Premycotic eruptions

Virtually any longstanding, recalcitrant inflammatory dermatosis may evolve into a cutaneous T-cell lymphoma. Although several entities within the parapsoriasis group can undergo malignant degeneration, most cases of cutaneous T-cell lymphoma are not preceded by parapsoriasis; a preceding inflammatory dermatosis that is not a parapsoriasis may be much more common. Among the parapsoriasis, lymphomatoid papulosis and large-plaque parapsoriasis and its variant, retiform parapsoriasis, have a variable tendency to undergo malignant degeneration. For any dermatosis deemed to have a significant premalignant potential, a plan of aggressive management with relatively non-aggressive modalities (for example, topical steroids, UVB light, and psoralen plus UVA light) should be considered.     

CD13 and TCR clone: markers of early mycosis fungoides

Making a differential diagnosis between early mycosis fungoides and parapsoriasis is often difficult at the clinical and histological level. The aim of this study was to explore markers that could help in this process. A total of 88 patients were included in 2 categories: large plaque parapsoriasis and digitiform parapsoriasis. A histological examination was performed for each patient, and expression of the antigen My7 (CD13), which is lacking in cutaneous T-lymphomas (but not in inflammatory lesions) and rearrangement of the T-cell receptor gene were analysed. A histological aspect of epidermotropic cutaneous T-cell lymphoma was observed in 23.5% of cases of large plaque parapsoriasis and 15% of cases of digitiform parapsoriasis. A disappearance of My7 antigen was noted in the 2 forms of parapsoriasis, more frequently when there was cutaneous T-cell lymphoma histology. A cutaneous clone was observed in 10.3% of cases of large plaque parapsoriasis, but not of digitiform parapsoriasis. For 3 patients, a cutaneous clone and a disappearance of My7 were associated with a non-specific histology. Considering these histological, immunological and molecular biological data, it appears that My7 antigen combined with T-cell clone may help the dermatologist to confirm the diagnosis of early mycosis fungoides. Moreover, further studies will determine whether CD13 is an early prognostic marker of evolution of a parapsoriasis to mycosis fungoides. Finally, these results demonstrate that digitiform parapsoriasis can be an early stage of MF.     

An evaluation of the treatment of parapsoriasis with phototherapy

Whether parapsoriasis represents an early stage of T-cell cutaneous lymphoma is still the subject of controversy. We evaluated the efficacy of phototherapy in the treatment of parapsoriasis and its relation with TCCL. Patients diagnosed with parapsoriasis and treated with phototherapy PUVA or UVB-NB were selected. Between 1 to 8 years following treatment the evolution of their disease was evaluated. In 62 patients the cure rate was 79.3% and 17.2% showed improvement of the lesions. Only two patients developed full blown T-cell cutaneous lymphoma. Phototherapy is an excellent treatment for parapsoriasis, with high cure rates, regardless of the type of phototherapy employed. Of the 62 patients under study, parapsoriasis showed no general tendency to progress to T-cell cutaneous lymphoma.     

Lack of evidence of human herpesvirus 8 DNA sequences in HIV-negative patients with various lymphoproliferative disorders of the skin

Human herpesvirus 8 (HHV-8) is a new virus which has been reported in Kaposi's sarcoma and some lymphoproliferative disorders such as Castleman's disease and body-cavity-based lymphoma. Because HHV-8 shares homology with Epstein-Barr virus (EBV), we searched for the presence of HHV-8 DNA sequences in various cutaneous T-and B-cell lymphoma by the polymerase chain reaction (PCR). Fortyseven HIV-negative patients with cutaneous lymphoma or large plaque parapsoriasis were enrolled in the study. For the detection of HHV-8 DNA sequences we used PCR followed by a hybridization with a digoxigenin-labelled probe and nested-PCR. HHV-8 DNA sequences could only be detected in a patient with large plaque parapsoriasis. Our study does not suggest any direct implication of HHV-8 in the pathogenesis of most cutaneous lymphoma. Serological studies will be helpful to appreciate if there is an epidemiological link between HHV-8 and cutaneous lymphomas.     

A retrospective study of the probability of the evolution of parapsoriasis en plaques into mycosis fungoides

Parapsoriasis en plaque has been suggested to be an early manifestation of mycosis fungoides (cutaneous T-cell lymphoma). We explored the disease course of patients with small plaque or large plaque parapsoriasis in a 26-year retrospective cohort analysis of 105 parapsoriasis patients, who were clinically and histopathologically followed up in Helsinki and Tampere University Hospitals. Eventual later cancers of these patients were verified from the Finnish Cancer Registry. In the small plaque parapsoriasis group, 7 patients (10%) and in the large plaque parapsoriasis group 12 patients (35%), developed histologically confirmed mycosis fungoides during a median of 10 and 6 years, respectively. No significant differences were found regarding the risk of developing mycosis fungoides or the tendency to remission in patients treated with or without phototherapy. Our results show that not only large plaque parapsoriasis, but also small plaque parapsoriasis, as currently defined in textbooks, can progress to mycosis fungoides. The benefits of phototherapy are equivocal in parapsoriasis treatment as far as progression to cancer is concerned.     

Immunoperoxidase examination of cutaneous infiltrates of mycosis fungoides and large-plaque atrophic parapsoriasis with OKT10

A monoclonal antibody (OKT10), which was developed recently, reacts with pro-thymocytes, T cell acute lymphoblastic leukemia (ALL) cells, cells in normal bone marrow (including plasma cells), and activated T cells. Tissues from patients with cutaneous T cell lymphoma were studied for the presence of OKT10-reactive cells with the use of an indirect immunoperoxidase technic. OKT10-reactive cells were identified in three of eight cases of mycosis fungoides, one of two cases of Sézary syndrome, with an equivocal reaction in one of ten cases of large-plaque parapsoriasis and in one of seven positive patch tests (allergic contact dermatitis). The biologic and possible clinical implications are discussed.     

Cutaneous lymphomas other than mycosis fungoides in Singapore: a clinicopathological analysis using recent classification systems

BACKGROUND: Cutaneous lymphomas other than mycosis fungoides (MF) are a heterogeneous group with wide variations in clinical presentation, biological behaviour and prognosis. New classification systems have been designed or proposed in recent years, with well-defined disease entities and emphasis on the importance of site. OBJECTIVES: This study aims to analyse a series of non-MF lymphomas in an institution-based dermatological setting in Singapore, based on the European Organization for Research and Treatment of Cancer (EORTC) classification and the World Health Organization (WHO) classification. A secondary objective is to highlight the clinical utility of both classification systems. PATIENTS AND METHODS: Forty cases diagnosed over a 12-year period were examined by immunohistochemistry with antibodies targeting CD3, CD4, CD5, CD8, CD20, CD30, CD43, CD45RO, CD56 and CD68 in paraffin-embedded specimens. The immunohistological diagnosis was correlated with the clinical presentation and staging investigations for the final diagnosis and the course of disease recorded. RESULTS: Non-MF T-cell lymphomas presenting in the skin comprised 31 cases (78%) and were 3(1/2) times more common than B-cell lymphomas, which comprised nine cases (22%). The common subtypes were lymphomatoid papulosis, CD30+ large cell cutaneous T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma. The commonly ascribed B-cell pattern with infiltrates in the mid and deep dermis and perivascular spaces was seen in 60% of T-cell lymphomas. Overall, there were equal numbers of primary cutaneous T-cell lymphomas and those due to concurrent or secondary cutaneous lymphoma. Five of six cases of subcutaneous panniculitis-like T-cell lymphoma had concurrent cutaneous and systemic involvement and their median survival was 7 months. CONCLUSIONS: The predominance of cutaneous T-cell lymphomas in this case series closely matched that reported from east Asia; cutaneous B-cell lymphomas are much less common than in Europe. The EORTC classification, which is designed only for primary cutaneous lymphomas, should be used in conjunction with the WHO classification because of the high prevalence of cutaneous lymphomas as the secondary site of disease from systemic lymphoma. In addition, subcutaneous panniculitis-like T-cell lymphoma is a primary cutaneous lymphoma where systemic involvement is common at initial presentation. We propose full immunophenotyping and complete clinical evaluation with staging investigations for all patients presenting with cutaneous lymphomas other than MF.     

Linear IgA dermatosis in association with angioimmunoblastic T-cell lymphoma infiltrating the skin: A case report with literature review

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive form of peripheral T-cell lymphoma, characterized by systemic symptoms, diffuse lymphadenopathy, hepatosplenomegaly and immunodysregulation. Half of AITL is associated with cutaneous symptoms, but only few cases with bullous eruption have been described. Association with a linear IgA dermatosis is extremely rare. Linear IgA dermatosis can be idiopathic, or linked with drug intake or neoplastic disorders. Some cases of linear IgA dermatosis presenting as toxic epidermal necrolysis (TEN) have been described, most of them being drug induced. We here present the case of a 72-year-old man recently diagnosed with AITL who developed a bullous eruption, presenting as TEN. Histopathology showed deep cutaneous involvement of the lymphoma with a sub-epidermal blistering and direct immunofluorescence revealed a heavy IgA linear deposit on the dermal-epidermal junction. A diagnosis of linear IgA dermatosis associated with cutaneous involvement of an angioimmunoblastic T-cell lymphoma was made. Chemotherapy and corticosteroids allowed cutaneous improvement but the patient died of his lymphoma shortly after.     

Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma with aggressive course

BACKGROUND: Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma is a recently described rare primary cutaneous lymphoma exhibiting aggressive clinical behavior. Only about twenty cases have been described in the literature. Below we report a case involving unusual association of cutaneous vasculitis and lymphoproliferation. CASE REPORT: A 42-year-old senegalese man was hospitalized for cutaneous nodular lesions, which rapidly spread and became necrotic and ulcerated. he had recent weight loss with fever and multiple enlarged lymph nodes. Cutaneous histological analysis showed epidermotropic dermal infiltrate comprising medium and large cd8+ cytotoxic t-cells of unusual angiocentricity with cutaneous vasculitis and fibrinoid necrosis. the patient died 4 months after initiation of treatment with multi-agent chemotherapy. DISCUSSION: This patient presented the characteristics of primary cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma described by Berti. The clinical findings in most cases consist of nodular and ulcerative cutaneous lesions. Histologically, the cutaneous infiltrate is composed of pleomorphic lymphocytes with marked and constant epidermotropism. Immunohistochemistry shows lymphocytes expressing a CD8+ phenotype and cytotoxic proteins, which probably accounts for the local and systemic aggressiveness of the disease, as well as the angiodestructive nature of the infiltrate and the necrotic lesions.     

Interleukin-15 expression in cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome)

BACKGROUND: Cytokines are of potential importance in the pathogenesis of cutaneous T-cell mediated disorders, including cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To compare interleukin (IL)-15 expression in certain inflammatory cutaneous diseases, with that in CTCL (mycosis fungoides and Sézary syndrome). METHODS: IL-15 mRNA and protein expression were examined by in situ hybridization and immunohistochemistry, respectively, on formalin-fixed, paraffin-embedded biopsies of normal human skin, atopic dermatitis, psoriasis, parapsoriasis and CTCL. RESULTS: Despite similar expression of IL-15 mRNA, we found differences in IL-15 protein expression between normal human skin, atopic dermatitis and psoriasis on the one hand, and parapsoriasis and CTCL on the other. IL-15 protein expression was not detected in normal human skin, atopic dermatitis or psoriasis, but was detected, mainly at low levels but in a few patients at higher levels, in epidermal keratinocytes in parapsoriasis, mycosis fungoides and Sézary syndrome. CONCLUSIONS: Induction of keratinocyte IL-15 expression appears to be a feature of CTCL. The factors stimulating such an expression remain unknown.     

Cutaneous graft-versus-host-like reaction in systemic T-cell lymphoma

We report a case of systemic T-cell lymphoma with cutaneous lesions showing histological features of a cutaneous graft-versus-host-like-reaction. Histology from liver, lymph node and bone marrow showed a malignant T-cell infiltrate. T-cell receptor gene rearrangement studies confirmed the diagnosis. A cutaneous graft-versus-host-like reaction has been reported with disseminated malignancy and one case has been reported with systemic lymphoma. Graft-versus-host disease normally occurs when lymphocytes from an immunocompetent donor are introduced into a histo-incompatible recipient who is incapable of rejecting them. In our patient a similar reaction may have occurred if the lymphoma was composed of cytotoxic cells or if a cell-mediated immune response against the malignant T-cells cross-reacted with epidermal keratinocytes. Alternatively the malignant T-cells could have been functionally active and induced a lichenoid reaction in the skin.     

Cutaneous T-cell lymphoma at a young age

A case of cutaneous T-cell lymphoma (CTCL) in a 22-month-old patient is discussed, emphasizing the importance of screening for CTCL even in very young patients with atypical symptoms of eczema, atopic dermatitis, or parapsoriasis. The clinical, histologic, and immunologic diagnostics can now be supported by molecular methods; therefore, patients at the earlier stages of CTCL can be diagnosed and treated with good results.     

Shortened telomere length is demonstrated in T-cell subsets together with a pronounced increased telomerase activity in CD4 positive T cells from blood of patients with mycosis fungoides and parapsoriasis

We have recently demonstrated that telomerase activity is increased and telomere length shortened in lymphocytes from peripheral blood of patients with cutaneous T-cell lymphoma. In order to determine which cell type has increased telomerase activity and shortened telomere length, CD4+, CD8+, CLA+ CD3+ and CLA- CD3+ T cells were isolated from peripheral blood of 25 patients, including 15 patients with mycosis fungoides and 10 patients with parapsoriasis. Eleven healthy individuals were used as controls; CD19+ B cells were separated from each individual as an internal control. The results showed that the increased telomerase activity was significantly predominating in the CD4+ T-cell subset. Significantly shortened telomere length was found in CD4+ and CD8+ T-cell subsets from the patients compared with the same cell subsets obtained from healthy individuals. However, no difference was observed between the subsets; CD19+ B cells collected from patients and healthy control individuals had similar telomerase activity and telomere length which was significantly different from the values found in T cells. The telomere length was significantly shorter in CLA+ CD3+ subset than in CLA- CD3+ subset. Interestingly, increased telomerase activity and shortened telomere length was also detected in CD4+ T cells from patients with parapsoriasis indicating that alteration of telomerase activity and telomere length in CD4+ T cells is an early event in the pathogenesis of cutaneous T-cell lymphoma. Thus, the results indicate that a significant high level of telomerase activity and shortened telomere length frequently occur in T cells of patients with CTCL and may reflect tumorigenesis.     

Chromosomal abnormalities in relation to clinical disease in patients with cutaneous T-cell lymphoma: a 5-year follow-up study

BACKGROUND: Patients with cutaneous T-cell lymphoma (CTCL) show chromosomal aberrations in skin and blood lymphocytes. OBJECTIVES: To evaluate the significance of peripheral blood clonal or non-clonal chromosomal abnormalities in comparison with the clinical course of cutaneous T-cell lymphoma patients. PATIENTS/METHODS: Five patients with large-plaque parapsoriasis (LPP) or with follicular mucinosis, eight with mycosis fungoides and two with Sézary syndrome were followed for an average of 54 months. G-banding and enzyme-detected in situ hybridization (EDISH) were used to identify aberrations in chromosomes 1, 6, 8, 9, 11, 13/21, 15 or 17, that had previously showed frequent aberrations. RESULTS: The aberration rates of all chromosomes studied differed between patients with active disease and healthy or photochemotherapy-treated controls by EDISH or G-banding (P < 0.01 to P < 0.05). Patients in complete remission differed from healthy controls for aberrations of chromosomes 1, 6 and 11, and from patients with active, progressing disease for chromosomes 1, 6, 8, 11 and 17 (P < 0.01 to P < 0.05, EDISH or G-banding). All 11 samples representing active, progressing disease showed elevated levels of chromosome 8 aberrations in EDISH. The change in chromosomal aberration rate and clinical condition between two consecutive samples agreed for chromosomes 1, 8, 9 and 15 (G-banding) and for chromosome 17 (G-banding and EDISH; kappa > 0.5-0.6). Six of seven patients (five CTCL, one LPP patient) with clonal chromosomal aberrations by G-banding showed continuously active disease and four of them, but none of the other patients, died within 30 months of the detection of the clone. CONCLUSIONS: The rate of chromosomal aberrations associates with the activity of CTCL, and has prognostic significance. Aberrations of chromosomes 1, 6 and 11, although increasing with activity of the disease, seem to be a hallmark of existing disease, detectable even in remission. Aberrations of chromosomes 8 and 17 especially associate with active or progressive disease.     

Dramatic response to brentuximab vedotin in refractory nontransformed CD30– mycosis fungoides allowing allogeneic stem cell transplant and long-term complete remission

The erythrodermic ulcerated form of mycosis fungoides (MF) is exceptional, and treatment of refractory cases is challenging. Brentuximab vedotin (BV) is a monoclonal antibody combined with monomethyl auristatin E, recently approved for the treatment of refractory CD30⁺ cutaneous T-cell lymphoma. We report a case of refractory MF in a 56-year-old man with a long history of large-plaque parapsoriasis, as revealed by psoriasiform erythroderma, treated initially with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) polychemotherapy, inducing a 2-year complete response. After relapse, interferon and gemcitabine were unsuccessful. Finally, treatment with BV was decided upon, despite the absence of CD30 expression. After three infusions of BV 1·8 mg kg⁻¹, we achieved a complete and stable response, allowing an allogeneic stem cell transplant. The patient is still in complete remission, 19 months after the graft. This case illustrates the possibility of using BV in refractory CD30^– MF as a salvage therapy.     

Meningeal involvement by a transformed mycosis fungoides following Hodgkin's disease

A 58-year-old man had long-standing lesions of presumed large plaque parapsoriasis. Following treatment for nodal Hodgkin's disease (HD), these became more infiltrated, with a diagnosis of mycosis fungoides (MF). A few months later, nodules appeared on the right leg, which was lymphoedematous after inguinal irradiation for HD. Histopathological examination showed CD3+, CD30-, CD15- large pleomorphic lymphocytes, leading to the diagnosis of transformed MF. The cutaneous lesions were successfully treated with topical nitrogen mustard and interferon alfa-2b then methotrexate, but his general health worsened with depression and malaise, without specific neurological symptoms or extracutaneous spreading of the lymphoma. Cerebral computed tomographic scan revealed a cerebellar subdural collection, arachnoid cyst and quadriventricular hydrocephaly, initially considered to be non-specific. After a few weeks, clinical symptoms of intracranial hypertension appeared, and a cerebrospinal fluid (CSF) examination revealed meningeal involvement by the lymphoma. These cells were CD3-negative and the diagnosis was confirmed by polymerase chain reaction (PCR) study, which revealed an identical clonal rearrangement of the T-cell receptor gamma gene between cutaneous biopsies and the CSF. Repeated intrathecal injections of methotrexate and cranial irradiation were performed and the patient was still alive after 13 months. This case illustrates the possible meningeal involvement of MF that may be preceded by atypical and mild neurological or psychiatric symptoms, which may be dissociated from the evolution of the cutaneous lesions. Moreover, PCR study may be useful for both diagnosis and monitoring.     

Cutaneous T-cell lymphoma (parapsoriasis en plaque). An association with pityriasis lichenoides et varioliformis acuta in young children

Pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC) are related benign disorders without recognized association with cutaneous T-cell lymphoma (CTCL). We report the cases of two children with documented PLEVA evolving into CTCL over several years. One child had the clinical lesions of PLC but the dermatopathologic findings of PLEVA at age 2 years. At age 12 years, he had skin changes of poikiloderma atrophicans vasculare and dermatopathologic findings consistent with parapsoriasis en plaque. The second child presented at age 7 years with scaling dermatitis and dermatopathologic findings of PLEVA. At age 12 years, the histologic diagnosis was parapsoriasis. Monoclonal antibody studies performed on biopsy specimens from both patients revealed 70% to 100% cells staining with CD5, 80% to 90% staining with CD4, 30% to 50% staining with CD8, and an increase in CD1-staining cells in the papillary dermis, indicating a predominantly helper T-cell infiltrate. We believe that PLC and PLEVA may be part of the spectrum of CTCL. Furthermore, CTCL may be more common in young children than once thought.     

The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants

Following consensus meetings of the two parent organizations, a new World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for primary cutaneous lymphomas has recently been published. This important development will now end the ongoing debate as to which of these was the preferred classification. The new classification will facilitate more uniformity in diagnosis, management and treatment of cutaneous lymphomas. In particular, it provides a useful distinction between indolent and more aggressive types of primary cutaneous lymphoma and provides practical advice on preferred management and treatment regimens. This will thereby prevent patients receiving high-grade treatment for low-grade biological disease. This review focuses on those diseases which have found new consensus agreement compared with the original WHO and EORTC classifications. In cutaneous T-cell lymphomas, these include folliculotropic mycosis fungoides, defining features of Sézary syndrome, primary cutaneous CD30+ lymphoproliferative disorders (primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis and borderline lesions) and subcutaneous panniculitis-like T-cell lymphoma. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are allocated provisional entry status and thereby afford better definitions for some cases of currently unspecified primary cutaneous peripheral T-cell lymphoma. In cutaneous B-cell lymphomas, diseases which have found new consensus agreement include primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular centre lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type and primary cutaneous diffuse large B-cell lymphoma, other. CD4+/CD56+ haematodermic neoplasm (early plasmacytoid dendritic cell leukaemia/lymphoma) now appears as a precursor haematological neoplasm and replaces the previous terminology of blastic NK-cell lymphoma. Other haematopoietic and lymphoid tumours involving the skin, as part of systemic disease, will appear in the forthcoming WHO publication Tumours of the Skin. The new classification raises interesting new problems and questions about primary cutaneous lymphoma and some of these are discussed in this article. It is, however, a splendid signpost indicating the direction in which research in cutaneous lymphoma needs to go. In the interim, we have an international consensus classification which is clinically meaningful.     

Staging laparotomy in cutaneous T-cell disease

Staging laparotomy performed in 13 patients with various forms of cutaneous T-cell disease (mycosis fungoides, Sézary syndrome, cutaneous lymphoma, atrophic parapsoriasis, and alopecia mucinosa) showed evidence of visceral or lymph node involvement in three (23%) patients; in two of these patients, noninvasive investigations and staging procedures did not disclose any abnormalities. All three patients were alive after a mean follow-up period of 3 1/2 years. In the ten patients with normal findings at laparotomy, the presence of intra-abdominal lymphoma was suggested in six by noninvasive staging procedures (lymphangiogram, spleen or liver-spleen scan, and computerized tomographic scan of the abdomen). Five of these ten patients died; four of the five patients died after relentless progression of the disease and visceral involvement. Staging laparotomy may have a role in the management of cutaneous T-cell disease because noninvasive investigations may be poor indicators of the presence or absence of intra-abdominal disease. The course of these patients, even those in whom laparotomies did not show any abnormalities, emphasizes the progressive potential of cutaneous T-cell disease.