Page 1110 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1074 ParT EIGhT Immunology of Neoplasia

Primary Cutaneous γ/δ T-Cell Lymphomas The homing pattern manifested by the malignant cells is similar
Primary cutaneous γ/δ T-cell lymphomas are clinically aggressive to that of normal γ/δ T cells, which also populate the sinusoidal
tumors that can present with involvement of the subcutis and areas of the spleen. The neoplastic cells have a phenotype that
the dermis or with epidermal infiltration. Skin is the most resembles normal γ/δ T cells, usually expressing neither CD4
common presenting site, however, similar lymphomas of γ/δ nor CD8. CD56 is often positive. The cells are positive for the
T-cell origin can present in other extranodal sites, including the cytotoxic protein TIA-1, but are not activated and generally lack
GI tract and lungs. The cells have a cytotoxic phenotype and granzyme B and perforin. In situ hybridization for EBV is negative.
express cytotoxic molecules, and like normal γ/δ T cells, lack The recognition of the atypical cells in bone marrow is greatly
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CD5. They may be CD8 or, more often, double-negative for aided by immunohistochemical stains showing a sinusoidal
CD4 and CD8. Few cutaneous γ/δ T-cell lymphomas appear to pattern of infiltration.
be TCR silent (negative for both TCR-β and TCR-γ) but share Isochromosome 7 is a consistent cytogenetic abnormality,
the same aggressive clinical behavior. Recurrent mutations of usually seen in conjunction with trisomy 8. Rare cases derived
STAT5B can be seen in T-cell lymphomas of γ/δ origin. 38 from α/β T cells but with similar morphological and biological
features can be seen. Recurrent mutations of STAT5B and less
Mycosis Fungoides and Sézary Syndrome often STAT3 are seen in HSTCL of γ/δ origin. 38
Mycosis fungoides (MF) and Sézary syndrome (SS) are closely Clinically, HSTCL is aggressive. Although patients may respond
related and often considered together from a clinical and biological initially to chemotherapy, relapse occurs in the vast majority of
standpoint but are now regarded as separate diseases. Both are cases. The median survival is less than 3 years. Allogeneic bone
primary cutaneous T-cell malignancies derived from mature skin marrow transplantation is required for sustained remission.
homing CD4 T cells. Epidermotropism is the hallmark of MF;
infiltration of the epidermis produces characteristic Pautrier Adult T-Cell Leukemia/Lymphoma
microabscesses. The cutaneous lesions are categorized as patches, Adult T-cell leukemia/lymphoma (ATLL) is a distinct form of
plaques, and tumors, based on the extent of the infiltrate. A γ/δ T-cell lymphoma associated with the retrovirus human
indolent variant of MF has also been described. SS presents with T-lymphotropic virus-1 (HTLV-1). The highest number of cases
exfoliative erythroderma and circulating cerebriform lymphocytes is seen in Southwestern Japan and the Caribbean basin. The
known as Sézary cells. Clinically, SS is more aggressive than MF. disease has a long latency, and affected individuals are usually
exposed to the virus very early in life. The virus may be transmit-
Enteropathy-Associated T-Cell Lymphoma ted in breast milk and through exposure to blood or blood
Enteropathy-associated T-cell lymphoma (EATL) is highly products. The cumulative incidence of ATLL is estimated to be
associated with celiac disease on a worldwide basis. This disease 2.5% among HTLV-1 carriers. The virus is monoclonally inte-
occurs in adults; the majority has either overt or clinically silent grated into tumor DNA. Different clinical variants of ATLL,
gluten-sensitive enteropathy (Chapter 75). Ulcerative jejunitis may including the acute, lymphomatous, chronic, and smoldering
precede the development of overt EATL and may share a common types, have been recognized. Cutaneous involvement is seen in
clonal T-cell population as with the subsequent lymphoma. The the majority of patients.
small bowel usually shows ulceration with frequent perforation, Peripheral blood involvement is very common, often without
with or without a mass. EATL shows a cytological composition bone marrow disease. The atypical cells are often markedly
of variably sized or polymorphic atypical lymphoid cells. The polylobated and have been referred to as “flower” cells. The cells
adjacent small bowel usually shows villous atrophy associated have a characteristic phenotype that resembles T-regulatory cells
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with celiac disease. The neoplastic cells are CD3 , CD7 T cells (Tregs)—CD3 , CD4 , and CD25 . FoxP3 is expressed in a
that also express the homing receptor CD103. Anaplastic cells minority of tumor cells. The function of the tumor cells as Tregs
strongly positive for CD30 can be present. The cells express may correlate with the associated immunodeficiency.
cytotoxic molecules, a feature shared by nearly all extranodal Somatic gain of function CCR4 mutations have been implicated
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T-cell lymphomas. The majority belong to the α/β TCR subset, in the pathogenesis of ATLL. Recent integrated molecular analysis
whereas only a minority expresses the γ/δ TCR. Other PTCLs has shown frequent intragenic deletions and mutations of key
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can present with intestinal disease, including EBV extranodal T-cell signaling molecules in ATLL. 41
T/NK-cell lymphomas and γ/δ T-cell lymphomas, and should
be distinguished from EATL. The clinical course is aggressive. CLINICaL PEarLS
The disease previously known as EATL type II has been now been Hodgkin Lymphoma
formally designated as monomorphic epitheliotropic intestinal T-cell
lymphoma (MEITL); it shows no association with celiac disease • B-cell lineage established in nearly all cases
and appears to have an increased incidence in Asian and Hispanic • Reed-Sternberg cell, the hallmark of the disease, represents a “crippled”
populations. Unlike classic EATL, MEITL is monomorphic, usually germinal-center B cell
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positive for CD8, CD56, and MAPK. STAT5B mutations are • Nodular lymphocyte-predominant Hodgkin lymphoma considered a
common in MEITL cases, many of which are of γ/δ T-cell origin. related but distinct entity
• Eighty percent of patients are curable with current therapy
Hepatosplenic T-Cell Lymphoma • Stage of disease guides the choice of therapy; even patients with
advanced-stage disease may be cured
Hepatosplenic T-cell lymphoma (HSTCL) shows a marked male • Late complications from treatment include acute leukemia (alkylating
gender predominance, and most patients are young adults. The agents with extended-field radiation therapy), second solid tumors
clinical presentation is that of marked hepatosplenomegaly in (radiation therapy), and premature atherosclerotic coronary artery
the absence of lymphadenopathy. disease (radiation therapy)
The liver and the spleen show marked sinusoidal infiltration, • Cause of death in the first 5–10 years is mainly Hodgkin lymphoma;
after 10 years, mainly secondary malignant tumors
with sparing of both portal triads and white pulp, respectively.