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WILLIAM'S HEMATOLOGY > 102 Cutaneous T-Cell Lymphoma (Mycosis Fungoides and Sezary Syndrome) > Flashcards

102 Cutaneous T-Cell Lymphoma (Mycosis Fungoides and Sezary Syndrome) Flashcards

1
Q

The skin manifestations of MF are divided into:

A
  • Patch stage (patch-only disease)
  • Plaque stage (both patches and plaques), and
  • Tumor stage (more than one tumor present, usually in the context of patches and plaques)
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2
Q

TRUE OR FALSE

Lesions usually are associated with pruritus, which may range from mild to excruciatingly severe, leading to insomnia, weight loss, depression, and suicidal ideation.

A

TRUE

Lesions usually are associated with pruritus, which may range from mild to excruciatingly severe, leading to insomnia, weight loss, depression, and suicidal ideation.

Pruritus is one of the most important quality-of-life issues for these patients.

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3
Q

Stopping skin-directed therapies (SDTs) for ___________ weeks before biopsy can be helpful in aiding diagnosis and is strongly recommended.

A

2 to 3 weeks

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4
Q

Characteristic lymphpocyte description of MF

A

Small to large, with characteristic convoluted (cerebriform) nuclei

  • Classically, MF lesions show a superficial bandlike (lichenoid) lymphocytic infiltrate
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5
Q

The hallmark of the malignant infiltrate in MF is epidermotropism (presence of lymphocytes in the epidermis without spongiosis) with formation of the epidermal clusters of lymphocytes around Langerhans cells termed

A

Pautrier microabscesses

Superficial dermal collagen may be thickened, so-called ropey collagen.

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6
Q

TRUE OR FALSE

Alternatively, high expression of CD30 in the setting of MF and SS may reflect concurrent presence of type C lymphomatoid papulosis (LyP) or primary cutaneous anaplastic large cell lymphoma (PCALCL) rather than transformed disease and carries a significantly poor prognosis.

A

FALSE

Alternatively, high expression of CD30 in the setting of MF and SS may reflect concurrent presence of type C lymphomatoid papulosis (LyP) or primary cutaneous anaplastic large cell lymphoma (PCALCL) rather than transformed disease and carries a significantly better prognosis.

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7
Q

Immunophenotype of CTCL

A

CD3+CD4+CD45RO+ CD8–

A phenotype associated with mature helper-inducer T lymphocytes

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8
Q

Are important markers for malignant T lymphocytes

A

Loss of maturation markers, such as CD7, and CD26 expression on CD4+ cells

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9
Q

Clonal rearrangement of the _____________________ gene can be identified in approximately 90% of advanced cases of MF but in only 50% of early-stage cases.

A

T-cell receptor (TCR) Vβ gene

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10
Q

MF is classified according to the widely accepted modified

A

Tumor, node, metastasis, blood (TNMB) classification

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11
Q

Cutaneous lesions are classified using the T staging system

A
  • T1: Limited patches, papules, or plaques covering < 10% of the skin surface (T1a = patch only; T1b = plaques ± patches)
  • T2: Generalized patches, papules, or plaques covering 10% or more of the skin surface (T2a = patch only; T2b = plaques ± patches)
  • T3: At least one tumor (≥1 cm in diameter)
  • T4: Generalized erythroderma over ≥80% body surface area

The area of the skin and type of the lesions were found to correlate with patient survival and are important prognostic predictors that need to be calculated at every visit to assess disease status.

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12
Q

TRUE OR FALSE

Lymphadenopathy is present in more than half of patients as disease advances and increases with progressive cutaneous involvement.

A

TRUE

Lymphadenopathy is present in more than half of patients as disease advances and increases with progressive cutaneous involvement.

Even the presence of dermatopathic changes alone in the lymph nodes carries prognostic significance

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13
Q

Imaging used to assess involvement of lymph nodes

A

Computerized tomography (CT) and positron emission tomography (PET) scans

Excisional lymph node biopsy is usually recommended to assess the extent of the disease and nodal architecture and is preferred over fine-needle aspiration cytology (FNAC) or core biopsy.

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14
Q

TRUE OR FALSE

The number of circulating Sézary cells increases with advancing disease, and the cells are particularly prominent in patients with generalized erythroderma.

A

TRUE

The number of circulating Sézary cells increases with advancing disease, and the cells are particularly prominent in patients with generalized erythroderma.

However, a clonal T-cell population in the blood may be detected in up to half of stage I patients using a highly sensitive polymerase chain reaction (PCR) technique, suggesting that early systemic disease is common.

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15
Q

Blood involvement is rated as the B category

A
  • B0: Absence of significant blood involvement: ≤ 5% of blood lymphocytes of < 0.25 × 109/L are atypical (Sézary) cells or < 15% CD4+/CD26- or CD4+CD7- cells of total lymphocytes
  • B1: Atypical circulating cells present (> 5%, minimal blood involvement) or >15% CD4+CD26- or CD4+CD7- of total lymphocytes but do not meet criteria for B0 or B2
  • B2: High blood tumor burden:** ≥ 1 × 109/L** Sézary cells determined by cytopathology or ≥ 1 × 109/L CD4+CD26- or CD4+CD7- cells or other abnormal subset of T lymphocytes by flow cytometry with clone in blood same as that in skin.

Other criteria for documenting high blood tumor burden in CD4+ MF and SS include CD4+/CD7- cells ≥40% and CD4+CD26- cells ≥30%

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16
Q

TRUE OR FALSE

Patients with blood involvement have a lower likelihood of lymphadenopathy and visceral involvement.

A

FALSE

Patients with blood involvement have a higher likelihood of lymphadenopathy and visceral involvement.

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17
Q

TRUE OR FALSE

Marrow infiltration with extracutaneous disease occurs but is infrequently detected by biopsy despite circulating malignant cells and is not a recommended procedure for staging.

A

TRUE

Marrow infiltration with extracutaneous disease occurs but is infrequently detected by biopsy despite circulating malignant cells and is not a recommended procedure for staging.

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18
Q

Classification of Erythrodermic Cutaneous T-Cell Lymphoma (T4)

A
  • Sézary syndrome
  • Erythrodermic MF
  • Erythrodermic cutaneous T-cell lymphoma, not otherwise specified
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19
Q

The triad that make SS have the worst prognosis among the other forms of erythrodermic CTCL.

A
  • Exfoliative erythroderma
  • Generalized lymphadenopathy
  • Leukemia
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20
Q

MYCOSIS FUNGOIDES VARIANTS

Characterized by a folliculotropic infiltrate that spares the epidermis, often with mucinosis, and principally affects the head and neck

Worse prognosis than plaque-stage classical MF

A

Folliculotropic MF

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21
Q

MYCOSIS FUNGOIDES VARIANTS

Rare variant of MF that consists of solitary or localized cutaneous plaques, usually found on the extremities, affecting young males almost exclusively

Benign, indolent course, and the prognosis is excellent

It is an epidermal process, with the majority of atypical lymphocytes found within hyperplastic epidermis.

A

Pagetoid reticulosis (Woringer-Kolopp disease)

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22
Q

Was previously considered the disseminated form of pagetoid reticulosis

Predominantly epidermal involvement of malignant cells and a poor prognosis

A

Ketron-Goodman disease

The WHO-EORTC classification now defines the disease as aggressive epidermotropic CD8+ CTCL, Cutaneous γ/δ-positive T-cell lymphoma, or tumor-stage MF

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23
Q

MYCOSIS FUNGOIDES VARIANTS

Rare but indolent variant of MF that causes slowly progressive laxity of skin folds and granulomatous clonal T-cell infiltrate on histology

A

Granulomatous slack skin

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24
Q

Skin-directed therapy

A
  • Topical therapy
  • Light therapy
  • Radiation therapy
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25
Q

Systemic therapy

A
  • Retinoids
  • Histone deacetylase inhibitors
  • Immunomodulators
  • Monoclonal antibodies and conjugates
  • Proteasome inhibitors
  • Chemotherapy
  • Allogeneic stem cell transplant
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26
Q

TRUE OR FALSE

Ultrapotent topical glucocorticoids can be used on the face, neck, and intertriginous areas.

A

FALSE

Ultrapotent topical glucocorticoids should not be used on the face, neck, and intertriginous areas.

Topical steroids are rarely used as monotherapy but may be effective as an additional modality for symptomatic relief of pruritus.

27
Q

Effective as mid- to low-potency glucocorticoids for use on facial skin and intertriginous areas in patients with MF

A major advantage: they do not suppress collagen synthesis to cause skin atrophy.

A

Topical Calcineurin Inhibitors
Topical tacrolimus and pimecrolimus

Associated with an increased risk of lymphoma, and their use in patients with CTCL is controversial.

Should be limited to small areas

28
Q

An alkylating agent approved by the FDA for stage IA and IB patients after one prior treatment

Major advantage: low toxicity
Disadvantages: inconvenience of daily application to large areas of skin, allergic reactions, the potential for development of skin cancer, and the inability to cure the disease

A

Topical Nitrogen Mustard (Mechlorethamine Hydrochloride)

  • It is approved for use from the neck down and applied three times weekly up to daily as tolerated.
  • Therapy is usually continued for up to 12 months in responders.
  • The frequency then is reduced to every other day for an additional 1 to 2 years.
  • Therapy is discontinued after 3 years or when cutaneous lesions disappear completely.
  • Should not be used together with UVA or UVB therapy
  • Contraindicated in pregnancy
29
Q

Not currently widely used for treatment of MF because of its severe irritant reactions and its absorption from the skin, which results in systemic toxicity

Causes marrow suppression

A

Bis-chloroethylnitrosourea (BCNU)

Carmustine causes irreversible skin thinning, telangiectasias, and hyperpigmentation.

30
Q

A topical retinoid (rexinoid) approved by the FDA for treatment of MF patients who are refractory to at least one other topical therapy.

A

Bexarotene

  • It is applied twice daily in a thin layer to the patches and plaques.
  • The major toxicity is irritation at the site.
  • Oral administration of bexarotene is associated with severe birth defects
31
Q

Not FDA approved for the treatment of patients with MF and SS because of a lack of prospective clinical trials but is considered to be one of the most effective therapies for early disease (mainly patches and thin plaques)

A

Phototherapy

32
Q

Hypothesized that the mechanism of action of phototherapy

A

Depletion of Langerhans cells from the epidermis

33
Q

Peak of therapeutic effectiveness of:

UVB:
UVA:

A

UVB: 295–313 nm
UVA: 320 to 400 nm

NBUVB is most appropriate for patch-stage disease
UVA penetrates deeper than UVB into the dermis, allowing treatment of thicker plaques.

34
Q

A phototoxic furocoumarin activated by UVA light

A

Psoralen

UVA radiation is used with psoralen and is referred to as PUVA

Given at a dose of 0.6 mg/kg orally, 2 hours before the UVA light therapy

35
Q

Adverse effects of PUVA therapy

A

Nausea, pruritus, and sunburn-like changes, with atrophy and dry skin

Long-term side effects: increased incidence of skin cancers and melanoma

Disadvantages of phototherapy include the necessity to visit the physician’s office frequently (from three times a week to once a month) and its expense.

36
Q

A photochemotherapy that uses two properties of porphyrins: their selective accumulation in tumor sites (eg, 5-aminolevulinic acid) and their ability to generate cytotoxic oxygen species at the tumor site after red-light irradiation

A

Photodynamic Therapy

Useful in patients with localized plaques or tumors; however, the pain induced during irradiation limits its use for larger areas

It is used for therapy of MF off label

37
Q

A natural porphyrin precursor and upon irradiation is converted in the tumor to the highly photoactive endogenous protoporphyrin IX

A

5-Aminolevulinic acid

38
Q

One of the most photoactive compounds, and it can be activated by fluorescent light, rather than UVA or UVB, decreasing the risk of cancer risks associated with treatment

A

Hypericin

39
Q

One of the oldest and the most effective forms of treatment of MF, appropriate for patients who have failed the aforementioned SDTs

A

Electron-Beam Therapy

40
Q

A Toll-like receptor-7 and -8 agonist that induces proinflammatory cytokines such as tumor necrosis factor-α and interferons (INFs), resulting in activation of a Th1-type immune response and rejection of cancer or virally infected cells

A

Imiquimod

41
Q

An FDA-approved, RXR-selective oral retinoid, or “rexinoid,” for therapy of MF

Recommended beginning with refractory or persistent stage IA disease through more advanced stages (NCCN guidelines)

A

Oral bexarotene

Other retinoids have been used for treatment of MF and SS, including isotretinoin, acitretin, etretinate (not available in United States), and all-trans retinoic acid (ATRA)

42
Q

FDA-approved dose for Oral bexarotene

A

300 mg/m2 per day

43
Q

All patients on bexarotene rapidly develop

A

Central hypothyroidism and hyperlipidemia (most significantly hypertriglyceridemia)

Requiring coadministration of thyroid supplements, lipid-lowering agents, and a high-protein, low-fat, low-carbohydrate die

Other rare adverse events include headaches, possibly a result of pseudotumor cerebri; leukopenia; hepatotoxicity; and pruritus.

44
Q

Examples of Histone Deacetylase Inhibitors

A

Vorinostat and romidepsin

45
Q

An oral pan- HDACi FDA approved for treatment of cutaneous manifestations of recurrent, refractory, or persistent MF and SS in 2008 at the dose of 400 mg daily

A

Vorinostat (suberoylanilide hydroxamic acid)

46
Q

The most common drug-related adverse event with Vorinostat

A

Diarrhea, fatigue, nausea, and anorexia

47
Q

Selective HDACi given as an IV infusion

Given as a weekly 4-hour infusion of 14 mg/m2 on days 1, 8, and 15 of a 28-day cycle

A

Romidepsin (depsipeptide)

48
Q

Are immunomodulatory polypeptides that both stimulate a Th1 immune response

Adverse effects include major depressive disorder, acute flulike symptoms and fatigue, and marrow suppression.

A

IFN-α and -γ

49
Q

Technique where white blood cells are collected by leukapheresis, exposed to a photoactivating drug, and irradiated with UVA

Was FDA approved in 1998 for the palliative treatment of patients with CTCL

A

Extracorporeal Photopheresis

Administered every 2–4 weeks until clearance of disease

50
Q

A humanized IgG1 monoclonal antibody that targets the CD52 antigen

Used off label for CTCL as salvage therapy

Capable of inducing long-term remission in SS patients, it is not effective in MF and CTCL with large-cell transformation

A

Alemtuzumab

It has a high rate of adverse events, including profound lymphopenia

51
Q

A humanized immunoglobulin (Ig) G1 monoclonal antibody that targets CC chemokine receptor 4 (CCR4) on CTCL tumor cells

A

Mogamulizumab

52
Q

An anti-CD30 antibody conjugated via a protease-cleavable linker to the potent antimicrotubule agent monomethyl auristatin E (MMAE)

Approved by the FDA in 2017 for treatment of patients with CD30+ MF who had received prior systemic therapy

A

Brentuximab vedotin

53
Q

Significant adverse event with Brentuximab vedotin

A

Peripheral sensory neuropathy

54
Q

An IL-2 diphtheria toxin fusion protein targeted to malignant cells that express the CD25 component of the IL-2 receptor

A

Denileukin diftitox (DD)

55
Q

Inhibits activity of the 20S unit of the proteasome to promote apoptosis in tumor cells and is approved for myeloma and mantle cell lymphoma but not approved for CTCL

Dose-limiting side effects included myelosuppression and sensory neuropathy.

A

Bortezomib

56
Q

A novel antifolate with high affinity for reduced folate carrier-1, which has been approved by the FDA for PTCL at 30 mg/m2 intravenously per week

A

Pralatrexate

57
Q

Reserved as palliation in end-stage disease or as a bridge to stem cell transplantation (SCT)

A

Multiagent chemotherapy

58
Q

TRUE OR FALSE

Autologous SCT is recommended for CTCL because of a durable response.

A

FALSE

Autologous SCT is not recommended for CTCL because of a lack of durable response.

59
Q

Candidates for hematopoietic SCT:

A

Patients with aggressive disease such as tumor-stage MF, transformed MF, or SS refractory to multiple lines of systemic therapies

60
Q

A large outcomes study of advanced MF and SS patients identified four independent prognostic variables affecting survival:

A
  • (a) stage IV disease
  • (b) age older than 60 years
  • (c) elevated serum lactate dehydrogenase, and
  • (d) large-cell transformation
61
Q

The second most common CTCLs after MF and represent approximately 30% of CTCL cases

Indolent, carry a favorable prognosis, and tend to regress spontaneously

A

Primary cutaneous CD30+ LPDs

Most cases are CD4+, with loss of pan–T-cell markers CD2, CD3, and CD5

Negative for CD15 and epithelial membrane antigen

Does not express anaplastic lymphoma kinase-1 (ALK-1) or the t(2;5) chromosomal translocation found in nodal ALCL

62
Q

Benign counterpart of PCALCL

A

Lymphomatoid Papulosis

63
Q

Three main histologic types of LyP:

A
  • Type A resemble immunoblasts or Reed-Sternberg cells
  • Type B cells resemble MF
  • Type C cells resemble ALCL
64
Q

LyP is extremely responsive to

A

Low-dose methotrexate therapy

10–15 mg orally weekly

WILLIAM'S HEMATOLOGY (109 decks)

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