Lymphomatoid papulosis: a study of 18 cases*

Lymphomatoid papulosis (LyP) is a cutaneous eruption that is clinically benign but histologically malignant. To date, more than 300 cases have been published. About 10–20% of the patients develop a lymphoma. The purpose of this study was to make a clinicopathological study of 18 patients diagnosed with LyP in our hospital from 1973 to 1990, to characterize cellular infiltrates in the lesions, to find clonal populations of T-cells and to look for predictive factors of malignant lymphoma in LyP patients. Mean age was 48.7 years. The most frequent clinical lesions were papules (88.8%) followed by plaques (38.8%). The localizations were on extremities (100%), trunk (88%), face (22%), palms or soles (11%), perigenital (11%) and scalp (5%). Two patients have been free of disease for more than 5 years. IgA levels are increased in LyP patients. Neither HTLV I nor III can be considered as a cause of the LyP in any of our patients. Associated diseases were found in 6 cases (1 mycosis fungoides, 1 Hodgkin's disease, 2 anaplastic large-cell lymphoma and 2 large plaque parapsoriasis). Some types of parapsoriasis should be included in the ‘spectrum of Ki-1 lymphomas’. 52 skin biopsies were studied. 17% were type A of Willemze, 67% were type B and 15% were transitional. In 12 of the samples follicular or perifollicular infiltration was found. Follicular LyP should not be considered as a distinct type of LyP. Vasculitis is an uncommon finding in LyP. In all the cases studied, large atypical cells were CD30 +; 5/7 cases had lost CD5 and 4/5 cases had lost CD7. In one case, all T-cell antigens were negative. Cerebriform mononuclear cells were always recognized by T-cell antibodies and they were CD30 positive in only two cases. In one case there were more CD8 + than CD4 + cells. In 5 patients skin and blood samples for genetic rearrangement (beta-T) were taken. Only germinal line was found. We did not find any significant difference between those cases in which malignant lymphoma developed and those in which it did not.     

Nitrogen mustard gel-induced inflammation triggers lymphomatoid papulosis in patients with mycosis fungoides

Lymphomatoid papulosis (LyP) is a paraneoplastic primary cutaneous CD30⁺ lymphoproliferative disorder (LPD) that has been associated with malignant lymphomas, most commonly mycosis fungoides (MF). We observed 10 patients with MF who developed severe inflammation after using nitrogen-mustard (NM) gel from 1 to 8 months and who developed LyP. We hypothesized that NM gel produced local inflammation, which induced CD30 expression in malignant T cells in situ leading to the appearance of LyP papules. The high frequency of induction of LyP lesions in patients with severe inflammation while on treatment with NM gel suggests an association between inflammatory stimuli and development of LyP. Our observation provides insight into the pathogenesis of CD30⁺ LPD.     

Primary cutaneous anaplastic large cell lymphoma with subsequent leg involvement

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is regarded as an indolent type of cutaneous T-cell lymphoma. However, a few recent publications revealed that C-ALCL patients with initial leg involvement had significantly worse survival than those without initial leg involvement. Herein, we report a case of C-ALCL with subsequent leg involvement, which led to death after chemoradiation therapy. A 75 years old Japanese man presented with multiple erythematous nodules in his left arm and the side of his left chest. Histopathological and immunohistochemical studies led to the diagnosis of primary C-ALCL. At the initial diagnosis, no leg lesion was found. One year after the initial diagnosis, C-ALCL appeared in his right lower thigh and left hip. Radiation therapy, low-dose etoposide and CHOP therapy were performed; however, the patient died of malignant lymphoma 4 years after the initial diagnosis. We speculated that the occurrence of subsequent leg involvement may also be indicative of a worse prognosis, as in the case with initial leg involvement in C-ALCL. Therefore, we propose that C-ALCL patients with initial or subsequent leg involvement should be classified as a distinct clinicopathological variant of C-ALCL (“leg-type” involvement) and that they may require intense therapy.     

Primary cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma with atypical presentation

Primary cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma is characterized by a proliferation of epidermotropic CD8(+) cytotoxic T cells and an aggressive clinical behavior. Patients present with localized or disseminated eruptive papules, nodules and tumors. We report a case of primary cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma with unusual clinical manifestation. The lesion occurred as multiple brownish macules and flat-topped papules on the hands, feet and face in a 25-year-old woman.     

Lymphomatoid papulosis: is a second lymphoma commoner among East Asians?

Background. Lymphomatoid papulosis (LyP) is a low‐grade cutaneous lymphoma, which lies within the spectrum of primary cutaneous CD30‐positive lymphoproliferative disorders. Around 10–20% of LyP cases are associated with a second lymphoma. Aim. To analyse a cohort of Asian patients with LyP, diagnosed from 1987 to 2007 at the National Skin Centre (NSC), Singapore, in terms of epidemiology, treatment and association with a second lymphoma. Methods. Patients were identified through the NSC clinical and histological databases. Results. During this period, 13 patients were diagnosed with LyP based on clinicopathological criteria. The mean age at diagnosis was 41 years, the male : female ratio was 2.3 : 1, and 92% of the patients were Chinese. Recurrent papulonecrotic lesions were present for a mean of 3 years before diagnosis. Treatment of LyP comprised monotherapy (n = 4) or combination therapy (n = 9) using corticosteroids, oral antibiotics, methotrexate and/or phototherapy. Mean duration of follow‐up was 6.4 years. Eight patients (61.5%) were diagnosed with a second lymphoma, either before (n = 2), concurrently with (n = 1) or after (n = 5) the diagnosis of LyP. Mycosis fungoides (MF) was the commonest lymphoma (78%, n = 7), followed by primary cutaneous anaplastic large‐cell lymphoma (12%, n = 2). There was one death (mortality rate 7.7%), which occurred in a patient who had developed stage IIA MF after LyP, which subsequently progressed to systemic T‐cell lymphoma. Conclusions. LyP is a chronic, relapsing disease with considerable morbidity, but an overall good prognosis. A strikingly large proportion of our Asian patients (61.5%) had a second lymphoma, compared with previous studies. This emphasizes the importance of regular lifetime surveillance for associated lymphomas in all patients with LyP.     

Lymphomatoid papulosis with a natural killer-cell phenotype

Lymphomatoid papulosis (LyP) is defined as a recurrent self-healing papulonodular eruption with the histological features of a (CD30+) cutaneous T-cell lymphoma. The atypical cells usually have a CD3+/-, CD4+/-, CD8-, CD30+, CD56- T-cell phenotype. We report an unusual case of LyP, in which the atypical cells expressed a CD3-, CD4-, CD8-, CD30+, CD56+ phenotype. Detailed phenotypic and genotypic analysis confirmed that these cells had a natural killer (NK)-cell phenotype. Lymphomas with an NK-cell phenotype usually have a poor prognosis. However, the waxing and waning of papular lesions for more than 20 years and the excellent response to low-dose oral methotrexate in this patient suggest similar clinical behaviour to LyP cases with a T-cell phenotype.     

Immunophenotypic and genotypic characterization of lymphomatoid papulosis

BACKGROUND: Lymphomatoid papulosis (LyP) is a chronic dermatosis that histologically resembles malignant lymphoma. Thus far, only a few cases of LyP have been characterized in detail with regard to immunophenotype, genotype, and karyotype. OBJECTIVE: Our purpose was to study seven patients with LyP and compare the results to those reported in the literature. METHODS: Skin biopsy specimens were analyzed by frozen section immunohistochemical and molecular biologic techniques. Cytogenetic analysis was also performed in three cases. RESULTS: The atypical lymphoid cells consisted of activated helper T cells; four of the seven patients had lesions with a detectable clonal T-cell population. A peripheral T-cell lymphoma developed in one patient before the emergence of a genotypically different LyP T-cell clone. Cytogenetic studies were abnormal in one case of LyP and normal in another, whereas the karyotype of the lymphoma was abnormal. CONCLUSION: LyP is a preneoplastic proliferation of activated helper T cells, which is often clonal and may regress and expand with the development of new LyP clones or lymphoma.     

Mycosis fungoides and chronic lymphocytic leukaemia--composite T-cell and B-cell lymphomas presenting in the skin

Composite lymphomas involving cutaneous B-cell and T-cell lymphomas are very uncommon. We report here the unique circumstance of a patient with mycosis fungoides (primary cutaneous T-cell lymphoma) who later developed chronic lymphocytic leukaemia (B-cell lymphoproliferation, B-CLL), which presented in the skin (leukaemia cutis) as a composite lymphoma affecting an earlobe. The presence of both lymphoproliferative disorders was confirmed with immunophenotyping and the finding of both immunoglobulin gene rearrangements and T-cell receptor gene rearrangements in the ear and the same T-cell receptor gene rearrangement in a plaque lesion of mycosis fungoides on the arm.     

Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation.     

Extranodal NK / T-cell lymphoma with cutaneous involvement: 'nasal' vs. 'nasal-type' subgroups— a retrospective study of 18 patients

Background  Extranodal natural killer T (NK/T) cell lymphoma is subcategorized into 'nasal' and 'nasal-type' NK/T-cell lymphomas according to the primary sites of anatomical involvement.
Objectives  The aim of this study was to characterize the cutaneous manifestations of the skin involving extranodal NK/T-cell lymphoma and to define the distinctive features of 'nasal' and 'nasal-type'. In addition, the prognostic factors that affect overall survival were investigated.
Methods  A retrospective case study of 18 patients with extranodal NK/T-cell lymphoma with cutaneous involvement was performed.
Results  The NK/T-cell lymphomas usually occurred in middle-aged, male patients. Most of the patients presented with either cellulitis or ulcer. A facial predilection for the location of the lesion was noted. The characteristic features of the 'nasal-type' compared with the 'nasal' were a localized involvement of the skin, less aggressive clinical course and better survival outcome.
Conclusions  Extranodal NK/T-cell lymphomas are extremely aggressive regardless of their subgroup. However, the 'nasal-type' NK/T-cell lymphoma was clinically less aggressive, more localized and had a better outcome compared with the other type. Cellulitis and ulcer were the major cutaneous manifestations.     

Cutaneous CD30 positive lymphoproliferative disorders with coexistent epithelial neoplasms: Report of two cases

Primary cutaneous large cell anaplastic lymphoma (C‐ALCL) and lymphomatoid papulosis (LyP) are cutaneous CD30+ lymphoproliferative disorders (CD30+ LPD). An association with CD30+ LPD and pseudoepitheliomatous hyperplasia has been recognized. Additionally, rare reports of epithelial neoplasms such as keratoacanthomas and squamous cell carcinomas (SCC) occurring in association with both C‐ALCL and LyP have been reported. We report two cases of CD30+ LPD with associated epithelial neoplasms; one patient with a primary cutaneous CD30+ LPD and SCC identified within the same lesion, and the other with a keratoacanthoma arising in a lesion of LyP. The pathogenesis of this association is poorly understood although various hypotheses exist. Awareness of the coexistence of these entities will avoid misdiagnosis and incorrect treatment.     

Expression of Fas and Fas-ligand in primary cutaneous T-cell lymphoma (CTCL): association between lack of Fas expression and aggressive types of CTCL

BACKGROUND: Fas (CD95; APO-1) is a transmembrane protein that mediates apoptosis upon cross-linking with Fas-ligand (Fas-L). Interaction of Fas-L expressed by cytotoxic T cells with Fas-expressing tumour cells plays an important part in antitumour immune responses. OBJECTIVES: We aimed to investigate Fas and Fas-L expression in frozen and paraffin-embedded material from a large group of patients with cutaneous T-cell lymphoma (CTCL). METHODS: Immunostaining with monoclonal antibodies against Fas and Fas-L was performed in material from 23 patients with mycosis fungoides (MF), 10 with lymphomatoid papulosis (LyP), 10 with CD30-positive primary cutaneous large T-cell lymphoma (LTCL) and nine with CD30-negative LTCL. The results were correlated with the type and stage of CTCL and clinical features. RESULTS: Expression of Fas by the large majority of the neoplastic T cells was observed in 15 of 15 cases of plaque-stage MF, 10 of 10 cases of LyP and 10 of 10 cases of CD30-positive LTCL, but only in four of 12 cases of tumour-stage MF and two of nine cases of CD30-negative LTCL. In three of four MF patients in whom both plaques and tumours could be studied, a significant decrease in Fas expression was observed with progression from plaque-stage to tumour-stage disease. Fas-L was expressed by > 50% of the neoplastic T cells in 46 of 56 biopsies, and no clear relationship with type of CTCL and clinical behaviour was observed. CONCLUSIONS: This study demonstrates loss of Fas expression in aggressive types of CTCL, but not in indolent types of CTCL. These data suggest that loss of Fas receptor expression may be one of the mechanisms that allow tumour cells to escape an effective immune response, and may contribute to the unfavourable prognosis of some types of CTCL.     

Lymphomatoid Papulosis Followed by Anaplastic Large Cell Lymphoma in a Pediatric Patient

Lymphomatoid papulosis (LyP) is a benign, self-healing, papular eruption that can wax and wane over time. Transformation to T-cell lymphoma has been well documented in 10% to 20% of adults with LyP. However, this transformation rarely occurs in patients younger than 20 years of age. Here, we present the first known pediatric patient in Korea, a 12-year-old boy who developed a subcutaneous nodule on the scrotum 13 months after papulonecrotic lesions of LyP were identified on both lower extremities and face. Histological and immunohistochemical examination of the subcutaneous nodule revealed anaplastic large cell lymphoma (ALCL). A T-cell receptor gene rearrangement analysis demonstrated an identical rearranged pattern in the two specimens, indicating that a common T-cell clone had proliferated over time in both the LyP and ALCL lesions.     

Cutaneous immunoblastic T-cell lymphoma

Summary The case of a 69-year-old male patient with an unusual type of malignant lymphoma is presented. Clinically, it was at first characterized by follicular papules and erythematous patches, later, by the development of cutaneous tumors and enlarged lymph nodes, and by a severe, finally excruciating pruritus. Treatment with PUVA (psoralen-ultraviolet-A) combined with 40–80 mg prednisolone and then with chemotherapy [COPP regimen (cyclophosphamide, vincristine, procarbacine, prednisone), high-dosage methotrexate followed by citrovorum factor rescue] was not successful. The patient died of pneumonia 2.5 years after the onset of the first clinical symptoms. An immunoblastic infiltrate was observed histologically and electromicroscopically in the initial lesions of the skin. Therefore, the diagnosis of a cutaneous immunoblastic T-cell lymphoma was tentatively made at the beginning, which was later confirmed in numerous biopsies and laboratory investigations. Immunocytologically and enzymecytochemically, the infiltrating cells were shown to be immature T cells; in the lymph nodes, numerous immunoblasts and large Sézary cells were noted beginning in the paracortical areas and leading to the destruction of the normal lymph node structure. A maximum of 18% Sézary cells was observed in the peripheral blood, though there were no very large Sézary cells or blast cells. In the autopsy, a systemic involvement with an atypical lymphoid infiltration was found in numerous internal organs.The special nature of this case justifies its classification as high-grade malignant lymphoma and its differentiation from normal cases of mycosis fungoides. In contrast, mycosis fungoides generally fulfils criteria typical of low-grade malignant lymphomas.Supported by the Deutsche Forschungsgemeinschaft     

Proapoptotic and antiapoptotic markers in cutaneous T-cell lymphoma skin infiltrates and lymphomatoid papulosis

BACKGROUND: In cutaneous T-cell lymphoma (CTCL) lesions, both reactive T cells and malignant T cells intermingle. The disease progression is mostly slow. Recent evidence suggests that even if clinical remission is reached, malignant cells persist and a relapse follows sooner or later. To wha extent tumour cell apoptosis occurs in the skin lesions either due to the reactive T cells or t therapeutic efforts is not known. OBJECTIVES: To determine the extent of tumour cell apoptosis and the expression of proapoptotic an antiapoptotic markers in serial skin lesion samples from patients with CTCL, and to compare th findings with those in patients with lymphomatoid papulosis (LyP). METHODS: Thirty-four skin samples were obtained from 12 patients with CTCL at the time o diagnosis and at a mean of 1.6, 3 and 6 years later. The patients received psoralen plus ultraviolet (PUVA), electron beam or cytostatic treatments. In addition, fresh post-treatment samples fro three patients with CTCL undergoing PUVA therapy were obtained. For comparison, skin biopsies o five patients with LyP were studied. Immunohistochemical demonstration of the expression of th following markers was performed on formalin-fixed skin sections: Fas (CD95), Fas ligand (FasL) bcl-2, granzyme B, the tumour-suppressor protein PTEN and the effector caspase, caspase-3. Th malignant cells were identified morphologically, and apoptotic cells were identified with th terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method on parallel sections. RESULTS: In untreated CTCL lesions, apoptotic lymphocytes were extremely rare, and no increase in the number of apoptotic cells was observed after any of the treatments used. In LyP, apoptotic cell were more frequent, comprising on average 5% of the infiltrate. The apoptosis-associated marker Fas, FasL, caspase-3 and granzyme B were expressed by morphologically neoplastic cells in CTCL and by large atypical cells in LyP, with no significant differences. However, only a few reactive cell in CTCL infiltrates expressed granzyme B while about 10% of the corresponding cells were positive in LyP. The expression of antiapoptotic bcl-2 was more frequent in CTCL than in LyP, while PTE expression was high in both instances. The number of bcl-2 + cells tended to decrease after therapy When comparing the findings between the first and the last samples, a decrease in the number of bcl-2+ cells and an increase in Fas+ cells was associated with disease progression, despite therapy, while the opposite was true for remissions. CONCLUSIONS: Apoptosis was found to be a rare event in CTCL lesions irrespective of precedin therapy During patient follow-up, no significant differences in the expression of apoptotic marker was observed while in most cases a lower level of antiapoptotic bcl-2 expression was observed after all types of therapies and in association with disease progression when compared with high expression in the untreated lesions. The absence of apoptosis and high expression of bcl-2 together with a low expression of apoptosis-inducing granzyme B in the reactive lymphocytes in CTC could explain the chronic nature of the disease and the poor response to therapy, while th more frequent occurrence of granzyme B and apoptosis together with a lower level of expressio of bcl-2 by the large atypical cells in LyP could contribute to the favourable outcome of the latter.     

Systemic varicella zoster virus reinfection in a case of angioimmunoblastic T-cell lymphoma

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma that causes immunological disorders such as immunosuppression, autoimmune disease-like symptoms and allergy. We report a case of a 67-year-old man with AITL who had a serious varicella zoster virus (VZV) reinfection that appeared clinically to be varicella. Forty percent of cases of AITL are associated with skin rash. A variety of cutaneous manifestations have been reported; however, the majority are macropapular eruptions that are often diagnosed as drug associated. Our study emphasizes the need to correctly diagnose opportunistic infections, such as the varicella that is documented in our patient, at early stages in AITL.     

A Case of Aggressive NK/T-cell Lymphoma/Leukemia with Cutaneous Involvement in Adolescence

NK/T-cell lymphoma (NKTCL) is characterized by the expression of the NK-cell antigen CD56. Non-nasal NK/T-cell lymphomas are subdivided into primary cutaneous and 4 subtypes of secondary cutaneous lymphomas; nasal type, aggressive, blastic (blastoid), and other specific NK-like cell lymphoma. Aggressive NK/T-cell lymphoma/leukemia is a rare leukemic variant of nasal type NKTCL. We herein report a rare case of aggressive NK/T-cell lymphoma/leukemia with cutaneous involvement in adolescence.     

Apoptosis in CD30-positive lymphoproliferative disorders of the skin

The spectrum of CD30-positive cutaneous lymphoproliferative disorders (CD30+ CLPD) includes lymphomatoid papulosis (LyP), primary cutaneous CD30+ large T-cell lymphoma (LTCL) and rare borderline patients. Despite their malignant histopathology, CD30+ CLPD exhibit a low-grade malignant course with an excellent prognosis and a characteristic tendency for spontaneous regression. Apoptosis of tumour cells is considered a principal mechanism of tumour regression. We examined the proliferation and apoptosis rates as well as the expression of apoptosis-related proteins in various clinical entities, tumour cell lines and evolutional (evolving and regressing) stages of CD30+ CLPD. Skin biopsies of LyP (n = 20) and LTCL (n = 19) and five CD30+ lymphoma cell lines were analysed by means of immunohistochemistry and Western blotting in order to evaluate the proliferation (Ki67), apoptosis (FragEl) and expression of Bax, Bcl-x, C-kit and Mcl-1. A significantly higher apoptotic index (AI) was found in LyP (AI = 12.5%) than in LTCL (AI = 3.1%, P < 0.005). Bax was expressed by the majority of tumour cells in all forms of CD30+ CLPD and CD30+ cell lines. However, no Bax expression was found in tumour cell lines derived from systemic CD30+ lymphomas, which lack spontaneous regression and display an aggressive clinical course. No significant correlation was found between the expression of apoptosis-related proteins and the tumour type and evolutional stage of CD30+ CLPD. We conclude that the higher AI in LyP may contribute to the regression of LyP lesions and the excellent prognosis of the disease. Pro-apoptotic protein Bax is expressed at high levels in CD30+ CLPD and may play a crucial role in mediating apoptosis of tumour cells.     

Cutaneous lymphomas showing prominent granulomatous component: clinicopathological features in a series of 16 cases

Background  The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon.
Objective  This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component.
Patients and methods  The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30⁺ cutaneous T-cell lymphoma (2 patients), CD4⁺ small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed.
Results  The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established.
Conclusion  The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.

Conflicts of interest

None declared.