Pathology 13
Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus
Super Notes!
€ = Benedum specifically mentioned this point
Also cover differentiation of BCs
For table 13.1 know ballparks, look at cases and review book
Platelet 150-450; White cells 4.8-10.8; RBCs 3.5-5 female 4.3-5 men
1.

2.
When do hematopoietic cells appear in the peripheral circulation, besides cancer?
Marked stress such as severe anemia can cause HSCs to be mobilized from the marrow,
sometimes going so far as to become foci of extramedullary hematopoiesis
What is agranulocytosis? What is the most common cause of agranulocytosis? What conditions
cause agranulocytosis to occur by accelerated removal or destruction of neutrophils (3)? €
 clinically significant neutropenia = agranulocytosis
 Drugs (test question!)
 Imunological disorder, splenomegally, and increased peripheral utilization
3. What do infections resulting from agranulocytosis look like?
 Agranulocytosis leads to infections in the oral cavity and pharynx, which are deep,
undermined, and covered by gray to green-black necrotic membranes
4. What is a leukemoid reaction? Putting aside infection and neoplasia, what are some lesserknown causes of leukocytosis (4)? What’s a strange cause of granulocytopenia?
 Elevation of WBCs due to infection or stress
 Hypoxia (release), exercise, catecholamines (decreased margination), and glucocorticoids
(decreased extravasation into tissues)
 Overwhelming bacterial infection can cause depletion of your granulocytes
5. When might you see toxic granules and Dohle bodies? €
 Sepsis or severe inflammatory disorders such as Kawasaki disease
6. When does lymphocytosis occur? When does neutrophilic lymphocytosis occur? €
 Viral infection
 Acute bacterial infection
7.
What are the two forms of nonspecific chronic lymphadenitis? And sort-of a third? €
Follicular hyperplasia is caused by stimuli that activate the humoral immune response
i. Features polarized germinal centers and tingible-body macrophages (which
comsume remains from apoptotic B cells)
 Paracortical hyperplasia results from stimuli that trigger T cell-mediated immune responses
i. T cell regions can replicate astoundinly fast and contain immunoblasts
 Sinus histoiocytosis can also occur in lymph nodes draining cancers
 Tenderness with acute infection

8.
Name the three categries of myeloid neoplasia: €
 Acute myeloid leukemias


9.
Myelodysplastic syndromes
Chronic myeloproliferative disorders
What’s the difference between leukemia and lymphoma? €
 Lymphomas proliferate in discrete tissue masses, and leukemias involve the bone marrow,
however these are not precise naming categorizations
10. What are the excpetions to the trend of widespread B and T cell neoplasia?
 Hodgkin lymphomas are usually restricted to one group of lymph nodes
 Marginal zone B-cell lymphomas (“MALTomas”) are often restricted to sites of chronic
inflammation
11. What is the most common cancer (any type!) of children? €
 Acute lymphocytic leukemia (ALL) is the most common cancer in children, usually white boys
i. Despite leukemogenic aberration at birth, a TF mutation is also required
12. How can you differentiate acute lymphocytic leukemia from acute myeloid leukemia (AML)?
 Clinical signs and symptoms are nearly identical: low Hgb, hematocrit, & platelet; high WBCs
 Differentiate ALL from acute myeloid leukemia based on antibodies, see next Question
 ALL Lymhoblasts will often have more condensed chromatin, less cytoplasm, and less
conspicuous nucleoli
13. What cluster of differentiation markers are expressed in B-ALLs? T-ALLs?
 B-ALLs express CD10, -19, and -20
 T-ALLs express CD1, -2, -5, and -7, plus -3, -4 and -8 when mature
14. When acute lymphocytic leukemia is present in adults, what is to blame in 25% of cases? What
mutation is prognostic of a favorable outcome? €
 t(9;22) => worse prognosis
i. Philadelphia chromosome causes epxpression of a constitutively active BCR-ABL
tyrosine kinase, mostly in adults
 t(12;21) => better prognosis
15. How must lymph nodes in chronic lymphocytic leukemia (CLL) and small leukocytic leukemia
(SLL) appear histologically? Who gets CLL/SLL? How can you tell when CLL/SLL transforms? €
 Proliferation centers are pathognomonic for CLL/SLL, smudge cells may also be present
 Mostly men over 60 years old
 Splenomegaly is a bad sign of “Richter syndrome” (transformation to B-cell lymphoma)
16. What cell types are present in follicular lymphoma (2)? What translocation causes it? €
 Centrocytes: small cells with irregular contours
 Centroblasts: large cells with open chromatin and several nucleoli
 t(14;18) causes overexpression of BCL2 and leads to follicular lymphoma
17. What is the most common NHL (non-Hodgkin lymphoma)? €
 diffuse large B-cell lymphoma (DLBCL) is the most common NHL
18. What lymphoma often transforms into diffuse large B-cell lymphoma (DLBCL)? What mutation
causes it? What other mutation leads to DLBCL?
 Follicular lymphoma often transforms into DLBCL—hence t(14;18)
 The other main cuase of DLBCL is overexpression of BCL6 (mutation)
19. What viruses can cause diffuse large B-cell lymphoma (DLBCL)?
 EBV + immunosupression can cause immunodeficiency-associated DLBCL
 KSHV/HHV-8 can cause subtype: primary effusion lymphoma
20. How treatable is DLBCL? €
 Pretty good, use chemotherapy and immunotherapy with anti-CD20 antibody
21. What form of Burkitt lymphoma is always caused by EBV? Signs? What’s the other type? €
 The endemic form of Burkitt lymphoma is caused by EBV, coupled with malaria
 Endemic Burkitt lymphoma usually strikes the mandible and abdominal viscera
 Sporadic Burkitt lymphoma appears as a mass involving the ileocecum and periotneum
i. both show “starry sky” appearance on microscopy due to rapid proliferation
22. What genetic translocation causes Burkitt lymphoma? Is Burkitt lymphoma treatable?
 c-MYC on chromosome 8, usually t(8;14) is to blame
 Burkitt lymphoma (both types) is very aggressive, but response well to chemo
23. What cytokine are multiple myeloma cells dependent on for proliferation and survival?
 Myeloma cells need IL-6
24. How do you describe the lesions caused by Multiple Myeloma? What cell types are present? €
 Radiographically: punched out lesions 1-4 cm wide caused by plasma cells
i. Caused by MIP1α, which upregulates RANKL (NF-КB)
 plasmablasts, bizarre multinucleated cells, flame cells, and Mott cells, which contain fibrils,
crystalline rods, globules, Russel bodies (cytoplasmic), and Dutcher bodies (nuclear)
 rouleaux RBCs
 Monoclonal M proteins (monoclonal IgG) with Many light chains=> Bence Joyce proteins in
urine
25. What are the two main causes of death in multiple myeloma? What treatment works well for
multiple myeloma? €
 Infection is the most common cause of death
 2nd: renal insufficiency due to Bence Jones proteinuira (excreted light chains)
 Drugs that inhibit proteasomes are effective for multiple myeloma, because they cause
misfolded Ig to accumulate and cause apoptosis of myeloma cells
26. What disease superficially resembles CLL/SLL? How can you tell it apart? €
 Lymphoplasmacytic lymphoma
 differs most strikingly in that in produces plasma cells which secrete IgM (normal light:heavy
ratio), and so cause Waldenstrom macroglobulinemia
 marrow examination shows Dutcher and Russel bodies
27. What are the signs of Waldenstrom macroglobulinemia?
 light and heavy chains are usually paired so no renal failure
 Visual impairment, neurologic problems due to sludging, bleeding, and cryoglobulinemia
28. How can you differentiate mantle cell lymphoma from CLL/SLL (2 or 3)? What marker is
expressed? €
 Mantle cell lymphoma consists of a homogenous population of small lymphocytes
 There are no proliferation centers like in chronic lymphocytic leukemia
 Cyclin D1 is expressed instead of CD23
29. Why do marginal zone (MALT) lymphomas come and go? €
 Marginal zone lymphomas arise in tissues of chronic inflammation, remain localized, and may
regress after inflammation is treated provided that no chromosomal translocation occurs.
[drink MALT shakes to feel better from an infection]
30. What disease causes “dry tap” during attempted aspiration of bone marrow? €
 Hairy cell leukemia causes dry tap because of the mesh of ECM it produces
31. What neoplasms fit under the definition: peripheral T cell lymphoma (5)?
 Anaplastic large-cell lymphoma
 Adult T-cell leukemia/lymphoma
 Mycosis fungiodes w/w/o Sézary Syndrome
 Large granular lymphocytic leukemia
 Extranodal NK/T cell lymphoma
32. What substance is a reliable indicator for Anaplastic Large-Cell Lymphoma?
 ALK (kinase)
 a protein not expressed in other lymphomas or normal lymphocytes, thus it is a reliable
indicator for anaplastic large-cell lymphoma
[Anaplastic Large Kell]
33. Who gets Anaplastic Large-Cell Lymphoma and how does it usually turn out?
 Children and young adults get it
 usually the prognosis is very good
34. What leukemia/lymphoma is only seen in adults infectd by HTLV-1? Where is it endemic? What
other disease does it resemble? €
 HTLV-1 causes adult T-cell leukemia/lymphoma
 it is endemic in Japan, Africa, and the Carribean
 it’s like a more deadly version of mycosis fungiodes
35. What peripheral T cell lymphoma exhibits massive infiltration of the epidermis and dermis?
What is the variant on this disease? €
 Mycosis fungoides features cerebriform T cells in the skin
 Sézary syndrome is a variant in which the skin involvement is manifested as a generalized
exfoliative erythroderma
i. CLA (adhesion molecule) levels elevated
36. What signs of disease are associated with Large granular lymphocytic leukemia? What
syndrome is it is it associated with?
 Neutropenia, anemia, and an increased risk of rhematologic disorders
 Can be the cause of Felty syndrome: rheumatoid arthritis, splenomegaly, and neutropenia
37. What peripheral T cell lymphoma is highly associated with EBV and features necrosis of small
vessels?
 Extranodal NK/T-cell lymphoma causes extensive ischemic necrosis through the invasion of
small vessels. Large azurophilic granules are seen in the cytoplasm of the tumor cells
38. How are Reed-Sternberg cells identified?
 Reed-Sternberg cells are large, either multinucleated or with a multilobed nucleus, each with
a large inclusion-like nucleolus around the size of a lymphocyte
i. They are former B cells
39. What is the most common form of Hodgkin lymphoma? Character? Markers? Other assoc.? €
 Nodular sclerosis is the most common form of HL
 It is characterized by the presence of lacunar variant reed-sternberg cells and the deposition
of collagen which divides lymph nodes into circumscribed nodules
 Positive for PAX5, CD15, and CD30 (classical)
 Uncommonly associated with EBV
40. Describe the mixed-cellularity type of HL:
 Reed-sternberg cells, usually infected with EBV
 classical immunophenotype
41. What variant of Hodgkin lymphoma has reactive lymphocytes making up the vast majority of
the cellular infiltrate in lymph nodes?
 The lymphocyte-rich type!
 Sometimes associated with EBV
 classical immunophenotype
42. What is the “opposite” of the lymphocyte rich type?
 The lymphocyte depletion type has a relative abundance of Reed-Sternberg cells compared
to lymphocytes
 Almost always associated with EBV
 classical immunophenotype
43. What is the nonclassical type of Hodgkin Lymphoma? What are the features? €
 The lymphocyte predominance type
 Not associated with EBV
 Expresses B cell markers typical of germinal-center B cells: CD20 & BCL6
i. That’s how it differs from lymphocyte-rich type
44. How do Reed-Sternberg cells engage in “cross talk?”
 Reed-Sternberg cells release a number of cytokines and chemokines, which attract cells that
support the growth and survival of tumor cells
i. T cells and eosinophils express ligands that activate the CD30 and CD40
receptors on Reed-Sternberg cells, causing them to produce NF-KB in turn
45. What secondary problems can result from chemotherapy for HL? €
 Chemotherapy for HL can cause:
1. myelodysplastic syndromes,
2. AML,
3. lung cancer, and especially
4. breast cancer in females who are treated during adolescence
46. What stage means that lymph nodes are involved on both sides of the diaphragm? €
 Stage III
47. Which myeloid neoplasms often transform into acute myeloid leukemia?
 Myelodysplastic syndromes and myeloproliferative disorders tend to transform into AML
48. How do patients with developing acute myeloid leukemia present? €
 Patients present within weeks to months of the onset of symptoms due to anemia,
neutropenia, and thrombocytopenia (causing mucosal and cutaneous bleeding)
i. it presents in a similar manner to acute lymphocytic leukemia (ALL). See #12
49. How is acute myeloid leukemia diagnosed? €
 The presence of at least 20% myeloid blasts in the bone marrow = acute myeloid leukemia
 Myeloblasts have delicate nuclear chromatin, 2-4 nucleoli, and voluminous cytoplasm, often
containing Auer rods. They can be completely absent from the blood.
50. What are the cytogenetics of AML? €
 Usually due to errors that disrupt differentiation genes CBF1α and CBF1β
 AML is due to either: balanced translocations, deletions or monosomies, or after treatment
with topoisomerase II inhibitors when translocations of the MLL gene occur
51. AML is difficult to treat, with one exception. What is it?
 t(15;17) can be treated by pharmacologic doses of all-trans retinoic acid (ATRA), which binds
to the PML-RARα fusion protein
52. Which form of myelodysplastic syndome is most likely to transform into AML?
 highest frequency and most rapid transformation occurs from myelodisplastic syndrome
arising 2-8 years after genotoxic drug or radiation therapy (t-MDS)
53. What 3 marrow biopsy signs only appear in myelodysplastic syndromes (MDS)?
 Pseudo-Pelger-Huet cells: neutrophils with only two lobes
 Pawn ball megakaryocytes: magakaryocytes with single nuclear lobes or multiple nuclei
 Increased Myeloid blasts (still less than 20% of marrow)
54. What mutation causes myeloproliferative disorders? €
 Mutated tyrosine kinases in myeloproliferative disorders allow growth factor-independent
proliferation and survival of marrow progenitors

These marrow progenitors often cause production of one or more mature blood elements
55. What are the common features in myeloproliferative disorders? €
 Increased proliferative drive in the bone marrow
 Extramedullary hematopoiesis (mutant stem cells think there’s a shortage of RBCs)
 Possible spent phase
 Variable transformation to acute leukemia
56. How is chronic myeloid leukemia genetically distinguised from other myeloproliferative
disorders? €
 In chronic myeloid leukemia, a chimeric BCR-ABL gene causes the synthesis of a 210 kDa BCRABL tyrosine kinase. It is usually due to t(9;22)(q34;q11) – the Philadelphia chromosome [Ph]
i. Dunno why [Ph] sometimes causes ALL and other times CML
57. What are the signs of CML? How does this disease develop? € € €
 Leukocytosis in CML often exceeds 100,000 cells/mm3, and the spleen is greatly enlarged
because of extramedullary hematopoiesis; platelets may be elevated above 450k
i. Erythroid progenitors may be slightly crowded out in the hypercellular marrow
 In half of patients, an accelerated phase occurs, which develops in 6-12 months into a blast
crisis
 In the other half of patients, the blast crisis comes on abruptly with no accelerated phase
58. What is the best therapy for cases of chronic myeloid leukemia?
 CML can be treated but not cured by imatinib. Imatinib does not extinguish the CML’s
version of stem cells, though it does control blood counts and delays blast crisis
59. What signalling error causes polycythemia vera?
 Constitutive JAK2 signalling (tyrosine kinase, rememeber?) in polycythemia vera causes
progenitor cells to remain active in the absence of erythropoietin
60. How does the late picture of PCV look? What indicator is often paradoxically normal?
 Polycythemia vera often progresses to a spent phase characterized by extensive marrow
fibrosis, along with prominent organomegaly due to extramedullary hematopoiesis
 Chronic bleeding and clotting due to PCV may cause iron deficiency, which normalizes the
hematocrit
i. Platelets will be down down down
61. How is PCV similar/contrasted to essential thrombocytosis (3 issues)? €
 Essential thrombocytosis is associated with JAK2 signalling half of the time, while the other
have MPL is mutated
 Instead of producing many RBCs, the trend is towards abnormally large platelets and mild
leukocytosis
 Hematocrit is normal
62. What does primary myelofibrosis most closely resemble? €
 Primary myelofibrosis appears identical to the spent phase of other myeloproliferative
diseases. Additionally, JAK2 and MPL mutations account for most cases.
63. What are important clinical features of primary myelofibrosis? €
 Fibrosis and teardrop RBCs (dacrocytes) in the marrow
[marrow is crying because it’s fibrosed]
 Gradual thrombocytopenia begins to occur as the disease progresses.
 Biopsy is essential for diagnosis
i. The fibrosis in the marrow causes extensive extramedullary hematopoiesis
64. Which myeloproliferative disorders cause enlarged spleen?
 CML, polycythemia vera, and myelofibrosis
65. How can Langerhans cell histiocytosis be identified?
 Birbeck granules are characteristic of Langerans cell histiocytosis. They are pentalaminar
tubules with a dilated terminal end producing a tennis-racket like appearance.
66. Which form of Langerhans cell histiocytosis occurs in those under 2 primarily, and what are its
symptoms? €
 Multifocal multisystem Langerhans cell histiocytosis (Letterer-Siwe disease) occurs most
frequently in those under 2
 It features cutaneous lesions resembling a seborrheic dermatitis the back of trunk and scalp,
as well as destructive lesions in bones, lung, and liver
67. How does unisystem Langerhans cell histiocytosis (unifocal or multifocal) present? €
 unisystem Langerhans cell histiocytosis typically involves only the bones and often causes
pathologic fractures
 involvement of the posterior pituitary stalk is common and causes the Hand-SchullerChristian triad of diabetes insipidus, exopthalmos, and cavarial bone defects
 smokers sometimes get pulmonary Langerhans cell histiocytosis
68. Here’s a translocations recap:
 t(8;14) = Burkitt lymphoma (mutates C-myc)
 t(11;14) = Mantle
 t(18;14) = Follicular=>DLBCL
 t(12;21) = ALL
 t(9;22) = adult ALL or CML (creates BCR-ABL fusion)
 t(15;17) = AML: all trans retinoic acid sensitive
Spleen and Thymus
69. What does splenomegally do to cells in the blood? €
 With splenomegally 80-90% of platelets can be sequestered in the red pulp, producing
thrombocytopenia
70. What are the consequences of splenic insufficiency or absence? € [test Q]
 Splenic insufficiency increases a person’s susceptibility to sepsis caused by encapsulated
bacteria such as pneumococcus, meningococcus, and Haemophilus influenzae
i. Asplenic individuals should be vaccinated for these three microbes
71. What is the main general cause of splenomegaly? €
 Cirrhosis of the liver is the major cause of splenomegaly, especially that of schistosomiasis
72. What type of cells are seen in thymic tissue? In what developmental syndrome does thymic
hypoplasia/aplasia occur? €
 Hassel corpuscles
 DiGeorge syndrome is marked by thymic hypoplasia/aplasia and hence severe defects in cellmediated immunity.
i. Hyoparathyroidism is also common in DiGeorge
73. What kind of thymoma has a substantial proportion of medullary-type epithelial cells?
 Noninvasive thymoma has many medullary-type epithelial cells
74. How is an invasive thymoma diagnosed? €
 Invasive thymomas are cytologically benign but locally invasive. They may also metastasize
75. Describe thymic carcinoma:
 Thymic carcinoma is relatively rare. It causes a fleshy and invasive mass that often
metastasizes to the lungs. Microscopically, most are squamous cell carcinomas.
 The rest are lymphoepithelioma-like carcinoma, whose sheets of cells cause it to resemble
nasopharyngeal carcinoma. Lymphoepithelioma-like carcinoma harbours EBV about 50% of
the time.
76. You start out not knowing anything, then you know the answer but answer with the wrong
answer, finally you get it. Don’t be angry with yourself. This is the learning process at work.