USMLE STEP 1 CANCER (Markers, Histology, Presentation) – Flashcards
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1. Cancer markers & metastasis
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Let's do this!
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S-100
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Melanoma Schwannoma Langerhans cell histiocytosis
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Vimentin
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Mesenchyme
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Desmin
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Muscle
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GFAP
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Neuroglia
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Neurofilament
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Neurons
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Alkaline phosphatase
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Paget Disease of Bone Mets to liver or bone Seminoma (placental ALP)
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AFP
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HCC Hepatoblastoma Yolk sac tumor (yellow-yolk sac, AFP, Schiller Duval bodies) Mixed germ cell tumor
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b-HCG
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Choriocarcinoma Hydatidiform moles (46, XX)
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Marker of breast cancer tumors
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CA 15-3/27-29
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Pancreatic adenocarcinoma
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CA 19-9
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CA 125
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Ovarian cancer
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Calcitonin
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Medullary Thyroid Carcinoma
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CEA
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Carcinoembryogenic antigen: colorectal, pancreatic, gastric, breast, MTC non-specific marker for assessment of recurrence.
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Chromogranin
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Neural crest tumors Carcinoid tumors
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Psamomma bodies
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Mesothelioma Serous papillary cystuadenocarcinoma of ovary Meningioma Papillary carcinoma of thyroid (Orphan Annie)
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Paraneoplastic syndrome of RCC
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EPO - Polycythemia PTHrP - Hypercalcemia ACTH - Cushing Patient presents with kidney stones, abdominal pain, elevated Hgb/Hct, immunosuppression and has a brain mets that looks like clear cells.
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Paraneoplastic syndrome of Small Cell Lung Carcinoma
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ACTH - Cushing SIADH - Euvolemic hyponatremia Lambert Eaton - muscle activity improves with movement Patient presents with low Na and Cushing symptoms with chronic cough and weight loss.
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PTHrP elevated in which lung cancer?
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Squamous cell lung carcinoma
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Osteoblastic mets
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Prostate cancer
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Mixed bone mets
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Breast, lung cancer
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Primary mets to the brain
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Lung, Breast, Prostate, Melanoma, GI LBPMG
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Primary mets to the liver
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Colon
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Primary mets to bone
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Prostate, Breast >> Lung, thyroid, kidney
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Toxins to the liver
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Ethanol, Aflatoxin/Aspergillus - HCC Arsenic, Vinyl Cl - Angiosarcoma of Liver CCl4 - Centrilobular necrosis, fatty change
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Toxins to Bladder
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Aromatic amines, Cigarette smoke - transitional cell cancer of bladder
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Ionizing Radiation
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Thyroid Cancer
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Cigarette smoke is risk factor for MANY diseases and cancers
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transitional cell cancer of bladder cervical carcinoma pancreatic adenocarcinoma squamous + small cell lung, esophageal, larynx cancer RCC
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Nitrosamines (smoked foods)
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Gastric cancer (remember: Japanese!)
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Radon
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Lung Cancer (basements)
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2. Overview of Cancer by Organ System
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Yay!
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Colorectal Cancer
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Familial Adenomatous Polyposis Lynch syndrome
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Colorectal progression (Lynch Syndrome)
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Micro satellite instability with MSH gene mutations, mismatch repair defect CP: family with endometrial, ovarian, skin, colorectal cancers diagnosed before 50 y/o
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Colorectal progression (FAP)
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APC - KRAS - p53 Chromosomal instability pathway CP: AD transmission chromosome 5, thousands of polyps in the rectum post puberty, must be removed
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Histology
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Neoplastic polyps (via FAP pathway) present with 1) tubular (less malignant) 2) villous (villanous - malignant!) Serrated - malignant
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Benign polyps associated disease
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Peutz-Jegher Juvenile polyposis syndrome
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Gastric carcinoma
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2 types: 1. Intestinal: H. pylori, nitrosamines 2. Diffuse: SIGNET RING CELLS, mets to ovaries (Krukenberg), periumbilical (Sister Mary Joseph nodules), Virchow node (supraclavicular node mets)
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Ulcers relieved with meals
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Duodenal ulcers Zollinger Ellison syndrome
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Ulcers worsened with meals
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Peptic ulcers NSAIDs
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Menetrier disease
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Precancerous hyperplasia of gastric mucosa (thickened rugae) with loss of parietal cells and decreased acid secretion CP: patient with brain-looking stomach on MRI, B12 deficiency, gastritis
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Liver cancers
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Cavernous hemangioma: collections of dilated blood vessels, most common HCC: tan nodules, risk with HBV/HCV, alcohol, fat, autoimmune disease, toxins (Aspergillus) Hepatic adenoma: OCPs, regress spontaneously Angiosarcoma: As and Vinyl chloride, malignant endothelial tumor Metastases: GI, breast, lung to liver
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Risk factors for pancreatic carcinoma
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Smoking, chronic pancreatitis, diabetes, 50+ y/o, Jewish/AA males Co-morbidity: depression
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Hematologic Cancers
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Leukemia & Lymphoma
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t(8;14)
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Burkitt Lymphoma Oncogene: c-myc Histology: Starry sky appearance (sheets of lymphocytes + tingible body macrophages) CP: EBV-jaw, AA; Sporadic-HIV, abdominal or pelvis
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t(15;17)
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Acute Myelogenous Leukemia Histology: increased myeloblasts with Auer Rods in bone marrow and peripheral blood, peroxidase (+) inclusions Rx: ATRA (vitamin A) CP: elderly onset - fatigue, easy bruising + low Hgb, low platelets, HIGH leukocytes // Down Syndrome
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t(9;22)
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Chronic Myelogenous Leukemia Gene: BCR-Abl fusion protein Histology: increased basophils, leukemia reaction Rx: Imatinib CP: elevated Leukocytes (neutrophils, basophils), splenomegaly, low LAP, middle-age to elderly
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t(11;14)
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Mantel cell lymphoma Gene: Cyclin D1 Histology: lymphadenopathy in older males CD5+
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t(14;18)
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Follicular lymphoma Gene: Bcl2 - no apoptosis Histology: hyperplasia of follicles in lymph node without tingible body macrophages CP: painless LAD
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Hodgkin Lymphoma markers
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CD 15, CD30 - Owl Eye nuclei (Reed Sternberg cells) B symptoms (fevers, chills, night sweats with fatigue) Nodular sclerosing most common, lymphocyte rich best prognosis
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T cell cancers with skin presentations
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T cell lymphoma Mycosis fungoides
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Mycosis fungicides
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CP: scaly skin patches/plaques (circular) Biopsy shows CD4+ cells with cerebriform nuclei, can progress to T cell leukemia (Sezary Syndrome) Adults
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HTLV is associated with
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Adult T cell lymphoma
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Cancers with fried egg histology
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Multiple myeloma
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Multiple Myeloma
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Histology: numerous B cells with clock-face chromatin Labs: M spike (IgG, IgA), Bence Jones proteins in urine (Ig light chains), peripheral Rouleaux CP: Elderly man with kidney stones/abdominal pain/personality changes, elevated BUN/Cr, low Hgb/Hct, and back pain. CRAB Waldenstrom macroglobulinemia - M spike is IgM, blurred vision and Raynaud - no CRAB
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MGUS can transform to MM
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MGUS: monoclonal expansion of B cells without CRAB
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Pseudo-Pelter-Huet anomaly
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Neutrophils with bilobed nuclei Post-chemotherapy disorder of stem cells leading to destruction of all non lymphoid lineages - AML transformation
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Down Syndrome cancers
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Acute Lymphoblast Leukemia/Lymphoma: mediastinal mass and SVC syndrome, Tdt+, CD10+, better prognosis with t(12;21) Acute Myelogenous Leukemia: Auer Rods Acute Megakaryoblastic Leukemia: mucosal tumors
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Hairy Cell Leukemia
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Mature B cell tumor of adults Histology: tartrate-resistant acid phosphatase (+) stain - TRAP, dry tap on bone marrow, peripheral smell with filamentous projections of lymphocytes Rx: Cladribine (-ADA), Pentostatin
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EWS-FLI 1
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t(11;22) Ewing Sarcoma - onion skin periosteal reaction, boys <15 y/o bones
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Brain tumors
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UGH!
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Glioblastoma Multiforme
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GFAP+, butterfly glioma, pseudopallisating pleomorphic cells with necrosis + hemorrhage
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Meningioma
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Psamomma bodies with dural attachment, spindle cells in whorled pattern, calcifications
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Hemangioblastoma
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//RCC and von Hippel Lindau (chrom 3) thin walled capillaries with lots of RBCs in brain
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Schwannoma
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S-100+ NF-2 bilateral schwannoma - Merlin protein, associated with fat tumors in kidney
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Oligodendroglioma
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FRIED EGG APPEARANCE IN BRAIN calcifications on MRI
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Pituitary adenoma
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PRLoma, bitemporal hemianopia
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CHILDHOOD BRAIN TUMORS
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Craniopharygioma - Rathke pouch ectoderm, calcifcation/tooth like histology Pilocytic astrocytoma - benign, GFAP+, ROSENTHAL fibers (Eos, corkscrew) Medulloblastoma - Homer-Wright pseudo rosettes (Neuroblastoma as well), drop mets to spinal cord, malignant, small blue cells Ependymoma - perivascular rosettes
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Renal Cancer
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Renal cell carcinoma Renal oncocytoma Wilms
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RCC
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PCT cortical origin clear cells with glycogen, lipids, carbohydrates Paraneoplastic: ACTH, EPO, PTHrP spread via renal vein to IVC, mets to lung and bone (osteolytic) CP: Patient presents with flank pain and hematuria, kidney stones, Hgb/Hct up, mass in abdomen *check for brain hemangioma, chromosome 3 problems VHL
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Renal oncoytoma
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Eosinophilic cells with abundant mitochondria, benign Tan center
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Wilms tumor
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Children - unilateral flank mass and hematuria Genes - WT1 and WT2 on chromosome 11 CP: WAGR - Wilms tumor, Aniridia (iris), GU malformation, mental retardation
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Neuroblastoma
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Children - neural crest adrenal medulla origin, abdominal mass that CROSSES midline Genes - N-myc *Homer-Wright pseudo rosettes, small round cells with blue nuclei, Bombesin and neuron-specific (+) CP - myoclonus opsoclonus, elevated HVA and VMA without elevated BP,
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Pheochromocytoma
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Adults - adrenal medulla, chromatin cells of neural crest CP - episodic hypertension (200/100 - much higher than panic attacks) NF-1 association* (chromosome 17, AD), VHL (chromosome 3), MEN 2A and 2B (chromosome 10) Rx: Phenoxybenzamine (a1-antagonist), B-blocker after Benign, unilateral, within the adrenal, non-calcifying, adults Chromaffin cell hyperplasia with enlarged, pleomorphic nuclei, tan nodule in medulla
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Save cyclophosphamide and ifosfamide OD - hemorrhagic cystitis, myelosuppression
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Mesna
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Leucovorin saves
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MTX myelosuppression
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Schistosome haematobium (straight poker)
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Squamous cell carcinoma of the bladder
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Reproductive Tumors
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Yay!
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Rhabdomyosarcoma grape tumor
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girls < 4 y/o spindle shaped, desmin (+) clear, grape-like mass from vagina
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Cervical cancer pathogenesis
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Disordered epithelial growth BEGINNING AT THE BASAL LAYER HPV 16, 18, 31, 33 association (high grade) E6 inhibits p53 - no apoptosis E7 inhibits RB suppressor gene - no cell cycle check G1-S DOES NOT metastasize - invades surrounding structures Histology: raisin nucleus (koilocytes) with perinuclear halo CP: bleeding with intercourse Risk: multiple partners, smoking, immunocompromised (HIV)
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Ovarian neoplasms
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Serous cyst adenoma: bilateral, psamomma body Mucinous cyst adenoma: mucus-secreting epithelium Endometrioma: endometriosis consequence Teratoma (mature): benign, multiple tissues, TSH - hyperthyroidism - struma ovary Brenner tumor: bladder, coffee bean nuclei Fibromas: spindle shaped, Meigs (ascites, hydrothorax, fibroma) Thecoma: estrogen in postmenopausal woman, abnormal bleeding
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Coffee bean nucleus
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Brenner tumor, ovarian tumor that looks like a bladder
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Fried egg in the ovaries
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Dysgerminoma elevated hCG, LDH
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Choriocarcinoma of ovary
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elevated b-HC, spread to lungs, no chorionic vili
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Yolk sac tumor of ovary
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yellow, friable mass Schiller-Duval bodies AFP
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Krukenberg tumor of ovary
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Signet cells GI malignant (gastric adenocarcinoma) mucin-secreting
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Immature teratoma of ovary
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Neural tissue, malignant, thyroid tissue
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Call-Exner Bodies
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Granulosa cell tumor Children - precocious puberty Adults - postmenopausal bleeding
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Heavy uterine bleeding with uniformly enlarged uterus in a middle age, multiparous woman
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Adenomyosis - invasion of myometrium with endometrial tissues
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Severe or abnormal uterine bleedings in middle age with nodules in the uterus, can have miscarriages
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Leiomyoma - benign
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Vaginal bleeding post menopause with endometrial hyperplasia, associated with Lynch syndrome
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Endometrial cancer
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Markers of Paget Disease of the Breast
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Cytokeratin, Mucin
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Ecadherin + on
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DCIS
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Invasive Lobular breast cancer
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E-cadherin negative
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Testicular cancers
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Seminoma: malignant, fried egg appearance (dysgerminoma ovary in females), elevated ALP Yolk sac: Schiller Duval, yellow, AFP Choriocarcinoma: b-HCG // elevated TSH, spread to lungs, gynecomastia Teratoma: malignant, elevated HCG and AFP Embryonal: THE WORST, mixed with other types
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Non-germ cell testicular cancers
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Leydig: Reinke crystals Sertoli: androblastoma of sex cord, Peutz-Jegher Testicular lymphoma: mass in elderly
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Prostate Cancer
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posterior lobe of prostate elevated PSA, ALP adenocarcinoma on biopsy osteoblastic metastases to the bone low back pain
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Lung Cancers
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Mesothelioma Small Cell Lung Carcinoma Adenocarcinoma Squamous Cell Lung Carcinoma Pancoast
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Central lung lesions
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Small cell lung carcinoma, squamous cell carcinoma
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Small cell lung carcinoma
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myc oncogene application chemotherapy Kulchitsky cells - small blue, dark cells chromogranin + ACTH, SIADH, Lambert-Eaton
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Squamous cell carcinoma
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cigarettes PTH keratin pearls and intercellular bridges
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Adenocarcinoma
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nonsmokers KRAS, EGFR, ALK activation Erlotinib mucin+
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Large cell carcinoma
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anapestic, malignant, b-HCG
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Bronchial carcinoid tumor
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carcinoid syndrome chromogranin A+
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Pedunculated mass in LA
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18 y/o+ Myxoma < 18 y/o Rhabdomyosarcoma - Tuberous sclerosis CP: syncope
