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CD56+ hematodermic neoplasm
P2702
P2704
Classic presentation of a rare entity: CD41/CD561 hematodermic neoplasm Charles Chia, MD, Mayo Clinic, Scottsdale, AZ, United States; David DiCaudo, MD, Mayo Clinic, Scottsdale, AZ, United States; Temitope Soares, MD, Mayo Clinic, Scottdale, AZ, United States
Glatiramer acetateeassociated CD301 primary cutaneous anaplastic largecell lymphoma Monica Madray, Scott & White Memorial Hospital and Clinic Texas A&M University College of Medicine, Division of Dermatology, Temple, TX, United States; David F. Butler, MD, Scott & White Memorial Hospital and Clinic, Texas A&M University College of Medicine, Division of Dermatology, Temple, TX, United States; John Greene, MD, Scott & White Memorial Hospital and Clinic, Texas A&M University College of Medicine, Department of Pathology, Temple, TX, United States
A 77-year-old white male presented with a 10-month history of a mildly pruritic truncal rash that slowly spread to the face and extremities. Physical examination revealed generalized, discreet, poorly demarcated, 1- to 3-cm, round, pink- to rustcolored nodules with surrounding petechiae. A complete blood cell count showed low platelets and a mildly elevated white blood cell count with absolute lymphocytes three times normal. Blood smear demonstrated numerous blast cells. Skin biopsies of the left and right flanks showed diffuse dermal and subcutaneous perivascular and interstitial infiltrate composed of atypical mononuclear cells with numerous mitotic figures. Immunostains demonstrated strong expression of CD4 and CD43 and moderate expression of CD56. CD3, CD20, CD68, CD30, CD138, lysozyme, myeloperoxidase, CD79a, and CD2 are negative. Blood flow cytrometry and bone marrow biopsy showed an acute myeloid leukemia with monocytic differentiation expressing CD4 and CD56. This was considered a second neoplasm. The patient elected to undergo chemotherapy. CD41/CD561 hematodermic neoplasm, formerly termed blastic natural killer cell lymphoma, is a rare but highly resistant and aggressive malignancy with a poor prognosis. Most cases present with cutaneous lesions with eventual involvement of lymph nodes and bone marrow. Mean age of presentation is 61 years and occurs equally frequently in both sexes. Histologically, epidermal appendage tropism with extension to reticular and deep dermis is a feature. The cells are small to medium-sized with round or indented nuclei with or without prominent nucleoli. Cytoplasm is moderately abundant without granules. Recent advancements in immunohistochemistry have demonstrated these neoplastic cells are likely derived from precursor plasmacytoid dendritic cells as they do not express common T cell, B cell, NK cell nor most myeloid lineage markers, hence the name change from blastic natural killer cell lymphoma. There exists, as in our patient, an association between CD41/CD561 hematodermic neoplasm and myelomonocytic leukemia yet the relationship is unclear. There remains no effective treatment. Historically, patients are treated with chemotherapy for either acute myelogenous leukemia or high grade non-Hodgkin lymphoma. Patients with cutaneous involvement and limited systemic disease often respond to initial therapy but invariably relapse.
Glatiramer acetate (GA), an injectable polypeptide immunomodulatory agent, is currently approved for the treatment of relapsing remitting multiple sclerosis (RRMS). Although the exact mechanism of action remains unknown, GA appears to alter immune function by acting on CD81 T cells, antigen-presenting cells, monocytes, B cells, and by altering T cell differentiation, ultimately dampening inflammation in the central nervous system. We describe the clinicopathologic features of a CD301 primary cutaneous anaplastic large cell lymphoma developing after initiation of GA therapy. A 33-year-old white female taking GA 20 mg subcutaneously daily for RRMS developed an 8-mm, firm, nontender, erythematous papule at the left pretibial region 4 months after beginning the medication. She was otherwise healthy and further work-up for systemic involvement was negative. Hematoxylineeosin stained sections showed a diffuse, dermal, nodular infiltrate of atypical lymphoid cells extending into the subcutaneous tissue in sheets. The infiltrate was positive for CD3 and [75% positive for CD30. Stains with ALK-protein, EMA, Keratin, Ber-EP4 and CD15 were negative. The gross and microscopic findings favored a diagnosis of primary cutaneous anaplastic T-cell lymphoma rather than lymphomatoid papulosis or pseudolymphoma, in accordance with the World Health Organization classification of hematologic malignancies and current convention. Drug-associated nodular cutaneous lymphomas and pseudolymphomas are rare, but have been reported in the literature. GA is a normally safe, well tolerated, effective medication used in the treatment of RRMS. The temporal association of starting treatment with GA and the T-cell modulating properties of this drug impute a possible relationship to the development of the T-cell lymphoma in our patient. Clinicians should be aware of this potential association in order to better inform patients of the risks of using the drug. Commercial support: None identified.
Commercial support: None identified.
P2705
Commentary: In our case, onset of symptoms was precocious. Extensive lesions of molluscum contagiosum were a consequence of immunodeficiency and clinical feature of plantar lesions allowed us to think of a severe viral infection. Histopathologic findings confirmed the diagnosis of a plantar localization of mycosis fungoides. MF is considered a great imitator. Palmoplantar localization in cutaneous T-cell lymphoma was reported several times. It occurs in the advanced stages of Se´zary syndrome. Keratoderma and vesiculopustular and keratoderma are the most common manifestations. Many atypical aspects have been described: bullous, ischemic, and ulcerous.
Coexistent B-cell lymphoma and acute myelogenous leukemia infiltrates within the same cutaneous nodule Nisha Mistry, MPH, MBChB, University of British Columbia, Vancouver, British Columbia, Canada; Richard Crawford, MD, Department of Pathology, St. Paul’s Hospital, Vancouver, British Columbia, Canada; Sheila Au, MD, University of British Columbia, Vancouver, British Columbia, Canada A 56-year-old female with a 3-year history of an untreated indolent B-cell lymphoma was admitted to hospital with a new diagnosis of acute myeloid leukemia (AML). The patient noted a 2-year history of cutaneous nodules which waxed and waned and occasionally spontaneously resolved. She complained of a recent acute exacerbation in her skin findings, and on examination was found to have extensive, tender, infiltrated, fluctuant, and ulcerated violaceous nodules. These changes correlated temporally with the onset of fatigue and weight loss that had led to her recent diagnosis of AML. A punch biopsy of one of these nodules revealed two major cell types: myeloid and lymphoid. The myeloid infiltrate consisted of immature myeloid cells and promyelocytes which stained positive for CD34 and myeloperoxidase. Staining of the lymphoid infiltrate demonstrated coexpression of CD20 and CD43. These stains were consistent with cutaneous infiltrates of both AML cells and B-cell lymphoma cells. The development of AML in patients with a history of nonHodgkins lymphoma is a well documented phenomenon, but this is almost always in the context of previous therapy with radiation, chemotherapy, or both. The mechanisms by which this second malignancy may develop are unknown, but a number of hypotheses exist: (1) lineage switching of a multipotential stem cell from lymphocytic to granulocytic differentiation; (2) treatment-induced chromosomal damage to hematopoietic stem cells leading to leukemogenesis; (3) treatmentinduced chronic immunosuppression resulting in poor immune surveillance and lack of control of a developing malignancy; (4) immunosuppression by the chronic malignancy itself, even in the absence of therapy; (5) underlying, intrinsic predisposition to AML in patients with lymphoma. Spontaneous development of AML in patients with untreated non-Hodgkin lymphoma is extremely rare. Coexistent infiltrates have been previously reported in lymph nodes and bone marrow, but a literature search did not reveal any instances of cutaneous nodules in either treated or untreated patients. Our patient is thus unique in two ways: (1) her leukemia developed in the absence of any treatment of her lymphoma with chemotherapy or radiotherapy; and (2) to the best of our knowledge, she represents the first documented case of simultaneous involvement of B-cell lymphoma and AML in a single cutaneous lesion.
Commercial support: None identified.
Commercial support: None identified.
P2703 Se´zary syndrome in a child with papillomatous lesions as a plantar localization of T-cell cutaneous lymphoma Boutheina Benharbit, UHC Ibn Rochd, Casablanca, Morocco; Hakima Benchikhi, UHC Ibn Rochd, Casablanca, Morocco; Hakima Lakhdar, UHC Ibn Rochd, Casablanca, Morocco; Khadija Khadir, UHC Ibn Rochd, Casablanca, Morocco; Sofia Azzouzi, UHC Ibn Rochd, Casablanca, Morocco Introduction: Mycosis fungoides (MF) can take many atypical forms. We report an uncommon feature of plantar lesions of MF in patient with Se´zary syndrome. Case report: A 10-year-old male presented in 2005 with erythroderma, intense pruritus, alopecia, and peripheral lymphadenopathy. The first symptoms occurred at 5 years of age. Cutaneous biopsies showed pilotropic MF with follicular mucinosis. Diagnosis of Se´zary syndrome was confirmed through identification of more than 11,000 circulating Se´zary cells/mm3. Moreover, topical corticosteroids, histamine H1-receptor antagonists, our patient was successively treated with ultraviolet B light narrow-band phototherapy, chemotherapy (cyclophosphamide/ prednisone), and interferon-alfa. The phototherapy increased erythema. Chemotherapy was unsuccessful. Interferon-alfa caused hepatitis. Then, we treated the patient with methotrexate (15 mg/wk) and this resulted in regression of erythroderma and pruritus, and in a reduction of the leukocyte count after 3 months. In March 2007, the patient stopped methotrexate. He presented 7 months later with erythroderma, alopecia, and severe molluscum contagiosum. He also showed papillomatous, verrucous lesions of the soles. A biopsy showed typical aspects of MF. The patient was treated with methotrexate. No side effects were observed and plantar lesions regressed partially after 4 months.
AB128
J AM ACAD DERMATOL
MARCH 2009
P2704
Classic presentation of a rare entity: CD41/CD561 hematodermic neoplasm Charles Chia, MD, Mayo Clinic, Scottsdale, AZ, United States; David DiCaudo, MD, Mayo Clinic, Scottsdale, AZ, United States; Temitope Soares, MD, Mayo Clinic, Scottdale, AZ, United States
Glatiramer acetateeassociated CD301 primary cutaneous anaplastic largecell lymphoma Monica Madray, Scott & White Memorial Hospital and Clinic Texas A&M University College of Medicine, Division of Dermatology, Temple, TX, United States; David F. Butler, MD, Scott & White Memorial Hospital and Clinic, Texas A&M University College of Medicine, Division of Dermatology, Temple, TX, United States; John Greene, MD, Scott & White Memorial Hospital and Clinic, Texas A&M University College of Medicine, Department of Pathology, Temple, TX, United States
A 77-year-old white male presented with a 10-month history of a mildly pruritic truncal rash that slowly spread to the face and extremities. Physical examination revealed generalized, discreet, poorly demarcated, 1- to 3-cm, round, pink- to rustcolored nodules with surrounding petechiae. A complete blood cell count showed low platelets and a mildly elevated white blood cell count with absolute lymphocytes three times normal. Blood smear demonstrated numerous blast cells. Skin biopsies of the left and right flanks showed diffuse dermal and subcutaneous perivascular and interstitial infiltrate composed of atypical mononuclear cells with numerous mitotic figures. Immunostains demonstrated strong expression of CD4 and CD43 and moderate expression of CD56. CD3, CD20, CD68, CD30, CD138, lysozyme, myeloperoxidase, CD79a, and CD2 are negative. Blood flow cytrometry and bone marrow biopsy showed an acute myeloid leukemia with monocytic differentiation expressing CD4 and CD56. This was considered a second neoplasm. The patient elected to undergo chemotherapy. CD41/CD561 hematodermic neoplasm, formerly termed blastic natural killer cell lymphoma, is a rare but highly resistant and aggressive malignancy with a poor prognosis. Most cases present with cutaneous lesions with eventual involvement of lymph nodes and bone marrow. Mean age of presentation is 61 years and occurs equally frequently in both sexes. Histologically, epidermal appendage tropism with extension to reticular and deep dermis is a feature. The cells are small to medium-sized with round or indented nuclei with or without prominent nucleoli. Cytoplasm is moderately abundant without granules. Recent advancements in immunohistochemistry have demonstrated these neoplastic cells are likely derived from precursor plasmacytoid dendritic cells as they do not express common T cell, B cell, NK cell nor most myeloid lineage markers, hence the name change from blastic natural killer cell lymphoma. There exists, as in our patient, an association between CD41/CD561 hematodermic neoplasm and myelomonocytic leukemia yet the relationship is unclear. There remains no effective treatment. Historically, patients are treated with chemotherapy for either acute myelogenous leukemia or high grade non-Hodgkin lymphoma. Patients with cutaneous involvement and limited systemic disease often respond to initial therapy but invariably relapse.
Glatiramer acetate (GA), an injectable polypeptide immunomodulatory agent, is currently approved for the treatment of relapsing remitting multiple sclerosis (RRMS). Although the exact mechanism of action remains unknown, GA appears to alter immune function by acting on CD81 T cells, antigen-presenting cells, monocytes, B cells, and by altering T cell differentiation, ultimately dampening inflammation in the central nervous system. We describe the clinicopathologic features of a CD301 primary cutaneous anaplastic large cell lymphoma developing after initiation of GA therapy. A 33-year-old white female taking GA 20 mg subcutaneously daily for RRMS developed an 8-mm, firm, nontender, erythematous papule at the left pretibial region 4 months after beginning the medication. She was otherwise healthy and further work-up for systemic involvement was negative. Hematoxylineeosin stained sections showed a diffuse, dermal, nodular infiltrate of atypical lymphoid cells extending into the subcutaneous tissue in sheets. The infiltrate was positive for CD3 and [75% positive for CD30. Stains with ALK-protein, EMA, Keratin, Ber-EP4 and CD15 were negative. The gross and microscopic findings favored a diagnosis of primary cutaneous anaplastic T-cell lymphoma rather than lymphomatoid papulosis or pseudolymphoma, in accordance with the World Health Organization classification of hematologic malignancies and current convention. Drug-associated nodular cutaneous lymphomas and pseudolymphomas are rare, but have been reported in the literature. GA is a normally safe, well tolerated, effective medication used in the treatment of RRMS. The temporal association of starting treatment with GA and the T-cell modulating properties of this drug impute a possible relationship to the development of the T-cell lymphoma in our patient. Clinicians should be aware of this potential association in order to better inform patients of the risks of using the drug. Commercial support: None identified.
Commercial support: None identified.
P2705
Commentary: In our case, onset of symptoms was precocious. Extensive lesions of molluscum contagiosum were a consequence of immunodeficiency and clinical feature of plantar lesions allowed us to think of a severe viral infection. Histopathologic findings confirmed the diagnosis of a plantar localization of mycosis fungoides. MF is considered a great imitator. Palmoplantar localization in cutaneous T-cell lymphoma was reported several times. It occurs in the advanced stages of Se´zary syndrome. Keratoderma and vesiculopustular and keratoderma are the most common manifestations. Many atypical aspects have been described: bullous, ischemic, and ulcerous.
Coexistent B-cell lymphoma and acute myelogenous leukemia infiltrates within the same cutaneous nodule Nisha Mistry, MPH, MBChB, University of British Columbia, Vancouver, British Columbia, Canada; Richard Crawford, MD, Department of Pathology, St. Paul’s Hospital, Vancouver, British Columbia, Canada; Sheila Au, MD, University of British Columbia, Vancouver, British Columbia, Canada A 56-year-old female with a 3-year history of an untreated indolent B-cell lymphoma was admitted to hospital with a new diagnosis of acute myeloid leukemia (AML). The patient noted a 2-year history of cutaneous nodules which waxed and waned and occasionally spontaneously resolved. She complained of a recent acute exacerbation in her skin findings, and on examination was found to have extensive, tender, infiltrated, fluctuant, and ulcerated violaceous nodules. These changes correlated temporally with the onset of fatigue and weight loss that had led to her recent diagnosis of AML. A punch biopsy of one of these nodules revealed two major cell types: myeloid and lymphoid. The myeloid infiltrate consisted of immature myeloid cells and promyelocytes which stained positive for CD34 and myeloperoxidase. Staining of the lymphoid infiltrate demonstrated coexpression of CD20 and CD43. These stains were consistent with cutaneous infiltrates of both AML cells and B-cell lymphoma cells. The development of AML in patients with a history of nonHodgkins lymphoma is a well documented phenomenon, but this is almost always in the context of previous therapy with radiation, chemotherapy, or both. The mechanisms by which this second malignancy may develop are unknown, but a number of hypotheses exist: (1) lineage switching of a multipotential stem cell from lymphocytic to granulocytic differentiation; (2) treatment-induced chromosomal damage to hematopoietic stem cells leading to leukemogenesis; (3) treatmentinduced chronic immunosuppression resulting in poor immune surveillance and lack of control of a developing malignancy; (4) immunosuppression by the chronic malignancy itself, even in the absence of therapy; (5) underlying, intrinsic predisposition to AML in patients with lymphoma. Spontaneous development of AML in patients with untreated non-Hodgkin lymphoma is extremely rare. Coexistent infiltrates have been previously reported in lymph nodes and bone marrow, but a literature search did not reveal any instances of cutaneous nodules in either treated or untreated patients. Our patient is thus unique in two ways: (1) her leukemia developed in the absence of any treatment of her lymphoma with chemotherapy or radiotherapy; and (2) to the best of our knowledge, she represents the first documented case of simultaneous involvement of B-cell lymphoma and AML in a single cutaneous lesion.
Commercial support: None identified.
Commercial support: None identified.
P2703 Se´zary syndrome in a child with papillomatous lesions as a plantar localization of T-cell cutaneous lymphoma Boutheina Benharbit, UHC Ibn Rochd, Casablanca, Morocco; Hakima Benchikhi, UHC Ibn Rochd, Casablanca, Morocco; Hakima Lakhdar, UHC Ibn Rochd, Casablanca, Morocco; Khadija Khadir, UHC Ibn Rochd, Casablanca, Morocco; Sofia Azzouzi, UHC Ibn Rochd, Casablanca, Morocco Introduction: Mycosis fungoides (MF) can take many atypical forms. We report an uncommon feature of plantar lesions of MF in patient with Se´zary syndrome. Case report: A 10-year-old male presented in 2005 with erythroderma, intense pruritus, alopecia, and peripheral lymphadenopathy. The first symptoms occurred at 5 years of age. Cutaneous biopsies showed pilotropic MF with follicular mucinosis. Diagnosis of Se´zary syndrome was confirmed through identification of more than 11,000 circulating Se´zary cells/mm3. Moreover, topical corticosteroids, histamine H1-receptor antagonists, our patient was successively treated with ultraviolet B light narrow-band phototherapy, chemotherapy (cyclophosphamide/ prednisone), and interferon-alfa. The phototherapy increased erythema. Chemotherapy was unsuccessful. Interferon-alfa caused hepatitis. Then, we treated the patient with methotrexate (15 mg/wk) and this resulted in regression of erythroderma and pruritus, and in a reduction of the leukocyte count after 3 months. In March 2007, the patient stopped methotrexate. He presented 7 months later with erythroderma, alopecia, and severe molluscum contagiosum. He also showed papillomatous, verrucous lesions of the soles. A biopsy showed typical aspects of MF. The patient was treated with methotrexate. No side effects were observed and plantar lesions regressed partially after 4 months.
AB128
J AM ACAD DERMATOL
MARCH 2009