Letters to the Editor
904
rdez,1 E. Martinez Barba,2 H. Kutzner,3 C. Berna L. Requena1,* 1 n Jim Department of Dermatology, Hospital Fundacio enez Dıaz, noma, Madrid, 2Department of Pathology, Hospital Universidad Auto Virgen de la Arrixaca, Murcia, Spain, 3Dermatopathologie, Friedrichshafen, Germany *Correspondence: L. Requena. E-mail: [email protected]
References 1 Nofal A, Sanad M, Assaf M et al. Juvenile hyaline fibromatosis and infantile systemic hyalinosis: a unifying term and a proposed grading system. J Am Acad Dermatol 2009; 61: 695–700. 2 Hanks S, Adams S, Douglas J et al. Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet 2003; 73: 791–800. 3 Tanaka K, Ebihara T, Kusubata M et al. Abnormal collagen deposition in fibromas from patient with juvenile hyaline fibromatosis. J Dermatol Sci 2009; 55: 197–200. 4 El-Kamah G, Fong K, El-Ruby M et al. Spectrum of mutations in the ANTXR2 (CMG2) gene in infantile systemic hyalinosis and juvenile hyaline fibromatosis. Br J Dermatol 2010; 163: 208–234. 5 Lindvall L, Kormeili T, Chen E et al. Infantile systemic hyalinosis: case report and review of the literature. J Am Acad Dermatol 2008; 58: 303– 307. 6 Thway K, Fisher C, Sebire N. Pediatric fibroblastic and myofibroblastic lesions. Adv Anat Pathol 2012; 19: 54–65. 7 Karacal N, Gulcelik N, Yildiz K, Mungan S, Kutlu N. Juvenile hyaline fibromatosis: a case report. J Cutan Pathol 2005; 32: 438–440. 8 Dowling O, Difeo A, Ramirez MC et al. Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet 2003; 73: 957–966. DOI: 10.1111/jdv.13073
Blastic plasmacytoid dendritic cell neoplasm following € m macroglobulinemia Waldenstro Editor A 60-year-old male patient, without previous significant medical history, was included in a wait-and-see strategy for a monoclonal IgM lambda band. Six years later, IgM lambda band and lambda light chains increased up to 30 g/L and 380 mg/L respectively. Kappa light chains were normal. A CT scan displayed mediastinal lymphadenopathy. Bone marrow aspirate was hypercellular, containing 45–60% lymphocytes and 5–12% plasma cells. The diagnosis of Waldenstr€ om Macroglobulinemia (WM) was determined. After six cycles of rituximab and chloraminophen, a partial response was reached including lymph node, IgM lambda band and lambda light chains decrease. One year later, he developed ecchymotic patches on trunk, lower limbs, face and oral mucosa (Fig. 1). Night sweats, fatigue
JEADV 2016, 30, 852–909
Figure 1 Clinical picture showing ecchymotic macules on the arm.
and palpable disseminated lymphadenopathy were reported. Thrombocytopenia was noted at 65 g/L. The IgM lambda band was stable at 5.8 g/L. A skin biopsy specimen revealed a dense, nodular, perivascular, monomorphous infiltrate of dermis and hypodermis (Fig. 2), made up of medium-sized cells, with fine chromatin pattern, small nucleoli and cytoplasmic vacuoles. Sparse mitotic figures were seen. After immunostaining, the tumoral cells were positive for CD4, CD56, CD45RA, CD123, HLA-DR, CD33 (weak) and were negative for CD3, CD11c, CD19. Lymph node aspirate, peripheral blood smear and bone marrow aspirate revealed a similar infiltrate, without residual WM cells. The diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) was determined. Five cycles of methotrexate and asparaginase were administered. Early relapse occurred in meninx and bone marrow, requiring a second-line therapy of carboplatin, etoposide, cytarabin, methylprednisolone and intrathecal methotrexate. Remission was obtained and a peripheral blood stem cell transplant was performed following a non-myeloablative conditioning regimen. BPDCN relapsed 9 months later and the patient eventually died. BPDCN is a rare and aggressive haematological malignancy, recognized as a specific entity in WHO classification of 2005. It affects elderly patients (with an average age at diagnosis of
Figure 2 Skin biopsy specimen (H&E with saffron, 9400 magnification).
© 2015 European Academy of Dermatology and Venereology
Letters to the Editor
67 years).1 Skin involvement often precedes the leukaemic involvement. The median overall survival is poor (10– 17 months).1 Tumoral cells are usually CD4, CD56, CD123, BDCA2, BDCA4, TCL1, CD2AP positive and do not express the lineage-specific markers for B cells (CD20, CD19), T cells (CD3, CD5) and myeloid cells (MPO,CD11c, CD163, lysozyme).1 Since the first description, the histogenesis of BPDCN remains unclear. It is reflected by the continuous evolution in nomenclature, from histiocyte-associated haematological malignancy, to myelomonocytic precursor cell-derived tumour, blastic NK-cell lymphoma and eventually BPDCN.1 BPDCN cells are currently considered as the malignant counterpart of Plasmactyoid Dendritic Cell (PDC), one of the two major subtypes of dendritic cells described. However, whereas the origin of Conventional Dendritic Cell (CDC) is agreed to be from myeloid lineage, the myeloid or a lymphoid origin of PDC is still unclear. In favour of a myeloid origin, BPDCN has been reported in association with haematological disorders mainly derived from the myeloid lineage, including Acute Myeloid Leukemia (AML), Chronic MyeloMonocytic Leukemia and Myelodysplastic Syndrome. Myeloid phenotypic markers, such as CD132 and CD33,3 and myeloid mutations, such as FLT3-Internal Tandem Duplication (FLT3-ITD),4 and TET2 gene mutations5 have been described in BPDCN. Combination of Thrombopoeitin, a growth factor for AML, and FLT3 ligand generated in vitro PDC precursors from human hematopoietic progenitors.6 Our observation, in addition to the few cases of lymphoproliferative disorders previously described in association with BPDCN, could be an additional argument for a non-strictly myeloid origin. PDC/BPDCN cells and lymphoid cells share common phenotypic markers, such as CD22,7 BDCA4/CD304,8 TCL1A transcripts,7 as well as transcription factors, such as SpiB9 and E2-2.10 PDC could rather arise from multiple potential myeloid and lymphoid progenitors, able to commit, with cell plasticity, over the course of development, either to PDC or CDC.
Acknowledgement The authors are grateful to Sarah Kabani for English review of the manuscript. S. Milley,1,2,3 L. Thomas,1,2,3 B. Balme,4 S. Dalle1,2,3,* 1
Department of Dermatology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 2Universite Claude Bernard Lyon 1, 3Cancer Research ^pital Center of Lyon, 4Unit of Pathology, Centre Hospitalier Lyon-Sud, Ho Edouard Herriot, Hospices Civils de Lyon, Lyon, France *Correspondance: S. Dalle. E-mail: [email protected]
References 1 Herling M, Jones D. CD4+/CD56+ Hematodermic Tumor. The features of an evolving entity and its relationship to Dendritic Cells. Am J Clin Pathol 2007; 127: 687–700.
JEADV 2016, 30, 852–909
905
2 Inoue D, Maruyama K, Aoki K et al. Blastic plasmacytoid dendritic cell neoplasm expressing the CD13 myeloid antigen. Acta Haematol 2011; 126: 122–128. 3 Garnache-Ottou F, Chaperot L, Biichle S et al. Expression of the myeloid marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells. Blood 2005; 105: 1256–1264. 4 Pagano L, Valentini CG, Pulsoni A et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an italien multi center study. Haematologica 2013; 98: 239–246. 5 Jardin F, Ruminy P, Parmentier F et al. TET2 and TET53 are frequently observed in blastic plasmacytoid dendritic cell neoplasm. Br J Hematol 2011; 153: 413–416. 6 Chen W, Antonenko S, Sederstrom JM et al. Thrombopoietin cooperates wth FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. Blood 2004; 103: 2547– 2553. 7 Garnache-Ottou F, Feuillard J, Ferrand C et al. Extended diagnostic criteria for plasmacytoid dendritic cell leukemia. Br J Haematol 2009; 145: 624–636. 8 Solly F, Angelot F, Garand R et al. CD304 is preferentially expressed on a subset of B-lineage Acute Lymphoblastic Leukemia and represents a novel marker for minimal residual disease detection by flow cytometry. Cytometry A 2012; 81A: 17–24. 9 Schotte R, Nagasawa M, Weijer K et al. The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development. J Exp Med 2004; 200: 1503–1509. 10 Cisse B, Caton ML, Lehner M et al. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 2008; 135: 37–48. DOI: 10.1111/jdv.13074
Progressive osseous heteroplasia in a 7-year-old girl with osteoma cutis and autoimmune thyroiditis: the importance of investigating GNAS mutations Editor Osteoma cutis (OC) is a rare dermatological disorder in which dermis and subcutaneous tissue become places of extra-osseous ossification. The hereditary form of OC is prevalently related to inactivating mutations of the GNAS gene, which have been associated with several disorders such as progressive osseous heteroplasia (POH), Albright’s hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP) and fibrodysplasia ossificans progressiva.1 We here report a 7-year-old girl with multiple OC associated with POH, in whom we also recognized an autoimmune thyroiditis. A 7-year-old girl presented two hard, painless and freely movable subcutaneous nodules, 4 9 2 mm in diameter, located in the parasternal region and in the right popliteal
© 2015 European Academy of Dermatology and Venereology
904
rdez,1 E. Martinez Barba,2 H. Kutzner,3 C. Berna L. Requena1,* 1 n Jim Department of Dermatology, Hospital Fundacio enez Dıaz, noma, Madrid, 2Department of Pathology, Hospital Universidad Auto Virgen de la Arrixaca, Murcia, Spain, 3Dermatopathologie, Friedrichshafen, Germany *Correspondence: L. Requena. E-mail: [email protected]
References 1 Nofal A, Sanad M, Assaf M et al. Juvenile hyaline fibromatosis and infantile systemic hyalinosis: a unifying term and a proposed grading system. J Am Acad Dermatol 2009; 61: 695–700. 2 Hanks S, Adams S, Douglas J et al. Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet 2003; 73: 791–800. 3 Tanaka K, Ebihara T, Kusubata M et al. Abnormal collagen deposition in fibromas from patient with juvenile hyaline fibromatosis. J Dermatol Sci 2009; 55: 197–200. 4 El-Kamah G, Fong K, El-Ruby M et al. Spectrum of mutations in the ANTXR2 (CMG2) gene in infantile systemic hyalinosis and juvenile hyaline fibromatosis. Br J Dermatol 2010; 163: 208–234. 5 Lindvall L, Kormeili T, Chen E et al. Infantile systemic hyalinosis: case report and review of the literature. J Am Acad Dermatol 2008; 58: 303– 307. 6 Thway K, Fisher C, Sebire N. Pediatric fibroblastic and myofibroblastic lesions. Adv Anat Pathol 2012; 19: 54–65. 7 Karacal N, Gulcelik N, Yildiz K, Mungan S, Kutlu N. Juvenile hyaline fibromatosis: a case report. J Cutan Pathol 2005; 32: 438–440. 8 Dowling O, Difeo A, Ramirez MC et al. Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet 2003; 73: 957–966. DOI: 10.1111/jdv.13073
Blastic plasmacytoid dendritic cell neoplasm following € m macroglobulinemia Waldenstro Editor A 60-year-old male patient, without previous significant medical history, was included in a wait-and-see strategy for a monoclonal IgM lambda band. Six years later, IgM lambda band and lambda light chains increased up to 30 g/L and 380 mg/L respectively. Kappa light chains were normal. A CT scan displayed mediastinal lymphadenopathy. Bone marrow aspirate was hypercellular, containing 45–60% lymphocytes and 5–12% plasma cells. The diagnosis of Waldenstr€ om Macroglobulinemia (WM) was determined. After six cycles of rituximab and chloraminophen, a partial response was reached including lymph node, IgM lambda band and lambda light chains decrease. One year later, he developed ecchymotic patches on trunk, lower limbs, face and oral mucosa (Fig. 1). Night sweats, fatigue
JEADV 2016, 30, 852–909
Figure 1 Clinical picture showing ecchymotic macules on the arm.
and palpable disseminated lymphadenopathy were reported. Thrombocytopenia was noted at 65 g/L. The IgM lambda band was stable at 5.8 g/L. A skin biopsy specimen revealed a dense, nodular, perivascular, monomorphous infiltrate of dermis and hypodermis (Fig. 2), made up of medium-sized cells, with fine chromatin pattern, small nucleoli and cytoplasmic vacuoles. Sparse mitotic figures were seen. After immunostaining, the tumoral cells were positive for CD4, CD56, CD45RA, CD123, HLA-DR, CD33 (weak) and were negative for CD3, CD11c, CD19. Lymph node aspirate, peripheral blood smear and bone marrow aspirate revealed a similar infiltrate, without residual WM cells. The diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) was determined. Five cycles of methotrexate and asparaginase were administered. Early relapse occurred in meninx and bone marrow, requiring a second-line therapy of carboplatin, etoposide, cytarabin, methylprednisolone and intrathecal methotrexate. Remission was obtained and a peripheral blood stem cell transplant was performed following a non-myeloablative conditioning regimen. BPDCN relapsed 9 months later and the patient eventually died. BPDCN is a rare and aggressive haematological malignancy, recognized as a specific entity in WHO classification of 2005. It affects elderly patients (with an average age at diagnosis of
Figure 2 Skin biopsy specimen (H&E with saffron, 9400 magnification).
© 2015 European Academy of Dermatology and Venereology
Letters to the Editor
67 years).1 Skin involvement often precedes the leukaemic involvement. The median overall survival is poor (10– 17 months).1 Tumoral cells are usually CD4, CD56, CD123, BDCA2, BDCA4, TCL1, CD2AP positive and do not express the lineage-specific markers for B cells (CD20, CD19), T cells (CD3, CD5) and myeloid cells (MPO,CD11c, CD163, lysozyme).1 Since the first description, the histogenesis of BPDCN remains unclear. It is reflected by the continuous evolution in nomenclature, from histiocyte-associated haematological malignancy, to myelomonocytic precursor cell-derived tumour, blastic NK-cell lymphoma and eventually BPDCN.1 BPDCN cells are currently considered as the malignant counterpart of Plasmactyoid Dendritic Cell (PDC), one of the two major subtypes of dendritic cells described. However, whereas the origin of Conventional Dendritic Cell (CDC) is agreed to be from myeloid lineage, the myeloid or a lymphoid origin of PDC is still unclear. In favour of a myeloid origin, BPDCN has been reported in association with haematological disorders mainly derived from the myeloid lineage, including Acute Myeloid Leukemia (AML), Chronic MyeloMonocytic Leukemia and Myelodysplastic Syndrome. Myeloid phenotypic markers, such as CD132 and CD33,3 and myeloid mutations, such as FLT3-Internal Tandem Duplication (FLT3-ITD),4 and TET2 gene mutations5 have been described in BPDCN. Combination of Thrombopoeitin, a growth factor for AML, and FLT3 ligand generated in vitro PDC precursors from human hematopoietic progenitors.6 Our observation, in addition to the few cases of lymphoproliferative disorders previously described in association with BPDCN, could be an additional argument for a non-strictly myeloid origin. PDC/BPDCN cells and lymphoid cells share common phenotypic markers, such as CD22,7 BDCA4/CD304,8 TCL1A transcripts,7 as well as transcription factors, such as SpiB9 and E2-2.10 PDC could rather arise from multiple potential myeloid and lymphoid progenitors, able to commit, with cell plasticity, over the course of development, either to PDC or CDC.
Acknowledgement The authors are grateful to Sarah Kabani for English review of the manuscript. S. Milley,1,2,3 L. Thomas,1,2,3 B. Balme,4 S. Dalle1,2,3,* 1
Department of Dermatology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 2Universite Claude Bernard Lyon 1, 3Cancer Research ^pital Center of Lyon, 4Unit of Pathology, Centre Hospitalier Lyon-Sud, Ho Edouard Herriot, Hospices Civils de Lyon, Lyon, France *Correspondance: S. Dalle. E-mail: [email protected]
References 1 Herling M, Jones D. CD4+/CD56+ Hematodermic Tumor. The features of an evolving entity and its relationship to Dendritic Cells. Am J Clin Pathol 2007; 127: 687–700.
JEADV 2016, 30, 852–909
905
2 Inoue D, Maruyama K, Aoki K et al. Blastic plasmacytoid dendritic cell neoplasm expressing the CD13 myeloid antigen. Acta Haematol 2011; 126: 122–128. 3 Garnache-Ottou F, Chaperot L, Biichle S et al. Expression of the myeloid marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells. Blood 2005; 105: 1256–1264. 4 Pagano L, Valentini CG, Pulsoni A et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an italien multi center study. Haematologica 2013; 98: 239–246. 5 Jardin F, Ruminy P, Parmentier F et al. TET2 and TET53 are frequently observed in blastic plasmacytoid dendritic cell neoplasm. Br J Hematol 2011; 153: 413–416. 6 Chen W, Antonenko S, Sederstrom JM et al. Thrombopoietin cooperates wth FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. Blood 2004; 103: 2547– 2553. 7 Garnache-Ottou F, Feuillard J, Ferrand C et al. Extended diagnostic criteria for plasmacytoid dendritic cell leukemia. Br J Haematol 2009; 145: 624–636. 8 Solly F, Angelot F, Garand R et al. CD304 is preferentially expressed on a subset of B-lineage Acute Lymphoblastic Leukemia and represents a novel marker for minimal residual disease detection by flow cytometry. Cytometry A 2012; 81A: 17–24. 9 Schotte R, Nagasawa M, Weijer K et al. The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development. J Exp Med 2004; 200: 1503–1509. 10 Cisse B, Caton ML, Lehner M et al. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 2008; 135: 37–48. DOI: 10.1111/jdv.13074
Progressive osseous heteroplasia in a 7-year-old girl with osteoma cutis and autoimmune thyroiditis: the importance of investigating GNAS mutations Editor Osteoma cutis (OC) is a rare dermatological disorder in which dermis and subcutaneous tissue become places of extra-osseous ossification. The hereditary form of OC is prevalently related to inactivating mutations of the GNAS gene, which have been associated with several disorders such as progressive osseous heteroplasia (POH), Albright’s hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP) and fibrodysplasia ossificans progressiva.1 We here report a 7-year-old girl with multiple OC associated with POH, in whom we also recognized an autoimmune thyroiditis. A 7-year-old girl presented two hard, painless and freely movable subcutaneous nodules, 4 9 2 mm in diameter, located in the parasternal region and in the right popliteal
© 2015 European Academy of Dermatology and Venereology
