The Principles of Clinical Cytogenetics - Extra Materials - Springer

404 Rizwan Naeem
Mycosis Fungoides and Sézary Syndrome
Mycosis fungoides (MF) is an indolent T-cell lymphoma that is distinguished from other lymphomas
by its initial appearance on the skin. The histological diagnosis of MF might be difficult because
there is significant overlap with features of neoplastic T-cell infiltrates and inflammatory dermatoses.
MF generally occurs in a mixed, reactive background and can show only a slight degree of
cytologic atypia, also rendering histological diagnosis difficult.
Mycosis fungoides is a mature T-cell lymphoma presenting in the skin with patches and flakes
characterized by epidermal and dermal infiltration of small to medium-sized T-cells with cerebriform
nuclei. It is also known as cerebriform T-cell lymphoma and small cell cerebriform lymphoma. The
disease, as a rule, is limited to skin for a prolonged number of years (216). Extracutaneous spreading
can occur in the advanced stage, mainly to lymph node, liver, spleen, lungs, and blood. When large
numbers of tumor cells are found in the blood, the condition is called Sézary syndrome (SS).
The complete pathogenesis of this disease process is unknown at present. HTLV or a related virus
has been implicated in some studies, which have shown that truncated provirus sequences, similar to
tax and/or pol, could be detected by PCR in 30–90% of patients (217,218). With immunophenotypic
studies, a lack of CD7 expression is frequent in all stages of the disease. However, this feature is of
limited value from a diagnostic point of view, because the lack of CD7 could also be seen in a benign,
cutaneous lymphoid lesion (219).
T-Cell receptor genes are clonally rearranged in most cases of MF (220). Inactivation of CDKN2A/
P16 and PTEN have been reported (221) and could be associated with disease progression.
Limited cytogenetic studies have shown complex nonspecific karyotypes in many SS patients,
particularly in advanced stages. Recently, FISH analysis showed chromosome 1p and 17q rearrangements
in 5 of 15 SS cases and chromosome 10 abnormalities in 4 SS cases, consistent with both the
G-banded karyotype and the CGH results (222). In addition, allelotyping analysis of 33 MF patients
using chromosome 1 markers suggested minimal regions of deletion at D1S228 (1p36), D1S2766
(1p22), and D1S397 (1q25).
In a recent study, Karenko et al. (223) studied correlations between cytogenetic abnormalities and
disease progress in patients with MM or SS. This small study has revealed that the rate of chromosomal
aberrations is associated with the activity of the disease and has a prognostic significance.
Aberrations of chromosomes 1, 6, and 11, although increasing with progression of the disorder, seem
to be a hallmark of existing disease, detectable even in remission. Aberrations of chromosomes 8 and
17 are associated with active or progressive disease (223). Both SS and late stages of MF showed a
similar pattern of chromosomal abnormalities, but no chromosomal changes were found in patients
with early-stage MF (222).
Angioimmunoblastic T-Cell Lymphoma
Angioimmunoblastic T-cell lymphoma (AILT) is a peripheral T-cell disorder always associated
with systemic disease. Evidence of polymorphic infiltrate involving lymph nodes, with a prominent
proliferation of high endothelial venules and follicular dendritic cells, is present.
Angioimmunoblastic T-cell lymphoma is a rare subtype of lymphoma, making up only 1–2% of
non-Hodgkin’s lymphomas; however, it accounts for a major subset of peripheral T-cell lymphomas. It
has clinical and pathologic features that set it apart from other B- and T-cell lymphomas. In past literature,
this disease was referred to as immunoblastic lymphadenopathy; AILT was initially felt to be an
atypical reactive process, angioimmunoblastic lymphadenopathy, with an increased risk of progression
to lymphoma. Currently, it is believed that AILT is a proliferative T-cell lymphoma. However, some
argue that atypical or clonal proliferation could precede the development of this lymphoma and believe
that angioimmunoblastic lymphadenopathy could be, in some cases, a preneoplastic process. Most
patients exhibit immunodeficiency, but the immune abnormalities appear secondary to the neoplastic
process rather than preceding it. Cells positive for EBV are found in the majority of cases.