Definition/General
Introduction:
Cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of extranodal non-Hodgkin lymphomas that primarily involve the skin
Mycosis fungoides (MF) is the most common type, accounting for 50-60% of all CTCL
Sézary syndrome (SS) represents the leukemic form
These lymphomas show epidermotropism and characteristic cerebriform nuclei
Most cases have indolent clinical course in early stages.
Origin:
Originates from mature T-helper cells that have undergone malignant transformation
Shows skin-homing properties due to expression of cutaneous lymphocyte antigen (CLA)
Clonal T-cell receptor gene rearrangements are present
Memory T-cell phenotype with CD45RO expression
Shows evidence of chronic antigenic stimulation
Tumor microenvironment plays crucial role in progression.
Classification:
WHO-EORTC classification recognizes multiple subtypes: Mycosis fungoides (classical and variants)
Sézary syndrome (leukemic form)
Primary cutaneous CD30+ lymphoproliferative disorders
Subcutaneous panniculitis-like T-cell lymphoma
Primary cutaneous gamma-delta T-cell lymphoma
Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma
Primary cutaneous peripheral T-cell lymphoma, rare subtypes.
Epidemiology:
Incidence 6-10 cases per million per year
Male predominance (M:F = 1.6-2:1)
Peak incidence in 5th-6th decades
Most common primary cutaneous lymphoma
Geographic variation exists
Higher incidence in certain populations
Environmental factors may contribute
Indian population data limited but shows similar patterns.
Clinical Features
Presentation:
Skin lesions are primary manifestation
Patches (flat, scaly, erythematous lesions)
Plaques (raised, indurated lesions)
Tumors (nodular lesions >1 cm)
Erythroderma (generalized redness >80% body surface)
Pruritus is prominent symptom
Lymphadenopathy in advanced stages
Alopecia in some cases.
Symptoms:
Intense pruritus (most common symptom)
Burning or stinging sensation
Skin tightness
Hair loss (alopecia)
Nail changes (dystrophy, onycholysis)
Constitutional symptoms in advanced disease
Secondary infections due to skin barrier disruption
Temperature dysregulation in erythrodermic patients.
Risk Factors:
Age (peak 5th-6th decades)
Male gender
Chronic skin inflammation
Immunosuppression (HIV, transplant recipients)
Environmental exposures (pesticides, chemicals)
Occupational exposures (industrial chemicals)
Genetic predisposition possible
HLA associations described.
Screening:
No routine screening available
Clinical examination of skin lesions
Photography for monitoring progression
Skin biopsy for histological diagnosis
Flow cytometry of peripheral blood in suspected Sézary syndrome
Imaging studies for staging
Complete blood count and peripheral smear.
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Gross Description
Appearance:
Skin lesions show variable morphology
Patches: flat, scaly, erythematous areas
Plaques: raised, indurated, well-demarcated lesions
Tumors: nodular lesions that may ulcerate
Erythroderma: generalized redness and scaling
Poikiloderma: atrophy, telangiectasia, dyspigmentation
Leonine facies in advanced cases.
Characteristics:
Irregular distribution of lesions
Sun-protected areas often involved
Bathing suit distribution characteristic
Well-demarcated borders in plaque stage
Scale and crust formation
Ulceration in tumor stage
Lymphadenopathy in advanced disease.
Size Location:
Patch stage: few cm to large areas
Plaque stage: 1-20 cm lesions
Tumor stage: >1 cm nodules
Predilection sites: trunk, extremities, buttocks
Sun-protected areas commonly involved
Face involvement in advanced cases
Palms and soles rarely involved.
Multifocality:
Multifocal skin involvement characteristic
Bilateral symmetric distribution common
Progressive involvement of new areas
Lymph node involvement in advanced stages
Visceral involvement in tumor stage
Bone marrow involvement in Sézary syndrome
CNS involvement rare but reported.
Microscopic Description
Histological Features:
Epidermotropism (lymphocytes infiltrating epidermis)
Cerebriform nuclei with convoluted nuclear contours
Pautrier microabscesses (collections of lymphocytes in epidermis)
Band-like infiltrate in upper dermis
Spongiosis (epidermal edema)
Hyperkeratosis and parakeratosis
Loss of CD7 expression in tumor cells.
Cellular Characteristics:
Small to medium-sized lymphocytes with cerebriform nuclei
Convoluted nuclear contours (coffee bean appearance)
Dense chromatin
Minimal cytoplasm
Nuclear grooves and folds
Mitotic activity variable
Large cell transformation may occur
Sezary cells in peripheral blood.
Architectural Patterns:
Epidermotropism without spongiosis (early sign)
Band-like dermal infiltrate
Perivascular and periadnexal distribution
Pautrier microabscesses pathognomonic
Lichenoid pattern in some cases
Nodular pattern in tumor stage
Diffuse dermal infiltration in advanced disease.
Grading Criteria:
Clinical staging more important than histological grading
Patch stage (IA-IB)
Plaque stage (IB-IIA)
Tumor stage (IIB-III)
Erythrodermic stage (III-IV)
Lymph node involvement affects staging
Visceral involvement indicates stage IV
Large cell transformation indicates aggressive behavior.
Immunohistochemistry
Positive Markers:
CD3 (positive)
CD4 (positive in >90% cases)
CD2 (usually positive)
CD5 (usually positive)
CD45RO (memory T-cell marker)
Cutaneous lymphocyte antigen (CLA)
CCR4 (chemokine receptor)
CD25 (activation marker in some cases)
FOXP3 (subset positive).
Negative Markers:
CD7 (characteristically lost)
CD8 (negative in typical cases)
CD20 (B-cell marker, negative)
CD30 (negative in MF, positive in some variants)
CD56 (NK marker, negative)
TIA-1 (cytotoxic marker, negative in typical MF)
Granzyme B (negative in typical MF).
Diagnostic Utility:
Loss of CD7 important diagnostic clue
CD4+ helper phenotype most common
Aberrant T-cell phenotype supports diagnosis
CLA expression indicates skin-homing property
Ki-67 shows variable proliferation
Flow cytometry useful for peripheral blood involvement
CD4/CD8 ratio >10 suggestive of Sézary syndrome.
Molecular Subtypes:
Helper T-cell phenotype (CD4+) predominant
Cytotoxic phenotype (CD8+) rare and aggressive
Regulatory T-cell features (FOXP3+) in subset
Follicular helper features rare
TCR-αβ type most common
TCR-γδ type rare and aggressive
Double-negative (CD4-, CD8-) rare.
Molecular/Genetic
Genetic Mutations:
Clonal TCR gene rearrangements (diagnostic requirement)
TP53 mutations in transformation
CDKN2A deletions common
MYC rearrangements in large cell transformation
TNFRSF1B mutations
PLCG1 mutations
CARD11 mutations
Complex chromosomal aberrations in advanced disease.
Molecular Markers:
Gene expression profiling shows distinct signature
Th2 cytokine profile predominant
Skin-homing markers upregulated
T-regulatory signatures in subset
MicroRNA dysregulation
Epigenetic modifications common
JAK/STAT pathway activation
NF-κB pathway dysregulation.
Prognostic Significance:
Stage most important prognostic factor
Early stage (IA-IIA): excellent prognosis
Advanced stage (IIB-IV): poor prognosis
Large cell transformation indicates poor prognosis
Folliculotropism associated with worse outcome
Sézary syndrome has poor prognosis
Age and performance status important.
Therapeutic Targets:
Topical therapies (corticosteroids, nitrogen mustard)
Phototherapy (PUVA, narrowband UVB)
Radiation therapy for localized lesions
Systemic retinoids (bexarotene)
HDAC inhibitors (vorinostat, romidepsin)
Monoclonal antibodies (alemtuzumab)
Immunomodulatory agents (interferon-α).
Differential Diagnosis
Similar Entities:
Chronic dermatitis (eczema, contact dermatitis)
Psoriasis (chronic plaque type)
Drug eruptions
Viral exanthems
Other cutaneous lymphomas (B-cell, NK/T-cell)
Atypical lymphoid infiltrates
Pseudolymphomas
Spongiotic dermatitis.
Distinguishing Features:
CTCL: epidermotropism without spongiosis, cerebriform nuclei, CD7 loss
Chronic dermatitis: spongiosis, eosinophils, polyclonal
Psoriasis: acanthosis, neutrophils, Munro microabscesses
Drug eruptions: eosinophils, interface dermatitis
B-cell lymphomas: CD20+, nodular pattern
Immunohistochemistry and molecular studies crucial.
Diagnostic Challenges:
Early patch stage may mimic benign dermatitis
Minimal epidermotropism in some cases
Reactive lymphoid infiltrates can be confusing
Large cell transformation may obscure diagnosis
Folliculotropic variant lacks epidermotropism
Interface dermatitis pattern unusual
Multiple biopsies often needed.
Rare Variants:
Folliculotropic mycosis fungoides
Pagetoid reticulosis (Woringer-Kolopp disease)
Granulomatous slack skin
Hypopigmented mycosis fungoides
Bullous mycosis fungoides
Poikilodermatous mycosis fungoides
Unilesional mycosis fungoides
Palmoplantrar mycosis fungoides.
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], [lesion type: patch/plaque/tumor]
Primary Diagnosis
Cutaneous T-cell lymphoma, [specific subtype if determinable]
WHO-EORTC Classification
[Specific CTCL subtype] (WHO-EORTC classification)
Histological Features
Shows epidermotropism with cerebriform lymphocytes and [band-like/perivascular] dermal infiltrate
Epidermotropism
Epidermotropism: [present/absent]; Pautrier microabscesses: [present/absent]; Spongiosis: [minimal/absent]
Cellular Morphology
Lymphocytes show cerebriform nuclei with convoluted contours; [size: small/medium/large cell component]
Immunohistochemistry
CD3+, CD4+, CD2+, CD7- (loss), CD8-, CD20-, Ki-67: [percentage]%
Molecular Studies
T-cell receptor gene rearrangement: clonal; [Additional molecular findings]
Clinical Correlation
Clinical stage: [IA/IB/IIA/IIB/III/IV]; Extent of disease: [limited/extensive]
Final Diagnosis
[Specific CTCL subtype], WHO-EORTC classification