Research paperPulmonary Langerhans cell histiocytosis, acute myeloid leukemia, and myelofibrosis in a large family and review of the literature
Introduction
Eosinophilic granuloma (now termed Langerhans cell histiocytosis) has been recognized as a distinct entity since described by Lichtenstein and Jaffe in 1940 [1]. Subsequently it was shown to be a histiocytic reticulosis related to Letterer-Siwe disease and Hand-Schüller-Christian disease [2]. Clinical aspects of primary pulmonary Langerhans cell histiocytosis (LCH) were well described by Friedman, et al. [3]. Here we report a large family with multiple cases of LCH of the lung, primary myelofibrosis and acute myeloid leukemia (AML). It is possible that there is a common genetic aberration in this family that caused or facilitated the development of these disorders. The recent discovery that LCH may be of hematopoietic origin makes the family reported here especially interesting [[4], [5]].
Section snippets
Materials and methods − new family
We present here a large family (Table 1, Fig. 1) with two cases of LCH of the lung, three cases of primary myelofibrosis, five cases of AML, and nine cases of other hematologic and non-hematologic malignancies, including one each of myelodysplastic syndrome and chronic myelocytic leukemia (CML). Although LCH was not biopsy proven in patient 6, he had classic radiographic findings of pulmonary LCH. In such cases biopsy is not necessary to establish the diagnosis [6]. The subjects in this family
Literature review
Familial LCH has been previously uncommonly reported in infants and children [[7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]] (Table 2) and even more rarely in adults [[20], [21], [22], [23], [24], [25]] (Table 3). Most pediatric familial cases have been male identical twins (Table 2) and most have had disseminated disease. Most multigenerational pairs have been concordant for sex, of adolescent or adult age and have had localized disease (Table 3).
Familial
Discussion
Lichtenstein et al. [54] coined the term, histiocytosis X to include Letterer-Siwe disease, Hand-Schüler-Christian disease and eosinophilic granuloma in 1953. The Histiocyte Society 34 years later suggested that the designation be changed to LCH [55], the term in current use.
Familial LCH has been well documented in the literature and suggests that a genetic mutation or other alteration may be responsible for the predisposition for the disease in such families. The multigenerational involvement
Role of the funding sources
The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit the paper for publication.
Contributors
MB, JPD, PHW identified the family of interest from the Familial Hematologic Malignancy Registry of the Cancer Research Foundation (Western Investigational Review Board approval 1164273). MB and JPD constructed case studies and Table 1. MB, JPD, PHW conducted the literature review. PHW wrote the initial draft and constructed Table 2, Table 3, Table 4, Table 5. MB and JPD constructed the pedigree (Fig. 1). All authors read and approved the final manuscript.
Declaration of interests
All authors declare no competing interests.
Acknowledgements
This study was funded in part by the Cancer Research Foundation of New York (thecrf.org) and a grant from Children’s Leukemia Research Association.
We thank Maria Thomas for translation of French References.
References (59)
- et al.
Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults
Blood
(2017) - et al.
Functional evidence for derivation of systemic histiocytic neoplasms from hematopoietic stem/progenitor cells
Blood
(2017) - et al.
Pulmonary Langerhans cell histiocytosis
Orphanet J. Rare Dis.
(2012) - et al.
Treatment of Langerhans cell histiocytosis with alpha-interferon
Lancet
(1987) - et al.
Langerhans cell histiocytosis in monozygotic twins
J. Am. Acad. Dermatol.
(1991) - et al.
Langerhans cell histiocytosis in acute leukemias of ambiguous or myeloid lineage in adult patients: support for a possible clonal relationship
Mod. Pathol.
(2014) - et al.
High prevalence of myeloid neoplasms in adults with non-Langerhans cell histiocytosis
Blood
(2017) - et al.
Eosinophilic granuloma of bone: with report of a case
Am. J. Pathol.
(1940) Histiocytosis X: integration of eosinophilic granuloma of bone, Letterer-Siwe disease, and Schüller-Christian disease as related manifestations of a single nosologic entity
Arch. Pathol.
(1953)- et al.
Clinical aspects of primary pulmonary histiocytosis in the adult
Medicine (Baltimore).
(1981)
Apparent cure of Letterer-Siwe disease: seventeen-year survival of identical twins with nonlipoid retciculoendotheliosis
JAMA
Remarks on a case of Letterer-Siwe disease in a pair of twins
Clin. Pediatr. (Bologna)
Genetic determination of acute disseminated histiocytosis X (Letterer-Siwe syndrome)
Pediatr
Langerhans-cell histiocytosis in twin sisters
Arch. Pediatr.
Familial clustering of Langerhans cell histiocytosis
Br. J. Haematol.
Eosinophilic granuloma of the skull in identical twins: case report
Neurol. Med. Chirurgie
Histocytoses Langerhansiennes congenitales cutanees:apropos of 7 cases
Ann. Dermatol. Venereol.
Letterer-Siwe disease in half-brothers
Arch Patol
Langerhans cells histiocytosis in one family
Pediatr. Hematol. Oncol.
Familial occurrence of Letterer-Siwe disease
Arch. Dis. Child.
Histiocytosis X: evidence for a genetic etiology
J. Nihon Univ. Sch. Dent.
Langerhans’ cell histiocytosis: is there a role for genetics?
Haematologica
Familial pulmonary histiocytosis XAm Rev Resp Dis
Am. Rev. Respir. Dis.
Hereditary Langerhans’ cell histiocytosis. Instances of apparent vertical transmission
Med. Pediatr. Oncol.
Different manifestations of Langerhans cell histiocytosis affecting two members of a family
Respiration
Langerhans cell histiocytosis in two generations: a new family and review of the literature
Med. Pediatr. Oncol.
Familial idiopathic myelofibrosis and multiple hemangiomas
Am. J. Hematol.
Familial myelofibrosis
Haematologia
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