Primary Cutaneous T-Cell Lymphomas: Rare Subtypes

Definition

This is a cutaneous lymphoma composed of CD8 ⁺ cytotoxic T lymphocytes, characterized morphologically by prominent epidermotropism and clinically by an aggressive clinical course. In the past, this lymphoma was classified as either aggressive MF (MF tumeur d'emblée) or generalized pagetoid reticulosis (Ketron-Goodman type).

Epidemiology

The tumor occurs in adults of both sexes with a slight male predominance. Only one case has been reported in children.

Etiology

The etiology is not known.

Clinical Features

Patients have localized or more frequently generalized patches, plaques, and tumors, almost invariably ulcerated ( Fig. 41-1 ). Involvement of the mucosal regions is common. Before a case is classified as primary cutaneous aggressive epidermotropic CD8 ⁺ cytotoxic T-cell lymphoma, it is crucial to exclude a diagnosis of MF or of lymphomatoid papulosis.

Morphology

Histology reveals a plaquelike, nodular or diffuse proliferation of lymphocytes with marked epidermotropism ( Fig. 41-2 ). Although prominent epidermotropism may confer a so-called pagetoid appearance to the infiltrate, it may be less pronounced or even missing in some lesions, particularly in advanced stages; thus, lack of epidermotropic lymphocytes is not sufficient to rule out this entity. Spongiosis and intraepidermal or subepidermal vesiculation may be observed. Invasion and destruction of adnexal skin structures are common, but angiocentricity and angiodestruction are infrequent. Cytomorphology is variable and can be characterized by small, medium-sized, or large pleomorphic cells.

Immunophenotype

Immunohistology reveals a characteristic phenotypic profile of neoplastic lymphocytes (βF1 ⁺ , TCRγ ⁻ , CD2 ^−/+ , CD3 ⁺ , CD4 ⁻ , CD5 ^−/+ , CD7 ⁺ , CD8 ⁺ , TIA-1 ⁺ , granzyme B ⁺ , CD30 ⁻ , CD45Ra ⁺ , CD45RO ⁻ , CD56 ⁻ ; Fig. 41-3 ), but pan–T-cell markers may be lost. The EBV is not detectable in neoplastic cells.

Genetics

Molecular biology shows a monoclonal rearrangement of the T-cell receptor (TCR) genes. Array comparative genomic hybridization investigations showed that gains (particularly in chromosomes 3, 7, 8, 11, 17, 18, and 22) are more frequent than losses (found frequently at 9p21, suggesting a role of p16).

Clinical Course

Primary cutaneous aggressive epidermotropic CD8 ⁺ cytotoxic T-cell lymphoma has a poor prognosis with an estimated 5-year survival of 0%. The disease often metastasizes to the lung, testis, and central nervous system.

Differential Diagnosis

Distinction from cases of CD8 ⁺ MF and from lymphomatoid papulosis type D is made mainly on the basis of the clinical presentation and behavior. In contrast to MF, patients with primary cutaneous aggressive epidermotropic CD8 ⁺ cytotoxic T-cell lymphoma present from the beginning with generalized plaques and tumors. Lymphomatoid papulosis type D is characterized by the typical “waxing and waning” of papules and small nodules.

Pediatric patients with a clinical presentation resembling hydroa vacciniforme and association with EBV should be better classified as hydroa vacciniforme–like T-cell lymphoma. Cases of CD8 ⁺ T-cell lymphoma with exclusive involvement of the subcutis should be classified as SPTCL. Distinction of primary cutaneous aggressive epidermotropic CD8 ⁺ cytotoxic T-cell lymphoma from cutaneous γδ T-cell lymphoma is achieved mainly by demonstration of expression of αβ and negativity for γδ. Primary cutaneous acral CD8 ⁺ T-cell lymphoma is characterized by dermal infiltrates devoid of epidermotropism histopathologically and usually by solitary, non-ulcerated lesions (mostly on the ear and face) clinically.

Definition

Primary cutaneous γδ T-cell lymphoma (pcγδTCL) is a tumor of cytotoxic γδ T lymphocytes with specific tropism for the skin. This lymphoma shows overlapping features with other CTCLs, particularly MF, SPTCL, and primary cutaneous aggressive epidermotropic CD8 ⁺ cytotoxic T-cell lymphoma. Cases of pcγδTCL in the past have been classified as aggressive MF (MF tumeur d'emblée), generalized pagetoid reticulosis (Ketron-Goodman type), or subcutaneous T-cell lymphoma.

It is crucial to remember that a γδ phenotype is not unique to pcγδTCL. It can be observed in several cutaneous (and extracutaneous) lymphoma types, including MF.

Epidemiology

pcγδTCL occurs in adults, with an equal distribution between men and women. Cases in children have been reported.

Etiology

Etiologic factors are not known.

Clinical Features

Patients have localized or generalized patches, plaques, and tumors, often ulcerated, and the clinical features may be indistinguishable from those of advanced MF ( Fig. 41-4 ). In some patients, lesions are restricted to the lower extremities. Subcutaneous tumors may also be seen. Involvement of the mucosal regions is common. Lactate dehydrogenase is elevated in the majority of patients, whereas bone marrow involvement is uncommon. A hemophagocytic syndrome is a frequent complication. Almost one fourth of the patients had an associated autoimmune disorder in one study, and onset of pcγδTCL has been observed also during treatment with etanercept for rheumatoid arthritis.

Besides cutaneous and hepatosplenic cases, γδ T-cell lymphomas can be observed also at other nodal or extranodal sites, thus underlying the need for staging investigations.