Neoplastic and Hematologic
Pathology
By Paulina Castillo
Primary Brain Tumors
• Clinical presentation due to mass effects
e.g., seizures, dementia, focal lesions
• 1° brain tumors...
Adult Brain Tumors
A. Glioblastoma Multiforme (grade IV astrocytoma)
- most common 1° brain tumor
- Grave prognosis  < 1-...
Glioblastoma Multiforme
B. Meningioma
• 2nd
most common 1° brain tumor
• Most often occurs in convexities of hemispheres
and parasagittal region
•...
Meningioma
Convexity meningioma attached to the dural leaflet
and indenting the underlying brain
Whorled pattern and psamm...
C. Schwannoma
• 3rd most common 1° brain tumor
• Schwann cell origin
• Often localized to 8th
nerve  Acoustic Schwannoma
...
Schwannoma
D. Oligodendroglioma
• Relatively rare
• Slow growing
• Most often in frontal lobes
• “Fried egg” cells – round nuclei wit...
Classic fried-egg appearance with perinuclear halos
Oligodendroglioma
E. Pituitary Adenoma
• Prolactin secreting is most common form
• Sequalae:
- Bitemporal hemianopia (due to pressure on
opt...
Pituitary Adenoma
Childhood Brain Tumors
F. Low-grade astrocytoma (pilocytic
astrocytoma)
- diffusely infiltrating glioma
- in children, mos...
G. Medulloblastoma
• Highly Malignant cerebellar tumor
• A form of primitive neuroectodermal tumor (PNET)
• Can compress 4...
H. Ependymoma
• Ependymal cell tumors
• Most commonly found in 4th
ventricle
• Can cause hydrocephalus
• Characteristic pe...
I. Hemangioblastoma
• Most often cerebellar
• Associated with von Hippel-Lindau syndrome
when found with retinal angiomas
...
J. Craniopharyngioma
• Benign childhood tumor
• Confused with pituitary adenoma (can also cause
bitemporal hemianopia)
• M...
Pathology - Neoplastic
• Metastasis to brain
- 1° tumors that metastasize to brain:
Lung Lots of
Breast Bad
Skin(melanoma)...
Pathology – Neoplastic Cont’d
• Metastasis to Liver
- the most common sites of metastasis after
regional lymph nodes are l...
Pathology – Neoplastic Cont’d
• Metastasis to bone
- 1° tumors that metastasize to bone are:
Breast, Lung, Thyroid, Testes...
Paraneoplastic Effects of Tumors
• Small cell lung carcinoma
- causes: ACTH or ACTH-like peptide
- effect: Cushing’s Syndr...
Paraneoplastic Effects Cont’d
• Renal cell carcinoma
- causes: erythropoietin
- effects: polycythemia
• Thymoma, bronchoge...
Cancer
Epidemiology
Incidence Mortality
Male Female
Lung (33%)
Prostate (13%)
Lung ( 23%)
Breast (18%)
Male Female
Prostat...
Pathology - Hematologic
- Anemias:
1. Microcytic, hypochromic (MCV<80)
a. Iron Deficiencies - ↓ serum iron, ↑ TIBC, ↓ferri...
Pathology – Hematologic cont’d
3. Normocytic, normochromic
a. acute hemorrhage
b. enzyme defects (e.g., G6PD deficiency, P...
Aplastic Anemia
• Pancytopenia characterized by severe anemia,
neutropenia, & thrombocytopenia
- caused by failure or dest...
Aplastic Anemia Cont’d
• Symptoms: fatigue, malaise, pallor, purpura,
mucosal bleeding, petechiae, infection
• Pathologic ...
Hereditary Spherocytosis
• intrinsic, extravascular hemolysis due to spectrin
or ankyrin defect
• RBCs are small & round w...
Blood Dyscrasias
• Sickle Cell Anemia
- HbS mutation is a single aa replacement
in β chain (Glu  Val)
- low O2 or dehydra...
Sickle Cell Anemia Cont’d
- HbC defect is a different β-chain mutation
- pts. w/ HbC or HbSC (1 of each mutant
gene) have ...
- 8% of African-Americans carry the HbS trait
- 0.2% have the disease
- sickle cells are crescent-shaped RBCs
- “crew cut”...
Blood Dyscrasias Cont’d
• α-thalassemia
- normally there are 4 α-globin genes
- in α-thalassemia, the α-globin is underpro...
Blood Dyscrasias Cont’d
• β-thalassemia
- β-thalassemia minor (heterozygote): β-chain is
underproduced
- β-thalassemia maj...
- β-thalassemia major (homozygote) results in severe anemia requiring
blood transfusions
- Cardiac failure due to 2° hemoc...
Sample
Questions
Hereditary Spherocytosis
Slide 1 - TAMU COM - Class of 2008
Slide 1 - TAMU COM - Class of 2008
Slide 1 - TAMU COM - Class of 2008
Slide 1 - TAMU COM - Class of 2008
Slide 1 - TAMU COM - Class of 2008
Slide 1 - TAMU COM - Class of 2008
Slide 1 - TAMU COM - Class of 2008
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Slide 1 - TAMU COM - Class of 2008

  1. 1. Neoplastic and Hematologic Pathology By Paulina Castillo
  2. 2. Primary Brain Tumors • Clinical presentation due to mass effects e.g., seizures, dementia, focal lesions • 1° brain tumors rarely undergo metastasis • Majority of adult tumors are supratentorial • Majority of childhood tumors are infratentorial • About ½ of adult brain tumors are metastasis (Tentorial membrane is a fold of the dura mater that has its free margin surrounding the midbrain and a fixed margin attached to the skull at the top of the posterior fossa. It separates the cerebellum from the cerebral hemispheres)
  3. 3. Adult Brain Tumors A. Glioblastoma Multiforme (grade IV astrocytoma) - most common 1° brain tumor - Grave prognosis  < 1-year life expectancy - found in cerebral hemispheres - can cross corpus callosum  butterfly glioma (CC – arched brigde of nervous tissue that connects the two cerebral hemispheres, allowing communication between the right and left sides of the brain) - “pseudopalisading” tumor cells border central areas of necrosis and hemorrhage
  4. 4. Glioblastoma Multiforme
  5. 5. B. Meningioma • 2nd most common 1° brain tumor • Most often occurs in convexities of hemispheres and parasagittal region • Arises from arachnoid cells external to brain • Resectable • Spindle cells concentrically arranged in a whorled pattern • Psammoma bodies (laminated calcifications)
  6. 6. Meningioma Convexity meningioma attached to the dural leaflet and indenting the underlying brain Whorled pattern and psammoma body
  7. 7. C. Schwannoma • 3rd most common 1° brain tumor • Schwann cell origin • Often localized to 8th nerve  Acoustic Schwannoma • Bilateral schwannoma found in neurofibromatosis type 2 • Resectable
  8. 8. Schwannoma
  9. 9. D. Oligodendroglioma • Relatively rare • Slow growing • Most often in frontal lobes • “Fried egg” cells – round nuclei with clear cytoplasm; often calcified
  10. 10. Classic fried-egg appearance with perinuclear halos Oligodendroglioma
  11. 11. E. Pituitary Adenoma • Prolactin secreting is most common form • Sequalae: - Bitemporal hemianopia (due to pressure on optic chiasm) - Hyper- or hypopituitarism • Rathke’s pouch
  12. 12. Pituitary Adenoma
  13. 13. Childhood Brain Tumors F. Low-grade astrocytoma (pilocytic astrocytoma) - diffusely infiltrating glioma - in children, most often found in posterior fossa - benign - good prognosis - Rosenthal fibers
  14. 14. G. Medulloblastoma • Highly Malignant cerebellar tumor • A form of primitive neuroectodermal tumor (PNET) • Can compress 4th ventricle  causing hydrocephalus • Rosettes or perivascular pseudorosette pattern of cells • radiosensitive
  15. 15. H. Ependymoma • Ependymal cell tumors • Most commonly found in 4th ventricle • Can cause hydrocephalus • Characteristic perivascular rosettes • Rod-shaped blepharoplasts (basal ciliary bodies) found near the nucleus
  16. 16. I. Hemangioblastoma • Most often cerebellar • Associated with von Hippel-Lindau syndrome when found with retinal angiomas • Can cause EPO  2° polycythemia • Foamy cells and high vascularity are characteristic
  17. 17. J. Craniopharyngioma • Benign childhood tumor • Confused with pituitary adenoma (can also cause bitemporal hemianopia) • Most common childhood supratentorial tumor • Derived from remnants of Rathke’s pouch • Calcification in common
  18. 18. Pathology - Neoplastic • Metastasis to brain - 1° tumors that metastasize to brain: Lung Lots of Breast Bad Skin(melanoma) Stuff Kidney(RCC) Kills GI Glia - Approximately 50% of brain tumors are from metastases
  19. 19. Pathology – Neoplastic Cont’d • Metastasis to Liver - the most common sites of metastasis after regional lymph nodes are liver and lung - 1° tumors that metastasize to the liver are: Colon > Stomach > Pancreas > Breast > Lung - Cancer Sometimes Penetrates Benign Liver - Metastasis to the liver >> 1° liver tumors
  20. 20. Pathology – Neoplastic Cont’d • Metastasis to bone - 1° tumors that metastasize to bone are: Breast, Lung, Thyroid, Testes, Kidney, Prostate BLT with a Kosher Pickle - metastases from breast and prostate are most common - metastatic bone tumors are much more common than 1° bone tumors - Lung = Lytic Prostate = blastic - Breast = Both lytic and blastic
  21. 21. Paraneoplastic Effects of Tumors • Small cell lung carcinoma - causes: ACTH or ACTH-like peptide - effect: Cushing’s Syndrome • Small cell lung carcinoma & intracranial neoplasms - causes: ADH or ANP - effect: SIADH • Squamos cell carcinoma, RCC, breast carcinoma, multiple myeloma, & bone metastasis (lysed bone) - causes: PTH-related peptide, TGF-β, TNF-α, IL-1 - effect: Hypercalcemia
  22. 22. Paraneoplastic Effects Cont’d • Renal cell carcinoma - causes: erythropoietin - effects: polycythemia • Thymoma, bronchogenic carcinoma - causes: antibodies against presynaptic Ca2+ channels at neuromuscular junction - effect: Lambert-Eaton Syndrome (muscle weakness) • Leukemias and Lymphomas - causes: hyperuricemia due to excess nucleic acid turnover (i.e., cytotoxic therapy) - effects: gout, urate nephropathy
  23. 23. Cancer Epidemiology Incidence Mortality Male Female Lung (33%) Prostate (13%) Lung ( 23%) Breast (18%) Male Female Prostate (32%) Lung (16%) Colon & Rectum (12%) Breast (32%) Lung (13%) Colon & Rectum (13%) -Deaths from lung cancer have plateaued in males but continue to increase in females -Cancer is the 2nd leading cause of death in the U.S. (heart disease is 1st )
  24. 24. Pathology - Hematologic - Anemias: 1. Microcytic, hypochromic (MCV<80) a. Iron Deficiencies - ↓ serum iron, ↑ TIBC, ↓ferritin b. Thalassemias – target cells c. Lead poisoning, sideroblastic anemias 2. Macrocytic (MCV > 100) a. megaloblastic – Vit. B12/folate deficiency - vit. B12& folate deficiencies are ass. with hypersegmented PMNs - vit. B12deficiency is ass. with neurologic problems b. drugs that block DNA synthesis (e.g., sulfa drugs, AZT) c. marked reticulocytosis
  25. 25. Pathology – Hematologic cont’d 3. Normocytic, normochromic a. acute hemorrhage b. enzyme defects (e.g., G6PD deficiency, PK deficiency) c. RBC membrane defects (e.g., aplastic anemia, leukemia) d. hemoglobinopathies (e.g., sicke cell disease) e. autoimmune hemolytic anemia f. anemia of chronic disease (ACD) - ↓TIBC, ↑ferritin, ↑storage iron in marrow macrophages - ↓serum haptoglobin & ↑serum LDH indicate RBC hemolysis - Direct Coomb’s – used to distinguish b/w immune vs. non- immune mediated RBC hemolysis
  26. 26. Aplastic Anemia • Pancytopenia characterized by severe anemia, neutropenia, & thrombocytopenia - caused by failure or destruction of multipotent myeloid stem cells w/ inadequate production or release of differentiated cell lines • Causes: radiation, benzene, chloramphenical, alkylating agents, antimetabolites, viral agents, Fanconi’s anemia, idiopathic; may also follow acute hepatitis
  27. 27. Aplastic Anemia Cont’d • Symptoms: fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection • Pathologic Features: pancytopenia w/ normal cell morphology; hypocellular bone marrow w/ fatty infiltration • Diagnosis: made w/ bone marrow biopsy • Treatment: withdrawal of offending agent, allogenic bone marrow transplant, RBC & platelet transfusion, G-CSF or GM-CSF
  28. 28. Hereditary Spherocytosis • intrinsic, extravascular hemolysis due to spectrin or ankyrin defect • RBCs are small & round w/ no central pallor ↑MCHC, ↑RDW, ↑reticulocytes • Osmotic fragility test used to confirm • Ass. w/ gallstones, splenomegaly, anemia, & jaundice • Distingued from warm antibody hemolysis by direct Coombs’ test • Coombs’ negative
  29. 29. Blood Dyscrasias • Sickle Cell Anemia - HbS mutation is a single aa replacement in β chain (Glu  Val) - low O2 or dehydration precipitates sickling - heterozygotes (SC trait) are relatively malaria resistant - complications in homozygotes: - aplastic crisis (due to parvovirus B19) - autosplenectomy - ↑ risk of encapsulated organism infection - salmonella osteomyelitis - painful crisis (vaso-occlusive) - splenic sequestration crisis
  30. 30. Sickle Cell Anemia Cont’d - HbC defect is a different β-chain mutation - pts. w/ HbC or HbSC (1 of each mutant gene) have milder disease than HbSS pts. - New therapies for SCA include hydroxyurea (↑HbF) & bone marrow tranplantation
  31. 31. - 8% of African-Americans carry the HbS trait - 0.2% have the disease - sickle cells are crescent-shaped RBCs - “crew cut” on skull x-ray due to marrow expansion
  32. 32. Blood Dyscrasias Cont’d • α-thalassemia - normally there are 4 α-globin genes - in α-thalassemia, the α-globin is underproduced - there is no compensatory increase of any other chains - HbH: β4-tetramer, lacks 3 α-globin genes - Hb Barts: γ4-tetramer, lacks all 4 α-globin genes; -results in hydrops fetalis & intrauterine fetal death - prevalent in Asia and Africa
  33. 33. Blood Dyscrasias Cont’d • β-thalassemia - β-thalassemia minor (heterozygote): β-chain is underproduced - β-thalassemia major (homozygote): β-chain is absent - in both, fetal hemoglobin production is compensatorily increased but is inadequate - HbS/β-thalassemia heterozygote has mild to moderate disease
  34. 34. - β-thalassemia major (homozygote) results in severe anemia requiring blood transfusions - Cardiac failure due to 2° hemochromatosis - Marrow expansion  skeletal deformities (“crew-cut” on skull x-ray) - Prevalent in Mediterranean popns. β-thalassemia
  35. 35. Sample Questions
  36. 36. Hereditary Spherocytosis

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