Lymphocytic Infiltrates Flashcards
Pseudolymphoma
@ cutaneous lymphoid hyperplasia
Not a specific disease
Benign lymphoid proliferations in the dermis
Difficult to distinguish with a low grade malignant lymphoma
May rarely transform to a lymphoma in some cases (true for some, though many of these cases may have been subtle low-grade lymphoma from the beginning)
May be T-cell or B-cell in origin
B cell psedolymphoma = lymphocytoma cutis (discussed later)
CLINICAL FEATURES
T cell pseudolymphoma
- Solitary or scattered Papules, nodules, plaques OR
- Persistent erythema —> develop into exfoliative erythroderma (esp if caused by drug or contact dermatitis) +/- persistent LN, low grade fever, headache, malaise, arthralgia
B cell pseudolymphoma
- Solitary or multiple
- Itchy or asymptomatic
- Smooth surfaced or excoriated
- Dermal or subcut papules and nodules
TRIGGERS Tattoos as reaction to certain pigments After vaccination Trauma Acupuncture Persistent arthropod bites Persistent nodular scabies Persistent contact dermatitis (lymphomatoid contact dermatitis)
Infections (B cell pseudolymphoma)
- Borrelia burgdoferi (Lyme disease)
- Leishmania
- Molluscum
- Herpes zoster
Drugs (T cell pseudolymphoma presents as drug eruption @ lymphomatoid drug reaction)
- anticonvulsants
- ACE-I
- B-blockers
- Antidepressants
IX
Skin biopsy for histo + TCR gene rearrangement
Borrelia burgdoferi serology (B cell pseudolymphoma)
FBC, ELFTs (if drug reaction)
APT (if lymphomatoid contact dermatitis)
HISTO T or B cell lymphoid proliferation Nodular in B cell Nodular or band-like in T cell Few mitoses Minimal cytological atypia Germinal centres may or may not be present in B cell proliferations No significant epidermotropism in T cell proliferations
IHC (T cell pseudolymphoma)
- Normal T cell phenotype
IHC (B cell pseudolymphoma)
- Bcl-2 negative if germinal centres present
TCR gene rearrangement
- Polyclonal
- rarely monoclonal (significance unclear)
DDX
Cutaneous B and T cell lymphoma
COURSE/PROGNOSIS
Remove potential cause as soon as possible
May take weeks or months for skin reaction to subside
May be persistent if there is no identifiable cause
Clear progression from apparent pseudolymphoma to malignant lymphoma (concept that chronic initially benign reactive inflammatory condition may rarely progress to frank lymphoma, or these cases may be low grade lymphomas from the get go)
MX Remove suspected cause TCS for symptomatic relief of itch ILCS for small solitary nodules HCQ for generalised disease
Pityriasis lichenoides
Children and young adults
Unknown cause
Has been considered to be a variant of parapsoriasis
Features overlap with LyP
T cell clonality has been detected in most PLEVA, and some PLC, febrile ulceronecrotic Mucha-Habermann disease
At least some cases represent a cytotoxic CD8+ T cell lymphoproliferative disease which may co-exist with other primary T cell lymphomas
CLASSIFICATION
PLC (Pityriasis lichenoides chronica) - most common
PLEVA (Pityriasis lichenoides eat varioliformis acuta) or Mucha-Habermann disease - most common in young children
FUMHD (Febrile ulceronecrotic Mucha-Habermann disease) - more rare and aggressive
Differences are based on clinical morphology and histology (rather than disease course)
CLINICAL FEATURES PLEVA
Develops in crops
Consequently appears polymorphic
Initial lesion oedematous pink papule that undergoes central vesiculation and haemorrhagic necrosis
Vesicular form —> vesicles may be small or large that eruption appears bullous
May be complicated by secondary infection
Lesions may cause irritation or burning in sensation, but often asymptomatic
Heal with scarring, which may be varioliform
Predilection sites
- Trunk
- Thighs
- Upper arms esp flexor aspects
May be generalised
Less common palms/soles
Face and scalp often spared
Mucous membranes may be affected - erythematous or necrotic lesions
Constitutional symptoms may precede or accompany onset of lesions
- Fever
- Headache
- Malaise
- Arthralgia
DDx necrotic lesions
- necrotic skin infections
- vasculitis
- PG
- LyP (more necrotic and papulonodular)
DDx vesicular form
- varicella
FUMHD
Large necrotic lesions
New crops may continue to develop over many months
Fulminant course that may even be fatal
May be complicated by secondary infection
Assoc symptoms
- High fever
- General malaise
- Weakness
- Myalgia
- Neuropsychiatric symptoms
- LN
Serology
- Raised ESR, CRP
- Viral infection
PLC
Small firm lichenoid papule
Reddish brown in colour
Adherent mica-like scale can be detached by gentle scraping to reveal shining brown surface (distinctive Dx feature)
Over the course of 3-4 weeks papule flattens, scale separates, leaving pigmented macule, gradually fades
Possible post inflammatory hypopigmentation, occasionally persistent
Scarring unusual
Predilection sites same as for PLEVA
- Trunk
- Thighs
- Upper arms esp flexor aspects
Isolated acral form may occur
Segmental forms reported
DDx
- guttate psoriasis
- lichen planus
- Insect bites
- Drug eruptions
- Gianotti-Crosti syndrome (less likely)
ASSOCIATED DISEASES
MF
Lymphoma
TRIGGERS Medications - Chemotherapy - OCP - Astemizole - Anti-TNFs (paradoxical as this is also a Rx option for refractory FUMHD) - Herbs
MMR vaccine
Viral infections
- EBV
- CMV
- Parvovirus B19
- Adenovirus
- Measles
- HSV
- VZV
- Hep C
- HIV
Bacterial infections
- Strep (with acute or chronic tonsillitis)
- Staph
- Mycoplasma
Toxoplasmosis (parasite infection)
NATURAL HISTORY
Episodic
PLEVA and PLC last on average 18 months
IX
Skin biopsy for histo, IHC, TCR gene rearrangement
In cases of FUMHD, IX for underlying infective trigger
- ASOT, throat swab (strep tonsillitis)
- LFTs (Hepatitis)
- EBV serology
- HIV serology
- Toxoplasma serology
HISTO
Varies with stage, intensity and extent of the reaction
Changes more severe in PLEVA than PLC
Epidermis oedematous
Lichenoid pattern comprised mainly CD8+ lymphocytes
Predominantly small lymphocytes surrounding and involving walls of dilated dermal capillaries (PLC) “lymphocytic vasculitis” picture
Infiltrate deep, dense, wedge shaped rather than predominantly perivascular (PLEVA)
Necrotic keratinocytes (esp PLEVA)
Intraepidermal and perivascular RBC extravasation
Later stages parakeratotic scale forms over centre of lesion with lymphocytic pseudo-Munro micro abscesses and prominent exocytosis of lymphocytes
Mild cytological atypia may be present
Frank necrosis (FUMHD)
Marked fibrinoid necrosis of deep vessels with intraluminal thrombi (FUMHD)
Partial necrosis of follicles (FUMHD)
Complete necrosis of eccrine glands (FUMHD)
PLC MX
1st line
TCS (improve symptoms and healing of lesions, do not alter course of disease)
Topical tacrolimus ointment
2nd line adults Phototherapy - heliothetapy - broad or nbUVB - PUVA Tetracyclines Erythromycin
2nd line children
Erythromycin (avoid tetracyclines due to staining of the teeth)
3rd line adults
Acitretin (combined with PUVA)
MTX, CSA, Dapsone, UVA-1 (Immunosuppressants)
3rd line children
MTX, CSA, Dapsone
PLEVA MX
1st line
Erythromycin
2nd line adults Phototherapy - heliothetapy - broad or nbUVB - PUVA Acitretin + PUVA
2nd line children
Phototherapy
- heliothetapy
- broad or nbUVB
3rd line adults Oral pred MTX CSA Dapsone UVA1
3rd line children Oral pred MTX CSA Dapsone
COURSE/PROGNOSIS
Varies
If acute onset, new crops may stop developing after a few weeks, many cases clear within 6 months
Acute recurrences may occur over a period of years, or may be chronic
In some cases all lesions are of PLC type and new crops of PLC type lesions develop from time to time over years
Uncommonly acute episodes occur after chronic lesions present for months/years
? Prognosis better if onset acute and lesions are of PLEVA type
Children
- Tend to run a longer course
- greater extent of lesions
- more pigmentation
- poor response to conventional Rx
COMPLICATIONS/SEQUELAE
PLEVA in pregnancy carries potential risk of premature labour if there are mucosal lesions in region of cervical os
Secondary infection in PLEVA and FUMHD
Parapsoriasis (overview)
2 VARIANTS
Small plaque parapsoriasis
Large plaque parapsoriasis
Unresolved controversy whether the variants are precursors of CTCL, MF variant (pre-mycotic eruption), or established early MF from the outset
TCR gene rearrangement studies inconclusive
Proportion of cases with monoclonality lower in small plaque parapsoriasis
Requires long term follow up
Small plaque parapsoriasis
@ Chronic superficial scaly dermatitis Persistent superficial dermatitis Digitate dermatosis Xanthoerythroderma perstans
Middle age Chronic asymptomatic condition Insidious (gradual, subtle) onset Monomorphic round or oval erythematous patches 2.5 - 5 cm diameter Slight scaling Slightly yellow waxy tinge
Predilection site trunk
Sometimes limbs
Digitate dermatosis (distinctive phenotype) - Finger-like projections following Dermatomes on lateral aspects of the chest and abdomen
Persist for years/decades
More obvious during winter
Spares pelvic girdle area (unlike MF)
Lacks polymorphic appearance of individual patches seen in MF
DDX Discoid eczema Guttate psoriasis Pityriasis versicolor ACD Early CTCL
IX
Clinical Dx as histology non-specific
If suspicious for MF —> skin biopsy for histo and TCR gene rearrangement studies
HISTO Non-specific Small focal areas of hyperkeratosis and parakeratosis Spongiosis Small aggregates of morphological normal CD4+ T lymphocytes, mainly perivascular May have exocytosis No epidermotropism No Pautrier microabscess IHC normal mature T cell phenotype
MX Emollients (control scaling) NbUVB (temporary clearance) PUVA (temporary clearance) Topical nitrogen mustard (complete and partial response)
COURSE/PROGNOSIS
May persist for years and then resolve spontaneously
Minority may progress to MF
Large plaque Parapsoriasis
@ Parakeratosis variegata Retiform parapsoriasis Atrophic parapsoriasis Poikilodermatous parapsoriasis
ASSOCIATED DISEASE
May progress to MF, although it may be early stage MF from the outset
CLINICAL FEATURES
Persistent large yellow orange ATROPHIC patches and thin plaques
Predilection sites trunk, limbs
Favour MF If patches are on covered skin on the breast and buttocks —> may show polymorphism and Poikiloderma with slow progression
IX
Skin biopsy for histo, IHC, TCR gene rearrangement
HISTO Epidermal atrophy Lichenoid or interface reaction at DEJ Band-like lymphocytic infiltrate in the papillary dermis May be few RBC Not diagnostic for MF Most bio-sites only show mild dermatitis IHC normal T cell phenotype TCR gene rearrangement may be monoclonal
MX Regular monitoring for possible progression to CTCL Emollients (symptomatic relief) NbUVB (symptomatic relief) PUVA (symptomatic relief) Topical nitrogen mustard Excimer laser 308nm Use TCS with caution d/t atrophic nature of lesions
Lymphocytoma cutis
@
Reactive cutaneous lymphoid hyperplasia
Benign skin B cell lymphoproliferative disorder
Subtype of pseudolymphoma
Response to a known or unknown antigenic stimuli
Result in accumulation of lymphocytes and other inflammatory cells in a localised region of the skin
ASSOCIATED DISORDERS Borrelia burgdoferi (Lyme disease) —> Borrelial lymphocytoma more common in children than adults, sites of low skin temp I.e. nose, earlobes, nipples, scrotum Molluscum contagiosum Leishmania Herpes zoster scars
TRIGGERS Arthropod bites Trauma Acupuncture Metallic pierced earrings Vaccinations Allergy hyposensitisation injections Drugs Treatment with leeches
CLINICAL FEATURES
Solitary or grouped
erythematous or plum-coloured papules, nodules, plaques
May have translucent appearance
Asymptomatic
Can be itchy or tender
Enlarge slowly
Predilection sites face, chest, upper extremities
May have sunlight sensitivity
DDX Sarcoidosis Granuloma faciale Rosacea Insect bite reaction Lupus erythematosus Jessner’s lymphocytic infiltrate (T cell infiltrate) Primary cutaneous marginal zone B cell lymphoma (atypical lymphoid cells, immunoglobulin light chain restriction, clonal immunoglobulin gene rearrangement)
IX
Skin biopsy for histo, IHC, immunoglobulin gene analysis
Borrelia burgdoferi serology
APT if suspect contact allergen
HISTO
Unaffected epidermis
Acellular Grenz zone
Nodular dense infiltrate extending through full thickness of the dermis
No cellular atypia
Lymphocytes and histiocytes form follicular arrangement (germinal centre) resembling appearance of a LN —> may have mitoses
Spares blood vessels and adnexae
IHC germinal centres neg for Bcl-2
Polytypic expression of kappa and lambda chains
HISTO DDX
Marginal zone primary cutaneous B cell lymphoma
MX
Remove causative agent
Localised disease
- Excision
- TCS
- ILCS
- Oral ABs (if positive Borrelia burgdoferi)
- Topical tacrolimus ointment
- LN2
- PDT
- superficial RTX
- Intralesional interferon-alpha
- intralesional rituximab
Generalised disease
HCQ
Subcut interferon-alpha
Thalidomide
COURSE/PROGNOSIS
Often chronic and indolent
Some resolve spontaneously
Lesions may resolve once cause is removed
Small proportion progress to or begin as primary cutaneous B cell lymphoma
Jessner’s lymphocytic infiltrate
Chronic benign inflammatory condition affecting photo exposed skin
Any similarities with tumid lupus, clinically and histologically
Adults < 50 yrs, children, familial cases
ASSOCIATED DISEASES
May be a variant of LE
CLINICAL FEATURES
May or may not be history of onset following sun exposure
Asymptomatic
Non-scaly Erythematous papules and plaques One, few, or numerous lesions Central clearing may occur —> annular appearance No atrophy (unlike LE) No follicular plugging (unlike LE)
May last months or years
Often resolve spontaneously, but can recur at same or different site
Predilection sites face, neck, upper chest (photoexposed skin)
DDX
Polymorphic light eruption (short duration of lesions)
LE
Lymphocytoma cutis
IX
Skin biopsy for histo, DIF, molecular gene rearrangement studies (exclude LE, lymphocytoma cutis)
Consider serology for SLE (ANA, ENA, ESR, FBC, urinalysis)
Photo testing may be useful for patients with Hx of photosensitivity (PMLE)
HISTO Epidermis usually normal - No atrophy - No follicular plugging - No BM thickening
Dense superficial and deep perivascular dermal lymphocytic infiltrate
May also be perifollicular
May extend to subcutis
Infiltrate contains small mature lymphocytes with occasional large lymphoid cells, plasmacytoid and plasma cells
No copious amounts of dermal mucin
IHC mixed lymphocytic infiltrate with dominant CD8+ population
DIF neg (unlike LE)
TCR, BCR gene rearrangement polyclonal
MX
If asymptomatic, no Rx may be acceptable
Photoprotection
Cosmetic camouflage
TCS
ILCS
Excision of small lesions
LN2
PDT
PDL
HCQ Oral pred MTX Retinoids Thalidomide
COURSE/PROGNOSIS
Good (benign)
May resolve spontaneously
No increase in mortality
