pagetoid reticulosis ( pr ) is an uncommon disease clinically characterized by the presence of solitary , psoriasiform , slowly growing cutaneous plaques located on the extremities and , at histological level , by a characteristic dense inflammatory infiltrate with pagetoid spread within the dermis and the upper dermis composed of atypical lymphocytes .
two clinical variants of pr may be distinguished : a localized form , also known as woringer - kolopp disease ( wkd ) , which consists of a single lesion , usually located on the extremities , presenting a good prognosis when it can be totally removed by excision or high - dose radiation , and the generalized type or ketron - goodman disease ( kgd ) with disseminated lesions and a poor prognosis [ 1 , 2 ] . in the who and eortc classification of cutaneous lymphomas in fact , wkd is classified as a relatively indolent variant of mycosis fungoides ( mf ) , whereas kgd , which is not classified yet , is generally considered an aggressive lymphoma with bad prognosis similar to the aggressive cd8-positive cutaneous t - cell lymphoma , the cutaneous /-positive t - cell lymphoma and the tumor stage of mf .
we present a case of an 84-year - old man with a 2-year history of erythematous patches located on the trunk and the upper and lower extremities in whom the diagnosis of kgd was made .
in april 2008 an 84-year - old man presented with a 2-year history of asymptomatic erythematous patches located on the trunk and the upper and lower extremities . on physical examination several round to oval lesions presented regular , well - defined and unindurated borders with mild desquamation and mild infiltration , associated with itching ( fig .
1 ) . he denied any dermatologic diseases and his personal history was unremarkable except for hypertension and diabetes .
2 ) showed marked acanthosis of the epidermis with infiltration of atypical lymphoid cells in a pagetoid pattern .
the phenotype of neoplastic cells was cd3 + ( 80% ) , cd5 + ( 25% ) , cd45 + ( 8590% ) , cd2 negative .
chest x - ray , echosonography of the abdomen and bone marrow examination revealed no systemic involvement .
the long clinical presentation , the typical histological examination and immunohistochemistry led to the diagnosis of kgd . the patient was treated with three cycles of inf therapy ( 0.5 mg / kg / day ) for 2 months that led to a regression of the skin lesions with apparent complete remission until now . during 8 months of follow - up
pr is a rare form of cutaneous t - cell lymphoma with a striking epidermotropism on histological examination [ 3 , 4 ] .
the term pr has been introduced by braun - falco et al . in 1973 to identify this clinical entity , first described by woringer and kolopp   in 1939 , for the resemblance of infiltrating cells characterizing this condition with paget 's cells present in the epidermotropic infiltrate of mammary paget 's disease .
different authors proposed various etiopathogenetic hypotheses for this disease : at the beginning it was considered as a reactive lymphoproliferative process induced by different stimuli , including arthropod bite and with evolution towards neoplastic disease . other authors
considered pr as a variant of cutaneous t - cell lymphomas [ 8 , 9 , 10 ] .
the origin of the pagetoid cells has been uncertain for many years : melanocytes , histiocytes , merkel cells , true paget cells and langerhans cells were all proposed , but with the advent of phenotypical studies a t - cell lineage was finally confirmed .
the classic skin lesions usually begin with asymptomatic scaly round or oval plaques that can be erythematous or yellowish with regular , well - defined and unindurated borders , associated with desquamation .
the basic criterion of diagnosis is the presence of an inflammatory infiltrate composed of atypical lymphoid cells within the epidermis and the upper dermis with pagetoid distribution .
the relationship between pr and mf is still unclear ; in fact different authors consider the first as a clinical variant of the second .
haghighi et al . in 2005   suggested that pr might be classified as a cutaneous t - cell lymphoma with uncertain clinical behavior , considering it as a distinct clinicopathologic entity , separate from mf .
in fact there are several clinical , histologic and immunophenotypic differences between these two entities .
a more difficult distinction is that of pr by mycosis palmaris et plantaris , a rare variant of mf , characterized by acral plaques resembling those of wkd .
therefore there are several features that make pr unique among the classification of cutaneous t - cell lymphomas : the acral distribution of lesions , the pronounced hyperkeratosis and acanthosis at histology , the prominent epidermotropism and the expression of e7 integrin on t - lymphocytes that binds cadherins on keratinocytes .
some authors have proposed that epidermotropism of lymphoid cells is probably due to the expression of integrin e7 on the cell surface , which interacts with e - cadherin on epithelial cells .
in fact expression of e7 on lymphocytes is often increased in those inflammatory conditions in which t - cells infiltrate epithelial tissues .
the function of e7 is not yet fully understood , but it is likely to be important in the retention of t - cells in mucosal tissues and may also have a role in cell signaling and heterotypic communication between lymphocytes and epithelial cells . in
pr three prevalent phenotypes of neoplastic cells were described : cd4 + ( t - helper phenotype ) , cd8 + ( t - cytotoxic / suppressor phenotypes ) or cd4/cd8 double negative phenotype .
neoplastic cells can express other cd45 isoforms ( cd45ra ) in the disseminated aggressive variant ( kgd ) but the complete cd45 family is lost from the cell surface in the benign localized variant ( wkd ) .
considering the fact that the presence of cd45 is crucial for activation of the lymphocyte - specific tyrosine kinase ( p561ck ) , which drives lymphocyte growth and transformation , lack of this molecule may be the molecular basis for the non - aggressive nature of this clonal t - cell proliferation . in our case
histological and phenotypical analysis suggested a diagnosis of kgd and , in particular , the presence of rare cd30 + cells and a component of langerhans cell type within the epidermis with a cd1a+ phenotype ( 30% ) has also been reported .
. only a few cases of kgd are described in the literature ; therefore we report this case for the rarity and for the unexpected complete regression of the skin lesions after ifn therapy . although kgd is characterized by an high rate of recurrence , during 8 months of follow - up our patient is in good condition without evidence of recurrent lesions . at this time
we can not exclude the possibility of recurrences and long - term observation is necessary .
 pagetoid reticulosis ( pr ) is a rare form of cutaneous t - cell lymphoma [ mod pathol 2000;13:502510 ] . 
 two variants of the disease are described : the localized type woringer - kolopp disease ( wkd ) and the disseminated type ketron - goodman disease ( kgd ) . 
 kgd may have disseminated lesions , high rate of recurrence and a guarded prognosis [ mod pathol 2000;13:502510 ] . in patients with kgd 
 , therefore , long - term observation is necessary . 
 disappearance of cutaneous lesions does not mean resolution of the disease [ j am acad dermatol 2002;47:183186 ] . 
 herein we report the case of an 84-year - old man with erythematous patches of the trunk and the upper and lower extremities in whom the diagnosis of kgd was made . 
 we describe this case for the rarity of this pathology and for the good response to therapy ( ifn ) . 
Introduction
Case Report
Discussion