Definition/General
Introduction:
Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a CD30-positive T-cell lymphoma that arises primarily in the skin without evidence of extracutaneous disease at presentation
It belongs to the spectrum of primary cutaneous CD30+ lymphoproliferative disorders
ALK-negative by definition (distinguishing from systemic ALCL)
Has excellent prognosis compared to systemic ALCL
Second most common cutaneous T-cell lymphoma after mycosis fungoides.
Origin:
Originates from activated T-lymphocytes expressing CD30 activation marker
Shows clonal T-cell receptor gene rearrangements
Skin-homing T-cells with cutaneous lymphocyte antigen (CLA) expression
Helper T-cell phenotype (CD4+) predominant
Lacks ALK gene rearrangements (ALK-negative)
Different pathogenesis from systemic ALCL
Local growth factors may contribute to pathogenesis.
Classification:
WHO-EORTC classification recognizes as distinct entity within primary cutaneous CD30+ lymphoproliferative disorders
Must exclude systemic disease at presentation
ALK-negative by definition
Relationship to lymphomatoid papulosis (spectrum of CD30+ disorders)
No histological grades recognized
Clinical stage more important than histological features.
Epidemiology:
Peak incidence in 6th decade (median age 60 years)
Male predominance (M:F = 2-3:1)
Second most common cutaneous T-cell lymphoma (20-25%)
Excellent prognosis (5-year disease-specific survival >95%)
Rare systemic dissemination (<5%)
Regional lymph node involvement in 5-10%
Indian population shows similar demographics.
Clinical Features
Presentation:
Solitary or localized skin lesions (75% of cases)
Large nodules or tumors (typically >2 cm)
Ulceration common (50-80%)
Rapid growth over weeks to months
No spontaneous regression (unlike lymphomatoid papulosis)
Trunk and extremities most common sites
No systemic symptoms typically.
Symptoms:
Localized pain or tenderness in some patients
Pruritus occasionally
Bleeding or discharge from ulcerated lesions
No constitutional symptoms (fever, weight loss, night sweats)
Functional impairment minimal unless large size
Cosmetic concerns
Secondary bacterial infection of ulcerated areas.
Risk Factors:
Age >50 years
Male gender
Previous lymphomatoid papulosis (10-20% association)
Immunosuppression (organ transplant recipients)
Chronic skin inflammation
UV exposure (controversial)
Genetic predisposition (rare familial cases)
Geographic factors not well established.
Screening:
Clinical examination of skin lesions
Palpation of regional lymph nodes
Complete blood count and peripheral smear
Imaging studies to exclude systemic disease (CT, PET-CT)
Bone marrow biopsy not routinely needed
Flow cytometry if blood involvement suspected
Staging workup essential to confirm primary cutaneous disease.
Master pcALCL Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Large nodules or tumors typically >2 cm
Solitary lesions in 75% of cases
Red to violaceous color
Ulceration with necrotic centers common
Well-circumscribed or infiltrative borders
Firm consistency
May be multinodular in some cases.
Characteristics:
Dome-shaped or polypoid configuration
Surface ulceration with crusting
Surrounding erythema
Palpable firmness
No spontaneous regression
Gradual enlargement if untreated
Bleeding tendency due to surface friability.
Size Location:
Size range: 2-15 cm (median 3-5 cm)
Trunk most common location (40%)
Extremities (arms and legs) frequent
Head and neck (15-20%)
Buttocks occasionally involved
Rarely involves palms, soles, or mucous membranes
Regional lymph nodes may be enlarged (reactive or involved).
Multifocality:
Solitary lesions predominant (75%)
Multiple lesions in same anatomical region (25%)
No generalized skin involvement
Regional lymph node involvement in 5-10%
Extracutaneous spread rare (<5%)
No systemic involvement at presentation by definition
Local recurrence possible if incompletely excised.
Microscopic Description
Histological Features:
Sheets of large anaplastic cells with uniform CD30 expression
Cohesive growth pattern
Hallmark cells with eccentric, kidney-shaped nuclei
Prominent nucleoli
Abundant eosinophilic cytoplasm
High mitotic activity
Necrosis often present
Minimal inflammatory background.
Cellular Characteristics:
Large anaplastic cells (>3 times normal lymphocyte size)
Hallmark cells pathognomonic (eccentric, convoluted nuclei)
Pleomorphic nuclei with irregular contours
Vesicular chromatin
Large, prominent nucleoli
Abundant cytoplasm
Multinucleated giant cells common
Frequent mitoses and apoptotic figures.
Architectural Patterns:
Diffuse growth pattern throughout dermis
Cohesive sheets of tumor cells
Nodular configuration common
May extend into subcutis
Ulceration of overlying epidermis frequent
Minimal epidermotropism
Perivascular accentuation may be seen
Pushing borders rather than infiltrative.
Grading Criteria:
No formal grading system as uniformly high-grade morphologically
Proliferation index (Ki-67) typically >70%
Degree of pleomorphism noted
Mitotic rate invariably high
Extent of necrosis variable
CD30 expression should be uniform and strong (>75%)
ALK negativity essential for diagnosis.
Immunohistochemistry
Positive Markers:
CD30 (uniformly positive, diagnostic requirement)
CD3 (variable, may be weak or lost)
CD4 (positive in majority)
CD2 (usually positive)
Granzyme B and Perforin (cytotoxic markers, often positive)
TIA-1 (cytotoxic marker)
EMA (epithelial membrane antigen, often positive)
Cutaneous lymphocyte antigen (CLA).
Negative Markers:
ALK (negative by definition)
CD8 (usually negative)
CD5 (often lost)
CD7 (often lost)
CD20 (B-cell marker, negative)
CD15 (usually negative)
PAX5 (B-cell marker, negative)
Cytokeratin (negative)
S-100 (negative).
Diagnostic Utility:
CD30 uniform positivity essential (>75% of tumor cells)
ALK negativity distinguishes from systemic ALCL
Cytotoxic markers often positive
Loss of pan-T-cell antigens supports neoplastic nature
EMA positivity helps confirm diagnosis
Ki-67 shows high proliferation
Cytokeratin negativity excludes carcinoma.
Molecular Subtypes:
Helper T-cell phenotype (CD4+) predominant
Cytotoxic features (granzyme B+, perforin+) common
ALK-negative phenotype defining feature
Loss of T-cell antigens (CD5, CD7) frequent
CD30+ large cell population characteristic
Different from systemic ALCL immunoprofile.
Molecular/Genetic
Genetic Mutations:
Clonal T-cell receptor rearrangements in most cases
DUSP22-IRF4 rearrangements in 30% of cases (better prognosis)
TP63 rearrangements in 8% of cases (worse prognosis)
TP53 mutations in subset
STAT3 mutations rare
Complex chromosomal abnormalities less common than systemic ALCL.
Molecular Markers:
CD30 overexpression characteristic
JAK/STAT pathway activation
NF-κB pathway dysregulation
Cell cycle dysregulation
Apoptosis resistance
Different gene expression profile from systemic ALCL
Skin-homing markers expression.
Prognostic Significance:
Excellent prognosis (5-year disease-specific survival >95%)
DUSP22 rearrangements associated with better outcome
TP63 rearrangements associated with worse prognosis
Size >5 cm may indicate worse outcome
Multiple lesions vs solitary lesion outcomes similar
Regional lymph node involvement doesn't significantly worsen prognosis.
Therapeutic Targets:
Surgical excision (treatment of choice for localized disease)
Radiation therapy for unresectable lesions
Anti-CD30 therapy (brentuximab vedotin) for advanced cases
Systemic chemotherapy rarely needed
Topical therapies for small lesions
Close follow-up for early detection of recurrence.
Differential Diagnosis
Similar Entities:
Systemic anaplastic large cell lymphoma (ALK+/-)
Lymphomatoid papulosis Type C
Classical Hodgkin lymphoma (cutaneous involvement)
Diffuse large B-cell lymphoma
Poorly differentiated carcinoma
Malignant melanoma (amelanotic)
Metastatic carcinoma to skin.
Distinguishing Features:
pcALCL: CD30+, ALK-, T-cell markers, primary cutaneous, excellent prognosis
Systemic ALCL: ALK+ (many cases), systemic disease, nodal involvement
LyP Type C: self-healing, smaller lesions, mixed infiltrate
Hodgkin lymphoma: CD15+, mixed inflammatory background
DLBCL: CD20+, B-cell markers
Carcinoma: cytokeratin+.
Diagnostic Challenges:
Distinguishing from systemic ALCL requires staging studies
LyP Type C vs pcALCL overlap (clinical behavior crucial)
Limited tissue samples may prevent full characterization
Need for ALK immunostaining
Exclusion of systemic disease essential
Clinical correlation important for final diagnosis.
Rare Variants:
pcALCL with neutrophil-rich infiltrate
pcALCL with histiocytic component
Small cell variant of pcALCL
pcALCL with keratoacanthoma-like features
Multiple pcALCL lesions
pcALCL with regional lymph node involvement
Transformed from lymphomatoid papulosis.
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 excision/biopsy] from [anatomical site], tumor measuring [size] cm
Primary Diagnosis
Primary cutaneous anaplastic large cell lymphoma
WHO-EORTC Classification
Primary cutaneous anaplastic large cell lymphoma (WHO-EORTC classification)
Staging Assessment
Primary cutaneous disease confirmed; No evidence of extracutaneous involvement at presentation
Histological Features
Shows sheets of large anaplastic cells with cohesive growth pattern and hallmark cell morphology
Cellular Morphology
Large anaplastic cells with pleomorphic nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm
CD30 Assessment
CD30: uniformly positive (>75% of tumor cells); Intensity: strong; Pattern: membranous and cytoplasmic
Immunohistochemistry
CD30+, ALK-, CD3+/-, CD4+, cytotoxic markers+, CD20-, cytokeratin-; Ki-67: [percentage]%
Molecular Studies
T-cell receptor rearrangement: clonal; [DUSP22/TP63 rearrangements if tested]
Prognosis
Excellent prognosis with >95% disease-specific survival; Local treatment usually curative
Treatment Recommendations
Complete surgical excision recommended; Radiation therapy if unresectable; Close follow-up for recurrence
Final Diagnosis
Primary cutaneous anaplastic large cell lymphoma, ALK-negative, WHO-EORTC classification