Pathology of White Blood Cells, Lymph Nodes, Spleen, and Thymus (Part 2 of 4) Flashcards
What are the three categories of White cell neoplasia?
lymphoid neoplasia, myeloid neoplasia, and histiocytic neoplasia
what are the five broad types of lymphoid neoplasia?
B-cell, T-cell, Plasma cell, Hodgkin, NK cell
what are the 3 types of myeloid neoplasia?
Acute myeloid leukemia, myelodysplasia, myeloproliferative neoplasia
what is an example of histiocytic neoplasia?
Langerhans Cell histiocytosis
what viral infections are common contributors to white cell neoplasms? (3)
HTLV-1, EBV, HHV-8
what chronic bacterial infection is a common contributor to white cell neoplasms?
H. pylori infections
what is the difference between leukemia and lymphoma?
leukemia involves the bone marrow/blood and lymphoma involves the lymph nodes
what is the most common cancer in kids?
acute lymphoblastic leukemia
how does ALL present?/ symptoms (6)
sudden onset of symptoms/ fever, fatigue, bleeding/bruising, pain, headache, n/v
What occurs in acute lymphoblastic leukemia (ALL)?
there are mutations to lymphoid stem cells to create a “leukemic stem cell” with self renewal capacity and simultaneous maturation arrest–> the lymphoid stem cells are shunted to form lymphoblasts
what might happen if the bone marrow is densely “packed” with leukemic cells?
they may not aspirate “sludgy”
why do you see a fever in ALL?
you’ve wiped out the granulocytes/neutrophils and there is an opportunistic infection
why do you see fatigue in ALL patients?
they are very anemic
why do you see bleeding/bruising in ALL patients?
they have no platelets
why do patients with ALL experience pain?
there is expansion of the leukemic cells inside their bone marrow
why do patients with ALL experience headaches, nausea/vomiting?
there are CNS manifestations bc these leukemia will go to the CNS- so there can actually be meningeal involvement
What is the morphology of ALL cells?
large cells, dark nuclear chromatin, inconspicuous nucleoli, scant agranular cytoplasm
When trying to diagnose a patient with ALL, what would you look for on flow cytometry?
TdT: if positive you can identify that these are prolymphocytes; because either B cells or T cells can have ALL, you need to determine whether it is a B cell or a T cell ALL; B-cell: CD 19, CD20, CD10, Pax-5; T cell: CD1-5, CD7, and CD8
what is the general treatment for ALL?
chemotherapy, intrathecal chemotherapy
who has a better prognosis when diagnosed with ALL? (4)
age 2-10, low peripheral WBC count, hyperdiploidy, t(12;21)
who has a worse prognosis when diagnosed with ALL? (3)
age <2, adolescence/adulthood, high WBC count (>100K)
what is the common demographic for chronic lymphocytic/small lymphocytic lymphoma (CLL//SLL)?
patients are typically older and may be asymptomatic or fatigued
what does a typical peripheral smear show in a patient with CLL/SLL?
lymphocytosis with small mature lymphocytes; smudge cells may be seen
what are the particular features that present in CLL/SLL? (think flow cytometry)
By flow, a clonal (kappa-restricted) population of CD19, CD5+ cells
what is the aggressive phenomena associated with CLL/SLL?
richter transformation
what drives the transformation of CLL/SLL into an aggressive tumor?
new mutations involving TP53 or MYC
what is follicular lymphoma?
a pattern of neoplastic lymphocytes that expand from the follicle center (germinal center)
what does follicular lymphoma resemble and what does this mean?
resembles follicular hyperplasia; so further testing is needed
what are the vast majority of follicular lymphomas associated with? (translocation wise)
a classic translocation: t(14;18)
what does the translocation (14;18) do?
places an IgH gene next to a BCL-2
what is bcl-2?
an apoptosis suppressor
what happens when bcl-2 is placed next to IgH?
there is overexpression of bcl-2- so you get less apoptosis- you have now enabled IgH to drive a neoplastic process
how can you stain for something you think is follicular lymphoma?
there will be a positive brown staining for bcl-2
How is follicular lymphoma graded?
graded from 1-3; higher grades correlate with higher proportion of large centroblasts
what is grade 3 follicular lymphoma related to?
diffuse large B cell lymphoma
what is diffuse large b cell lymphoma?
when large masses form in the lymph nodes or in organs like the spleen; aggressive and fast growing
what are the two different types of diffuse large b cell lymphomas?
immunodeficiency-related LCL and primary effusion lymphoma
what are immunodeficiency-related LCLs linked to?
EBV activation
what is primary effusion lymphoma associated with and where does it occur?
associated with HHV-8 and it occurs in plural fluid
what somatic mutation is associated with DLBCLs?
BCL-6
what is the classic morphology of Burkitt lymphoma?
the neoplasm is a B cell neoplasm and it grows in this diffuse sheet
what is the cellular composition in Burkitt lymphoma?
diffuse growth of intermediate-sized cells with numerous tingible body macrophages
what translocation is associated with Burkitt lymphoma?
8;14 translocation (IgH/MYC)
what occurs in an 8;14 translocation?
it allows for an upregulated MYC oncogene to be immediately adjacent to IgH
what marker can be used when trying to diagnose Burkitt lymphoma?
Ki-67 proliferation marker
what are the three different types of Burkitt lymphoma?
endemic african burkitt lymphoma, sporadic, and HIV-related
what is the endemic african burkitt lymphoma associated with??
EBV; mandibular and maxillary growth
what is mantle cell lymphoma?
malignancy of B cells resembling those in the mantle layer
what translocation is associated with mantle cell lymphoma?
t(11;14)
what occurs in the translocation 11;14?
places an IgH next to cyclin D1
what is the driver for mantle cell lymphoma?
cyclin D1
what can you stain for to make the diagnosis of mantle cell lymphoma?
an immunostain for cyclin D1
where can marginal zone lymphomas arise?
in LNs or in extranodal sites (MALT-omas)
what are extranodal MALTomas associated with?
chronic inflammation
what is a gastric maltoma associated with?
H pylori infection
what can hashimoto thyroiditis result in?
mantle zone lymphoma of the thyroid
what can be associated with salivary gland marginal zone lymphoma?
chronic sialadenitis
what does the bone marrow look like in a patient with hairy cell leukemia?
back-to-back cells; the hairy cytoplasm keeps a distance between cells
what effect does hairy cell leukemia have on the bone marrow?
it creates reticulin fibrosis, which can lead to a dry tap on bone marrow aspiration- so patients with hairy cell leukemia have low blood counts
what is a common side effect of hairy cell leukemia?
splenic involvement is very striking with typical massive splenomegaly
what are the markers for hairy cell leukemia?
CD25 and CD11c
CLL/SLL will show particular features; what is an interesting marker that you can see in association with this particular neoplasm?
CD5
How can you differentiate between follicular lymphoma and follicular hyperplasia?
flow cytometry isn’t a bad idea, but there is something more commonly done: genetic testing for translocation 14;18
what is the purpose of tingible-body macrophages?
they clear apoptotic debris due to the extreme cell turn over
What do patients with hairy cell leukemia present with?
splenomegaly but mostly pancytopenia
what can flow cytometry demonstrate?
clonality and light chain restriction
