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Malignancy Flashcards

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1
Q

Immunophenotype CTCL

A
  • To immunophenotype:
    • antigen retrieval techniques allow immunophenotyping on formalin-fixed tissue sections
    • loss of one or more T cell associated antigens such as CD 2,3,4 and 5 by the neoplastic T cells is important criteria
    • loss of CD7 can be a variation of normal
    • Clonal T cell populations have been identified in CTCL but also PLEVA, LP, lichen sclerosus, pseudolymphomas
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2
Q

B/G info CTCL

A
  • heterogenous group of neoplasms of skin homing T cells
  • represent ~ 75-80% of cutaneous lymphomas
  • neoplastic T cells in most CTCLs express cutaneous lymphocyte antigenand the CC-chemokine receptors CCR4 and CCR10, indicating they are the neoplastic counterparts of normal skin-homing T cells
  • To diagnose: 4-6 mm PB or excisional/incisional from untreated skin
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3
Q

Approach to CTCL diagnosis

A
  1. Distinction is made between MF, MF variants and SS and the remainder of CTCL –> these are the 65% most common
  2. Consider primary cutaneous CD30 positive lymphoprolifrative disorders –> do CD30 immunostaining
  3. After this, 90% will be diagnosed. Then consider the rest.
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4
Q

MF Epidemiology

A
  • 50% of cutaneous lymphomas
  • 0.4 per 100 000 per year
  • Adults and men more affected
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5
Q

MF Pathogenesis

A
  1. Genetics:
    1. ?overexpression of TOX
    2. gains of chromosomes
    3. Loss of 9p21.3 - harbours the CDKN2a, CDKN2B and MTAP tumour suppressor genes associated wtih shorter survival
    4. Whole genome sequencing has implicated NF-KB signalling
  2. Environmental
    1. Persistent antigenic stimulation
    2. MALT, H pylori, CBCL (Lyme disease), coeliac disease
  3. Immunologic
    1. CD8 T cells higher in dermal infiltrates, associated with better prognosis
    2. Neoplastic T cells are derived from CD4 T cells with a Th2 cytokine profile (IL-4, IL-5 and IL-10)
    3. Believed to be a gradual shift from type 1 cytokine profiles to type 2 –> increased levels of Th2 cytokines may impair the Th1 cell mediated antitumour response
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6
Q

MF clinical

A
  1. Pre-MF: many years of non-specific lesions with no diagnostic biopsies, 4-6 years median
  2. Early patch MF: variably sized erythematous, finely scaling lesions which may be pruritic, +/- atrophy, poikiloderma, mottled hyper and hypopigmentation,a trophy, telangiectasia (poikiloderma vasculare atrophicans). Prediliction for sunhidden spots.
    1. Annular, polycyclic, typical shorse show
  3. <10% develop nodules or tumours
    1. if tumours present without preceding or co-existing patches then unlikely to be MF
  4. Extra-cutaneous
    1. lymph nodes usually always first, then any visceral
    2. bone marrow rarely involved
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7
Q

MF histology

A
  • Early patch:
    • superficial band like or lichenoid infiltrate, primarily lymphocytes
    • atypical cells, highly convoluted (cerebriform)
    • epidermotropism
    • colonize basal layer as single cells surrounded by vacuolated halos, often in a linear configuration
  • Plaques:
    • Epidermotropism: Pautrier microabscesses (intra-epidermal nests of atypical cells)
    • Acanthosis and elongation of rete ridges
    • +/_ eos and plasma cells
  • Tumour:
    • epidermotropism gone
    • small, medium or large cells with cerebriform nuclei, blast cells with prominent nuclei
    • Large cell transofrmation: presence of CD30 negative or CD30 positive large cells exceeding 25% of the infiltrate or forming microscopic nodules. Of these, CD30 positive have a better prognosis
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8
Q

MF Immunophenotype

A
  • Mature CD3+, CD4+, CD45RO+, CD8- memory T cell phenotype
  • Minority CD3+, CD4-, CD8+
  • May demonstrate partial loss of T cell antigens
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9
Q

MF DDx

A
  • Benign dermatoses
    • Eczema
    • Psoriasis
    • Superficial fungal infections
    • Drug reactions
    • Parapsoriasis
  • Benign dermatoses with histologic features of MF
    • Lymphomatoid contact dermatitis
    • Lymphomatoid drug reactions
    • Actinic reticuloid
  • Other types of epidermotropic CTCL
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10
Q

MF TNMB classification

A
  • T skin:
    • 1 - <10% body patch/plaque
    • 2 - generalised patch/plaque >10%
    • 3 - tumours
    • 4 - erythroderma
  • N nodes
    • 1 - enlarged, no histological findings
    • 2 - enlarged, histo findings, nodal architecture uneffaced
    • 3 - enlarged, nodal architecture partially effaced
  • M - visceral
    • 1 - involvement
  • B - bloods
    • 0 - no Sezary cells (or <5% of lymphocytes)
    • 1 - low blood tumour burden (>5% of lymphocytes are Sezary)
    • 2 - high blood tumour burden - >1000/mcl Sezary cells + positive clone
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11
Q

MF staging

A
  • 1A: T1N0M0,B0-1
  • 1B: T2,N0M0, B0-1
  • 2A: T1-2, N1-2, M0, B0-1
  • 2B: T3, N0-1, M0, B0-1
  • 3: T4, N0-2, M0, B0-1
  • 4A1: T1-4, N0-2, M0, B2
  • 4A2: T1-4, N3, M0, B0-2
  • 4B: T1-4, N0-3, M1, B0-2
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12
Q

MF Monitoring

A
  • No further examinations are recommended for patients with Stage 1A-B disease except for monitoring and checking for clinical lymphadenopathy
  • Do CT chest in patients in whom extracutaneous disease is suspected
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13
Q

MF Treatment options

A
  • Early stages - skin directed therapies:
    • Topical steroids –> complete remission in up to 60%
    • Topical chemotherapy - mechlorethamine –> remission in 60-80%
    • Radiation treatment - total skin electronc beam irradiation with an energy of 4-6 MeV, total dose of 36 Gy over an 8-10 week period.
    • Phototherapy - PUVA, NBUVB, Broadband, UVA1
      • PUVA has become standard for early stages of MR, 80-90% complete response rates have been reported
  • Later stage - systemic therapies
    • Interferons - interferon-alpha inhibitors, can cause flu-like symptoms, hair loss, nausea, depression, BM suppression
    • Retinoids - isotretinoin, acitretin, bexarotene + PUVA –> with PUVA gives similar results as just PUVA but require less treatments
    • Denileukin diftitox - fusion protein, diphtheria toxin is linked to IL-2, binds to the high affinity IL-2 receptor expressed on neoplastic T cells in MF, and internalization of the toxin results in inhibition of protein synthesis and cell death
    • Histone deacetylase inhibitors - vorinostat and romidepsin - inhibition of the enzyme HDAC affects the expression of many genes that are involved in cellular proliferation. ?unsure if patients benefit
    • Systemic chemotherapy - only used in patients with unequivocal lymph node or visceral involvement, or in patients with progressive skin tumours. Get 6 cycles of CHOP.
    • Young patients: allogeneic haematopoietic stem cell transplantation may be considered
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14
Q

MF Guide to treatment

A
  • Pre-mycotic –> steroids, NBUVB
  • Stage 1A-2A –> PUVA, NBUVB, topical steroids or retinoids, RT, TSEB (total skin electron beam irradiation)
  • Stage 2B –> PUVA or HN2 + RT, TSEB, if relapse PUVA + IFN-alpha, PUVA + retinoids, HDACi
  • Stage 3 –> ECP, if not effective add INF-alpha, low dose chlorambucil + prednisone, add skin directed therapies if necessary. Second line: oral bexarotene, denileukin, HDACI, low dose alemtuzumab
  • Stage 4 –> chemotherapy, biologics - denileukin, IFN-alpha, oral retinoids, skin-directed therapies, if recalcitrant allogeneic haemotopoietic stem cell transplant
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15
Q

MF prognosis

A
  • Stage 1A - 96% survival 10 years
  • 1B - 77-83%
  • 2B - 42%
  • 4 - 20%
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16
Q

Folliculotropic MF Epi

A
  • Approximately 10% of MF patients

- M>F

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17
Q

Folliculotropic MF clinical and staging

A
  • Grouped follicular papules, acneiform lesions, indurated plaques and sometimes tumours
  • Preferentially involve the head and neck
  • Associated with alopecia, and mucinorrhoea
  • Infiltrated plaques in the eyebrow region with concurrent alopecia are highligh characteristic
  • Pruritis
  • Secondary bacterial infections
  • Is not helpful
  • Peri-follicular localization makes it hard to respond to cutaneous treament
  • Assume they are at tumour stage
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18
Q

Folliculotropic MF Histology

A
  • Peri-vascular and peri-adnexal localization of dermal infiltrates, with variable infiltration of the follicular epithelium by small, medium sized or sometimes large T cells with hyperchromatic and cerebriform nuclei
  • Has folliculotropism instead of epidermotropism
  • Mucinous degeneration of follicular epithelium
  • Stain: Alcian blue or colloidal iron staining will show mucin
  • In peri-follicularm neoplastic T cells may be blasts rather than cerebriform
  • Phenotypes: CD3+, CD4+ and CD8-, may have CD30 positive blast cells
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19
Q

Folliculotropic MF DDx

A
  • Other epidermotropic CTCL
  • Seb derm and atopic dermatitis
  • Follicular mucinosis
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20
Q

Folliculotropic MF Rx

A

Combination of PUVA with either IFN-alpha or retinoids, local radiotherapy or TSEB

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21
Q

Pagetoid Reticulosis Clinical

A
  • extremely rare, <1% of CTCL

- Solitary psoriasiform or hyperkeratotic patch or plaque, localized to extremity and slowly progressive

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22
Q

Pagetoid Reticulosis Histology

A
  • hyperplastic epidermis
    • marked infiltration of large atypical pagetoid cells into epidermis - arranged singly or in nests or clusters
    • Atypical cells have medium sized or large, sometimes hyperchromatic and cerebriform ncueli
    • Superficial dermis may have small lymphocytes
  • Immunophenotype:
    • CD3+, CD4+, CD8- or CD3+, CD4- and CD8+
      CD30 often expressed
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23
Q

Pagetoid Reticulosis Treatment

A

radiotherapy or surgical excision

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24
Q

Granulomatous Slack Skin

A
  • also very rare
  • pendulous lax skin with a prediliction for axillae and groin
  • association with Hodgkin lymphoma
  • Indolent course
  • Histology:
    • dense granulomatous dermal infiltrates containing atypical T cells with cerebriform nuclei, macrophages
    • Destruction of elastic tissue and elastophagocytosis
    • Epidermis may be infiltrated by small atypical T cells
    • CD3+, CD4+ and CD8=
  • Treatment: radiotherapy
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25
Q

What is a primary cutaneous lymphoma

A

malignant lymphoma confined to the skin at presentation after complete staging procedures

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26
Q

WHO classification of CBCL (i.e. name them)

A
  • Primary cutaneous follicle centre lymphoma
  • Primary cutaneous diffuse large B cell, leg type
  • Primary cutaneous marginal zone b cell lymphoma - Extranodal marginal zone lymphoma of MALT lymphoma
  • Diffuse large B cell lymphoma, NOS
  • Intravascular diffuse large B-cell lymhoma
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27
Q

CBCL epidemiology

A
  • Varies worldwide, seem to be more in Europe
  • Borrelia associated - so more in endemic regions
  • M=F
  • Uncommon in kids a part from B lymphoblastic lymphoma/leukaemia
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28
Q

Pathogenesis of CBCL

A
  • Unknown
  • Little data on genetics
  • Possible longstanding antigenic stimulation due to chronic infection with specific microorganisms –> H pyloria, Borrelia
  • Immune dysregulation: associated with immunosuppression, AIDS, transplant recipients, methotrexate
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29
Q

CBCL how to stage

A

comple blood exam, flow cytometry, CT chest, abdomen and pelbis, and PET
- Internationally, BM biopsy still recommended in follicle centre lymphoma, leg type and intravascular but not helpful in marginal zone

30
Q

Primary cutaneous follicle centre lymphoma clinical

A
  • Neoplastic proliferation of germinal centre cells confined to the skin
  • Most common
  • Solitary or grouped, pink-plum coloured papules, plaques or tumours
  • Particularly to trunk, can be surrounded by patches of erythema
  • ‘Crosti’s lymphoma’ = peripheral patch of erythema
  • Rarely - miliary or clustered small papules that are acneiform in nature
  • Preferences scalp, forehead, back
  • B symptoms are rare, LDH is normal and has good prognosis
  • Recurrences in up to 50% of patients, but dissemination to lymph nodes and internal organs are rare
31
Q

Primary cutaneous marginal zone B cell lymphoma (Extranodal marginal zone lymphoma of the MALT) clinical

A
  • Previously classified as primary cutaneous immunocytoma or primary cutaneous plasmacytoma
  • Recurrent asymptomatic pink-violet to red-brown papules, plaques and nodules that favour extremities (upper > lower) or trunk
  • Rarely generalized, raerly ulcerate
  • B symptoms are not present, LDH within normal limits, good prognosis
  • Resolution - may be accompanied by secondary anetoderma due to loss of elastic fibres int he area of the tumour
  • Can arise in areas affected by acrodermatitis chronica atrophicans - Europe
32
Q

Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type clinical

A
  • Characterised by predominance of large round cells - centroblasts, immunoblasts - that are positive for Bcl-2, MUM-1 and FOX-P1
  • Exclusively in older patients and mostly women
  • Solitary or clustered erythematous to red-brown nodules, located primarily on the distal aspect of one leg (therefore leg type). Small erythematous papules adjacent to larger nodules
  • Lesions may arise on both lower extremities within a short time interval
  • Ulceration
  • In ~20% will not be on the legs
  • Prognosis: not as good, 5 year survival 40-50%, loss of CDKN2A associated with a worse prognosis
  • Ddx: large B cell lymphoma with leg involvement, so need complete work up prior to diagnosis of leg type
33
Q

Intravascular diffuse large B cell lymphoma clinical

A
  • Rare, malignant proliferation of large B lymphocytes within blood vessels
  • Occasionally, skin is the only affected site but often there is systemic involvement including the CNS
  • Clinically: indurated, erythematous or violaceous patches and plaques - trunks and thighs, prominent telangiectasia
  • Not typical of cutaneous lymphoma, and may suggest diagnosis of panniculitis or vascular tumour
  • Prognosis is bad, it is aggressive
  • Several patients, was observed to be confined to cherry angioma lesions
34
Q

Precursor B Lymphoblastic Lymphoma/Leukaemia clinical

A
  • Malignant proliferation of precursor B lymphocytes
  • rarely is the skin the primary site, if it is still treat them like it is systemic
  • Children and young adults
  • Solitary, large erythematous tumours - commonly located on the head and neck
  • Often asymptomatic for a few weeks
  • If secondary skin lesions - B symptoms present, LDH elevated
  • Agressive, poor prognosis
35
Q

Plasmablastic lymphoma clinical

A

arises in oral cavity of immunosuppressed, associated with EBV

36
Q

CBCL how to diagnose

A
  • Histology

- PCR + FISH –> detect rearrangements in immunoglobulin genes as well as specific chromosomal translocations

37
Q

Primary cutaneous follicle centre lymphoma histo

A
  • Epidermis is spared
  • Bottom heavy infiltrate in varying size and shape
  • 25% have clear cut follicular pattern with formation of neoplastic germinal centres
    • neoplastic follicles show morphologic features of malignancy: reduced or absent mantle zone, lack of tingible body macrophages, monomorphism of follicles
  • Centroblasts and medium-large sized centrocytes (large, cleaved follicle centre cells)
  • Keep in mind, if monotonous proliferation of centroblasts and/or immunoblasts then classify as diffuse large B cell lymphoma
  • There is a variant that looks like spindle cell tumours
38
Q

Primary cutaneous follicle centre lymphoma stains and molecular analysis

A
  • CD10 (follicular has 10 letters)
  • bcl-6
  • CD20
  • MIB-1
  • CD79a
    How to differentiate - lower degree of proliferative activity within malignant follicles by anti-Ki 67 antibody in contrast to strong Ki-67 positivity in reactive follicles
    Negative for CD5, CD23, bcl-2 and MUM-1
    Genetic analysis: immunoglobulin heavy chain rearrangement in 60-70% of patients
39
Q

Primary Cutaneous Marginal Zone B cell Lymphoma histo

A
  • Patchy, nodular or diffuse infiltrate involving the dermis and subcutaneous fat
  • Epidermis is spared
  • Characteristic pattern:
    • nodules of reactive lymphocytes which have reactive germinal centre. These are surrounded by neoplastic marginal zone cells
    • surrounded by marginal zone cells pale staining small to mediu sized cells with indented nuclei, inconspicious nucleoli and abundant pale cytoplasm
    • in addition, plasma cells at the margins of the infiltrate, lymphoplasmacytoid cells, small lymphocytes, eosinophils
    • Dutcher bodies: PAS positive intranuclear inclusions - eosinophilic
  • Rarely, the predominant cell type is the plasma cell
40
Q

Primary Cutaneous Marginal Zone B cell Lymphoma stains and molecular analysis

A
  • Stains: bcl-2, CD20, CD79a
  • Negative for CD5, CD10, CD23, Bcl-6
  • Intracytoplasmic monotypic expression of immunoglobulin light chains - kappa or gamma - can be observed
  • Monoclonal rearrangement of IGH can be detected in 60-80% of cases
    • Express class switched immunoglobulins
    • although the B lymphocyte changes antibody production from one class to another, the cell retains affinity for the same antigen
    • Particular translocation that has been detected: IGH and MALT1
    • In 50% patients no molecular abnormalities are found
    • Other genetic aberrations in trisomy 3
41
Q

Primary Cutaneous Diffuse Large B Cell Lymphoma histo

A
  • Grenz zone
  • Diffue infiltrate in dermis and subcutis
  • Can involve epidermis - Pautrier microabscesses
  • Immunoblasts (large round cells with abundant cytoplasm and prominent nucleoli) and centroblasts
  • Cells are + large
42
Q

Primary Cutaneous Diffuse Large B Cell Lymphoma stains and molecular analysis

A
  • Positive for CD20, CD79a, PAX-5 and IgM (B cell markers) but there can be a partial loss of antigen expression
  • Neoplastic cells mostly express Bcl-2, MUM-1, FOX-P1 and MYC
  • Demonstrate monoclonal rearrangement of IGH
43
Q

Approach to diagnosis of cutaneous large b cell lymphoma:

A
  • if the predominant cell type is large and cleaved then it is a follicle centre diagnosis
  • if large round –> check where it is
    • Intra-vascular –> intravascular dx
    • Dermis or subcutis –> do BcL immunophenotype
      • Bcl-2 positive –> diffuse large cell, leg type
      • Bcl-2 negative –> diffuse large cell, other
  • So basically - marginal and diffuse large cell are positive for Bcl-2 and follicle cell isn’t
44
Q

Intravascular diffuse large b cell lymphoma histo, stains and molecular analysis

A
  • proliferation of large atypical lymphocytes that fills dilated blood vessels within the dermis and subcutaneous tissues
  • positive for B cell markers and Bcl-2 and MUM-1 and FOX-P1
  • Stain with CD31 and CD34 to highlight intravascular location
  • Monoclonal rearrangement of IGH or molecular analysis
45
Q

Precursor B lymphoblastic lymphoma/leukaemia histo, stains and molecular analysis

A
  • monomorphous proliferation of medium-sized cells with scanty cytoplasm and round or convoluted nuclei with fine chromatin
  • ‘Starry sky’ due to tingible bodies: macrophages with inclusion bodies
  • Mosaic stone pattern
  • Mitoses + necrotic cells
  • Positive for Tdt (present on precursor T and B cells), PAX-5, CD10, CD20, CD79 and cytoplasmic mu chain of immunoglobulins
  • Monoclonal rearrangement of IGH and polyclonal for TCR
46
Q

CBCL management

A
  • Once you have diagnosis from histo, molecular and immunohistochemistry then you must stage
    Low grade:
  • watchful waiting - follow up every 6 months
  • papulonodules - can use IL-kenacort
  • Few lesions –> surgical excision with close margins, radiation treatment with wide margins (10-20 cm)
  • Reports of antibiotics (similar to treating H pylori and MALT). Complete response in those caused by borrelia
  • Subcutaneous or intralesional interferon
  • IL rituximab
    High grade:
  • Chemotherapy + rituximab - CHOP
  • IV rituximab
47
Q

Sezary triad and diagnostic criteria

A
  • triad: erythroderma, generalized lymphadenopathy, presence of neoplastic T cells (Sezary) in the skin, LN and blood
  • Diagnostic criteria:
    • demonstration of a T-cell clone in the peripheral blood
    • Absolute Sezary cell count >1000 cells or immunophenotypical abnormalities
48
Q

Sezary epi

A
  • rare - 5% of all CTCL

- exclusively in adults

49
Q

Sezary clinical

A
  • erythroderma with marked exfoliation, oedema and lichenification
  • ++ pruritic
  • Lymphadenopathy, alopecia, onychodystrophy, palmoplantar hyperkeratosis
  • Prior - may have non-diagnostic dermaittis
  • Poor prognosis - 5 year survival 25%, most die of opportunistic infections due to immunosuppression
50
Q

Sezary histology

A
  • Can be similar to MF
  • Cellular infiltrates more monotonous, and epidermotropism may be absent
  • 1/3 –> may be non-specific
  • LN: dense, monotonous infiltrate of Sezary, with effacement of the normal lymph node architecture
  • BM may be involved
  • Phenotype: CD3+, CD4+, CD8- phenotype, lack CD7 and CD26, and express programmed death-1
51
Q

Sezary pathogenesis

A
  • unknown
  • Neoplastic CD4+ T cells have the phenotype of a central memory T-cell subset, and are capable of circulating between skin, LN and peripheral blood, whereas MF iits derived from non-circulating skin resident effector memory T cells
  • SS and MF have major genomic differences
  • Deletions of chromosomes that encode PTEN, and gains of those including MYC
52
Q

Sezary ddx

A
  • Psoriasis
  • Atopic dermatitis
  • PRP
  • Drug reaction
  • Actinic reticuloid –> CD3+, CD4- and CD8+
53
Q

Sezary Rx

A
  • Skin directed therapies as an adjuvant may be helpful - PUVA and topical steroids
  • Extracorporeal photopheresis - alone or in combination with others –> overall response rate ~25%
  • Others: interferon alpha, and prolonged treatment with MTX or low dose chlorambucil + pred, CHOP –> higher response rates but generally short lived
  • Recent studies indicated: bexarotene, denileukin, diftitox, HDACi, alemtuzumab (anti-CD52)
  • Curative for advanced disease: allogenic haemotpoietic stem cell transplant
54
Q

Adult T Cell Leukaemia-Lymphoma epi

A
  • Endemic to areas with high HTLV-1 –> southwestern Japan, the Carribean, parts of Central Africa
  • Jewish population in Mashad, Iran
  • Only minority who are seropositive develop ATLL
  • Occurs in adults, M>F
  • Vertical transmission more common than horizontal
55
Q

Adult T Cell Leukaemia-Lymphoma clinical

A
  • Acute: lymphadenopathy, organomegaly, hypercalcaemia, skin lesions
  • Chronic: more smoldering, patches, plaques, papular skin –> closely resemble MF –> more protrated clinical course
56
Q

Adult T Cell Leukaemia-Lymphoma Histology

A
  • Superficial or diffuse infiltrate of small, medium sized or large pleomorphic T cells
  • Marked epidermotropism
  • May be difficult to distinguish from MF
  • Express: CD3+, CD4+, CD8-, CD25+, strongly expressed PD-1
57
Q

Adult T Cell Leukaemia-Lymphoma Ddx

A
  • MF

- Dx of ATLL requires demonstration of clonally integrated HTLV-1

58
Q

Adult T Cell Leukaemia-Lymphoma Rx

A
  • Zidovudine and interferon-alpha, but mostly needs chemotherapy
  • In Japan - anti-CCR4 (mogamulizumab) is approved for treating ATLL
  • If chronic, can do skin-directed therapies
59
Q

Primary Cutaneous CD30 Positive Lymphoproliferative disorders

A
  • Second most common group, accounting for 25% of CTCL
  • Includes:
    • Primary cutaneous anaplastic large cell lymphoma
    • Lymphomatoid papulosis
    • Borderline cases –> cannot decide between ALCL and LyP
  • Should be differentiated from:
      1. Skin involvement by systemic ALCL
      1. CD30 positive transformed MF
      1. Other well-defined types of CTCL which may be CD30 positive
      1. Reactive skin conditions with infiltrates containing CD30 positive blast cells - viral, arthropod, scabies, etc
60
Q

Primary Cutaneous Anaplastic Large Cell Lymphoma Epi

A
  • ~12% of all CTCLs
  • M>F, 2:1, mostly adults
  • More common in breast implants - relative risk of 421.8
61
Q

Primary Cutaneous Anaplastic Large Cell Lymphoma clinical

A
  • Solitary or localized nodules or tumours (occasionally papules) that often develop ulceration
  • 20% –> multifocal lesions
  • May show partial or complete spontaneous regression, and frequently relapse in the skin
  • Extracutaneous in 10% –> mainly regional lymph nodes
  • Prognosis is good –> 10 year disease related survival exceeding 85%
62
Q

Primary Cutaneous Anaplastic Large Cell Lymphoma Histology

A
  • Diffuse non-epidermotropic infiltrates with cohesive sheets of large CD30 positive tumour cells
  • Most cases, the tumour cells have characteristic morphology of anaplastic cells, with round, oval or irregularly shaped nuclei, prominent eosinophilic nucleoli, and abundant cytoplasm
  • Less commonly tumour cells have a plemorphic, immunoblastic or Reed-Steenberg cell-like appearance
  • High mitotic index
  • Reactive lymphocytes at the periphery of the tumour
  • Ulcerating lesions may show an LyP-like histology –> abundant inflammatory infiltrate of reactive T cells, histiocytes, eosinophils, neutrophils and relatively few CD30 positive cells. Epidermal hyperplasia may be prominent. Intra-lymphatic complexes of tumour cells are common
63
Q

Primary Cutaneous Anaplastic Large Cell Lymphoma IMmunophenotype

A
  • CD4+, loss of CD2, CD5 and CD3
  • CD30 must be expressed by the majority of neoplastic cells
  • 70% of cases - expression of cytotoxic proteins - granzyme, TIA-1, perforin
  • MUM1/IRF4 expressed in almost all cases
  • Express cutaneous lymphocyte antigen, but do not express EMA (epithelial membrane antigen) or ALK (anapplastic lymphoma kinase)
64
Q

Primary Cutaneous Anaplastic Large Cell Lymphoma genetics

A
  • Systemic ALCL in kids has t(2;5) translocation
  • There have been unusual cases of ALK+ C-ALCL including:
    • Strong nuclear and cytoplasmic staining of the t(2;5) chromosomal translocation
    • Or expression of cytoplasmic ALK protein
  • C-ALCL: rearrangements of the DUSP22-IRF4 locus onf 6p25.3 almost exclusively in C-ALCL and small subset of LyP
  • There are other chromosomal aberrations
  • High expression of skin-homing chemokine receptor genes CCR10 and CCR8 –> may explain affinity for skin and low incidence of dissemination to extracutaneous sites
65
Q

Primary Cutaneous Anaplastic Large Cell Lymphoma Rx

A
  • Initial: radiation therapy or surgical excision
  • If solitary lesion disappears spontaneously, no further therapy is required
  • Multi-focal: radiation treatment, low dose MTX, interferon alpha
  • Extra-cutaneous: doxorubicin-based multi-agent chemotherapy
  • If on one or both legs then risk for more aggressive clinical course
  • Brentuximab - anti-CD30 is FDA approved for relapsed systemic ALCL
    • In an international open-label randomized phase 3 trial - 56.3% of patients receiving brentuximac versus 12.5% receiving methotrexate or bexarotene responded at 22.9 months
    • major side effect: peripheral neuropathy in 2/3 of patients
66
Q

Lymphomatoid papulosis pathogenesis

A
  • Unknown
  • ?viral –> no real evidence
  • randomly goes away as well
  • Interactions between CD30 and its ligand may contribute to apoptosis of the neoplastic T cells and subsequent regression of skin lesions
  • Mutation in TGF-beta has been suggested
67
Q

Lymphomatoid papulosis epi

A
  • 15% of all CTCL
  • Any age
  • Average age 35-45 years
  • Male:female - 1.5:1
68
Q

Lymphomatoid papulosis clinical

A
  • red-brown papules and nodules - can develop central haemorrhage, necrosis and crusting
  • spontaneously dissappear 3-12 weeks later
  • lesions in different stages of evolution coexist
  • residual transient hypopigmented or hyperpigmented macules, and superficial atrophic varioliform scars that may disappear without ulceration or sequelae
  • number of lesions varies from several to >100
  • lesions may be localized, sometimes clustered within rather well-defined areas or generalized
  • predominant sites: trunk and limbs
  • asymptomatic
  • Ranges from a few months to 40 years
  • 20% –> associated with cutaneous or systemic lymphoma - generally MF< C-ALCL, Hodgkin lymphoma
  • Prognosis: excellent
69
Q

Lymphomatoid papulosis histology

A
  • Correlates with the age of the sampled skin lesion
  • Several histologic subtypes have been described, not helpful in therapeutic or prognostic implications
    • Type A: classic, most common. >75%. Wedge-shaped infiltrate, with scattered or small clusters of atypical CD30 T cells. Prominent epithelial hyperplasia with focail vesiculation, and subepidermal oedema, and dense lymphoid infiltrates in the dermis
    • Type B: epidermotropic, superficial perivascular to band0like and sometimes wedge-shaped infiltrate of small to medium sized, atypical CD4+, CD30+ or CD30-
    • Type C: diffuse infiltrates or large clusters of large CD30 T cells
    • Type D: marked epidermotropism of atypical, small to medium sized, CD8+, CD30+, pleomorphic T cells, necrotic keratinocytes
    • Type E: angioinvastion and destruction by CD8, CD30
    • Type F: perifollicular infiltrates with variable degree of folliculotropism of atypical CD30 T cells
70
Q

Lymphomatoid papulosis ddx

A
  • Folliculitis
  • Arthropod bites
  • PLEVA and PLC
71
Q

Lymphomatoid papulosis Rx

A
  • Topical or systemic steroids and antibiotics are not helpful
  • Systemic chemotherapy or TSEB irradiation may help, but once you stop therapy it comes back
  • If have few non-scarring lesions, can just monitor
  • Cosmetically disturbing: low dose methotrexate
  • Consider PUVA, topical mechlorethamine or carmustine, low dose etoposide
  • If large skin tumour –> observe for 4-12 weeks, if doesn’t remit then excise or radiotherapy
  • Long term follow up for all patients
72
Q

5 year survival for anogenital melanoma

A

25-60% for vulval
10% penile
<20% anorectal

Derm (57 decks)

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