Goljan Pics - Hematology

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Normal PB smear and schematic of mature RBC
Note that RBCs are a biconcave disc. Since less Hb is concentrated in the area of depression in the membrane, it appears pale when flat on a slide, hence the central area of pallor. If the central area of pallor expands, then there is a problem with Hb synthesis, which implicates one of the microcytic anemias. If the cell is a spherocyte, there is no central area of pallor. If there is excess membrane, there is a bulge in the center of the cell collecting more Hb, hence the appearance of a target cell. Mature RBCs do not have mitochondria and use glucose for a fuel (anaerobic glycolysis).

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Asymptomatic patient
This is a normal smear. Note the uniformity of the RBCs, the normal amount of central pallor, and the compression pallor induced by platelets sitting on top of the RBC membrane. This can be confused with malarial ring forms.

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Supravital stain of RBCs in an asymptomatic person
Two reticulocytes are present in the slide. Reticulocytes are RBCs that within 24 hours will be changed into a mature biconcave disc by macrophages in the spleen. The supravital stain identifies RNA filaments, indicating that the cell is still synthesizing Hb. The reticulocyte count is the most important test to order after identifying an anemia since it tells the clinician how the bone marrow is responding to the anemia.

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Reticulocyte stain
Note the RNA filaments in these young RBCs.

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PB in a 9 year old child with b-thalassemia major and a severe microcytic anemia and elevated reticulocyte count
The arrow points to a marrow reticulocyte or shift cell, which, unlike a peripheral blood reticulocyte, requires 48-72 hours before it becomes a mature RBC and has a bluish discoloration (polychromasia). In severe thalassemia, the excess production of a-chains are toxic to RBCs causing a hemolytic anemia. Stimulation of marrow erythropoiesis causes the release of polychromasia cells as well as nucleated RBCs. In a reticulocyte count, the count must first be corrected for the degree of anemia and then further corrected (divide by 2) if polychromasia is present, since they have RNA filaments like PB reticulocytes and would falsely increase the reticulocyte count.

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Normal bone marrow
Note the proportion of cells to fat is ~70 cells to 30 fat. Large cells are megakaryocytes. Cells with round nuclei are either nucleated RBCs or young neutrophils (myelocytes, etc). Cells with "squiggly" nuclei are segmented neutrophils and bands. The normal myeloid to erythroid ratio is usually 3/1 indicating more WBCs than RBCs in the marrow.

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Patient with anemia and jaundice
What is the most likely diagnosis?
This child most likely has sickle cell disease. Note the pallor of the lips, scleral icterus, and chipmunk facies (prominent zygomatic bones) due to marrow expansion from excessive erythropoiesis. Sickle cells are removed by macrophages, hence releasing large amounts of unconjugated bilirubin.

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Skull x-ray from a child with sickle cell disease
Note the expansion of the marrow cavity in the skull giving it a "hair on end" appearance. Frontal bossing and prominence of the zygomatic bone is also noted. These changes occur owing to massive erythropoiesis in the bone marrow and indicate a severe hemolytic anemia (e.g., sickle cell disease, thalassemia major).

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Patient with a severe anemia. What is the most likely diagnosis?
She has a classic chipmunk face from prominence of her zygomatic bones. This indicates expansion of the marrow space by a brisk erythropoiesis. Since she is black, the most likely diagnosis is HbSS disease.

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PB in an asymptomatic patient who had his spleen removed 10 years ago following its rupture in a car accident
The arrow points to a spherocyte. In the background are target cells (cells with a bullseye center). Both types of RBCs are commonly seen post-splenectomy. Unlike spherocytes, which have too little membrane ("skinny RBC"), hence forming a sphere rather than a biconcave disc, target cells have excessive membrane ("obese RBC"), hence forming a bulge in the middle that collects more Hb. Howell Jolly bodies and reticulocytes, and siderocytes may also be present in the PB.

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PB from a patient with sickle cell disease
Note the nucleated RBC (NRBC), sickle cells, and target cells, which are markers of a hemoglobinopathy. NRBCs are commonly seen when patients are briskly hemolyzing and overtaxing the bone marrow.

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PB in an asymptomatic patient who had a surgical scar in the LUQ
The arrow is pointing to a target cell containing a remnant of nucleus called a Howell Jolly body. The patient had a ruptured spleen after a car accident and had his spleen removed. Note the increase in target cells. Target cells are increased after splenectomy, in hemoglobinopathies, and in alcoholics with liver disease.

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PB demonstrating rouleaux and agglutination
Rouleaux (stack of coins) is associated with an increase in IgG or fibrinogen, while agglutination seen with an increase in IgM, which owing to its pentameric configuration is able to bridge the negative charge around RBCs and agglutinate them. Cold agglutinins contain IgM antibodies, which clump RBCs in digital vessels in cold weather and produce Raynaud’s phenomenon.

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Patients fingers: there is a history of craving for eating ice chips and a severe microcytic anemia
The nails exhibit spooning or koilonychia, a characteristic feature of iron deficiency.

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Patient with a severe microcytic anemia and dysphagia for solids (not liquids)
Note the cracking at the angles of the mouth (cheilosis, stomatitis). With a history of a microcytic anemia, and dysphagia for solids, the patient probably has the Plummer Vinson syndrome with iron deficiency producing an esophageal web, glossitis, cheilosis, and achlorhydria.

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PB from a 4 year old child with a microcytic anemia and an increase in the RDW. What is the most likely diagnosis?
The cells are hypochromic. The most likely cause is iron deficiency secondary to GI blood loss, most often a bleeding Meckel’s diverticulum.

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PB in a 22 year old woman with menorrhagia and a microcytic anemia with an increase in the RDW. What is the most likely diagnosis?
The findings illustrate marked variation in the size of the RBCs, hence the increase in the RDW, and pronounced hypochromasia, indicating a defect in Hb synthesis. With a history of menorrhagia, iron deficiency is most likely present. Iron deficiency is the only microcytic anemia with an increase in RDW. Serum ferritin should be low in this patient.

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PB in a patient with b-thalassemia minor and a mild microcytic anemia
Note the tear drops cells, and cells with a fine stippled appearance, the latter representing persistence of ribosomes (basophilic stippling). This is a nonspecific finding in any anemia with a defect in Hb synthesis, which characterizes the microcytic anemias. Thalassemias characteristically have an elevation in the RBC count.

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BM with a Prussian blue stain in an alcoholic with a microcytic anemia
The patient has a sideroblastic anemia. The ringed sideroblast in the slide represents a nucleated RBC with iron trapped in the damaged mitochondria (alcohol is a mitochondrial poison). Damage to the mitochondria interferes with normal heme synthesis. Siderocytes with iron (Pappenheimer bodies) often accompany sideroblastic anemias. Alcohol is the most common cause of acquired sideroblastic anemia. Pyridoxine deficiency and Pb poisoning are additional causes.

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PB from the alcoholic with microcytic anemia
Note the irregular dark inclusions in the RBCs. These are clumps of hemosiderin in the cytosol called Pappenheimer bodies and the cells are called siderocytes (sideroblasts are NRBCs in the bone marrow). These are present in iron overload diseases, in this case, alcohol induced sideroblastic anemia.

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BM with Prussian blue stain in a patient taking INH for an active case of TB who has a microcytic anemia.
What is the most likely diagnosis?
Iron stores are increased and ringed sideroblasts are present indicating a defect in heme synthesis. INH produces deficiency of pyridoxine (B6), which is a cofactor in the reaction between glycine and succinyl CoA to form D ALA. Iron enters the mitochondria but cannot exit the mitochondria, so it accumulates in mitochondria located around the nucleus and produces the ringed sideroblast (ring around the collar).

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X-ray of hand of 9 month old black child with dactylitis and sickle cell disease
Note the white out of the bones owing to infarction and the densities in the epiphyses of the digits, the latter indicating lead poisoning. Pb is the only heavy metal that deposits in the epiphyses.

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PB from the 9 month old child with severe microcytic anemia and a history of eating paint chips from his crib
The PB exhibits classic coarse basophilic stippling owing to denaturation of ribonuclease by Pb. Basophilic stippling is due to persistence of ribosomes (Pb denatures ribonuclease). Note also the hypochromic microcytic cells owing to a defect in heme synthesis (ferrochelatase and ALA dehydrase are denatured by Pb). There is an increase in RBC protoporphyrin and d ALA

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PB finding in a 35 year old man with epigastric distress, dark stools, and a microcytic anemia. What is the most likely diagnosis?
The smear shows marked microcytosis and hypochromasia and the history suggests GI blood loss, most likely from a bleeding duodenal ulcer.

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Teeth of a patient with a peripheral neuropathy and normal anion gap metabolic acidosis. What is the most likely diagnosis
A lead line is noted along the gum margin. In adults lead poisoning targets the peripheral nervous system producing foot drop (peroneal nerve palsy), wrist drop (radial nerve palsy), claw hand (ulnar nerve palsy) and the kidneys (proximal renal tubular acidosis), owing to the toxic effect of Pb (coagulation necrosis) on renal tubular cells in the proximal tubule. Patients lose amino acids, glucose, phosphate, and uric acid in the urine.

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Physical diagnostic finding
You would expect what type of anemia in the patient? Koilonychia is present which suggests iron deficiency.

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Physical diagnostic finding
Playing odds, what anemia would you expect in this patient? Iron deficiency anemia. Note the pale conjunctiva.

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Physical findings in a patient compared to a normal hand
What is the difference? The patient’s nail beds are pale and the palmar creases are pale compared to normal indicating anemia.

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BM from a 65 year old woman with a macrocytic anemia, pancytopenia, and absent vibratory sensation in the lower extremities. What is the most likely diagnosis?
The BM shows megaloblastic RBC and WBC precursors consistent with B12/folate deficiency, in this case, the former owing to the neurological findings of posterior column disease. These large cells are destroyed outside the sinusoids in the marrow by macrophages, hence producing pancytopenia, a possibility for unconjugated hyperbilirubinemia with jaundice, and a marked increase in serum LDH from the destroyed RBCs.

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PB in a 35 year old alcoholic with a macrocytic anemia. What is the most likely diagnosis?
The slide exhibits a hypersegmented neutrophil (pathognomonic of B12 or folate deficiency) and a mature lymphocyte. The RBCs are macroovalocytes (egg shaped). The most likely origin is folate deficiency owing to only a 3-4 supply of folate in the liver. Alcohol also blocks the reabsorbtion of folate in the jejunum. Serum folate, RBC folate, and B12 levels should be ordered.

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PB in a 67 year old woman with a macrocytic anemia
The arrow points to a tear drop cell, which may be seen in patients with B12 deficiency, myelofibrosis, and thalassemia. The other RBCs are macroovalocytes. The patient has pernicious anemia.

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PB from a patient with Crohn’s disease and a macrocytic anemia
What is the most likely diagnosis?
The WBC is hypersegmented indicating either B12 or folate deficiency. Since the terminal ileum is involved in 80% of cases of CD, the most likely diagnosis is B12 deficiency, since it is absorbed in the terminal ileum.

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PB in an alcoholic with alcoholic hepatitis and a macrocytic anemia
What are these cells called? Note the round, macrocytic target cell. Alcohol increases the cholesterol in the RBC membrane resulting in excess membrane and target cell formation. Hypersegmented neutrophils are not present in this type of macrocytic anemia.

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PB findings in a woman on birth control pills who has a mild macrocytic anemia
What is the most likely diagnosis? Note the 2 hypersegmented neutrophils indicating B12 and/or folate deficiency. Birth control pills inhibit the uptake of the monoglutamate form of folate in the jejunum, hence producing a folate deficiency.

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PB finding in a patient with celiac disease, a normocytic anemia, and an increased RDW
Note the two populations of RBCs (dimorphic), both small and large cells, the former representative of iron deficiency and the latter folate/B12 deficiency secondary to malabsorption in celiac disease. Since the MCV is a mean of the average size of the RBCs, the MCV is normal, however, the RDW, which detects size variations is increased. Malabsorption and the myelodysplastic syndrome are common causes of dimorphic RBC populations.

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BM finding in a patient.
What would you expect the CBC to show?The patient has an aplastic anemia, hence one would expect pancytopenia.

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Schematic of the nonincubated and incubated osmotic fragility test for congenital spherocytosis and pyruvate kinase (not discussed)
Note that in spherocytosis, the cells lyse more easily than normal cells in hypotonic salt solutions because they have less membrane than normal RBCs and no extra space to contain water and salt. Note that incubation makes the defect more pronounced.

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PB from a 26 year old woman with acute cholecystitis and a mild normocytic anemia with an increased corrected reticulocyte count
The patient has hereditary elliptocytosis, an AD disease, with either a defect in spectrin (similar to spherocytosis) or protein 4.1 in the RBC membrane. Increased extravascular hemolysis by macrophages in the spleen increases the release of unconjugated bilirubin, which increases the amount of bilirubin metabolized in the liver and excreted in the bile, hence predisposing to calcium bilirubinate stones.

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PB from a 27 year old with splenomegaly and a mild normocytic anemia with an elevated corrected reticulocyte count
The patient has congenital spherocytosis, an AD disease with a defect in spectrin in the cell membrane causing the cell to lose membrane ("skinny RBC") and form a sphere rather than a biconcave disc. Spherocytes are trapped and removed by macrophages in the cords of Billroth (extravascular hemolysis). Osmotic fragility testing confirms the diagnosis.

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Gallstones removed from a 22 year old female with a chronic hemolytic anemia. What is the most likely diagnosis?
The stones are calcium bilirubinate stones, which indicate the presence of increased generation of unconjugated bilirubin from extravascular hemolysis in a chronic hemolytic state such as congenital spherocytosis or sickle cell disease. The excess amount of conjugated bilirubin that will be generated from metabolism of the unconjugated bilirubin will combine with calcium to form these small, jet black stones.

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PB from a patient with a brisk hemolytic anemia. What is the most likely diagnosis?
Note the presence of spherocytes and polychromasia, the latter indicating a pronounced erythropoiesis in the bone marrow, which is common in hemolytic anemias like congenital spherocytosis or autoimmune hemolytic anemia.

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PB from a patient with jaundice and a mild normocytic anemia with an increased corrected reticulocyte count. What is the most likely diagnosis?
The arrows point to spherocytes in a patient with congenital spherocytosis (AD disease). A lymphocyte is present in the center of the slide. Jaundice is due to extravascular hemolysis by macrophages and increased production of unconjugated bilirubin.

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Hb electrophoresis patterns in various hemoglobinopathies
Note the normal migration sites for a normal person with HbA, HbA2, and HbF. Patients with HbSA (trait) have ~40% HbS, with the remainder representing A, A2 and F. In HbSS (disease), there is no HbA and varying amounts of HbF, the latter a potent inhibitor of sickling (the more the better). b-Thal major has a proportionately greater concentration of HbF than all the other types, while b-thal minor has a slightly increased amount of F and A2.

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PB and sickle cell prep. Note the sickle cells and target cells in the PB and how the sickle prep resulted in sickling of most of the cells. Sodium metabisulfite is used to reduce oxygen tension in the test tube hence precipitating sickling. It is a more sensitive and specific test than the solubility test using dithionite.

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PB finding in a patient with sickle cell disease. The cell in question is a nucleated RBC with a background of target cells (bulls-eye appearance) and a mature lymphocyte for comparison. Note that an NRBC has a more pyknotic (ink dot) appearance than a lymphocyte. In brisk hemolytic episodes, NRBCs may be released from the bone marrow.

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PB from a 9 month old black child with painfully swollen hands and feet The patient has sickle cell disease and is presenting with dactylitis (infarctions in the bones of the digits). Note the sickle cells and the target cells in the background. HbS is the substitution of valine for glutamic acid in the sixth position of the b-chain.

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Hands from the 9 month old black child with sickle cell disease and dactylitis, the first manifestation of sickle cell disease
HgF protects the child from this complication for the first few months by inhibiting sickling.

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Two year old child with sickle cell disease: What does the RBC finding signify in this patient?
Note the single RBC with a Howell Jolly body (nuclear remnant). This indicates that the patient's spleen is non-functional.

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PB in a 22 year old black man with chest pain. What is the most likely diagnosis?

The patient has sickle cell disease (note sickle cells and the background of target cells) and the acute chest syndrome. The latter is associated with fever, hypoxemia, a pulmonary infiltrate, and pleuritic chest pain. It is treated with oxygen and blood transfusion.

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Schematic of the pentose phosphate shunt and G6PD deficiency
Note that the absence of G6PD (SXR disease) reduces the production of NADPH (this shunt is most responsible for this substrate) and glutathione (GSH) which neutralizes peroxide and other free radicals (acetaminophen FR). Peroxide is a by-product of every living cell, hence the need for GSH and catalase in peroxisomes for neutralizing peroxide. In the RBC, peroxide may increase in the presence of oxidizing agents (primaquine, dapsone) or infection, the latter representing the most common precipitating cause of RBC hemolysis in the enzyme deficiency. Left unneutralized, peroxide denatures Hb (forms Heinz bodies) and damages SH- groups in the RBC membrane resulting in an intravascular hemolytic anemia. It should not be surprising that infection is the most common precipitating event, because the oxygen dependent MPO system requires NADPH as a cofactor with NADPH oxidase to generate superoxide for the most potent of the bactericidal systems in neutrophils and monocytes.

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PB on the left and special supravital stain on the right in a black man who developed a hemolytic anemia when he took primaquine for malaria.
The patient has G6PD deficiency, or Heinz body anemia. The absence of the enzyme reduces the amount of glutathione synthesized which is necessary to neutralize peroxide in the RBC when infections occur or oxidizing drugs are used. Peroxide damages the Hb producing Heinz bodies and damages the sulfhydryl groups in the RBC membrane, producing a predominantly intravascular hemolysis. The Heinz body prep is best to diagnose the disease in the active stage of hemolysis, while the enzyme assay confirms the diagnosis when hemolysis has subsided and new RBCs are synthesized that are either deficient in the enzyme or contain a defective enzyme that degrades as the RBC matures.

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BM finding in a patient with a hemolytic anemia and positive direct Coombs test
The arrow points to a macrophage that has phagocytosed a number of RBCs (erythrophagocytosis) that are coated by IgG and C3 for which the macrophages have receptors. In the direct Coombs test, rabbit anti-human IgG and C3 antibodies crosslink RBCs coated by IgG and C3 causing them to visibly clump under the microscope. Extravascular hemolysis is the most common mechanism of RBC destruction in autoimmune hemolytic anemias. The end-product of the RBC destruction is unconjugated bilirubin. The iron and amino acids are recycled.

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PB in a patient with SLE and a normocytic anemia with an elevated corrected reticulocyte count
What is the most likely diagnosis? Note the spherocytes and shift cells (marrow reticulocytes) in the smear and the segmented neutrophil. The patient has an autoimmune hemolytic anemia with a brisk erythropoiesis in the BM causing the release of shift cells. Spherocytes are noted in autoimmune hemolytic anemias, since macrophages in the spleen may only take part of the RBC membrane in an attempt at phagocytosis, hence causing the cell to lose its biconcave configuration. A direct Coombs test was positive in this patient.

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PB in a patient with severe calcific aortic stenosis and a mild normocytic anemia with an increased corrected reticulocyte count. What is the most likely diagnosis?
Note the increased number of schistocytes that have traumatized by the calcified valve. This is a microangiopathic anemia. Haptoglobin levels would be low and hemosiderin present in the urine sediment. Iron deficiency and thrombocytosis commonly occur in chronic cases.

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Peripheral blood from a missionary with spiking fever: What is the most likely diagnosis?
The patient has falciparum malaria. Note the ring forms in many of the RBCs. Some are multiply infected, which is a characteristic of falciparum malaria. Only ring forms and gametocytes are present in the peripheral blood in this type of malaria. Fever corresponds with rupture of the RBCs (intravascular hemolysis).

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Peripheral smear from a 3 year old boy with recurrent infections
Arrow points to neutrophil with giant lysosomes of Chediak Higashi syndrome. AR disease with a membrane defect in transferring lysosomal enzymes into phagocytic vacuoles. Since the lysosomes have never been emptied, they are markedly enlarged. Patients also have severe neutropenia.

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PB finding in a 5 year old child with Streptococcus pneumoniae pneumonia and a WBC count of 55,000 cells/m L. The WBCs are predominantly segmented neutrophils and a few band neutrophils. Since the count is >50,000 cells/m L, this would qualify as a leukemoid reaction secondary to the underlying bacterial pneumonia. A leukocyte alkaline phosphatase score (LAP is a marker of mature neutrophils) would be elevated.

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PB finding in a child with cystic fibrosis who has fever, productive cough and a left shifted smear
The cell is a neutrophil demonstrating toxic granulation (increased number of nonspecific, azurophilic granules containing myeloperoxidase), phagolysosomes (arrows pointing to vacuoles in the cytoplasm) indicating that phagocytosis has occurred. The patient most likely has a bacterial pneumonia, which is responsible for this type of neutrophil response.

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Peripheral smear from a 15 year old boy with fever, RLQ pain, and rebound tenderness
Segmented neutrophil, band, and metamyelocyte are present. There is toxic granulation and increased vacuoles (phagolysosomes). This is a left shifted smear and the history suggests acute appendicitis.

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Peripheral smear normal patient
Cell #1 is a mature lymphocyte and cell #2 an eosinophil. Note how the red granules do not cover the nucleus and match the color of the RBCs.

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PB finding in a child with fever and severe cough characterized by paroxysms of coughing followed by an inspiratory whoop
The WBC count is 60,000 cells/m L. All of the cells, except for the eosinophil, are mature lymphocytes, hence the smear is characterized as an absolute lymphocytosis. Since the count is >50,000 cells/m L, it qualifies as a leukemoid reaction, which is commonly encountered in whooping cough (Bordetella pertussis). Note that the lymphocytes are mature and have no atypical features.

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Asymptomatic 25 year old man
Note the hyperchromatic nuclear chromatin and the bilobed nucleus. This patient has Pelger-Hu�t syndrome, an AD disease with no clinical significance. The cells function normally. Pseudo-Pelger-Huet cells are noted in myeloproliferative diseases (e.g., chronic myelogenous leukemia).

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Peripheral smear from a 65 year old man with colon cancer metastatic to the liver
The cell in the slide accounted for 15% of the WBC count. The cell in question is a monocyte with linear appearing chromatin and a slate gray cytoplasm with vacuoles. Monocytosis is commonly present in malignancy and chronic inflammation.

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PB finding in a 3 month old infant with fever and wheezing
The cell is a mature lymphocyte in a patient with a bronchiolitis secondary to the respiratory syncytial virus. Lymphocytosis is common in viral infections.

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Peripheral smear from a 20 year old college student with malaise, exudative tonsillitis, cervical lymphadenitis, and hepatosplenomegaly
Note the large lymphocyte with activated nuclear features and abundant blue cytoplasm. These are atypical lymphocytes (antigenically stimulated lymphocytes) in a patient with EBV induced infectious mononucleosis. The lymphocytes are activated T cells responding to EBV infecting B cells after attaching to CD21 receptors on their surface.

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Peripheral smear from a 20 year old college student with malaise, exudative tonsillitis, cervical lymphadenitis, and hepatosplenomegaly
Note the large lymphocyte with activated nuclear features and abundant blue cytoplasm. These are atypical lymphocytes (antigenically stimulated lymphocytes) in a patient with EBV induced infectious mononucleosis. The lymphocytes are activated T cells responding to EBV infecting B cells after attaching to CD21 receptors on their surface.

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Mouth of a 25 year old woman with generalized fatigue, hepatosplenomegaly, cervical lymph-adenopathy and atypical lymphocytosis
Palatal petechiae are commonly seen in patients with infectious mononucleosis. However, they are not pathognomonic of the disease.

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PB from a 60 year old man with splenomegaly
The cell depicted in the slide accounted for 8% of the WBC differential count. The cell in question is a basophil with dark purple granules covering the nucleus. Basophilia is a hallmark for myeloproliferative diseases such as PRV, CML, agnogenic myeloid metaplasia, and essential thrombocythemia. With the presence of splenomegaly, a myeloproliferative disease is likely in this patient.

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55 year old man with flushing of the face, headaches, splenomegaly, and a Hb of 19 gm/dL
The patient has a plethoric face and polycythemia with splenomegaly, hence polycythemia rubra vera is the most likely diagnosis. Plethora is due to the release of histamine from the increased numbers of mast cells/basophils.

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45 year old man with anemia, 110,000 WBC count, thrombocytopenia, hepatosplenomegaly
Note the mixture of mature and immature WBCs. Cells with round nuclei are myeloblasts, progranulocytes, or myelocytes. Metamyelocytes (slight indentation of nucleus), band neutrophils, and segmented neutrophils also present. Leukocyte alkaline phosphatase score was zero and the Philadelphia chromosome positive indicating chronic myelogenous leukemia.

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PB finding in a 60 year old woman with massive splenomegaly and a dry tap on attempted bone marrow aspiration
The RBC is a tear drop cell, which is a characteristic finding of agnogenic myeloid metaplasia, a myeloproliferative disease. The disease begins in the bone marrow and shifts to the spleen where extramedullary hematopoiesis takes over the bone marrow functions. Megakaryocytes in the bone marrow stimulate fibrogenesis, which traps erythroid islands and damages RBCs as they try to enter the sinusoids. Tear drop cells are also noted in the thalassemias and megaloblastic anemias due to folate and B12 deficiency.

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Bone marrow biopsy from a 60 year old patient who has massive splenomegaly and a dry bone marrow aspirate
Note that the marrow is replaced by fibrous tissue. The large cells represent benign megakaryocytes, which secreted platelet derived growth factor, an agent that stimulates reactive fibrosis in the marrow. Reactive marrow fibrosis may also occur with metastatic disease and radiation.

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PB findings in a 65 year old woman with GI bleeding, hepato-splenomegaly, mild neutrophilic leukocytosis, and a platelet count over 1,000,000 cells/m L
The patient has essential thrombocythemia, a myeloproliferative disease with excessive production of platelets (>600,000 cells/m L). Bleeding is more characteristic than thrombosis, since the platelets are defective and do not aggregate. A bone marrow would reveal large, dysplastic appearing megakaryocytes. This is the least common of the myeloproliferative diseases.

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BM findings with Prussian blue stain from a 79 year old man with a refractory macrocytic anemia, pancytopenia, and dimorphic RBC cell populations (small and large)
The patient has myelodysplastic syndrome (MDS) with megaloblastoid RBCs and ringed sideroblasts (defect in heme synthesis). These patients frequently have chromosome defects and commonly progress into acute leukemia.

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PB finding in a 3 year old child with fever, bone pain, anemia, thrombocytopenia, elevated WBC count, hepatosplenomegaly, and generalized lymphadenopathy
The cells are all lymphoblasts, many of which contain nucleoli. The patient has acute lymphoblastic leukemia (ALL), which is not only the most common cancer in children, but also the most common leukemia up to 15 years of age. The majority are common ALL antigen positive CD10 B cell leukemias. The type of ALL is the most important prognostic factor.

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Peripheral smear from a 70 year old man with generalized non-tender lymphadenopathy, hepatospleno-megaly, normocytic anemia, thrombocytopenia, and a WBC count of 35,000 cells/m L
All of the cells are lymphocytes with hyperchromatic nuclei. Note the smudge cells as well (fragile lymphocytes crushed in the smear preparation). The patient has chronic lymphocytic leukemia, the most common overall leukemia, and the most common one in patients over 60 years old. The majority are B cell malignancies.

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PB from a 65 year old man with hepatosplenomegaly, normocytic anemia, thrombocytopenia, and these abnormal cells in the smear
The patient has hairy cell leukemia. Note the hairy cytoplasmic projections. The tartrate resistant acid phosphatase stain is positive in these neoplastic B cells. The spleen is the reservoir for the neoplastic cells, hence splenectomy is usually performed as part of the treatment. Lymphadenopathy is characteristically absent, an unusual feature for leukemia. Splenomegaly is invariably present. Unlike most leukemias which infiltrate both the red and white pulp, HCL only infiltrates the red pulp.

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Peripheral blood in a 25 year old man with normocytic anemia, thrombocytopenia, WBC count of 20,000 cells/m L, hepatosplenomegaly and generalized lymphadenopathy
The cell with the arrow is a myeloblast with an Auer rod (red splinter) in the cytoplasm. Acute myelogenous leukemia is the most common leukemia from 15-39 years of age.

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PB from a 32 year old male with anemia, thrombocytopenia, and an elevated WBC count containing cells similar to those noted in the slide
The patient has acute myelogenous leukemia. Note the myeloblast with the Auer rods.

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22 year old man with acute leukemia
The patient has gum infiltration by leukemic cells. This is characteristic of acute monocytic leukemias.

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Peripheral blood from a 25 year old man with disseminated intravascular coagulation: What is the treatment for this type of leukemia?
The patient has acute progranulocytic leukemia (M3), which almost invariably presents with DIC. These patients have a t(15;17) translocation and can be treated with retinoic acid (vitamin A). Retinoic acid increases maturation of the blasts.

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12 year old boy with epistaxis

Patient with petechial lesions on skin. These do not blanch with pressure. Platelet count was 5000 cells/m L consistent with idiopathic thrombocytopenic purpura, an autoimmune disorder with IgG antibodies against a platelet antigen (type II hypersensitivity).

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Bone marrow aspirate from a woman with SLE who has thrombocytopenia

The marrow exhibits clumps of megakaryocytes that are not budding off platelets from their cytoplasm. This is a characteristic feature of autoimmune thrombocytopenia and would also have been present in the previous patient as well.

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NO PIC
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Finger of a 23 year old man with severe iron deficiency and a positive stool guaiac.
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Finger of a 23 year old man with severe iron deficiency and a positive stool guaiac

The patient has Osler-Weber-Rendu disease (hereditary telangiectasia). Note small vascular lesions on the pad of the finger. These are also located in the mouth and GI tract, hence predisposing to blood loss and iron deficiency.

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Hands of a 70 year old woman with a normal platelet count and CBC. The patient has senile purpura with rupture of small vessels producing these ecchymotic areas in the subcutaneous tissue. Vascular instability is common in the elderly. These could also have occurred as a response to being over-anticoagulated with warfarin or heparin.

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Patient with hyperextensible joints and skin: What is the defect in this patient?

The patient has Ehlers-Danlos syndrome, which is a group of diseases with various defects in collagen. Note the ecchymoses related to vessel instability.

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15 yr old boy with palpable purpura, hematuria, and polyarthritis. What is the mechanism of the patient's vascular problem?

The patient has Henoch-Schönlein purpura, the MC vasculitis in children. It is a small vessel vasculitis due to IgA-anti-IgA immunocomplexes (type III hypersensitivity).

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Tooth socket in a 22 year old with a recent extraction and problems with persistent bleeding

The bleeding time is normal and the aPTT prolonged. Persistent bleeding from a tooth extraction is characteristic of a coagulation disorder, in this case, hemophilia A. A temporary platelet plug is formed in the socket, however, a stable clot is not formed, hence late rebleeding is commonly observed. The single best question to ask a patient that will exclude any significant hemostasis abnormality is how well they did after a molar extraction.

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18 year old boy with a prolonged aPTT. The patient has an intramuscular hematoma secondary to severe hemophilia A. Bleeding into closed spaces or fascial planes is a feature of a coagulation deficiency.

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Cervical lymph node biopsy from a 25 year old man with painful cervical lymphadenopathy

The node shows the classic features of reactive hyperplasia: sharply demarcated follicles (B cells) with a mantle of darkly staining B cells, and paracortex (T cells). Note the variety of cellular types in the node which distinguishes it from a malignant lymphoma. The follicles have been antigenically stimulated, hence the node becomes enlarged and painful. The cells in the center of the follicles are antigenically stimulated B cells in different stages of development: small cleaved -> large cleaved -> small non-cleaved -> large non-cleaved -> immunoblast -> plasma cell.

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Child with ataxia telangiectasia:

This is an AR chromosome instability syndrome (increased susceptibility to chromosomal mutations involving defects in DNA repair enzymes) that predisposes to malignant lymphomas and leukemias. Note the vessel telangiectasias in the eye. Cerebellar ataxia, recurrent sinus infections, and B and T cell defects are present.

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Child with Wiskott-Aldrich syndrome:

This is an SXR disease with a triad of eczema (evident in this child), thrombocytopenia, and recurrent sinopulmonary infections. They have both B and T cell defects and an increased incidence of leukemia and lymphomas. Rx: bone marrow transplant.

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Lymph node biopsy from a 55 year old woman with non-tender cervical lymphadenopathy

The biopsy shows a monomorphic infiltrate of cells forming nodular areas. The normal sharply demarcated follicles (B cells) and the paracortex (T cells) have been replaced by these neoplastic cells. This is follicular B cell lymphoma, the most common non-Hodgkin’s lymphoma in adults. It commonly involves the bone marrow and peripheral blood, but is considered a low grade malignancy.

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Cross-section of trachea and arch vessels in a patient with a malignant lymphoma:

Note the bulging, fish flesh appearance of the tumor. Note that the tumor cells cannot invade elastic tissue or cartilage.

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African child with a jaw tumor: What is the etiologic agent?

The patient has the African variant of Burkitt's lymphoma, which has a high association with EBV. Patients also have a t(8;14) translocation of the c-myc oncogene, which is a nuclear transcriber.

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Lymph node biopsy of a para-aortic node from a 5 year old child

The patient has Burkitt’s lymphoma, the most common lymphoma in children. Unlike the African variant, the American variant is more commonly located in the abdominal cavity. Note the characteristic "starry sky" appearance, where the dark of night are the small noncleaved malignant B cells and the stars are tingible macrophages with apoptotic remnants of phagocytosed B cells. It is a high grade lymphoma. There is an association with EBV and a t(8;14) translocation.

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Patient with an abnormal infiltrate of cells in the skin. The patient has the nodular, ulcerated plaques of mycosis fungoides, a malignancy of CD4 T helper cells

Skin infiltration by the malignant T cells results in these lesions. Collections of malignant cells in skin are called Pautrier’s microabscesses. When the cells enter the blood stream, they are called Sezary cells and the disease changes its name to Sezary syndrome.

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Abnormal cells in the blood of the above patient

The cells with the nuclear cleft are malignant CD4 T helper cells, or Sezary cells. They stain positive for PAS (not demonstrated in this slide) and have PAS positive chunks of material located around the nucleus ("ring around the collar" analogous to ringed sideroblasts in sideroblastic anemias").

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Lymph node in cross-section from a 32 year old female with nonpainful cervical lymphadenopathy and an anterior mediastinal mass

The lymph node shows the characteristic features of nodular sclerosing Hodgkin’s lymphoma, the most common HL and the one most commonly seen in women. The fibrotic areas separate the lymphoid tissue into nodular appearing areas. These areas contain spaces (not easily visible on this slide) within which are lacunar cells, a variant of Reed-Sternberg cells.

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100. Cell found in the right supraclavicular lymph node of a 19 year old man

The cell is a Reed-Sternberg (RS) cell. The RS cell is a single large cell with two or more nuclei or nuclear lobes with a large inclusion body-like eosinophilic nucleolus surrounded by a halo of clear nucleoplasm (has an "owl eye" appearance). Mononuclear variants (single, round nucleus) of the RS cell are noted in the different subtypes. The L and H variant ("popcorn cell") is noted in the lymphocyte predominant HL, which frequently has a lymphocytic and histiocytic infiltrate, hence the term L and H cell. The lacunar cell variant is noted in nodular sclerosing HL and consists of a multilobulated nucleus surrounded by a clear space, which may represent artifactual distortion related to formalin fixation of the node. Mononuclear variants are noted in mixed cellularity HL which resemble RS cells but for the presence of a single nucleus with a prominent nucleolus. Unlike NHL, the lymphocytes in the lymph nodes involved with HL are not neoplastic, which has a binucleate cell with prominent red nucleoli surrounded by a clear space. RS cells are the neoplastic cell in HL. They are of B cell origin in some variants or T cell origin in other variants. It is essential for securing the initial diagnosis of HL in lymph nodes but is not pathognomonic of HL, since there are many look-alikes, e.g., immunoblasts in infectious mononucleosis.

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Lymph node (higher magnification) from a patient with nodular sclerosing HL

Note the spaces within which are multinucleated cells with small nucleoli (lacunar cells). This is characteristic of nodular sclerosing HL.

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Lymph node biopsy in a 17 year old with painless cervical lymphadenopathy

A classic RS cell is present. The patient most likely has a lymphocyte predominant HL, where RS cells are very difficult to find, hence the better prognosis, since they are the neoplastic cell of HL.

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EM finding of interstitial tissue from a rectal biopsy in a patient with macroglossia, hepatosplenomegaly, and massive proteinuria

The EM shows the non-branching fibril with a hollow core of amyloid. The patient has secondary (reactive) amyloidosis, the amyloid, in this case, derived from serum associated amyloid (SAA) protein synthesized in the liver. Amyloid is Congo red positive, which fluoresces apple green (Granny Smith apple) under the polarizing microscope.

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Patient with macroglossia, restrictive cardiomyopathy, and the nephrotic syndrome. What systemic disease is most likely present?

The patient has macroglossia secondary to secondary (reactive) amyloidosis. Chronic diseases are most often associated with this type of amyloidosis, which is due to conversion of serum associated amyloid into amyloid.

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BM finding in a 70 year black woman with bone pain, anemia, rouleaux, and a pathologic fracture of the rib

The patient has multiple myeloma. Note the sheets of malignant plasma cells with eccentric nuclei, perinuclear clearing, and bright blue cytoplasm (increased RER with immunoglobulin synthesis). Light chains in the urine are called Bence Jones protein. The cells produce osteoclast activating factor (IL-1), which is responsible for the lytic areas in bone and hypercalcemia. Rouleaux occurs when immunoglobulins are increased.

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Skull x-ray from the black woman in the above case

Note the lytic areas in the skull associated with the release of osteoclast activating factor from malignant plasma cells in multiple myeloma.

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Serum immunoelectrophoresis in a patient with multiple myeloma. Which immunoglobulin and light chain are abnormal in this patient?

N refers to the normal control and P refers to the patient. There is an abnormal arc for IgG and k light chain. Light chains in the urine are called Bence Jones protein, which is toxic to the renal tubules and leads to renal failure.

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Bone marrow finding in an adult with massive splenomegaly and increased total acid phosphatase levels

The cell is a macrophage containing a fibrillary material. This is a cell in Gaucher’s disease, which is an AR lysosomal storage disease with a deficiency of glucocerebrosidase and an accumulation of glucocerebroside. Infantile and adult types of the disease are recognized. The cells contain large amounts of acid phosphatase.

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Bone marrow finding from an infant with severe mental retardation and hepatosplenomegaly

The foamy appearing cell with a small nucleus is a macrophage containing lysosomes filled with sphingolipid. The patient has Niemann Pick disease, an AR disease with an absence of lysosomal sphingomyelinase.

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EM of a cell which was part of an infiltrate in the skin of a 3 year old child with an eczematous rash, hepatosplenomegaly, and generalized lymphadenopathy

The cells were CD1 positive. The finding in the cell is a Birbeck granule (looks like a tennis racket), which is a characteristic finding in Langerhan’s cells, a true histiocyte. The patient has Letterer Siwe disease, which is part of the histiocytosis X complex of diseases.

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Lymph node biopsy from the above patient. What are the pink staining cells called and where are they normally located?

The pink staining aggregates are malignant histiocytes, which are normally present in the sinuses of a lymph node.

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Child with Rh hemolytic disease of the newborn: Why is the fetus edematous?

The child has hydrops fetalis. Patients with Rh hemolytic disease have severe anemias, which lead to high output failure and both left and right heart failure, the latter responsible for peripheral edema and ascites. The liver in this fetus had massive hepatomegaly secondary to extramedullary hematopoiesis.

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Brain of the above fetus. What is causing the yellowish discoloration?

The yellow pigment is unconjugated, lipid soluble bilirubin derived from macrophage destruction of the Rh-sensitized fetal RBCs. The condition is called kernicterus.

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Kleihauer-Betke test in maternal blood post-delivery. The mother is O negative and the baby is O positive. Who do the normal colored RBCs belong to and what should the mother be given to prevent sensitization?

The normal staining cells contain Hgb F and represent fetal RBCs, while the pale staining cells contain Hgb A from the mother. She should be give Rh immune globulin (anti-D) to prevent sensitization to the D antigen.