Malignancy Flashcards

Question

What is a primary cutaneous lymphoma

Answer 1

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

Answer 2

- 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

Answer 3

- 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

Answer 4

- 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

Answer 5

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

Answer 6

- 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

Answer 7

- 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

Answer 8

- 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

Answer 9

- 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

Answer 10

- 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

Answer 11

arises in oral cavity of immunosuppressed, associated with EBV

Answer 12

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

Answer 13

- 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

Answer 14

- 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

Answer 15

- 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

Answer 16

- 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

Answer 17

- 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

Answer 18

- 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

Answer 19

- 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

Answer 20

- 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

Answer 21

- 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

Answer 22

- 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

Answer 23

- 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

Answer 24

- rare - 5% of all CTCL | - exclusively in adults

Answer 25

- 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

Answer 26

- 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

Answer 27

- 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

Answer 28

- Psoriasis - Atopic dermatitis - PRP - Drug reaction - Actinic reticuloid --> CD3+, CD4- and CD8+

Answer 29

- 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

Answer 30

- 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

Answer 31

- Acute: lymphadenopathy, organomegaly, hypercalcaemia, skin lesions - Chronic: more smoldering, patches, plaques, papular skin --> closely resemble MF --> more protrated clinical course

Answer 32

- 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

Answer 33

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

Answer 34

- 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

Answer 35

- 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 - 2. CD30 positive transformed MF - 3. Other well-defined types of CTCL which may be CD30 positive - 4. Reactive skin conditions with infiltrates containing CD30 positive blast cells - viral, arthropod, scabies, etc

Answer 36

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

Answer 37

- 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%

Answer 38

- 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

Answer 39

- 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)

Answer 40

- 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

Answer 41

- 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

Answer 42

- 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

Answer 43

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

Answer 44

- 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

Answer 45

- 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

Answer 46

- Folliculitis - Arthropod bites - PLEVA and PLC

Answer 47

- 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

Answer 48

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

Malignancy Flashcards

(72 cards)