A case of lymphomatoid papulosis type E in a young adult: An uncommon entity.

Lymphomatoid papulosis (LyP) type E is a rare variant of the primary cutaneous CD30+ lymphoproliferative disorders, characterized clinically by large necrotic eschar-like lesions and histopathologically by angiodestructive and angioinvasive infiltrates of CD30+ lymphocytes. As in other forms of lymphomatoid papulosis, type E lesions may undergo spontaneous regression after weeks, with frequent recurrences. We report a 21-year old male with an angiodestructive infiltrate of CD30+ lymphocytes manifesting as a papular eruption rather than ulceration, and suggest that this clinical phenotype might be related to the presence of CD4+ lymphocytes in the inflammatory cell infiltrate.

Lymphomatoid papulosis types D and E: a multicentre series of the French Cutaneous Lymphomas Study Group.

BACKGROUND: Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports. AIM: To further describe the clinical and histological features of LyP D and E based on a retrospective multicentre study. METHODS: The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms. RESULTS: After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow-up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self-regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar-like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma. CONCLUSION: LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas.

Lymphomatoid papulosis - making sense of the alphabet soup: a proposal to simplify terminology.

Clinically, lymphomatoid papulosis (LYP) is characterized by recurrent papulonodular lesions. Unlike this stereotypical clinical presentation, the histological spectrum of LYP is very wide, comprising distinct growth patterns, variably sized neoplastic cells, and different immunophenotypes. The revised 2016 WHO classification includes the histological LYP types A to E as well as another type characterized by a specific chromosomal alteration. In addition, new LYP types are going to be proposed, based not only on histological but also on clinical and genetic features. The ensuing expansion of the alphabetical list of histological types will add to the complexity of the terminology of LYP, thereby potentially increasing the risk of complicating rather than facilitating the diagnostic approach to the disease. Moreover, there may be overlap between individual disease types. This development raises the question as to how to simplify the terminology of LYP while still respecting its histological complexity. Herein, we advocate a practical approach to the terminology of LYP based on descriptive terms rather than the designation of LYP types by alphabetical characters. Our proposal aims to contribute to a pragmatic and user-friendly approach, thus not only facilitating the diagnostic process but also the communication between clinicians and pathologists.

[Cutaneous lymphomas: new entities and rare variants]. / Kutane Lymphome: Neue Entitäten und seltene Varianten.

Primary cutaneous lymphomas are the second most common group of extranodal non-Hodgkin lymphomas. Recently several new variants and entities have been described but have not yet become part of the World Health Organization (WHO) classification. These forms include the granulomatous form of mycosis fungoides, which is associated with a poorer prognosis, as well as indolent CD8+ lymphoproliferations on the head and at acral localizations. Within the group of cutaneous CD30+ lymphoproliferative disorders, new histological types of lymphomatoid papulosis have been identified, such as type D (CD8+ epidermotropic) and type E (angioinvasive) which simulate aggressive lymphomas. Cutaneous peripheral T-cell lymphomas are a prognostically heterogeneous group of cutaneous lymphomas. The cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are very aggressive neoplasms, whereas cutaneous CD4+ small to medium-sized T-cell lymphoma in its solitary or localized form represents an indolent lymphoproliferation: the terminology, histogenesis and differentiation from nodular T-cell pseudolymphoma are still a matter of debate. Among B-cell lymphomas, disorders associated with Epstein-Barr virus (EBV) are discussed focusing on EBV diffuse large B-cell lymphoma of the elderly and EBV-associated mucocutaneous ulcer. This review describes the clinical, histological and immunophenotypic features of new and rare entities and variants of cutaneous lymphomas and highlights the impact of the clinicopathological correlation in the diagnostic process.

Lymphomatoid papulosis type D: a newly described variant easily confused with cutaneous aggressive CD8-positive cytotoxic T-cell lymphoma.

Lymphomatoid papulosis (LyP) is defined as a chronic recurrent skin disease characterized by waxing and waning papules and nodules with histologic features of a CD30-positive T-cell lymphoma. Three histological subtypes (A, B, and C) were already recognized, and only more recently, a further variant simulating histologically an aggressive epidermotropic CD8-positive T-cell lymphoma was described, which was named LyP type D by the authors. We report the case of a 38-year-old woman presenting with a 1-year history of recurrent self-healing papules and nodules, predominantly affecting her upper and lower limbs but also the face, including the lower lip, with no associated systemic symptoms. A biopsy from 1 lesion revealed an infiltrate of atypical lymphoid cells extending throughout the dermis with massive epidermotropism displaying a pagetoid reticulosis-like pattern and a CD8(+)CD30(+) cytotoxic T-cell phenotype. The clinicopathologic features conformed to the newly described type D variant of LyP. Diagnostic studies did not reveal any systemic involvement, and the patient remains otherwise well with no active treatment. In the present report, we discuss the need for clinicopathologic correlation to establish an accurate diagnosis and its importance for an adequate management of these patients.

Lymphomatoid papulosis.

Lymphomatoid papulosis (LyP) is a non-aggressive skin disorder characterized by papulonodular injuries, sometimes necrotic, often scattered, relapsing, which frequently regress spontaneously. LyP represents about 12% of cutaneous lymphomas. The etiology of LyP is unknown. Based on its histopathology, in 2018, the World Health Organization (WHO) classified LyP into six types with similar prognosis (A,B,C,D,E and DUSP22). Once the diagnosis of LyP has been made, having an excellent prognosis, this pathology must be managed mainly with a "watch and wait" strategy. Treatment should be given only in the presence of diffuse, symptomatic lesions with disfiguring evolution, with the aim of reducing time of resolution and preventing recurrences or the formation of new lesions.

[Investigation on clinicopathologic features of lymphomatoid papulosis].

OBJECTIVE: To investigate the clinicopathologic features, immunophenotype and prognosis of lymphomatoid papulosis (LyP). METHODS: Clinicopathologic analysis, immunohistochemical staining (LSAB and EliVision method) and in situ hybridization for EBER were undertaken in this study. RESULTS: Thirteen cases of LyP were studied, derived from six male and seven female patients with a median age of 26.4 years. The most common presentation was multiple symptomless papules or nodules, involving predominately the extremities and trunks. Histologically, the tumor primarily involved the dermis and subcutaneous layer. Six tumors were type A, one was type B and six were type C. The main infiltration patterns were wedge-shaped, band-like, sheet-like or nodular. There was epidermotropism in eight cases. Immunohistochemical staining showed that the large tumor cells in all 12 types A and C cases expressed CD30. All 13 cases expressed two to three T-cell associated antigens (CD3, CD5 or CD45RO) and one to three cytotoxic granule associated antigens (TIA-1, GrB or Perforin). All cases expressed CD4, four expressed CD8, and one expressed CD15. Only one case expressed CD20; and all cases were negative for ALK-1. The tumor cells showing epidermotropism had CD3(+), CD4(+) and CD8(-) phenotype in most cases. Only one case was EBER1/2 positive. Follow up information was available in 12 patients; all were alive at the end of the follow up period. CONCLUSIONS: LyP has distinctive clinicopathologic features and immunophenotype with favorable prognosis. In types A and C, the atypical cells showing epidermotropism were similar to those in MF, these cells possess cerebriform and hyperchromatic nuclei. The epidermotropic tumor cells and the CD30(+) large cells may be derived from different clones. EB virus may not be correlated with LyP.

IL-4 production by CD8+ lymphomatoid papulosis, type C, attracts background eosinophils.

There are two subsets of CD8+ T cells: Tc1 and Tc2. INF-gamma production by Tc1 cells causes granulomatous inflammation. IL-4 production by Tc2 cells attracts eosinophils. A 76-year-Caucasian female presented with CD8+ lymphomatoid papulosis (LyP), type C. We hypothesized that the LyP cells belonged to the Tc2 subset because of abundant background eosinophils. Hematoxylin and eosin and immunohistochemical stains were carried out on tissue sections from a skin punch biopsy. Antibodies for immunohistochemical stains included CD3, CD4, CD5, CD7, CD8, CD30, CD56, ALK-1, clusterin and IL-4. There was involvement of the dermis by a dense lymphoid infiltrate composed of large atypical cells and numerous eosinophils. The LyP cells expressed CD5, CD8, CD30 and IL-4. Keratinocytes showed a membranous pattern of immunoreactivity for IL-4. IL-4 production by CD8+ LyP, type C indicates that it belongs to the Tc2 subset. The cytokine milieu produced by the LyP cells attracted eosinophils. The IL-13R complex on keratinocytes bound IL-4 and produced a membranous staining pattern. Although CD8+ LyP is rare, we believe that this CD30+ lymphoproliferative disorder should be included in the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous T-cell lymphomas.

Practical Management of CD30⁺ Lymphoproliferative Disorders.

Primary cutaneous CD30⁺ lymphoproliferative disorders (LPDs) account for approximately 25% of cutaneous lymphomas. Although these LPDs are clinically heterogeneous, they can be indistinguishable histologically. Lymphomatoid papulosis rarely requires systemic treatment; however, multifocal primary cutaneous anaplastic large cell cutaneous lymphoma and large cell transformation of mycosis fungoides are typically treated systemically. As CD30⁺ LPDs are rare, there is little published evidence to support a specific treatment algorithm. Most studies are case reports, small case series, or retrospective reviews. This article discusses various treatment choices for each of the CD30⁺ disorders and offers practical pearls to aid in choosing an appropriate regimen.

Lymphomatoid papulosis: reappraisal of clinicopathologic presentation and classification into subtypes A, B, and C.

OBJECTIVES: To analyze clinicopathologic features of lymphomatoid papulosis and delineate the characteristics of histopathologic variants (types A, B, and C). DESIGN: Retrospective nonrandomized study. SETTING: University-based dermatologic referral center. PATIENTS: Eighty-five patients with lymphomatoid papulosis. Clinical data and 1 or more biopsy specimens were available for review in all cases. When possible, immunophenotypic and molecular analyses were carried out. RESULTS: Of these patients, 78 presented only 1 histopathologic subtype of lymphomatoid papulosis (64 had type A, 3 had type B, and 11 had type C). The last 7 patients presented more than 1 subtype (1 had A and B, 5 had A and C, and 1 had A, B, and C). Two patients had regional lymphomatoid papulosis, an unusual clinical presentation characterized by groups of lesions localized to 1 anatomic region. We observed, we believe for the first time, that some histopathologic patterns, ie, follicular mucinosis (n = 1), syringotropic infiltrates (n = 1), epidermal vesicle formation (n = 2), and syringosquamous metaplasia (n = 1), were associated with lymphomatoid papulosis. A distribution along hair follicles, or follicular lymphomatoid papulosis, was observed in 5 biopsy specimens. A bandlike rather than a wedge distribution of the infiltrate was seen in 5 specimens from patients with lymphomatoid papulosis type A. Of 8 patients who had associated lymphoid malignancies, 4 had Hodgkin disease and 4 had mycosis fungoides. CONCLUSIONS: Lymphomatoid papulosis is a cutaneous disorder with multiple clinicopathologic features. Differentiating between mycosis fungoides and anaplastic large cell lymphoma may be very difficult and sometimes impossible. In the spectrum of CD30(+) cutaneous lymphoproliferative disorders, boundaries between these 2 entities are not clear-cut.

Lymphomatoid papulosis: a low-grade T-cell lymphoma?

Lymphomatoid papulosis is a chronic cutaneous lymphoid disease characterised clinically by the presence of recurrent papulonodular or plaque like lesions, which appear benign. Paradoxically, histological and cytopathological features demonstrate features of malignancy. This annotation highlight the current theories and technical advances into the assessment of this condition, with emphasis on possible pathogenic disease mechanisms.

Chromosomal rearrangements of 6p25.3 define a new subtype of lymphomatoid papulosis.

Lymphomatoid papulosis (LyP) is an indolent cutaneous lymphoproliferative disorder with clinical and pathologic features overlapping those of both reactive conditions and aggressive lymphomas. Recurrent genetic abnormalities in LyP have not been previously identified. Here, we describe the clinical, immunophenotypic, and genetic characteristics of cutaneous lymphoproliferative lesions showing distinctive and previously undescribed histologic features in 11 patients. All patients were older adults (67 to 88 y) with predominantly localized lesions and clinical presentations suggesting benign inflammatory dermatoses or low-grade epithelial tumors. Histologically, lesions showed a biphasic growth pattern, with small cerebriform lymphocytes in the epidermis and larger transformed lymphocytes in the dermis. All had a T-cell immunophenotype. The pathologic features raised the possibility of an aggressive T-cell lymphoma such as transformed mycosis fungoides. However, no patient developed disseminated skin disease or extracutaneous spread. Untreated lesions regressed spontaneously. All cases harbored chromosomal rearrangements of the DUSP22-IRF4 locus on 6p25.3. The overall findings suggest that these cases represent a newly recognized LyP subtype characterized by 6p25.3 rearrangements. The benign clinical course in all 11 patients despite pathologic features mimicking an aggressive lymphoma emphasizes the importance of clinicopathologic correlation, incorporating molecular genetic analysis when possible, during the evaluation of cutaneous lymphoproliferative disorders.

A variant of lymphomatoid papulosis simulating primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Description of 9 cases.

Lymphomatoid papulosis (LyP) is a recurrent, self-healing eruption belonging to the spectrum of cutaneous CD30+lymphoproliferative disorders. Three main histologic subtypes of LyP are recognized: type A (histiocytic), type B (mycosis fungoides-(MF)-like), and type C (anaplastic large cell lymphoma-like). We reviewed 26 biopsies from 9 patients (M:F=6:3, median age: 29; mean age 27,2; age range 10 to 38) who presented with clinical features typical of LyP but with histopathologic aspects that resembled primary cutaneous aggressive epidermotropic CD8+cytotoxic T-cell lymphoma. In all but 1 case atypical lymphoid cells showed expression of CD30, and in 8 of 9 cases a T-cell cytotoxic phenotype could be observed (betaF1+, CD3+, CD4-, CD8+). Expression of at least 1 cytotoxic marker (TIA-1, granzyme B) was observed in all cases. Polymerase chain reaction analysis of the T-cell receptor genes revealed a monoclonal rearrangement in 2 of 5 cases tested. Follow-up data available for 8 patients (mean follow-up time: 84 mo, median: 32.5 mo; range: 1 to 303 mo) revealed that none of them developed systemic involvement or signs of other cutaneous lymphomas. This cytotoxic variant of LyP may be histopathologically indistinguishable from primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, and may be the source of pitfalls in the diagnosis and classification. We propose the term LyP type D for this unusual variant of the disease. Accurate clinicopathologic correlation is required in this setting, with crucial implications regarding prognosis and management of patients.

[Clinical course and therapy of lymphomatoid papulosis. Experience with 17 cases and literature review]. / Klinische Verlaufsformen und Therapie der lymphomatoiden Papulose. Beobachtungen an 17 Fällen mit Literaturübersicht.

Lymphomatoid papulosis is a rare disease with a worldwide incidence of 1.2 to 1.9 per 1 million. It affects all age groups with a peak incidence between 30 and 40 years and an apparent male predominance. Occurrence in childhood has also been described. Both the etiology and pathogenesis of the disease are unknown. The clinical presentation is extremely variable and frequently uncharacteristic. A papulonodular eruption, characterized by self-healing skin lesions appearing in crops can often be seen, particularly on extremities. We report on 17 patients, including 2 children. By detailing 6 cases we point out the variable morphologic manifestations, the different courses of disease and therapeutic options.

Lymphomatoid papulosis and cutaneous CD30+ lymphoma.

Lymphomatoid papulosis and cutaneous CD30+ lymphoma are closely related conditions in which large atypical lymphocytes that have similar immunophenotypic features occur. In lymphomatoid papulosis, the lesions are papules and nodules that spontaneously involute. There are two polar histologic patterns, type A and B, in which the large atypical cells resemble those of Hodgkin's disease and mycosis fungoides, respectively, but in many cases, features of both types are present, either separately or in the same lesions. Variants of lymphomatoid papulosis include cases with a perifollicular distribution and those with lymphocytic vasculitis or dermal mucin deposits. Clinical lesions that tend to be stable, a monomorphous cellular composition, and in the case of immunocompromised patients, the presence of Epstein-Barr viral genome characterize cutaneous CD30+ lymphoma. A loss of response to transforming growth factor-beta, which normally dampens cellular proliferation, may differentiate CD30+ lymphoma from lymphomatoid papulosis.