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Expression of the Coxsackie adenovirus receptor in cutaneous T-cell lymphomas
P2101
P2103
Total skin electron beam irradiation in mycosis fungoides Ma Luisa Garcı´a-Melgares Linares, PhD, Servicio Dermatologia, Consorcio Hospital General Universitario de Valencia, Valencia, Spain; Elena Roche ´ n, PhD, Consorcio Hospital General Universitario de Valencia, Valencia, Gamo Spain; Amparo Gonza´lez Sanchı´s, PhD, Servicio Radioterapia, Consorcio Hospital General Universitario de Valencia, Valencia, Spain; Juan Jose´ Vilata Corell, PhD, Consorcio Hospital General Universitario de Valencia, Valencia, Spain Introduction: Mycosis fungoides (MF) is the most frequent cutaneous T-cell lymphoma, and radiotherapy is an effective treatment because of the high radiosensitivity of the neoplastic cells. The aim of this study is to review the clinical response of patients with MF treated with radiotherapy. Methods: From 1999 to 2005, 24 patients (14 men, 10 women, aged between 17 and 86 years) with mycosis fungoides were treated with total skin electron irradiation (TSEI) using the Stanford technique, a ‘‘Siemens Primus’’ linear accelerator with an electron energy of 6 MeV, and delivering the total dose of 36 Gy in 7 weeks of treatment (1 Gy/session, 5 sessions/week).
Expression of the Coxsackie adenovirus receptor in cutaneous T-cell lymphomas Joshua May, Louisiana State University Health Sciences Center School of Medicine, Shreveport, LA, United States; Jonathan Ledet, LSU Health Sciences Center School of Medicine, Shreveport, LA, United States; Mary LoweryNordberg, PhD, LSU Health Sciences Center, Shreveport, LA, United States; Francisco Turturro, PhD, LSU Health Sciences Center, Shreveport, LA, United States
Results: All patients were staged as follows: stage I, 10 patients; stage II, 8 patients; stage III, 5 patients; stage IV, 1 patient. Twenty patients were free of nodal or visceral involvement at the beginning of the treatment. All patients, except 2 of them, were previously treated for their MF. All patients completed treatment and had a minimum follow-up of 2 months (range, 2 to 69 months). The 6-year absolute survival rate was 91.6% (22 patients). Complete remission was achieved in 21 patients. Response duration, concerning only complete responders, are calculated from the time of documented complete remission until the date of documented relapse or death from MF, was between 1 and 9 months. If we consider all the patients who achieved complete remission, at the end of the 6-year follow-up period, the response duration varied from 1 to 69 months. Discussion: TSEI may be a curative treatment in stage I MF (T1-2, NO). In stages II and III, it has a palliative purpose, but could increase the duration of the complete response if it is combined with another modality of treatment for the MF. The current literature does not adequately support that overall survival is improved in patients who are treated with TSEI, but there is a general consensus about the fact that TSEI produces high response rates without severe toxicity. Commercial support: None identified.
Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders characterized by localization of the neoplastic T lymphocytes to the skin at presentation. The groups of clinicopathologic entities that comprise the CTCLs differ widely in biologic course, histologic appearance, and, in some cases, immunologic and cytogenetic features. Some of these features include the expression levels of anaplastic lymphoma kinase protein (ALK) and a cell-cell adhesion protein called the Coxsackie-adenovirus receptor (CAR). It has been well established that many primary cutaneous lymphomas of T-cell lineage have shown a high prevalence of ALK protein expression. In fact, the level of ALK expression in CTCLs, such as anaplastic large cell lymphoma (ALCL), has been shown to be an independent predictor of survival and can serve as a useful biologic marker for the disease. However, the association between CTCL and the level of CAR expression is not as well defined. CAR is the primary site for adenovirus attachment during infection and has been used as a delivery mechanism for gene therapies. The expression profile of the CAR receptor in cancer, particularly lymphomas, is poorly reported. The presence of CAR in CTCL may be helpful in developing therapeutic modalities such as gene or targeted molecular therapy. This report describes the immunohistochemical expression of CAR and ALK in 10 adult patients with cutaneous T-cell lymphomas who were treated with curative intent. The median age of the patients was 58 (range, 32 to 73). There were 7 men and 3 women. These included 5 cases of mycosis fungoides (MF), 4 of anaplastic large cell lymphoma (ALCL), and 1 peripheral T-cell lymphoma (PTCL). ALK staining was positive in 90% of the tissue samples. CAR staining was positive in 50% of the samples, ranging through all 3 types and all of which also showed concurrent ALK expression. In 20% of the samples, including a PTCL and an ALCL, CAR expression was [ 80% based on semiquantitative evaluation as percentage of positive cells. Positive ALK staining in 90% of the tissue samples is expected since there is established correlation between ALK expression and CTCL tumorigenesis. However, the presence of CAR in 50% of the cutaneous lymphomas suggests that CAR may play a role in the pathogenesis and its presence may be useful in developing therapeutic modalities such as gene therapy or targeted molecular therapy for their treatment. Commercial support: None identified.
P2102 Clinical, histopathologic features, and T-cell receptor gene rearrangement findings of cutaneous T-cell lymphoma in children Kee-Suck Suh, MD, Department of Dermatology, Kosin University College of Medicine, Busan, South Korea; Soo-Young Choi, MD, Department of Dermatology, Kosin University College of Medicine, Busan, South Korea; Young-Seung Jeon, MD, Department of Dermatology, Kosin University College of Medicine, Busan, South Korea; Sang-Tae Kim, MD, Department of Dermatology, Kosin University College of Medicine, Busan, South Korea Primary cutaneous T-cell lymphomas (CTCL) are rare in children and are mostly represented by mycosis fungoides and CD301 lymphoproliferative disorders. There has been increased recognition that CTCL may arise in children. Patients who were diagnosed with CTCL in young adulthood often report onset of symptoms during childhood. In this retrospective study, we reviewed the clinical, pathologic, TCR g gene rearrangement findings, and follow-up study of 22 CTCL patients under the age of 20. Patients included 20 cases (91%) of mycosis fungoides, one case of subcutaneous ‘‘panniculitis-like’’ T-cell lymphoma (SPTCL) and one case of CD 30 lymphoma. In 20 patients with MF, the mean disease duration was 2 years (range, 1 month - 10 years). Clinically, patches and plaques were observed in all cases. Based on TNM staging, all cases were classified as T1N0M0 (stage IA) or T2N0M0 (stage IB) that showed an early stage of mycosis fungoides. Histopathologic findings revealed epidermotrophism and a perivascular infiltrate in all 20 cases. In most cases, histopathologic findings showed Pautrier’s microabscess, haloed lymphocytes, coarse collagen in the papillary dermis, and atypical cells with hyperchromatic nuclei. TCR g gene rearrangement was performed except for one case and monoclonality was detected in 83% (15/18). In our series, the treatment modalities included PUVA, ultraviolet A-1, narrow band UVB, topical steroid, retinoic acid, and calcipotriol. Most of our patients showed a good response. A follow-up study was done for a mean period of 81.7 months in 20 cases of MF, there were no exacerbations of the disease or extracutaneous involvement. A female patient with primary cutaneous CD30 lymphoma was followed-up for 42 months. At present, she remains in clinical remission until the last follow-up. After an 11-year and 5-month follow-up in a case of subcutaneous ‘‘panniculitis-like’’ T-cell lymphoma, the combination chemotherapy was done. The therapy was well tolerated, and a complete remission was persisted for 7 months. However, she relapsed with multiple skin lesions. After an autologous blood stem cell transplantation, a complete remission was achieved. This study demonstrated that CTCL occurring in children were mostly MF. Compared with adult-onset MF, MF in children may show a variety of clinical features. A good prognosis is predicted in children with MF. Moreover, TCR gene rearrangement study is a useful diagnostic modality in children with MF.
Human T-cell leukemia virus (HTLV)-1 is a human retrovirus endemic to the Caribbean, Japan, South America and parts of Africa. HTLV-1 is known to spread via blood products, childbirth, and sexual intercourse. The vast majority of infected people do not develop sequelae. However, 2-5% of infected people develop one of two diseases: Adult T-cell leukemia/lymphoma (ATLL) or HTLV-1 associated myelopathy (HAM). This is a case of a 37-year-old female originally from Romania who presented with an unusual intensely pruritic generalized eruption of erythematous scaling papules coalescing into plaques. Skin biopsy revealed an atypical lymphoid infiltrate of large mononuclear cells with Pautrier’s microabscesses and extensive epidermotropism, suggestive of CTCL. The patient’s HTLV-1 serology was positive. Flow cytometry revealed 6.5% leukemic cells. A diagnosis of smoldering adult T-cell leukemia was made. The patient’s eruption improved with treatment of narrowband UVB and mid-potency topical steroids. ATLL associated with HTLV-1 infection was, until lately, limited to Japan; however, recent case reports of patients from Romania have been published. ATLL is an invariably fatal proliferative disorder of CD4 1 T-cells that is characterized by skin lesions, lymphadenopathy, hepatosplenomegaly, leukemia, lytic bone lesions, and hypercalcemia. Treatment of ATLL remains frustrating. Case reports of treatment with zidovudine in combination with IFN-alpha, arsenic trioxide in combination with IFN-alpha, allogenic stem cell transplantation, methylprednisolone in combination with cyclosporin A, immunotherapy with humanized monoclonal antibodies against IL-2 receptor, and PUVA have been published with equivocal results. This case of adult T-cell leukemia is unique because of the generalized papulosquamous eruption on presentation, the patient’s country of origin, and her initial response to narrow band UVB treatments.
Commercial support: None identified.
Commercial support: None identified.
FEBRUARY 2007
P2104 Human T-cell leukemia virus-1 infection progressing to adult T-cell lymphoma in a woman from Romania Nicole Fett, MD, UW Madison Hospital and Clinics, Madison, WI, United States; Gary Wood, MD, UW Madison Hospital and Clinics, Madison, WI, United States
J AM ACAD DERMATOL
AB139
P2103
Total skin electron beam irradiation in mycosis fungoides Ma Luisa Garcı´a-Melgares Linares, PhD, Servicio Dermatologia, Consorcio Hospital General Universitario de Valencia, Valencia, Spain; Elena Roche ´ n, PhD, Consorcio Hospital General Universitario de Valencia, Valencia, Gamo Spain; Amparo Gonza´lez Sanchı´s, PhD, Servicio Radioterapia, Consorcio Hospital General Universitario de Valencia, Valencia, Spain; Juan Jose´ Vilata Corell, PhD, Consorcio Hospital General Universitario de Valencia, Valencia, Spain Introduction: Mycosis fungoides (MF) is the most frequent cutaneous T-cell lymphoma, and radiotherapy is an effective treatment because of the high radiosensitivity of the neoplastic cells. The aim of this study is to review the clinical response of patients with MF treated with radiotherapy. Methods: From 1999 to 2005, 24 patients (14 men, 10 women, aged between 17 and 86 years) with mycosis fungoides were treated with total skin electron irradiation (TSEI) using the Stanford technique, a ‘‘Siemens Primus’’ linear accelerator with an electron energy of 6 MeV, and delivering the total dose of 36 Gy in 7 weeks of treatment (1 Gy/session, 5 sessions/week).
Expression of the Coxsackie adenovirus receptor in cutaneous T-cell lymphomas Joshua May, Louisiana State University Health Sciences Center School of Medicine, Shreveport, LA, United States; Jonathan Ledet, LSU Health Sciences Center School of Medicine, Shreveport, LA, United States; Mary LoweryNordberg, PhD, LSU Health Sciences Center, Shreveport, LA, United States; Francisco Turturro, PhD, LSU Health Sciences Center, Shreveport, LA, United States
Results: All patients were staged as follows: stage I, 10 patients; stage II, 8 patients; stage III, 5 patients; stage IV, 1 patient. Twenty patients were free of nodal or visceral involvement at the beginning of the treatment. All patients, except 2 of them, were previously treated for their MF. All patients completed treatment and had a minimum follow-up of 2 months (range, 2 to 69 months). The 6-year absolute survival rate was 91.6% (22 patients). Complete remission was achieved in 21 patients. Response duration, concerning only complete responders, are calculated from the time of documented complete remission until the date of documented relapse or death from MF, was between 1 and 9 months. If we consider all the patients who achieved complete remission, at the end of the 6-year follow-up period, the response duration varied from 1 to 69 months. Discussion: TSEI may be a curative treatment in stage I MF (T1-2, NO). In stages II and III, it has a palliative purpose, but could increase the duration of the complete response if it is combined with another modality of treatment for the MF. The current literature does not adequately support that overall survival is improved in patients who are treated with TSEI, but there is a general consensus about the fact that TSEI produces high response rates without severe toxicity. Commercial support: None identified.
Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders characterized by localization of the neoplastic T lymphocytes to the skin at presentation. The groups of clinicopathologic entities that comprise the CTCLs differ widely in biologic course, histologic appearance, and, in some cases, immunologic and cytogenetic features. Some of these features include the expression levels of anaplastic lymphoma kinase protein (ALK) and a cell-cell adhesion protein called the Coxsackie-adenovirus receptor (CAR). It has been well established that many primary cutaneous lymphomas of T-cell lineage have shown a high prevalence of ALK protein expression. In fact, the level of ALK expression in CTCLs, such as anaplastic large cell lymphoma (ALCL), has been shown to be an independent predictor of survival and can serve as a useful biologic marker for the disease. However, the association between CTCL and the level of CAR expression is not as well defined. CAR is the primary site for adenovirus attachment during infection and has been used as a delivery mechanism for gene therapies. The expression profile of the CAR receptor in cancer, particularly lymphomas, is poorly reported. The presence of CAR in CTCL may be helpful in developing therapeutic modalities such as gene or targeted molecular therapy. This report describes the immunohistochemical expression of CAR and ALK in 10 adult patients with cutaneous T-cell lymphomas who were treated with curative intent. The median age of the patients was 58 (range, 32 to 73). There were 7 men and 3 women. These included 5 cases of mycosis fungoides (MF), 4 of anaplastic large cell lymphoma (ALCL), and 1 peripheral T-cell lymphoma (PTCL). ALK staining was positive in 90% of the tissue samples. CAR staining was positive in 50% of the samples, ranging through all 3 types and all of which also showed concurrent ALK expression. In 20% of the samples, including a PTCL and an ALCL, CAR expression was [ 80% based on semiquantitative evaluation as percentage of positive cells. Positive ALK staining in 90% of the tissue samples is expected since there is established correlation between ALK expression and CTCL tumorigenesis. However, the presence of CAR in 50% of the cutaneous lymphomas suggests that CAR may play a role in the pathogenesis and its presence may be useful in developing therapeutic modalities such as gene therapy or targeted molecular therapy for their treatment. Commercial support: None identified.
P2102 Clinical, histopathologic features, and T-cell receptor gene rearrangement findings of cutaneous T-cell lymphoma in children Kee-Suck Suh, MD, Department of Dermatology, Kosin University College of Medicine, Busan, South Korea; Soo-Young Choi, MD, Department of Dermatology, Kosin University College of Medicine, Busan, South Korea; Young-Seung Jeon, MD, Department of Dermatology, Kosin University College of Medicine, Busan, South Korea; Sang-Tae Kim, MD, Department of Dermatology, Kosin University College of Medicine, Busan, South Korea Primary cutaneous T-cell lymphomas (CTCL) are rare in children and are mostly represented by mycosis fungoides and CD301 lymphoproliferative disorders. There has been increased recognition that CTCL may arise in children. Patients who were diagnosed with CTCL in young adulthood often report onset of symptoms during childhood. In this retrospective study, we reviewed the clinical, pathologic, TCR g gene rearrangement findings, and follow-up study of 22 CTCL patients under the age of 20. Patients included 20 cases (91%) of mycosis fungoides, one case of subcutaneous ‘‘panniculitis-like’’ T-cell lymphoma (SPTCL) and one case of CD 30 lymphoma. In 20 patients with MF, the mean disease duration was 2 years (range, 1 month - 10 years). Clinically, patches and plaques were observed in all cases. Based on TNM staging, all cases were classified as T1N0M0 (stage IA) or T2N0M0 (stage IB) that showed an early stage of mycosis fungoides. Histopathologic findings revealed epidermotrophism and a perivascular infiltrate in all 20 cases. In most cases, histopathologic findings showed Pautrier’s microabscess, haloed lymphocytes, coarse collagen in the papillary dermis, and atypical cells with hyperchromatic nuclei. TCR g gene rearrangement was performed except for one case and monoclonality was detected in 83% (15/18). In our series, the treatment modalities included PUVA, ultraviolet A-1, narrow band UVB, topical steroid, retinoic acid, and calcipotriol. Most of our patients showed a good response. A follow-up study was done for a mean period of 81.7 months in 20 cases of MF, there were no exacerbations of the disease or extracutaneous involvement. A female patient with primary cutaneous CD30 lymphoma was followed-up for 42 months. At present, she remains in clinical remission until the last follow-up. After an 11-year and 5-month follow-up in a case of subcutaneous ‘‘panniculitis-like’’ T-cell lymphoma, the combination chemotherapy was done. The therapy was well tolerated, and a complete remission was persisted for 7 months. However, she relapsed with multiple skin lesions. After an autologous blood stem cell transplantation, a complete remission was achieved. This study demonstrated that CTCL occurring in children were mostly MF. Compared with adult-onset MF, MF in children may show a variety of clinical features. A good prognosis is predicted in children with MF. Moreover, TCR gene rearrangement study is a useful diagnostic modality in children with MF.
Human T-cell leukemia virus (HTLV)-1 is a human retrovirus endemic to the Caribbean, Japan, South America and parts of Africa. HTLV-1 is known to spread via blood products, childbirth, and sexual intercourse. The vast majority of infected people do not develop sequelae. However, 2-5% of infected people develop one of two diseases: Adult T-cell leukemia/lymphoma (ATLL) or HTLV-1 associated myelopathy (HAM). This is a case of a 37-year-old female originally from Romania who presented with an unusual intensely pruritic generalized eruption of erythematous scaling papules coalescing into plaques. Skin biopsy revealed an atypical lymphoid infiltrate of large mononuclear cells with Pautrier’s microabscesses and extensive epidermotropism, suggestive of CTCL. The patient’s HTLV-1 serology was positive. Flow cytometry revealed 6.5% leukemic cells. A diagnosis of smoldering adult T-cell leukemia was made. The patient’s eruption improved with treatment of narrowband UVB and mid-potency topical steroids. ATLL associated with HTLV-1 infection was, until lately, limited to Japan; however, recent case reports of patients from Romania have been published. ATLL is an invariably fatal proliferative disorder of CD4 1 T-cells that is characterized by skin lesions, lymphadenopathy, hepatosplenomegaly, leukemia, lytic bone lesions, and hypercalcemia. Treatment of ATLL remains frustrating. Case reports of treatment with zidovudine in combination with IFN-alpha, arsenic trioxide in combination with IFN-alpha, allogenic stem cell transplantation, methylprednisolone in combination with cyclosporin A, immunotherapy with humanized monoclonal antibodies against IL-2 receptor, and PUVA have been published with equivocal results. This case of adult T-cell leukemia is unique because of the generalized papulosquamous eruption on presentation, the patient’s country of origin, and her initial response to narrow band UVB treatments.
Commercial support: None identified.
Commercial support: None identified.
FEBRUARY 2007
P2104 Human T-cell leukemia virus-1 infection progressing to adult T-cell lymphoma in a woman from Romania Nicole Fett, MD, UW Madison Hospital and Clinics, Madison, WI, United States; Gary Wood, MD, UW Madison Hospital and Clinics, Madison, WI, United States
J AM ACAD DERMATOL
AB139