What is the approach to a T-cell cutaneous workup, including diagnosis, treatment, and management?

T-Cell Cutaneous Lymphoma Workup

The workup for cutaneous T-cell lymphoma requires obtaining adequate tissue via excisional or large ellipse biopsies (not punch biopsies) for histology, immunophenotyping, and T-cell receptor gene analysis, followed by comprehensive staging that includes physical examination, blood work with flow cytometry, and imaging studies (CT ± PET) for all patients except those with early-stage mycosis fungoides (stage IA/IB). 1, 2

Diagnostic Tissue Acquisition

Biopsy technique is critical for accurate diagnosis:

• Obtain excisional or ellipse biopsies rather than punch biopsies to ensure adequate tissue architecture for evaluation 2, 1
• Use at least 4mm diameter if punch biopsy is unavoidable 2
• Multiple biopsies from different sites may be required if initial sampling is non-diagnostic, as CTCL can be challenging to diagnose histologically 1, 2
• Biopsy the most indurated area if only obtaining one specimen 1

Essential tissue analyses include:

• Routine histology with assessment of epidermotropism, folliculotropism, and dermal infiltrate patterns 1
• Immunophenotyping with CD3 (T-cell confirmation), CD4 and CD8 (subset identification), CD7, and CD26 1, 2
• T-cell receptor (TCR) gene rearrangement analysis to detect clonality - this is critical as patients with detectable clones have shorter response duration and higher failure rates 1
• Fresh tissue is ideal for molecular studies 1

Blood Work and Laboratory Evaluation

Mandatory blood tests at diagnosis:

• Complete blood count with manual differential and absolute Sézary cell count 1
• Flow cytometry of peripheral blood analyzing CD4+/CD7- or CD4+/CD26- populations 1
• Comprehensive metabolic panel, liver function tests, and lactate dehydrogenase (LDH) 1
• Lymphocyte subsets with CD4/CD8 ratios 1
• TCR gene rearrangement analysis of blood to compare with skin clone 1
• HTLV-I serology 1

Important caveat: Flow cytometry is debatable in early-stage MF patients not suspected of having Sézary syndrome, though most guidelines recommend it for all stages 1

Staging Imaging Studies

The extent of imaging depends on disease stage:

For early-stage mycosis fungoides (stage IA/IB):

• CT scans of chest, abdomen, and pelvis are optional 1
• Consider deferring imaging in these patients to avoid overtreatment 1

For stage IIA/IIB/III/IV mycosis fungoides and all other CTCL variants:

• CT scans of chest, abdomen, and pelvis are mandatory 1
• Consider FDG-PET for more accurate staging, particularly in aggressive subtypes 1, 2
• FDG-PET is essential for predominantly subcutaneous presentations (subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous gamma/delta T-cell lymphoma) 1

For lymphomatoid papulosis or primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder:

• CT and PET scans are not required 1

Physical Examination Components

Complete examination must document:

• Type and distribution of all skin lesions (patches, plaques, tumors) with body surface area involvement for staging 1, 3
• Identification of any palpable lymph nodes ≥1.5 cm or those that are firm, irregular, clustered, or fixed 1
• Assessment for hepatosplenomegaly or other organomegaly 1
• Evaluation for B symptoms (fever, night sweats, weight loss) 2

Lymph Node Evaluation

When to biopsy lymph nodes:

• Excisional biopsy (not core or fine needle) is required for any node ≥1.5 cm in diameter and/or firm, irregular, clustered, or fixed 1, 2
• Perform routine histology, immunohistochemistry, and TCR gene rearrangement analysis on nodal tissue 1

Bone Marrow Evaluation

Bone marrow biopsy and aspirate indications:

• Required for all CTCL variants except lymphomatoid papulosis 1
• Should be considered for stage IIB/III/IV mycosis fungoides 1
• Not indicated for early-stage MF (IA/IB) or lymphomatoid papulosis 1
• Essential in cutaneous lymphomas with intermediate or aggressive clinical behavior 1

Multidisciplinary Team Review

All patients should ideally be reviewed by a multidisciplinary team including dermatologist, clinical/medical oncologist, and dermatopathologist with CTCL experience 1

Possible exceptions:

• Early-stage mycosis fungoides (stage IA) 1
• Lymphomatoid papulosis 1

Central pathology review is desirable for all cases 1

Critical Diagnostic Pitfalls

Distinguishing primary from secondary cutaneous lymphoma:

• Immunophenotype pattern is decisive - strong Bcl-2, Bcl-6, and CD10 expression in follicular structures indicates systemic follicular lymphoma rather than primary cutaneous disease 2
• CD5+ cyclin D1+ indicates mantle cell lymphoma 2
• CD5+ CD23+ with dim CD20 indicates chronic lymphocytic leukemia/small lymphocytic lymphoma 2
• Never rely on morphology alone - immunohistochemistry is mandatory 2

Molecular analysis interpretation:

• Identically sized peaks by TRG PCR in skin and blood may not represent the same clone - high-throughput sequencing provides more specificity 4
• HTS has 100% specificity versus 88% for TRG PCR in distinguishing definitive CTCL from reactive processes 4

Prognostic Stratification

Survival varies dramatically by stage and guides treatment intensity 1:

• Stage IA: 96-100% 5-year survival, 84-100% 10-year survival
• Stage IB: 73-86% 5-year survival, 58-67% 10-year survival
• Stage IVB (visceral involvement): 0-15% 5-year survival, 0-5% 10-year survival

The presence of extracutaneous disease fundamentally changes treatment strategy from skin-directed to systemic therapy 5