WBC Hematopathology Part 2 Flashcards
Peripheral T-cell tumors are what % of NHL’s in US and Asia?
5-10%
Peripheral T cell and NK cell tumors are most common where?
In Far East
How do nodes appear in peripheral T cell neoplasms?
Diffuse effacement of nodal architecture
Markers for T-cell neoplasms? 2
- Pan-T Markers (CD2/3/5)
2. CD4 or CD8 possibly
What defines a T-cell malignancy?
Clonal T-cell receptor gene rearrangements
How do T cell neoplasms generally present? (5)
Disseminated adenopathy Eosinophilia pruritis Fever Weight loss
How do T cell neoplasms respond to therapy?
Respond poorly due to being so aggressive
5 Peripheral T cell neoplasms?
- Anaplastic large cell lymphoma
- Adult T-cell leukemia/Lymphoma
- Mycosis Fungoides and Sezary Syndrome
- Large Granular Lymphocytic Leukemia
- Extranodal NK/T-Cell lymphoma
Anaplastic Large Cell lymphoma has what rearrangement?
This produces what?
Rearrangement of ALK gene on chromosome 2p23
Active tyrosine kinases
What is the hallmark cell in Anaplastic Large Cell lymphoma
Large, anaplastic cells
What does Anaplastic Large Cell lymphoma’s lymph node pattern mimic? (2)
- Metastatic carcinoma
2. Hodgkin lymphoma variants
Anaplastic Large Cell lymphoma with ALK rearrangement are seen in what population?
What is prognosis?
Kids
Good prognosis
Anaplastic Large Cell lymphoma without ALK rearrangement is seen in what population?
What is prognosis?
Older adults
Worse prognosis
Adult T-cell leukemia/lymphoma is seen in adults infected with what?
Retrovirus HTLV-1
Where is HTLV-1 seen in the world? 3
Japan
West Africa
Caribbean
Clinical findings in Adult T-cell leukemia/lymphoma? 4
- Skin lesions
- Hypercalcemia
- Hepatosplenomegaly
- Elevated WBC count with multilobulated CD4’s
Prognosis of Adult T-cell leukemia/lymphoma?
Less than a year, extremely aggressive
Mycosis Fungoides and Sezary syndrome are two manifestations of what?
What are the hallmark cells involved?
Cutaneous T-cell lymphoma
Peripheral CD4 T cells wth a crebriform appearance
How does Mycosis FUnoides present as?
Where do the T cells go?
Inflammatory pre-mycotic phase and progresses through a plaque phase to a tumor phase.
infiltrate skin
Sezary syndrome has what main presentation?
What is prognosis?
Generalized exfoliative erythroderma
Incurable but long survival
Large granular lymphocytic leukemia is seen how?
What population mainly has it?
What organs does it avoid?
With granules which is strange for lymphocytes
Adults
Lymph nodes and liver
Hallmark of Large granular lymphocytic leukemia?
Lymphocytes in peripheral blood and BM with blue cytoplasm and scattered azurophilic granules
Two symptoms of Large granular lymphocytic leukemia?
Neutropenia
Anemia
Two variants of Large granular lymphocytic leukemia
Which is more severe?
Which has splenomegaly and lymphocytosis?
T cell: Mild/Lymphocytosis + Splenomegaly
NK Cell: Aggressive
What are the five subtypes of hodgkin lymphomas?
– Nodular sclerosis – Mixed cellularity – Lymphocyte-rich – Lymphocyte depletion (rare) – Lymphocyte predominance (LP)
Which of the hodgkin subtypes are classical hodgkin lymphoma?
First four (not LP) since the R-S cells have similar immunophenotype
What makes LP different from other hodgkin subtypes?
Malignant cells express a different B-cell phenotype (CD20, CD15 and CD30 -)
Hodgkin lymphoma neoplasm is located where in body?
What virus causes some of these?
Prognosis
Best prognosis indicator?
Germinal center or post-germinal center B lymphocytes
EBV
Very good
Clinical stage is great indicator
Side effects of chemo/radiotherapy against Hodgkin lymphoma?
- Myelodysplasia
- Acute leukemia
- Lung cancer
- Melanoma
- breast cancer
- Gastric cancer
- NHL
How does one avoid the cancers caused by chemo and radiotherapy?
Use new drug combinations and less of the drugs
What is Stage I Hodgkin?
Involvement of single lymph node region or single extra-nodal site
Stage II hodgkin?
Two or more lymph node regions (or extranodal sites) on same side of diagphragm
Stage III Hodgkin’s
Involvement of lymph node regions on both sides of the diaphragm.
May include spleen or localized extranodal disease
Stage IV Hodgkin’s
Diffuse extralymphatic disease in liver BM, lung, skin
Most common Hodgkin subtype?
Nodular sclerosis
Nodular sclersosis is what % of HL?
Difference in sexes?
65-70%
Sexes are equal
What are the two histo signs of nodular sclerosis?
Lacunar cells
Bands of collagen fibrosis
R-S cells in nodular sclerosis have what markers?
- Positive for CD15 and CD30
2. Negative for CD45 and other B and T markers
Age of nodular sclerosis patients?
- young adults
Mixed cellularity hodgkin lymphoma is the most common form of HL in what group of patients?
Sex difference?
Males older than 50
Immunophenotype of mixed cellularity hodgkin?
Same as Nodular
- Positive for CD15 and CD30
- Negative for CD45 and other B and T markers
Patients with mixed cellularity hodgkin are more likely to present how?
Prognosis
Advanced disseminated disease
Prognosis remains really good
RS cells in mixed cellularity hodgkin contain what at 70%?
EBV
Lymphocyte-Rich hodgkin lymphoma has what cell predominate?
Reactive lymphocytes
How to distinguish between Lymphocyte Rich and Lymphocyte Predominance?
Lymphocyte Rich has frequent mononuclear R-S cells of characteristic HL immunophenotype
Lymphocyte-Rich hodgkin lymphoma is associated with what virus at 40%
EBV
Prognosis of Lymphocyte-Rich HL?
Very good to excellent prognosis
What is the least common form of hodgkin lymphoma?
Lymphocyte Depletion
What cells are low in Lymphocyte-Depletion?
Which are high?
What is immunotype for these cells?
Few lymphocytes
Abudant R-S cell variants
HL immunotype
Age and patient group of Lymphocyte depletion HL?
Elderly
HIV-positive
EBV positive in what % of Lymphocyte depletion HL?
90%
What is prognosis in Lymphocyte depletion HL?
Less favorable
Lymphocyte predominance HL is what patient group?
Males younger than 35
Lymphocyte predominance HL is characterized by what cells? Other cells (2)
Lymphohistiocytic variant cells/Popcorn cells
Reactive lymphocytes and histiocytes
Are RS cells present in Lymphocyte predominance HL?
Yes, but very rare
L and H cells have what markers? (4)
What does this mean?
- Positive for CD20 and BCL6 (b cell lymphoma characteristic)
- Negative for CD15 and CD30 (RS cells)
This is really a B-cell lymphoma
Is LP associated with EBV?
No
three major categories of myeloid neoplasms?
Acute myeloid leukemias
Myelodysplastic Syndromes
Myeloproliferative disorders
What is AML?
blockage in differentiation of early myeloid cells which causes blasts to accumulate in BM and then circulate in peripheral blood
What is Myelodysplastic syndrome?
Terminal differentiation of early myeloid cells occurs but is disordered and ineffective
How is MDS marked?
Presence of dysplastic marrow precursors and peripheral blood cytopenias
What is a myeloproliferative disorder?
Neoplastic clone retains capacity to undergo terminal differentiation with dysregulated goal.
Myeloproliferative disorders result in what peripheral blood?
Increased RBC’s, WBC’s and platelets
Acute myeloid leukemia is due to what?
Acquired oncogenic mutation blocking normal cell differentiation –> Accumulation of myeloblasts in marrow
AML leads to what?
Which appears how (3)
Marrow failure
Anemia, thrombocytopenia, neutropenia
Acute Myeloid Leukemia occurs when?
What age most?
All ages
Peaks after 60
Acute myeloid leukemia signs and symptoms resemble what?
Related to what?
Acute lymphoblastic leukemia
Splenomegaly and lymphadenopathy
How might AML rarely prsent?
Infiltration of what suggests monocytic types?
Discrete tissue mass like a sarcoma or myeloid tumor
Infiltration of skin and gingiva
Diagnosis of AML
What is done first?
What is the key diagnostic finding?
Karyotypic findings
Greater than 20% myeloblasts in BM
Cytogenetic abberations in AML? (2)
- Disrupt genes encoding TF’s for normal differentiation
2. Activate mutated tyrosine kinases –> Constant proliferation signals
The M3 AML affects what population most?
What does it progresss to?
Chromosomal abnormality?
Genes involved?
Younger people
DIC
t(15;17)(q22:q21)
PMU/RARA
What stains do you do for AML? 3
- Myeloperoxidase (myelocytic)
- Specific esterase (myelocytic)
- Nonspecific esterase (monocytic)
Markers of AML? 4
CD13
CD14
CD15
CD33
What are the WHO classifications of AML? 4
- AML with particular genetic abnormalities
- AML with MDS-like features
- AML, therapy related
- AML not otherwise specified
AML has what particular genetic abnormalities?
t(8;21)
inv(16)
t(15;17)