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Clearance of refractory nodular and follicular mycosis fungoides with topical 5% imiquimod
P7852
P8637
Blastic plasmacytoid dendritic cell neoplasm: An asymptommatic nodular eruption masking an internal malignancy Israel Andrews, MD, Roger Williams Medical Center: Department of Dermatology & Skin Surgery, Providence, RI, United States; Laura Della Torre, MD, Roger Williams Medical Center: Department of Dermatology & Skin Surgery, Providence, RI, United States Blastic plasmacytoid dendritic cell neoplasm (BPDCN), first described in 1994, is a rare hematologic malignancy derived from the precursor of plasmacytoid dendritic cells. Categorized by the World Health Organization as an acute myeloid leukemia, BPDCN has a characteristic phenotype of CD4 and CD56 positive lymphocytes with [90% of cases reported expressing CD123, a marker for plasmacytoid dendritic cells. A literature review of approximately 200 reports of BPDCN has found involvement limited to the skin in 50% of cases. Cutaneous involvement may present as solitary or multifocal nodules, patch-plaques, or ecchymoses. BPDCN can be limited to the skin, lymph nodes or the bone marrow, but several reports have shown that tumor infiltration can involve any combination of these systems. In 1 series of 30 patients, 57% demonstrated limited cutaneous involvement while 4% had cutaneous, bone marrow, and lymphatic disease. Prognosis, while independent of system involvement, is poor, with a median survival following diagnosis of 14 months. Although allogeneic stem cell transplantation with myeloablative therapy has yielded the most effective outcomes, there is no consensus for an optimal treatment of BPDCN. We report the case of a 69-year-old male who presented with multifocal asymptomatic cutaneous nodules that on pathology and immunohistochemical analysis was consistent with blastic plasmacytoid dendritic cell neoplasm. A systemic work-up of BPDCN, including complete system analysis, revealed a gastrointestinal adenocarcinoma with multiorgan metastasis, but failed to reveal any additional involvement of the BPDCN. Treatment was initiated for the adenocarcinoma with carboplatin and gemcitabine. Resolution of the cutaneous lesions occurred following the second cycle of chemotherapy. A repeat biopsy was performed at the site where a cutaneous nodule had previously existed, demonstrating no evidence of BPDCN. The patient later succumbed to his internal malignancy. Blastic plasmacytoid dendritic cell neoplasm can present with cutaneous involvement alone; however, a complete work-up of the blood, bone marrow, lymphatic system, and additional internal systems should follow. Despite the initial presentation of BPDCN, and independent to the manner of its involvement, this malignancy should be pursued aggressively. More data are necessary in order to develop an optimal treatment strategy for this malignancy.
Cutaneous composite lymphoma in the setting of chronic patch-stage mycosis fungoides Katherine Willard, MD, Mayo Clinic, Jacksonville, FL, United States; Jason Sluzevich, MD, Mayo Clinic, Jacksonville, FL, United States Composite lymphoma is defined as $ 2 distinctly separate populations of malignant lymphocytes in the same organ or tissue at the same site. Cutaneous composite lymphoma, consisting of concurrent B-cell and T-cell neoplasms, is exceedingly rare and has previously been described in the setting of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). Here, we describe a patient with chronic patch-stage mycosis fungoides who developed a composite lymphoma comprised of a distinct cutaneous marginal zone lymphoma in the same tissue site of previously established patch-stage mycosis fungoides. To our knowledge, this is the first described case of a cutaneous composite lymphoma consisting of these particular concurrent neoplasms. A 73-year-old man with chronic patch-stage mycosis fungoides presented with the acute onset of indurated, smooth papules within several chronic annular patches of mycosis fungoides. Skin biopsy revealed discrete nodular aggregates of atypical B-cells positive for CD79a, CD20, and BCL-2 and negative for CD5, BCL-6, and CD10, consistent with marginal zone lymphoma. These aggregates were surrounded by a T-cell infiltrate that was positive for CD3 and CD4, negative for CD8 and CD30, and otherwise histopathologically consistent with mycosis fungoides with band-like inflammation at the dermal epidermal junction. Immunoglobulin IgH gene rearrangement studies were positive for a clonal B-cell population. TCR gene rearrangement was positive for clonality and demonstrated an identical clonal T-cell population to that previously seen on initial diagnosis of mycosis fungoides. PET-CT staging was negative for nodal or systemic involvement. The phenomenon of composite lymphoma in the skin is exceptionally rare or otherwise underreported. It is suggested that the phenotypic and genotypic features of malignant cell infiltrates be included in the criteria for diagnosis of cutaneous composite lymphoma in addition to the requirement for morphologically distinct neoplasms at the same site. This case illustrates the utility of molecular techniques in identifying these independent malignant subpopulations that should be present when making a diagnosis of cutaneous composite lymphoma. Commercial support: None identified.
Commercial support: None identified.
P8478 Diagnostic challenge in extranodal NK/T lymphoma, nasal type Juan M. Ruiz-Matta, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico; Judith Domınguez-Cherit, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico; Marcela Saeb-Lima, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico; Michelle Gatica-Torres, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico; Silvia Mendez-Flores, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico
P8557 Clearance of refractory nodular and follicular mycosis fungoides with topical 5% imiquimod Matthew Gordon, MD, Mayo Clinic, Jacksonville, FL, United States; Anokhi Jambusaria, MD, MS, Mayo Clinic, Jacksonville, FL, United States; Jason Sluzevich, MD, Mayo Clinic, Jacksonville, FL, United States We present 2 patients with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type, resistant to multiple previous therapies that clinically cleared with the use of topical imiquimod 5% cream. Patient 1 is an 80-year-old female with a 15-year history of MF, stage IB, with a 6-year history of progressive involvement of the periocular skin despite previous use of class I topical corticosteroids, carmustine, bexarotene, PUVA, and systemic methotrexate. Physical examination revealed infiltrated plaques involving the left upper and lower eyelids and right nasal sidewall with variable alopecia. Biopsies confirmed mycosis fungoides with follicular involvement. Monotherapy with topical imiquimod 5% cream initiated at twice weekly and titrated to 3 times weekly resulted in complete clinical clearance after 6 months of therapy with no recurrence after 3 months since discontinuation. Patient 2 is a 65-year-old male with a 6-month history of MF, stage IIB, with a refractory tumor involving the right ankle and instep of plantar foot resistant to topical class I corticosteroids and narrowband UVB phototherapy. Treatment with imiquimod 5% cream 5 times per week resulted in clearance after 2 months with no recurrence 4 months after discontinuation. Imiquimod is an immunomodulator that activates Toll-like receptor 7 on plasmacytoid dendritic cells, inducing the production of interferon-alfa, tumor necrosis factorealfa, and interleukin-12, which drives a TH1 response. Induction of this inflammatory cytokine milieu is postulated to be the mechanism of action of imiquimod in MF. These cases suggest that topical imiquimod is a useful and well tolerated treatment for locally advanced and refractory areas of skin involvement. Commercial support: None identified.
AB122
J AM ACAD DERMATOL
Introduction: Extranodal NK/T lymphomas, nasal type, are rare non-Hodgkin lymphomas occurring predominantly in Asia and Latin America. They are typically seen in nasal area and paranasal sinuses, being the skin the second most affected site. The common presenting symptoms are facial edema, epistaxis, rapidly progressive ulcers, and pain. A distinctive feature is the association with EpsteineBarr virus (EBV) infection. Metastases of these lymphomas are rare. Histopathologic examination may show a nonspecific mixed inflammatory infiltrate. The immunophenotype of these lymphomas is classically positive for CD2, CD56, and cytoplasmic CD3; therefore, repeated biopsies are required for diagnosis. Case report: A 26-year-old man presented with a 1-year history of an asymptomatic diffuse facial edema and increased volume, predominantly on the lips. He also referred a 20-kg weight loss and night fever. The histopathologic examination of the oral mucosa biopsy showed lymphoid follicular hiperplasia. However, the patient persisted symptomatic and, therefore, a second biopsy was taken showing an infiltration by NK/T lymphoma associated with EBV infection. Liver and lymph nodes biopsies also revealed lymphoma cell infiltration. Treatment was started with methotrexate, L-asparaginase, and dexamethasone, resulting in reduction of the tumoral masses. Conclusion: Despite repeated biopsies, diagnosis of the extranodal NK/T lymphoma, nasal type, is difficult to make because of massive necrosis, vascular occlusion, and the mixture of inflammatory cells in the examined tissue. This means patients could receive inadequate treatments, because these lymphomas can be confused clinically and histologically with infections or inflammatory diseases. The use of imaging studies can be useful to guide the biopsy site. Currently, the use of chemotherapy based on L-asparaginase, methotrexate, and dexamethasone reported complete responses in up to 79% at earlier stages. However, positivity to EBV, lymphadenopathies, extractuaneous involvement and a high proliferation index have all been associated with a poorer prognosis. Commercial support: None identified.
MAY 2014
P8637
Blastic plasmacytoid dendritic cell neoplasm: An asymptommatic nodular eruption masking an internal malignancy Israel Andrews, MD, Roger Williams Medical Center: Department of Dermatology & Skin Surgery, Providence, RI, United States; Laura Della Torre, MD, Roger Williams Medical Center: Department of Dermatology & Skin Surgery, Providence, RI, United States Blastic plasmacytoid dendritic cell neoplasm (BPDCN), first described in 1994, is a rare hematologic malignancy derived from the precursor of plasmacytoid dendritic cells. Categorized by the World Health Organization as an acute myeloid leukemia, BPDCN has a characteristic phenotype of CD4 and CD56 positive lymphocytes with [90% of cases reported expressing CD123, a marker for plasmacytoid dendritic cells. A literature review of approximately 200 reports of BPDCN has found involvement limited to the skin in 50% of cases. Cutaneous involvement may present as solitary or multifocal nodules, patch-plaques, or ecchymoses. BPDCN can be limited to the skin, lymph nodes or the bone marrow, but several reports have shown that tumor infiltration can involve any combination of these systems. In 1 series of 30 patients, 57% demonstrated limited cutaneous involvement while 4% had cutaneous, bone marrow, and lymphatic disease. Prognosis, while independent of system involvement, is poor, with a median survival following diagnosis of 14 months. Although allogeneic stem cell transplantation with myeloablative therapy has yielded the most effective outcomes, there is no consensus for an optimal treatment of BPDCN. We report the case of a 69-year-old male who presented with multifocal asymptomatic cutaneous nodules that on pathology and immunohistochemical analysis was consistent with blastic plasmacytoid dendritic cell neoplasm. A systemic work-up of BPDCN, including complete system analysis, revealed a gastrointestinal adenocarcinoma with multiorgan metastasis, but failed to reveal any additional involvement of the BPDCN. Treatment was initiated for the adenocarcinoma with carboplatin and gemcitabine. Resolution of the cutaneous lesions occurred following the second cycle of chemotherapy. A repeat biopsy was performed at the site where a cutaneous nodule had previously existed, demonstrating no evidence of BPDCN. The patient later succumbed to his internal malignancy. Blastic plasmacytoid dendritic cell neoplasm can present with cutaneous involvement alone; however, a complete work-up of the blood, bone marrow, lymphatic system, and additional internal systems should follow. Despite the initial presentation of BPDCN, and independent to the manner of its involvement, this malignancy should be pursued aggressively. More data are necessary in order to develop an optimal treatment strategy for this malignancy.
Cutaneous composite lymphoma in the setting of chronic patch-stage mycosis fungoides Katherine Willard, MD, Mayo Clinic, Jacksonville, FL, United States; Jason Sluzevich, MD, Mayo Clinic, Jacksonville, FL, United States Composite lymphoma is defined as $ 2 distinctly separate populations of malignant lymphocytes in the same organ or tissue at the same site. Cutaneous composite lymphoma, consisting of concurrent B-cell and T-cell neoplasms, is exceedingly rare and has previously been described in the setting of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). Here, we describe a patient with chronic patch-stage mycosis fungoides who developed a composite lymphoma comprised of a distinct cutaneous marginal zone lymphoma in the same tissue site of previously established patch-stage mycosis fungoides. To our knowledge, this is the first described case of a cutaneous composite lymphoma consisting of these particular concurrent neoplasms. A 73-year-old man with chronic patch-stage mycosis fungoides presented with the acute onset of indurated, smooth papules within several chronic annular patches of mycosis fungoides. Skin biopsy revealed discrete nodular aggregates of atypical B-cells positive for CD79a, CD20, and BCL-2 and negative for CD5, BCL-6, and CD10, consistent with marginal zone lymphoma. These aggregates were surrounded by a T-cell infiltrate that was positive for CD3 and CD4, negative for CD8 and CD30, and otherwise histopathologically consistent with mycosis fungoides with band-like inflammation at the dermal epidermal junction. Immunoglobulin IgH gene rearrangement studies were positive for a clonal B-cell population. TCR gene rearrangement was positive for clonality and demonstrated an identical clonal T-cell population to that previously seen on initial diagnosis of mycosis fungoides. PET-CT staging was negative for nodal or systemic involvement. The phenomenon of composite lymphoma in the skin is exceptionally rare or otherwise underreported. It is suggested that the phenotypic and genotypic features of malignant cell infiltrates be included in the criteria for diagnosis of cutaneous composite lymphoma in addition to the requirement for morphologically distinct neoplasms at the same site. This case illustrates the utility of molecular techniques in identifying these independent malignant subpopulations that should be present when making a diagnosis of cutaneous composite lymphoma. Commercial support: None identified.
Commercial support: None identified.
P8478 Diagnostic challenge in extranodal NK/T lymphoma, nasal type Juan M. Ruiz-Matta, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico; Judith Domınguez-Cherit, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico; Marcela Saeb-Lima, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico; Michelle Gatica-Torres, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico; Silvia Mendez-Flores, MD, Instituto Nacional de Ciencias Medicas y Nutrici on Salvador Zubiran, Mexico City, Mexico
P8557 Clearance of refractory nodular and follicular mycosis fungoides with topical 5% imiquimod Matthew Gordon, MD, Mayo Clinic, Jacksonville, FL, United States; Anokhi Jambusaria, MD, MS, Mayo Clinic, Jacksonville, FL, United States; Jason Sluzevich, MD, Mayo Clinic, Jacksonville, FL, United States We present 2 patients with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type, resistant to multiple previous therapies that clinically cleared with the use of topical imiquimod 5% cream. Patient 1 is an 80-year-old female with a 15-year history of MF, stage IB, with a 6-year history of progressive involvement of the periocular skin despite previous use of class I topical corticosteroids, carmustine, bexarotene, PUVA, and systemic methotrexate. Physical examination revealed infiltrated plaques involving the left upper and lower eyelids and right nasal sidewall with variable alopecia. Biopsies confirmed mycosis fungoides with follicular involvement. Monotherapy with topical imiquimod 5% cream initiated at twice weekly and titrated to 3 times weekly resulted in complete clinical clearance after 6 months of therapy with no recurrence after 3 months since discontinuation. Patient 2 is a 65-year-old male with a 6-month history of MF, stage IIB, with a refractory tumor involving the right ankle and instep of plantar foot resistant to topical class I corticosteroids and narrowband UVB phototherapy. Treatment with imiquimod 5% cream 5 times per week resulted in clearance after 2 months with no recurrence 4 months after discontinuation. Imiquimod is an immunomodulator that activates Toll-like receptor 7 on plasmacytoid dendritic cells, inducing the production of interferon-alfa, tumor necrosis factorealfa, and interleukin-12, which drives a TH1 response. Induction of this inflammatory cytokine milieu is postulated to be the mechanism of action of imiquimod in MF. These cases suggest that topical imiquimod is a useful and well tolerated treatment for locally advanced and refractory areas of skin involvement. Commercial support: None identified.
AB122
J AM ACAD DERMATOL
Introduction: Extranodal NK/T lymphomas, nasal type, are rare non-Hodgkin lymphomas occurring predominantly in Asia and Latin America. They are typically seen in nasal area and paranasal sinuses, being the skin the second most affected site. The common presenting symptoms are facial edema, epistaxis, rapidly progressive ulcers, and pain. A distinctive feature is the association with EpsteineBarr virus (EBV) infection. Metastases of these lymphomas are rare. Histopathologic examination may show a nonspecific mixed inflammatory infiltrate. The immunophenotype of these lymphomas is classically positive for CD2, CD56, and cytoplasmic CD3; therefore, repeated biopsies are required for diagnosis. Case report: A 26-year-old man presented with a 1-year history of an asymptomatic diffuse facial edema and increased volume, predominantly on the lips. He also referred a 20-kg weight loss and night fever. The histopathologic examination of the oral mucosa biopsy showed lymphoid follicular hiperplasia. However, the patient persisted symptomatic and, therefore, a second biopsy was taken showing an infiltration by NK/T lymphoma associated with EBV infection. Liver and lymph nodes biopsies also revealed lymphoma cell infiltration. Treatment was started with methotrexate, L-asparaginase, and dexamethasone, resulting in reduction of the tumoral masses. Conclusion: Despite repeated biopsies, diagnosis of the extranodal NK/T lymphoma, nasal type, is difficult to make because of massive necrosis, vascular occlusion, and the mixture of inflammatory cells in the examined tissue. This means patients could receive inadequate treatments, because these lymphomas can be confused clinically and histologically with infections or inflammatory diseases. The use of imaging studies can be useful to guide the biopsy site. Currently, the use of chemotherapy based on L-asparaginase, methotrexate, and dexamethasone reported complete responses in up to 79% at earlier stages. However, positivity to EBV, lymphadenopathies, extractuaneous involvement and a high proliferation index have all been associated with a poorer prognosis. Commercial support: None identified.
MAY 2014