pathology

Terminology Adjuvant therapy - given in addition to standard therapy Consolidation therapy - given after induction therapy with multidrug regimens to further reduce tumor burden Induction therapy - initial dose of treatment to rapidly kill tumor cells and send the patient into remission Maintenance therapy - given after induction and consolidation therapies or after the initial standard therapy to kill any residual tumor cells and keep the patient in remission Neoadjuvant therapy - given before the standard therapy for a particular disease Remission - less than 5% tumor burden Salvage therapy - given when standard therapy fails Adjuvant therapies in various cancers Metastasis to bone - bisphosphonates (e.g. zoledronic acid) are given to prevent lytic lesions and pathologic fractures as well as malignant hypercalcemia. Bisphosphonates work by inhibiting osteoclasts and thereby preventing bone breakdown. Breast cancer Tamoxifen , a selective estrogen recep...

Patient will have a ruddy face (facial plethora), high blood pressure, and itching that occurs after exposure to water e.g. after bath/ shower (aquagenic pruritis). Physical exam will show splenomegaly. Some patients may present with burning in hands/ feet (erythromelalgia), transient visual disturbances, bleeding, and gouty arthritis (increased RBC turnover). CBC will show very high hemoglobin and hematocrit, high platelet count and WBC count. Increased blood viscosity is responsible for the visual disturbances, the hypertension, etc. It is important to know the mutation responsible for PV - a JAK2 mutation that results in the gene always being active. The gene produces a JAK2 tyrosine kinase that differentiates myeloid cells into erythrocytes (red blood cells). Normally, the gene is activated by erythropoietin (EPO) released by the kidneys (less so the liver) when there is tissue hypoxia. With the always active gene, erythropoietin isn't needed and the levels are low. This i...

Patient will have a severe infection that may require longer than normal to improve even with antibiotics. On CBC, the WBC count will be markedly elevated (typically >50,000). On peripheral smear, there will be many immature forms of neutrophils (myelocytes, promyelocytes, metamyelocytes, bands). However, most will be further along in maturation (i.e. more bands). Look for a high leukocyte alkaline phosphatase (LAP) score. Differential Dx The LAP score helps differentiate this from CML which can also present with infections as well as immature forms of neutrophils (myelocytes, metamyelocytes) but has a low LAP score. This is because the neutrophil precursors are so immature that they don't function as well. CML also usually has a higher WBC count (typically >100,000). Also unlike CML, leukemoid reaction does not present with increased basophils. Relevant Images More of the mature neutrophil precursors e.g. bands, metamyleocytes as well as mature (segmented) neutrophil...

Quick Review Patient is often older, and can no symptoms or have B symptoms (night sweats, etc), fatigue, and weight loss (caused by early satiety due to enlarged spleen). On physical exam, an enlarged spleen can be palpated. CBC shows very high WBC count (typically >100,000) with elevated basophils on differential. Peripheral smear shows early, immature neutrophil precursors (myelocytes, metamyelocytes) as well as many basophils. It is important for CML to know the details of the genetic abnormality because it relates to the treatment. CML is due to a translocation of BCR and ABL on chromosomes 9 and 22 resulting a fusion BCR-ABL gene that produces a tyrosine kinase that is always active. The treatment of choice is a tyrosine kinase inhibitor e.g. imatinib. They work to suppress the tyrosine kinase and can induce disease remission. Relevant Images Immature neutrophil precursors on peripheral smear BCR-ABL translocation

Quick Review Patient is an adult (usually older, but can also be younger) with fatigue (due to anemia) and bleeding (due to thrombocytopenia) and on CBC there is decreased hemoglobin, decreased platelets, and WBC varies (can be normal, increased or decreased).  LDH will be elevated. The most important form of AML to know is acute promyelocytic leukemia (APML). On peripheral smear, AML presents with myeloblasts with Auer rods. Bone marrow biopsy will show myeloid blasts, for APML this would be atypical promyelocytes. In AML, the bone marrow is crowded with immature myeloid cells ("blasts") preventing development of other cell types (platelets, RBCs, normal WBCs). These myeloblasts are also present in the peripheral blood in large numbers. This is why patients have fatigue (anemia), bleeding/ bruising (thrombocytopenia), increased infections (granulocytopenia). APML can present with DIC (disseminated intravascular coagulation) which results in elevated PT and aPTT and re...

Quick Review Patient will be elderly (>65 y.o), have fatigue (due to anemia) and large firm mobile lymph nodes (supraclavicular, axillary and/or cervical lymph nodes). Splenomegaly on abdominal exam. Some patients may have B symptoms (night sweats, fever, etc). Some may have increased infections or weight loss. Some may be asymptomatic. The key features are elderly patient with abnormal CBC and peripheral smear. CBC will show elevated WBC count, and on differential elevated lymphocytes. Peripheral smear will show increased lymphocytes (lymphocytosis) and they will be mature (small, little cytoplasm); smudge cells may also be seen. Flow cytometry confirms presence of clonal expansion of B lymphocytes by finding CD20, CD19, CD5 etc. Biopsy of the lymph nodes and bone marrow is not usually needed. Key Features most common leukemia in the USA elderly "mature" patients lymphocytosis (elevated WBC count due to lymphocytes, increased lymphocytes on smear) lymphocyte...

Screening Mammography in women over 50 is the screening test that lowers mortality the most. Mammography begins at age 50 and is not routinely done once over 75.  BRCA genetic testing is not routinely done. BRCA gene is likely to be positive if there is a family history of breast cancer or increased risk of ovarian cancer.  Diagnosis A positive mammography is followed by sentinel node biopsy . Sentinel node = the first lymph node that a dye/ tracer injected into the operative field reaches. If biopsy sample is positive for cancer it is tested for markers including ER (estrogen receptor), PR (progesterone receptor), HER2/neu . A positive biopsy result is followed by axillary lymph node dissection .  Prevention Tamoxifen is given if 2 or more first-degree relatives have breast cancer. It reduces risk of breast cancer by 50% and is started at age 40.  Treatment Surgical remova l of the tumor is best done with lumpectomy with ra...