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patch stage mycosis fungoides successfully treated with ingenol mebutate
2434
2920
Peripheral T-cell lymphoma, not otherwise specified with prominent cutaneous involvement Ben Friedman, MD, Henry Ford Hospital, Department of Dermatology, Detroit, MI, United States; Chauncey McHargue, MD, Henry Ford Hospital, Department of Dermatology, Detroit, MI, United States; Michael Nauss, MD, Henry Ford Hospital, Department of Emergency Medicine, Detroit, MI, United States
Plaque/patch stage mycosis fungoides successfully treated with ingenol mebutate Eve Lebas, MD, CHU du Sart Tilman, Liege, Belgium; Florence Libon, MD, CHU du Sart Tilman, Liege, Belgium; Pascale Quatresooz, MD, PhD, CHU du Sart Tilman, Liege, Belgium; Arjen F. Nikkels, MD, PhD, CHU du Sart Tilman, Dept of Dermatology, Liege, Belgium
A 39-year-old African American man presented to our emergency department with an approximately 1-year history of painful enlarging skin nodules. Examination revealed multiple, variably sized, indurated skin nodules, with central ulceration and yellowbrown crusting distributed on the scalp, face, umbilicus, buttocks, bilateral thighs and right arm. In addition, there was palpable matted lymphadenopathy in both the axillae and groin. Multiple skin biopsies and an excisional lymph node biopsy from the right axillae were obtained. Histopathologic analysis of the skin revealed a nodular lymphohistiocytic infiltrate filling the dermis, which consisted of many large and atypical lymphocytes. No significant epidermotropism was identified though there were some focal areas of perifollicular necrosis. A T-cell gene rearrangement study revealed a monoclonal population of cells which on further immunotyping was consistent with a mature CD4+ T-cell lymphoma. Similar analysis together with flow cytometry of the sampled lymph node revealed identical morphologic and immunophenotypic features of lymphoma as detected in the skin. A staging positron emission tomography computed tomography (PET-CT) scan revealed intense fluorodeoxyglucose uptake in the lymph nodes of neck, parotid glands, axillae, inguinal and iliac chains, as well as spleen. Bone marrow biopsy, flow cytometry of the blood and bone marrow and human T-cell lymphotropic virus-1/2 serologies were negative. In view of these findings, a diagnosis of peripheral T-cell lymphoma, not otherwise specified (PTCL- NOS) was rendered with a stage of IIIES. PTCL-NOS, is a poorly defined and heterogeneous group of predominantly nodal T-cell lymphomas not meeting histopathologic or immunophenotypical criteria for the other well-defined subtypes of peripheral T-cell lymphoma. Initial treatment may include cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP) -based chemotherapy, radiation therapy and/or autologous hematopoietic cell transplantation. The prognosis is considered poor, with previously reported 5-year survival rates of under 20%. Our patient was initially treated with radiation to reduce the size of the larger and most symptomatic tumors. He then completed 6 cycles of CHOP-Etoposide, with follow-up PET-CT revealing interval resolution of all the previously identified foci of lymphoma. All skin lesions have been replaced by atrophic hypopigmented scars.
Introduction and objectives: Topical treatment options for patch/plaque stage mycosis fungoides (MF) and folliculotropic MF (FMF) include, among others, topical potent steroids, topical chemotherapy (carmustin, metchloramine), imiquimod, resiquimod, topical methotrexate and retinoids. Ingenol mebutate (PEP005) is a new topical field-directed treatment option for actinic keratosis. Furthermore, PEP005 has demonstrated in vitro and in vivo effectiveness on melanoma and melanoma cell lines. The action mechanisms of PEP005 are related to the induction of proinflammatory events (PMN oxidative burst and keratinocyte cytokine release) and apoptosis. Whether PEP005 is clinically effective for MF and FMF remains undetermined. Materials and methods: In four male patients suffering from longstanding and extensive MF (n ¼ 3) and FMF (n ¼ 1), stage T2b, a single target lesion was selected for mebutate therapy (0.05%, 2 applications at 1 week interval). All patients received furthermore systemic methotrexate (15-20 mg/w). Biopsies were performed at 2 months as well as photographic recordings. Results: All the patients experienced treatment related adverse effects including, burning sensations, slight oozing and crusting for 3 to 5 days. The skin biopsies of all the patients revealed signs of postinflammatory hyperpigmentation without further signs of MF of FMF. Immunohistochemistry did not favor MF or FMF. No monoclonal TCR rearrangement was observed in any of the biopsies. Conclusion: Topical mebutate ingenol 0.05% may be considered as effective alternative topical treatment for localized plaques/patches of MF and FMF. Larger studies are required to establish efficacy and tolerance as well as the place of mebutate ingenol in the therapeutic armamentarium of MF. Commercial support: None identified.
Commercial support: None identified.
3839 Persistent agmination of lymphomatoid papulosis—Case series and review of the literature You-Chen Serena Liu, MD, Hsinchu Cathay General Hospital, Hsinchu City, Taiwan; Cher-Wei Liang, MD, National Taiwan University Hospital, Taipei, Taiwan; Hsien-Ching Chiu, MD, National Taiwan University Hospital, Taipei, Taiwan Introduction: Persistent agmination of lymphomatoid papulosis (PALP) is a chronic recurrent disease with clustered papulonecrotic lesions circumscribed within a mycosis fungoides (MF)-like patch area, usually on the trunk and thighs. We report two cases of persistent agmination of lymphomatoid papulosis. Case report: Case 1: A 33-year-old male presented with two asymptomatic, palm-sized, mild scaly erythematous patches studded with several agminated papules on the left anterior thigh for two years. The skin biopsy showed dense subepidermal small lymphocytic infiltration with significant epidermotropism of single cells or cell clusters (which were immunohistochemically CD3+/CD20-), and large CD30+ atypical cells in the dermis. The initial diagnosis was mycosis fungoides with CD30+ transformation. Staging work-up included normal findings in complete blood cell count, differential count, whole body positron emission tomography - computed tomography, and bone marrow biopsy. He was treated with photochemotherapy and localized electron beam radiation therapy, and there was no other organ involvement in the following eight years. The skin lesions would reappear on his trunk, arms or thighs after several months of remission. Given the clinical features with recurrent course, histological characters suggestive of lymphomatoid papulosis type A, we diagnosed this patient as persistent agmination of lymphomatoid papulosis (PALP) mimicking limited papular and patchy mycosis fungoides. Case 2: A 53-year-old female had recurrent mild itchy clustered pea-sized papules within a palmsized patch over her bilateral thighs for more than one year. Pathology revealed perivascular and upper dermal diffuse infiltration of small lymphocytes and some large CD30+ atypical cells, which was compatible with lymphomatoid papulosis type C. The lesions had partial response to topical clobetasol, but did not remit completely. Discussion: Persistent agmination of lymphomatoid papulosis was first described in 2007 and 16 cases had been reported in the English literature. Age of onset ranges from 6 to 62 years old. The lesions involve circumscribed areas of trunk and thighs with persistent localized eruptions of papulonodules. It runs a chronic course with lesions appearing up to 12 years, waxing and waning without complete resolution if left untreated. Histology displays features of a CD30+ lymphoproliferative disorder, 80% compatible with lymphomatoid papulosis type A. PALP differs from localized or regional lymphomatoid papulosis in its specific morphology with multiple anatomic areas, and MF-like characteristics. Papular mycosis fungoides should also be differentiated from PALP, but it lacks typical patches, does not resolve spontaneously, and the cells are CD30- immunohistologically. Clinical behavior and outcome of PALP are usually benign. Staging work-up has not revealed systemic involvement. Most of the cases had long-standing remissions after localized radiotherapy, but one progressed to MF-type cutaneous T cell lymphoma. There remains an ongoing debate concerning whether PALP represents a composite lymphoma such as anaplastic large-cell lymphoma, which will warrant further treatment and close follow-ups. Commercial support: None identified.
MAY 2016
2922 Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma, rare subtype of cutaneous T-cell lymphoma in a Chinese patient Wen Chun Liu, MBBS, National Skin Centre, Singapore, Singapore; Chee Leong Cheng, MBBS, Singapore General Hospital, Singapore, Singapore; Haur Yueh Lee, MBBS, Dermatology Unit, Singapore General Hospital, Singapore, Singapore Background: Primary cutaneous aggressive epidermotropic CD8 T-cell lymphoma (PCAETCL) is a rare subtype of cutaneous T-cell lymphoma (CTCL). Patients present with a rapidly progressive course, clinically manifest as widely distributed ulcerative lesions which are histopathologically characterized by epidermotropic infiltrates of CD8 cytotoxic T cells. PCAETCL runs an aggressive course with a high tendency to spread to extranodal sites. Unfortunately, treatment response to conventional therapies is poor, leading to an unfavorable prognosis. Case study: We report a case of PCAECTL in a Chinese patient with a long standing psoriasiform rash presenting with new onset of ulcerative lesions. Histology revealed CD 8+ epidermotropic lymphoma. In view of the aggressive clinical history, immunohistochemistry findings and absence of systemic and visceral involvement, a diagnosis of primary cutaneous aggressive epidermotropic CD 8+ cytotoxic T-cell lymphoma was made. Patient received CHOP chemotherapy but suffered relapses with recurrent plaques and tumors over the body requiring subsequent radiotherapy. Discussion: Differential diagnoses of other types of CD8+ lymphoma are discussed. Conclusion: Primary cutaneous aggressive epidermotropic CD8 T-cell lymphoma is a rare lymphoma and its aggressive clinical course with poor treatment response is observed in this Chinese patient. It is a rare but important diagnosis not to be missed in patients presenting with ulceration of preexisting dermatoses or new primary ulcerative lesions. Commercial support: None identified.
J AM ACAD DERMATOL
AB181
2920
Peripheral T-cell lymphoma, not otherwise specified with prominent cutaneous involvement Ben Friedman, MD, Henry Ford Hospital, Department of Dermatology, Detroit, MI, United States; Chauncey McHargue, MD, Henry Ford Hospital, Department of Dermatology, Detroit, MI, United States; Michael Nauss, MD, Henry Ford Hospital, Department of Emergency Medicine, Detroit, MI, United States
Plaque/patch stage mycosis fungoides successfully treated with ingenol mebutate Eve Lebas, MD, CHU du Sart Tilman, Liege, Belgium; Florence Libon, MD, CHU du Sart Tilman, Liege, Belgium; Pascale Quatresooz, MD, PhD, CHU du Sart Tilman, Liege, Belgium; Arjen F. Nikkels, MD, PhD, CHU du Sart Tilman, Dept of Dermatology, Liege, Belgium
A 39-year-old African American man presented to our emergency department with an approximately 1-year history of painful enlarging skin nodules. Examination revealed multiple, variably sized, indurated skin nodules, with central ulceration and yellowbrown crusting distributed on the scalp, face, umbilicus, buttocks, bilateral thighs and right arm. In addition, there was palpable matted lymphadenopathy in both the axillae and groin. Multiple skin biopsies and an excisional lymph node biopsy from the right axillae were obtained. Histopathologic analysis of the skin revealed a nodular lymphohistiocytic infiltrate filling the dermis, which consisted of many large and atypical lymphocytes. No significant epidermotropism was identified though there were some focal areas of perifollicular necrosis. A T-cell gene rearrangement study revealed a monoclonal population of cells which on further immunotyping was consistent with a mature CD4+ T-cell lymphoma. Similar analysis together with flow cytometry of the sampled lymph node revealed identical morphologic and immunophenotypic features of lymphoma as detected in the skin. A staging positron emission tomography computed tomography (PET-CT) scan revealed intense fluorodeoxyglucose uptake in the lymph nodes of neck, parotid glands, axillae, inguinal and iliac chains, as well as spleen. Bone marrow biopsy, flow cytometry of the blood and bone marrow and human T-cell lymphotropic virus-1/2 serologies were negative. In view of these findings, a diagnosis of peripheral T-cell lymphoma, not otherwise specified (PTCL- NOS) was rendered with a stage of IIIES. PTCL-NOS, is a poorly defined and heterogeneous group of predominantly nodal T-cell lymphomas not meeting histopathologic or immunophenotypical criteria for the other well-defined subtypes of peripheral T-cell lymphoma. Initial treatment may include cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP) -based chemotherapy, radiation therapy and/or autologous hematopoietic cell transplantation. The prognosis is considered poor, with previously reported 5-year survival rates of under 20%. Our patient was initially treated with radiation to reduce the size of the larger and most symptomatic tumors. He then completed 6 cycles of CHOP-Etoposide, with follow-up PET-CT revealing interval resolution of all the previously identified foci of lymphoma. All skin lesions have been replaced by atrophic hypopigmented scars.
Introduction and objectives: Topical treatment options for patch/plaque stage mycosis fungoides (MF) and folliculotropic MF (FMF) include, among others, topical potent steroids, topical chemotherapy (carmustin, metchloramine), imiquimod, resiquimod, topical methotrexate and retinoids. Ingenol mebutate (PEP005) is a new topical field-directed treatment option for actinic keratosis. Furthermore, PEP005 has demonstrated in vitro and in vivo effectiveness on melanoma and melanoma cell lines. The action mechanisms of PEP005 are related to the induction of proinflammatory events (PMN oxidative burst and keratinocyte cytokine release) and apoptosis. Whether PEP005 is clinically effective for MF and FMF remains undetermined. Materials and methods: In four male patients suffering from longstanding and extensive MF (n ¼ 3) and FMF (n ¼ 1), stage T2b, a single target lesion was selected for mebutate therapy (0.05%, 2 applications at 1 week interval). All patients received furthermore systemic methotrexate (15-20 mg/w). Biopsies were performed at 2 months as well as photographic recordings. Results: All the patients experienced treatment related adverse effects including, burning sensations, slight oozing and crusting for 3 to 5 days. The skin biopsies of all the patients revealed signs of postinflammatory hyperpigmentation without further signs of MF of FMF. Immunohistochemistry did not favor MF or FMF. No monoclonal TCR rearrangement was observed in any of the biopsies. Conclusion: Topical mebutate ingenol 0.05% may be considered as effective alternative topical treatment for localized plaques/patches of MF and FMF. Larger studies are required to establish efficacy and tolerance as well as the place of mebutate ingenol in the therapeutic armamentarium of MF. Commercial support: None identified.
Commercial support: None identified.
3839 Persistent agmination of lymphomatoid papulosis—Case series and review of the literature You-Chen Serena Liu, MD, Hsinchu Cathay General Hospital, Hsinchu City, Taiwan; Cher-Wei Liang, MD, National Taiwan University Hospital, Taipei, Taiwan; Hsien-Ching Chiu, MD, National Taiwan University Hospital, Taipei, Taiwan Introduction: Persistent agmination of lymphomatoid papulosis (PALP) is a chronic recurrent disease with clustered papulonecrotic lesions circumscribed within a mycosis fungoides (MF)-like patch area, usually on the trunk and thighs. We report two cases of persistent agmination of lymphomatoid papulosis. Case report: Case 1: A 33-year-old male presented with two asymptomatic, palm-sized, mild scaly erythematous patches studded with several agminated papules on the left anterior thigh for two years. The skin biopsy showed dense subepidermal small lymphocytic infiltration with significant epidermotropism of single cells or cell clusters (which were immunohistochemically CD3+/CD20-), and large CD30+ atypical cells in the dermis. The initial diagnosis was mycosis fungoides with CD30+ transformation. Staging work-up included normal findings in complete blood cell count, differential count, whole body positron emission tomography - computed tomography, and bone marrow biopsy. He was treated with photochemotherapy and localized electron beam radiation therapy, and there was no other organ involvement in the following eight years. The skin lesions would reappear on his trunk, arms or thighs after several months of remission. Given the clinical features with recurrent course, histological characters suggestive of lymphomatoid papulosis type A, we diagnosed this patient as persistent agmination of lymphomatoid papulosis (PALP) mimicking limited papular and patchy mycosis fungoides. Case 2: A 53-year-old female had recurrent mild itchy clustered pea-sized papules within a palmsized patch over her bilateral thighs for more than one year. Pathology revealed perivascular and upper dermal diffuse infiltration of small lymphocytes and some large CD30+ atypical cells, which was compatible with lymphomatoid papulosis type C. The lesions had partial response to topical clobetasol, but did not remit completely. Discussion: Persistent agmination of lymphomatoid papulosis was first described in 2007 and 16 cases had been reported in the English literature. Age of onset ranges from 6 to 62 years old. The lesions involve circumscribed areas of trunk and thighs with persistent localized eruptions of papulonodules. It runs a chronic course with lesions appearing up to 12 years, waxing and waning without complete resolution if left untreated. Histology displays features of a CD30+ lymphoproliferative disorder, 80% compatible with lymphomatoid papulosis type A. PALP differs from localized or regional lymphomatoid papulosis in its specific morphology with multiple anatomic areas, and MF-like characteristics. Papular mycosis fungoides should also be differentiated from PALP, but it lacks typical patches, does not resolve spontaneously, and the cells are CD30- immunohistologically. Clinical behavior and outcome of PALP are usually benign. Staging work-up has not revealed systemic involvement. Most of the cases had long-standing remissions after localized radiotherapy, but one progressed to MF-type cutaneous T cell lymphoma. There remains an ongoing debate concerning whether PALP represents a composite lymphoma such as anaplastic large-cell lymphoma, which will warrant further treatment and close follow-ups. Commercial support: None identified.
MAY 2016
2922 Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma, rare subtype of cutaneous T-cell lymphoma in a Chinese patient Wen Chun Liu, MBBS, National Skin Centre, Singapore, Singapore; Chee Leong Cheng, MBBS, Singapore General Hospital, Singapore, Singapore; Haur Yueh Lee, MBBS, Dermatology Unit, Singapore General Hospital, Singapore, Singapore Background: Primary cutaneous aggressive epidermotropic CD8 T-cell lymphoma (PCAETCL) is a rare subtype of cutaneous T-cell lymphoma (CTCL). Patients present with a rapidly progressive course, clinically manifest as widely distributed ulcerative lesions which are histopathologically characterized by epidermotropic infiltrates of CD8 cytotoxic T cells. PCAETCL runs an aggressive course with a high tendency to spread to extranodal sites. Unfortunately, treatment response to conventional therapies is poor, leading to an unfavorable prognosis. Case study: We report a case of PCAECTL in a Chinese patient with a long standing psoriasiform rash presenting with new onset of ulcerative lesions. Histology revealed CD 8+ epidermotropic lymphoma. In view of the aggressive clinical history, immunohistochemistry findings and absence of systemic and visceral involvement, a diagnosis of primary cutaneous aggressive epidermotropic CD 8+ cytotoxic T-cell lymphoma was made. Patient received CHOP chemotherapy but suffered relapses with recurrent plaques and tumors over the body requiring subsequent radiotherapy. Discussion: Differential diagnoses of other types of CD8+ lymphoma are discussed. Conclusion: Primary cutaneous aggressive epidermotropic CD8 T-cell lymphoma is a rare lymphoma and its aggressive clinical course with poor treatment response is observed in this Chinese patient. It is a rare but important diagnosis not to be missed in patients presenting with ulceration of preexisting dermatoses or new primary ulcerative lesions. Commercial support: None identified.
J AM ACAD DERMATOL
AB181