What are the diagnostic tests and treatment options for a patient suspected of having T-cell lymphoma?

Diagnostic Tests for T-Cell Lymphoma

For suspected T-cell lymphoma, obtain an excisional lymph node biopsy with comprehensive immunophenotyping (including CD3, CD4, CD8, CD7, CD30, ALK-1, and T-cell receptor markers), molecular TCR gene rearrangement analysis, and EBV evaluation by EBER in situ hybridization, followed by PET/CT staging, bone marrow biopsy, complete blood count, comprehensive metabolic panel with LDH, and full skin examination. 1, 2

Essential Tissue Diagnosis

• Excisional lymph node biopsy is mandatory rather than fine needle aspiration or core biopsy, as adequate tissue architecture is critical for accurate subtype classification 1, 2
• The immunohistochemistry panel must include: CD20, CD3, CD10, BCL6, Ki-67, CD5, CD30, CD2, CD4, CD8, CD7, CD56, CD21, CD23, TCRbeta, TCRdelta, PD1/CD279, ALK, and TP63 1
• ALK-1 status determination is essential in all anaplastic large cell lymphoma (ALCL) cases, as ALK-positive disease has significantly better prognosis and may not require autologous transplant consolidation 1, 2
• DUSP22 and TP63 rearrangement testing should be performed in ALK-negative ALCL, as DUSP22 rearrangement confers favorable prognosis similar to ALK-positive disease 1, 2
• EBV evaluation using EBER in situ hybridization is mandatory, as EBV positivity occurs in specific subtypes (particularly angioimmunoblastic T-cell lymphoma) and affects prognosis and treatment selection 1, 2
• Molecular TCR gene rearrangement analysis detects clonal T-cell populations and helps distinguish malignant from reactive processes 1, 2

Staging Workup

• PET/CT of chest, abdomen, and pelvis is essential for accurate staging and baseline assessment 1, 2
• Bone marrow biopsy with aspirate is required for all T-cell lymphoma subtypes to assess marrow involvement 1, 2
• Complete blood count with differential identifies cytopenias and circulating lymphoma cells 1, 2
• Comprehensive metabolic panel including LDH, liver function tests, creatinine, and electrolytes assesses organ function and tumor burden 1, 2
• Full skin examination is mandatory as cutaneous involvement is common in T-cell lymphomas, particularly in ALCL and peripheral T-cell lymphoma 1, 2
• CT or MRI of head/neck may be useful in selected cases, particularly for NK/T-cell lymphomas which have predilection for nasal and upper aerodigestive tract involvement 2, 3

Cardiac Assessment

• Multigated acquisition scan (MUGA) or echocardiogram is required before initiating anthracycline-based chemotherapy to establish baseline cardiac function 1, 2

Infectious Disease Screening

• HTLV-1 serology must be performed in appropriate clinical contexts, as HTLV-1 positivity indicates adult T-cell leukemia/lymphoma rather than peripheral T-cell lymphoma, fundamentally changing diagnosis and management 1
• HIV serology should be obtained given potential for immune suppression with therapy 1
• Hepatitis B and C serology is recommended before treatment initiation, as reactivation may occur with immunosuppressive therapy 1

Cutaneous T-Cell Lymphoma Specific Workup

For cutaneous presentations, the diagnostic approach differs:

• Large ellipse or excisional skin biopsies are preferred over punch biopsies to ensure adequate tissue architecture, targeting the most indurated area 4
• Flow cytometry of peripheral blood with lymphocyte subsets and CD4/CD8 ratios is mandatory 4
• CT imaging is optional for early-stage mycosis fungoides (stage IA/IB) but mandatory for stage IIA/IIB/III/IV and all other cutaneous T-cell lymphoma variants 4
• Excisional lymph node biopsy is required for any node ≥1.5 cm in diameter and/or firm, irregular, clustered, or fixed 4

Critical Pitfalls to Avoid

• Do not rely on punch biopsies alone for cutaneous presentations, as inadequate tissue may lead to misdiagnosis 4
• Do not omit ALK-1 testing in ALCL, as this fundamentally changes prognosis and treatment intensity 1, 2
• Do not skip HTLV-1 serology when considering peripheral T-cell lymphoma diagnosis, as positive serology indicates adult T-cell leukemia/lymphoma requiring different management 1
• Do not perform routine abdominal CT for early-stage cutaneous disease (stage IA/IB mycosis fungoides), as it provides minimal clinical benefit 4

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Treatment Options for T-Cell Lymphoma

For nodal peripheral T-cell lymphoma in patients under 60-65 years with good performance status, administer CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) for 6 cycles followed by autologous stem cell transplantation in chemosensitive patients; for ALK-positive ALCL with low-risk IPI, omit transplant consolidation as outcomes are favorable with chemotherapy alone. 2

First-Line Treatment by Subtype

Nodal PTCL (PTCL-NOS, AITL, ALCL)

• CHOEP regimen (6 courses bi-weekly) achieves 82% overall response rate with 51% complete response for patients under 60-65 years 2
• Five-year overall survival: 70% for ALCL ALK-negative, 52% for angioimmunoblastic T-cell lymphoma, and 47% for PTCL-NOS 2
• Autologous stem cell transplantation consolidation is recommended for chemosensitive patients after CHOEP 2
• ALK-positive ALCL with low-risk IPI does not require transplant consolidation, as outcomes are favorable with chemotherapy alone 2
• Standard CHOP (without etoposide) may be used for older patients (>60-65 years) due to CHOEP toxicity 2

CD30-Positive Peripheral T-Cell Lymphomas

• Brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone is FDA-approved for previously untreated systemic ALCL or other CD30-expressing peripheral T-cell lymphomas including angioimmunoblastic T-cell lymphoma and PTCL-NOS 5
• Dosing: 1.8 mg/kg up to maximum 180 mg every 3 weeks for 6-8 doses 5

Relapsed/Refractory Disease

• Brentuximab vedotin monotherapy (1.8 mg/kg up to 180 mg every 3 weeks) is FDA-approved for systemic ALCL after failure of at least one prior multi-agent chemotherapy regimen 5
• Brentuximab vedotin is FDA-approved for primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy 5
• Allogeneic hematopoietic stem cell transplantation should be considered for stage III/IV disease in suitable patients with chemosensitive disease 3

NK/T-Cell Lymphomas

• Non-anthracycline asparaginase-based regimens are required, as NK/T-cell lymphomas express multidrug resistance phenotype rendering anthracycline-containing regimens ineffective 3
• Stage I/II nasal cases: asparaginase-based regimens plus sequential/concurrent radiotherapy 3
• Stage III/IV nasal and non-nasal cases: asparaginase-containing regimens consolidated by allogeneic HSCT in suitable patients 3
• Autologous HSCT does not improve outcome in NK/T-cell lymphomas 3

Response Monitoring

• Radiological assessment after every 2-4 cycles of therapy, at treatment completion, and whenever response is questioned 2
• Therapeutic goals: achieve undetectable plasma EBV DNA (for EBV-positive subtypes) and normal PET/CT with Deauville score ≤3 3
• Repeat biopsy should be strongly considered for persistent or new PET-positive lesions prior to additional therapy, particularly for angioimmunoblastic T-cell lymphoma which may present with concurrent DLBCL 1

Surveillance After Treatment

• Clinical monitoring with history and physical examination every 3-6 months for 2 years, then as clinically indicated 2
• Surveillance imaging no more often than every 6 months for 2 years, then annually for 5 years or as clinically indicated 2
• Laboratory monitoring including complete blood count, comprehensive metabolic panel, and LDH at baseline and during follow-up 2

Treatment Toxicity Management

• Monitor for peripheral neuropathy and institute dose modifications accordingly, as this is common with brentuximab vedotin and vinca alkaloids 5
• Monitor complete blood counts for hematologic toxicities and manage with dose delays and growth factor support 5
• Avoid concomitant bleomycin with brentuximab vedotin due to pulmonary toxicity 5
• Reduce brentuximab vedotin dose in mild hepatic impairment; avoid use in moderate/severe hepatic impairment or severe renal impairment 5

Novel Approaches for Relapsed/Refractory Disease

• Immune checkpoint blockade of PD1/PD-L1 3
• EBV-specific cytotoxic T-cells for EBV-positive subtypes 3
• Histone deacetylase inhibitors 3