Cutaneous lymphomas Dan Flashcards
What investigations should you do for CTCL pts?
Diagnostic (see criteria; need 4 out of 6 points for MF); - H+E and immunopathology - TCR gene rearrangement Staging/prognostic (all pts); - FBC, ELFT, blood film - lymphocyte subsets - Sezary cell count (Buffy coat prep) - LDH - Calcium - Uric acid If stage 1B or higher also do; - Blood flow cytometry - Blood TCR gene rearrangement - CXR If extensive stage 1B or stage IIA or higher also do; - CT chest/abdo/pelvis - PET CT if IIB or higher - Refer for BM biopsy if IIB or higher Also; - Biopsy any persistently enlarged LN - HIV test – must do if CD30+ve (see later) - HTLV-1 serology if suspected ATLL
What is treatment ladder for MF?
Australian treatment ladder;
Depends on subtype and extent as well as local availability;
1. TCS
2. PUVA
3. UVB
4. Tazarotene - not used much
5. MTX or TSEBT or IFNα
6. Acitretin/isotretinoin
7. IFNα + PUVA
8. Chemo – doxorubicin, gemcitibine, CHOP
9. Stem cell transplant
ECP – Melbourne only
Alemtuzumab – erythrodermic MF or Sezary
Danileukin diffitox – rarely used but has been used in studies at Peter Mac
Topical nitrogen mustard or mechloethamine are not used in Aus as too hard to get. Same for topical and systemic Bexarotene
What LNs should be biopised in CTCL?
Peripheral nodes >1.5cm or central nodes >1cm are considered pathological until proven otherwise
Biopsy any persistently enlarged LN
Or any node 1.5cm diameter or greater + fixed, firm and irregular
surgical LN biopsy preferred
T/F
FNA is useful for LN assessment in MF pts
False
FNA doesn’t allow proper node staging
Refer to surgeon for surgical biopsy of whole nodes
What ratio of T cell markers on immunopathology or flow cytometry is of interest in MF or Sezary syndrome?
CD4:CD8 ratio >6 in MF
CD4:CD8 ratio >10 in Sezary syndrome
- not diagnostic but very suggestive
What special stain is important in Extranodal NK/T cell lymphoma, nasal type?
EBER-ISH stain for EBV
T/F
electron beam therapy may help leonine facies in cutaneous lymphoma
True
T/F
erythrodermic MF is when over 95% of BSA is involved
False
over 80%
T/F
stage 1A MF has 88% 5 year survival
False
Stage 1A has normal survival
MF overall has 88% 5 year survival
T/F
In erythrodermic MF pts, nodal involvement is most important prognostic indicator
True
What are poor prognostic markers in MF?
think - clinical, histo, bloods
Age over 60 at onset
More advanced skin stage (T stage)
Nodal or visceral disease
Folliculotropic disease
Granulomatous pathology (GMF)
Large cell transformation
Presence of a detectable T cell clone in blood (esp if identical in blood and skin)
Raised LDH (marker of anaerobic respiration in tumour cells)
Raised β2 microglobulin (>2mg/L; lymphoma tumour marker)
T/F
MF pts are at increased risk of other cancers
True NMSC Small cell lung cancer Other lymphomas and leukaemias (esp in GMF and GSS, esp Hodgkins) Pts relatives also higher risk
T/F
PCR is helpful to distinguish benign follicular mucinosis from true folliculotropic MF
False
as both can have clonal gene rearrangements
T/F
folliculotropic MF has a better prognosis than classical (Alibert-Bazin) MF
False
worse
80% 5 year survival, 35% 10 yr survival
What are Rx of folliculotropic MF?
skin directed therapy systemic IFNalpha PUVA UVB XRT of isolated areas Total skin electron beam
What is syringotropic MF
2014 JAAD case series
Rare variant of folliculotropic MF
Lymphoid infiltrate centred on the eccrine epithelium
Eccrine structures may become hyperplastic
Punctated erythematous patch esp on limbs or trunk which may have; alopecia, comedo-like changes, ulceration or hypochromia
PPK is a common finding in some reports
often resistant to skin-directed therapy
present earlier than folliculotropic MF
but better prognosis than folliculotropic MF
T/F
Pagetoid reticulosis has a poor prognosis
False
very good
excision or low dose superficial DXT can be curative
T/F
Pagetoid reticulosis is chacterised by striking atypical cells – large, pale atypical lymphocytes – look like Pagets cells
True
NOT pagetoid spread
TCR usually shows clone
What is the triad of Sezary syndrome?
Erythroderma
Peripheral lymphadenopathy
Sezary cells comprising 5% or more of peripheral blood lymphocytes or over 20% of total lymphocyte count or total Sezary count over 1000 x 10 to the 9/L (not in erythrodermic MF)
T/F
To diagnose Sezary T-cell lymphoma leukaemia need to confirm a peripheral blood T-cell clone
True
CD4:CD8 ration over10
- not diagnostic but very suggestive
Aberrant expression of pan T-cell antigens
Cytogenetic or TCR gene analysis evidence of clonal T cell proliferation
T/F
Sezary syndrome is an aggressive leukaemic variant of MF
True
typically arises de novo (cf erythrodermic MF) but can also be a progression of classical MF
What are the clinical features of Sezary syndrome?
Exfoliative erythroderma
May be symptoms of high output cardiac failure (due to very dilated skin vasculature) or other complications
Ectropion
Scalp alopecia
Palmoplantar hyperkeratosis (keratoderma) +/- fissuring (PRP important differential in this case)
Subungual hyperkeratosis
What do Sezary cells look like?
Sezary cells have very large nucleus and minimal cytoplasm
Large ones are easier to recognise but small sezary cells are seen more commonly
Large cells confer worse prognosis
What is the immunophenotype of Sezary cells?
CD3+, CD4+
CD26-
CD7 may be negative = worse prognosis
What is the staging and Rx of Sezary syndrome?
On same scale as MF
By definition stage is T4, N0-3, M0-1, B2
= stage IVA
Treated in same way as advanced MF
What is granulomatous slack skin?
How is it treated?
Rare MF variant
Slow development of pendulous folds of slack skin, usually in flexures
Dense granulomatous infiltrate in dermis
Elastolysis in upper dermis due to histiolytic giant cells (EVG stain shows)
Atypical lymphocytic infiltrate in dermis with abnormal lymphocyte immunophenotype
TCR gene rearrangement shows clonal abnormalities
Treat with retinoids or XRT or surgery
T/F
granulomatous slack skin is the same as granulomatous MF
False
GMF is a histological variant which clinically looks the same as classical MF.
T/F
skin extension from primary nodal CD30+ lymphoma can be B or T or Null cell derived
True
whereas always T cell origin if true primary cutaneous CD30+ disease
What are the causes of causes of cutaneous CD30+ lymphoproliferation
primary cutaneous CD30+ lymphoproliferative disease
MF w/ large cell transformation;
HIV associated Or post transplant lymphoma
Skin extension of systemic ALCL
Reactive (non malignant) CD30+ infiltrate in PLEVA, eczema, viral infection, scabies, insect bites etc
What conditions make up primary cutaneous CD30+ lymphoproliferative disease
Lymphomatoid papulosis
Primary cutaneous anaplastic large cell lymphoma - localised or widespread
these condtions are on a spectrum - borderline cases are those in whom a distinction cannot be made between these
How do you differentiate MF w/ CD30+ large cell transformation from primary cutaneous CD30+ lymphoproliferative disease?
Histological appearance and CD30 positivity in new nodules/tumours in a pt with typical patch/plaque MF suggests large cell transformation
One or a small number of isolated tumours in a pt without MF and very high number of CD30+ large cells (>75%) is indicative of Primary cutaneous CD30+ lymphoproliferative disorder
T/F
nodal extension of primary cutaneous CD30+ lymphoproliferative disease can strongly resemble Hodgkins lymphoma
True
probably often misdiagnosed
Why is clinical evaluation of lesions of LyP throught time important?
For LyP lesions should heal over 3-12 weeks; often with varioliform scarring
‘waxing and waning’ is typical of LyP
MUST ensure that every single lesion resolves regardless of formation of new lesions – if not resolving consider upgrading diagnosis to cutaneous CD30+ anaplastic large cell lymphoma
T/F
classical histo signs of MF are seen in cutaneous CD30+ lymphoproliferative disease
False
Mixed dermal infiltrate of atypical lymphocytes (large cerebriform nuclei), eos, neuts, histiocytes and extravasated RBCs – can extend deep into reticular dermis
Doesnt usually have much epidermotropism or Pautrier micorabscesses. Epi may be ulcerated
Frequent mitoses
4 types of pathology seen in LyP A-D
What are the sub types of histo in LyP?
A – mainly large atypical CD30+ cells resembling Reed-Sternberg cells
B – smaller atypical T cells similar to those in MF; CD3+ and CD4 +; may or may not be CD30+ve
C – large clusters of CD30+ cells w/ pattern typical of anaplastic large cell lymphoma
D – CD8+, CD30+ cells; path mimics aggressive CD8+ epidermotropic T-cell lymphoma
Common to have several histo types in same pt
What are the DDs of LyP?
Clinical;
PLEVA – Also, some cases of ‘PLEVA’ sometimes show histo like type B LyP and probably should be diagnosed as LyP
nodular prurigo
lues maligna
papulonecrotic tuberculid
disseminated histoplasmosis
drug eruption esp halogenoderma
Histo +/- clinical;
(Multifocal) C-ALCL - major DD if doesnt wax and wane
MF w/ large cell transformation (esp type B LyP);
HIV associated Or post transplant lymphoma
Skin extension of systemic ALCL
Reactive (non malignant) CD30+ infiltrate in PLEVA, eczema, viral infection, scabies, insect bites etc
Hodgkins disease - major DD of nodal extension
T/F
LyP never turns into primary cutaneous or nodal CD30+ large cell anaplastic T-cell lymphoma
False
5% of cases progress to primary cutaneous or nodal CD30+ large cell anaplastic T-cell lymphoma
T/F
Aggressive chemo can cure LyP
False
Some evidence that aggressive chemo can cause transformation to a more aggressive CD30+ lymphoproliferative disorder
How is LyP treated?
How is primary cALCL treated?
LyP often resolves eventually
No curative treatments available
Long term f/u to monitor for disease progression
new lesions can use TCS or ILCS or topical nitrogen mustard to accelerate clearance (dont help older lesions)
Low dose MTX is best systemic
Dapsone may help
UVB or PUVA
Primary cALCL;
Some lesions resolve spontaneously even if large so can observe for a short period (?1-3/12)Treat isolated lesions with excision or local DXT
Even variants with regional LN secondary involvement have been treated successfully with DXT
Low dose MTX
Systemic chemo e.g. CHOP
T/F
In primary cALCL bone marrow biopsy is only needed if skin disease is extensive
False
refer to haematologist is this is diagnosed;
BM biopsy required to exclude skin extension of visceral disease - much worse prognosis
Also must biopsy any enlarged LNs - do PET CT to look for enlarged nodes
T/F
If nodal and skin involvement of primary cutaneous CD30+ lymphoma present at same time diagnosis is most likley primary nodal disease with skin extension
False
very difficult to determine site of primary
need good history
can be nodes or skin or both due to underlying systemic disease
must investiaget fully and biopsy all sites for histo, immunophenotype and TCR gene rearrangement
T/F
In primary cALCL there is a 50% risk of extension to LNs or other extracutaneous sites
False
10% risk
high risk if extensive localized disease
T/F
Subcutaneous panniculitis-like T-Cell lymphoma (SPTL) is derived from γδ T cells
False
from αβ T-cells
T/F
lupus panniculitis is the main DD for Subcutaneous panniculitis-like T-Cell lymphoma (SPTL)
True
similar clinical features and pathology
T/F
Subcutaneous panniculitis-like T-Cell lymphoma (SPTL)
has a poor prognosis
False
good prognosis
80% 5 year survival
systemic steroids are mainstay of treatment
T/F
Subcutaneous panniculitis-like T-Cell lymphoma (SPTL) affects young adults
True
T/F
Rimming of tumour cells around fat cells is characteristic of Subcutaneous panniculitis-like T-Cell lymphoma (SPTL)
True
Which primary cutaneous T cell lymphomas are considered to have indolent behaviour?
Mycosis fungoides (MF) and variants‘Granny Folds Pages’;
- Folliculotropic MF
- Pagetoid reticulosis
- Granulomatous slack skin
Primary cutaneous CD30+ lymphoproliferative disorders
- Lymphomatoid papulosis
- Primary cutaneous anaplastic large cell lymphoma
Subcutaneous panniculitis-like T-Cell lymphoma (SPTCL)
Primary cutaneous CD4+ small/medium-sized pleomorphic T-Cell lymphoma
Which primary cutaneous T cell lymphomas are considered to have aggressive behaviour?
Sezary syndrome
Cutaneous γ/δ T-Cell lymphoma
Extranodal NK/T-Cell lymphoma (nasal type)
Primary cutaneous aggressive epidermotropic CD8+ Cytotoxic T-Cell lymphoma
CD4+/CD56+ haematodermic neoplasm (Blastic NK-Cell lymphoma)
Adult T-Cell leukaemia/lymphoma (ATLL)
Primary cutaneous peripheral T-Cell lymphoma, unspecified
Which primary cutaneous B cell lymphomas are considered to have indolent behaviour?
Primary cutaneous follicle centre lymphoma (PCFCL)
Primary cutaneous marginal zone B-cell lymphoma (PCMZL)
Which primary cutaneous B cell lymphomas are considered to have aggressive behaviour?
Be Big and Bad - the B-cell lymphomas with Large in the name are bad
Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL)
- leg type
- intravascular
- other
T/F
It is necessary to exclude a history of MF in pts with suspected Primary Cutaneous CD4-Positive Small/Medium Pleomorphic T-cell Lymphoma
True
If Hx of MF then more likely to be MF recurrence
T/F
Primary Cutaneous CD4-Positive Small/Medium Pleomorphic T-cell Lymphoma commonly presents with generalised skin lesions
False
generalised lesions uncommon
Usually a solitary plaque to tumour on face, neck or upper trunk
T/F
Primary Cutaneous CD4-Positive Small/Medium Pleomorphic T-cell Lymphoma has a poor prognosis
False good prognosis Rx is; Surgical excision Radiotherapy Systemic chemotherapy for generalised skin lesions
T/F
Primary Cutaneous Aggressive epidermotropic CD8+ T cell lymphoma can resemble
Subcutaneous panniculitis-like T-Cell lymphoma (SPTCL)
False
Primary Cutaneous Gamma/Delta T cell lymphoma can have a subcutaneous type can resembling SPTCL
β-F1 stain for αβ receptor is positive in SPTCL but negative in γ/δ T cell lymphoma
T/F
Adult T-Cell Leukemia/Lymphoma (ATLL) is caused by the HTLV-1 virus
True - Long latency, median age onset 55yrs - M>F - Only minor proportion of seropositive patients eventually develop ATLL V poor prognosis
T/F
Adult T-Cell Leukemia/Lymphoma (ATLL) may be indistinguishable from MF on histo
True
often marked epidermotropism and typical MF features
think of diagnosis in pts from Japan, central Africa, Caribbean, South-Eastern USA and test for HTLV-1
T/F
can get haemophagocytic syndrome in panniculitis-like Primary Cutaneous Aggressive epidermotropic CD8+ T cell lymphoma
True
life threatening acute disease of active lymphocytes and macrophages with splenomegally and pancytopenia
T/F
Extranodal NK/T-cell Lymphoma always causes nasal destruction
False
but nasal type most common
Skin second most common - Multiple plaques or tumours on trunk and extremities resembling MF
T/F
Extranodal NK/T-cell Lymphoma and Extranodal NK/T-cell Lymphoma, nasal type are associated with HTLV-1
False
associated with EBV
+ve EBER-ISH stain for EBV
pathology usually different to MF with prominent angiocentricity and angiodestruciton accompanied by extensive necrosis and deep dense infiltrates
T/F
Primary Cutaneous Aggressive epidermotropic CD8+ T cell lymphoma can resemble other CTCLs histologically
True
other CD8+ CTCLs;
>50% of pagetoid reticulosis
and rare cases of MF, LyP and primary C-ALCL
Usually differs clinically and on immunostains;
eruptive papules, nodules, and tumours with central ulceration and necrosis or superficial, hyperkeratotic patches and plaques
CD3+, CD4−, CD8+, CD7−/+, CD45RA+, granzyme B+, perforin+, TIA-1+ phenotype
T/F
CD4+/CD56+ haematodermic neoplasm is the same as Blastic NK-Cell lymphoma
True
Highly aggressive type of CTCL presents with red-purple nodules and disseminates to BM and viscera
T/F
Primary Cutaneous Peripheral T cell lymphoma, unspecified may have good or poor prognosis
False
always poor
5 year survival
T/F
B-cell lymphomas involving skin always require complete staging
True
Skin can be site of secondary involvement for all types of extracutnaeous (usually nodal) B-cell lymphoma and leukemias, therefore all patients with confirmed diagnosis of B-cell lymphoma involving skin require complete staging;
FBC, ELFT, LDH, lymphocyte subsets, flow cytometry of peripheral blood, PET/CT chest/abdo/pelvis, Bone marrow biopsy with flow cytometry of aspirate
T/F
Primary Cutaneous Marginal Zone B-Cell Lymphoma is the commonest type of primary cutaneous B cell lymphoma
False
Most common is;
Primary Cutaneous Follicle Centre Lymphoma
(Crosti’s Lymphoma)
T/F
Prognosis always gets worse as stage goes up in MF
False
Often tumour stage (IIB) has worse prognosis than stage III and is equivalent to stage IV disease for prognosis
How is large cell transformation diagnosed in MF?
2 methods;
Over 25% large cells in total cell population of skin or LN biopsy (after 25% the percentage doesnt matter)
Or;
Microscopic nodules of atypical lymphocytes which are 4x greater than normal size
What are the clinical clues to possible large cell transformation?
New solitary nodule/tumour in classic patch/plaque MF
Abrupt onset of multiple persistent nodules
A new or enlarging tumour in ant MF pt
- must biopsy all these
T/F
The following are markers of a poorer prognosis in pts with large cell transformation;
- Transformation less than 2 years after diagnosis (but transformed early disease at diagnosis not so bad)
- Late stage disease at time of transformation
- Extracutaneous sites of transformation
- Raised LDH or Beta2 microglobulin
True
Note that large cell transformation always incurs a worse prognosis
Also transformed early disease at diagnosis not as bad a prognosis as diease that transforms soon after diagnosis or transformed late disease
T/F
large cell transformation of MF results in;
Median survival around 24 months
35% 5 year survival
True
T/F
In MF there is benefit in aggressive treatment of early disease
False
What is the most common B cell lymphoma to occur primarily in skin?
(primary cutaneous) follicle centre lymphoma
‘occur primarily’ means where did it start? i.e. primary cutaneous means it started in the skin
T/F
Biopsy down to fat is needed to diagnose B cell lymphomas
True
4-6mm punch, incisional, or excisional biopsy specimen, including reticular dermis and fat necessary for the diagnosis of CBCL
What bloods are needed in the work up of B cell lymphomas?
FBC, ELFT, LDH, Beta2 microglobulin
flow cytometry of peripheral blood
+ In PCMZL check immunoglobulins and EPP
Lyme serology, syphilis serology, Hepatitis serology
T/F
Primary Cutaneous Follicle Centre Lymphoma (PCFCL) can be associated with Borrelia burgdorferi infection
True
Lyme disease, USA
treat w/ doxy 100mg BD for 3 weeks
What is the appearance of the cells in Primary Cutaneous Follicle Centre Lymphoma?
Charcterisitic cleaved cells
usually large but size can vary
T/F
Primary Cutaneous Follicle Centre Lymphoma (PCFCL) has 95% 5 year survival except for cases on the arm
False
95% 5 year survival
cases on the leg have worse prognosis - 41% 5 year survival
NB - this has nothing to do with Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type although this may be a clinical and pathological differential
T/F
Primary Cutaneous Follicle Centre Lymphoma (PCFCL) rarely relapses
False
relapses 50% of time but still good prognosis
T/F
Excision or XRT or a combination of these are adquate Rx for most indolent primary cutaneous B cell lymphomas
True Follicle Centre and marginal zone Lymphomas often repsond well to these If not responding can do; IL or S/C interferon IL or systemic rituximab Also antibitocs given if Borrelia +ve
T/F
Primary Cutaneous Marginal Zone B-Cell Lymphoma (PCMZL) has close to 100% 5 year survival
True
often 99% quoted
T/F
Primary Cutaneous Marginal Zone B-Cell Lymphoma commonly affects the over 60 age group
False
affect 40-60 yr olds esp in 50s
skin primary of marginal zone type very unusual if >60
must assess thoroughly as more likely that disease is nodal in origin
T/F
Primary Cutaneous Marginal Zone B-Cell Lymphoma affects women twice as often as men
False
men twice as often as women
Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type affects women twice as often as men
T/F
Primary Cutaneous Marginal Zone B-Cell Lymphoma can be conisdered a type of MALT or SALT lymphoma
True
Part of spectrum of extranodal MZLs which often involve mucosal sites (MALT lymphomas of stomach associated with H. Pylori or skin-associated lymphoid tissue (SALT))
T/F
Primary Cutaneous Marginal Zone B-Cell Lymphoma may be triggered by Lyme disease
True
sometimes have acrodermatitits chronica atrophicans
T/F
Be cell lymphomas are always CD20 positive and usually CD79a positive
True
T/F
Primary Cutaneous Marginal Zone B-Cell Lymphoma is positive for Bcl6 and neg for Bcl2
False
this is true of Follicle Centre B cell lymphoma
(F for Follicle is 6th letter of alphabet)
Marginal zone is the other way around; Bcl2 positive and 6 negative
T/F
Primary Cutaneous Marginal Zone B-Cell Lymphoma carries the Bcl-2 gene t(14:18) translocation in 75% of cases
False
in 25%
T/F
Primary Cutaneous Follicle Centre Lymphoma
carries the Bcl-2 gene t(14:18) translocation in 25% of cases
False
skin types doesnt have this mutation
If positive suggests skin extension from systemic lymphoma
T/F
Primary Cutaneous Marginal Zone B-Cell Lymphoma most often presents with solitary or several pink-violet to red-brown papules, plaques and nodules on the trunk
True
then; arms>legs>head
asymptomatic
T/F
Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type (PCDLBCL-LT) has the worst prognosis of the Primary Cutaneous B-cell lymphomas
False
Not the worst overall but the the worst out of the 3 most common B-cell lymphoma types
Intravascular Diffuse Large B-cell Lymphoma seems to have worst prognosis overall
T/F
Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type always involves the leg
False
Most commonly arises on distal unilateral leg
But 10-20% in areas other than leg
always called leg type if Bcl-2 and MUM-1 +ve w/ otherwise consistent looking lesions and histopath
T/F
Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type is always positive for Bcl-6 and MUM-1
False
+ve for Bcl-2 and MUM-1 (2 legs-Bcl2) and also FOX-P1
-ve for CD10
Bcl-6 is variable
T/F
Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type has a better prognosis if not on the lower leg
True 5 yr survival - 43% if leg - 77% if non-leg site Multifocal disease has worst prognosis - 39% 5yr Overall 50% 5yr survival
T/F
It is important to rule out primary nodal origin in cases of possible Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type
True
important with all B cell lymphomas
T/F
Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type is treated with XRT, CHOP or rituximab or combinations
True
may also go into clinical trial
T/F
Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type may have epidermotropism on histo
True
What are poor prognostic factors in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type?
occurs on leg
multifocal disease
T/F
Intravascular Diffuse Large B-cell Lymphoma is a highly aggressive type
True
3yr survival 20-56%
(not 5 year)
What is R-CHOP?
rituximab cyclophosphamide doxorubicin vincristine prednisone
T/F
The presence of monoclonal plasma cells at the periphery of nodules favours Primary Cutaneous Marginal Zone B-Cell Lymphoma
True
plasma cells are either kappa or lamda positive
T/F
The presence Bcl-2 positive follicular type lymphocytes in a skin tumour favours Primary Cutaneous Follicle Centre Lymphoma
False
Favours skin extension from a nodal primary
Primary Cutaneous Follicle Centre Lymphoma is usually Bcl-2 negative
What is the TNM staging of cutaneous lymphoma other than MF/Sezary syndrome?
(includes other T cell lymphomas, NK cell and B cell lymphomas)
T1 - solitary skin involvement
- T1a; lesion 5cm
T2 - Regional skin involvement
Multiple lesions in one body region or 2 contiguous body regions
- T2a; all lesion within a 15cm diameter circle
- T2b; all lesions within a 15-30cm circle
- T2c; area of all lesions >30cm circle
T3 - Generalised skin involvement
- T3a; multiple lesions in 2 non-contiguous body sites
- T3b; multiple lesions across 3 or more body sites
N0-3
- 1 and 2 relate to regional skin nodes
- N3 if internal nodes involved
M0-1
- M1 if any extracutaneous, non-LN involvement
T/F
Drug-induced pseudolymphoma is almost always T cell predominant
True
What are triggers for cutaneous pseudolymphomas?
Mostly idiopathic Drugs esp T cell pseudolymphoma esp anticonculsants Persistent contact dermatitis Persistent nodular scabies or arthropod bites Lyme disease (Borrelia burgdorferi) esp Europe within scars after herpes zoster virus Molluscum contagiosum chronic folliculitis tattoo pigments vaccinations (esp VZV, Hep A or B) trauma acupuncture gold earrings
T/F
Drug-induced pseudolymphoma is usually a widepsread eruption
False
most often a single lesion (papule/nodule/plaque)
can be exfoliative erythroderma
Onset weeks-months after starting drug
What are pseudo-pseudolymphomas?
True malignant lymphomas occuring after apparent resolution of phenytoin- and carbamazepine-induced pseudolymphomas
Pseudolymphomas are benign but sometimes persistent lymphoid proliferations in dermis, difficult to distinguish from low-grade malignant lymphoma and may rarely transform into a malignant lymphoma
True
occur in adults
twice as common in women
What are the minor clinical variants of MF?
PPD type Poikilodermatous type Hypopigmented type (esp in dark skin) Bullous type
T/F
Lymphocytoma cutis
=cutaneous lymphoid hyperplasia
True
same thing
a type of pseudolymphoma w/ sevral other names
cutaneous lymphoid hyperplasia is preferred term as most descriptive and least confusing
What is cutaneous lymphoid hyperplasia?
A type of pseudolymphoma which histologically usually mimics a cutaneous B cell lymphoma esp follicle centre or marginal zone types
Classically a benign, cutaneous B-cell-rich lymphoproliferative condition (pseudolymphoma)
C for cutis follows B in alphabet
But usually composed of B and T cells
Trigger are the same as other pseudolymphoma triggers but usually not drugs as these mostly cause T cell pseudolymphomas
Histo composed of dense nodualr infiltrates of lymphocytes + histiocytes forming follicle-like structures
- involves whole dermis except a Grenz zone
Epidermis is spared
T/F
the inciting agent should be included along with the diagnosis of cutaneous pseudolymphoma
True The term pseudolymphoma without modification should be reserved for idiopathic cases Eg; Borrelial lymphocytoma cutis Tattoo induced lymphocytoma cutis Lymphomatoid drug reaction
How is pseudolymphoma managed?
Remove the cause if found Avoid that stimulus in future Drug cases resolve in months after cessation Other cases often self resolve Can progress to true lymphoma – re-evaluate of clinical progression TCS Topical tacrolimus Excision ILCS 2nd line; Cryo PDT PDL HCQ Short course oral pred XRT
T/F
If an equivocal lymphoid infiltrate regresses it must be a pseudolymphoma
False
True lymphoma cutis can regress spontaneously
What are the DDs of lymphocytoma cutis (cutaneous lymphoid hyperplasia)?
Primary cutaneous lymphoma esp follicle centre (Bolognia) or marginal zone (Rook) Lymphocytic infiltrate of Jesner Granuloma faciale Polymorphic light eruption LE tumidus Angiolymphoid hyperplasia w/ eosinophilia Met Merkel CC Deep figurate erythema Syphilis Infectious granuloma histiocytoma MUST rule out cutanoue B cell lymphoma and leukaemia cutis
T/F
Lymphocytic Infiltrate of Jessner is a controversial entity
True
some believe is variant of LE, cutaneous lymphoid hyperplasia, or polymorphic light eruption depending on the individual case
T/F
Lymphocytic Infiltrate of Jessner is a mixed B and T cell infiltrate
False
T-cell infiltrate with predominance of CD8-positive cytotoxic T-cells
T/F
Pts with Lymphocytic Infiltrate of Jessner only need to sun protect if they have a history of flaring in Summer
False
all pts should sun protect all year round
T/F
Lymphocytic Infiltrate of Jessner classically presents with infiltrated nsoules or plaques on the face
True
can be head, neck, upper back
What is the natural Hx of Lymphocytic Infiltrate of Jessner?
Often waxes and wanes for months-years
Often worse in Winter but some cases flare in Summer
May resolve spontaneously without scarring
What is the histo of Lymphocytic Infiltrate of Jessner?
Superficial and deep perivascular, lymphocytic infiltrate that may surround hair follicles
Normal epidermis
T-cell infiltrate with predominance of CD8-positive cytotoxic T-cells
What is the Rx of Lymphocytic Infiltrate of Jessner?
Sun protect – all pts camouflage TCS ILCS PUVA or UVA1 PDT Hydroxychloroquine Thalidomide Cyclophosphamide XRT
T/F
pseudolymhomas can be classified as T cell only or mixed B and T cell types (Fitz classification)
True
Most are T cell types
cutaneous lymphoid hyperplasia is mixed but B-cell predominant
Other mixed pseudolymphomas are;
Angiolymphoid hyperplasia w/ eosinophilia + Kimuras Dx
Castleman disease
T/F
PLEVA is acute PLC runs a chronic course
False
despite names they can each run a short or more chronic course
Differentiate by appearance of lesions and symptoms;
PLC;
- lesion is small, firm erythematous to red-brown (lichenoid) papule with adherent fine ‘mica-like’
- Can be more trunk and prox limbs or more distal variant
- asymptomatic
PLEVA
- Constitutional symptoms (fever , headache, malaise, arthralgia) at onset
- crops of polymorphic oedematous pink papules
- lesions develop crusts, ulcers, vesicles, pustules, or, haemorrhagic necrosis and heal with varioliform scars
- Trunk, thighs, upper arms – flexor aspects
- Burning/itch sensation
What is natural Hx of Pit lichenoides?
Variable course
Acute onset usually which stops developing within weeks and resolves after after six months
Recurrence can occur or chronicity may supervene
Diffuse distribution had shortest course of disease (11 months) while those with a peripheral distribution had the longest clinical course (33 months), central distribution was intermediate
PLEVA can evolve into FUMHD
What is Rx of Pit lichenoides?
Cease drug if suspected cause TCS Topical coal tar Oral EES or doxy UVB or PUVA MTX CSA Antihistamines for pruritus Course of pred may help severe forms Can try tonsillectomy for chronic cases with chronic tonsillitis
T/F
Angiolymphoid hyperplasia w/ eosinophilia occurs on or around the nose
False
on or around the ear
T/F
Chronic superficial scaly dermatitis often has a clonal infiltrate
False
v rarely - doesnt mean its malignant
T/F
Chronic superficial scaly dermatitis lesions are
False
T/F
Chronic superficial scaly dermatitis often becomes poikilodermatous and has atrophy on biopsy
False
this is true of large plaque parapsoriasis
(Chronic superficial scaly dermatitis is small plaque paraposriasis)
T/F
Both large plaque parapsoriasis and Chronic superficial scaly dermatitis (small plaque paraposriasis) have an infiltrate characterised by CD8+ T-cells
False
Both are CD4-positive T-cells
T/F
Chronic superficial scaly dermatitis has histo very similar to MF
False
usually not
spongiosis and lacks epidermotropism etc
lymhocytic infiltrate is mild-mod and perivascular not band like
What is the management of large plaque parapsoriasis and Chronic superficial scaly dermatitis?
Should do FBC w/ differential and blood film in all cases
If any concerns do full MF work up and assess against diagnostic criteria for early MF
Treat mainly to relieve itch and for appearance
Emollients
TCS - w/ caution in large plaque as often atrophic
UVB phototherapy (temporary clearance, but recurrence invariable)
May also temporarily clear with sunlight
Need long term follow up even for small plaque despite low risk as rarely may deteriorate
large plaque parapsoriasis develop MF at a rate of 10-35% per decade
T/F
The plaques in large plaque parapsoriasis are >5cm
True
should be >5cm and usually are >10cm
T/F
large plaque parapsoriasis is often atrophic and may be poikilodermatous
True
Variant; poikiloderma vasculare atrophicans (Pre-lymphomatous poikiloderma)
However;
involvement of covered skin on breast and buttock areas with striking polymorphism and poikiloderma should suggests poikilodermatous MF
What are the variants of large plaque parapsoriasis?
Poikiloderma vasculare atrophicans (Pre-lymphomatous poikiloderma)
Retiform parapsoriasis variant (100% progression to overt MF over long-term)
T/F Actinic reticuloid (chronic actinic dermatitis) commonly transforms into CTCL
False
very rare
T/F
Leukaemia cutis is most often associated with lymphoblastic leukaemias
False
Cutaneous lesions occur most often in myelomonocytic leukaemia (AML, CML) and T-cell malignancies (ATLL)
Can also be; ALL, CLL, hairy cell leukaemia
T/F
Leukaemia cutis occurs in up to 13% of leukaemias
False
3%
T/F
Hodgkins disease never involves skin
False
V rarely does
Only occurs as direct extension from an underlying involved regional lymph node
T/F Lymphomatoid granulomatosis (LYG) is a T-cell lymhoma which starts in lungs usually but may involve skin
False
B-cell lymphoproliferative Dx
the rest is true
affects skin in 40% of cases
T/F
Lymphomatoid granulomatosis (LYG) is associated with
EBV infection + immunosuppression
True
Can be AI disease or congenital immunodeficy E.g. Wiskott-Aldrich, renal transplant, HIV
However usually not known immunodeficiency but low numbers of CD4 and CD8 T-cells when tested
T/F
Lymphomatoid granulomatosis (LYG) histo shows
Mononuclear infiltrate of small and large lymphocytes
Lymphocytes show angioinvasion and angiodestruction
Fibrinoid and infarct-like tissue necrosis
Histiocytes but usually no granulomas
True
Mostly small lymphocytes
Larger lymphocytes are atypical & +ve for CD20 +, EBER-ISH (EBV) +/- LMP-1
T/F Lymphomatoid granulomatosis (LYG) is a granulomatous disease primarily
False
Histiocytes but usually no granulomas
Is lymphocytic primarily
T/F Lymphomatoid granulomatosis (LYG) has a highly variable prognosis
True
Can spontaneously resolve or cause death (from lung involvement)
Poor prognosis if multiorgan involvement or constitutional symptoms
