T-Cell Lymphomas

Published on 04/03/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 22/04/2025

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Chapter 37 T-Cell Lymphomas

Owen A. O’Connor, Enrica Marchi, Govind Bhagat, Paolo Corradini, Joan Guitart, Steven T. Rosen, Timothy M. Kuzel

Treatment of Peripheral T-Cell Lymphoma

Given that the mature T-cell lymphomas are relatively rare diseases, there is a lack of large randomized clinical trials comparing the “standard” CHOP and CHOP-like regimens to other more-intensified chemotherapy strategies, or even other novel drug platforms. Our approach involves tailoring the treatment to the specific histologic subtype and age of the patient. From the outset, we send HLA typing for possible allogeneic stem cell transplant, assuming the patient is eligible, and request immunohistochemical staining of the primary tissue for CD30. Where possible, we preferentially try to put all patients on a clinical trial. For the majority of peripheral T-cell lymphomas, our standard initial approach is to use an etoposide-based regimen (CHOEP or EPOCH), especially for young patients or older adult patients with an excellent performance status. As alluded to earlier, there are some data to suggest a reduced failure-free interval and higher complete response rate. For patients with a poor performance status or older adult patients, standard CHOP administered on an every-21-day basis for six to eight cycles would be our preferred recommendation. In select cases, where an older adult patient is not a candidate for combination chemotherapy and requires palliative care, we have successfully used single-agent gemcitabine to obtain disease control and improve performance status. Those patients who attain a complete remission are usually referred for an autologous stem cell transplant. Those patients who do not attain a complete remission with standard frontline chemotherapy are typically referred for treatment with one of the drugs recently approved by the FDA for patients with relapsed or refractory disease, including pralatrexate, romidepsin, or brentuximab vedotin (if CD30⁺ positive). For patients who relapse or are refractory to frontline and beyond therapy, we typically consider allogeneic stem cell transplant, assuming they are transplant eligible and have an appropriate HLA match.

CHOEP, Cyclophosphamide, hydroxydaunomycin, vincristine (Oncovin), etoposide, and prednisone; CHOP, cyclophosphamide, hydroxydaunomycin, vincristine (Oncovin), and prednisone; EPOCH, etoposide, prednisone, vincristine (Oncovin), cyclophosphamide, and hydroxydaunomycin; FDA, Food and Drug Administration; HLA, human leukocyte antigen.

Figure 37-1 WHO CLASSIFICATION OF THE MATURE T-CELL NEOPLASMS.

NK, Natural killer; NOS, not otherwise specified; TCL, T-cell lymphoma.

Figure 37-2 ANAPLASTIC LARGE CELL LYMPHOMA.

Anaplastic large cell lymphoma has variable morphologic features but is typically composed of large, highly irregular “anaplastic” cells, which include giant cells sometimes with a wreath-like or horseshoe-shape nuclei, and “hallmark” cells, which are cells with a folded-up nucleus with an embryo shape (A). The cells are typically brightly CD30 positive (B). ALK1 staining with cytoplasmic and nuclear localization (C) is associated with the t(2;5)(p23;q35) translocation, whereas other patterns are associated with the variant translocations (C). Whether ALK1-negative cases should be considered as a separate group or classified together with peripheral T-cell lymphoma not otherwise specified is somewhat debatable.

Figure 37-3 PERIPHERAL T-CELL LYMPHOMA NOT OTHERWISE SPECIFIED (PTCL-NOS).

PTCL-NOS is morphologically heterogeneous. Typically, cases have a spectrum of small to large lymphoma cells, frequently with irregular nuclear borders and sometimes with clear cytoplasm. Other cases can have more of a predominance of small or large cells. Features of the other defined types of T-cell lymphoma should be lacking.

Figure 37-4 ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA (AITL).

A prominent feature of AITL is the prominent vasculature in the background. The vessels usually show branching and prominent endothelial cells (A). The cellular component is made up of a mix of plasma cells, immunoblasts, and small lymphocytes; the lymphoma cells can be of intermediate or large size and they tend to cluster and exhibit clear cytoplasm (A, B). Some cases can develop a superimposed Epstein-Barr virus–driven large B-cell lymphoma.

Figure 37-5 NATURAL KILLER (NK)/T-CELL LYMPHOMA, NASAL TYPE.

The nasal type of NK/T-cell lymphoma (A, B) is usually associated with marked necrosis and karyorrhectic material indicating high cell turnover. The lymphoma cells are variable from case to case, but they invariably are Epstein-Barr virus (EBV) positive as demonstrated by in situ hybridization for EBV-encoded ribonucleic acid (RNA; B).

Figure 37-6 HUMAN T-LYMPHOTROPIC VIRUS-1–ASSOCIATED LEUKEMIA/LYMPHOMA.

The leukemic process (adult T-cell leukemia/lymphoma) is characterized by circulating neoplastic T cells with a “flower-like” form. In some cases this cytologic feature is more prominent than in others.

Figure 37-7 ENTEROPATHY-ASSOCIATED T-CELL LYMPHOMA.

In enteropathy-associated T-cell lymphoma there is prominent infiltration of gastrointestinal glandular elements by neoplastic T cells (A). These are typically CD3⁺ (B) and almost always CD5⁻ and CD4⁻ negative, and CD8, and CD56 variable, depending on the type.

Figure 37-8 HEPATOSPLENIC T-CELL LYMPHOMA.

Hepatosplenic γδ-T-cell lymphoma is commonly diagnosed from a bone marrow biopsy specimen in a patient being evaluated for hepatosplenomegaly. The bone marrow typically shows a subtle lymphoid infiltrate (A), which becomes more evident with a T-cell stain such as CD3 (B). This highlights the classic sinusoidal distribution of the lymphoma. Lymphoma cells may be seen in the circulation or in the marrow aspirate and can resemble monocytes or blasts (C). The lymphoma is typically associated with isochromosome 7q, as illustrated in the partial karyotype (D).

Table 37-1 WHO Classification of the Mature T-Cell Lymphomas

ALCL, Anaplastic large cell lymphoma; ATL, adult T-cell leukemia/lymphoma; EBV, Epstein-Barr virus; HTLV-1, human T-lymphotropic virus-1; LPD, lymphoproliferative disease; LYP, lymphomatoid papulosis; NK, natural killer; NOS, not otherwise specified; PTCL, peripheral T-cell lymphoma; WHO, World Health Organization.

Table 37-2 Recent FDA-Approved and Emerging New Drugs in Peripheral T-Cell Lymphoma

ATL, Adult T-cell leukemia/lymphoma; CTCL, cutaneous T-cell lymphoma; DOR, duration of response; FDA, Food and Drug Administration; HTLV-1, human T-lymphotropic virus-1; PFS, progression-free survival; PTCL, peripheral T-cell lymphoma.

Algorithm for Care of Patients With Mycosis Fungoides or Sézary Syndrome

CHOP, Cyclophosphamide, hydroxydaunomycin, vincristine (Oncovin), and prednisone; CVP, cyclophosphamide, vincristine, and prednisone; EPOCH, etoposide, prednisone, vincristine (Oncovin), cyclophosphamide, and hydroxydaunomycin; MF, mycosis fungoides; nSS, Sézary syndrome.

Table 37-3 TNM Staging System for Cutaneous T-Cell Lymphomas

Classification	Description
T	Skin
T0	Clinically or histopathologically suspicious lesions
T1	Limited plaques, papules, or eczematous patches covering 10% of the skin surface
T2	Generalized plaques, papules, or erythematous patches covering 10% of the skin surface
T3	Tumors (one or more)
T4	Generalized erythroderma
	Pathology of T1 to 4 is diagnostic of a cutaneous T-cell lymphoma. When more than one T stage exists, both are recorded and highest is used for staging. Record other features if appropriate (e.g., ulcers, poikiloderma, scale)
N	Lymph nodes
N0	No clinically abnormal peripheral lymph nodes
N1	Clinically abnormal peripheral lymph nodes (record number of sites)
NP0	Biopsy performed, not CTCL
NP1	Biopsy performed, CTCL
PB	Peripheral blood
PB0	Atypical circulating cells not present (≤5%)
PB1	Atypical circulating cells not present (>5%), record total white blood cell count, total lymphocyte count, and percentage of abnormal cells
M	Visceral organs
M0	No visceral organ involvement
M1	Visceral involvement (must have pathologic confirmation), record organ involved
Staging
Stage IA	T1, N0 NP0, M0
Stage IB	T2, N0 NP0, M0
Stage IIA	T1-2, N1 NP0, M0
Stage IIB	T3, N0 NP0, M0
Stage III	T4, N0 NP0, M0
Stage IVA	T1-4, N0,1 NP1, M0
Stage IVB	T1-4, N0,1 NP0,1, M1