Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior

Abstract

Cutaneous T cell lymphomas (CTCL) generally have the phenotype of CD3+, CD4+, CD45RO+ memory T cells. CTCL expressing a CD8+ T cell phenotype are extremely rare and ill-defined. To elucidate whether these CD8+ CTCL represent a distinct disease entity, the clinical, histological, and immunophenotypical features of 17 CD8+ CTCL were reviewed. None of the 17 cases expressed markers characteristic of natural killer cells or gamma/delta T cells. Nine of 17 cases showed the characteristic clinical and histological features as well as clinical behavior of well defined types of CTCL, such as mycosis fungoides (2 cases), pagetoid reticulosis (2 cases), lymphomatoid papulosis (2 cases), and CD30+ large T cell lymphoma (2 cases), all of which usually express a CD4+ T cell phenotype, and 1 case of subcutaneous panniculitis-like T cell lymphoma. The other 8 cases formed a homogeneous group showing a distinctive set of clinicopathological and immunophenotypical features, not consistent with that of other well defined types of CTCL. Clinical characteristics included presentation with generalized patches, plaques, papulonodules, and tumors mimicking disseminated pagetoid reticulosis; metastatic spread to unusual sites, such as the lung, testis, central nervous system, and oral cavity, but not to the lymph nodes; and an aggressive course (median survival, 32 months). Histologically, these lymphomas were characterized by band-like infiltrates consisting of pleomorphic T cells or immunoblasts, showing a diffuse infiltration of an acanthotic epidermis with variable degrees of spongiosis, intraepidermal blistering, and necrosis. The neoplastic cells showed a high Ki-67 proliferation index and expression of CD3, CD8, CD7, CD45RA, betaF1, and TIA-1 markers, whereas CD2 and CD5 were frequently lost. Expression of TIA-1 pointed out that these lymphomas are derived from a cytotoxic T cell subset. The results of this and other studies reviewed herein suggest that these strongly epidermotropic primary cutaneous CD8+ cytotoxic T cell lymphomas represent a distinct type of CTCL with an aggressive clinical behavior.

Figure 1.

A: Clinical features of case no. 6: widespread eruption of patches, plaques, and papulonodular verrucous and hemorrhagic lesions. B: Clinical features of case no. 2: typical hemorrhagic and necrotic evolution of some lesions. C: Histology (H&E; original magnification, ×2.5) of case no. 2: a perivascular and periadnexal, lichenoid, strongly epidermotropic infiltrate in an acanthotic and hyperplastic epidermis with spongiosis, blistering, and necrosis. D: Clinical features of case no. 5: particularly of the papulonodular and verrucous lesions. Note the central resolution of some lesions.

Figure 2.

A: Histology (H&E; original magnification, ×100) of case no. 4: well developed nodular lesion. Note the diffuse pleomorphic strongly epidermotropic T cell infiltrate. B: Histology (H&E; original magnification, ×100) of case no. 1: early lesion. Note the intraepithelial pleomorphic atypical lymphoid infiltrate; the involved epidermis shows extensive keratinocyte necrosis. C: Histology (H&E; original magnification, ×200) of case no. 3: the strongly adnexotropic small- to medium-size pleomorphic lymphocytes show a lymphoepitheliod pattern. D: Histology (H&E; original magnification, ×200) of case no. 2: well developed tumoral lesion. High magnification of the infiltrate shows perivascular, strongly epidermotropic immunoblasts in the superficial dermis.

Figure 3.

A: Immunohistochemistry (APAAP; original magnification, ×200) (Leu-2a/CD8-frozen section) of case no. 1: early erythemato-scaling lesion. Note in the superficial dermis many CD8+ strongly epidermotropic T lymphocytes. B: Immunohistochemistry (APAAP; original magnification, ×400) (TIA-1-paraffin section) of case no. 2: well developed nodular lesion. The intraepithelial neoplastic lymphocytes in a spongiotic and blistering area show strong cytoplasmic TIA-1 positivity. C: Immunohistochemistry (APAAP; original magnification, ×200) (F8–11-13/CD45RA-paraffin section) of case no. 1: papulonodular lesion showing that the dermal and intraepithelial neoplastic lymphocytes uniformly express the CD45RA marker. D: Immunohistochemistry (APAAP; original magnification, ×200) (Leu-5/CD2-frozen section) of case no. 1: early erythemato-scaling lesion showing that the epidermotropic neoplastic lymphocytes are CD2−, whereas perivascular reactive lymphocytes in the superficial dermis are clearly labeled.