title: Clonal reticulohistiocytosis of the skin and bone marrow associated with systemic mastocytosis and acute myeloid leukaemia.
abstract: OBJECTIVE
  The aims of this study were to define whether diffuse cutaneous reticulohistiocytosis could be underpinned by somatic genetic alterations and represent a precursor of more aggressive forms of disease.
  
  
  RESULTS
  A 59-year-old man with diffuse cutaneous reticulohistiocytosis experienced bone marrow localization of the disease, with associated systemic mastocytosis and acute myeloid leukaemia. Cytogenetic analyses of the bone marrow aspirate revealed the presence of a derivative chromosome giving rise to a partial trisomy of chromosome 1q and a partial monosomy of chromosome 9q. Therefore, we characterized the cutaneous lesions before and after chemotherapy by using an integrative approach combining histopathology, electron microscopy, and fluorescence in-situ hybridization. Histologically, the skin lesions belonged to the spectrum of diffuse cutaneous reticulohistiocytoses, as confirmed by immunohistochemistry and ultrastructural analyses. Fluorescence in-situ hybridization in the skin nodules confirmed the presence of the genetic alterations previously detected in the bone marrow.
  
  
  CONCLUSIONS
  Here, we provide circumstantial evidence to suggest that at least a subset of cutaneous reticulohistiocytoses harbour clonal molecular alterations. Furthermore, we confirm that these lesions have the potential to arise in the setting of concurrent haematological disorders. In this hypothesis-generating study, two possible tumorigenesis models are proposed.
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Biomedical, Surgical and Dental Sciences, Milan, Italy.
authors.forename: Nicola
authors.identifier: http://orcid.org/0000-0002-9101-9131
authors.initials: N
authors.lastname: Fusco
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|School of Medicine, University of Milan, Milan, Italy.
authors.forename: Arturo
authors.initials: A
authors.lastname: Bonometti
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Augello
authors.affiliation: Oncohaematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Division of Anatomical and Molecular Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Boiocchi
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|School of Pathology, University of Milan, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiori
authors.affiliation: Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Morotti
authors.affiliation: Oncohaematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fracchiolla
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Biomedical, Surgical and Dental Sciences, Milan, Italy.|Department of Dermatology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Emilio
authors.identifier: http://orcid.org/0000-0001-6753-4910
authors.initials: E
authors.lastname: Berti
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.|Haematopathology Service, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Gianelli
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D019046:Bone Marrow Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology; D002999:Clone Cells / Q000473:pathology; D015620:Histiocytic Disorders, Malignant / Q000150:complications* / Q000235:genetics / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008297:Male; D034721:Mastocytosis, Systemic / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D012878:Skin Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology
keywords: acute myeloid leukaemia; fluorescence in-situ hybridization; reticulohistiocytosis; systemic mastocytosis; t(1;9)