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S3B5 Pathology > Acute Lymphoblastic Leukemia/Lymphomas & T/NK-cell Non-Hodgkin Lymphoma > Flashcards

Acute Lymphoblastic Leukemia/Lymphomas & T/NK-cell Non-Hodgkin Lymphoma Flashcards

1
Q

What are lymphoblasts? They express what cytogenic markers?

A

lymphocyte precursors - few or none of the morphologic or immunologic features of mature lymphocytes

small to medium size with round, oval nuclei & fine chromatin - few/inconspicuous nucleoli & frequent mitotic figures, scant cytoplasm, PAS-positive cytoplasmic granules

most express CD34, CD19, CD10, TdT, HLA-DR

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2
Q

What is the difference between lymphoblastic leukemeia & lymphoblastic lymphoma?

A
  • leukemia
    • significant blood/bone marrow involvement (most are B-cell)
  • lymphoma
    • mass lesion with no/minimal blood/bone marrow involvement (most are T-cell)
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3
Q

If a patient presents with tissue mass & blood/bone marrow involvement, what blast count qualifies the condition as Acute Lymphoblastic Leukemia?

A

25%

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4
Q

What is the most common childhood malignancy?

A

B-ALL (leukemia)

>75% cases are seen in children under 6 yrs

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5
Q

What is the difference in age demographics most commonly affected by B-ALL and B-LBL?

A

B-ALL >75% under 6 yrs

B-LBL teenagers & young adults

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6
Q

What is the clinical picture of patients with B-ALL/LBL?

A
  • common extramedullary involvement
  • lymphadenopathy, hepato/splenomegaly
  • bone pain
  • fever, weight loss, night sweats
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7
Q

Is B-ALL or T/NK-ALL more common?

A

85% of all ALL are B-cell

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8
Q

Is B-LBL or T/NK-LBL more common?

A

most are T/NK-LBL

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9
Q

What CBC laboratory findings would you expect to see in a patient with B-ALL?

A

variable WBC count

anemia & thrombocytopenia

rarely - reactive eosinophilia

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10
Q

What are the environmental risk factors associated with B-ALL/LBL?

A

radiation

toxins

previous chemotherapy

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11
Q

What are the genetic factors associated with B-ALL/LBL?

A

genetic abnormalities

second “hit” may be required for development overt leukemia

clonal IgH (heavy chain) gene

Down Syndrome

familial predisposition

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12
Q

What would you expect to see in a peripheral blood smear in a patient with B-ALL/LBL?

A
  • leukoerythroblastosis
    • granulocyte precursors, nucleated RBC & lymphoblasts
    • L1 blasts- smaller, scant & condensed chromatin (circled) - mimic mature cells
    • L2 blasts- larger, moderate cytoplasm & “smudgy chromatin, prominent nucleoli (blue curved arrow)
    • blasts are negative for myeloperoxidase & other myeloid markers
  • cell morphology of non-neoplastic cells is normal - NO dysplastic myeloid cells

*won’t have to recognize difference between L1 & L2

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13
Q

What would you expect to see from a bone marrow aspirate in a patient with B-ALL/LBL?

A

hypercellular w/ high percentage lymphoblasts & numerous mitoses- think monotonous population

rarely, regions of necrosis (areas where they outgrew blood supply- will look more pink than blue)

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14
Q

What condition is indicative of the provided peripheral blood smear & bone marrow aspirate?

A

B-ALL/LBL

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15
Q

What would you expect to see in a lymph node biopsy from a patient with B-ALL/LBL?

A

partial to complete effacement of architecture

diffuse infiltrative pattern with no nodularity

many mitoses

similar to blastoid mantle cell lymphoma & Burkitt lymphoma

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16
Q

What cytogenic markers are seen in patients with B-ALL/LBL?

A

CD19 (& other pan-B cell markers)

CD34 and TdT (markers of immaturity)

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17
Q

What variables are good prognostic indicators in B-ALL/LBL?

A

1-10 yrs

female

WBC < 50,000

absence CNS disease

common inmmunophenotype

hyperdiploidy > 50 chromosomes

(>95% remission rate & about 80% cured)

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18
Q

What variables are poor prognostic indicators in B-ALL/LBL?

A

<1 yr and >10 yrs

male

WBC > 50,000

presence CNS disease

absence CD10

hypodiploidy < 45 chromosomes

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19
Q

T-ALL/LBL is most common in what demographic of people?

A

adolescent males

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20
Q

What clinical picture would you expect to see in a patient with T-ALL?

A
  • adolescent male
  • bone marrow involvement (by definition)
  • mediastinal involvement is common (rapidly growing mass)
  • lymphadenopathy & hepatosplenomegaly
  • CNS involvement is more common than in T-LBL
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21
Q

What clinical picture would you expect to see in a patient with T-LBL?

A
  • adolescent male
  • rapidly growing anterior mediastinal/thymic mass
  • pleural/pericardial effusion
  • bone marrow (<25% lymphoblasts)
  • may have involvement of lymph nodes & extranodal sites
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22
Q

What values would you expect to see from a CBC and peripheral blood smear from a patient with T-ALL/LBL?

A

marked peripheral blood leukocytosis with high blast count

blasts are usually indistinguishable from B-ALL

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23
Q

What cytogenic markers would you expect to see in a patient with T-ALL/LBL?

A

TdT, CD34, CD2, CD5, CD7, +/-CD10

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24
Q

What is the difference in prognosis for in comparison to their B-cell counterparts:

Childhood T-ALL

Adult T-ALL

Pediatric T-LBL

Adult T-LBL

A
  • Childhood T-ALL
    • higher risk than B-ALL/LBL
  • Adult T-ALL
    • better prognosis than B-ALL
  • Pediatric T-LBL
    • worse prognosis than with B-LBL
  • Adult T-LBL
    • varies with age, worse if >40 yr
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25
Are mature T-cell neoplasms more or less common than mature B-cell neoplasms?
much less common
25
Are mature T-cell neoplasms more or less common than mature B-cell neoplasms?
much less common than B-cell neoplasms
26
Mature T-cell neoplasm typically have what type of growth pattern?
diffuse usually with mixed inflammatory cell background
27
Why are mature T-cell neoplasms difficult to diagnose by flow cytometry?
more likely to be detected by T-cell antigens lost than expressed
28
As a group, do mature T-cell lymphomas have a better or worse prognosis than most B-cell lymphomas?
T-cells generally have a significantly worse prognosis
29
What is Mycosis Fungoides?
malignancy of **CD4(+)**, **CD8(-)** T lymphocytes with **loss of CD7** or another T-cell marker
30
What is the most common primary cutaneous T-cell cell lymphomas?
Mycosis Fungoides
31
What is the general clinical manifestation of a patient with Mycosis Fungoides?
* 5-6th decade * black * M:F=2:1 * indolent * non-specific skin lesions * patches on trunk, alopecia * palpable lesion - often scaling * tumor - skin nodules, may ulcerate
32
What are the 4 stages of MF & their characteristics?
* **Pre-mycotic** (can occur for years) * non-specific skin lesions * slight scaling/pruritis * non-specific skin biopsies * **Initial Patch Stage** * trunk (can be anywhere) * flat lesions with discoloration - little scaling & not palpable * **Infiltrated Plaque Stage** * palpable lesion - rise above surface of surrounding skin * often with scaling * can coexist with patches * **Tumor Stage** * usually manifest as skin nodules * may ulcerate * can coexist with patches & plaques
33
The provided image is an example of what condition? What stage?
MF Initial Patch Stage
34
The provided image is an example of what condition? What stage?
MF Infiltrated Plaque Stage
35
The provided image is an example of what condition? What stage?
MF Tumor Stage
36
What condition/stage is shown in the provided histological slides?
MF - patches small/medium sized lymphocytes with cerebriform nuclei superficial _band-like_ lymphoid infiltrate of lymphocytes & histiocytes; neoplastic lymphocytes may line up along the basal layer of epidermis (may show single-cell epidermotropism)
37
What condition/stage is shown in the provided histological slides?
**MF** **Plaque**- dense, subepidermal, band-like infiltrate with many atypical lymphocytes; **epidermotropism** (lymphocytes colonizing the epidermis) is more prominent may have intraepidermal clusters of atypical lymphocytes & **Pautrier microabscesses** (not real microabscesses b/c not neutrophils) (arrow)
38
What condition/stage is shown in the provided histological slides?
**MF** **Tumor** - dermal infiltrate becomes more diffuse and prominent epidermotropism may be lost (may be ulcerated)- large cell transformation may occur; large lymphocytes comprising more than 25% of tumor (often +CD30)
39
What is the treatment & prognosis of Mycosis Fungoides?
* Treatment * early: direct skin therapy * late: extracorporeal photophersis * hematopoietic stem cell transplantation * Prognosis * clinical stage is most important prognostic feature * poor in more advanced disease
40
What is Sezary Syndrome? Classic Triad?
T-cell neoplasm of atypical T-cells “Sezary cells” with imunophenotype & morphology like MF (can arise from MF) * Clinical triad * Erythroderma * generalized lymphadenopathy * \>1,000/microliter Sezary cells in peripheral blood (cerebriform nuclei)
41
What is the name of the cell type shown in the provided images? They are characteristically seen in what conditions?
“Sezary cells” with cerebriform nuclei - nucleus folds upon itself MF & Sezary Syndrome
42
What is the general clinical picture of a patient with Sezary Syndrome?
* middle-aged / elderly * M \> F * Symptoms * _Triad_: * erythroderma, * lymphadenopathy, * clonal proliferation T-cell with cerebriform nuclei in skin, peripheral blood & lymph nodes * pruritis * alopecia * immunosuppression * ectropion (eyelid turns outward) * palmar/plantar hyperkeratosis * onychodystrophy (weirdness w/ nails) * visceral involvement - sparing of bone marrow
43
What tumor markers are seen in patients with Sezary Syndrome?
**CD4+** loss of CD7 or another T-cell antigen CD4:CD8 usually \>10
44
What would you expect to see in a peripheral blood smear from a patient with Sezary Syndrome?
atypical lymphocytes with cerebriform nuclei
45
What would you expect to see in a lymph node biopsy from a patient with Sezary Syndrome?
partial or total effacement by a dense, monotonous infiltrate of Sezary cells B-cell follicles are often reduced in number, and/or small
46
What is the treatment & prognosis of Sezary Syndrome?
palliative - not curative poor prognosis (most die of opportunistic infection)
47
Adult T-cell leukemia/lymphoma on occurs in individuals who have been infected by what virus?
HTVL-1
48
The neoplastic cell is Adult T-cell leukemia/lymphoma have what cytologic markers?
**CD4+** **CD25+** may have other T cell markers (CD3, CD5) but have **LOST CD7**
49
What demographics are most commonly affected by Adult T-cell leukemia/lymphoma?
* only adults (5-6th decade) * but acquired HTLV-1 in childhood * endemic to Southwest Japan, south America, Australia, Central Africa
50
What are the general clinical features of a patient with Adult T-cell leukemia/lymphoma?
* skin lesions (50%) * generalized lymphadenopathy * Subtypes * **Acute (MC)** * marked leukocytosis * increased LDH * hypercalcemia, lytic bone lesions, renal dysfunction, neuropsychiatric problems
51
What would you expect to see in a peripheral blood smear of a patient with Adult T-cell leukemia/lymphoma?
medium-large pleomorphic lymphocytes with coarse chromatin, small to inconspicuous nucleoli multilobulated “flower cells” (flowering outward)
52
What is the name of the cells seen in the provided image? They are characteristic of what condition?
“Flower cells” Adult T-cell leukemia/lymphoma
53
What would you expect to see in a lymph node biopsy of a patient with Adult T-cell leukemia/lymphoma?
architecture effaced by diffuse infiltrated of heterogeneous lymphocytes
54
What is the treatment & prognosis of Adult T-cell leukemia/lymphoma?
* Treatment * Indolent - antiretroviral therapy (or watch & wait) * Aggressive forms - multiagent chemotherapy, hematopoietic stem cell transplant, monoclonal antibodies * Prognosis * acute & lymphomatous \<10% 5 yr survival * better in chronic & smoldering, but may transform into acute of lymphomatous variant
55
What condition is seen in the provided images?
Adult T-cell leukemia/lymphoma Left: ulcerating lesion Right: epithelium infiltrated by **Pautrier-like** microabscesses (kinda like MF)
56
What is T-cell Large Granular Lymphocytic Leukemia?
Persistent (\>6mo) clonal proliferation of CD8(+) T-cell large granular lymphocytes. T-cell receptor is clonally rearranged.
57
In what age group do you most commonly see patients with T-cell large granular lymphocytic leukemia?
median age 60 M=F
58
T-cell large granular lymphocytic leukemia is commonly seen in what sites?
peripheral blood bone marrow spleen liver
59
What mutations are associated with T-cell large granular lymphocytic leukemia?
* **STAT3**: provides pro-survival & growth signals * Chronic antigenic stimulation: proliferation T-LGLs * Inhibition apoptosis: prolonged survival
60
What is the clinical presentation of a patient with T-cell large granular lymphocytic leukemia?
* may be asymptomatic * associated disorders * RA (other autoimmune) * splenomegaly * myelodysplasia, PNH, aplastic anemia, acquired pure red cell aplasia * symptomatic cytopenias * recurrent infection
61
What would you expect to see in the peripheral blood smear of a patient with T-cell large granular lymphocytic leukemia? Bone marrow?
* Peripheral blood * Large granular lymphocyte lymphocytosos \>2 x 10,000 / microL * intermediate size, round/indented nucleus * inconspicuous nucleoli, condensed chromatin * abundant pale cytoplasm * no dyspoiesis usually * bone marrow * variable; often hypocellular
62
What is the prognosis of T-cell large granular lymphocytic leukemia?
indolent- related to control of cytopenias & symptoms
63
What condition is indicative of the provided peripheral blood smear?
T-cell large granular lymphocytic leukemia * large granular lymphocytes w/ intermediate size, round/indented nucleus * inconspicuous nucleoli, condensed chromatin * abundant pale cytoplasm
64
What is Anaplastic Large Cell lymphoma, ALK positive?
lymphoma of CD30(+) T-cells with chromosomal abnormalities involving 2p23/ALK
65
In Anaplastic Large Cell lymphoma, ALK positive - what does ALK stand for?
anaplastic lymphoma kinase
66
What genetic mutation is associated with Anaplastic Large Cell lymphoma, ALK positive?
**t(2;5)(p23;q35)** formation of fusion protein NM-ALK causing constitutively activated tyrosine kinase that trigger RAS & JAK/STAT signalling
67
Anaplastic Large Cell lymphoma, ALK positive is most common in what age group?
adolescents & young adults
68
What is the clinical presentation of a patient with Anaplastic Large Cell lymphoma, ALK positive?
often have “B” symptoms (**fever**, night sweats, weight loss) - mimic serious infection involve lymph nodes & extranodal sites generally present late stage
69
What is the prognosis of Anaplastic Large Cell lymphoma, ALK positive?
very good response to chemotherapy - 5 yr survival is 80-90%
70
What is a good test to differentiate Anaplastic Large Cell Lymphoma, ALK positive from Hodgkin lymphomas & DLBCL?
Anaplastic Large Cell Lymphoma is consistently negative for EBV
71
What cytologic markers are seen in Anaplastic Large Cell Lympohma, ALK positive?
CD30 and some T-cell markers
72
What is the name of the cell circled in yellow? If the stain on the right is a CD30 immunostain, the provided histological slides are from what condition?
Anaplastic Large Cell Lymphoma, ALK positive “Hallmark cells” - large, pleomorphic & often bizarre, with occasional horseshoe shaped nucleus
73
What feature of a peripheral blood smear can help you differentiate a lymphoblastic neoplasm from a myeloid neoplasm?
* Lymphoblastic: * NEVER Auer Rods * should be no background dyspoiesis * Not SPECIFIC - but much more commonly see “handle” on blasts - seen in image
74
What is the minimum percentage for blast count need for diagnosis of ALL
no minimum percentage blast count needed
75
What symptoms are frequently seen in mature T-cell & NK-cell neoplasms?
generalized lymphadenopathy peripheral blood eosinophilia pruritus skin lesions fever weight loss

S3B5 Pathology (13 decks)

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