Background: Disorders characterized by the presence of a Monoclonal Ig (M protein) or its components, produced by: Clonal population of plasma cells: Monoclonal Gammopathy of Undetermined Significance (MGUS) IgG >> IgA , IgM Smoldering Multiple Myeloma (SMM) IgG >> IgA Multiple Myeloma (MM) IgG >> IgA AL amyloidosis POEMS syndrome Clonal population of B-lineage/lymphoplasmacytic cells: Waldenström Macroglobulinemia (WM) IgM Monoclonal Gammopathy of Clinical Significance (MGCS

Non-Small Cell Lung Cancer (NSCLC) T1 T2: 3 cm T3: 5 cm T4: 7 cm N1: Hilar nodes N2: Ipsilateral N3: Contralateral or supraclavicular Stage I: N0 Stage Ia: T1 (<3 cm, No NGS) Stage Ib: T2a (3-4 cm): Alectinib if ALK mutated Osimertinib if EGFR exon 19 deletion or L858R Stage II: >N1 If unresectable: Radiation If resectable: Alectinib if ALK mutated Osimertinib if EGFR exon 19 deletion or L858R Chemotherapy: Platinum/Taxol x4 Platinum

Hodgkin lymphoma (HL): B-cell lymphoma Non-Hodgkin lymphomas (NHL): B-cell lymphomas (85–90%): DLBCL: The most common, aggressive Follicular lymphoma (FL): Indolent, arising from germinal center B cells Marginal zone lymphoma (MZL): Extranodal, Nodal, Splenic Mantel cell lymphoma (MCL): More aggressive, Derived from mantle zone B cells Burkit lymphoma (BL): Highly aggressive, germinal center origin Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) Lymphoplasm

Genetics: Consider VHL, Tuberous sclerosis, Birt-Hogg-Dube (spontaneous pneumothorax is a hallmark) Genetic testing in patients with: Multiple renal masses, bilateral or multifocal tumors, diagnosis age < 45, family history of RCC (more than one first/second degree relatives with RCC) Types: Clear cell RCC: 75% Non-Clear Cell RCC: 25% Papillary RCC is associated with MET mutation. Collecting Duct RCC Chromophobe RCC Associated with Birt-Hogg-Dube Medullary RCC Associated wit

Iron Metabolism: ~ 4000 mg of iron per person Mostly stored in the erythrocytes ( ~ 2700 mg) and liver ( ~ 1000 mg) Homeostasis is balance between absorption vs. loss Absorption is regulated Intestinal absorption can fluctuate in response to Iron status Erythropoietic demand Hypoxia Inflammation Normally absorb 1-2 mg iron/day Loss is unregulated Physiologic exfoliation (hair, skin) Bleeding (physiologic, hemorrhage) Reproductive (iron needed to make a new human) Transferrin

CBC & differential See "How to interpret a CBC with differential" lecture for a detailed discussion. Retic Reticulocytes are immature red blood cells that spend ~3 days maturing in the bone marrow, followed by 1–2 days in the peripheral blood before becoming mature RBCs. Retic count is a real-time indicator of bone marrow erythropoietic activity. Corrected reticulocyte count = % Retic × (Patient's Hct / Normal Hct) Reticulocyte production index (RPI) = Corrected retic count /

Major components of hemostasis: Primary hemostasis (platelet plug) Defects lead to mucosal bleeding (petechiae, purpura, epistaxis)...

Background: Highest incidence: East Asia (Japan, Korea, China) Increased in Eastern Europe & South America Male predominance (~2:1) Major Risk Factors: Chronic H. pylori infection (strongest risk factor) Chronic atrophic gastritis / intestinal metaplasia Smoking High salt/smoked foods, low fruits/vegetables Pernicious anemia Partial gastrectomy (long-term) CDH1 mutation → hereditary diffuse gastric cancer Histologic types: Intestinal: Gland-forming Associated with: H. pylori,

Normal ranges varies slightly by labs. WBC Elevated WBC (>11k) Common causes of significant leukocytosis (>15k): Sepsis/ bacterial infection C.difficile C. diff detected in ~25% of patients with WBC >30k without hematologic malignancy Leukocytosis can even precede diarrheal symptoms If no obvious source, test for C. diff even without diarrhea Malignancy (hematologic malignancy, neoplastic syndrome from solid malignancies) Medication (steroid, G-CSF) Physiologic stress (surger

Risk Factors: Cirrhosis of any cause (viral, alcoholic, metabolic, autoimmune, genetic etiologies) Cirrhosis present in over 80% of HCC cases Chronic HBV and HCV infection (with or without cirrhosis, especially with high viral load or active replication) Screening: At-risk populations requiring screening: Child-Pugh Class A or B cirrhosis of any etiology Child-Pugh Class C cirrhosis patients who are transplant candidates Hepatitis B carriers without cirrhosis Screening using

Background: B-cell lymphoid malignancy, characterized by Reed-Sternberg cells ( resemble owl’s eyes ) Most commonly affecting young adults Presenting with painless LAP and sometimes B symptoms Types: Classic Hodgkin Lymphoma: CD15+, CD30+ and CD20- Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL): CD15-, CD30- and CD20+ Deaville Scoring System: Used to interpret FDG-PET scans for response assessment in HL and aggressive NHLs: 1 = No uptake 2 = Uptake ≤ mediastinum 3 =

Types of transplant: Allogeneic HCT: Infusion of hematopoietic cells ( CD34⁺ ) from a HLA-compatible donor after cytotoxic conditioning to eradicate disease and enable engraftment. Used in order to deliver high doses of chemotherapy + “graft vs. tumor” (GVT) effect GVT affect: immune-mediated cytotoxic effect exerted by donor-derived immune cells against the recipient’s neoplastic cells following allo-HCT ~30-50% of allo-HCT develops with acute GVHD (aGVHD) Most commonly used

Background: Types: ~90% of head & neck cancers are squamous cell carcinoma (HNSCC). ~10% are salivary gland tumors, lymphomas, sarcomas, mucosal melanomas Risk factors: HPV infection (16, 18, 33, 35) HPV 16 is by far the dominant subtype (>80% of HPV-positive HNSCC) HPV 18 is the second most common but plays a much smaller role than in cervical cancer (~2.5% of all HNSCC) Smoking Alcohol use (synergistic with smoking) EBV esp in nasopharyngeal carcinoma Betel nut chewing Gene

Erythropoiesis Stimulating Agent (ESA) Mechanism: Regulates RBC production Produced in liver in fetus, kidney is primary site in adults Regulated by the HIF transcription factors Functions by stabilizing CFU-e and promotes terminal differentiation of erythroid cells Ensure iron stores is adequate before using EPO Medications: Erythr o poietin / E poetin alfa (Epogen) Darbo poietin alfa Biosimilars Indications: Chronic Kidney Disease Start when Hb <10 Lowest dose necessary t

Background: Most common mesenchymal tumors of GI tract Risk assessment uses: Tumor size Mitotic rate Anatomic location Tumor rupture Significantly increases recurrence risk. Gastric GIST generally have better prognosis than non-gastric GIST. For example, a >10 cm gastric tumor with >5 mitoses/50 HPF has 34% metastasis risk, while the same parameters in small bowel GIST carry 71-90% risk. Work up: Histology + IHC: Confirm GIST with positive KIT and/or DOG1 immunostaining. Imag

Work up: CT CAP with IV and oral contrast EGD with biopsy Endoscopic Ultrasound (EUS) If no M1 unresectable disease Bronchoscopy for tumors at/above the carina to rule out fistula PET/CT scan Consider staging laparoscopy: To assess peritoneal metastases (mostly in signet ring histology) At least 15 LNs need to be removed during surgery Biomarker testing: MSI/MMR in all newly diagnosed patients PD-L1 in all newly diagnosed patients HER-2 if advanced/metastatic adenocarcinoma i

Background: 10-15% of all leukemias Male/Female: 1.5 Median age of 65 years old Ionizing radiation is the only known causative factor (usually within 6 to 8 years of exposure) No known genetic factors determine susceptibility to CML Pathophysiology: >95% of CML patients have Philadelphia chromosome (Ph) in the marrow. Contains BCR-ABL1 fusion gene (translocation between BCR on chromosome 22 and ABL1 on chromosome 9) BCR-ABL1 oncoprotein has tyrosine kinase activity. BCR-ABL1

Increased risk of CRC: Personal history of adenoma, Sessile Serrated polyp (SSP)/ lesion (SSL), CRC, IBD, Cystic fibrosis, childhood cancers Positive family history of CRC Screening: Average risk adults: Age 45–75 years with a life expectancy of ≥10 years Screening between ages 76–85 should be individualized based on comorbidity status, life expectancy, and prior screening history. Colonoscopy Every 10 years Flexible sigmoidoscopy Every 5-10 years CT Colonoscopy Every 5 years

Background: 25% of all leukemias Morphologically mature but immunologically incompetent B lymphocytes Incidence increase with age Male/Female: 2 Predominantly found in caucasians, less common in African-Americans, Hispanics and Asians Positive family history: 2-8 fold increased risk Work-up: CBC: Clonal B-lymphocytes >5000 Anemia and thrombocytopenia are common PBS: Small lymphocytes with round nuclei, clumped chromatin, scant cytoplasm Medium/large sized cells: less than 10

Below is a list of common chemotherapy regimens in alphabetical order: ABVD: Doxorubicin (Adriamycin), Bleomycin, Vinblastine, Dacarbazine Hodgkin lymphoma AC: Doxorubicin (Adriamycin), Cyclophosphamide Breast cancer AD: Doxorubicin (Adriamycin), Dacarbazine Soft tissue sarcoma (esp leiomyosarcoma) AIM: Doxorubicin (Adriamycin), Ifosfamide, Mesna Soft tissue sarcoma BEP: Bleomycin + Etoposide + Cisplatin Testicular cancer Ovarian malignant germ cell tumors BR: Bendamustine +

Bone marrow failure: Disrupted hematopoietic stem and progenitor homeostasis → Inadequate WBC, RBC, Plt Pancytopenia differential diagnosis: Autoimmune: HLH, TTP, Lupus, Evan’s syndrome Malignancy: Leukemia, lymphoma, metastatic tumors (myelophthistic), myelofibrosis Infectious Metabolic/Toxins: B12/folate deficiency, excess zinc, storage diseases, alcoholism Bone marrow failure (least common cause) Acquired Bone Marrow Failure: Rapid onset, no family history, usually associa