Webpath and Pathpedia Flashcards
1
Q
Describe what you see here.
A
- Normal mature lymphocyte on the left
- Segmented PMN on the right
- RBC about 2/3 the size of a normal lymphocyte
1
Q
What is the large, central cell here?
A
- Monocyte
- Slightly larger than a lymphocyte, and has a folded nucleus
- Can migrate out of the bloodstream and become tissue macrophages under the influence of cytokines
- Note the many small smudgy blue platelets between the RBC’s.
1
Q
What is going on here? What nutrient deficiency is most often associated with this appearance?
A
- RBC’s here smaller than normal and have increased zone of central pallor -> indicative of a hypochromic (less hemoglobin in each RBC) and microcytic (smaller size of each RBC) anemia
- Also increased anisocytosis (variation in RBC size) and poikilocytosis (variation in RBC shape)
- Iron is needed to produce the heme in hemoglobin; most common cause for hypochromic microcytic anemia
1
Q
What is this?
A
- Adult T-cell leukemia, HTLV1-associated
- T-cell neoplasm endemic in certain parts of the world including southwest Japan, Caribbean, and central Africa. The neoplasm may present clinically in one of four forms: acute leukemic form, smoldering forms, chronic form, and lymphomatous form. Pts acquire virus early in life and deco disease decades later.
- Acute form characterized by circulating leukemic T-cells in lg #’s with serum Hypercalcemia and evidence of organ-system involvement. Peripheral blood smear in this case shows many lymphocytes ranging from small to larger with nuclear contour irregularity.
2
Q
What is this?
A
- Severe autoimmune hemolytic anemia
- Nucleated red blood cells are commonly seen (arrowhead)
- Note the presence of numerous spherocytes (long arrow) and several reticulocytes (curved arrow)
- These patients generally show high serum LDH levels, low haptoglobin, and increased unconjugated bilirubin. Autoimmune hemolytic anemia may be seen in patients with certain autoimmune disorders and B-cell lymphoproliferative disorders. Other causes of immune hemolytic anemia include drug reaction to certain drugs and cold agglutinins.
2
Q
What is this?
A
- Patients with hemoglobin SC generally show many target cells (long arrow) and only a few sickle cells (arrowhead). Typical sickle cells may be absent and sickle cell crisis is generally not seen.
2
Q
What is this?
A
- CLL
- Most cases involve blood and bone marrow with or without involvement of lymph nodes, spleen, liver, and other organs. The neoplastic lymphocytes are small but slightly larger than normal small lymphocytes and show scant cytoplasm and round to slightly irregular nuclei containing clumped chromatin (three arrows). Nucleoli are small to indistinct
- Characteristic morphologic feature is the presence of “smudge” or “basket” cells (two arrowheads) which are essentially neoplastic cells that got “smudged” during slide preparation because of the fragile nature of these cells. Compare the cell size of CLL cells with a single large granular lymphocyte (curved arrow).
3
Q
What is going on here?
A
- RBC’s in the background appear normal
- Important finding here is presence of many PMN’s. An elevated WBC count with mainly neutrophils suggests inflammation or infection
- A very high WBC count (>50,000) that is not a leukemia is known as a “leukemoid reaction”. This reaction can be distinguished from malignant WBC’s by the presence of large amounts of leukocyte alkaline phosphatase (LAP) in the normal neutrophils
5
Q
What do you see here?
A
- Megaloblastic anemia
- In an attempt to compensate for severe anemia intensely basophilic reticulocytes may also circulate in the peripheral blood (arrowhead). The reticulocyte count is typically low in contrast to other hemolytic anemias. This is because of ineffective hematopoiesis seen in the marrow. Other laboratory findings include a high RDW.
6
Q
Is this normal? Find some erythroid precursors and granulocytic precursors.
A
- Normal bone marrow smear at high magnification
- Erythroid precursors: bottom right
- Granulocytic precursors: top, middle
7
Q
Is this normal? Find an eosinophilic, a basophilic myelocyte, and plasma cell.
A
- Normal bone marrow smear at high magnification
- Eosinophilic myelocyte: top left, bordered by some dark blue cells -> are these lymphocytes or erythroid precursors?
- Basophilic myelocyte: middle of the image, directly above the large steatocyte
- Plasma cell: large, tear-drop looking cell at the bottom right
7
Q
What do you see here? Who is at risk? What might you eat to make this better?
A
- Larger zones of central pallor in these small RBCs, along with poikilocytosis
- Most common cause for hypochromic microcytic anemia is iron deficiency. The most common nutritional deficiency is lack of dietary iron. Iron def anemia is common. Persons most at risk are children and women in reproductive years (from menstrual blood loss and from pregnancy)
- Meats, green, leafy vegetables, breakfast cereals, Vit C
7
Q
What do you see here?
A
- Megaloblastic anemia
- The larger RBC size is due to continued hemoglobin production and accumulation because of delayed nuclear maturation. Both folate and cobalamin (B-12) are required for DNA synthesis and in the absence of either one or both full nuclear maturation is delayed or incomplete. As a result enlarged nuclei may persist in red cells as shown in this photomicrograph (arrowhead).
8
Q
What do you see in the center of this field? What is its role? What is underneath it?
A
- Eosinophil with a bilobed nucleus and numerous reddish granules in the cytoplasm -> can increase with allergic reactions and with parasitic infestations
- Underneath it is a small lymphocyte
8
Q
What do you see here?
A
- AML
- “Auer rods”: abnormal condensation of azurophilic cytoplasmic granules -> confirm myeloid nature of blasts and presence of AML (since no other pathologic entity contains Auer rods)
- Presence of even a single well-characterized Auer rod in a blast in blood smear confirms the existence of acute leukemia
9
Q
What do you see here? What type of crisis might these cause, and how might the patient present? Explain your answer.
A
- Sickled erythrocytes in a patient with Hgb SS who presented with severe chest, abdominal, and back pain along with hemoglobinuria in sickle crisis
- Sickled cells prone to stick together and to endo of microvasculature, plugging smaller vessels and leading to decreased blood flow w/ischemia -> sickled erythrocytes undergo hemolysis, depleting serum haptoglobin and overwhelming bilirubin clearance mechanisms
10
Q
What is going on here?
A
- Peripheral blood smear shown here appears normal, because it is. A normal neutrophil and lymphocyte are present. Only a CBC will demonstrate anemia. This is a normochromic, normocytic anemia
- Anemia of chronic cisease is a possibility because this type of anemia is typically normocytic or mildly microcytic
10
Q
What do you see here?
A
- Megaloblastic anemia (MA)
- One of the hallmarks of MA is the presence of hyper-segmented neutrophils -> results from delayed and continued DNA synthesis but intact segmentation mechanism
- Hypersegmentation: defined as 6 or more distinct nuclear lobes. At least 9 lobes could be identified in this neutrophil (arrowhead)
- Note also macro-ovalocytes (arrows)
12
Q
Describe the RBCs here. Find some platelets, a band neutrophil, and a segmented neutrophil.
A
- RBCs here are normal -> zone of central pallor about 1/3 the size of the RBC (normochromasia)
- Minimal variation in size (anisocytosis) and shape (poikilocytosis)
- In the center of the field are a band neutrophil on the left and asegmented neutrophil on the right
12
Q
What is going on here? Explain the pathology.
A
- Sickle cell anemia in sickle crisis
- Abnormal hemoglobin SS prone to form tactoids with crystallization in RBC’s when oxygen tension is low, and RBC’s change shape to long, thin sickle cells that are “sticky” and sludge in capillaries, further decreasing blood flow and oxygen tension
- Sickled RBCs tend to adhere to endothelium, and the bioavailability of endothelial nitric oxide (NO) is reduced as well, further promoting vaso-occlusion
- Persons with sickle cell trait (Hemoglobin AS) are much less likely to have this sickling phenomenon
14
Q
What is anemia of chronic disease? What diseases might cause it?
A
- Most common anemia in hospitalized persons
- Impaired use of iron, w/o absolute def or excess. Cytokine-mediated blockage in iron transfer from storage pool to erythroid precursors in bone marrow. Defect is inability to free iron from macros or to load it onto transferrin. Inflammatory cytokines also depress erythropoiesis from action on erythroid precursors or from EPO levels too low for the degree of anemia
- Inflammatory conditions release cytokines like IL-1 & IL-6& IL6 that stimulate hepatic production of hepcidin, reducing iron absorption and decreasing release of iron from stores in macros
- Result is decreased total serum iron, but iron binding capacity reduced too, resulting in somewhat decreased saturation, but increased ferritin. Serum soluble transferrin receptors unaffected by chronic disease
- Anemia of chronic disease is addressed by treating the underlying condition, which may be: chronic infections, ongoing inflammatory conditions (IBS), auto-immune disease, or malignant neoplasms
16
Q
What are the normal ranges for RBC, Hgb, Hct, MCV, PLT, and MCH?
A
- RBC: around 5
- Hgb: around 14 (a little lower for women)
- Hct: around 47
- MCV: 80-100
- PLT: 150,000 - 450,000
- MCH: around 30
16
Q
What is going on in this CBC?
A
- Markedly increased MCV, typical for megaloblastic anemia
- MCV can be mildly increased in persons recovering from blood loss or hemolytic anemia b/c newly released RBC’s, the reticulocytes, are increased in size over normal RBC’s, which decrease in size slightly with aging
17
Q
What might this CBC suggest?
A
- Spherocytosis: RBC’s small and round (rather than the normal biconcave appearance) w/increased Hgb, shown by increased MCHC (mean corpuscular hemoglobin concentration)
- Rare condition known as hereditary spherocytosis; RBC’s in autoimmune hemolytic anemia can also appear similarly
18
Q
What do you see here?
A
- Megaloblastic anemia (MA): most common cause of macrocytic (MCV > 100fl) anemia is insufficient nuclear DNA synthesis due either to nutritional or functional lack of vitamin B12 and/or folate
- RBCs not only large, also show oval morphology (macro-ovalocytes)
- Increase in cell size can be calibrated using nucleus of a small lymphocyte. A normal red blood cell is usually the same size as the nucleus of a small lymphocyte. Most red cells in this picture are larger than the nucleus of a small lymphocyte.
19
Q
Describe what you see here. What age is this person?
A
- Normal bone marrow
- Megakaryocytes, erythroid islands, and granulocytic precursors
- Taken from posterior iliac crest in a middle aged person, so it is about 50% cellular, with steatocytes admixed with the marrow elements
21
Q
What’s up with this CBC?
A
- Person with severe anemia who underwent transfusion
- This accounts for dual RBC population seen in graph at the lower left
- Reticulocytosis in response to anemia has also increased the MCV
21
Q
What is this?
A
- Immune hemolytic anemia
- Caused by an autoimmune or alloimmune antibody directed against one of various red cell antigens and may result in extravascular or intravascular hemolysis. Laboratory tests show a positive antiglobulin (Coombs) test
- This example of an autoimmune hemolytic anemia shows numerous spherocytes (long arrows) which are smaller than normal RBCs and show no central pallor. The MCV is generally normal or slightly low but the MCHC is either normal or higher than normal. Thus, these cells appear denser than normal RBCs. A prominent morphologic feature is the presence of reticulocytes (arrowhead) which appear basophilic due to the presence of abundant ribosomal RNA.
22
Q
Normal or not? If not, what is going on?
A
- CBC in a person with iron deficiency anemia
- Low hemoglobin (HGB)
- Microcytosis indicated by the low MCV (mean corpuscular volume)
- Hypochromia correlates here with the low MCH (mean corpuscular hemoglobin)
25
Q
What is going on here?
A
- Numerous fragmented RBC’s, some appear as “helmet” cells -> “schistocytes,” indicative of a microangiopathic hemolytic anemia (MAHA) or other cause for intravascular hemolysis
- This finding is typical for disseminated intravascular coagulopathy (DIC) -> D-dimer test is most specific for this condition, and measures fibrin degradation products that form w/activation of coagulation system and subsequent fibrinolysis
27
Q
What is going on here?
A
- This patient has hemoglobin SC disease, w/hemoglobin S and hemoglobin C both present
- With SC disease, RBC’s may sickle, but not as commonly as with Hemoglobin SS disease
- The hemoglobin C leads to formation of “target” cells–RBC’s that have a central reddish dot
- In the center of the field is a rectangular RBC that is indicative of a hemoglobin C crystal, also characteristic for hemoglobin C disease
28
Q
What do you see here?
A
- Acute lymphoblastic leukemia, B-cell (ALL)
- Lymphoblasts: deeply basophilic cytoplasm, fine nuclear chromatin, small nucleoli, and cytoplasmic vacuoles
- Immunophenotype: CD19, and almost always CD34, HLA-DR, and TdT. Most cases also show expression of CD10, but only small # show CD20
- Typical precursors of B-cell lymphoblastic leukemia don’t show surface expression of Ig kappa or lambda light chains. Expression of myelomonocytic antigens CD13 and/or CD33 may be seen in a small # of cases, but MPO expression is not a feature.
28
Q
What is this?
A
- Megaloblastic anemia
- Thrombocytopenia is also a clinical feature of severe MA. Larger than normal platelets (macro-thrombocytes) can be seen in blood. Pancytopenia with low reticulocyte count and circulating megaloblasts is a typical finding in severe form of MA.
30
Q
What’s up with this bone marrow?
A
- Hematopoietic elements in this bone marrow biopsy are markedly reduced
- This is a case of aplastic anemia -> RBC’s, platelets and granulocytes will often be diminished
- Sometimes a drug or toxin is the cause and sometimes infection; when no known cause can be found, it is termed idiopathic aplastic anemia
32
Q
What do you see here?
A
- Many of the RBC’s are small and lack central pallor, consistent with spherocytes lacking central pallor.
- Hereditary spherocytosis can be accompanied by anemia, splenomegaly, and jaundice
- Immune extravascular hemolysis may lead to spherocytes when portions of RBC membrane coated with antibody are excised in the spleen
33
Q
What is up with this skull?
A
- Severe, chronic anemias (i.e., thals, sickle cell anemia) can increase bone marrow response to form RBC’s
- Drive for erythropoiesis may increase mass of marrow and lead to increase in marrow in places, such as the skull seen here, that is not normally found (extramedullary hematopoiesis)
- Such an increase in marrow in skull may lead to “frontal bossing” or forehead prominence because of the skull shape change
34
Q
What do you see here? Describe the associated hereditary condition.
A
- Size of many RBC’s small, with lack of central zone of pallor -> spherocytes
- Hereditary spherocytosis: lack of spectrin, a key RBC cytoskeletal membrane protein, producing membrane instability that forces cell to smallest volume -> a sphere
- In the laboratory, this is shown by increased osmotic fragility -> spherocytes don’t survive as long as normal RBC’s.
- 1 in 2000 Northern Europeans; 75% autosomal dominant
35
Q
What do you see here?
A
- Severe iron deficiency: characteristic morphologic changes include microcytosis (low MCV), hypochromasia (low MCHC), anisocytosis (high RDW), and poikilocytosis (abnormal shaped RBCs) with elliptocytes (arrowheads) and target cells. Reticulocytes are decreased
- Other microcytic anemias such as thalassemia, sideroblastic anemia, anemia of chronic diseases and certain hemoglobin disorders should be excluded based on clinical history and laboratory tests
36
Q
What do you see in the center of this field? What is their significance? What other cells do you see?
A
- Basophil with a lobed nucleus (like PMN’s) and numerous coarse, dark blue granules in the cytoplasm
- Infrequent in a normal peripheral blood smear, and their significance is uncertain
- Band neutrophil on left, & large, activated lymphocyte on the right.
37
Q
What is going on in this CBC?
A
- Patient with microangiopathic hemolytic anemia (MAHA)
- Markedly increased RDW (red cell distribution width; normal 10.2-14.5) due to the marked variation in size and shape of the RBC population
38
Q
What is the cell in the center of the field? What is this cell characteristic of?
A
- Hypersegmented neutrophil present with megaloblastic anemias -> 8 lobes instead of the usual 3 or 4
- These anemias can be due to folate or to B12 deficiency. Size of the RBC’s also increases (macrocytosis, which is hard to appreciate in a blood smear)
- Some dietary sources of B12 are animal tissue, particularly liver, and some cereals and dairy products
40
Q
Is this normal? Identify a megakaryocyte, erythroid precursor, and granulocytic precursor.
A
- Normal bone marrow smear at high magnification
- Megakaryocytes: large one at bottom right
- Granulocytic precursors: to the left of the megakaryocyte
- Erythroid precursors: to the left of the granulocytic precursor
41
Q
What is up with this spleen, yo?
A
- Though in early childhood spleen may be enlarged with sickle cell anemia, continual stasis and trapping of abnormal RBC’s leads to infarctions that reduce size of spleen tremendously by adolescence -> sometimes called “autosplenectomy”
- Seen here is the small remnant of spleen in a patient with sickle cell anemia
- Sickle cell inheritance auto recessive with homos severely affected and heteros minimally affected
42
Q
What do you see here? What might be going on?
A
- Nucleated RBC in the center contains basophilic stippling of the cytoplasm
- Suggests a toxic injury to the bone marrow, such as with lead poisoning
- Such stippling may also appear with severe anemia, such as a megaloblastic anemia
44
Q
Do these numbers look normal?
A
Yes. Know these.
45
Q
What do you see here? Describe the associated anemia and its indicators.
A
- Macro-ovalocytes in a case of pernicious anemia are larger than the normal small lymphocyte -> these large RBCs lack a zone of central pallor
- No polychromasia, and if a reticulocyte count were done, it would be low; anisocytosis and poikilocytosis.
- Serum homocysteine and methylmalonic acid (MMA) levels are increased, often before macrocytosis and a decrease in cobalamin (B12) occurs -> as the disease progresses cobalamin (vitamin B12) levels will be consistently decreased as well (only homocysteine will be increased with folate deficiency)
46
Q
What are the major clinical features of hereditary spherocytosis? What do you see here?
A
- Sinusoids packed with RBC’s in this case of hereditary spherocytosis -> osmotic fragility of spherocytes INC b/c RBC’s have decreased surface area per unit volume
- Major clinical features are anemia, splenomegaly, and jaundice; aplastic crisis may occur w/parvovirus infection
47
Q
What do you see here (and at each #)?
A
- Chronic myelogenous leukemia (CML): chronic myeloproliferative disorder characterized molecularly by t(9;22), philadelphia chromosome
- Peripheral blood generally shows myeloid elements in all stages of maturation including blasts (#1), promyelocytes, myelocytes (#2), metamyelocytes, band and segmented neutrophils. In most cases an increase in basophils and eosinophils is also seen. Cells with both eosinophilic and basophilic granules are also seen (#3)
49
Q
What is this?
A
- CLL
- Four small neoplastic lymphocytes and three smudge cells (arrowheads)
- Dx on blood smear suspected based on morphology and confirmed using flow cytometric analysis of blood and/or bone marrow which usually shows a characteristic immunophenotype
- The neoplastic cells generally express CD19, dim CD20, monoclonal immunoglobulin kappa or lambda light chain, and co-expression of CD5 and CD23. The cells do not express CD10 or bcl-6. Dim expression of CD20 and surface immunoglobulins is very common.
53
Q
What is going on here?
A
- Atypical lymphocytes are shown here: these WBC’s are “atypical” because they are larger (more cytoplasm) and have nucleoli in their nuclei -> cytoplasm tends to be indented by surrounding RBC’s
- Such atypical lymphocytes are often associated with infectious mononucleosis from Epstein-Barr virus (EBV) infection
55
Q
What do you see here?
A
- RBC in the center of the field contains several Howell-Jolly bodies, or inclusions of nuclear chromatin remnants
- Also a nucleated RBC just beneath this RBC
- Abnormal, aged RBC’s typically removed by spleen
1. Increased poikilocytosis, anisocytosis, and RBC inclusions suggests spleen not present
56
Q
What is this?
A
- AML
- Acute minimally differentiated myeloid leukemia (AML-M0) is characterized by lack of obvious myeloid differentiation by routine histologic examination and presence of myeloperoxidase in medium-sized blasts in comparison to a small normal lymphocyte (thin arrow). Blasts contain evenly distributed chromatin and prominent nucleoli (arrowhead).
57
Q
What is this? Find some megakaryocytes, erythroid islands, steatocytes, and granulytic precursors.
A
- Normal bone marrow taken from the posterior iliac crest in a middle aged person, so it is about 50% cellular, with steatocytes admixed with the marrow elements
- Granulocytic precursors: middle, top
- Erythroid islands: center of image
- Megakaryocytes: middle, bottom
58
Q
What do you see here?
A
- Megaloblastic anemia
- Under bone marrow stress hematopoiesis and hypercellularity immature myeloid precursors of neutrophils can be seen circulating in the blood. This photomicrograph shows a circulating myelocyte. Neutropenia is often a feature of severe Megaloblastic anemia.
