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ALK ‐rearranged histiocytosis: Report of two cases with involvement of the central nervous system
Author(s) -
Rossi Sabrina,
Gessi Marco,
Barresi Sabina,
Tamburrini Gianpiero,
Giovani Isabella,
Ruggiero Antonio,
Colafati Giovanna Stefania,
Frassanito Paolo,
Carboni Alessia,
Alexandre Andrea,
Cacchione Antonella,
Trombatore Pietro,
DiomediCamassei Francesca,
Gaspari Stefania,
Gianno Francesca,
Marras Carlo Efisio,
Cecinati Valerio,
Carai Andrea,
Mastronuzzi Angela,
Alaggio Rita
Publication year - 2021
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12739
Subject(s) - pathology , medicine , histiocytosis , crizotinib , lesion , anaplastic lymphoma kinase , disease , malignant pleural effusion , lung cancer
Aims Histiocytoses are a heterogeneous group of localized or disseminated diseases. Clinical presentation and patients' outcome vary greatly, ranging from mild to life‐threatening disorders. Rare cases of systemic or localized histiocytosis harboring ALK rearrangement have been reported. Methods Two cases of CNS histiocytosis were thoroughly investigated by implementing multiple molecular tests, i.e. FISH, RT‐qPCR, NGS analysis. Results In a 10‐month old girl (patient #1), MRI showed two left hemispheric lesions and a right fronto‐mesial lesion histologically consisting of a moderately cellular infiltrative proliferation, composed by CD68(PGM1)+/CD163+ spindle cells. ALK 5’/3’‐imbalance and a KIF5B(exon 24)‐ALK(exon 20) fusion were documented by RT‐qPCR and NGS analysis, respectively. A subsequent CT scan showed multiple hepatic and pulmonary lesions. The patient was started on chemotherapy (vinblastine) associated to an ALK‐inhibitor (Alectinib) with remarkable response. In a 11‐year‐old girl (patient #2), MRI showed a right frontal 1.5 cm lesion. Neuropathological examination revealed a histiocytic proliferation composed by medium sized CD68(PGM1)+/HLA‐DR+ cells, showing moderate ALK1 positivity. ALK rearrangement and a KIF5B(exon 24)‐ALK(exon 20) fusion were demonstrated also in this case. Subsequent CT, 18F‐FDG‐PET and MRI scans showed the presence of a single right femoral lesion, proved to be a fibrous cortical defect. Conclusions In ALK‐histiocytoses, CNS involvement may occur as part of a systemic disease or, rarely, as its only primary disease localization, which could remain otherwise asymptomatic. The diagnosis often relies on neuropathological examination of brain biopsy, which may pose a diagnostic challenge due to the variable histopathological features. An integrated histological and molecular approach in such cases is recommended.