Malignancy

Basic Definitions

  • Cancer/Malignancy: Uncontrolled cell division & invasive potential.
  • Neoplasia: Abnormal cell proliferation.
  • Neoplasm: Tumor (mass from unregulated growth).
  • Dysplasia: Abnormal, disorganized cell growth.
  • Benign: Non-invasive.
  • Malignant: Invasive, can metastasize.
  • Metastasis: Cancer spread.
    • Hematogenous (bloodstream)
    • Lymphatic
    • Direct seeding

Cancer Statistics (US - 2024)

  • Diagnoses: ~2.0 million new cases.
  • Mortality: ~611,720 deaths.
  • Risk: ~39.3% lifetime risk.
  • Mortality Rank: 2nd leading cause of death behind heart disease, but #1 cause of death in those < 65 years of age
  • Most Common Cancers: Breast, Prostate, Lung
  • Most Deadly Cancers: Pancreas, Esophagus, Liver & intrahepatic duct

Metastasis

  • Most cancer deaths result from metastases.
  • Common Sites: Lung, Liver, Brain, Bone (spine).
  • Bone Metastasis: Breast, lung, thyroid, kidney, prostate cancers.

Risk Factors

  • Tobacco: Leading cause.
  • Alcohol: Mouth, throat, esophageal, laryngeal cancers.
  • UV Light: Skin cancer (sunburns).
  • Radiation: Previous cancer treatment.
  • Infections:
    • HPV: Genitourinary, anal, oropharynx.
    • HIV: Lymphoma.
    • Hepatitis: Hepatocellular carcinoma.
    • H. pylori: Stomach cancer.
    • EBV: Lymphoma.
    • Diethylstilbestrol (DES): Breast cancer

General Signs & Symptoms

  • Fever, fatigue, weight loss, early satiety, night sweats, nausea, pain, infections, bleeding, thrombosis.

Cancer Diagnosis

  • Radiography:
    • Ultrasound: Superficial structures.
    • CT/MRI: Tumor size, surrounding structures, metastases.
    • PET: Metabolic activity, metastases.
  • Histology: Biopsy for definitive diagnosis.

Cancer Staging

  • TNM System:
    • T: Tumor size (T1-4, TX, T0)
    • N: Nodal involvement (N1-3, NX, N0)
    • M: Metastases (M1, M0, MX)

Other Staging Terms

  • Stage 0: Carcinoma in situ (non-invasive).
  • Stage I-III: Cancer present, higher number = larger tumor and more invasive.
  • Stage IV: Cancer with distant metastases.

Treatment Concepts

  • Goal: Eradication.
  • Surgery: Tumor removal.
  • Radiation Therapy: Localized treatment.
  • Chemotherapy: Systemic, targets rapidly dividing cells.
  • Hormone Therapy: For hormone-sensitive cancers.
  • Immunotherapy: Targets cancer cell components.
  • Targeted Therapy: growth signal, angiogenesis, apoptosis inhibitors

Tumor Markers

  • Substances produced by the body in response to cancer or by the cancer itself.
  • Examples:
    • S−100S-100: Melanoma
    • CA15−3CA15-3: Breast
    • CA19−9CA19-9: Pancreatic
    • CA−125CA-125: Ovarian
    • CEACEA: Colon/rectum
    • PSAPSA: Prostate
    • α\alpha-fetoprotein: Hepatocellular, testicular
    • β\beta-hCG: Trophoblastic tumors, choriocarcinoma, testicular

Screening Guidelines

Screening guidelines can differ based on the organization. The following is a summary:

  • Breast Cancer
    • Mammograms: Start at 40-50, every 1-2 years.
  • Cervical Cancer
    • Pap Smears + HPV: Start at 21-25, every 3-5 years.
  • Colon Cancer
    • Multiple options to start at 45.
  • Lung Cancer
    • Low-dose CT scan: People 50-80 years old with a 20 pack-year history, who are current smokers or have quit within the past 15 years
  • Prostate Cancer
    • PSA: Discuss at 50-55 with MD.
  • Endometrial Cancer
    • Education/discuss at menopause with MD.

Multiple Myeloma

  • Plasma cell cancer (abnormal plasma cells in bone marrow).
  • Key Features:
    • Monoclonal immunoglobulins
    • Osteoblast inhibition (lytic bone lesions).
  • Symptoms: Bone pain, fractures, infections, fatigue, anemia, renal failure, hypercalcemia.
  • Hallmark Infiltration: greater than or equal to 20% abnormal plasma cells in the bone marrow
  • Risk factor: age 50-70 years of age.
  • Diagnosis
    • SPEP (Serum Protein Electrophoresis): Identifies paraproteins in the serum
    • UPEP (Urine Protein Electrophoresis): Detects Bence Jones proteins (free light chains) in the urine.
  • Treatment: Chemotherapy, stem cell transplant.

Myelodysplastic Syndrome (MDS)

  • Stem cell disorders leading to cytopenias, risk of AML.
  • Ineffective hematopoiesis.
  • 5-year survival ~50% with treatment.
  • Risk factors:
    • > 65 years old
    • Exposure to chemo (alkylating agents)
    • Environmental toxins (benzene)
    • Radiation

Leukemia Overview

  • Uncontrolled proliferation of abnormal blood cells.
  • Acute vs. Chronic (immature vs. mature cells).
  • Rule out hematologic malignancy when 2+2+ cell lines are decreased.

Acute Myeloid Leukemia (AML)

  • Aggressive, rapid accumulation of abnormal myeloid cells.
  • Can be from prior chemo (alkylating agents) or radiation therapy.
  • Diagnosis: Bone marrow (hypercellular with >90%> 90\% cellularity, lineage via flow cytometry, chromosomal abnormalities.
  • Auer Rods: Key diagnostic feature in AML.

AML M3: Acute Promyelocytic Leukemia (APL)

  • High risk of DIC.
  • Genetic Marker: > 90% have t(15;17) translocation, which is diagnostic
  • Treatment: ATRA (all-trans retinoic acid), encourages promyelocyte differentiation.

Acute Lymphoblastic Leukemia (ALL)

  • Primarily affects children.
  • lymphoblasts, with ≥ 20% in the bone marrow.
  • Diagnosis: Bone marrow analysis, cytogenetics.
  • High remission rates in children (~98% within weeks of starting treatment), with ~90% achieving a cure.

Chronic Myeloid Leukemia (CML)

  • Middle-aged adults.
  • Myeloid lineage with immature and mature cell types.
  • Phases: Chronic, accelerated, blast crisis.
  • Philadelphia Chromosome: t(9;22).
  • Targeted treatment: imatinib (Gleevec), a tyrosine kinase inhibitor

Chronic Lymphocytic Leukemia (CLL)

  • Older adults.
  • Excess mature lymphocytes.
  • Generally least severe of major leukemias.
  • CD5+, CD19+, CD23+
  • Smudge Cells: "Crushed Little Lymphocytes" are characteristic of CLL
  • Treatment: Based on symptoms; "watchful waiting" in early stages.

Richter's Transformation

  • Development of diffuse large B cell lymphoma arising from one CLL clone.
  • Symptoms: Fever, night sweats, unintentional weight loss.
  • Diagnosis Need biopsy, PET scan because Neither Richter's transformation nor prolymphocytic leukemia responds to standard CLL therapy

Hairy Cell Leukemia

  • Rare, slow-growing B-cell malignancy.
  • Splenomegaly.
  • "Dry" marrow taps due to scarring in marrow.
  • Cell markers: Aberrant expression of T-cell marker CD103+, TRAP-positive (stain):

Key Leukemia Points

  • AML: Auer rods, may occur after chemo/MDS.
  • ALL: Pediatric, high cure rates.
  • CML: Philadelphia chromosome t(9;22), Gleevec.
  • CLL: Smudge cells, slow-growing.

Lymphoma Overview

  • Uncontrolled proliferation of neoplastic lymphocytes.
  • genetic abnormalities. Bone marrow and thymus.
  • Hodgkin vs. Non-Hodgkin.

Hodgkin Lymphoma

  • Adolescents/young adults.
  • Non-Hodgkin Lymphoma (NHL).
  • Nontender lymphadenopathy.
  • Risk Factors: EBV, HIV/AIDS, family history.
  • B symptoms: Fever, drenching night sweats, unintentional weight loss.
  • Reed-Sternberg cells: Bi-nucleated, prominent nucleoli, CD30+, CD15+.
  • Classical subtypes: Nodular sclerosing (most common), mixed cellularity (EBV).
    Treatment: Chemotherapy +/- radiation therapy

Non-Hodgkin Lymphoma (NHL)

  • More common than Hodgkin lymphoma, accounts for ~4% of all cancers.
  • Older adults.
  • Variable treatment based on type.
  • Specific Subtypes
    • Burkitt’s Lymphoma: One of the fastest-growing tumors that exists. All have cytogenetic abnormality involving chromosome 8
    • Diffuse Large B Cell Lymphoma: Most common intermediate grade NHL (~30%). Very responsive to chemo (standard treatment is R-CHOP: rituximab, cyclophosphamide, hydroxy-doxorubicin, oncovin (vincristine), prednisone)
    • Follicular Lymphoma: Most common low-grade NHL (~22%).

Key Lymphoma and Leukemia Points

  • B Symptoms: Fever, weight loss, night sweats.
  • EBV and HIV: Associated with lymphoma.
  • Hodgkin Lymphoma: Reed-Sternberg cells, common in teenagers.
  • Non-Hodgkin Lymphoma: More common in elderly, many subtypes.