Patient 1

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Patient 1

• CC 5YOWFpresents with fever, marked weakness,
  pallor, bone pain, and bleeding from her nose
• HPI progressively increasing fatigability and
  infections over the past few months
• PE marked pallor epistaxis ecchymotic patches
  over skin sternal tenderness slight
  hepatosplenomegaly with nontender
  lymphadenopathy no signs of meningitis normal
  funduscopic exam.

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Gross Pathology

• Neoplastic infiltration of lymph nodes, spleen,
  liver and bone marrow.
• Loss of normal bone marrow architecture.

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Micro Pathology

• Myelophthisic bone marrow (distorted architecture
  secondary to a space-occupying lesion) with
  lymphoblastic infiltration
• Lymphoblasts with inconspicuous nucleoli,
  condensed chromatin, scant cytoplam

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Labs

• Normocytic, normochromic anemia
• Absolute lymphocytosis with excess blasts (gt30)
• Negative monospot test for Epstein-Barr virus.
• Positive terminal deoxytransferase (TdT)(marker
  for immature T and B lymphocytes)
• Positive CD10 marker (CALLA-Common Acute
  Lymphoblastic Leukemia Antigen

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Diagnosis and Discussion

• Diagnosis
• Acute Lymphocytic Leukemia (ALL)
• Discussion
• ALL is the most common pediatric neoplasm it
  accounts for 80 of all childhood leukemias. It
  carries a good prognosis.

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Patient 2

• CC 25YOF presents with high grade fever,
  menorrhagia, and marked weakness
• HPI recurrent infections over the last few
  weeks
• PE Marked pallor multiple purpuric patches
  over skin hepatosplenomegaly gingival
  hyperplasia sternal tenderness normal
  funduscopic and neurologic exam

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Gross Pathology

• Bone erosion due to marrow expansion
• Chloroma formation, mainly in skull
• Splenomegaly

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Micro Pathology

• Auer Rods (basophilic cytoplasmic bodies) in
  myelocytes
• Peroxidase positive stains on bone marrow and
  gingival biopsy
• Myeloblasts with myelomonocytic differentiation
  replace normal marrow

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Labs

• Normocytic, normochromic anemia.
• Thrombocytopenia
• Neutropenia.
• Prolonged PT/PTT
• Leukocytosis composed mainly of myeloblasts and
  promyelocytes

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Diagnosis and Discussion

• Diagnosis
• Acute Myelogenous Leukemia (AML)
• Discussion
• Not as common as ALL. Increased risk associated
  with ionizing radiation, benzene exposure, Downs
  syndrome, and cytotoxic chemotherapeutic agents

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AML/ALL Common Symptoms

• Fever, pallor, weakness, bone pain, epistaxis,
  recurrent infections
• Thrombocytopenia neutopenia
• Minor hepatosplenomegaly

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AML vs. ALL

• Gingival lesions
• Auer Rods

• Nontender lymphadenopathy
• Scant cytoplasm
• CD10 (CALLA) positive
• TdT positive

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Patient 3

• 11Month Old M of Indian descent
• CC Presents with marked pallor, failure to
  thrive, and delayed developmental motor
  milestones.
• PE Marked pallor, mild icterus frontal bossing
  and maxillary hypertrophy chipmunk face
  splenomegaly

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Imaging

• XR, Skull (lateral) maxillary overgrowth and
  widening of diploic spaces with hair on end
  appearance of frontal bone, caused by vertical
  trabeculae

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Gross Pathology

• Expansion of hematopoietic bone marrow
• Thinning of cortical bone

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Micro Pathology

• Red marrow increased
• Yellow marrow decreased
• Marked erythoid hyperplasia in marrow

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Labs

• Microcytic hypochromic anemia
• Decreased reticulocytosis
• Mildly increased unconjugated bilirubin
• Anisopoikilocytosis
• HbA-absent
• HbF-95

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Diagnosis and Discussion

• Diagnosis
• Beta Thalassemia
• Discussion
• Beta-Thalassemia results from decreased
  synthesis of beta-globulin chains due to errors
  in transcription, splicing or translation of
  mRNA.
• Alpha-Thalassemia results from decreased
  synthesis of alpha-globulin chain due to deletion
  of one or more of the four alpa genes normally
  present.

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Treatment

• Blood transfusion, folic acid supplementation,
  iron chelation therapy, bone marrow
  transplantation

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Patient 4

• 24YOWM
• CC Rapid enlargement of his abdomen, producing a
  dragging sensation, along with a painless lump in
  his neck for the past two months
• HPI Intermittent fever, drenching night sweats,
  pruritus, and significant weight loss
• PE Pallor unilateral nontender, rubbery,
  enlarged cervical lymph nodes splenomegaly no
  enlargement of tonsils

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Labs

• Neutrophilic leukocytosis with lymphopenia
• Normocytic anemia
• Elevated ESR
• Elevated serum Cu and ferritin
• Negative Mantoux test

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Imaging

• CXR bilateral hilar lymphadenopathy

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Gross Pathology

• Involved lymph nodes are rubbery
• Have cut-potato appearance of cut surface

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Micro Pathology

• Lymph node biopsy shows large histiocyte cells
  with multilobed nuclei and eosinophilic nucleolus
  resembling owls eyes (Reed-Sternberg Cells)
• No bone marrow involvement.

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Diagnosis and Discussion

• Diagnosis
• Hodgkins Lymphoma
• Discussion
• Four patterns seen on biopsy. Common symptoms
  are the fever, night sweats, and weight loss.
  The disease spreads to contiguous lymph nodes
  before moving into the blood.

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Patient 5

• 40YOWM
• CC Life insurance physical exam
• HPI No complaints except occasional fatigue and
  increasing abdominal girth.
• PE Pallor of skin and mucus membranes markedly
  enlarged spleen pain on palpation of sternum no
  lymphadenopathy

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Gross Pathology

• Skull chloromas
• Enlarged congested spleen with areas of
  thrombosis and microinfarcts
• Hepatomegaly

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Labs

• Markedly elevated WBC count (130,000)
• Immature granulocytes mixed with normal appearing
  ones
• Basophilia, eosinophilia, early thrombocytosis,
  late thrombocytopenia
• Low leukocyte alkaline phosphatase
• Elevated serum vitamin B12
• Chromosomal translocation t(922)/bcr-abl gene
  (Philadelphia Chromosome)

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Micro Pathology

• Hepatic sinusoidal leukemic infiltrates
• Congestive splenomegaly with myeloid metaplasia
• Philadelphia chromosome in all myeloid progeny

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Diagnosis and Discussion

• Diagnosis
• Chronic Myelogenous Leukemia (CML)
• Discussion
• Death usually results from accelerated
  transformation into acute leukemia (blast crisis)
  within 2-5 years.

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Patient 6

• 65YOWM
• CC Routine checkup
• HPI On directed history, he admits to a weight
  loss of about 12lbs over the past 4 mos, together
  with episodes of epistaxis and extreme fatigue
• PE Generalized nontender lymphadenopathy
  pallor enlargement of spleen and liver

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Gross Pathology

• Lymph node enlargement
• Hepatosplenomegaly with tumor nodule formation

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Micro Pathology

• Bone marrow biopsy reveals extensive
  infiltration, normal-looking lymphocytes and a
  few lymphoblasts
• Blood smear shows many lymphocytes with small,
  dark, round nucleus and scant cytoplasm

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Labs

• Markedly elevated WBC (124,000)
• 90 Lymphocytes
• No lymphoblasts
• Mild thrombocytopenia
• Cooms-positive hemolytic anemia
• Smudge cells
• B-cells express CD5 (normally a T-cell marker)

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Diagnosis and Discussion

• Diagnosis
• Chronic Lymphocytic Leukemia (CLL)
• Discussion
• CLL is a malignant neoplastic disease of B
  Lymphocytes that express surface marker CD5.
  Characterized by slow progression of anemia,
  hemolytic anemia, recurrent infections, lymph
  node enlargement, and bleeding episodes.

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Patient 7

• 10YOBM
• CC Chronic nonhealing ulcer on lower leg
• HPI Recurrent episodes of abdominal and chest
  pain along with diminution of vision.
• PE Fever pallor mild icterus funduscopy
  shows hypoxic spots with neovascularization
  nonhealing chronic ulcer on left lower leg

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Imaging

• CT/US of Abdomen
• small, calcified spleen

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Labs

• Decreased HCT
• Megaloblastic anemia
• Serum bilirubin moderately elevated
• Howell-Jolly bodies and Cabot rings

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Diagnosis

• Sickle Cell Anemia

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Patient Next

• 10 Month old Female
• CC Mother claims the child is a retard. She
  cannot see properly, and falls repeatedly.
• PE No lacerations of fractures noted normal
  physical development for size and weight bruises
  in different stages of healing bilateral retinal
  hemorrhages

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Imaging and Labs

• Imaging
• XR No new or old fractures
• Labs
• Coagulation profile is normal.

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Diagnosis and Discussion

• Diagnosis
• Shaken Baby Syndrome---Abuse
• Discussion
• Vigorous shaking can produce vitreous and
  retinal hemorrhages that may be the only
  verifiable sign of child abuse.
• We are required by law to report any suspicion
  of child abuse or neglect to state protection
  agencies

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Patient Last

• 64YOBM
• CC Bone pain, weight loss, easy fatigability
• HPI Recurrent URIs and frequent nose bleeds
• PE Pallor bone tenderness in lower back and
  ribs petechiae on buccal mucosa no
  hepatosplenomegaly.

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Labs

• Normocytic, normochromic anemia
• Neutropenia
• Rouleau formation
• Elevated Serum Ca
• Normal alkaline phosphatase
• Increased ESR
• Gamma spike on serum protein electrophoresis
• UA Bence Jones Proteinuria

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Imaging and Gross Pathology

• Imaging
• Punched out lytic bone lesions in vertebrae,
  long bones, and skull
• Gross Pathology
• Multifocal replacement of normal bone tissue
  with tumor cells (plasmacytoma)

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Micro Pathology

• Infiltration of bone marrow by normal-looking
  plasma cells.
• Amyloid deposits in kidney with renal tubular
  cast formation and interstitial fibrosis.

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Diagnosis and Discussion

• Diagnosis
• Multiple Myeloma
• Discussion
• Primary malignancy of plasma cells with
  replacement of normal bone marrow it is the most
  common primary bone cancer.