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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
Q

Are mature T-cell neoplasms more or less common than mature B-cell neoplasms?

A

much less common

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25
Q

Are mature T-cell neoplasms more or less common than mature B-cell neoplasms?

A

much less common than B-cell neoplasms

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26
Q

Mature T-cell neoplasm typically have what type of growth pattern?

A

diffuse

usually with mixed inflammatory cell background

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27
Q

Why are mature T-cell neoplasms difficult to diagnose by flow cytometry?

A

more likely to be detected by T-cell antigens lost than expressed

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28
Q

As a group, do mature T-cell lymphomas have a better or worse prognosis than most B-cell lymphomas?

A

T-cells generally have a significantly worse prognosis

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29
Q

What is Mycosis Fungoides?

A

malignancy of CD4(+), CD8(-) T lymphocytes with loss of CD7 or another T-cell marker

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30
Q

What is the most common primary cutaneous T-cell cell lymphomas?

A

Mycosis Fungoides

31
Q

What is the general clinical manifestation of a patient with Mycosis Fungoides?

A
  • 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
Q

What are the 4 stages of MF & their characteristics?

A
  • 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
Q

The provided image is an example of what condition? What stage?

A

MF

Initial Patch Stage

34
Q

The provided image is an example of what condition? What stage?

A

MF

Infiltrated Plaque Stage

35
Q

The provided image is an example of what condition? What stage?

A

MF

Tumor Stage

36
Q

What condition/stage is shown in the provided histological slides?

A

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
Q

What condition/stage is shown in the provided histological slides?

A

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
Q

What condition/stage is shown in the provided histological slides?

A

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
Q

What is the treatment & prognosis of Mycosis Fungoides?

A
  • 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
Q

What is Sezary Syndrome? Classic Triad?

A

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
Q

What is the name of the cell type shown in the provided images? They are characteristically seen in what conditions?

A

“Sezary cells” with cerebriform nuclei - nucleus folds upon itself

MF & Sezary Syndrome

42
Q

What is the general clinical picture of a patient with Sezary Syndrome?

A
  • 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
Q

What tumor markers are seen in patients with Sezary Syndrome?

A

CD4+

loss of CD7 or another T-cell antigen

CD4:CD8 usually >10

44
Q

What would you expect to see in a peripheral blood smear from a patient with Sezary Syndrome?

A

atypical lymphocytes with cerebriform nuclei

45
Q

What would you expect to see in a lymph node biopsy from a patient with Sezary Syndrome?

A

partial or total effacement by a dense, monotonous infiltrate of Sezary cells

B-cell follicles are often reduced in number, and/or small

46
Q

What is the treatment & prognosis of Sezary Syndrome?

A

palliative - not curative

poor prognosis (most die of opportunistic infection)

47
Q

Adult T-cell leukemia/lymphoma on occurs in individuals who have been infected by what virus?

48
Q

The neoplastic cell is Adult T-cell leukemia/lymphoma have what cytologic markers?

A

CD4+

CD25+

may have other T cell markers (CD3, CD5)

but have LOST CD7

49
Q

What demographics are most commonly affected by Adult T-cell leukemia/lymphoma?

A
  • only adults (5-6th decade)
    • but acquired HTLV-1 in childhood
  • endemic to Southwest Japan, south America, Australia, Central Africa
50
Q

What are the general clinical features of a patient with Adult T-cell leukemia/lymphoma?

A
  • skin lesions (50%)
  • generalized lymphadenopathy
  • Subtypes
    • Acute (MC)
      • marked leukocytosis
      • increased LDH
      • hypercalcemia, lytic bone lesions, renal dysfunction, neuropsychiatric problems
51
Q

What would you expect to see in a peripheral blood smear of a patient with Adult T-cell leukemia/lymphoma?

A

medium-large pleomorphic lymphocytes with coarse chromatin, small to inconspicuous nucleoli

multilobulated “flower cells” (flowering outward)

52
Q

What is the name of the cells seen in the provided image? They are characteristic of what condition?

A

“Flower cells”

Adult T-cell leukemia/lymphoma

53
Q

What would you expect to see in a lymph node biopsy of a patient with Adult T-cell leukemia/lymphoma?

A

architecture effaced by diffuse infiltrated of heterogeneous lymphocytes

54
Q

What is the treatment & prognosis of Adult T-cell leukemia/lymphoma?

A
  • 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
Q

What condition is seen in the provided images?

A

Adult T-cell leukemia/lymphoma

Left: ulcerating lesion

Right: epithelium infiltrated by Pautrier-like microabscesses (kinda like MF)

56
Q

What is T-cell Large Granular Lymphocytic Leukemia?

A

Persistent (>6mo) clonal proliferation of CD8(+) T-cell large granular lymphocytes. T-cell receptor is clonally rearranged.

57
Q

In what age group do you most commonly see patients with T-cell large granular lymphocytic leukemia?

A

median age 60

M=F

58
Q

T-cell large granular lymphocytic leukemia is commonly seen in what sites?

A

peripheral blood

bone marrow

spleen

liver

59
Q

What mutations are associated with T-cell large granular lymphocytic leukemia?

A
  • STAT3: provides pro-survival & growth signals
    • Chronic antigenic stimulation: proliferation T-LGLs
    • Inhibition apoptosis: prolonged survival
60
Q

What is the clinical presentation of a patient with T-cell large granular lymphocytic leukemia?

A
  • may be asymptomatic
    • associated disorders
      • RA (other autoimmune)
      • splenomegaly
      • myelodysplasia, PNH, aplastic anemia, acquired pure red cell aplasia
  • symptomatic cytopenias
  • recurrent infection
61
Q

What would you expect to see in the peripheral blood smear of a patient with T-cell large granular lymphocytic leukemia?

Bone marrow?

A
  • 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
Q

What is the prognosis of T-cell large granular lymphocytic leukemia?

A

indolent- related to control of cytopenias & symptoms

63
Q

What condition is indicative of the provided peripheral blood smear?

A

T-cell large granular lymphocytic leukemia

  • large granular lymphocytes w/ intermediate size, round/indented nucleus
  • inconspicuous nucleoli, condensed chromatin
  • abundant pale cytoplasm
64
Q

What is Anaplastic Large Cell lymphoma, ALK positive?

A

lymphoma of CD30(+) T-cells with chromosomal abnormalities involving 2p23/ALK

65
Q

In Anaplastic Large Cell lymphoma, ALK positive - what does ALK stand for?

A

anaplastic lymphoma kinase

66
Q

What genetic mutation is associated with Anaplastic Large Cell lymphoma, ALK positive?

A

t(2;5)(p23;q35)

formation of fusion protein NM-ALK causing constitutively activated tyrosine kinase that trigger RAS & JAK/STAT signalling

67
Q

Anaplastic Large Cell lymphoma, ALK positive is most common in what age group?

A

adolescents & young adults

68
Q

What is the clinical presentation of a patient with Anaplastic Large Cell lymphoma, ALK positive?

A

often have “B” symptoms (fever, night sweats, weight loss) - mimic serious infection

involve lymph nodes & extranodal sites

generally present late stage

69
Q

What is the prognosis of Anaplastic Large Cell lymphoma, ALK positive?

A

very good response to chemotherapy - 5 yr survival is 80-90%

70
Q

What is a good test to differentiate Anaplastic Large Cell Lymphoma, ALK positive from Hodgkin lymphomas & DLBCL?

A

Anaplastic Large Cell Lymphoma is consistently negative for EBV

71
Q

What cytologic markers are seen in Anaplastic Large Cell Lympohma, ALK positive?

A

CD30 and some T-cell markers

72
Q

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?

A

Anaplastic Large Cell Lymphoma, ALK positive

“Hallmark cells” - large, pleomorphic & often bizarre, with occasional horseshoe shaped nucleus

73
Q

What feature of a peripheral blood smear can help you differentiate a lymphoblastic neoplasm from a myeloid neoplasm?

A
  • Lymphoblastic:
    • NEVER Auer Rods
    • should be no background dyspoiesis
    • Not SPECIFIC - but much more commonly see “handle” on blasts - seen in image
74
Q

What is the minimum percentage for blast count need for diagnosis of ALL

A

no minimum percentage blast count needed

75
Q

What symptoms are frequently seen in mature T-cell & NK-cell neoplasms?

A

generalized lymphadenopathy

peripheral blood eosinophilia

pruritus

skin lesions

fever

weight loss

S3B5 Pathology (13 decks)

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