Chapter 11

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Leukopenia

Low WBC count

Possible Causes of Malignant Disorders of WBCs

Viruses Radiation exposure Chemical exposure (slight) Reduction or alteration in normal hematopoiesis Some genetic diseases

CA 19-9

cancer marker for pancreatic cancer

Plasma Cell Myeloma

(Multiple Myeloma) Malignant disorder of plasma cells, develops in the bone marrow (form tumors within the bone) Plasma cells excrete abundance of 1 type of immunoglobulin Occurs exclusively in adults, median age = 65 years Men > women

A 58-year-old woman is seen in the clinic for reports of severe back pain. Her chest X-ray demonstrates generalized bone demineralization and compression fracture. Blood studies demonstrate elevated calcium levels. The most likely diagnosis is A) leukemia. B) myeloma. C) Hodgkin disease. D) back trauma.

B) myeloma

Diagnosis confirmation of Plasma Cell Myeloma

Bone marrow biopsy done for definitive diagnosis Plasma cells occupy 30-95% of bone marrow, minimum of 10-15% for diagnosis

Plasma Cell Myeloma symptoms

Bone pain (usually first symptom) Protein in urine High serum calcium levels Bone marrow depression indicators - Anemia - Recurrent infections - Bleeding tendencies

Renal insufficiency is a common complication of which disease? A) Chronic myeloid leukemia (CML) B) Chronic lymphoid leukemia (CLL) C) Myeloma D) Hodgkin disease

C) Myeloma

S/S of Thrombocytopenia

Platelet count <20,000 (threshold for transfusion) Petechiae Ecchymosis Bleeding gums Occult hematuria Retinal hemorrhages

What does chemo and radiation cause/what does cancer treatment revolve around?

Preventing infection and intracranial hemorrhage Bone marrow suppression Causes Pancytopenia (all WBCs,RBCs, platelet counts low)

Chronic Myeloid Leukemia Pathogenesis

Represents 15% of all cases of leukemia in US Middle age onset Occurs only occasionally in childhood/adolescence

Hodgkin Disease figures

Represents 30% of malignant lymphoma Occurs across lifespan - half of cases 20-40 yrs old Men > women Overall 5-year survival rate with treatment = 85%

Renal Insufficiency

Seen in Plasma Cell Myeloma (50% of patients) Resulting from: hyperproteinemia Bence Jones protein hypercalcemia hyperuricemia (from rapid cell turnover) Culminates with end-stage renal disease

Hodgkin Disease - pathogenesis

Usually presents in sentinel node or localized node chain Inflammatory cells accumulate within node, Reed-Sternberg cells constitute around 2% of cells in lymph node tumor

Occult Hematuria

blood in the urine

Ecchymosis

bruising (black and blue mark)

CEA

carcinoembryonic antigen Non-specific but used for colon cancer, response to therapy

Leukemias

circulating tumors that primary involve blood and bone marrow (liquid tumors)

Paraneoplastic syndrome

ectopic release of hormones from tumor that is distant from gland itself. Cancer cells produce hormones from tumor itself, not gland it is supposed to come from.

CA 125

marker for ovarian cancer

BRCA1

mutations in this gene increase a person's risk of breast cancer

AFP

non-specific test should be high in newborn but not in adult

Petechiae

pinpoint black and blue spots from minute hemorrhages under the skin

PSA

prostate-specific antigen

Plasma Cell Myeloma onset

slow, insidious

Bands

Immature neutrophils Normal is 0-5, more than 5 bands = body is fighting bacteria infection (When body fighting infection = body says OMG we need to make more neutrophils)

Most Common Clinical Manifestations of Malignant Disorders of WBCs

Leukopenia Lymphadenopathy Joint swelling and pain Weight loss Anorexia Hepatomegaly Splenomegaly Anemia Thrombocytopenia

Bence Jones protein

Light chain antibody fragments produced by malignant plasma cells, that accumulate in blood and urine - Helps confirm diagnosis of Plasma Cell Myeloma - Can accumulate in kidneys and damage them

Typical S/S of Malignant Disorders of WBCs

Malaise, weakness Unexplained fever, night sweats Recurrent infections Lymphadenopathy with lymphoma and some leukemias Very high total WBC count or presence of abnormal cell types

Diagnosis of Plasma Cell Myeloma based on

Monoclonal antibody peak (M spike) Presence of Bence Jones protein Hypercalcemia Evidence of bone lesions

Lymphomas

Neoplastic disease of mature lymphocytes in lymphoid tissue

Most common cancer diagnosis in HIV patient

Non-Hodgkin Lymphoma - have extranodal masses outside of continuous chain. SVC syndrome - these masses press on superior vena cava and impairs brain perfusion *medical emergency*

Characterizing clinical manifestations of Plasma Cell Myeloma

*Diagnosis usually with routine examination during asymptomatic phase* *Most caused by bone/renal damage* Malignant plasma cells invade bone and form bone tumors (on x-ray bone will have "honeycomb" appearance); pathologic fractures common May also target other tissues, including lymph nodes, liver, spleen and kidneys (50% of patients will have renal failure)

Hodgkin Disease characterization

*Reed-sternberg cells* - malignant but grow in predictable way (contiguous lymphatic pathways), which sets HD apart from other lymphomas

What is Chronic Myeloid Leukemia characterized by?

1 mutation - the Philadelphia chromosome (Ph+) that is carried by malignant granulocytes

Burkett's lymphoma

100% of pts diagnosed also test positive for Epstein Barr Virus

M Spike

A result of urine or serum protein electrophoresis test that shows excess of monoclonal antibodies. Highly suspicious for Plasma Cell Myeloma, warrants bone marrow biopsy to diagnose

The major cause of death from leukemic disease is A) infection. B) malnutrition. C) hypovolemic shock. D) kidney failure.

A) infection

Neutropenia

Absolute neutrophil count <500 cells/mcL (normal range = 1500-4500 mcL) Main concern with neutropenia is preventing bacterial infections

Philadelphia chromosome

Characteristic mutation of CML Translocation of chromosomes 9 and 22, causes two genes to be juxtaposed and creates new fusion gene: bcr/abl. Protein product of bcr/abl spurs cell proliferation and reduces apoptotic cell death.

Which form of leukemia demonstrates the presence of the Philadelphia chromosome? A) ALL (acute lymphoid leukemia) B) CLL (chronic lymphoid leukemia) C) AML (acute myeloid leukemia) D) CML (chronic myeloid leukemia)

D) CML (chronic myeloid leukemia)

CLL cell characterization

Defective apoptosis (lack ability to turn off growth) and longer lifespan Abundance of them, but they are not functional

Hodgkin Disease - clinical manifestations

Depend on origin site and dissemination stage Lymphadenopathy (cervical nodes most common site) Possible: Fever Night sweats Pruritus Weight loss Malaise Disease spreads from site or origin to other lymph nodes/lymphatic tissue, including spleen and bone marrow

Lymphadenopathy

Enlarged NON-tender lymph nodes

Hepatomegaly

Enlarged liver

Splenomegaly

Enlarged spleen

Hodgkin Disease - virus precursor

Epstein-Barr Virus frequently found in genome of Reed-Sternberg cells, may be important factor in development of HD

Hypercalcemia

Excessive calcium in the blood - suspicious for cancer in bone Bone destruction in MM releases calcium into the bloodstream

Symptoms of CLL (if present)

Fatigue Weight loss Anorexia Increased susceptibility to infections Lymphadenopathy Splenomegaly

Symptoms of CML (when present)

Fatigue Weight loss Sweats Bleeding Abdominal discomfort (from splenomegaly)

Chronic Lymphoid Leukemia

Follows an indolent course; asymptomatic Usually found by accident in routine blood examinations Malignant lymphocytes invade lymphoid tissues and bone marrow, disrupts function and reduces production of red blood cells/platelets Preponderance of lymphoid cells

Usual clinical presentation of CML

High granulocyte count on CBC Splenomegaly


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