BJD

British Journal of Dermatology

C L I N I C A L A N D L A B O R A T O R Y I N V E S TI G A T I O N S

cd T-cell-rich variants of pityriasis lichenoides and lymphomatoid papulosis: benign cutaneous disorders to be distinguished from aggressive cutaneous cd T-cell lymphomas M.E. Martinez-Escala,1 M. Sidiropoulos,1 J. Deonizio,1 P. Gerami,1 M.E. Kadin2 and J. Guitart1,3 1

Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1600, Chicago, IL 60611, U.S.A. Department of Dermatology, Boston University, Roger Williams Medical Center, Providence, RI, U.S.A. 3 Department of Dermatology, Robert H. Lurie Cancer Center, Chicago, IL, U.S.A. 2

Summary Correspondence Joan Guitart. E-mail: [email protected]

Accepted for publication 15 August 2014

Funding sources None.

Conflicts of interest None declared. DOI 10.1111/bjd.13364

Background T cells with a cd phenotype have been associated with aggressive lymphomas. Yet, inflammatory skin disorders and low-grade lymphoproliferative disorders have rarely been described with a predominant cd T-cell infiltrate. Objectives To review our experience and determine the clinical relevance of the cd T-cell phenotype in lymphomatoid papulosis (LyP) and pityriasis lichenoides (PL). Methods A retrospective dermatopathology file review looking for LyP and PL characterized by a cd T-cell phenotype was performed. Clinical manifestations and course, histological features and molecular data were analyzed. Results Six of 16 cases of LyP and four of 23 cases diagnosed as PL during a 5-year period (2009–14) were identified. The median follow-up for the whole group was 16 months (range 3–64), showing an indolent clinical course in all cases. Conclusions The detection of a predominantly cd T-cell phenotype in papular lymphoid-rich infiltrates in the absence of other lesions is not associated with a clinically aggressive course. cd T-cell-rich variants of LyP and PL may reflect a spectrum of related conditions. This is a single academic centre retrospective chart review of a relatively small sample.

What’s already known about this topic?

•

Most lymphoid-rich inflammatory skin conditions are composed of T cells expressing ab T-cell receptors (TCRs) and, in general, TCR cd T-cell infiltrates of the skin are associated with aggressive cutaneous lymphomas.

What does this study add?

•

Regardless of the presence or absence of lymphoid atypia, a subset of cd T-cell-rich cutaneous lymphoid infiltrates are self-limited and indolent. Pityriasis lichenoides and lymphomatoid papulosis may present as a predominant cd T-cell infiltrate.

A small subset (< 5%) of human peripheral blood and skin lymphocytes are characterized by cd heterodimer expression. cd T cells are mostly distributed in lymphoid or intraepithelial tissues.1–3 While their precise function remains elusive, they seem to play an important role in the innate immune system, 372

British Journal of Dermatology (2015) 172, pp372–379

as well as a modulatory role in adaptive immunity. The cd T cells originate from CD4 CD8 ‘double negative’ precursors in the bone marrow, sharing functional and molecular similarities with other cytotoxic cells like natural killer (NK) T cells. Mature cd T cells, when activated, are larger and granular, © 2014 British Association of Dermatologists

Clinical relevance of cd T cells in cutaneous lymphoproliferative disorders, M. E. Martinez-Escala et al. 373

expressing one or more NK-associated surface molecules (CD56, CD16, CD57) and cytotoxic cytoplasmic molecules like granzyme B and perforin in addition to T-cell intracellular antigen-1 (TIA-1), which is regularly expressed.3 cd T cells play an important role in human pathology, including the early phases of autoimmune disorders and the inflammatory responses associated with certain infections.3 The cd T-cell phenotype has also been associated with highly aggressive behaviour in cutaneous lymphomas. However, most cutaneous dermatoses may also have a small population of cd T cells that, in the vast majority of cases, does not exceed 10% of the mononuclear cell infiltrate.2 Until recently, the detection of cd T-cell receptor (TCR) was not possible in formalin-fixed paraffin-embedded (FFPE) sections, requiring frozen tissue immunohistochemical or flow cytometric analysis for its detection. Roullet et al.4 characterized a commercially available antibody that can successfully detect cd TCR (clone c3.20) in FFPE sections and has allowed further studies in Tcell lymphocyte-related disorders. Lymphomatoid papulosis (LyP) is a low-grade cutaneous lymphoproliferative disorder (LPD) that clinically manifests with recurrent and self-healing papules with histologically atypical lymphocytes. The immunophenotype of the T cells is typically described as CD3+, CD4+, CD8 , CD30+.5 A subset of LyP cases is also characterized by clinical and histological signs of cytotoxicity and may demonstrate cytoplasmic expression of cytotoxic molecules, regardless of the predominant CD4 or CD8 immunophenotype of the tumour cells.6 This includes reports of LyP with CD56 and TIA-1 expression, as well as the newly described type D and type E variants.7–9 Type D LyP is characterized by a pagetoid CD8+ T-cell infiltrate.10 Type E LyP is an angioinvasive variant with necrosis, haemorrhage, ulceration and CD8 expression.11 Most recently, a single case report of LyP showing the cd T-cell phenotype was published.12 Pityriasis lichenoides (PL) is an inflammatory skin condition of unknown aetiology and is characterized by polymorphic papules of variable severity, temporal development and course. Three classical subtypes of PL have been described: pityriasis lichenoides et varioliformis acuta (PLA), pityriasis lichenoides chronic (PLC), and febrile ulceronecrotic Mucha–Habermann disease (FUMHD). All three variants are currently believed to be on a spectrum of the same disease. PLA is clinically manifested by acute papular eruption that evolves into a papulovesicular phase and often resolving with haemorrhagic–necrotic crusts with or without final scar. PLC typically manifests as erythematous-to-brownish maculopapules with centrally attached fine scales. FUMHD is an exceptionally rare subtype that manifests with ulcero-necrotic confluent papules that evolve into plaques, involving mucous membrane, usually associated with systemic symptoms. PL is considered a nonspecific cytotoxic hypersensitivity reaction secondary to an unknown antigenic stimulus. Multiple viral agents and drugs have been associated with PL but the definitive aetiology remains unknown.13,14 PL has also been labelled as a cutaneous lymphoid dyscrasia owing to the common © 2014 British Association of Dermatologists

detection of T-cell clonality and the occasional reports of evolution to frank lymphomas.13,14 Herein we report six cases of LyP and four cases of PL that showed a predominant cd T-cell phenotype. A review of the clinical presentation, histological features, molecular data and follow-up data is performed.

Patients and methods A retrospective chart review was performed for a 5-year period (from 2009, when the cd TCR monoclonal antibody was first used at our laboratory, to 2014). Skin biopsies of 39 patients with a diagnosis of PL or LyP from the Department of Dermatopathology at Northwestern University were retrieved. Skin biopsies that showed either positive immunohistochemical staining for TCRc (mouse monoclonal antibody, clone c3.20; Thermo Scientific, Waltham, MA, U.S.A.). An infiltrate of cd T cells of ≥ 20% was included. A clinicopathological correlation in order to confirm the diagnosis was performed. Age, sex, ethnicity, time of the lesions before diagnosis, clinical presentation and distribution of the lesions, serum lactate dehydrogenase (LDH), treatment received and follow-up data were collected. This project had institutional review board approval. Histological features assessed by two dermatopathologists (P.G. and J.G.) included density of the infiltrate, extent of exocytosis, necrotic keratinocytes or confluent necrosis, atypia and predominant cell type, presence of vasculitis, eosinophils and/or other inflammatory cells. The diagnosis of LyP was rendered when significant nuclear atypia was noted. Clinical data, including chronicity of the process and clustering of the papules, were also taken into consideration in the clinicopathological correlation. Cases diagnosed as PL tended to lack significant nuclear atypia and be composed mostly of small- or medium-sized cells without infiltrating granulocytes and, in general, associated with an evenly distributed papular distribution and eventual resolution of the process. All skin biopsies collected were performed before any treatment was prescribed, except for one patient, who had received topical steroids and tacrolimus. An immunohistochemistry panel, including TCRc, bF1, CD3, CD4, CD5, CD7, CD8, CD20, CD30, CD45RA, CD56, TIA-1, granzyme B, Epstein–Barr virus-encoded RNA immunostain (EBER) and anaplastic lymphoma kinase-1, was reviewed for all cases. TCRc gene rearrangements analysis using polymerase chain reaction and Genescan capillaroscopy methods were reviewed from skin biopsies and blood samples when available.

Results Ten patients (five men, five women) with a median age of 38
5 years (range 3
0–71
0) were included. Seven patients were white, one was Hispanic and two were of unknown ethnicity. Based on the pathological findings and clinical presentation, four patients were diagnosed with PL and six with LyP. British Journal of Dermatology (2015) 172, pp372–379

374 Clinical relevance of cd T cells in cutaneous lymphoproliferative disorders, M. E. Martinez-Escala et al.

This subset represents 17% (four of 23) of the total number of PL cases diagnosed since 2009 and 37% (six of 16) of the LyP cases in which the cd TCR marker was tested. The median duration of the lesions before diagnosis was 7 months (range 2–60) (Table 1). Follow-up data were available in nine patients. The median follow up was 14 months (range 1–62). Pityriasis lichenoides Four patients (two men and two women) with a median age of 20 years (range 3–33) were diagnosed with PL; three were white and one was of unknown ethnicity. Three of the four patients had eroded and crusted papules rapidly spreading to the entire body over a few days. The last patient showed generalized waxing and waning crusted papules, with some hypopigmented macules in a generalized distribution but with fewer lesions than the other three patients (Fig. 1a). No mucosal involvement was noted in any of the four cases. The median length of follow-up was 16 months (range 3–29). One of the patients was lost to follow-up; the other three evolved as follows: one patient achieved complete remission with topical steroids; the other two patients remain with persistent disease, one after a course of oral antibiotics with a few residual papules lingering for several more months, and the second after oral antibiotic and narrowband ultraviolet B (NB-UVB) light therapy (Table 2). All four biopsies showed extensive exocytosis of lymphocytes occupying the full thickness of epidermis, except for one case, which showed a more juxtabasilar pattern. The lymphocytes were small to medium in size and displayed reactive changes without frank atypia. Necrotic keratinocytes were observed in all cases, with single cells in two cases and confluent necrosis in the other two. There was dermal oedema with a superficial and deep perivascular lymphocytic infiltrate. Rare eosinophils were observed in one biopsy. Vasculitis was not identified (Table 3, cases 1–4), but extravasation of erythrocytes was a common feature (Fig. 1b–d). The mean ratio of TCRc/CD3 was 0
3 (range 0
2–0
6). The infiltrating lymphocytes were predominantly CD8+ in two cases and double negative (CD4 /CD8 ) in the remaining two cases. Expression of at least one cytotoxic marker (TIA-1 and granzyme B) was

noted in all but one biopsy. These markers highlighted the cell cytoplasm with a granular pattern. Two cases tested for EBER were negative (Table 4). Lymphomatoid papulosis Six patients, with a median age of 50
5 years (range 30
0–71
0), were diagnosed with LyP. The male : female ratio was 3 : 3; four were white, one was Hispanic and one was of unknown ethnicity. Four of the six patients presented with diffuse papules with focal cluster formation and with erosive features in one patient. One patient had patch lesions surrounding LyP papules, which corresponded to the clinical presentation of persistent agminated LyP (Fig. 2). The other two were reported to have solitary papulonodular lesions involving the left shin and neck. Overall, legs were most commonly involved, followed by the upper extremities and trunk. None of the patients had lymphadenopathy, and mucous membranes were spared in all six patients. Serum LDH was normal in all patients and systemic symptoms were not reported. Past medical history was remarkable for one patient who had a remote history of histoplasmosis, and another patient with a history of uterine cancer and toxic nodular goitre. The median length of follow-up for patients diagnosed with LyP was 25 months (range 1–62). One patient achieved complete remission spontaneously or with topical steroids. Two patients showed complete response after NB-UVB in one and after oral antibiotics in another patient (Table 2). One patient persisted with minimal residual disease, and no treatment was applied owing to the low number of lesions. Two patients showed complete remission after surgical excision; however, one of them had a follow-up of only 1 month. Seven biopsies from six patients were reviewed and classified as type A (n = 2), type C (n = 2), type B (n = 2) and type D (n = 1). One patient had two biopsies with different histological LyP types, A and C. The infiltrates had, for the most part, a wedge-shaped pattern and overall denser infiltrate than cases of PL. Prominent exocytosis occupying the entire epidermal thickness was observed in all cases, except for one case that showed exocytosis involving the lower epidermis. Extensive epidermal necrosis was noted in one case, and

Table 1 Epidemiological data Data

Total

Lymphomatoid papulosis

Pityriasis lichenoides

Patients (n) Sex (male : female) Median age (range), years Ethnicity White Hispanic Unknown Time before diagnosis (range), months Median length of follow-up (months)

10 5:5 38
5 (3
0–71
0)

6 3:3 50
5 (30
0–71
0)

4 2:2 20
6 (3
0–33
0)

7 1 2 7
0 (2
0–60
0) 14
50 (1
0–62
0)

4 1 1 24
8 (2
0–60
0) 25
0 (1
0–62
0)

3 – 1 13
3 (2
0–36
0) 15
7 (2
3–29
0)a

a

One patient was lost to follow-up.

British Journal of Dermatology (2015) 172, pp372–379

© 2014 British Association of Dermatologists

Clinical relevance of cd T cells in cutaneous lymphoproliferative disorders, M. E. Martinez-Escala et al. 375

Fig 1. Pityriasis lichenoides. (a) Erythematous papules and patches, some of them with pitiryasiform scale in an annular shape, others with necrotic centre on the buttocks (patient 2). (b) Extensive epidermal necrosis and lichenoid infiltrate on the superficial dermis (patient 1; haematoxylin and eosin, 109). (c) Confluent necrotic keratinocytes, epidermotropic small lymphocytic infiltrate and red blood cell extravasation on the superficial dermis (haematoxylin and eosin, 209). (d) Lymphocytic infiltrate is positive for T-cell receptor gene rearrangement cells with clone c3.20 immunostain (haematoxylin and eosin, 209).

(a)

(b)

(c)

(d)

Table 2 Clinical data of the sample

Status

Length of follow-up (months)

Diagnosis

U Oral ATB Topical steroids Oral ATB, NB-UVB

U AWD AWOD AWD

U 14
1 2
3 29
1

PL PL PL PL

NB-UVB

AWOD

62
6

LyP

None

AWD

33
0

LyP

Topical steroids

AWOD

13
6

LyP

Surgical excision Oral ATB

AWOD AWOD

22
0 14
9

LyP LyP

Surgical excision

AWOD

1
0

LyP

Patient no.

Sex/age (years)

Ethnicity

Clinical presentation

Distribution

Treatment

1 2 3 4

M/26 F/3 F/33 M/13

U W W W

Crusted papules Crusted papules Crusted and eroded papules Crusted papules hypoand hyperpigmentation

5

F/53

W

6

M/57

W

Papules, overlap with eczematous patches Crops of papules

7

M/48

W

Papules

8 9

M/71 F/30

U W

Single lesion Papules, some eroded

10

F/44

U

Solitary papule

Generalized Generalized Generalized Trunk, upper and lower extremities Trunk and lower extremities Upper and lower extremities Upper and lower extremities Left lower extremity Trunk, upper and lower extremities Neck

M, male; F, female; U, unknown; W, white; ATB, antibiotics; NB-UVB, narrowband ultraviolet B; AWD, alive with disease; AWOD, alive without disease; PL, pityriasis lichenoides; LyP, lymphomatoid papulosis.

scattered necrotic keratinocytes were observed in three biopsies. One biopsy demonstrated pseudoepitheliomatous hyperplasia (Fig. 3). Cellular atypia was consistently present in all biopsies, with pleomorphic small-to-medium-sized cells in LyP type B and D cases and medium-to-large-sized cells in LyP type A and C biopsies (Fig. 4). Lymphocytic vasculitis was observed in one biopsy, but red blood extravasation was noted in two biopsies. Scattered neutrophils and eosinophils were present in four and two biopsies, respectively (Table 3). Five patients showed a predominantly CD8+ infiltrate and one case showed a double negative phenotype (CD4 /CD8 ). The mean ratio of TCRc/CD3 was 0
5 (range 0
3–0
9). At © 2014 British Association of Dermatologists

least one cytotoxic marker (CD56+, TIA-1+, granzyme B) was observed in all but one biopsy in the atypical cells, with the same cytoplasmic granular pattern as in PL. One was positive for CD45RA and all cases tested were EBER negative (Table 4). Molecular analysis TCR rearrangement analysis was performed on the blood of six patients (two with PL and four with LyP) and on the skin biopsies of four cases (two with PL and two with LyP). One case of PL revealed a T-cell clone in the skin, but not in the British Journal of Dermatology (2015) 172, pp372–379

376 Clinical relevance of cd T cells in cutaneous lymphoproliferative disorders, M. E. Martinez-Escala et al. Table 3 Histological features Patient no. 1 2 3 4 5 6 7 8 9 10

Exocytosis

Type of exocytosis

Epidermal necrosis

+++ + ++ +++ ++ +++ ++ ++ ++ ++ +++

PR-L JB PR-L PR-L PR-L PR-L PR-L LE PR-L PR-L PR-L

+++ + ++ + + + +++ +

Cell size/atypia

Infiltrate distribution

Eos/PMN

Small–medium/ Small–medium/ Medium/ Medium/ Small–large/+ Medium/+ Medium/+ Small–large/+ Medium–large/+ Medium–large/+ Medium/+

Wedge-shaped Wedge-shaped Wedge-shaped Wedge-shaped Wedge-shaped Wedge-shaped Wedge-shaped Wedge-shaped Wedge-shaped Wedge-shaped Wedge-shaped

+/ / / / / / /+ /+ +/+ +/ /+

Vasculitis

RBC extravasation

Diagnosis

+ + + +

PL PL PL PL LyP LyP LyP LyP LyP LyP LyP

+

+

+

type type type type type type type

B D A C A B C

Eos, eosinophils; PMN, polymorphonuclear leucocytes; RBC, red blood cell; PR-L, pagetoid reticulosis-like, full-thickness epidermis; JB, juxtabasilar; LE, lower layers of epidermis; PL, pityriasis lichenoides; LyP, lymphomatoid papulosis. +, occasional necrotic keratinocytes; ++, confluent necrotic keratinocytes; +++, epidermal necrosis.

Table 4 Immunohistochemistry features Case no.

Diagnosis

TCRc

bF1

CD3

1 2 3 4 5 6 7 8 9 10

PL PL PL PL LyP LyP LyP LyP LyP LyP

+ + + + NA + + + + +

NA

NA + + NA NA + NA NA + +

type type type type type type

B D C A B C

NA

NA

NA NA

CD4

CD8

CD30

CD5

NA

NA +

+ + + + + + +

NA

+ +

+ + + + +

NA

N/A N/A

CD56

NA + + + +

TIA-1

GB

EBER

CD45RA

TCR

NA + + + + NA + + +

NA + NA NA + NA + NA NA NA

NA

NA NA

+ NA NA

NA NA NA NA

NA NA + NA

+ NA NA NA NA

TCRc, T-cell receptor gene rearrangement cells stained with clone c3.20; TIA-1, T-cell intracellular antigen-1; GB, granzyme B; EBER, Epstein–Barr virus-encoded RNA immunostain; TCR, T-cell receptor gene rearrangement; PL, pityriasis lichenoides; LyP, lymphomatoid papulosis; NA, not applicable.

(a)

(c)

(b)

(d)

British Journal of Dermatology (2015) 172, pp372–379

Fig 2. Lymphomatoid papulosis. (a) Erythematous papules surrounded by scaly patches on the trunk (patient 5). (b) Epidermotropism of atypical lymphocytes with marked spongiosis (haematoxylin and eosin, 209). (c) Necrotic and crusted papule surrounded by erythema on the right thigh (patient 7). (d) Epidermal necrosis and serohaemorraghic crust with juxtabasilar epidermotropism of atypical lymphocytes (haematoxylin and eosin, 409). © 2014 British Association of Dermatologists

Clinical relevance of cd T cells in cutaneous lymphoproliferative disorders, M. E. Martinez-Escala et al. 377

Fig 3. Lymphomatoid papulosis type C (patient 10). (a) Dermal lymphocytic infiltrate associated with pseudoepitheliomatous hyperplasia (haematoxylin and eosin, 109). (b) Pleomorphic lymphocytic infiltrate occupying the entire dermis (haematoxylin and eosin, 209). (c) Medium-to-large-sized atypical lymphocytes (haematoxylin and eosin, 409). (d) The lymphocytic infiltrate is positive for T-cell receptor gene rearrangement cells with clone c3.20 (haematoxylin and eosin staining, 209). Dermis and epidermis are divided by the black line.

Fig 4. Lymphomatoid papulosis type B (case 9). (a) Atypical lymphocytic infiltrate of the superficial dermis and epidermotropism of medium-to-large-sized lymphocytes is noted (haematoxylin and eosin, 209). (b) The lymphocytic infiltrate is positive for T-cell receptor gene rearrangement cells with clone c3.20 (haematoxylin and eosin, 209). (c) Atypical cells express T-cell intracellular antigen-1 (haematoxylin and eosin, 209). (d) Atypical cells express CD56 (haematoxylin and eosin, 209).

(a)

(b)

(c)

(d)

(a)

(b)

(c)

(d)

blood, while the other cases did not demonstrate any clonality, either in the skin or in the blood. Regarding LyP cases, patient 6 had a positive T-cell clone in the skin, without clonality detected in the blood, and patient 8 had a positive clone in the blood, while clonality was not evaluated in the skin.

Discussion Primary cutaneous cd T-cell lymphoma was first recognized as a distinct entity by the 2008 World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissue.15 In general, patients present with plaques or tumours that become necrotic and ulcerated, and with an aggressive course resistant to chemotherapy and radiation therapy, and occasionally aggravated by a haemophagocytic syndrome. The cd phenotype has also been reported in 5% of © 2014 British Association of Dermatologists

extranodal NK/T-cell lymphomas, nasal or extranasal type, a lymphoma that seems to overlap with other cytotoxic lymphomas sharing cytotoxic granules and other markers, as well as an aggressive clinical behaviour.16 A subset of primary cutaneous cd T-cell lymphoma presents with patches resembling psoriasis or mycosis fungoides. While some of them remain indolent for many years, others become more aggressive, acquiring cytotoxic features.17,18 LyP is a low-grade CD30+ LPD included in the WHO’s 2008 classification of cutaneous lymphoma, with the cytomorphology of a neoplastic process, yet, for the most part, an indolent clinical behaviour. The neoplastic T cells were first described as CD30+ CD4+, but in 1997 Kummer et al. reported a subset of cytotoxic LyP cases characterized by ulcero-haemorrhagic features and the expression of granzyme B or TIA-1.6,19 More recently, several case reports and case British Journal of Dermatology (2015) 172, pp372–379

378 Clinical relevance of cd T cells in cutaneous lymphoproliferative disorders, M. E. Martinez-Escala et al.

series have described numerous cases of CD8+ LyP. This variant seems to occur more commonly in young adults and children, and it may carry a more benign and shorter course than the conventional CD4+ counterpart, with complete resolution in many cases. CD8+ LyP also differs morphologically from CD4+ variants by the characteristic pagetoid intraepidermal pattern, with a predominance of medium-sized lymphocytes with or without necrotizing features.9,20–24 de Souza et al. reviewed a total of 14 cases of LyP in a paediatric population, 10 of which were CD8+. The median age of disease onset was 12 years (range 1–19), and the clinical course in all cases was characterized by recurrent eruption of the lesions, with complete resolution in three cases, partial improvement in three and persistent lesions in the other four.25 A series of nine cases of CD8+ LyP was felt to resemble aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. bF1+ was positive in seven of nine cases. After a median follow-up period of 32 months, five patients had completely resolved and four continued to suffer recurrent crops.24 Five cases of LyP with a CD56+ CD8+ phenotype have also been reported in the literature. At least one of the five showed a CD4 CD8 bF1 phenotype, suspicious for the cd TCR phenotype.7–9,25 The recently described type D and E variants of LyP are characterized by cytotoxic features and at least a subset is likely to express a cd phenotype.10,11 Lastly, a 37-year-old man diagnosed with cd phenotype LyP has been reported. The work-up showed negative results for systemic involvement, and evolved with an indolent clinical behaviour in the 20 months after the initial diagnosis.12 Acute PL is a cytotoxic lymphoid reaction characterized by keratinocyte necrosis occasionally resulting in ulcerated and haemorrhagic papules. While the process tends to be transient, there seems to be some overlap with cases reported as CD8+ LyP. For instance, both conditions are predominantly reported in young patients with the common detection of T-cell clonality, the confinement CD8+ T cells in the intraepidermal compartment with frequent necrotic keratinocytes and likely reactive rather than neoplastic atypia of lymphocytes.26 Kempf et al.27 reported cases of acute PL with large numbers of CD8+ cells and co-expression of CD8 and CD30 in the intraepidermal and dermal components of the infiltrate. Patient 4 with PL in our study had CD30+ cells predominantly within the epidermis and there was difficulty in distinguishing between PL and LyP, as reported by Kempf et al.27 Wenzel et al.28 suggested that cytotoxic cutaneous T-cell lymphoma and PL share a developmental pathway, where a common antiviral immune response leads to aberrant skin recruitment of skin-homing CD8+ lymphocytes. Indeed, Epstein–Barr virus (EBV) has been suggested in the pathogenesis of both entities, as elevated serum titres of anti-IgG–EBV or anti-IgM–EBV has been reported in both conditions, as well as improvement in some patients after treatment with either aciclovir or valaciclovir.13,26,29 However, we found no evidence of active EBV involvement in our cohort. Nevertheless, the similar clinical presentation and course, pathological findings, cytotoxic features and in some cases cd T-cell infiltrate, also suggest a common pathomechanism for both entities. British Journal of Dermatology (2015) 172, pp372–379

At least a subset of PL and LyP present with similar indolent and often transient papular eruption with cytotoxic clinical and pathological features and a common cd T-cell-rich infiltrate. In summary, we have described a subset of PL and LyP cases that share a cd T-cell-rich papular eruption and an indolent, often transient, course. So far, none of our patients has shown progression to lymphoma. It is possible that some cases diagnosed as CD8+, type D or type E LyP may belong to the same disease spectrum and should perhaps be diagnosed as PL rather than a CD30 LPD, given the lymphoma connotations that this diagnosis carries. Most importantly, we provide evidence that the presence of a predominant cd T-cell phenotype in cutaneous lymphoid infiltrates is often not associated with aggressive lymphomas.

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British Journal of Dermatology (2015) 172, pp372–379

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