Pediatric Lymphoma, Leukemia, and Non-Neoplastic WBC Disorders (Newman) Flashcards
Calculate the absolute neutrophil count if given the results of a complete blood count and determine the degree of neutropenia.
ANC= (% neutrophils + % bands) X (total WBC)
(100)
Define “neutropenia” in regards to absolute neutrophil count (ANC).
Neutropenia= ANC less than 1500/uL
ANC count at which the risk for serious infection is high
<500
Recognize the clinical manifestations, defect, inheritance pattern, and method of diagnosis, and risk of malignancy associated with Kostmann syndrome
Kostmann Syndrome (Severe Congenital Neutropenia)
- clinical manifestations:
- life-threatening pyogenic inections, often in infancy
- defect:
- impaired myeloid differentiation caused by maturational arrest of neutrophil precursors
- inheritance pattern:
- autosomal recessive
- method of diagnosis:
- bone marrow myeloid maturation arrest, 60-80% have neutrophil ELA-2 mutations.
- neutropenia; ANC<200 since birth, associated with mild anemial, and occasional monocytosis and eosinophilia
- risk of malignancy:
- increased risk of leukemia (AML)
Recognize the clinical manifestations, defect, inheritance pattern, and method of diagnosis, and risk of malignancy associated with Cyclic neutropenia.
Cyclic Neutropenia
- clinical manifestations:
- cyclic fever, oral ulcers, gingivitis, periodontal disease, recurrent bacterial infections
- defect:
- stem cell regulatory defect resulting in defective maturation
- inheritance pattern:
- sporadic or autosomal dominant
- method of diagnosis:
- ANC <200 for 3-7 days every 3 weeks (15 to 35 days). Tip: do a CBC each time the child is running a fever to look for this.
- risk of malignancy: none
Recognize the clinical manifestations, defect, inheritance pattern, and method of diagnosis, and risk of malignancy associated with Shwachman-Diamond syndrome
Shwachman-Diamond Syndrome
- clinical manifestations:
- triad of neutropenia, exocrine pancreas insufficiency, and skeletal abnormalities
- defect:
- defects in neutrophil mobility, migration, and chemoataxis, in addition to neutropenia
- inheritance pattern:
- autosomal recessive
- method of diagnosis:
- neutropenia, low serum trypsinogen, elevated fecal fat excretion, metaphyseal dysotosis, rib cage abnormalities, short stature, SBDS mutation in 90%
- risk of malignancy:
- increased risk for myelodysplastic syndrome or leukemia
Recognize the clinical manifestations, defect, inheritance pattern, and method of diagnosis, and risk of malignancy associated with Fanconi anemia
Fanconi Anemia
- clinical manifestations:
- bone marrow failure syndrome; GU and skeletal abnormalities, increased chromosome fragility
- defect:
- bone marrow failure syndrome (all cell lines affected). is the “classic example” of pancytopenia/bone marrow failure/aplastic anemia.
- inheritance pattern:
- autosomal recessive; presents in the first 10 years of life
- method of diagnosis:
- ?
- risk of malignancy:
- risk of AML, brain tumors, Wilms tumor
Recognize the clinical manifestations, defect, inheritance pattern, and method of diagnosis, and risk of malignancy associated with Leukocyte adhesion deficiency
Leukocyte Adhesion Deficiency
- clinical manifestations:
- delayed separation of the umbilical cord (>3 weeks), recurrent and severe bacterial and fungal infections WITHOUT PUS accumulation, poor wound healing, periodontal disease
- defect:
- neutrophils have diminished adhesion to surfaces and cannot maigrate out of blood vessels
- inheritance pattern:
- autosomal recessive
- method of diagnosis: ?
- risk of malignancy:?
Recognize the clinical manifestations, defect, inheritance pattern, and method of diagnosis, and risk of malignancy associated with Hyper-immunoglobulin E syndrome (Job syndrome)
Hyper-immunoglobulin E syndrome (Job syndrome)
- clinical manifestations:
- severe eczema, bacterial infections of skin and lungs, fungal infections
- defect:
- defect in chemotaxis of neutrophil
- inheritance pattern:
- sporadic, autosomal dominant
- method of diagnosis:
- increased IgE, eosinophilia
- risk of malignancy: no; good prognosis
Recognize the clinical manifestations, defect, inheritance pattern, and method of diagnosis, and risk of malignancy associated with Chronic granulomatous disease
Chronic Granulomatous Disease
- clinical manifestations:
- recurrent purulent infections with fungal or bacterial catalase-positive organisms, usually starting in infancy
- chronic inflammatory granulomas
- defect:
- defect in oxidative metabolism, absent generation of superoxide (which is toxic to microbes)
- inheritance pattern:
- primarily X-linked recessive
- method of diagnosis:
- nitrobule tetrazolium test
- risk of malignancy:
- no
- good prognosis with aggressive mangement of infeciton
Recognize the clinical manifestations, defect, inheritance pattern, and method of diagnosis, and risk of malignancy associated with Chediak-Higashi syndrome
Chediak-Higashi Syndrome
- clinical manifestations:
- partial oculocutaneous albinism, peripheral and cranial neuropathies, neutropenia, recurrant pyogenic infections
- defect:
- defects in granule morphogenesis, chemotaxis, and degranulation, ineffective granulopoiesis
- inheritance pattern:
- autosomal recessive
- method of diagnosis:
- azurophilic granules in neutrophils, eosinophils, and other granulocytes
- risk of malignancy: not sure about malignancy, but few patients survive past 20 years old
Name a common virus that causes neutropenia.
- Parvovirus B19 viral infection (Fifth disease)
- “slapped cheek” appearance, 1-2 weeks after infection with the virus
Name the class of drugs notorious for causing neutropenia.
Cytotoxic drugs for treatment of malignancies.
List some of the nutritional deficiencies that can cause neutropenia.
vitamin B 12, folate, copper, starvation
Know the immune deficiency associated with DiGeorge syndrome
T cell deficiency due to no thymus.
Discuss the significance of the presence of Reed-Sternberg cells in a biopsy specimen.
- Reed sternberg cells
- A large cell with multiple or multilobulated nuclei
- pathognomonic feature of Hodgkin Lymphoma
