Definition/General
Introduction:
Lymphomatoid papulosis (LyP) is a chronic, recurrent, self-healing cutaneous lymphoproliferative disorder characterized by CD30-positive cells
It belongs to the spectrum of primary cutaneous CD30+ lymphoproliferative disorders
Despite alarming histological features, it has an excellent prognosis
Spontaneous regression of individual lesions is characteristic
Associated with increased risk of developing other lymphomas.
Origin:
Originates from activated T-lymphocytes expressing CD30 activation marker
Shows clonal T-cell receptor gene rearrangements in most cases
Skin-homing T-cells with cutaneous lymphocyte antigen (CLA) expression
Cytotoxic phenotype common
Chronic antigenic stimulation may contribute to pathogenesis
Different clones may be present in different lesions.
Classification:
WHO-EORTC classification recognizes five histological subtypes: Type A (mixed inflammatory infiltrate, CD30+ large cells scattered)
Type B (epidermotropic, mycosis fungoides-like)
Type C (large cell predominant, anaplastic large cell lymphoma-like)
Type D (CD8+ epidermotropic)
Type E (angioinvasive/angiodestructive)
Clinical behavior remains benign regardless of subtype.
Epidemiology:
Peak incidence in 4th-5th decades
Slight female predominance (F:M = 1.2-1.5:1)
Rare disease with incidence 1.2-1.9 per million
Associated lymphomas develop in 10-20% of patients
Mycosis fungoides (5-45% association)
Primary cutaneous ALCL (5-25% association)
Hodgkin lymphoma (3-6% association)
Indian population data limited.
Clinical Features
Presentation:
Recurrent papules and nodules that spontaneously regress
Different stages of lesions present simultaneously
Crops of lesions appear over months to years
Central necrosis and ulceration common
Healing with atrophic scars
Trunk and extremities preferentially involved
Pruritus variable
No systemic symptoms typically.
Symptoms:
Mild to moderate pruritus in some patients
Pain or tenderness in ulcerated lesions
Cosmetic concerns due to scarring
Psychological impact due to chronic recurring nature
No constitutional symptoms (fever, weight loss, night sweats)
Functional impairment minimal
Secondary bacterial infection of ulcerated lesions occasionally.
Risk Factors:
Age (peak 4th-5th decades)
Female gender (slight predominance)
Genetic predisposition possible (rare familial cases)
Immunosuppression may worsen course
Environmental factors not well established
Previous lymphoma history (may be associated)
Chronic skin inflammation (possible association).
Screening:
Clinical examination and photography for monitoring
Skin biopsy from fresh lesions for diagnosis
Complete blood count and peripheral smear
Imaging studies not routinely needed
Lymph node examination
Long-term follow-up for associated lymphoma development
Patient education about disease course and monitoring.
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Gross Description
Appearance:
Papules and nodules ranging from few mm to 2 cm
Red to violaceous color
Central ulceration and necrosis in many lesions
Scaling and crusting
Different stages of evolution present
Healing lesions with atrophic scars
Linear arrangement occasionally (Koebner phenomenon).
Characteristics:
Well-circumscribed lesions
Raised, dome-shaped appearance
Central crater with necrotic material
Surrounding erythema
Variable consistency (soft to firm)
Spontaneous resolution over weeks to months
Residual hypopigmentation or scarring.
Size Location:
Lesion size: few millimeters to 2 cm diameter
Trunk most commonly involved
Extremities (arms and legs)
Buttocks frequently affected
Face involvement less common
Palms and soles rarely involved
Mucous membranes spared
Number varies from few to hundreds.
Multifocality:
Multiple lesions at different stages of evolution
Bilateral and symmetric distribution common
Crops of new lesions appear periodically
Continuous disease activity over years
No extracutaneous involvement
Regional lymphadenopathy may occur but is reactive
Systemic involvement absent.
Microscopic Description
Histological Features:
Wedge-shaped dermal infiltrate characteristic
CD30-positive large cells scattered throughout
Mixed inflammatory infiltrate (small lymphocytes, histiocytes, eosinophils, neutrophils)
Epidermotropism variable depending on subtype
Ulceration and necrosis common
Mitotic activity variable
Apoptotic figures frequent.
Cellular Characteristics:
Large atypical cells (CD30+ cells) scattered individually
Reed-Sternberg-like cells may be present
Pleomorphic nuclei with prominent nucleoli
Abundant eosinophilic cytoplasm
Frequent mitoses in large cells
Small reactive lymphocytes predominate in infiltrate
Histiocytes and eosinophils admixed.
Architectural Patterns:
Type A: mixed infiltrate with scattered CD30+ cells
Type B: epidermotropic pattern resembling mycosis fungoides
Type C: sheet-like arrangement of large CD30+ cells
Type D: CD8+ epidermotropic infiltrate
Type E: angiocentric/angiodestructive pattern
Ulceration frequent across subtypes.
Grading Criteria:
No grading system as behavior is benign regardless of histology
Degree of CD30 expression noted (should be >75% of large cells)
Proportion of large cells varies by subtype
Proliferation index (Ki-67) variable
Extent of necrosis assessed
Depth of infiltration noted
Histological subtype designation important.
Immunohistochemistry
Positive Markers:
CD30 (strongly positive in large atypical cells)
CD3 (positive in T-cells)
CD4 (often positive in large cells)
CD8 (positive in Type D)
Granzyme B and Perforin (cytotoxic markers, often positive)
TIA-1 (cytotoxic marker)
CD2 (usually positive)
Cutaneous lymphocyte antigen (CLA).
Negative Markers:
ALK (negative, unlike systemic ALCL)
CD15 (negative, unlike Hodgkin lymphoma)
CD20 (B-cell marker, negative)
CD5 (may be lost in large cells)
CD7 (may be lost)
EBER (EBV marker, negative)
CD56 (usually negative)
BCL2 (variable).
Diagnostic Utility:
CD30 positivity in >75% of large cells (diagnostic requirement)
ALK negativity distinguishes from systemic ALCL
Cytotoxic markers often positive
T-cell lineage confirmed by pan-T-cell markers
Ki-67 shows variable proliferation
Loss of pan-T-cell antigens may occur
CD68 highlights histiocytes in mixed infiltrate.
Molecular Subtypes:
Helper T-cell phenotype (CD4+) most common
Cytotoxic phenotype (CD8+) in Type D
CD30+ large cell population characteristic
Cytotoxic features (granzyme B+, perforin+) common
Mixed T-cell populations in background
Clonal vs oligoclonal patterns variable.
Molecular/Genetic
Genetic Mutations:
Clonal T-cell receptor rearrangements in 60-100% of cases
Different clones in different lesions possible
DUSP22-IRF4 rearrangements in some cases
TP63 rearrangements rare
Chromosomal instability limited
No specific oncogene activation identified
STAT3 mutations rare.
Molecular Markers:
T-cell receptor clonality variable between lesions
CD30 overexpression characteristic
Cytokine dysregulation
Apoptosis pathway alterations
Cell cycle dysregulation minimal
Telomerase activity variable
Gene expression profiling shows activated T-cell signature.
Prognostic Significance:
Excellent prognosis with no impact on survival
Risk of associated lymphomas (10-20% lifetime risk)
Mycosis fungoides most common associated lymphoma
Primary cutaneous ALCL also associated
Histological subtype does not affect prognosis
Clonality does not predict behavior
Long-term monitoring required.
Therapeutic Targets:
Topical corticosteroids for symptomatic lesions
Localized radiation therapy for persistent lesions
Methotrexate for widespread disease
PUVA phototherapy for multiple lesions
No treatment often appropriate (self-healing)
Excision for cosmetic concerns
Anti-CD30 therapy under investigation.
Differential Diagnosis
Similar Entities:
Primary cutaneous anaplastic large cell lymphoma
Mycosis fungoides (especially Type B LyP)
Classical Hodgkin lymphoma (cutaneous involvement)
Arthropod bite reactions
Pityriasis lichenoides et varioliformis acuta
Drug eruptions
Viral exanthems
Other CD30+ lymphoproliferative disorders.
Distinguishing Features:
LyP: spontaneous regression, excellent prognosis, ALK-
Primary cutaneous ALCL: no regression, larger lesions, may need treatment
MF: epidermotropism, different clinical course
Hodgkin lymphoma: CD15+, different clinical presentation
Arthropod bites: acute onset, different histology
Clinical correlation essential for diagnosis.
Diagnostic Challenges:
Distinguishing from primary cutaneous ALCL (clinical behavior crucial)
Type B LyP vs mycosis fungoides (epidermotropism overlap)
Type C LyP vs primary cutaneous ALCL (histological overlap)
Reactive vs neoplastic CD30+ cells
Need for clinical correlation
Long-term follow-up helps confirm diagnosis.
Rare Variants:
Angioinvasive LyP (Type E)
CD8+ epidermotropic LyP (Type D)
Giant cell-rich LyP
Follicular LyP
LyP with granulomatous features
LyP in children (rare)
Familial LyP (extremely rare)
LyP transforming to other lymphomas.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Skin biopsy from [anatomical site], [papule/nodule] with [ulceration/intact surface]
Primary Diagnosis
Lymphomatoid papulosis, Type [A/B/C/D/E]
WHO-EORTC Classification
Lymphomatoid papulosis (primary cutaneous CD30+ lymphoproliferative disorder)
Clinical Correlation
History of recurrent self-healing lesions: [consistent with LyP]; Duration: [months/years]
Histological Features
Shows mixed inflammatory infiltrate with scattered CD30-positive large atypical cells
Histological Subtype
Type [A/B/C/D/E]: [characteristic features of the subtype]
CD30 Assessment
CD30-positive large cells: [>75%]; Distribution: [scattered/clustered]; Intensity: [strong/moderate]
Immunohistochemistry
Large cells: CD30+, CD3+, [CD4+/CD8+], ALK-, CD15-; Ki-67: [percentage]%
Molecular Studies
T-cell receptor rearrangement: [clonal/oligoclonal/polyclonal]
Prognosis and Follow-up
Excellent prognosis with spontaneous regression; Long-term follow-up recommended for associated lymphoma risk
Final Diagnosis
Lymphomatoid papulosis, Type [A/B/C/D/E], WHO-EORTC classification