37 - Pathology of WBCs II Flashcards
We have finished B cell…
Now moving onto T cell lymphomas
Mature (peripheral) lymphoid neoplasms
- T cell lymphomas (adult T-cell leukemia/lymphoma, mycosis fungoides/Sezary syndrome)
Immature (precursor) T cell neoplasms
- T lymphoblastic leukemia/lymphoma
- Anaplastic large T cell lymphoma
Describe adult T-cell leukemia/lymphoma
- MATURE T cell neoplasm ***
- Caused by the HTLV-1 human retrovirus (Human T-cell Leukemia virus type 1)
- Commonly seen in Central Africa, Caribbean, Southwestern Japan
- Long latency period
- 2.5% of Japanese people are carriers
- Occurs ONLY in adults ***
- CD52 is involved in the pathogenesis ***
VERY uncommon in the US (except some cities in FL)
How does adult T-cell leukemia/lymphoma present?
May present with
- lymphadenopathy
- skin lesions
- hepatosplenomegaly
- lymphocytosis
- hypercalcemia
Describe the properties of adult T-cell leukemia/lymphoma
- It is a CD4+ T cell lymphoma ***
- The appearance of cells varies
- You can see immature cells with smooth even chromatin
- You can also see mature, multi-lobulated nuclei called FLOWER CELLS ***
- The HTLV-1 provirus is found in the tumor cell
KNOW ALL THIS
Describe the clinical progression and treatment of adult T-cell leukemia/lymphoma
- Disease is rapidly progressive, death within 1 year despite chemotherapy
- New therapy – anti-CD52 (Alemtuzumab)
- Disease with primarily skin involvement is more indolent (causes little to no pain)
What is the relationship between Mycosis fungoides and Sézary syndrome
One disease; two clinical manifestations that overlap
Describe Mycosis fungoides/Sézary syndrome
- Skin always involved***
- Malignant lymphocytes are CD4+ ***
- Indolent disease (average survival is 8-9 yr )
- Malignant cells have cerebriform nuclei, nuclei with highly folded nuclear membrane ***
KNOW ALL OF THIS
Early on – just red skin, later on – masses on the skin
Cerebriform nuclei (nuclei with highly folded nucearl membrane)
Describe mycosis fungoides
- Skin lesions start with premycotic (patch) phase, which has few/a few neoplastic lymphoid cells
What are the two phases of mycosis fungoides?
- Plaque phase
- Tumor phase
Describe the plaque phase and the tumor phase of mycosis fungoides
Plaque phase
- Few/a few neoplastic lymphoid cells in epidermis***
Tumor phase
- Tumor masses, predominantly in dermis***
What happens when mycosis fungoides progresses?
Disease progresses to involve LN and BM
LN = lymph node BM = bone marrow
Describe what you see on the skin in the premycotic phase and the tumor phase of Mycosis fungoides/Sézary syndrome
Premycotic – a lot of red patches
Tumor phase – tumor cells are mainly in the dermis, making it a protruding mass
What is Sezary Syndrome?
Presents with 2 simultaneous manifestations
- Leukemia
- Generalized exfoliative erythroderma (peeling of the skin)
Now we are moving on to our last section… Immature T cell lymphoid neoplasms (lymphomas)
Immature (precursor) T cell neoplasms
- T lymphoblastic leukemia/lymphoma
- Anaplastic large T cell lymphoma
Describe the clinical presentation of T lymphoblastic leukemia/lymphoma
- Medical emergency
- 85% presents as a mass (lymphoma)
- Mass is typically located in the anterior mediastinum or cervical lymph nodes
- 15% present as leukemia (ALL= acute lymphocytic leukemia)
- The symptoms of the T-cell ALL is similar to B-cell ALL
Describe the symptoms of T cell ALL
ALL = Acute lymphocytic leukemia
- Abrupt stormy onset: within days to few weeks of symptoms
- Depression of normal marrow: fatigue due to anemia, infection, bleeding secondary to thrombocytopenia (low platelets b/c bone marrow is involved).
- Mediastinal mass, Lymphadenopathy, splenomegaly, hepatomegaly due to neoplastic infiltration.
CNS INVOLVEMENT***
- headache, vomiting, nerve palsies due to meningeal spread.
What morphology will you see with T cell ALL?
- Monotonous population of blasts (all look the same)
- May have more clumped chromatin
This is described as a “sheet of blasts” ****
- Found in lymph node, soft tissue or bone marrow
- When you see this, think T cell ALL
What immunophenotypes will you see in T cell ALL? Which will be negative?
KNOW THIS **
Positive
- CD34, TdT, CD1a (immature markers)
- Cytoplasmic*** CD3 (surface CD3 negative)
- Other T cell markers dependent upon stage
Describe why CD3 is found in the cytoplasm but not on the cell surface?
Cytoplasmic CD3 positive, surface CD3 negative
- NOT found on the surface of mature T cell
- The CD3 was produced by the cytoplasm, but they have not matured enough to be found on the surface
What is the prognosis of T cell ALL?
- Unlike B-ALL, most T-ALL are considered higher risk
- More factors relate to poor outcome
What factors of T cell ALL predict a poor outcome?
Factors that predict poor outcome
- Age under 2
- Presentation in adolescence or adulthood
- Presence of Philadelphia chromosome t(9;22) or translocation involving the MLL gene on ch 11
- ** If this is positive, prognosis is NOT good
- WBC > 100,000
What is the next lymphoma we will study?
Anaplastic Large (T) cell Lymphoma (ALCL)
What do we call anaplastic Large (T) cell Lymphoma (ALCL)?
Non-Hodgkin lymphoma
Describe the prevalence of Anaplastic Large (T) cell Lymphoma (ALCL)
- Accounts for 10-20% of childhood lymphomas
- Also found in adults
Describe the clinical manefestations of Anaplastic Large (T) cell Lymphoma (ALCL)
- Involves lymph nodes and extranodal sites
- Mediastinal disease is less frequent than in Hodgkin lymphoma
- 70% present with stage III-IV disease and (B) meaning they have symptoms
- This can present as an aggressive lymphoma
Describe the significance of the ALK-1 marker in ALCL
Anaplastic lymphoma kinase-1
Positive ALK-1
- Children/young adults
- Better prognosis, Overall 5 yr survival rate ~80%
Negative ALK-1
- Especially in elder adults
- Poor prognosis.
KNOW THIS ***
Describe the morphology of ALCL
KNOW THIS **
Pleomorphic (variable size and shape) with characteristic “Hallmark” cells
Describe the hallmark cells of ALCL (anaplastic large cell lymphoma)
Hallmark cells:
(1) medium size
(2) abundant cytoplasm
(3) kidney shaped nuclei,
(4) paranuclear eosinophilic region (pink around nucleus)
What are the immunophenotype markers seen in ALCL?
KNOW THIS ***
Positive
- CD30
- EMA (epithelial membrane antigen)
Negative
- CD3 is negative in 75%
***ALK+/-
A 45 year old female presents with palpable mass in her abdomen.
Abdominal CT scan shows retroperitoneal mass and extensive lymphadenopathy and splenomegaly. After lymph node biopsy, the cells are found to be positive for CD10, CD19, CD20 and Bcl-2 by immunohistochemistry. The MOST LIKELY diagnosis is
A. mantle cell lymphoma. B. Burkitt lymphoma. C. Sézary syndrome/mycosis fungoides. D. follicular lymphoma. E. extranodal NK cell lymphoma
D. follicular lymphoma.
