Citations 2
ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition
Kemps, Paul G. , Picarsic, Jennifer , Durham, Benjamin H. , Hélias‐Rodzewicz, Zofia , Hiemcke‐Jiwa, Laura S. , Bos, Cor van den , Noesel, Carel J.M. van , Laar, Jan van , Verdijk, Robert M. , Flucke, Uta , Hogendoorn, Pancras C.W. , Woei-A-Jin, Feng Jung Sherida H. , Beilken, Andreas , Ebinger, Martin , Möhle, Robert, Bornemann, Antje, Wiegering, Verena , Ernestus, Karen, Méry, Tina, Gryniewicz–Kwiatkowska, Olga , Evseev, D. A. , Gaspari, Stefania , Gessi, Marco , Tamburrini, Gianpiero , Héritier, Sébastien , Bonneau‐Lagacherie, Jacinthe, Lamaison, Claire, Farnault, Laure , Fraitag, Sylvie , Jullié, Marie‐Laure , Haroche, Julien , Allotey, Jackie, Madni, Majid, Turner, Kerry , Picton, Susan, Barbaro, Pasquale , Poulin, Alysa, Tam, Ingrid S. , Empringham, Brianna , Whitlock, James A. , Swanson, Amy A. , Suchi, Mariko, Brandt, Jon M., Yaseen, Nabeel R. , Weinstein, Joanna , Eldem, İrem , Sisk, Bryan A. , Sridhar, Vaishnavi , Atkinson, Mandy, Massoth, Lucas R. , Alexandrescu, Sanda , Yeo, Kee Kiat , Petrova‐Drus, Kseniya , Peeke, Stephen , Muñoz-Arcos, Laura , Leino, Daniel , Grier, David D. , Lorsbach, Robert B., Kumar, Ashish R. , Garg, Shipra , Tiwari, Nishant , Schafernak, Kristian T. , Henry, M M , Halteren, Astrid G. S. van , Abla, Oussama , Kumar, Ashish , Hiemcke-Jiwa, Laura , van den Bos, Cor , van Noesel, Carel J M , van Laar, Jan A M , Verdijk, Robert M , Flucke, Uta E , Hogendoorn, Pancras C W , Woei-A-Jin, F J Sherida H , Sciot, Raf , Beilken, Andreas , Feuerhake, Friedrich , Ebinger, Martin , Fend, Falko , Wiegering, Verena , Gryniewicz-Kwiatkowska, Olga , Dembowska-Baginska, Bozenna , Evseev, Dmitry A , Potapenko, Vsevolod , Baykov, Vadim V , Gaspari, Stefania , Rossi, Sabrina , Gessi, Marco , Tamburrini, Gianpiero , Héritier, Sébastien , Donadieu, Jean , Farnault, Laure , Fraitag, Sylvie , Jullié, Marie-Laure , Collin, Matthew , Turner, Kerry , Barbaro, Pasquale M , Tam, Ingrid S , El Demellawy, Dina , Empringham, Brianna , Raghunathan, Aditya , Suchi, Mariko , Weinstein, Joanna L , Eldem, Irem , Sisk, Bryan A , Massoth, Lucas R , Hornick, Jason L , Alexandrescu, Sanda , Yeo, Kee Kiat , Petrova-Drus, Kseniya , Peeke, Stephen Z , Muñoz-Arcos, Laura S , Leino, Daniel G , Grier, David D , Roy, Somak , Kumar, Ashish R , Henry, Michael M , van Halteren, Astrid G S , Abla, Oussama , Diamond, Eli L , Emile, Jean-François , Picarsic, Jennifer L , Schafernak, Kristian , Durham, Benjamin , Wetering, Marianne D. van de , Sciot, Raf , Rossi, Sabrina , Collin, Matthew , Raghunathan, Aditya , Hornick, Jason L. , Diamond, Eli L. , Emile, Jean‐François
Blood | November 2, 2021 | Volume: 139 | Issue: 2 | Pages: 256-280
Abstract ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.
Plasma Cell Myeloma and Related Neoplasms
Lorsbach, Robert B., Hsi, Eric D. , Doǧan, Ahmet , Fend, Falko
American Journal of Clinical Pathology | July 14, 2011 | Volume: 136 | Issue: 2 | Pages: 168-182
Abstract Session 1 of the 2009 Workshop of the Society for Hematopathology/European Association of Haematopathology, Cleveland, OH, focused on plasma cell neoplasms. This report summarizes the salient diagnostic, clinical, and genetic features of plasma cell myeloma (PCM) and related neoplasms. Based on the cases submitted to the workshop, we highlight common diagnostic issues and unusual manifestations of plasma cell neoplasms, such as t(11;14)+ PCM, plasma cell leukemia, and nonsecretory plasmacytoma, as well as plasmablastic transformation of PCM. Additional issues repeatedly raised at the workshop included the differential diagnosis of extramedullary dissemination of PCM vs primary extramedullary plasmacytoma and plasmablastic lymphoma; systemic plasma cell neoplasms in immunocompromised people; and Epstein-Barr virus–associated plasma cell neoplasms. Difficult cases with borderline features presented by submitters emphasized the necessity of integrating clinical, immunophenotypic, and genetic features for appropriate classification of these disorders.