications of chemo, tumor lysis syndrome

Answer 22

1. T-cell acute lymphoblastic leukemia 2. Cutaneous T cell lymphoma/mycosis fungoides 3. HTLV1 + Adult T-cell lymphoma: - Rare - Associated with hypercalcemia, high EBC (w/o anemia, thrombocytopenia) and opportunistic infections 4. Anaplastic large cell lymphoma: - treated like diffuse large B cell lymphoma (without rituximab) - children do well, adults need stem cell transplant

Answer 23

Nodes enlarge over months - Starts in neck and works its way down body Bimodal age distribution (15-30 years, very old) Presentation: - B-symptoms (fever, weight loss, night sweats) more common than in non-Hodgkin's - Pruritis - Adenopathy : cervical, axillary, mediastinal - Nodal pain on alcohol ingestion - Enlarged mediastinal mass (SVC syndrome, cough- tracheobronchial compression) - Bone pain (metastatic involvement) - Marrow depletion with metastases

Answer 24

See "Reed Sternberg" (RS) cell variant: - Owl's eye appearance - Stains positive for CD30 (80-100%), CD15 (75-85%), BSAP (B-cell specific activating protein, PAX5 gene product- 90% cases) RS cells seen with polyclonal lymphocytes, eosinophils, neutrophils, plasma cells, fibroblasts, histiocytes - High number of associated macrophages * Need biopsy (open) NOT FNAB Unable to make intact antibodies Two types: 1. Nodular lymphocyte predominant HL 2. Classical HL: subtypes: - Nodular sclerosis - Mixed cellularity - Lymphocyte-depleted - Lymphocyte-rich

Answer 25

Tumor effaces lymph nodes - Vaguely nodular Pathology: - Popcorn cells - Lobated nuclei - Lacks CD30 and CD15 - Expresses sig, other B cell markers - EBV negative - Skips lymph node groups, does not involve solid organs - Excellent prognosis - Uncommon disease

Answer 26

70% of cases Characteristic Mononuclear CD30+ RS-like cells (lacunar cells) - Mediastinal involvement - Favorable prognosis Broad bands of fibrosis separating: - lymphoplasmacytic reactive cells - occasional eosinophils - neutrophils - classic RS cells

Answer 27

``` Seen in HIV+ individuals Reactive cellular infiltrate with: - Eosinophils - small lymphocytes - histiocytes - abundant RS cells, variants ``` Resembles NS-HL without fibrosis - Less mediastinal involvement - Seen in cervical lymph nodes - EBV+

Answer 28

Rarest - Few lymphocytes in infiltrate - Lots of fibrosis, RS cells/variants - Seen in higher stages, poorer prognosis

Answer 29

Classical RS cells in sea of lymphocytes | - Infrequent to see other inflammatory cells

Answer 30

``` ABVD: Doxorubicin (Adriamycin) Bleomycin Vinblastin Dacarbazime - 90% cure rate with chemo + radiation in advanced disease ``` * *EXCEPT NLP: Chemo, rituximab - ONLY cure is allogeneic stem cell transplant Prognosis: good Index for prognosis (each decreases likelihood of remission): - serum albumin < 4 g/dL - hemoglobin < 10 g/dL - male - age >= 45 years (elderly who receive similar doses of chemo have same outcomes) - Stage IV disease (Ann Arbor) - WBC >= 15,000 - Absolute lymphocyte count < 600/mm3 or < 8% total lymphocyte count

Answer 31

- SVC syndrome - Infection - Interstitial pneumonitis (Bleomycin treatment) Late complications: - Infections (esp. strep pneumo)- vaccinate! - Cardiac (CV disease) - Pulmonary - Infertility - Second malignancies (AML, MDS, solid tumors) - Thyroid disease - Reduced saliva (head and neck radiation)--> dental problems

Answer 32

CD1- CD8: Mainly T-cell CD11-CD15: Mainly myeloid CD19-23: Mainly B-cell CD 30: R-S cells (Hodgkin)

Answer 33

Tumors with high tunover/ tumor burden: - related to rapid turnover and destruction of cells. - hyperkalemia (and associated arrythmias); - hypocalcemia; - hyperphosphatemia, - acidemia; - hyperuricemia (and uric acid nephropathy); - high LDH (may be >100X normal). Treatment: - Prophylaxis and therapy with vigorous hydration and allopurinol. - Monitor labs every 6-8 hours or more often as needed. * Seen in high tumor burden with: - acute leukemias - lymphoblastic lymphomas - Burkitt lymphoma - mantle cell lymphoma - diffuse large cell lymphoma. Major cause of morbidity and mortality.

Answer 34

- Cytopenias – infections, bleeding, anemia (multiple agents - Cardiac – decreased ejection fraction (anthracyclines – doxorubicin) - Secondary malignancies – radiation and alkylators (cyclophosphamide) – breast, lung, bone, hematologic - Neuropathy – vinca alkaloids - Infertility – patients need counseling up front and discussion of fertility preservation

Answer 35

Solid tumor | Caused by anything that suppresses the immune system (incidence on rise with AIDS)

Answer 36

Human t-lymphtrophic virus type-1 | - Associated with ALL cases of adult T-cell lymphoma/leukemia (3% lifetime risk)

Answer 37

``` EBV HTLV-1 HHV-8 C virus H. pylori: gastric lymphoma (cured with infection!) ```

Answer 38

``` B Symptoms (fever, chills, weight loss, night sweats) Palpable, hard, nontender lymph nodes Immunologic abnormalities: - AIH (autoimmune hemolytic anemia) - Immune thrombocytopenia ``` Peripheral neuropathies (due to overproduction of monoclonal proteins) Paraneoplastic neurologic complications

Answer 39

1. Biopsy to establish diagnosis 2. History, exam 3. Labs: - CBC - Chem screen (LDH) 4. Imaging studies: - CT of chest, abdomen, pelvis - PET scan 5. Additional biopsies: - Bone marrow - Any other suspicious site

Answer 40

``` LARGE mass (> 10 cm) Similar pathology, treatment to large B-cell lymphoma ``` Seen in younger women Prognosis similar to Large B-cell lymphoma - Relapses seen in CNS, lungs, GI tract, liver, ovaries, kidneys

Answer 41

Non-Hodgkin's Lymphoma: AIDS-defining illness (in HIV-infected) - More aggressive than in others - Involve CNS, GI tract, anus, rectum, skin, soft tissue - Poor prognosis with: low CD4=, low performance, older age, advanced stage Chemo + HAART= good control Hodgkin's lymphoma: - Increased 5-10-fold incidence - Associated with EBV within Hodgkin-Reed-Sternberg cells - **Mixed Cellularity** or Lymphocyte Depleted types - Involves bone marrow most commonly - 80% seen in late stage (B symptoms)

Answer 42

Marked increase in risk for solid organ transplant patient - Receive aggressive immunosuppression after transplantation - Use acyclovir/ganciclovir to reduce risk of EBV development post-transplantation

Answer 43

1. Complete history (B symptoms) 2. Physical exam 3. CBC, ESR, liver/renal function tests, hepatitis, HIV 4. Serum creatinine, alk-phos, LDH, bilirubin, protein electrophoresis (+serum albumin) 5. Chest x-ray (PA and lateral) 6. CT scan of neck, thorax, abdomen, pelvis * PET more sensitive/specific than CT/gallium- no improvement in outcome

Answer 44

Staging Hodgkin's Lymphoma: Stage I: Single nodal Stage II: 2+ nodal areas on one side of diaphragm Stage III: nodal disease on both sides of diaphragm - Spleen, lymph of Waldeyer's ring= nodal sites Stage IV: extranodal disease

Answer 45

Grow and spread slowly, respond to therapy (radiation, chemo) but always come back - SLL - CLL

Answer 46

Grow rapidly, may be cured with standard chemo +/- radiation | - Diffuse Large B cell lymphoma

Answer 47

Grow and spread very rapidly, often cured with chemo - Patients may die at time of presentation.during therapy from tumor lysis syndome, other complications - Acute Lymphocytic Leukemia (ALL)

Answer 48

1. Chemo: CHOP, purine analogs, bendamustine 2. Radiotherapy 3. Monoclonal antibodies 4. Radiolabelled monoclonal antibodies (target CD20) 5. Stem cell transplantation (allogeneic or autologous stem cell rescue)

Answer 49

MDS= clonal hematopoietic stem cell disorders characterized by marrow failure, peripheral cytopenias, dysplastic morphology - Ineffective hematopoiesis: increased apoptosis of progenitors, limited response to growth factors - Abnormalities in proliferation, differentiation, apoptosis of precursors and progeny High grade: genetically unstable (mutator) - Increased risk of transformation to AML (increased blasts--> increased transformation) - Survival: 6-30 months - 7q- genotype Low grade (lack mutator phenotype) - More stable - Survival: 6-8 years

Answer 50

- Men, > 70 years - Sporadic - Risk factors: previous chemo (solid tumor < lymphoma), radiation, toxic exposures (pesticides, benzene) - Genetic syndromes: Diamond-Blackfan, Schwachman-Diamond, Fanconi's anemia, Dyskeratosis congenita, congenital neutropenia

Answer 51

Peripheral blood: - Anemia (normocytic or macrocytic)- acclerated apoptosis of increased progenitor cells - dual RBC population (may be transfusion related) - +/- Neutropenia, thrombocytopenia - Low reticulocyte count - Dimorphic red cells on histology - Dysgranulopoiesis (pseudo-Pelger-Huet cells= hyposegmented neutrophils): abnormal granulocyte nucleus, staining, shape - Dyserythropoiesis (dysplastic erythroid lineage) - Ringed sideroblasts in RBC precursors (iron accumulation in mitochondria) - Dysplastic megakaryocytes - Dacrocytes (teardrop cells), red cell fragments, rouleaux formation, helmet cells Bone marrow (perform aspirate and biopsy) - Hypercellular - Dysplasia (10% cells in lineage show dysplastic features) - +/- increased blasts (myeloblasts, monoblasts)

Answer 52

``` Clonal abnormalities seen in: 5q deletion (-5) IMPORTANT - Seen in elderly women - Macrocytic anemia, nL/high platelet count, increased megakaryocytes (hypolobulated nuclei) - Mild clinical course ``` 7q- (-7) 20q- (020) +8 * 50% have normal karyotype

Answer 53

Acquired clonal hematopoietic disorders of pluripotent bone marrow stem cells - See proliferation of 1+ myeloid lineages Initially: BM proliferation effective--> neoplastic cells mature - See increased RBCs, granulocytes, platelets in periphery - EFFECTIVE hematopoeisis Pathogenesis: - Genetic stem cell abnormality - Myeloid cell lineage proliferation/expansion - See normal cell progression (initially) vs acute leukemia (arrested in one stage) - Cells hypersensitive to cytokines - Associated with TYROSINE KINASE constitutive activation: BCR/ABL fusion, JAK-2 mutations * See SECONDARY non-clonal fibrosis Epidemiology: 5th-7th decade of life - BM hypercellularity--> increased granulocytes, PBC, platelets in periphery - Can progress to: 1. Marrow failure or 2. Transform to acute blast phase Presentation: - Increased cellularity in peripheral blood - Hepatosplenomegaly

Answer 54

Philadelphia Chromosome: BCR-ABL1 positive t(9:22) - 9= abl1 - 22= BCR (breakpoint cluster region) - -> increased P210 protein leads to: 1) increased proliferation (constitutive tyrosine kinase activity) 2) MYC/BCL-2 transcription--> cells protected from apoptosis (MYC/BCL-2) - Translocation seen in 90-95% CML patients, some ALL (acute lymphoblastic leukemia) Clonal evolution: 70% of patients in blast phase; relapse after BMT: - +Ph (duplication of Ph chromosome) - +8 - isochromosome 17q

Answer 55

MOST COMMON myeloproliferative disease (15-20% leukemias) - Seen in 5th-6th decade - more common in males Bi or Tri-phasic disease; Expansion in GRANULOCYTE pool Chronic phase= insiduous, 2-8 years 1. Bone marrow: - Increased granulocytes (WBC precursors) - Smaller megakaryocytes with hypolobated nuclei= "dwarf" - decreased erythropoiesis - elevated myeloid to erythroid ratio - reticulin fibrosis 2. Peripheral blood: - Increased WBCs (leukocytosis) - Increased thrombocytes (+ abnormal platelets) - Basophilia - Anemia correcting on treatment - Enlarged spleen due to red pulp infiltration by leukemic cells Accelerated phase - Increased blasts: 10-19% in PB or BM - Increased PB basophils (>20%) - Thrombocytopenia/thrombocytosis - Increasing WBC/spleen size - Clonal cytogenetic evolution Blast phase= < 1 year survival - Increased myeolobasts (20%) or extamedullary blast proliferation - Abnormal platelets - Blasts= myeloid (70%) or lymphoid (30%)

Answer 56

Increased production of RBCs with normal arterial O2 saturation (no secondary polycythemia) Clinical/lab criteria: BOTH major, 1+ minor: Major: 1. Elevated RBC mass (> 25% above mean) or Hb > 18.5 in men, > 16.5 in women 2. **Presence of JAK2 V617F (or similar mutation)** Minor: 1. Bone marrow: hypercellular (pan-myelosis) 2. Serum EPO below reference range 3. Erythroid colony formation in vitro (endogenous)

Answer 57

JAK2 mutation - Changes interaction between EPO receptor and JAK2 - Mutation in position 617--> constituitively active JAK--> clonal expansion Bone marrow: - Increased cellularity - Panmyelosis with full maturation (no increase in blasts) - Mild/moderate increase in WBCs, platelets - No iron stain (all being used in RBC production) - Increased reticulin fibers Peripheral blood: - Persistant leukocytosis (elevated WBC) - Persistant thrombocytosis (elevated platelets) Polycythemic phase= most patients - 10% go to "spent" phase (anemia) - 10% show myelofibrosis (with splenogmealy due to extramedullary hematopoieses - 5-10% transform to AML

Answer 58

Mean survival= 13 years Terminal events: see cytogenetic abnormalities (trisomy 18, deletion 20q) - Myelodysplastic transformation - Leukemic transformation - Postpolycythemic myelofibrosis

Answer 59

Megakaryocyte clonal, autonomous proliferation - Must distinguish from inflammatory/malignant processes Epidemiology: - 1/100,000 individuals - 55 years (M=W) - Second peak in women ~30 years - Usually incidental finding Clinical presentation: - may see life-threatening bleeding (common in GI tract) - Erythromelagia (dramatic vasomotor symptoms)= warmth, pain in distal extremities - Splenomegaly - Large vessel thrombosis - May progress to fibrotic phase (like PMF/AML)- rare - Venous thrombosis to unusual sites or PE

Answer 60

50% due to JAK-2 V617F mutation or MPL mutations ``` Proliferation of marrow megakaryocytes Peripheral: - Increased circulating platelets (abnormal morphology) - Normal Hb, WBC - Splenomegaly ``` Bone marrow: - Increased in megakaryocytes - Abnormal clustering of megakaryocytes - Enlarged with hyperlobulated (stag-horn) nuclei, abundant cytoplasm

Answer 61

ALL required for diagnosis: 1. Sustained platelet >= 450,000/uL 2. Megakaryocytic hyperplasia (enlarged and mature) in marrow 3. Exclude other myeloproliferative disorders: - CML (no BCR/ABL fusion) - no PC - no myelodysplasia - no PMF (no collagen/reticulin fibrosis) 4. JAK2 V617F mutation or MPL (EPO receptor) mutation, or exclusion of reactive (secondary) thrombocytosis

Answer 62

Proliferation of Megakaryocytes and Granulocyte elements in bone marrow--> reactive fibrosis - Fibrosis= response to growth factors produced by megakaryocytes (clonally abnormal hematopoietic cells) 1. See reticulin fibers 2. Later: overt collagen fibrosis Marrow fibrosis--> extramedullary hematopoiesis (spleen, liver, etc.)

Answer 63

Major (all 3 needed): 1. Collagen fibrosis/prefibrotic disease in marrow 2. Rule out: CML (no BCR/ABL), PV, other MDS 3. JAK2 V617F mutation or other clonal marker (MPL) Minor (2+ needed): 1. Leukoerythroblastosis (low RBCs, WBCs) 2. Increased LDH 3. Anemia 4. Splenomegaly

Answer 64

1/100,000 Most common in 6th-7th decade 60% have cytogenetic abnormality - Unknown cause (could be radiation- seen in Hiroshima survivors, benzene) Clinical: - Anemia (due to ineffective hematopoeisis, hypersplenism) - Marked splenomegaly (extramedullary hematopoeisis- also seen in liver) - Fatigue, weight loss, night sweats, fever - Peripheral edema, early satiety - Portal HTN (varices, ascites) - Bleeding and thrombotic events

Answer 65

``` Early: - Hypercellular marrow - Prominent, abnL megakaryocytes - Increased reticulin Later: - Increased fibrosis (collagen) - Reduced hematopoeitic elements - End stage: osteosclerosis (thickened bony trabeculae--> decreased marrow space) ``` * Fibrosis in marrow also seen in: PV, CML

Answer 66

Leukoerythroblastosis= increased immature granulocytes and nucleated RBCs (normoblasts) due to: - Extramedullary hematopoeisis - Disruption of normal bone marrow-blood barrier (fibrosis) * Can also be seen in metastatic solid tumors Marrow fibrosis leads to: - myelophthisic anemia (weird RBCs made in other parts of body) - anisopoikilocytosis (abnL RBC shapes + sizes) - Dacrocytes (teardrop-shaped cells) - Giant platelets - Megakaryocytes in circulation Spleen: - Red pulp expansion - Extramedullary hematopoeisis - Focal splenic infarcts

Answer 67

``` Median survival= 3-5 years Poor prognosis: - age > 70 - Hg < 10g/dL - Leukocyte > 25 x 10^9 - Circulating blasts > 1% - Constitutional symtoms ``` Plus: - Platelet < 100,000/uL - Immature WBCs in peripheral blood - Abnormal karyotypes

Answer 68

``` Blood hyperviscosity (due to increased RBCs) causing: - Headaches - blurry vision - Altered hearing - Mucous membrane bleeding - Shortness of breath - Malaise Splenomegaly Thrombosis (arterial most common) - can be in unusual sites (mesenteric, Budd-Chiari) Pruritis (provoked by warm water) Vasomotor symptoms (paresthesias) ```

Answer 69

1. Hypoxia-driven: - Chronic lung disease - R to L cardiopulmonary shunt - High-altitude - Tobacco/CO poisoning - Sleep apnea (hypoventilation) - Renal artery stenosis 2. Hypoxia-independent - Androgen use, EPO - Post-renal trasnplant - Cerebellar hemangioblastoma, meningioma - Pheochromocytoma, uterine leiomyoma, renal cysts, PTH adenoma - HCC, renal cell carcinoma

Answer 70

Reduced p50 (partial pressure of O2 where Hg saturated): - High-oxygen-affinity hemoglobinopathy (Autosomal dominant disease) - 2,3 BPG deficiency (autosomal recessive) - Methemoglobinemia Diagnosis: 1. Measure Serum EPO - low EPO= mutation of EPO receptor - normal/elevated? 2. Measure p50 - decreased p50= high-O2-affinity hemoglobinopathy or 2,3 BPG deficiency - Normal p50--> VHL

Answer 71

1. Infection 2. Rebound thrombocytosis 3. Tissue damage (surgery) 4. Chronic inflammation 5. Malignancy 6. Renal disorders 7. Post-splenectomy status (see Howell-Jolly bodies) 8. Primary thrombocythemia

Answer 72

Main objective= 1. prevent thrombosis in high risk patients (> 60 years, history of thrombosis) 2. Alleviate non-life-threatening symptoms: - microvascular disturbance (headaches, acral parasthesia, erythromelalgia), - pruritis (responds to JAK-inhibitor) - symptomatic splenomegaly (hydroxyurea) * Pruritis related to JAK-STAT signalling-related cytokines 3. Phlebotomy in all patients (target Hct < 50%--> 45% ideal) Prognosis: Median survival ~20 years

Answer 73

Lack of drug therapy: | Bone Marrow Transplant in patients with median survival < 5 years and leukemia risk > 20%

Answer 74

MLL gene translocation: t(11;16)(q23;p13) --> leads to fusion between promoter of cyclic adenosine monophosphate response element binding protein (CBP) and MLL protein > 20% blasts

Answer 75

Peripheral blood: - Persistent, progressive cytopenia - Neutropenia (diabetic with infections, poor wound healing) - Anemia (may see increased angina) - Thrombocytopenia- petechia, bruising, frank hemorrhage * 30% of patients will develop AML - mainly in older patients - See dysplasia in > 50% cells in at least 2 cell lines - 20%+ blasts Clinical signs/symptoms: - Fatigue - Weakness - Infection - Easy bruising - Pallor, petechiae, purpura - No lymphadenopathy, no hepatosplenogmegaly

Answer 76

Seen in elderly predominantly: - Polypharmacy - Vitamin deficiencies (iron, folate, B12) - Parvovirus 19 - HIV - Viral hepatits - Splenic sequestration due to portal hypertension, myelofibrosis, infiltrating lymphoma - Alcoholism

Answer 77

1. Refractory anemia 2. Refractory anemia with ring sideroblasts (RARS) 3. Refractory anemia with excess blasts (RAEB) 4. CMML 5. Refractory anemia with excess blasts in transformation (RAEB-t)

Answer 78

1. Hematopoeitic growth factors: - Recombinant erythropoietic stimulating agent (ESA) - Best in patients with low EPO - G-CSF 2. Epigenetic therapy: - 5-AZA, decitabine 3. Immunomodulatory drugs: - Lenalidomide (for 5q deletion, low risk pts) 4. Immunosuppressive: - antithymocyte globulin plus cyclosporine 5. HSCT= ONLY cure for MDS 6. Iron chelation (for iron overload in transfusion-dependent patients)

Answer 79

Tyrosine Kinase Inhibitor: Imatinib | - Blocks effects of BCR/ABL fusion protein

Answer 80

20% or more blasts in bone marrow Blasts= immature hematopoietic cells of myeloid or lymphoid lineage - Monocytic leukemias= increased tissue infiltration, tumor lysis syndrome, bad cytogenetics Clonal disorder (somatic mutation in hemoatopoietic precursor) of bone marrow--> 1) Accumulation of clonal abnormal blasts 2) Impaired production of normal blood cells - leads to anemia, infection, bleeding Two types: 1) Acute myelogenous leukemia (AML) 2) Acute lymphoblastic leukemia (ALL) Causes: - Clonal hematopoietic disorders: CML, PMF, ET, PV, MDS, PNH - Ionizing radiation - Oncogenic viruses: HTLV-1 (T-cell leukemia), EBV (mature B-cell ALL) - Benzene - Prior chemo with alkylating agents--> myelodysplastic syndromes 4-6 years later (chromosomes 5, 7, 8 abnormalities) - Prior chemo with Topoisomerase Inhibitors: Epipodophyllotoxin (teniposide, etoposide): 1-2 years later, no myelodysplasia--> progresses right to monocytic leukemia (chrom 11 q23 or chrom 21 q22) Genetics: - 20% chance in identical twin with affected twin - Trisomy 21 - Trisomy 13 (Patau) - XXY (Klinefelter) - Bloom's syndrome - Fanconi's anemia - Ataxia-telangiectasia ``` Clinical presentation: - Anemia - Thrombocytopenia - White blood count can be low or high - Neutropenia - Marrow expansion – bone pain - Leukostasis – high WBC modified by cell size and plasticity (Lung and CNS) - Tissue Infiltration; Granulocytic sarcoma (Gums, skin, testes, meninges, retina) - Organomegaly: Hepatosplenomegaly - Mediastinal mass or adenopathy - ALL - Tumor lysis syndrome: uric acid, LDH - Coagulopathy – especially in t(15;17) or with infection ```

Answer 81

``` Neonates= predominant leukemia form Childhood/adolescence= Less common than ALL Adults= 80% of leukemias (incidence increases with age, vs ALL) ```

Answer 82

See symptoms due to: 1) Expansion of malignant clone (w/ or w/o organ involvement) 2) Deficiencies in normal blood cells ``` 1. Leukocytes: low, normal, high High Leukocyte levels--> alterations in blood flow in organs/compromise function (cells sticker, larger, stiffer): - Respiratory failure - Stroke, cerebral ischemia - Infiltration different organs - Skin, CNS, gums ``` 2. Organomegaly with other myeloproliferative disorders 3. Platelet deficiency (thrombocytopenia)--> bleeding, bruising 4. Low granulocytes--> infections 5. Suppression of RBCs--> severe anemia, cardiopulmonary symptoms * See DIC in acute promyelocytic anemia (APL) * Elderly at increased risk for pancytopenia

Answer 83

Labs: - Decreased hemoglobin, platelets - Stains for MPO, non-specific esterases Path: 1. Arrest of myeloid cells at blast phase (>20%): medium to large cells with abundant cytoplasm 2. Cytoplasmic granularity: - Neoplastic promyelocytes= high granularity - Granulocytic blasts= present/absent - Monoblasts= no granularity * AUER RODS= condensed granules - Seen in any AML, more numerous in neoplastic promyelocytes (APL) - Stain red with Wright-Geimsa - NEVER seen in normal myeloid/lymphoblastic precursors

Answer 84

- Stem cell marker (CD34) in myeloid or lymphoid basts - Granulocytic antigens: CD117, CD13, CD15, CD33, MPO - Monocytic antigens: CD14, CD64 - Erythroid marker: glycophorin A - Megakaryocytic antigens: CD41, CD61 * TdT not usually seen in AML, usually in ALL Genetics: - t(8;21)--> core binding factor (transcription factor) abnormalities - inv(16)--> core binding factor (transcription factor) abnormalities - t(15;17)--> PML and RAR (= APL) - t(9;11) due to chemotherapy - t11q23: MLL - trisomy 9 - trisomy 21, 11 - Deletion of 5, 7 - FLT3 mutation (20-40% AML): poor prognosis

Answer 85

CANNOT be cured without HSCT - Admission: cultures, antibiotics if febrile - Fluids, allopurinol to treat/prevent tumor lysis syndrome - M0-M7 treated the same EXCEPT for M3 1. Induction therapy: achieve hematological remission (peripheral blood normal) - Anthracycline for 3 days - Cytarabine for 7 days ex: APL= t(15;17)--> retinoic acid + chemo + arsenic - Retinoic acid induces maturation of tumor cells, prevents accumulation of granules that can cause DIC 2. Consolidation therapy: - High dose Cytarabine: particularly good in t(8;21) and inv16- use high dose ARA-C - Autologous HSCT: after remission, store bone marrow stem cells--> myeloablative chemo--> rescue hematopoeisis with stem cells - Allogeneic HSCT: replenish cells post chemo, allow for graft-versus-leukemia effect (less likely to be effective in older patients) 3. Remission induction: - Anthracycline, cytarabine 4. Maintenance therapy: APL ONLY Side efects: 1. Effects on proliferating cells (skin, gut, marrow) - Cytopenias get worse before they get better - Mucositis - Infections and bleeding worsen 2. Anthracycline cardiac effects

Answer 86

Good Prognosis: - t(8;21), t(15;17), inv(16) - trisomy 21 - NPM1 mutation (nucleophosmin)- normal karyotype - Absence of myelodysplasia - Younger age - CEBPA mutation= normal karyotype Poor prognosis: - Unfavorable karyotypes: 5-, 7-, 5q-, trisomy 8, t(6,9), trisomy 11 - FLT3 - Multidrug resistant (MDR1) - Pre-existing clonal hematological disorder - Older age (> 60) - Higher WBC (> 30,000/uL) - Low platelet count (< 30,000) - Co-morbidities - Prior chemo/radiation therapy

Answer 87

APL: translocation t(15;17)(q22;q21) Forms novel gene: PML-RARA= tumor suppressor (PML) + alpha receptor for nuclear transcription factor retinoic acid - Chimera--> abnormal function--> can't mature past promyelocytic stage Highly responsive to all trans-retinoic acid (ATRA) - dissociates nuclear repression factors (histone deacetylase)--> genes transcribed again - Retinoic acid induces maturation of tumor cells, prevents accumulation of granules that can cause DIC - Adverse effect of ATRA= ATRA syndrome (all cells pushed through maturity--> can cause organ infiltration, like lung failure) +Arsenic= combination therapy that can cure disease * ONLY AML that requires maintenance therapy

Answer 88

12% of all Leukemias 60% of leukemias for people < 20 years MOST COMMON malignancy in patients < 15 years (25% of all malignancies, 75% of all leukemias) - Bimodal distribution: peaks at ages 2-5, again in 60s Subdivided into B-cell and T-cell Etiology: - Down syndrome, Bloom syndrome, neurofibromatosis type 1, ataxia-telangiectasia - Environmental exposures: ionizing radiation in utero, pesticides, solvents

Answer 89

Manifestations due to: 1) expanded malignant clone (may or may not involve organs) 2) deficiencies in normal blood cells Manifestations similar to AML May also involve: 1. CNS/meninges 2. Bone marrow necrosis: pain, fever, high LDH levels 3. Painless testicular enlargement 4. Mediastinal mass (T-ALL) or adenopathy (B-ALL) 5. No symptoms (v. rare)

Answer 90

Labs: Diagnose with peripheral blood, bone marrow morphology, flow cytometry, cytogenetics, molecular genetics Peripheral blood: - Decreased hemoglobin, platelets - May or may not see leukemic cells Bone Marrow: - replaced by malignant clone Immunophenotype: - CD10+, CD19+, TdT, intracytoplasmic IgM+, CD22+, CD79a+, HLA-DR+ Genetics: - t(1;19)(E2A-PBX1) - t(9;22)= BAD prognosis (25% adult AML, 3% child AML)--> 190kD fusion protein - t(12;21)(TEL-AML1)= most common childhood translocation- good prognosis - 11q23 (MLL) abnormalities= BAD prognosis - > 50 chromosomes= good prognosis - < 49 chromosomes= bad prognosis

Answer 91

85% of ALL cases= B-cell type - Malignant cells= immature B-lymphoblasts (B-ALL/LBL) - Lymph node involvement - Leukemic cells smaller than AML blasts, no granules Organ involvement: - Kidney damage: spontaneous/therapeutic tumor lysis - CNS involvement: assess CSF for leukemic blasts * more organ infiltration than AML

Answer 92

ALL in children= curable - NOT in neonates, infants - After 12, cure rate decreases with age 1. Induction therapy: - Glucocorticoids, vincristine, L-asparaginase - CNS prophylaxis 2. Intensification consolidation therapy: - Antimetabolite agents (methotrexate, 6-mercaptopurine) 3. Maintenance Therapy: - Required for children with ALL (other than mature B-ALL): methotrexate, 6MP - Unclear value for adults 4. Allogeneic HSCT: - Children with high risk cases - Less successful in adults - Standard of care in Phl ALL t(9;21) 5. Tyrosine kinase inhibitor (Imatinib)

Answer 93

Good prognosis: - Age > 1, < 12 - Hyperploidy > 50 chromosomes/cell - ETV6-CBFA2 fusion - t(12;21) Poor prognosis: - Phl chrom (esp in adults) - CNS disease - Age < 1, > 12 - Rearrangement of MLL gene (Chromosome 11q23) - High WBC - co-morbidities

Answer 94

- Maturation along neutrophil lineage (M2) - Occurs predominantly in younger adults - Good prognosis - Therapy with high dose ARA-C may be curative. - AML with t(8;21) and inv(16) cause alterations to proteins which are part of the Core Binding Factor transcription complex.

Answer 95

Usually shows monocytic and granulocytic differentiation (myelomonocytic) - Characterized by conspicuous presence of abnormal eosinophils (M4Eo) Occurs predominantly in younger adults - Good prognosis Therapy with high dose ARA-C may be curative. AML with t(8;21) and inv(16) cause alterations to proteins which are part of the Core Binding Factor transcription complex.

Answer 96

Occurs 5-10 years after exposure - Patients present with t-MDS and cytopenias Complex chromosomal abnormalities, frequently similar to those in MDS: -5/del(5q), -7/del(7q) etc.

Answer 97

Follows treatment by 1-5 years - Presents as AML usually without a preceding MDS phase Predominant cytogenetic finding involves translocation of MLL gene (11q23)

Answer 98

Genetic predisposition: - Higher incidence in blacks than whites (blacks have higher physiologic Ig levels) - Familial clusters (>= 2 1st degree relatives with myeloma Environmental: - 3-4 times higher incidence in farmers, cosmetologists - Higher incidence in exposure to pesticides, petroleum products, radiation, long-standing infections (chronic osteomyelitis), chronic antigen stimulation (RA) 93% have MGUS within 8 years of MM diagnosis (100% within 2 years)

Answer 99

1. M-protein in serum or urine (IgG, IgA, light chain) 2. Bone marrow clonal plasma cells or plasmacytoma 3. Organ/tissue impairment (CRAB= hyperCalcemia, Renal insufficiency, Anemia, Bone lesions) ``` C= Calcium > 11.5 R= Renal; Creatinine > 2mg/dL A= Anemia; Hg < 10 g/dL or 2 g/dL below lower end of normal B= Bone disease: lytic lesions or osteopenia ``` * MM treated on the basis of end-organ damage * Bence-Jones Proteinemia= elevated free light chains

Answer 100

Pain, fatigue, anemia, mental status changes, headaches, visual changes, CHF 1. Bone lesions: pain - Osteolytic lesions more common than osteoblastic - plasma cells secrete IL-6--> bone breakdown - MRI (or x-ray) shows "punched out" lytic lesions, osteoporosis, fractures - Seen in vertebrae (MRI detection), skull, thoracic cage, pelvis, proximal humerus/femur - Can also use PET CT (FDG= F- deoxyglucose bone uptake measured) * Do NOT use bone scan 2. Kidney problems: fatigue (anemia) - Cast Nephropathy (light chain deposition) - Decreased EPO (kidney damage) - Uremia/renal failure (light chain deposition= acquired Fanconi's) - Nephrocalcinosis (hypercalcemia from bone destruction) - Amyloidosis (light chain deposition) - Hypercalcemia: thirst 3. Bone marrow infiltration: anemia - Plasma cells replace hematopoeitic cells - Normocytic, normochromic anemia 4. Hypercalcemia: mental status changes, polydypsia/polyuria 5. Blood hyperviscosity: mental status changes, headache, renal failure, visual changes, CHF 6. Radiculopathy due to bone compression: pain 7. Plasmacytomas 8. Infections: s. pneumo, s. aureus, gram-negatives - Impaired antibody response due to abnormal Ig production 9. Bleeding: M-proteins coat platelets - risk of DVT

Answer 101

1. M-protein in serum at myeloma levels (> 30 g/dL) - Higher than in MGUS - IgG, IgA, light chain most common AND/OR 2. 10% or more clonal plasma cells in bone marrow * NO related organ/tissue impairment (end organ damage, bone lesions, myeloma-related symptoms

Answer 102

Progression to symptomatic disease: - 51% at five years - 66% at 10 years - 73% at 20 years Median time to progression= 4.8 years Risk of progression related to amount of M-protein (>= 3 g/dL vs < 3 g/dL) and amount of plasma cells in bone marrow (> 10% or < 10%)

Answer 103

Bone marrow infiltrated with plasma cells (10+%) - Sheets of plasma cells= suggestive of diagnosis CD38+, CD138+, kappa, lambda chain - Diagnose extent of plasmacytosis, light chain restriction * Aberrancies in phenotype, amount of plasma cells exist

Answer 104

Serum Protein Electrophoresis (SPEP) and Immunofixation (IF) of M-protein 1. SPEP: Electrical field used to separate serum proteins (on cellulose acetate) - Separated proteins fixed to membrane, stained with protein-binding dye - Normal: should see smooth, broad gamma globulin distribution - Myeloma: sharp, dominant monoclonal band (M-spike)--> homogenous Ig (with lower than normal levels of other Ig) - Infections: excess polyclonal Ig 2. Immunofixation (IF): proteins separated by electrophoresis incubated with monoclonal antisera - Membranes removed, gels washed - Proteins precipitating with antisera remain in gel--> dried and stained - Typically IgG elevated (then IgA, light chains) with other Ig levels lower * More sensitive than SPEP (used in combination most times) 3. Can also measure concentration of unbound (free) kappa and lambda light chains in serum and 24-hour urine - Kappa:Lambda ratio helps diagnose MM - > 4:1--> kappa population - < 1:2--> lambda population

Answer 105

Durie Salmon Myeloma staging system Stage I: all of the following: - beta-2 microglobulin < 3.5 - Mild anemia - Normal calcium - Few bone lesions - Low M-protein (paraprotein) levels * Good prognosis (low tumor mass) Stage II= in between I and III Stage III: 1+ of following: - beta-2 microglobulin > 5.5 - Hg < 8.5 g/dL - Elevated calcium - Advanced lytic bone lesions - High M-protein levels * Poor prognosis (high tumor mass) Subclassification: A= normal renal function (serum creatinine < 2 mg/dL B= Abnormal renal function (serum creatinine > 2mg/dL * Renal failure= poor prognostic indicator Beta-2 microglobulin and LDH levels have also been linked to prognosis

Answer 106

Bad prognostic indicators: - Deletion 13, aneuploidy - t(4;14) or t(14;16) or t(14;20) by FISH - Deletion 17p13 by FISH - Hypoploidy * Median survival= 25-29 months Good prognostic indicators: - Absence of genetic markers above - Hyperdiploidy - t(11;14) or t(6;14) * Median survival= 50-62 months

Answer 107

Order of treatment: 1. Induction phase 2. Autologous stem cell transplant 3. Maintenance phase Chemo for MM: 1. Lenalidomide, Thalidomide 2. Bortexomib HSCT: 1. Autologous: improve quality of life, survival (even in elderly) 2. Allogeneic: may be curative, but lack of donors, many co-morbidities Treatment of complications: 1. Vaccines (due to Ig disorder) 2. Hydration (prevent renal failure) 3. Avoid nephrotoxic IV contrast 4. NSAIDs, bisphosphonates to prevent skeletal morbidity 5. Calcium, vitamin D in non-hypercalcemic patients 6. Radiculopathy - Palliative radiation, dexamethasone-based therapy 7. Hydration, bisphosphanates to correct hypercalcemia 8. Pamidronate, zoledronic acid (bisphosphanates) to prevent fracture

Answer 108

Precursor lesion in all MM patients= M-protein in patients without evidence of: - plasma cell myeloma - Waldenstrom macroglobulinemia - Primary amyloidosis M-protein elevations also seen in lymphoproliferative diseases, CLL (with no effect on clinical course) See expanded clone of Ig-secreting cells

Answer 109

- Discovered on routine blood work - Increases with age (3% of people over 50, 5% over 70 years) - More common in men than women (1.5:1) and African Americans than caucasians (2:1)

Answer 110

``` May never advance to MM: 20 years after diagnosis: 50% patients die of unrelated causes 25% have no M-protein change 25% develop plasma cell neoplasm/lymphoproliferative disease: - IgA progression > IgG progression - Increased risk with increase M-protein - Increased with abnormal free light chain ratio (Kappa:lambda) ``` * Constant 1% progression rate to malignancy (vs variable progression rate of smoldering multiple myeloma) * NO TREATMENT for MGUS

Answer 111

- M-protein present at lower levels than in myeloma (M-protein < 30g/L), other Ig normal - Bone marrow plasma cells < 10% - NO lytic bone lesions - NO end-organ damage (CRAB) - No evidence of other B-cell lymphomas

Answer 112

RARE (need > 20% peripheral blood cells to be plasma or 2x10^9 plasma cells/L) Clinical features: - Renal failure - Lymphadenopathy - Organomegaly Labs: - See higher proportion of light chain, IgD, IgE myelomas - More unfavorable cytogenetic abnormalities

Answer 113

3% of plasma-cell myelomas have no M-protein on IF - Seen within cytoplasm in 85% - Remaining 15%--> no Ig synthesis (non-producer); light chain gene mutations implicated

Answer 114

Localized tumors of neoplastic plasma cells - Seen in bone (solitary lesions) or soft tissues (extraosseous, extramedullary) - Solitary or part of systemic plasma cell myeloma - Occur without other features of plasma cell myeloma 4 criteria must be met: 1. Biopsy-proven solitary lesion with evidence of clonal cells 2. Normal bone marrow. 3. No anemia, hypercalcemia, or renal disease. (No other evidence of disseminated multiple myeloma.) 4. Normal levels of immunoglobulins.

Answer 115

1. IgM monoclonal gammopathy (with lower than normal levels of other Ig) 2. > 10% bone marrow lymphoplasmacytic infiltration exhibiting: - IgM+ - CD19+ - CD20+ - CD22+ - CD5 +/- - CD10-/+ - CD23-

Answer 116

Symptoms: - Weakness - Fatigue - Bleeding (oronasal) - Vision changes - Dyspnea - Weight loss - Neurologic symptoms - Recurrent infections - Heart failure - Retinal hemorrhages, exudates, venous congestion with vascular segmentation - Sensorimotor peripheral neuropathy Signs: - Pallor - Hepatosplenomegaly - Lymphadenopathy Rare: - Bone lesions, renal insufficiency, amyloidosis

Answer 117

- Anemia (moderate to severe)- normocytic, normochromic - Elevated IgM (on IF) - Rouleau formation, increased ESR - Dutcher bodies (IgM inclusions)

Answer 118

``` Similar to treatment of MM Only treated if they have symptoms: - Anemia - Weakness, fatigue, night sweats, weight loss - Hyperviscosity - Hepatosplenomegaly - Lymphadenopathy ``` Plasmapheresis, autologous HSCT, lanolidomide (chemo)

Answer 119

- Chronic nasal bleeding, oozing from gums - Post-surgical, GI bleeding - Retinal hemorrhages - Sausage-like segmentation of vessels in eye, papilledema--> vision issues - Dizziness, headache, vertigo, nystagmus, decreased hearing, ataxia, parasthesias, diplopia, somnolence, coma Treatment: - Plasmapheresis for symptoms (may need more than one treatment with IgG M-proteins as they extravasate) - Chemotherapy for underlying malignancy

Answer 120

Plasma cell dyscrasia - related to myeloma - Light chain misfolding--> beta-pleated sheets (instead of normal alpha chains) - Leads to insoluble protein deposits in tissues - Stains with Congo red (apple-green birefringence under polarized light) Three types: 1. Systemic light chain amyloidosis (most common)= AL 2. Amyloidosis due to chronic infection, inflammatory arthropathies= Secondary AA - Tuberculosis, Osteomyelitis 3. Inherited familial cardiomyopathies/neuropathies (familial AA or AF) Symptoms: - organ infiltration of heart, nerves, kidneys, autonomic dysfuction, gut involvement Workup: - SPEP/IEP (immuno electrophoresis) - Light chains - Marrow biopsy - Fat pat biopsy

Answer 121

Signs: - Tongue enlargement with dental indentations - "pinch" or periorbital purpura due to vascular fragility - hepatomegaly Symptoms: - Fatigue - Edema - Dyspnea - Anorexia - Parasthesias Syndromes: - nondiabetic nephrotic-range proteinuria - Cardiomyopathy ("hypertrophy" on ECG) - Peripheral neuropathy (4% patients)--> bowel dysfunction

Answer 122

Up to 50% of amyloidosis patients effected - Poor filling in diastole - Poor stroke volume despite normal EF - ECG: thickening of heart walls due to infiltration of amyloid appears like Left Ventricular hypertrophy (LVH) Heart Failure due to: - silent hypertension - hypertrophic cardiomyopathy *Prognosis of disease depends on cardiac involvement

Answer 123

13% of patients - Hepatomegaly - Increased serum alkaline phosphatase - Deficiency of coagulation factor X

Answer 124

Must perform SPEP with IF - Monoclonal proteins very small--> not detectable on SPEP alone Confirmatory diagnosis (needed due to complications): - Biopsy with congo red stain - Subcutaneous fat aspiration (fat pat): recognizes 70% amyloid deposits - Bone marrow biopsy (to rule out multiple myeloma)- 50% sensitive - BOTH: 87% recognition

Answer 125

``` Much better prognosis Seen commonly in: - Ureter - Bladder - Urethra - Prostate - Brain (Alzheimer's) ```

Answer 126

Transthyretin (normal serum protein) deposited on myocardium

Answer 127

Only 3% of cases One variant has transthyretin amino acid substitution (122: Val--> Ile) - 3.9% of blacks in USA - Heterozygotes: late onset cardiomyopathy with wall thickening - Mild heart failure

Answer 128

``` Polyneuropathy Organomegaly Endocrinopathy M-protein Skin changes ``` High levels of VEG-F--> sclerotic bone lesions (similar to clubbing) - Associated with polyneuropathy, organomegaly, small plasma cell clone

Answer 129

1. Immediate: hours to days - N/V, flushing, hemorrhagic cystitis (cyclophosamide), fever and chills (bleomycin) 2. Early effects: days to weeks - Hematopoietic depression, alopecia, stomatitis, cerebellar ataxia (5-FU), pancreatitis (L-asparaginase), pulmonary infiltrate (MTX) 3. Delayed effects: weeks to months - Anemia, Azoospermia, hepatocellular damage, skin hyperpigmentation, pulmonary fibrosis (bleomycin, busulfan), cardiotoxicity (anthracyclines), SIADH (cyclophosamide, VCR), cholestatic jaundice (6MP) 4. Late effects: months to years - Sterility, hypogonadism, second malignancies, hepatic fibrosis, encephalopathy

Answer 130

Grade 0= no harm Grade 1= no interference with activity (unnoticed) Grade 2= interferes with activity; outpatient treatment Grades 3, 4= Hospitalization, change in functional status Grade 5= fatal

Answer 131

1: Bronchospasm, wheezing, agitation, angioedema (starts within minutes) 2. Delayed; includes hemolytic anemia 3. Interstitial pneumonitis and vasculitis (ex. from methotrexate toxicity) Caused by: - L-asparginase - Paclitaxel, docetaxel (vehicle causes reaction--> premedicate with steroids) - Procarbazine - Teniposide

Answer 132

Most chemo causes N/V - May see anticipatory emesis (Pavlovian) Neurotransmitters 5HT3 adn NK1--> medullar, nucleus tractus solitarus, cerebral cortex, GI tract afferent stimuli, vestibular stimuli Treatment of Nausea (from highest level): - 5HT 3 receptor antagonist and steroid - Phenothiazine, steroid, benzodiazepine - Phenothizines, corticosteroids (delayed antiemetic)

Answer 133

Radiation and chemotherapy - 5 days after therapy with cytotoxic agent: recovery within days of cessation - May require narcotics for relief - Bacterial/fungal superinfection common

Answer 134

Bone marrow depression: 7-10 days after therapy - neutropenia: susceptibility to infection - thrombocytopenias: hemorrhage - Recovery by 3-4 weeks post-treatment (some can cause long-term dysplasia) Treatment: cytokines, GCSF, GMCSF, EPO, oprevleukin - Epoetin alfa (procrit) - Oprelvekin - G-CSF - GM-CSF

Answer 135

1. Alkylating agents: - Progressive ovarian follicle loss--> menopause - Prolonged azoospermia Radiation: - Ovarian and testicular failure

Answer 136

* Must evaluate pituitary-gonadal axis (FSH, testosterone, estradiol, prolactin, TSH) * May also see Addisonian like syndrome from Busulfan use - Hyperpigmentation, malaise, fatigue, anorexia, weight loss - NO adrenal failure labs Hyperglycemia: steroids, pazopanib Ipilumumab, pazopanib--> hypothyroidism

Answer 137

Chemo causing neuropathy: numbness, tingling, weakness, footdrop, autonomic neuropathy (cramping, constipation) - Vinca alkaloids, vincristine, vinblastine, taxanes (paclitaxel, docetaxel) - Heavy metal drugs (cisplatin) Cisplatin--> high tone hearing loss (damages organ of Corti) Ara-C--> cerebellar toxicity (Purkinje fiber drop out) Reversible posterior leukoencephalopathy Peripheral neurotoxicity: - Taxanes - Vincas - Platinum-based compounds Central neurotoxicity: - Ifosphamide - high dose methotrexate - 5-FU - Procarbazine - ara-C - Fludarabine

Answer 138

Brain-capillary leak due to HTN, fluid retention, cytotoxicity on vascular endothelium Symptoms: acute bilateral loss of vision, headache, confusion Caused by: tacrolimus, cisplatin, epoetin, immune globulin, VEGF-inhibitor Diagnostics: white matter changes Treatment: reversible with control of BP, fluid status

Answer 139

Seen long after treatment (ex. CNS prophylaxis for childhood leukemias Symptoms: 1-year post-cranial RT: - Confusion, drooling, somnolence, irritability, ataxia, dementia, tremors, quadriparesis, slurred speech Diagnosis: - Abnormal CT: ventricular dilatation, subarachnoid space dilatation - Significant cognitive defecits - Path: demyelination, multifocal necrosis, astrocytic reaction, axonal damage Causes: - Cranial radiotherapy, intrathecal methotrexate, intravenous MTX

Answer 140

Classic: Bleomycin pulmonary fibrosis - Also associated with mitomycin, alkylating agents, methotrexate, ara-C - ATRA: respiratory distress - Taxol/Taxotere: bronchospasm, anaphylaxis/pulmonary edema Dose-related Pathophysiology: - Decreases in DLCO, +/- change in FVC, decreased O2, CO2 - aggravated by high dose inspired O2 and previous/concomittant radiation - Free radical formation, activation of inflammation--> upregulated collagen synthesis, cytokines Symptoms: dry cough, exertional dyspnea, rare chest pain or hemoptysis Path: Type 1 pneumocyte decrease, Type 2 pneumocyte increase--> migrates into alveolar sacs, sepate become thicker

Answer 141

#1 example: Dose-limiting effect of anthracyclines (lifetime dose limit) - Occurs within 3 years (typical): increasing tachycardia, fatigue, pulmonary edema, CHF - Due to mitochondrial injury, depletion of ATP/phosphocreatine, depression of contractility, free radical formation/lipid peroxidation - Add dezrazoxone for cardioprotection Cardiotoxicity also seen with: - cyclophosphamide, ifophosphamide (high doses) - Paclitaxel (arrhythmias, sinus bradycardia) - Vincristine, vinblastine (autonomic dysfunction) - 5-FU (chest pain, atrial arrhythmia, ventricular dysfunction, cardiac failure, coronary artery spasm) - Ondansetron (antiemetic), pazopanib - Herceptin (traztuzumab

Answer 142

Cisplatin= prototype nephrotoxic drug - Heavy metal--> acute proximal tubular necrosis (weeks post-therapy) - Given with forced hydration to prevent high concentrations in tubule - Can also cause K+, Mg+2 wasting Methotrexate, mitomycin C= also nephrotoxic Tumor lysis syndrome--> urate nephropathy

Answer 143

Mild transaminitis from agents excreted in biliary tree - Anthracyclines - Anti-tumor antibiotics (actinomycin D) Hepatic fibrosis: - Chronic methotrexate Veno-occlusive disease: - Chemo in transplants - See fluid retention, painful hepatomegaly, elevated bilirubin, high mortality

Answer 144

Carcinogenesis from therapy (could also be due to environmental trigger): Acute leukemia: - radiation exposure - alkylating agents for hematologic neoplasms - Topoisomerase II inhibitors (myelodysplasia risk) - Rare after solid tumors (ovarian ca, bladder ca, lymphoma) - Seen after Hodgkin's treatment Lymphoma: - Second neoplasm in Hodgkin's treated with radiation, chemo - B-cell lymphoma after transplant (can be reversed by withdrawing immunosuppressive therapy)

Answer 145

May occur early or late: suprapubic pain, dysuria, urgency, hematuria Caused by: - Cyclophosamide - Ifosphamide - Mesna (mercaptoethanol)

Answer 146

ex: Bevacizumab ``` HTN Proteinuria Increased bleeding Clotting Bowel perforation ```

Answer 147

ex: Cetuximab Folliculitis Diarrhea Interstitial pulmonary fibrosis

Answer 148

5-10 years post-exposure - See t-MDS and cytopenias - Chromosomal abnormalities similar to MDS: -5/del(5q), -7/del(7q)

Answer 149

1-5 years after treatment - Presents as AML without MDS phase - Translocation of MLL gene (11q23)

Answer 150

``` T0= no evidence of primary tumor invasion (carcinoma in situ) T1= Tumor invades lamina propria, muscularis mucosa, submucosa T2= Tumor invades muscularis propria T3= Tumor invades muscularis propria into subserosa T4= Tumor invades adjacent organs, perforates viscera ```

Answer 151

``` N0= no regional lymph node involvement N1= 1-2 regional lymph nodes N2= 3-6 regional lymph node metastases N3= 7+ regional lymph node metastases ``` M stage: M0= no distance metastases M1= distant metastatic sites - Need to examine at least 15 lymph nodes to rule out metastases

Answer 152

``` R0= all tumor cells removed (only in 50% of GE surgeries)- complete resection with 4 cm margins R1= some cells remain (microscopic residual) R2= macroscopic residual disease ```

Answer 153

Improves survival, but may be intolerable to patients

Answer 154

Improved outcomes after peri-operative chemo

Answer 155

Risk factors: - Barrett's esophagus - H. pylori - Smoking - High salt diet - Inherited syndromes (1-3%): diffuse, e-cadherin mutations, CDH1 UES + biopsy - Stain specimen for HER2 (in 20% of cancer) PET/CT

Answer 156

Strong correlation: Cigarette smoking Weaker: - Diabetes - Obesity - Diet - Chronic pancreatitis

Answer 157

``` BRCA2 Familial atypical multiple mole-melanoma syndrome (p16 mutation) Peutz Jehers Familial pancreatitis HNPCC Ataxia-Telangiectasia (ATM) FAP- 4.5 relative risk ```

Answer 158

``` Weight loss Jaundice Greasy stools Abdominal pain/back pain Nausea Anorexia Depression Sudden onset diabetes ```

Answer 159

``` CT scan (pancreatic protocol) - Triphasic, thin slices Endoscopic US with biopsy Histology: - 90% adenocarcinoma - 10% less common variants (neuroendocrine- better prognosis) CA 19-9: - Sialylated Lewis blood group antigen: not tumor specific but can be helpful with follow-up ```

Answer 160

Makes it difficult to reach tumor with radiation "soil in which tumor can grow" - Provides nutrients, growth factors

Answer 161

``` T1= < 2 cm T2= > 2 cm T3= Extends beyond pancreas, NOT to celiac axis, SMA T4= involves celiac axis, SMA - Can cause lots of pain ```

Answer 162

``` N0= no regional N1= positive regional lymph node metastases ``` ``` M0= no distant metastases M1= distant metastases ```

Answer 163

Only 20-25% have resectable disease - Only 20-25% of these survive for 5 years Overall, 5% 5-year survival rate

Answer 164

Resectable: - No distant metastases - Clear fat plane around celiac, SMA - Patent SMV, portal vein Borderline: - Severe uni/bilateral SMV/portal impingement - < 180 degree tumor abutment on SMA - If reconstructible, abutment or encasement of hepatic artery or SMV occlusion Unresectable: - Distant metastases - Encases SMA by > 180 degrees - Abuts celiac axis: unreconstructible SMV/portal vein occlusion - Lymph node metastases beyond field of resection

Answer 165

Whipple procedure - R0= complete resection with negative margins - R1= incomplete tumor resection - R2= Substantial remaining tissue * Only 20% resectable - < 5% mortality in experienced hands - Median survival 15-19 months - 5-year survival only 20%

Answer 166

Chemo alone: Gemcitabine Chemo + XRT: 1. sandwich gem 2. 5FU/XRT 3. sandwich gem Post-op XRT 45-54 Gy with chemo sensitizer Clinical trial post-op

Answer 167

Prolonged recovery from surgery prevents/delays post-op treatment - Selects for patients with more stable, repsonsive disease for surgery - More sensitive to treatment - Can downsize tumor

Answer 168

Orally bioavailable tyrosine kinase inhibitor for HER1/EGFR - Used in post-op pancreatic cancer patients 10-day increase in survival (what?)

Answer 169

80% of patients have pain at presentation Celiac plexus nerve block to manage pain + medications

Answer 170

5th most common malignancy worldwide < 30% cure rate with surgical resection

Answer 171

Hepatitis B and C infection - 1.5 million people in US with Hep B - 4 million with hep C - Annual HCC is 0.5% in asymptomatic HBV, 2.5% in symptomatic HBV - Annual HCC in HCV= 3-8% Cirrhosis: - Alcoholic - NAFLD - Autoimmune hepatitis - Primary biliary cirrhosis

Answer 172

Metabolic disorders: - Herditary hemochromatosis - Wilson's disease - alpha-1 antitrypsin - Prophyria cutanea tarda Environmental toxins: - Arsenic - Aflatoxin (aspergillus)

Answer 173

Necroinflammatory changes/regeneration leading to accelerated turnover--> spontaneous mutations, DNA damage HBV: x-protein inactivates p53 and interacts with transcriptional activation functions HCV: activates NFkB to stimulate proliferation, inhibit apoptosis

Answer 174

Cirrhosis, alcoholics, HCV, HBV, NASH, primary biliary cirrhosis Serial ultrasound, AFP testing every 6-12 months - Follow-up CT/MRI is abnormal

Answer 175

``` RUQ pain Weight loss Early statiety Anorexia Jaundice Abdominal distension Weakness Bleeding ```

Answer 176

``` Hepatomegaly Splenomegaly Wasting Hepatic bruits Plummer erythema Fever Ascites Liver nodularity Spider angiomata ```

Answer 177

``` Hyperbilirubinemia Abnormal liver function tests Prolonged coagulation parameters Thrombocytopenia Hypoalbuminemia Hypoglycemia Erythrocytosis Hypercalcemia Hypercholesterolemia ```

Answer 178

``` Hepatitis serology LFTs, CBC, chems, AFp PT/PTT Child-Pugh classification Imaging: CT of chest, bone scan ```

Answer 179

``` Ultrasound CT (triphasic) MRI (triphasic) Angiography PET: less useful (20-50% accuracy) ```

Answer 180

Diagnosis of HCC can be made radiographically - Lesions 1-2 cm in size: classic appearance on two different imaging modalities - Lesions > 2cm or AFP > 200 with arterial enhancement on one imaging modality

Answer 181

Child-Pugh score TNM (tumor, nodes, metastases) Okuda Cancer of the liver Italian program (CLIP) Barcelona Clinic Liver Cancer (BCLC) Chinese University Prognostic Index (CUPI) Obstacles to systemic treatment: - advanced Child-pugh score - Poor performance status - Thrombocytopenia - Bleeding disorders - Poor liver reserve - Underlying liver dysfunction: change dosing

Answer 182

< 1/3 patients are ideal surgical candidates - Child-pugh class A - Small < 5 cm tumors - Encapsulated (50%) - Unilobar disease - No portal HTN - No tumor in portal vein, IVC - Minimal cirrhosis - No distant metastases - 5 yr Overall Survival (OS) 50-70%

Answer 183

``` Solitary tumor < 5 cm No more than 3 tumors, each < 3 cm No vascular invasion No extrahepatic disease Childs-pugh B or C ``` 4 year Disease free status (DFS): 92% 4 year OS: 85%

Answer 184

Normal hepatic tissue= portal vein supply Hepatic tumors= hepatic artery supply - Gelatin sponge particles +/- chemo, radio microbeads delivered to tumor * Ensure liver has adequate portal inflow/outflow Chemoembolization= more effective than embolization alone - 2-year survival= 63% vs 50%

Answer 185

H&P, LFTs, AFP every 3-6 months | Imaging: dynamic CT, MRI q 6months

Answer 186

``` * Experimental drug Multitargeted Tyrosine Kinase inhibitor - Targets Raf, VEGFR, etc. - Raf= overexpressed, activated in HCC - Raf/Ras/MEK pathway: hepatic tumorigenesis ``` Induces apoptosis in HCC xenograft models - Phase II data promising

Answer 187

Two types: - Stromal tumors (leiomyomas): submucosal, benign - Squamous papillomas (RARE): from HPV infection

Answer 188

Squamous cancer: 1. Smoking (5-10-fold risk) 2. Alcohol (+ Smoking) 3. HPV 4. Chronic esophagitis Adenocarcinoma: 1. Barrett esophagus (10-fold) 2. Obesity, male, heartburn, older age, white

Answer 189

cardia: Mucin-secreting Gastric body: parietal cells (HCl), oxynitis cells (pepsinogen)' Antrum/pyloris: Mucin-producing cells

Answer 190

H.pylori= greatest risk factor - Cigarette smoking - Dietary substances: nitrites - Microbial contaminants in food (aflatoxin B) - Incidence has decreased significantly - Strophic gastritis - Adenomatous polyps - FAP

Answer 191

Early refers to size, not duration; early lesions may have spread to nodes - No necessarily precursors - Even with metastases, more curable - "early" gastric cancer= misnomer, as it has different biological morphology

Answer 192

Benign: - Adenomatous polyps (uncommon) - Peutz-Jehers polyps - GISTs Malignant: - Adenocarcinoma (uncommon) - NETs (carcinoid tumors): ileum= most malignant - Lymphomas

Answer 193

Adenomas: very common - Tubular adenoma: on stalks, potentially premalignant, cancer probability depends on size - Villous adenoma: Sessile, more malignant - Tubulovillous: mixed histo (25-75% villous), intermediate cancer risk Hyperplastic polyps Familial polyposis coli Juvenile polyps Adenocarcinoma

Answer 194

Large broad-based cauliflower-liked lesion - Finger-like processes with fibrovascular cores with hyperchromatic nuclei - > 2 cm at time of discovery Higher malignancy rates than tubular adenomas - 50% of adenomas > 2 cm

Answer 195

Hereditary non-polyposis coli cancer (Lynch syndrome) - AD inherited mutation in DNA mismatch repair (MSH2), MLH1 (40%), MSH6 - Predisposition to mutation in other allele - Methylation can also decrease expression of mismatch repair genes - 80% lifetime risk for colon cancer - younger age (< 44 years) - RIGHT sided - Increased risk of endometrial carcinoma (80% lifetime in women) - Digestive system cancer risk (pancreas, hepatobiliary, stomach, small intestine) - Urinary tract cancers

Answer 196

Originates anywhere within biliary tree - Age= 60 years Causes: - Chinese liver fluke (C. sinensis) - Primary sclerosing cholangitis (PSC)

Answer 197

Family history: - 1st degree relative < 60 with colon cancer, adenomatous polyps - two 1st-degree relatives with cancer at any age Screen at 40 or 10 years prior to age of youngest individual (whichever is first) - Surveillance at 5 year intervals

Answer 198

3+ relatives with associated cancer (colorectal, cancer of endometrium, small intestine, ureter, renal pelvis) 2 successive generations involved 1 of cancers diagnosed before 50 (1 should be 1st degree relative of other 2) - Criteria can miss 1/2 of all HNPCC families Bethesda criteria: - CRC in patient < 50 years - Synchronous/metachronous HNPCC associated tumors (colon, small bowel, endometrial, GI/GU) - CRC in patient= 1+ first degree relatives with HNPCC related cancer, one at < age 50 - CRC in patient with 2+ 1st or 2nd degree relatives with HNPCC related to cancer at any age

Answer 199

FAP Attenuated FAP MYH associated polyposis Peutz Jeghers

Answer 200

Muir-Torre syndrome: - HNPCC with skin lesions (sebaceous adenoma/carcinoma) - Genitourinary cancers Gardner Syndrome - FAP with cutaneous lesions (osteomas, epidermoid cysts), desmoid tumors Turcot syndrome: - HNPCC + glioblastoma - FAP + medulloblastoma Peutz-Jeghers syndrome - Small bowel + colonic hamartomas - Increased GI cancer risk (CRC, small bowel, pancreatic cancer) - Perioral pigmentation

Answer 201

Advanced lesion : screen every 1-3 years - > 1 cm - Villous - High grade dysplasia More than 2 lesions: screen every 3-5 years 1-2 lesions without advanced features: screen every 5 years

Answer 202

Increased cancer risk, esp in inflamed segments Initiate screening after: - Pancolitis: 8 years of disease - Left-sided colitis: 8-15 years of disease Biopsy 4 quadrants every 10 cm Attention to strictures and polyps Surveillance every 1-2 years

Answer 203

1. Remove entire cancer with enough bowel proximal and distal: submucosal lymphatic tumor spread 2. Remove regional mesenteric draining lymphatics (pedicle) - Predictable lymphatic spread - Regional mesenteric involvement without concurrent distant involvement 3. En bloc resection of involved structures 4. Exploration: visual, tactile, ultrasound 5. Minimize psychological/functional consequences without compromising first four concepts

Answer 204

5FU: inhibits thimydylate synthase Capecitabine: Metabolized to active 5FU within tumor - Side effects; diarrhea, hand-foot syndrome (redness and blistering) Oxaliplatin: Platinum derivative--: DACH adducts, impairs DNA synthesis; bulkier and more hydrophobic - Pharyngolaryngodysesthesia - Doubled remission rate, prolonged time to prognosis

Answer 205

Palliative therapy: increase lifespan, decrease side-effects of cancer

Answer 206

Key pro-angiogenic protein - Helps tumor grow - Increases vascular permeablity - Tumor endothelial receptor expression > normal tissue endothelium Bevacizumab= Anti-VEGF antibodies - inhibits downstream VEGF signalling Aflibercept= Part of human VEGF receptors 1 and 2 fused to Fc of human IgG1 - "trap" for VEGFR to prevent activation of VEGF receptors, inhibit angiogenesis

Answer 207

Overexpressed in 60-70% solid tumors - ligands upregulated: EGF, TGF alpha TK inhibitors= EGFR blockade 1. Cetuximab (first generation) 2. Panitumumab: fewer infusion reactions (human monoclonal) 3. Regorafenib: small molecule inhibitor of VEGFR, FGFR, PDGFR, BRAF, KIT< RET - all involved in tumor growth/angiogenesis - Overall survival improvement: 6.4 months vs 5 months - Can cause skin rash (acneiform)

Answer 208

Breast and lung cancer

Answer 209

Back pain, exacerbated by lying down, Valsalva - Weakness below level where pain exists - Bladder/rectum dysfunction

Answer 210

Plain films: bony destruction MRI: anatomic detail of involvement Obtain pathologic specimen if patient does not carry a known malignant diagnosis

Answer 211

Urgent high dose steroid administration (dexamethasone) - Surgery due to progressive deficit - Radiotherapy to shrink tumor in inoperable/less urgent cases

Answer 212

Sudden changes in hemodynamic function due to compression of myocardium by fluid around it - Treated timely, can be fully resolved - Need high index of suspicion: may have complex differential diagnosis (pulmoary parenchymal problems, TB infiltrate, etc.) Pathophys: - Sudden accumulation of fluid in pericardial space preventing full ejection Etiology: - Most common with lung, breast cancer, lymphoma, metastatic melanoma - 10-15% autopsies - Differential diagnosis: lymphangtitic spread, CHF, radiation pneumonitis, pulmonary toxicity Signs/Symptoms: - Insiduous - Severe dyspnea, orthopnea, cough, fatigue, palpitations, dizziness, chest pain, Kussmaul's sign, paradoxical pulse - tachycardia/tachypnea - XRAY: waterbottle heart - ECHO - RARELY need cardiac catheterization Treatment: - Acute: Pericardiocentesis, window - Chronic: pericardiocentesis with sclerosing agent, chemo and surgery, radiation

Answer 213

Most common metabolic emergency in cancer patients Due to: - Excess bone reabsorption, calcium release, increased renal absorption of calcium - Most common in lung, breast, hematologic malignancies Clinical diagnosis: - CNS, PNS symptoms, GI symptoms (dyspepsia, constipation, severe bone pain) - May be due to skeletal invasion by humoral mechanisms--> osteoclast activation - Classic neoplasms associated with it Pathophys: - Release of calcium from bone due to invasion - Horomonal process causing calcium release - PTH of vit-D mechanisms (T-cell lymphomas) increasing Ca absorption Etiology: - Lung, breast, renal, multiple myeloma, lymphoma (T-cell more common), breast cancer with skeletal metastases Signs/Symptoms: - N/V, dysphagia, anorexia, constipation - polyuria, polydypsia - muscle weakness, hyporeflexia, mental status changes, kidney stones - Severe bone pain - Pancreatitis/kidney stones= rare - Serum Ca > 14 - EKG changes: prolonged PR, shortened QT interval Treatment: Saline rehydration - Diuresis with furosemide - IV bisphophonates - Calcitonin, steroids (v. effective in plasma cell dyscrasias), dialysis for renal dysfunction

Answer 214

Can be avoided by prepping for anti-tumor treatment Pathophys/etiology: - Rapid necrosis of bulky tumors after chemo and radiation therapy - Acute cell destruction, release of intracell products - URic acid, phsphates, calcium, potassium released - Causes kidney damage--> hyperkalemia, hyperphos, hypocalcemia, uremia Most common with: - Acute leukemia, chronic leukemias, lymphomas, small cell lung cancer Signs and symptoms: - Uremia: lethargy, decreased sensorium - Hyperkalemia: EKG abnormalities, arrhythmias Treatment: - IV hydration - Allopurinol with alkalinization or urine - Rarely need rasburicase - Dialysis in rare occasions

Answer 215

Rare: usually have time for something to be done nonemergently (radiation, surgery) Pathophys: - Tumor-induced destruction with rupture of arteries--> hemoptysis Etiology: - Lung cancer - Metastatic renal cancer - Metastatic melanoma - Bevacizumab (Avastin): block VEGF receptor- do not use in squamous cell carcinoma of lungs Treatment: - Surgical resection - Radiation therapy

Answer 216

Destruction of skin, vessels, muscle, connective tissue--> ulceration - Much more avoidable with access ports (ports can cause thrombosis and infection) - Antidotes are marginally effective - Careful documentation and notification of patients Etiology: - Drugs in chemo: Doxorubicin, vinca alkalyoids, nitrogen mustard, antibiotics for tumor Signs/symptoms: - Pain/erythema at site - Rapid swelling of injection site - thrombosis of vessels

Answer 217

Mitomycin, gemcitabine - difficult to differential from DIC: plasmapheresis and steroids to treat - Can present with excessive fibrinolysis due to hormone-refractory prostate cancer See: - Hemolytic uremia - Kidney dysfunction - Blood abnormalities (schistocytes, clotting, bleeding)

Answer 218

Only emergency with severe respiratory/neurologic symptoms Pathophys: - Compression of SVC by tumor- blood can't get back to heart Etiology: - 70-75% due to lung cancer - 15-20% due to lymphoma (mediastinal B-cell lymphoma, lymphoblastic lymphoma) Signs/symptoms: - Venous dilatation of arms/chest - Facial flushing and swelling - Dyspnea - Cerebral edema Diagnosis: - High index of suspicion key - CT/MRI can confirm Treatment: - High dose steroids - Anti-coagulants - Radiation/chemo if sensitive tumor (lymphoma, small cell lung cancer)

Answer 219

Breast cancer= #1 cancer risk in women (1 in 3), #2 killer 1. Gender 2. Age 3. BRCA1/2 Previous history BrCA Ovulation Estrogen (start menstruating sooner, end later, nulliparous) Alcohol Race Obesity Radiation to chest Family History Genetic syndromes - BRCA1/2 - Peutz-Jaegers - Cowden syndrome - Li Fraumeni - Ataxia/telangectasia

Answer 220

Normal risk: annual mammogram starting at age 40 Increased risk: mutation carrier, strong family history, prior history of BrCa, history of premalignant lesion—annual MG starting age 35 Very increased risk—radiation to upper thorax--MG starting age 25 or 10 years after radiation

Answer 221

1. Image guided needle biopsy: - Adv: no surgery, fast, good for unresectable lesions, metastatic disease - Disadv: less tissue, may miss spot 2. Excisional biopsy - Adv: lesions far from surface, more tissue extracted Disadv: requires surgery, more scarring 3. Biopsy with lymph node sampling: - Adv: accurate staging, good for neoadjuvant therapy - Disadv: Requires blue dye/radiation; must have strong pretest probability

Answer 222

``` Stage 0=DCIS/LCIS Stage I=T1, N0 Stage II=T0-2, N1 or T2-3, N0 **Stage III= T3, N1 or any T4 or any N2, 3** **Stage IV= M1** ``` T1= less than 2cm T2 2-5cm T3 more than 5cm **T4 chest wall or skin** ``` N1 movable axillary *N2 fixed or matted* *N3 other nodes* M0 no mets *M1 mets* ``` Staging: - Decide if a tumor is resectable - Gives a rough estimate of ability to cure the patient - Helps decide what treatment modalities are necessary Staging does NOT: - Determine longevity of patient - Help decide type of chemotherapy

Answer 223

All gross tumor must be removed Mastectomy and lumpectomy plus radiation are equivalent therapies Radiation recommended for-- - Lumpectomy - Positive lymph nodes

Answer 224

Advantages: - Less risk of lymphedema - Shorter OR time - Pathology can section the most important node - In most patients, this is the only positive node Disadvantages: - Number of positive lymph nodes not known - Not indicated for clinically positive nodes - Blue dye contraindicated in pregnancy - Requires experience

Answer 225

1. Patients with positive lymph nodes 2. Triple negative 3. Her-2 positive (receptive to herceptin) 4. High oncotype score - ER/PR: estrogen receptors present - Her-2 neu - "Triple negative"= worst prognosis (nothing to target)- no ER/PR, Her-2 neu - Lymphovascular invasion - Tumor grade * Can use computer modeling to help with decision (based on population data) * DNA microarray: tells person what her risk of relapse is without chemo based on tumor DNA NOT contraindications to chemo: - Being pregnant - Being over age 70 - Having comorbid conditions - Being a man - Wishing to have children in the future Contraindications: - Benefit vs. risk not favorable - Performance status greater than 2 - Patient is unable to consent - Comorbid conditions—with caveats (ex. difficult with dialysis patients)

Answer 226

Anyone with positive hormone receptors and no contraindications

Answer 227

In general: less toxic, as effective or more effective - Her-2 targeted therapies - Tyrosine kinase inhibitors - Parp inhibitors - Bisphosphonates

Answer 228

- Use the least toxic therapy available - Single agent is preferable to combination - Tailor treatment to the histology - Tailor treatment to the patient’s lifestyle - Use monthly bisphosphonates for bone metastases

Answer 229

Gail score (women over 35 with 1.7% or greater risk: Premenopausal—tamoxifen is the only choice Postmenopausal can also use raloxifene

Answer 230

Amastia (no glandular tissue develops and no nipple areolar complex present) Aplasia (nipple areolar complex present but no glandular tissue develops) Hypoplasia (underdevelopment of glandular tissue) Athelia (no nipple areolar complex) Supernumary nipples or accesory breast tissues Nipple inversion

Answer 231

Seen in nursing women, related to staph

Answer 232

Young females with mass lesion

Answer 233

Periductal mastitis with dilated ducts, foamy histiocytic lymphoid cell infiltrate

Answer 234

Non-proliferative: production of cysts within breast (blue-domed), apocrine metaplasia (eosinophilic), stromal fibrosis - NO increased risk in developing invasive carcinoma Proliferative without atypia: - Usual ductal hyperplasia - benign adenosis, sclerosing adenosis (SA) - Radial scars - columnar cell change/hyperplasia - Only small increased risk of breast cancer Proliferative with atypia - Atypia ductal - Atypical lobular hyperplas (ADH, ALH) - Flat epithelial atypia * Need excision to determine what is occurring in lesion - Significant risk of breast cancer risk

Answer 235

pediatric brain tumors as a group are becoming as common as acute leukemia - incidence is increasing - mortality is decreasing Risk factors: - More common in boys than girls - More common in whites - Ionizing radiation (tinea capitis, lice, leukemia treatment--> 1 Gy carcinogenic) - Syndromes: NF-1, tuberous sclerosis (phakomatoses), Gorlin, Li-Farumeni Most common types: 0-4 years: embryonal medulloblastoma 5+ years: pilocytic astrocytoma

Answer 236

History: - lethargy - headaches - declining school performance - personality change - nausea/vomiting, **especially morning vomiting** - precocious puberty - loss of milestones Exam: irritability somnolence macrocephaly: pediatricians check head circumference cranial nerve palsies: double vision seizures papilledema: optic disc pushed forward visual loss: not always obvious is the very young precocious puberty weakness paresthesias Syndromes: - Gorland's syndrome: skin and brain abnormalities - NF-1 (prone to gliomas) Sprengel’s deformity: failure of the scapula to descend to its normal position. Vertebral anomalies: hemivertebrae (vertebral rings incomplete) Scans: - CT (quick look) - MRI of brain, spine - MR Spectroscopy: metabolic signature of tumor, central necrosis, etc.

Answer 237

1. Surgery 2. Chemotherapy 3. Radiation: Delivery: - 3D conformal technique - Intensity modulated radiation therapy (IMRT) - Proton scatter beam - Proton pencil beam - **Protons specially beneficial for children*: no exit dose, more precise, less radiation to neighboring tissue - Stereotactic radiosurgery/CyberKnife

Answer 238

Dependent on location and pathology Infants do worse because of the constraint of limited radiation therapy Problem of late recurrences - 5-10 years after diagnosis

Answer 239

ANC= WBC x (polys + bands) Neutropenia= low ANC Neutropenia in children: - Mild (1000-1500) - Moderate (500-1000) - Severe (< 500)

Answer 240

1. Viral induced: - RSV, EBV, CMV, influenza A and B, varicella, hepatitis A, hepatitis B, parvovirus, HIV 2. Drug-induced: - Ibuprofen, penicillin, cephalosporins, Bactrim, hydralazine, Zantac, phenytoin, carbamazepime - May occur 1-2 weeks after exposure to drug; can last for months 3. Cancers: infiltration and replacement of normal marrow with malignant cells - Leukemias: ALL, AML; rarely only presenting sign of leukemia, but can be only hematologic abnormality - Solid tumors metastatic to bone marrow (rhabdomyosarcoma, retinoblastoma, neuroblastoma) - Diagnosis: Bone marrow exam

Answer 241

ELANE-related: (ELAstase, Neutrophil Expressed); neutropenias include congenital neutropenias and cyclic neutropenia These are hematologic disorders with: - recurrent fever - skin and oropharyngeal inflammation - mouth ulcers, gingivitis - Sinusitis - Pharyngitis - cervical adenopathy Infectious complications are generally more severe in congenital neutropenia than in cyclic neutropenia. Infections are much more common in the ELANE disorders than in the common pediatric neutropenias Symptoms: - Typically presents at =5 g/kg/day (granulocyte colony stimulating factor) to boost ANC and decrease infections Prognosis: - ongoing risk of developing AML with or without the use of G-CSF By age 15: - 36% chance of developing myelodysplasia - 25% chance of developing acute myelogenous leukemia **Ultimate cure: allogeneic bone marrow transplant

Answer 242

Rare, relatively benign disorder with periodic oscillations of ANC, often in remarkably regular 21 day cycles Patients typically have periods of count dependent wellness alternating with periods of illness Etiology: - Autosomal dominant or sporadic - Ask about family history Signs and symptoms: - fever, oral ulcerations, perianal cellulitis Pathophys: - ANC nadir is usually 90% of patients have mutations in neutrophil elastase (ELANE) Treatment: - daily G-CSF injections >=3 g/kg/day Prognosis: - NOT typically associated with an increased risk of malignancy/leukemia - Neutropenia and associated morbidities typically lessen into adulthood

Answer 243

Very rare cystic fibrosis-like exocrine pancreatic insufficiency with neutropenia; Etiology: - Autosomal recessive inheritance presents in early childhood Symptoms: - short stature, failure to thrive, infections, neutropenia (may be chronic or cyclic) - may have anemia, thrombocytopenia as well Diagnosis: - test pancreatic enzymes - check CBC twice weekly for several months to follow ANC - bone marrow examination Pathophys: - 80-90% have mutations in SBDS gene - undergoes recurrent mutations because of the presence of a nearby pseudogene, an inactive copy of the SBDS gene. - Gene conversion: transfer pseduogene mutations to real gene Treatment: - enzyme replacements for pancreatic insufficiency - G-CSF for neutropenia - Ultimately, bone marrow transplant for marrow failure/transformation Prognosis: - increased risk of myelodysplasia/ malignant transformation

Answer 244

Autosomal recessive disorder: not uncommon, look for it, many cases not diagnosed until teenage years or later - Initial hematologic problem is usually thrombocytopenia, not neutropenia - 80% of patients have phenotypic anomalies Symptoms: - Bone problems: Absent bones from hands/thumbs, wrists, forearms; scoliosis - Skin problems: Hyperpigmentation, cafe au lait spots, vitiligo - Short stature - Microcephaly

Answer 245

Common cause of chronic neutropenia in childhood; typically healthy and do not get invasive infections as a result of their neutropenia - Often diagnosed incidentally on a CBC drawn for some other reason; panic often ensues - Most cases resolve within 6-18 months Etiology: - Infections, drugs, other autoimmune disorders, cancer - Disorders that can trigger AIN: ITP, Lupus, EBV infections, Hodgkin disease Morbidity: - Serious infections rare - Primary morbidity is the onset of fever related to a minor coincidental viral infection Diagnosis: - Serial blood counts, ANC is usually 1000)

Answer 246

Basic categories: 1. Anemia: secondary to antibody mediated RBC destruction 2. Neutropenia: secondary to antibody mediated WBC destruction 3. Thrombocytopenia: secondary to antibody mediated platelet destruction

Answer 247

Alloimmune anemia of the newborn Antibody mediated destruction of RBC; antibodies directed against: - Rh antigens - ABO antigens - other minor antigens Pathophys: - maternal Immune system rejects fetal (paternal) antigens--> lysis - rejection is humoral/IgG mediated; there is no direct cellular or IgM attack as these cannot cross the protective placental membranes

Answer 248

ABO incompatability: - not as severe as Rh incompatable - Infant= A or B, mother= O - 20% of ABO incompatable--> clinical jaundice Clinical presentation: - can occur in first born child - subsequent pregnancies less severely affected (opposite of Rh incompatibility) - jaundice within first 24 hours (umbilical cord was clearing bilirubin before birth) - typically milder than Rh incompatibility because the diffuse expression of ABO antigens on tissues absorb much of the harmful antibodies Diagnosis: - ABO set-up needs to be present - anemia: mild or absent - smear: reticulocytosis, NRBC, spherocytes present - direct Coombs: can be + or – (Don’t be misled by negative Coombs test) - may be difficult to definitively prove ABO hemolysis is occurring especially if the Coombs test is negative Treatment: - phototherapy in some - aggressive therapy (transfusion, exchange) in the rare severe case

Answer 249

Lytic maternal antibodies cross the placenta to attack baby’s paternal WBC antigens NOT: - autoimmune neonatal neutropenia - neutropenia due to passive transfer of maternal autoimmune neutropenia antibodies 40% of mothers of these babies have had miscarriages possibly related to early fetal injury Pathophys: - antibody mediated destruction of WBC like ABO/Rh, several common antigen targets identified - maternal antibodies= NA1 and NA2 Clinical presentation: - usually picked up incidentally in well babies - occasionally present with invasive infections due to neutropenia: omphalitis, pneumonia, meningitis (Babies with omphalitis should have a CBC) Diagnosis: - CBC - antineutrophil antibody studies on mother, child looking for lytic antibodies - WBC typing on parents and child looking for incompatibility at the NA locus Treatment: - Neutropenic well baby: no therapy, follow counts - Neutropenic sick/infected baby: IV antibiotics, G-CSF

Answer 250

Also known as neonatal alloimmune thrombocytopenia (NAIT) - rare, < 0.1% of all newborns have thrombocytopenia due to this, although 3% of pregnancies at risk due to tissue type incompatibility NOT autoimmune neonatal thrombocytopenia (neonatal ITP) Pathophys: - Antibody mediated destruction of platelets Clinical presentation: - TNHAP that most frequently causes intrauterine morbidity/mortality (intracranial bleed) - incidentally detected post-partum - thrombocytopenia usually severe (<50,000) - occasionally present with bleeding, petechiae (incidence of serious bleeds low) ``` Diagnosis: - Antiplatelet antibodies - Major platelet antigen is HPA-1 - demonstration of HPA mismatch: mother HPA-1 negative father (baby) HPA-1 positive ``` Treatment: - prenatal interventions: maternal IVIg infusions; fetal platelet transfusion (tricky in a thrombocytopenic fetus) - newborn interventions - transfuse baby with washed, maternal (HPA-1 negative) platelets (convenient source) - transfuse with non-maternal HPA-1 negative platelets (blood bank, often hard to get) - IVIG infusions

Answer 251

Malignancy in children 4 types: 1. Botryoid: genital, young children 2. Head and neck: children < 8 years 3. Embryonal: orbital 4. Alveolar: extremities; teens and young adults Treatment: VAC: - Vincristine - Actinomycin-D - Cyclophosphamide + Doxorubicin (anthracycline antibiotic) + Ifosfamide (cyclophosphamide analog) + Etoposide (topoisomerase I inhibitor)

Answer 252

Rare (1 in 3000 inpatient peds) potentially fatal syndrome of pathologic immune activation characterized by clinical signs and symptoms of extreme inflammation - familial disorder (primary): fixed defects of cytotoxic function - sporadic disorder (secondary): triggered by infections, malignancies, or rheumatologic disorders (EBV, CMV, parvo) Pathophys: Activated hematopoietic cells infiltrate target organs, leading to severe end organ damage - Activated macrophages engulf healthy tissue Symptoms: - Fever - Hepatomegaly (liver inflammation - Splenomegaly - Neurologic symptoms - Rash - Lymphadenopathy Diagnosis: - sCD5 (IL-2) - Ferritin (v. elevated) - Genes: PRF1, hMUNC13-4, Syntaxin 11

Answer 253

Smoking: - Smoking accounts for 80-85% of bronchogenic cancer - Risk related to number cigs/day, years smoked, depth of inhalation, age of initiation of smoking, amount of tar Occupational: - Asbestos: higher when combined with cigarette smoking; 50 times greater risk than non-smokers, non-asbestos exposed men - Chloromethyl methyl ether - Ionizing radiation - Nickel, arsenic (glass, paints, pesticides) - Aromatic hydrocarbons (petroleum industry)

Answer 254

Small Cell Lung Cancer (SCLC): - includes oat cell, intermediate and combined subtypes Non-Small Cell lung cancer (NSCLC) - squamous cell carcinoma - adenocarcinoma (includes bronchioloalveolar subtype) - large cell carcinoma

Answer 255

``` "Driver" mutations: 1. EGFR: targeted by TKI 2 EML-4-ALK: fusion gene of EML4 and anaplastic lymphoma kinase: seen in non-smokers; - treated by Crizotinib 3. KRAS - Her-2 Neu (small number) - BRAF (rare) - MET - AKT1 - PIP3 Kinase - ERCC 1: Platinum - RRM-1: Gemcitibine ``` Chromosome 3, alterations in telomerase expression, KRAS mutations "Passenger" mutations

Answer 256

Mutations: - Cluster in L868, exon19- sensitive to TKI Overexpression: - Not sensitive to chemotherapy drugs Epidemiology: - Asians - Women - Never smokers - Independent predictor of response, progression free survival

Answer 257

30-50% of US lung tumors; adenocarcinomas increasing in frequency - Usually arise in the epithelium of proximal bronchi (but NOT always case) Histo: - Keratinization and “pearls” (flattened cells surrounding central core of keratin) - intercellular bridges - Cytokeratin - EM: densely pack filaments Labs: - Hypercalcemia is common secondary to elaboration of PTH-like substance Least likely to metastasize - over 50% at autopsy are confined to the thorax - brain mets only about 13%

Answer 258

Precursor: Atypical Adenomatous Hyperplasia - Usually are found peripherally - Commonly metastasize (liver, adrenal, bone and CNS) - At autopsy, brain is involved in over half of the cases ``` May secrete GH, corticotropin, calcitonin, FSH Hypertrophic osteoarthropathy (HO) more frequent with adenocarcinoma ``` M=F More peripheral May produce mucin Contains cytokeratin

Answer 259

CK7+ CK20 negative (except mucinous) TTF-1+: thyroid transcription factor-1 NAPSIN A+

Answer 260

CK5/6 | P63

Answer 261

``` NSCLC that is not classified as adeno or squamous by light microscope Variants: - Giant cell - Clear cell - Spindle cell ``` Grouped with adenocarcinoma, least common

Answer 262

Difficult to diagnose based on symptoms, history and X-ray - Non-smokers - Resembles pneumonia (see infiltration on both sides) - Oxygen-dependent, difficult to treat

Answer 263

Epithelial tumor with neuroendocrine markers - NSE= neuron specific enolase - Chromogranin, synaptophysin, CD56 - Centrally located - younger patients, male=female, symptoms of bronchial obstruction ``` Low-grade malignant tumor Derived from neurosecretory line Atypical carcinoid has worse prognosis Cured by resection 2% of lung cancers ```

Answer 264

Neuroendocrine tumor: systemic illness at presentation - 18% of all lung cancers - Due to: heavy cigarette smoking, uranium miners, CMME (chloro methyl methyl ether) exposure Histo: - Small cell, classic oat, intermediate types - 2X size of small lymphocytes - Cells with very little cytoplasm thus appear small - Nucleus occupies almost entire cell- v. little cytoplasm - Usually manifested grossly by central masses and lymphadenopathy - Mucosal and submucosal invasion appreciated bronchoscopically - Staged and treated differently than NSCLC: radiation v. important part of control (25-30% cure rate if less extensive- can use chemo and radiation) ``` More malignant compared to carcinoid tumors--> still has neuroendocrine function Develop Paraneoplastic syndrome: - SIADH: low Na, altered mental status, urine/serum osmolality mismatch - Cushing's: hypokalemic alkalosis (someone NOT on diuretic with lung tumor) - Eaton Lambert syndrome - Never see elevated calcium - Gynecomastia - Hypoglycemia - Acromegaly - Hyperthyroidism - Clubbing of fingers - Pulmonary osteoathropathy ``` Systemic disease at outset: - Treated with chemo - Frequent metastases to endocrine organs (thyroid, pituitary testes, parathyroid) - Moon metastases to elsewhere in lung, liver, bone, brain, adrenal, pericardium - Brain metastases occur up to 40% of small cell lung cancers!! ``` Cytogenetics: - Deletion of 3q Abnormalities of Rb on Chrom 13 - Abnormal p53 on chrom 17 - cMyc amplification prominent ```

Answer 265

``` Family history Chest pain Smoking history Recurrent nerve palsy Change in cough Superior vena cava syndrome New onset hemoptysis Airway obstruction Recurrent/refractory infections Pneumonia Atelectasis Exposure to environmental factors Pleural effusions ```

Answer 266

``` 10% stage I disease; (60% 5yr survival) 20%, stage II; (40% 5-year survival) 15%, stage IIIA; (20% 5-year survival) 15% stage IIIB; (5% 5-year survival) 40%, stage IV. (2% 5-year survival) ```

Answer 267

``` Locoregional disease: Cough Atelectasis/pneumonia Wheezing Pleural effusions Stridor Pleuritic pain Hemoptysis Shortness of breath ``` ``` Advanced disease: Fatigue Decreased appetite Cough Weight loss Dyspnea ```

Answer 268

``` Cough Hemoptysis Wheeze Dyspnea Post obstructive pneumonia ```

Answer 269

Cough Restrictive dyspnea Lung abscess

Answer 270

- Tracheal obstruction: wheezing, stridor - Dysphagia due to esophageal compression - Hoarseness due to recurrent laryngeal nerve entrapment and paralysis - Phrenic nerve paralysis: elevated diaphragm - Superior vena cava obstruction

Answer 271

Generally seen with NSCLC (grows less rapidly): Horner's syndrome: ptosis, miosis, anhydrosis - Cervical sympathetic chain trapped by tumor (Pancoast tumor) Right shoulder pain Pain, weakness in arms, back

Answer 272

Myasthemia-Gravis like syndrome (opposite) | - Muscle response gets STRONGER with stimulation

Answer 273

CT MRI Fine needle aspiration of tumors (CT, Bronchoscopy guided) Bronchoscopy

Answer 274

CT study of chest: lung, nodes, liver, adrenals PET: NSCLC (and useful in SCLC) - Inferior for CNS evaluation - Mediastinal evaluation - Stage I or II (extensive disease--> no surgery recommended) - FALSE POSITIVES: infection, inflammation (will take up glucose- not specific) - FALSE NEGATIVES: low-grade malignancy don't pick up PET agent Brain: MRI or contrast CT (needed for staging of SCLC) Bone scan Liver: MRI; clarification of PET scan for mets

Answer 275

Early stage lesions, stages I and II: surgery preferred - Chemo-radiotherapy for locally advanced disease - Chemotherapy for systemic disease - Radiation therapy for local palliation and control - New paradigms in adjuvant chemotherapy for earlier stages are emerging Stage II disease, early chemotherapy has been shown to have advantage as adjuvant therapy In recent trials Stage II B: Pancoast tumors: radiation or radiation plus chemotherapy with surgery Stage III: combined modality therapy: usually chemo-radiotherapy followed by chemotherapy Stage IV (formerly IIIB): pleural effusion: chemotherapy Stage IV: chemotherapy

Answer 276

WHITE premalignant neoplasia | - Hyperkeratotic epithelium

Answer 277

RED mucosa, fragile, easily traumatized

Answer 278

- Includes tonsillar and base of tongue carcinoma - HPV related (p16 positive) - More common in young adults, male predominance - Often presents as a “neck mass” - Nonkeratininzing, poorly differentiated histology - Good prognosis, better response to radiation therapy

Answer 279

The most common malignant neoplasm of the larynx (95%) Clinical presentation: - Hoarseness or alteration of voice - Throat pain, dysphagia - Neck mass - Airway compromise in large, bulky tumors (advanced cases) Glottic carcinoma - Most common - Vocal cord involvement - Early symptoms, while still curable Supraglottic carcinoma - Next most frequent - Foreign body sensation, pain, hemoptysis, muffled voice - Later symptoms than glottic carcinoma- takes longer for noticeable symptoms (spreads to glottis)

Answer 280

Tonsillar: don’t see nests as in normal squamous cell carcinoma- basilloid appearance (blue), no keratin production - Majority HPV related - Immunohistochemistry stains for p16 (HPV)

Answer 281

Mucoepidermoid carcinoma- most common - Definition: tumor characterized by the presence of squamous, mucus-producing cells and cells of intermediate type - 5th and 6th decades; - most common salivary gland malignancy in children Clinical presentation - Low grade tumors: prolonged period of - painless enlargement (several years) - High grade tumors: rapid growth, pain, ulceration - Involvement of facial nerve in tumors of the parotid

Answer 282

Most difficult to manage - Definition: malignant tumor with three growth patterns: glandular (cribriform), tubular or solid. It is composed of two types of cells: duct-lining cells and myoepithelial cells - One of the most biologically deceptive and difficult to manage (bland histologic appearance and favorable short-term therapeutic results) Clinical behavior: - Slow, but relentlessly malignant natural course - High incidence of local recurrence and distant metastases - The success of treatment and ultimate prognosis must be considered in terms of 15-20 years. - Distant metastases occur late in the course of disease (patients with distant metastases have uncontrolled disease in the primary site or neck) * * PERINEURAL INVASION** Histo: Tumor cells: small, round, with dark –staining nuclei and scant cytoplasm Three basic patterns: - Tubular = well formed ducts or tubules with central lumina, lined by 2-3 layers of cells - Cribriform = classical pattern; “Swiss cheese” or “sieve-like” appearance - Solid = solid epithelial islands completely filled with cells

Answer 283

- Rare tumor in the general population - Has striking and characteristic epidemiologic, virologic and pathologic characteristics - “NPC” – refers to conventional squamous cell carcinoma and to nonkeratinizing or undifferentiated carcinoma arising from the surface of tonsillar crypt epithelium of the nasopharynx Epidemiology: - Common in Southern China and among Chinese in Taiwan, Singapore and Hong Kong - First-generation Chinese immigrants to other countries maintain a high incidence of NPC - Common among Alaskan, Canadian and Greenland Eskimos - Twice more common in men than in women Etiology: - EBV-driven tumor (non-keratinizing forms) - IgA and IgG EBV antibodies: Ab levels tend to increase in relation to tumor burden - EBV-encoded RNA (EBER) is present in NPC cells Clinical presentation: - Most common – neck mass secondary to metastatic disease - Unilateral hearing loss, otitis media - Nasal obstruction, bleeding, pain or cranial nerve palsies - Primary tumor: often small, difficult to visualize on clinical exam/exophytic ``` Histo: Keratinizing SCC Nonkeratinizing SCC (EBV related): - Differentiated - Nondifferentiated – syncytial growth of undifferentiated tumor cells, admixed with lymphocytes ``` Non-Keratinizing: better prognosis more radiosensitive than keratinizing SCC; better prognosis 70% and 59% survival at 3 and 5 years for nonkeratinizing SCC

Answer 284

Increased risk with exposure to wood dust, paints, varnishes, glues and adhesives - Risk in woodworkers is 70-500 x non woodworkers - High incidence in middle-aged and old men Clinical presentation: - Involvement of nasal cavity and maxillary sinuses - Polypoid or papillomatous masses in the nasal cavity - Destructive manifestations in the sinuses - Unilateral nasal obstruction, epistaxis, pain, usually of a few months duration Histo: Origin – surface epithelium, accessory seromucous glands ducts, seromucous glands Low grade – uniform glandular architecture, bland cytologic characteristics High grade – necrosis, inflammation - Subtypes: papillary, colonic, solid, mucinous, mixed Prognosis: - All grades of sinonasal adenocarcinoma tend to be locally aggressive, frequent invading orbit and the base of skull - Distant metastases are rare - Complete surgical removal with clear margins is the treatment of choice

Answer 285

NKT cells - Aggressive type of lymphoma - Insidious onset - Ulcerations of nasal mucosa, erosion of the cartilage and bone - Destructive lesions of the nasal septum, hard palate and nasopharynx - Former designation “lethal midline granuloma” Histo: - Pleomorphic atypical lymphoid infiltrate - Malignant lymphoid cells surround small to medium sized blood vessels, infiltrate through vascular walls and can occlude vessel lumens and cause necrosis in adjacent tissue

Answer 286

Malignancy arising from the olfactory mucosa; no predisposing carcinogen known Epidemiolgy: Bimodal peak incidence in the 2nd and 6th decades of life Symptoms: Nasal obstruction, epistaxis Prognosis: Locally aggressive tumor, low incidence of distant metastases Histo: - Polypoid, highly vascular tumor displaying diverse histologic patterns - Lobular architecture - Uniform tumor cells set in a neurofibrillary matrix - Rosettes - Intracytoplasmic dense core granules (by EM)

Answer 287

Better prognosis with HPV-caused cancers HPV Related: based of tongue, tonsil, oropharynx Younger patients Better outcomes with radiation treatment See p16 marker

Answer 288

Surgery Radiation therapies Chemo

Answer 289

``` Neck mass Odynophagia, Disphagia Hoarseness Trismus (cant open mouth- muscle spasm) Otalgia, unilateral otitis media Loose teeth, ill-fitting dentures Cranial nerve deficits Non-healing oral/oro-pharyngeal ulcers ```

Answer 290

- HNPCC with skin lesions (sebaceous adenoma/carcinoma) | - Genitourinary cancers

Answer 291

FAP with cutaneous lesions (osteomas, epidermoid cysts), desmoid tumors

Answer 292

- HNPCC + glioblastoma | - FAP + medulloblastoma

Answer 293

Peutz-Jeghers syndrome - Small bowel + colonic hamartomas - Increased GI cancer risk (CRC, small bowel, pancreatic cancer) - Perioral pigmentation

Answer 294

Tongue= most common site Risk factors= Smoking, Betel nuts - Male predominance Pre-malignant lesions= leukoplakia, erythroplakia

Oncology Flashcards

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