Although initially found in primary nodal ALCL, recent studies suggest that NPM-ALK expression may occur in lymphoma at extranodal sites, including the skin; it remains controversial, however, whether CD30+ primary cutaneous lymphoma and its benign counterpart, lymphomatoid papulosis (LyP), express NPM-ALK in some cases.
Fusion of the NPM and ALK genes was detected in three of 18 patients with ALCL who had amplifiable DNA (17%, 95% confidence intervals 4% to 41%), but not in any patients with other NHL, HD, or lymphomatoid papulosis.
BIA-ALCL resembles CD30+ cutaneous LPD: ALK-, CD30+ anaplastic cells with an aberrant T cell phenotype; overexpression of oncogenes (JUNB, SATB1, pSTAT3, SOCS3) in lymphomatoid papulosis (LyP); frequent apoptosis; complete spontaneous regression in LyP and partial spontaneous regression in cutaneous ALCL.
Lymphomatoid papulosis (LyP) is a benign chronic often relapsing skin condition that belongs to the CD30-positive cutaneous lymphoproliferative disorders.
Although the papular clinical appearance, lymphocyte atypia, and focal CD30 positivity may resemble LyP, the relatively low number of atypical lymphocytes, low intensity of CD30 staining, and absence of spontaneous resolution help to distinguish PPPD from LyP.
Cutaneous CD30+ lymphoproliferative disorders constitute many cutaneous T-cell lymphomas and comprise lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (ALCL).Both have an excellent prognosis.
At present, brentuximab vedotin, an antibody-drug conjugate composed of an anti-cluster of differentiation (CD)-30 antibody covalently linked to monomethyl auristatin E, is approved for the treatment of CD30+ lymphoproliferative disorders [lymphomatoid papulosis (LyP) and primary cutaneous-anaplastic large-cell lymphoma (pc-ALCL)] as well as transformed CD30+ mycosis fungoides (MF).
CD30+ lymphoproliferative disorders (LD) represent a spectrum of entities ranging from self-limited proliferations or cutaneous lesions with favorable prognosis, such as lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (ALCL), to more aggressive malignancies such as systemic ALK-positive and ALK-negative ALCL.
Lymphomatoid papulosis (LyP) type E is a recently described variant characterized by the occurrence of large necrotic eschar-like lesions displaying microscopically angioinvasive and angiodestructive infiltrates of CD30+ lymphocytes, frequently coexpressing CD8.
The expression of CD30, which defines anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis, might also occur in a subset of patients with MF, with or without large-cell transformation.
Within this nosologic umbrella are nodular and diffuse infiltrates resembling low grade T and B cell lymphoma consistent with lymphocytoma cutis, drug associated reversible T cell dyscrasias which draw a strong morphologic and phenotypic parallel with mycosis fungoides and the various pre-lymphomatous T cell dyscrasias, and angiocentric CD30 positive infiltrates mirroring lymphomatoid papulosis.
T-cell lymphoma represented 78.7% of all cases, the majority being early mycosis fungoides (MF) (64%; median age: 66 years), followed by lymphomatoid papulosis (LyP) (19%; median: age 48 years), and others (median age: 72 years), including eight cases of anaplastic large CD30+ T-cell lymphoma, four CD4+ small-medium pleomorphic T-cell lymphoproliferative disorder, four Sézary syndrome, one subcutaneous panniculitis-like T-cell lymphoma, one extranodal NK/T-cell lymphoma nasal-type, and one angioimmunoblastic T-cell lymphoma.
Lymphomatoid papulosis type E (LyP) is a recently described subtype of LyP characterized by an angioinvasive infiltrate of atypical lymphocytes expressing CD30.
Another photoresponsive CTCL variant is lymphomatoid papulosis (LP), a CD30+ lymphoproliferative disease characterised by chronically recurring papules.
Lymphomatoid papulosis (LyP) type E is a recently delineated variant characterized by the occurrence of large necrotic "eschar"-like lesions displaying microscopically angioinvasive and angiodestructive infiltrates composed of CD30 lymphocytes, frequently coexpressing CD8.
We present a case of LyP showing CD30+ atypical lymphocytes around the hair follicle, eccrine gland and nerve fiber, with varying degrees of infiltrates.
Four of these patients subsequently developed MF; (3) Lymphomatoid papulosis (waxing and waning lesions and positivity for CD30) (n=10; M:F=4:6; median age, 41 y; range, 16 to 83 y); (4) MF (clinical features typical of MF) (n=11; M:F=6:5; median age, 17 y; range, 8 to 85 y).
Overlapping features of LyP and pcALCL with themselves and with other cutaneous and systemic lymphomas emphasize the importance of careful clinicopathologic correlation and staging in the diagnosis of CD30+ T-LPD.
Nine patients were enrolled in a physician-initiated, open-label, single-center, phase 2 clinical trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphomas and LyP from 2011 to 2013.
More specifically the original report and subsequent authors suggest that the patients fall on the spectrum of CD30+ LPD most reminiscent of Lymphomatoid papulosis (LyP) seen in the skin.