J Cutan Pathol 2014 © 2014 John Wiley & Sons A/S. doi: 10.1111/cup.12353 Published by John Wiley & Sons Ltd John Wiley & Sons. Printed in Singapore Journal of Cutaneous Pathology Review A review of the solitary cutaneous T-cell lymphomas Cutaneous T-cell lymphomas (CTCL) account for almost 65-92% Mina S. Ally1 and Alistair of all cutaneous lymphomas, many of which usually present with Robson2 multiple lesions. However, a number of well-recognized and rare 1Department of Dermatology, Stanford types of CTCL, including mycosis fungoides, can present in University School of Medicine, Redwood City, isolated fashion. These solitary lesions often run a relatively CA, USA, and indolent clinical course but often pose diagnostic difficulties. We 2St. John’s Institute of Dermatology, review histopathologically challenging solitary cutaneous T-cell St. Thomas’ Hospital, London, UK lymphomas, including criteria for diagnosis, clinical course and prognosis, particularly for primary cutaneous CD4+ small/medium pleomorphic lymphoma and indolent CD8+ lymphoid proliferation of acral sites. In addition, we suggest an algorithm and nomenclature to aid in the diagnosis of such problematic lesions. Keywords: solitary mycosis fungoides, pagetoid reticulosis, indolent Alistair Robson, FRCPath Dip RCPath, CD8+ lymphoid proliferation of acral sites, primary cutaneous St. John’s Institute of Dermatology, St. Thomas’ CD4+ small/medium pleomorphic lymphoma Hospital, Westminster Bridge Road, London SE1 7EH, UK Ally MS, Robson A. A review of the solitary cutaneous T-cell Tel: 0207 1887188 Fax: +44 207 1886382 lymphomas. e-mail: [email protected] J Cutan Pathol 2014. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Accepted for publication December 16, 2013 Primary cutaneous T-cell lymphomas present run a relatively indolent clinical course, they in the skin with no evidence of extra-cutaneous continue to pose diagnostic difficulty. involvement.1 Cutaneous T-cell lymphomas In this review, we present an overview of the (CTCL) account for almost 65–92% of all cuta- solitary cutaneous T-cell lymphomas that, in neous lymphomas,2 of which, mycosis fungoides our opinion, present the greatest challenge in (MF) is the most common and characteristically diagnosis and that have been emerging over the presents with multiple lesions. However, solitary last 5 years. We have excluded some of the more MF, including and distinct from pagetoid retic- clinically aggressive tumors that may present as ulosis (Woringer-Kolopp), is well documented;3 solitary lesions as they tend to be well recognized similarly, other well-characterized forms of and histopathologically and immunopheno- lymphoma can present as an isolated lesion. typically distinct. We discuss the criteria for Finally, a number of increasingly recognized diagnosis, particularly for primary cutaneous rarer CTCL commonly present with an isolated CD4+ small/medium pleomorphic lymphoma lesion, including CD4+ small/medium pleomor- and indolent CD8+ lymphoid proliferation phic T-cell lymphoma (SMPTCL) and indolent of acral sites. Finally, we suggest an algorithm CD8+ lymphoid proliferation of acral sites.4 to aid in the diagnosis of such problematic Although it seems that these isolated lesions lesions. 1 Review Cutaneous lymphoma classification and review single erythematous scaly patch or plaque, in non-sun-exposed areas.1 Solitary MF has been The recent détente and concord between 3,13,14 the World Health Organization (WHO) and reported to have an excellent prognosis, European Organization for the Research and although recurrence of treated lesions has been 2,13,15–18 Treatment of Cancer (EORTC) classifications reported six of which occurred distant acknowledges the unique features of primary from the site of the original lesion (Table 1). Two cutaneous lymphomas, which differ greatly from of these distant recurrences presented as multi- the nodal and other extranodal lymphomas.1,5 ple lesions, but in both cases, there was complete An accurate diagnosis of primary cutaneous resolution with further treatment and no further 2 lymphoma requires the correlation of the clini- disease at follow-up. The other four cases pre- 11,17 cal findings with the microscopic, immunophe- sented as a unilesional recurrence. In addi- notypic and genetic features. Given that the tion, four cases of solitary MF have progressed to further cutaneous involvement, three of which majority of lymphomas usually present with mul- , , , tiple lesions it is difficult to make a diagnosis had large cell transformation.2 8 16 19 of a specific cutaneous lymphoma when faced Solitary lesions of follicular and syringotropic with the clinical presentation of a solitary lesion. MF are also clinically and pathologically indis- Moreover, in the absence of multiple lesions the tinguishable from lesions seen in classical dis- surgical pathologist is frequently in difficulty in ease. Solitary folliculotropic MF presents as an determining whether an infiltrate is neoplastic infiltrated patch, plaque or an isolated areaof or reactive. follicular papules without prominent scaling, , , To date, of the solitary cutaneous T-cell usually in the head and neck area.2 6 8 Solitary lymphomas reported in the literature, approxi- syringotropic MF usually presents with a single mately 166 cases represent MF,3 231 represent erythematous, indurated plaque, often studded SMPTCL, 22 represent indolent CD8+ lym- with small pinhead-sized papules, in the trunk, , phoid proliferation and 62 represent pagetoid hip and thigh area,11 20 although cases have reticulosis (Table 1). been reported in the head and neck area.11,12 Alopecia is a prominent feature in both cases.11 Solitary MF There is still uncertainty about the relation- ship between these two MF subtypes, but they MF accounts for almost 50% of all primary cuta- often co-exist.6,11,20 When compared with clas- neous lymphomas and is characterized by mul- 1 sic MF, folliculotropic MF is typically associated tiple patches and plaques. Indeed, given that with a poorer prognosis.21 This is sometimes,8 the finding of multiple patches and plaques but not always the case for solitary lesions.2,6 is a defining feature it is somewhat contradic- Syringotropic MF, however, has a prognosis sim- tory to consider a solitary variant. Nevertheless, ilar to that of classic MF.22 Out of the nine soli- since 1981, 166 solitary cases of MF have been tary cases of syringotropic MF reported, one has described that are distinct from pagetoid retic- shown recurrence of the lesion distant from the ulosis, including 10 of the folliculotropic variant 11 , , original site. (follicular MF)2 3 6–8 and 9 cases of syringotropic Finally, the report of an EORTC workshop con- MF.9–12 cerning granulomatous MF and granulomatous slack skin (GSS) detailed one solitary example Clinical features of GSS.23 Recently, at the senior author’s insti- Solitary MF, clinically and histopathologically tution, a case of GSS presented with a single resembles classic MF. Clinically, it presents as a pendulous axillary skin fold, which was followed Table 1. Number of reports of each solitary cutaneous T-cell lymphoma and reported instances of recurrence or disease progression Cutaneous Cases with cutaneous/ Cases with lesion recurrence lymphoma type Total cases systemic progression post-treatment* Solitary MF 166 4 (Cutaneous spread, 3 × large cell transformation) 15 (six distant from original site) Pagetoid reticulosis (Woringer-Kolopp) 62 1 (Cutaneous spread) 8 (1 distant from original site) SMPTCL 231 5 (Extracutaneous spread, one died of lymphoma) 12 Indolent CD8+ lymphoid proliferation of 22 0 4 (one distant from original site) acral sites *Recurrence occurred at the same site of the original lesions unless stated otherwise. 2 Review Fig. 2. ’Lining up’ of atypical lymphocytes at the dermoepider- mal junction and fibrotic changes in the papillary dermis are Fig. 1. A solitary plaque of granulomatous slack skin, affecting noted in a solitary patch of mycosis fungoides involving the the groin. thigh of a 75-year male (hematoxylin/eosin, ×100). several years later with involvement of the groin 24 3 loss of T-cell associated antigens, T-cell clonality (Fig. 1). A recent report by Ally et al. of 15 and appropriate clinical appearance. cases suggested that the observation of solitary MF might be expected, albeit exceptional, in Immunocytochemistry which the disease is simply found at an uncom- monly early stage. The unsurprising excellent Immunophenotypically, solitary MF, like classic prognosis of such cases indicates that therapy MF, is usually a neoplasm of CD4+ T-helper shouldaimtobecurative. cells, although CD8+ and double negative CD4−/CD8− variants have been described.28 In addition, there may be variable antigen loss of Histopathologic features CD2, CD5 and CD7.3 These immunophenotypes In solitary MF, microscopic sections show a super- do not seem to affect prognosis.28,29 ficial lymphoid infiltrate of epidermotropic and atypical lymphocytes.20,25 Atypia is usually more pronounced in the epidermotropic lymphocytes T-cell receptor gene analysis than those in the dermis.26,27 Other histopatho- T-cell receptor (TCR) gene rearrangements are logic features include lining up of atypical detected in approximately 57–71% of cases of lymphocytes at the dermoepidermal junction, early MF,29 so solitary lesions might be expected Pautrier microabscesses and fibrotic changes in to have a similar or perhaps lower clonal preva- the papillary dermis, none of which