Hematopathology - Cancer Flashcards
In a patient with leukocytosis and neutrophilia, how can you distinguish Leukemoid Reaction versus Leukemia – how do the following differ in LR?
1) Peripheral blood smear
2) What enzyme has a high activity in LR?
3) What is found in cytoplasm of neutrophils in LR?
Leukemoid Reaction
1) Peripheral blood smear shows more mature cells
2) Leukocyte alkaline phosphatase activity is high
3) Neutrophils contain “Dohle bodies” or “toxic granulation” in cytoplasm
This neoplasm’s blood smear features mature and maturing granulocytes, myelocytes, basophils, and occasional myeloblasts.
The BM is hypercellular (image below) and dominated by WBC precursors. Megakaryocytes are numerous; RBC precursors are less prominent.
Cytogenetic studies reveal t(9;22)
Chronic Myelogenous Leukemia
CML is derived from an abnormal pluripotent BM stem cell and results in prominent neutrophilic leukocytosis over the full range of myeloid maturation.
[image displays granulocyte precursors in BM aspirate]
Diagnostic features of this disease include a low EPO level, a JAK2 mutation, or endogenous erythroid colony (EEC) formation.
The BM is hypercellular, with hyperplasia of all elements: erythroid, granulocytic, and megakaryocytic. BM iron is depleted.
It generally occurs at ~age 60, and patients are at risk of developing strokes due to hyperviscosity.
Polycythemia Vera
“a myeloproliferative neoplasm characterized by autonomous production of RBCs, not regulated by EPO”
In this neoplasm, marrow fibrosis is accompanied by megakaryopoiesis and granulopoiesis.
Transformation to AML occurs in ~15% of cases.
[top] - peripheral smear shows teardrop cells (arrow)
[bottom] - BM fibrosis
Primary Myelofibrosis aka Chronic Idiopathic Myelofibrosis
This neoplasm is characterized by uncontrolled proliferation of megakaryocytes, an increase in circulating platelets, and recurrent episodes of thrombosis and mild hemorrhage.
The BM is hypercellular, with decreased fat cells and lots of large, hyperlobulated, “stag-horn” shaped megakaryocytes. (image)
Essential Thrombocythemia
This disorder is characterized by an abnormal accumulation of mast cells in certain tissues, mainly the skin and bone marrow.
Patients suffer from anaphylactic episodes (pruritis, flushing, asthma symptoms), GI pain, and diarrhea due to overproduction of mediators produced by mast cells.
Serum tryptase levels are elevated.
Mastocytosis
(cutaneous mastocytosis)
(systemic mastocytosis)
(mast cell leukemia)
[image: lymph node shows sheets of mast cells]
These neoplasms present with symptoms related to pancytopenia: weakness (anemia), infections (neutropenia), and bleeding (thrombocytopenia).
Common histo findings (image) include ringed sideroblasts (iron-laded mitochondrias surrounding nuclei, left) and dysplastic megakaryocytes with nuclear separation (right).
Myelodysplastic Syndromes
MDS are clonal disorders that cause ineffective hematopoiesis.
Progression to AML is common.
Image below shows dysplastic, multinucleated megaloblastoid RBC precursors.
Patients with this neoplasm present with bleeding or purpura (thrombocytopenia), fatigue (anemia), and granulocytopenia.
Frequently, they present with symptoms or lab values suggesting DIC.
A key histo finding is the presenec of Auer rods in the cytoplasm (image).
The BM is usually hypercellular.
The underlying genetic defect is a translocation between 15 (PML) and 17 (RAR).
Acute Myelogenous Leukemia
Accumulation of myeloblasts (which lack potential for maturation) in BM leads to suppression of normal hematopoiesis.
The DIC is due to senescent leukemic cells degranulating and activating the coagulation cascade.
Image displays hypercellular bone marrow with myeloblasts displacing normal hematopoietic cells.
(Acute Promyelocytic Leukemia)
A young child presents with constitutional symptoms; physical exam reveals bone pain and arthralgias. Labs disclose anemia, thrombocytopenia, and leukocytosis.
The WBC differential shows 90% blasts, and BM biopsy with immunohistochemical staining is positive for TdT.
In the peripheral smear, lymphoblasts have indented nuclei, fine nuclear chromatin, and agranular cytoplasm.
B-Cell Acute Lymphoblastic Leukemia/Lymphoma
Most common childhood leukemia.
Leukemic cells proliferate in BM and displace normal elements, producing anemia, thrombocytopenia, and neutropenia.
Rapidly growing tumor cells in BM cause bone pain and arthralgias.
TdT, CD10, and CD19 are common immunophenotypic patterns.
Site of lymphoblast proliferation:
bone marrow or blood –> leukemia
lymph nodes –> lymphoma
This neoplasm usually occurs in an adolescent male and features mediastinal adenopathy. Patients sometimes present with a respiratory emergency due to compression of central airways.
Lymphoblasts will be positive for Tdt.
T-cell Acute Lymphoblastic Leukemia/Lymphoma
WBC is high, and a mediastinal mass is often present.
Rapid growth of tumor in mediastinum causes pleural effusions or other respiratory emergencies.
Name the neoplasm.
Genetics
t(11;14)
Pathology
1) lymphoma cells are all very similar in size & shape
2) scattered epithelioid histiocytes and hyalinized small blood vessels are present
Immunophenotype is positive for cyclin D1
Affects adults at age ~60; mostly males
Mantle Cell Lymphoma
Name the neoplasm.
Patients most often present with rapidly growing tumor in lymph node or extranodal sites, often in the GI tract.
Symptoms relate to site of tumor (eg, bowel obstruction or perforation).
Frequently associated with immunodeficiency: HIV, EBV.
Pathology: sheets of large lymphoma cells with prominent nucleoli
Immunophenotyping is NEGATIVE for TdT, cyclin D1.
Diffuse Large B-Cell Lymphoma
Name the neoplasm.
t(8;24) which involves MYC oncogene
Various clinical presentations:
1) deformities of jaw or facial bones, EBV-positive
2) abdominal mass involving ileocecum
3) occurrence in HIV-infected person
Pathology:
1) BM aspirate shows lipid vacuoles in deeply basophilic cytoplasm of tumor cells (image below)
2) lymph node displays neoplastic lymphocytes with “starry-sky” macrophages (next image)
Burkitt Lymphoma
Endemic form
-jaw, facial bones, EBV-positive
Sporadic form
-abdominal masses
Immunodeficiency-associated form
-HIV
Name the neoplasm.
t(14;18) involving Ig heavy chain (IgH) gene on 14 and BCL2 gene on 18
(staining will be positive for Bcl-2, see inset in image)
Common presentation is generalized lymphadenopathy – painless with waxing & waning course.
Pathology: neoplastic follicles are densely packed with back-to-back arrangement (image below)
Follicular Lymphoma
Name the neoplasm.
Most common leukemia in adults in Western world.
Peripheral blood (image) displays small lymphocytes + prominent “smudge cells.” Nuclear chromatin is clumped, resembles cracked mud.
Leukemic cells often show Ig gene rearrangements.
Gross observation of lymph node reveals a uniform, glistening, fish-flesh appearance (next image)
B-Cell Chronic Lymphocytic Leukemia / Small Lymphocytic Leukemia
CLL: disease is found in blood + BM
SLL: tumor cells give rise to lymphadenopathy or solid tumor masses
A patient with B-Cell CLL/SLL presents with rapid onset of fever, abdominal pain, and progressive lymphadenopathy and hepatosplenomegaly.
Cytopenias are worsened, and there is a progressive increase of prolymphocytes in peripheral blood or paraimmunoblasts in lymph nodes.
Serum LDH is high.
What is occurring?
Richter transformation/syndrome
Transformation of B-cell CLL/SLL into a large cell lymphoma.
Name the neoplasm.
Commonly arises in context of a chronic inflammatory process or autoimmune disease.
Most often involve the stomach or other mucosal sites, including the respiratory tract. Tumor cells invade glandular or mucosal epithelium, resulting in characteristic lymphoepithelial lesions (image).
Marginal Zone Lymphoma (MALT lymphoma)
Mucosal-Associated Lymphoid Tissue
Prototypical MALT lymphoma is a gastric lymphoma associated with H. pylori gastritis
Name the neoplasm.
Most often occurs in adults, in 5th to 6th decades
Lymph node biopsy reveals small lymphocytes and plasmacytoid lymphocytes containing Dutcher and Russell bodies.
Immunohistochemical staining demonstrates cytoplasmic accumulation of IgM.
Increased blood viscosity may be associated with visual impairment, neurological problems, bleeding, and cryoglobulinemia.
Waldenstrom macroglobulinemia
(Lymphoplasmacytic Lymphoma)
Patients with this neoplasm – typically, middle-aged or elderly men – present with splenomegaly, leukopenia, and monocytopenia or pancytopenia.
Histologically, affected lymphocytes display clear cytoplasm, which gives them a “fried-egg” appearance (below), and hair-like protrusions of the cell membrane (next image).
Neoplastic cells are positive for tartrate-resistant acid phosphatase.
Hairy Cell Leukemia
This neoplasm is primarily bone marrow based, associated with M-protein, and produces multifocal lytic bone lesions throughout the skeleton that have a “punched out” appearance radiographically.
Clonal rearrangement of the Ig light & heavy chains in present, and light-chain proteinuria can result in renal failure.
The M-protein can suppress normal Ig production, leading to infection. M-protein also causes peripheral RBC cells to stick together, end-on-end like a stack of coins (Rouleaux formation).
Characteristic symtpoms are CRAB: hyperCalcemia, Renal insufficiency, Anemia, and Bone lesions.
Plasma Cell Myeloma (Multiple Myeloma)
Overview of pathogenesis of Plasma Cell Myeloma (Multiple Myeloma)
What does CRAB stand for?
Plasma Cell Myeloma (Multiple Myeloma)
C: hypercalcemia
R: renal failure
A: anemia
B: bone lesions
This condition is defined by:
1) presence of M-protein of less than 3.0g/dL
2) fewer than 10% plasma cells in BM
3) lack of end-organ damage (ie, lack of CRAB)
4) exclusion of other B-cell neoplasms that produce M-protein
It’s very common – 3% older than age 50, and 5% older than age 70 have this condition.
Monoclonal Gammopathy of Undetermined Significance (MGUS)
*lack of CRAB is key distinction
This neoplasm is caused by HTLV-1, and is endemic in southwestern Japan, the Caribbean basin, and parts of Central Africa.
There are systemic manifestations, which commonly include hypercalcemia and skin involvement.
Neoplastic lymphoid cells display prominent nuclear convolutions and lobations – “flower cells”.
Tumor cells are positive for HTLV-1 and show a clonal T-cell receptor gene rearrangement pattern.
Adult T-Cell Leukemia/Lymphoma
HTLV-1 = human T cell leukemia virus type 1
This neoplasm is a common cutaneous T cell lymphoma. It is characterized by infiltration of the epidermis with malignant CD4+ T cells.
Peripheral blood smears may show Sezary cells, which are circulating lymphoma cells that display “cerebriform nuclei”. (image)
Sometimes, intraepidermal accumulations of tumor cells (Pautrier microabscesses) may be present.
It often presents as Sezary syndrome:
1) erythroderma
2) generalized lymphadenopathy
3) presence of Sezary cells in the peripheral blood
Mycosis Fungoides
Name the neoplasm.
t(2;5) involving ALK gene on chromosome 2, and NPM gene on chromosome 5
Key pathologic finding is cells with horseshoe or kidney shaped nuclei and a distinct eosinophilic area near the nucleus. These are known as “hallmark cells,” and they are positive for CD30. (image)
Anaplastic Large Cell Lymphoma
t(2;5)
Chromosome 2: ALK = anaplastic lymphoma kinase gene
Chromosome 5: NPM = nucleophosmin gene
Clinical findings of this neoplasm include constitutional symptoms and a nontender peripheral adenopathy.
It is a B-cell neoplasm composed of large atypical mononuclear or multinucleated tumor cells – called Reed-Sternberg cells – in an inflammatory background of small lymphocytes, plasma cells, bland histiocytes, and eosinophils. Reed-Sternberg cells are a diagnostic hallmark. (image)
Hodgkin’s Lymphoma
Hodgkin’s Lymphoma can be divided into 4 subtypes.
What is the name of the most common subtype?
It is characterized by a fibrous thickening of the lymph node capsule, with bands of sclerosis extending from the capsule into the nodal cortex. (image)
Lacunar cells, a retraction artifact, are a common histological finding. (next image)
Nodular Sclerosis subtype of Hodgkin’s Lymphoma
In the image below:
double arrow = Reed-Sternberg cells
arrowhead = eosinophils
arrow = Lacunar cells
(Rubin’s, p. 1026)
Match each subtype of Hodgkin’s Lymphoma with its descriptor…
- Mixed Cellularity Hodgkin Lymphoma (MCHL)
- Lymphocyte-Rich Hodgkin Lymphoma
- Lymphocyte-Depleted Hodgkin Lymphoma
A) associated with HIV infection; marked absence of background lymphocytes
B) lacks nodular fibrosis; most frequent subtype in HIV1 infected patients
C) inflammatory infiltrate lacks eosinophils, neutrophils, and sclerosis
less common Hodgkin Lymphoma subtypes
- Mixed Cellularity Hodgkin Lymphoma
(B) lacks nodular fibrosis; most frequent subtype in HIV1 infected patients - Lymphocyte-Rich Hodgkin Lymphoma
(C) inflammatory infiltrate lacks eosinophils, neutrophils, and sclerosis - Lymphocyte-Depleted Hodgkin Lymphoma
(A) associated with HIV infection; marked absence of background lymphocytes
This neoplasm occurs in individuals who are immunosuppressed as a result of being a recipient of an organ, bone marrow, or stem cell allograft.
The pathogenesis is usually rooted in EBV infection.
Image: diffuse proliferation of large lymphoid cells with clonal Ig gene rearrangement; the insert displays neoplastic lymphocytes staining positive for EBV
Posttransplant Lymphoproliferative Disorders
This neoplasm usually occurs in children, and clinical manifestations of this neoplasm include:
The classic triad of…
1) diabetes insipidus (increased urination)
2) exopthalmos
3) membranous bone pain (eg, skull)
…and other common symptoms such as…
4) dermatitis
Histological findings include accumulation of neoplastic cells in an environment containing eosinophils, histiocytes, and small lymphocytes. Electron microscopy shows Birbeck granules.
Langerhans Cell Histiocytosis
Image: large Langerhans cells and numerous eosinophils; inset shows a Birbeck granule, which is a rod-shaped cytoplasmic inclusion with a dense core and double outer sheath
