Cutaneous T-Cell Lymphoma and Cutaneous B-Cell Lymphoma
Summary of Key Points
Incidence
• Cutaneous lymphomas represent 3.9% of non-Hodgkin lymphomas.
• The annual incidence of cutaneous T-cell lymphoma (CTCL) in the United States is approximately 9.6 cases per 1 million population with a median age of 60 years at initial presentation.
• CTCL accounts for up to 71% and cutaneous B-cell lymphoma (CBCL) accounts for up to 29% of all cutaneous lymphomas.
Biological Characteristics
• CTCL may be indolent as in mycosis fungoides (MF) or aggressive as in Sézary syndrome (SS).
• The malignant T cells in MF/SS are characterized by a CD4+ T-helper (Th)/memory cell phenotype with frequent loss of CD7 and/or CD26 and the expression of skin homing markers such as CLA, CCR4, and CCR10. MF/SS demonstrate an altered immune biology and the accumulation of cytogenetic abnormalities during disease progression with a predominant Th2 cytokine profile in advanced stages.
• Primary CBCLs such as cutaneous follicle center lymphoma have failed to show similar alterations compared with their nodal counterpart. The prognosis of both primary cutaneous follicle center lymphoma and cutaneous marginal zone lymphoma is usually excellent.
• The gene expression profile of primary cutaneous large B-cell lymphoma, leg type, is similar to that of nodal diffuse large B-cell lymphoma (DLBCL) arising from germinal center or post–germinal center–activated B cells with constitutive nuclear factor–κB (NF-κB) pathway activation and strong expression of the IRF4/MUM1 transcription factor and carries a worse prognosis.
Staging Evaluation
• All patients with cutaneous lymphoma should initially be seen and co-managed by a multidisciplinary cutaneous lymphoma team consisting of members from dermatology and oncology with the support of other health care professionals such as radiation oncologists, pathologists, and clinical psychologists.
• Routine evaluation should include complete physical examination, complete blood cell count with differential, and chemistry panel with lactate dehydrogenase (LDH) level, skin biopsy for histology, immunophenotyping and gene rearrangement studies, and lymph node biopsies in cases with enlarged nodes at presentation.
• Imaging studies and flow cytometry panel of peripheral blood should be reserved for patients with clinical and laboratory findings suggestive of systemic disease and/or prominent lymphadenopathy. Bone marrow biopsy is a consideration in advanced-stage disease. Histopathological and molecular results should be correlated with clinical findings and patients classified according to the World Health Organization/European Organization of Research and Treatment of Cancer (WHO/EORTC) consensus classification.
Therapy
• Early-stage MF usually responds well to skin-directed therapies such as phototherapy, radiation, topical nitrogen mustard, retinoid, or corticosteroid skin creams.
• Treatment for patients with advanced stages of MF or SS generally requires systemic therapies, including biological or immune therapies, histone deacetylase inhibitors, conventional chemotherapeutic agents, or combinations of these agents.
1. The most common form of primary cutaneous B-cell lymphoma (CBCL) is
2. Immunohistochemistry on skin biopsy specimens to determine a B-cell lymphoma most likely demonstrates
3. Treatment options for primary cutaneous B-cell lymphoma may include all of the following except
4. Which of the following statements regarding mycosis fungoides is true?
A It is usually a proliferation of CD8+ T cells.
B The 5-year survival rate for a patient with stage IB is 40%.
C It is an aggressive disease.
D Advanced stages are associated with increased production of Th2 cytokines.
E Human T-cell lymphotropic virus type I infections cause the disease.
5. A 40-year-old man has a 20-year history of waxing and waning papules that necrotize and heal spontaneously. A skin biopsy would most likely reveal
6. Appropriate therapy for early-stage mycosis fungoides (Ia/IIa) includes each of the following therapies except
A Psoralens and ultraviolet-A light therapy (PUVA)
B Narrow band ultraviolet-B light therapy (NB-UVB) and low-dose oral Targretin
7. Which of the following treatments is/are not appropriate for Sézary syndrome?
8. All of the following statements regarding treatment-related side effects are true except
A Topical nitrogen mustard and contact hypersensitivity reactions
B Monoclonal antibody and depression
C Denileukin diftitox and vascular leak syndrome
D Total-skin electron-beam therapy (TSEBT) and increased risk for developing nonmelanoma skin cancers
9. In patients diagnosed with lymphomatoid papulosis, which of the following statements is not true?
A Aggressive neoplasms have an estimated 15% 5-year survival rate.
B This is a benign, chronic, recurrent, self-healing skin eruption.
C Large atypical CD30+ T cells are characteristic histologic findings.
D Disease progression is associated with increased fascin levels.
E Observation, ultraviolet light therapy, and low-dose methotrexate are the preferred treatment options.
10. All of the following statements regarding primary cutaneous lymphomas are true except
A Primary cutaneous T-cell lymphoma is an extranodal non-Hodgkin disease.
B Sézary syndrome is a nodal lymphoma with secondary skin involvement.
C Mycosis fungoides is the most common type.
D Primary cutaneous lymphomas are rare.
E Adhesion molecules and chemokines are associated with cutaneous T-cell homing.
1. Answer: A. Follicle center lymphoma is the most common CBCL, comprising 40% of all CBCLs, followed by marginal zone lymphoma.
2. Answer: B. The B cells are positive for CD20 surface marker with a clonal rearrangement of immunoglobulin heavy-chain gene in 60% to 70% of cases. T cells are positive for CD4. The infiltrate in mycosis fungoides shows a CD4:CD8 ratio greater than 10 : 1.
3. Answer: A. Appropriate treatments for CBCL would be local excision, irradiation, polychemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], CHOP-based) with or without rituximab. B cells do not express CD30 marker, so there is no role for anti-CD30 therapy.
4. Answer: D. Mycosis fungoides is an indolent disease arising from CD4+ T cells. The 5-year survival rate for stage IB is about 85%. Advanced stages express Th2 type cytokines, leading to or enhancing immunosuppression.
5. Answer: D. The history of waxing and waning papules that necrotize and heal spontaneously is typical of lymphomatoid papulosis.
6. Answer: C. Appropriate treatments for early-stage mycosis fungoides are skin directed and include PUVA, NB-UVB, and topical nitrogen mustard. The use of NB-UVB and low-dose bexarotene (Targretin) is considered when topical treatment alone does not clear the lesions effectively. Romidepsin is given for advanced-stage (IIB and higher) disease.
7. Answer: E. All of these treatments are effective and have been used for patients with Sézary syndrome.
8. Answer: B. Depression has not been seen with use of monoclonal antibodies such as anti-CD20 or anti-CD4 or anti-CD30 in patients with cutaneous lymphoma; all other side effects are typical with associated treatment.
9. Answer: A. Lymphomatoid papulosis is an indolent disorder presenting as recurrent, self-healing crops of lesions. The 5-year survival rate is above 95%. It can be associated with other malignancies in 20% to 25% of cases, thus monitoring patients is advised.
10. Answer: B. Sézary syndrome is a cutaneous lymphoma with primary skin involvement and a leukemic component with or without lymph node involvement.
