Diseases of WBCs, LNs, Spleen, and Thymus Flashcards
What are the three categories of myeloid neoplasms?
acute myeloid leukemia’s, chronic myeloproliferative disorders, myelodysplastic syndromes.
What are histiocytoses?
uncommon proliferative lesions of macrophages and dendritic cells.
What are some predisposing genetic factors for developing acute leukemias?
down syndrome, type 1 NF, Faconi anemia, bloom syndrome, ataxia telangiectasia.
HTLV-1 is associated in what cancer?
adult T cell leukemia/ lymphoma.
How can reactive and malignant lymphocytosis be differentiated?
Based on clonality: monoclonal is malignant and polyclonal is reacitve.
What is the most common childhood cancer?
Acute Lymphoblastic Leukemia/ lymphoma
Children <15
What is the most common type of ALL?
B-ALL makes up 85%
Ethnicity of ALL?
white-3x more likely.
hispanics have highest risk
Peak age of B-ALL?
3
Peak age of T-ALL?
15
- predominately adolescent males
70% of T-ALLs have what genetic mutation?
NOTCH-1
What translocation is associated with B-ALL?
balanced t(12;21)
*other genes include PAX6,E2A,EBF
What is the morphology of the marrow in leukemic presentations?
Hyper cellular and packed with lymphoblasts.
What are the morphological features of a peripheral smear in a patient with ALL?
Punched out nuclei, blasts appear larger, chromatin is delicate and finely stippled.
What are the differentiating features of myeloblasts compared to lymphoblasts?
Lymphoblasts have more condensed chromatin, less conspicuous nucleoli, and smaller amounts of cytoplasm that usually lacks granules.
What stain can be used to identify myeloblasts?
myeloperoxidase (MPO)
Lymphoblasts are characterized by positive nuclear staining for what?
TdT.
What CDs are expressed in B-ALLs?
CD-10, 19, 20
What CDs are expressed in T-ALLs?
CD-1,2,5,7
** not CD-10!
What are the common symptoms associated with ALL?
Anemia (fatigue), thrombocytopenia (bleeding), neutropenia (infection)
What is the prognosis of ALL in children?
aggressive chemotherapy–> 95% success rate
What factors favor a good prognosis in ALL?
t(12;21), age 2-10, hyperdiploidly, trisomy of chromosomes 4,7,10.
What translocation in ALL yields a poor prognosis?
t(9;22)
What fusion gene is created in the t(9;22) form of ALL?
BCR-ABL tyrosine kinase
- Philadelphia +
What is the most common leukemia of adults in the world?
Chronic Lymphocytic Leukemia
What staining can be used on peripheral smear for AML?
MPO
What microscopic feature is found in AML?
Auer rods-> distinctive needle-like azurophilic granules.
What is the average age of onset for AML?
50-60 years of age
What is the translocation that leads to acute promyelocytic leukemia?
t(15;17) that creates a fusion gene encoding a chimeric protein consisting of the retinoid acid receptor.
What is the treatment for acute promyelocytic leukemia?
all-trans retinoid acid or arsenic trioxide.
What is necessary for a diagnosis of AML?
presence of at least 20% myeloid blasts in the bone marrow
What is characteristic of myeloblasts?
delicate nuclear chromatin, two to four nucleoli, and more cytoplasm than lymphoblasts.
What are some clinical features of AML?
- fatigue, fever, spontaneous mucosal and cutaneous bleeding.
- Infections of the oral mucosa, skin, lungs, kidneys, bladder, and colon.
What is the prognosis of AML?
60% obtain complete remission with chemotherapy.
t(15;17)->best prognosis
t(8;21)->good prognosis in absence of KIT mutations.
What are Myelodysplastic syndromes (MDS)?
group of clonal stem cell disorders characterized by maturation defects that are associated with ineffective hematopoiesis and a have a high risk of transformation to AML.
What are the two causes of MDS?
Either primary (idiopathic) or secondary to previous genotoxic drug of radiation therapy.
*Genotoxic drugs have highest rate of transformation to AML
How do patients present with MDS?
Cytopenias, hypercellular bone marrow, increased myeloid blasts.
what is a common abnormality seen in MDS within the erythroid series?
Ring Sideroblasts. Erythroblasts with iron-laden mitochondria visible as perinuclear granules in Prussian blue-stained aspirates or biopsies.
What morphological features can be seen in MDS?
- megaloblastic maturation
- nuclear budding abnormalities
- Pseudo-Pegler-Huet Cells (neutrophils with only two nuclear lobes)
What are the clinical features of MDS?
- primarily affects older people only (>70)
- weakness, infections, hemorrhages
What is the prognosis of MDS?
primary-> 9-29 months
secondary-> 4-8 months
What is a common theme of the Myeloproliferative disorders?
presence of a mutated, constitutively, activated tyrosine kinase.
What are the common features of myeloproliferative disorders?
- increased proliferative drive in the bone marrow
- extramedullary hematopoiesis (splenomegaly)
- marrow fibrosis
- variable transformation to acute leukemia
What is the translocation and mutation that is found in Chronic Myelogenous Leukemia?
t(9;22) BCR-ABL fusion gene that results in a constitutively active tyrosine kinase.
What is the morphology of CML?
- bone marrow is hypercellular (especially basophils)
- scattered macrophages with abundant green-blue cytoplasm (sea-blue histiocytes)
What does the blood count revel in CML?
Leukocytosis with consists of predominantly of neutrophils, band forms, metamyelocytes, myelocytes, eosinophils, and basophils.
What is the average age of onset of CML?
5-6th decade of life
What are the common presenting symptoms in patients with CML?
insidious onset of mild-moderate anemia, hypermetabolism leading to fatigibility, weakness, weight loss, and anorexia.
How is CML best differentiated from other myeloproliferative disorders?
detection of the BCR-ABL fusion gene
What activating mutation is seen in polycythemia vera?
activating point mutations in the tyrosine kinase JAK2
What cells are increased in polycythemia vera?
red cells, granulocytes, and platelets.
*but the increase in red cells is what causes most clinical symptoms.
What are the levels of erythropoietin in primary polycythemia compared to secondary forms of polycythemia?
primary-> low
secondary-> high
What is the level of hematocrit in primary polycythemia vera?
elevated and leads to increased viscosity and sludging
What are patients with PCV at risk for?
prone to both thrombosis and bleeding.
- DVT, MI, Stroke
- budd-chiari syndrome
What is the morphology of PCV?
increase in red cell progenitors as well as an increase in granulocytic precursors and megakaryocytes.
What is the morphology of late phase PCV?
“spent phase” characterized by marrow fibrosis that displaces hematopoietic cells.
-extramedullary hematopoiesis in spleen and liver
What are the clinical symptoms of PCV?
- plethoric and cyanotic
- HA, dizziness, HTN, and GI symptoms
- intense pruritus and peptic ulceration
- hyperuricemia and gout
What mutations are often associated with Essential Thrombocytosis?
JAK2 -50%
MPL- 5/10%
How is essential thrombocytosis separated from PCV and primary myelofibrosis?
absence of polycythemia and marrow fibrosis
What cell types are increased in Essential Thrombocytosis?
Megakaryocytes (large platelets), RBCs and granulocytes are also increased.
What is a characteristic finding of Essential Thrombocytosis?
Erythromelalgia –> burning and throbbing of hands and feet caused by occlusion of small arterioles by platelet aggregation.
- can also be seen in PCV
What is the hallmark finding in Primary Myelofibrosis?
Development of obliterative marrow fibrosis
What does primary myelofibrosis lead to?
extensive extramedullary hematopoiesis and cytopenias
What is the chief pathologic feature of primary myelofibrosis?
Extensive deposition of collagen in the marrow by non-neoplastic fibroblasts
What two growth factors are associated with primary myelofibrosis?
PDGF and TGF-beta
With progression of primary myelofibrosis, what morphological features are seen?
marrow becomes hypocellular and diffusely fibrotic
Marrow distortion in primary myelofibrosis leads to what?
-premature release of of nucleated erythroid and early granulocytic cells progenitor cells (leukoerythroblastosis)
What is the name of the damaged cells that are released into circulation from the fibrotic marrow in primary myelofibrosis?
Tear-drop cells
What are some clinical features of primary myelofibrosis?
left upper quadrant fullness, fatigue, weight loss, night sweats, hyperuricemia and gout
What type of anemia is seen in primary myelofibrosis?
moderate to severe normochromic mocmocytic anemia accompanied by leukoerythroblastosis.
What is a characteristic finding in Langerhans Cells Histiocytosis?
Birbeck granules in the cytoplasm.
Tennis racket like in appearance
What do the tumor cells express in Langerhans Cells Histiocytosis?
HLA-DR, S-100+, CD1a+
What is Letterer-Siwe Disease?
- Malignant proliferation of langerhans cell
- Classic presentation is skin rash and cystic skeletal defects
- <2 YOA
What is Eosinophilic Granuloma?
- Benign proliferation of langerhans cells in bone
- Presents as pathological fractures or multiple erosive bone masses
- affects young children
What is Hand-Schuler-Christian Disease?
-triad of calvarial bone defects, diabetes insidious, and exopthalamus in a child.
What are the most common chromosomal deletions in CLL and SLL?
deltions in 13q14.3, 11q, 17p, and trisomy 12q
What is seen on a blood smear in patients with CLL?
increased lymphocytes and smudge cells
What morphological feature is pathognomonic for CLL/SLL?
- proliferation centers
- small lymphocytes with condensed chromatin and can’t cytoplasm
What cell markers can be found in CLL/SLL?
CD 5,19,20, 23
What are some complications of CLL/SLL?
- Hypogammaglonulinemia–> infections
- Autoimmune hemolytic anemia
What is Richter syndrome?
- Transformation of CLL/SLL to a more aggressive diffuse large B-cell lymphoma.
- Heralded by development of a rapidly enlarging mass within a lymph node or spleen
What is the most common form of indolent NHL in the US?
Follicular Lymphoma
What is the demographics of follicular lymphoma?
- affects middle aged individuals
- men=women
What is the translocation that is associated with follicular lymphoma?
t (14;18) involving the BCL2 gene that inhibits apoptosis
In addition to BCL2, what else is mutated in 90% of cases of follicular lymphoma?
MLL2–> encodes histone methyltransferase that regulates gene expression
What is the morphology of follicular lymphoma?
nodular or nodular to diffuse growth pattern is observed in involved lymph nodes
What two cells can be found in follicular lymphoma?
- Centrocytes: small cleaved cells
- Centroblasts: several nucleoli with modest amounts of cytoplasm
What cell markers are expressed in follicular lymphoma?
CD 10,19,20
How does follicular lymphoma present?
painless generalized lymphadenopathy
What is the most common form of NHL?
Diffuse large B-cell lymphoma (median age 60)
What is a frequent pathological event in DLBCL?
dysregulation of BCL6
What is the morphology of DLBCL?
Large cell size and a diffuse pattern of growth
What cell markers are seen in DLBCL?
CD 19 ,20 with variable expression of CD10 and BCL6
How does DLBCL present?
Rapidly enlarging mass at a nodal or extra nodal site.
What is the prognosis of DLBCLs?
With intensive combination chemotherapy, 60-80% gain complete remission
What translocation is associated with all types of Burkitt Lymphomas?
MYC gene on chromosome 8
- most commomy the t(8;14)
All endemic Burkitt lymphomas as latently infected with what?
EBV
What is the morphology of Burkitt lymphoma?
- high mitotic index and contains numerous apoptotic cells
- “starry sky” pattern due to phagocytes with abundant clear cytoplasm
- royal blue cytoplasm containing clear cytoplasmic vacuoles
What are the cell markers that are present in Burkitt lymphoma?
- CD 10, 19, 20
- surface IgM
- BCL6
What are the common sites affected in the sporadic form and endemic form of Burkitt Lymphoma?
Sporadic-> abdomen
Endemic-> jaw
What is the prognosis of Burkitt Lymphoma?
Responds very well to aggressive chemotherapy
What is multiple myeloma?
Plasma cell neoplasm commonly associated with lytic bone lesions, hypercalcemia, renal failure, ad acquired immune abnormalities.
The proliferation and survival of myeloma cells is most dependent on what cytosine?
IL-6
- high levels are associated with a poor prognosis
What activates osteoclasts activity in multiple myeloma?
MIP1 alpha upregualtes expression of NF-kappaB ligand (RANKL) resulting in increased osteoclast activity
What are the most commonly involved bones in multiple myeloma and how do they appear?
vertebral column, ribs, skull, pelvis, femur
punched-out defects
What is the Rouleaux formation?
RBCs stick together in a linear pattern
What is excreted in the urine in multiple myeloma?
- free light chains are excreted in the urine as Bence Jones proteins.
- Deposition in the kidney tubules leads to risk for renal failure
What cell marker is present in multiple myeloma?
CD 138
What are the clinical features of multiple myeloma?
pathological fractures, hypercalcemia, bone pain
What is the elevated serum protein in multiple myeloma show up as?
“M spike” that is present on serum protein electrophoresis (SPEP).
Most commonly due to monoclonal IgG for IgA
What is the most common plasma cell dycrasias?
monoclonal gammopathy of uncertain significance (MGUS)
1% will develop multiple myeloma
What age population does MGUS affect?
3% >50
5%>70
What is the common translocation that is associated with mantel cell lymphoma?
t(11;14) involving the IgH locus on chr 14 and cyclin D1 on chr 11
What does cyclin D1 promote in mantel cell lymphoma?
G1-S transition in mitosis
What do a majority of patients present with at diagnosis of mantel cell lymphoma?
generalized painless lymphadenopathy
What cell markers can be found in mantel cell lymphoma?
CD 5,19, 20
*CD23- which helps distinguish it from CLL/SLL
What is the prognosis of mantel cell lymphoma?
poor; 3-4 year survival
What are marginal cell lymphomas associated with?
- chronic inflammation: sjogrens, Hashimoto thyroiditis, helicobacter gastritis
- remain localized until late in course
- regress if inciting agent is removed (H. pylori removed MALToma risk back to 0)
What mutations are seen in over 90% of Hairy Cell Leukemias?
BRAF mutations- a serine/threonine kinase
What is the morphology of Hairy Cell Leukemia?
Fine hairlike projections with round, oblong, or reniform nuclei with moderate amounts of pale blue cytoplasm,
What are the cell markers that are seen in Hairy Cell Leukemia?
CD 19,20
CD11c, 25, 103, annexin A1
What is the most common clinical feature of Hairy Cell Leukemia?
- Splenomegaly
- some patients will have pancytopenia
What is the prognosis of Hairy Cell Leukemia?
- very sensitive to chemotherapy although the tumors tend to return.
- respond well to same drug on second chemo course
What is characteristic of Peripheral T-cell Lymphoma, Unspecified?
Tumors are composed of a pleomorphic mixture of variably sized T cells.
How do patients present with Peripheral T-cell Lymphoma, Unspecified?
Generalized lymphadenopathy, sometimes accompanied by eosinophilia, pruritus, fever, and weight loss.
What is Anapestic Large-Cell lymphoma defined by?
uncommon entity defined by presence of rearrangement of the ALK gene on chromosome 2p23
What cells are found in Anapestic Large-Cell lymphoma?
“hallmark cells” with horseshoe shaped nuclei
What neoplasm is associated with HTLV-1?
Adult T-cell leukemia/lymphoma- neoplasm of CD4+ cells
Where is Adult T-cell leukemia/ lymphoma most commonly occur?
southern japan, west africa, and the caribbean
What are the common findings in Adult T-cell leukemia/ lymphoma?
Skin lesions, generalized lymphadenopathy, HSM, hypercalcemia
What is Mycosis Fungoides?
manifestations of a tumor of CD4+ helper T cells that home to the skin
Histologically, where do the CD4 T cells localized in Mycosis Fungoides?
Epidermis and upper dermis and have a cerebriform appearance
What is Sezary syndrome?
variant in which skin involvement is manifested as a generalized exfoliative erythroderma.
What is a difference seen morphologically between B cell and T cells?
T cells tend to have more cytoplasm than B cells and larger nuclei
What translocation has a favorable prognosis in CML but a unfavorable prognosis in ALL?
t(9;22)
What is the most common form of indolent NHL in the US?
Follicular Lymphoma
Where do HL arise and how does it spread?
Arises in a single node or chain of nodes and spreads first to anatomically contiguous lymphoid tissue.
Waldeyer ring and mesenteric node involvement is characteristic of HL or NHL?
NHL
What is the neoplastic cell found in HL?
Reed-Sternburg Cells
Average age of diagnosis of HL?
32
What CD marker are Reed-Sternburg Cells positive for?
CD 15, CD 30, PAX 5
Activation of what transcription factor is a common event in classical HL?
NF-kappaB
*EBV can active this via LMP-1
What is the morphology of a Reed-Sternburg Cell?
- multiolobed nuclei with prominent nucleoli.
- can appear “owl eyed”
What type of cells are seen in the nodular sclerosing type of HL?
Lacunar cells- delicate, folded, or multilobate nuclei and abundant pale cytoplasm.
What type of cells are seen in the lymphocyte predominance subtype of HL?
Lymphohistiocytic variant- polyploid nuclei, inconscpicious nucleoli, and moderately abundant cytoplasm.
What is the most common form of HL?
Nodular Sclerosing type
- deposition of collagen in bands that divide the LN into circumscribed nodules
- uncommonly associated with EBV
What types of HL have a strong association with EBV?
Mixed-Cellularity type -70%
Lymphocytic Depletion type -90%
Who is affected most commonly by the mixed-cellularity type of HL?
men, older age, and systemic symptoms (night sweats)
What is the morphology of the Lymphocyte-Rich type of HL?
Reactive lymphocytes make up the vast majority of cellular infiltrate.
Who is affected by lymphocyte depletion HL?
Older adults, HIV+ individuals, nonindustralized countries.
What is the “nonclassical” type of HL?
Lymphocyte Predominance Type
What is the morphology of Lymphocyte Predominace type of HL?
-Reed-Sternburg cells are difficult to find.
- Nodes are effaced by nodular infiltrate of small lymphocytes admixed with variable numbers of macrophages.
- Eosiniphils and plasma cells are absent
Who is most commonly affected by the L&H variant of HL?
35 y/o male with cervical or axillary lymphadenopathy.
How does HL most commonly present?
painless lymphadenopathy
What is the predicted pattern of HL spread?
nodal disease–> splenic diseae–> hepatic disease–> marrow involvemt.
What cell markers are expressed by the lymphocyte predominate type of HL?
CD 20+
*CD15, CD30-, EBV -
What is a common presenting symptom in HL?
Fever related to release of cytokines
What type of lymphoma is associated with KSHV/HHV-8?
Primary Effusion Lymphoma
What is associated with Immunodeficiency-assoacited large B-cell lymphoma?
EBV
Waldeyer ring is frequently involved in what cancer?
DLBCL
What is characteristic of Lymphoplasmacytic lymphoma?
- No bone destruction, or secretion of Ig light chains.
- Most commonly a monoclonal IgM is secreted
- 6th-7th decade of life
- Hyperviscosity
