title: Diagnostic red flags: steroid-treated malignant CNS lymphoma mimicking autoimmune inflammatory demyelination.
abstract: The presence of inflammation and demyelination in a central nervous system (CNS) biopsy points towards a limited, yet heterogeneous group of pathologies, of which multiple sclerosis (MS) represents one of the principal considerations. Inflammatory demyelination has also been reported in patients with clinically suspected primary central nervous system lymphoma (PCNSL), especially when steroids had been administered prior to biopsy acquisition. The histopathological changes induced by corticosteroid treatment can range from mild reduction to complete disappearance of lymphoma cells. It has been proposed that in the absence of neoplastic B cells, these biopsies are indistinguishable from MS, yet despite the clinical relevance, no histological studies have specifically compared the two entities. In this work, we analyzed CNS biopsies from eight patients with inflammatory demyelination in whom PCNSL was later histologically confirmed, and compared them with nine well defined early active multiple sclerosis lesions. In the patients with steroid-treated PCNSL (ST-PCNSL) the interval between first and second biopsy ranged from 3 to 32 weeks; all of the patients had received corticosteroids before the first, but not the second biopsy. ST-PCNSL patients were older than MS patients (mean age: ST-PCNSL: 62 ± 4 years, MS: 30 ± 2 years), and histological analysis revealed numerous apoptoses, patchy and incomplete rather than confluent and complete demyelination and a fuzzy lesion edge. The loss of Luxol fast blue histochemistry was more profound than that of myelin proteins in immunohistochemistry, and T cell infiltration in ST-PCNSL exceeded that in MS by around fivefold (P = 0.005). Our data indicate that in the presence of extensive inflammation and incomplete, inhomogeneous demyelination, the neuropathologist should refrain from primarily considering autoimmune inflammatory demyelination and, even in the absence of lymphoma cells, instigate close clinical follow-up of the patient to detect recurrent lymphoma.
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Alonso
authors.identifier: 0000-0001-9988-4667
authors.initials: A
authors.lastname: Barrantes-Freer
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Aylin Sophie
authors.initials: AS
authors.lastname: Engel
authors.affiliation: Neuroscience Research Center, University of Costa Rica, San José, Costa Rica.
authors.forename: Odir Antonio
authors.initials: OA
authors.lastname: Rodríguez-Villagra
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Winkler
authors.affiliation: Institute of Neuropathology, Hospital Bremen Mitte, Bremen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bergmann
authors.affiliation: Institute of Neuropathology, University Hospital Magdeburg, Magdeburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Kuempfel
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Pellkofer
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Metz
authors.affiliation: Department of Haematology-Oncology, University Medical Center Göttingen, Göttingen, Germany, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Annalen
authors.initials: A
authors.lastname: Bleckmann
authors.affiliation: Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Hernández-Durán
authors.affiliation: Clinic for Neurology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Schippling
authors.affiliation: Institute of Neuropathology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rushing
authors.affiliation: Institute of Neuropathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Frank
authors.affiliation: Institute of Neuropathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.affiliation: Institute of Neuropathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Matschke
authors.affiliation: Department of Neuropathology, Institute of Pathology, University Medical Center Hannover, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.affiliation: Institute of Neuropathology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.affiliation: Department of Neuropathology, University Medical Center Leipzig, Leipzig, Germany.
authors.forename: Wolf
authors.initials: W
authors.lastname: Müller
authors.affiliation: Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D001706:Biopsy; D016543:Central Nervous System Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology*; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008223:Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents
keywords: corticosteroids; demyelination; diffuse large B cell lymphoma; inflammation; multiple sclerosis