Differential Diagnosis of Tumor-like Brain Lesions

Abstract

Purpose of review: Tumor-like brain lesions are rare and commonly suggest a neoplastic etiology. Failure to rapidly identify non-neoplastic causes can lead to increased morbidity and mortality. In this review, we describe 10 patients who presented with atypical, non-neoplastic tumor-like brain lesions in which brain biopsy was essential for a correct diagnosis and treatment.

Recent findings: There has been increasing recognition of autoimmune conditions affecting the nervous system, and many of those diseases can cause tumor-like brain lesions. Currently available reports of non-neoplastic tumor-like brain lesions are scarce. Most case series focus on tumefactive demyelinating lesions, and a comprehensive review including other neuroimmunological conditions such as CNS vasculitis, neurosarcoidosis, histiocytic and infectious etiologies is lacking.

Summary: We review the literature on tumor-like brain lesions intending to increase the awareness and differential diagnosis of non-neoplastic brain tumor mimics. We advocate for earlier brain biopsies, which, in our case series, significantly changed diagnosis, management, and outcomes.

Figure 1. Demyelinating Diseases

(A–D) Patient 1, tumefactive multiple sclerosis. (E–I) Patient 2, neuromyelitis optica. (J–M) Patient 3, myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD).

Figure 2. Examples of Pathologic Findings

(A) Shows typical histopathologic features of a demyelinating lesion, with perivascular lymphocytes (lower left), reactive astrocytosis, and macrophage accumulation, in viable neuropil (relative axonal preservation) (magnification = ×20 before enlargement). (B, C) Images correspond to patient 2. Shows dense perivascular lymphocytic infiltrates in the meninges and the cortex, geographic areas of dystrophic calcifications and gliosis in the cortex and degenerative change in the white matter with macrophages aggregates and cavitary lesion. (D) Demonstrates histopathologic features of vasculitis, with transmural and perivascular infiltrates of mononuclear inflammatory cells affecting the medium-sized and small sized vessels (magnification = ×20 before enlargement). (E) Displays features of vasculitis with perivascular infiltrates of mononuclear inflammatory cells and intraparenchymal macrophages (magnification = ×20 before enlargement). (F) Shows features of neurosarcoidosis with well-formed non-necrotizing granuloma composed of epithelioid histiocytes (magnification = 20X before enlargement). (G) Images correspond to patient 9. Immunohistochemical stain using antibodies to Toxoplasma gondii, demonstrating tachyzoites in cerebral toxoplasmosis (magnifications = 60X before enlargement). (H) Images correspond to patient 10. Periodic acid-Schiff (PAS) special stain highlights numerous yeast-form fungal organisms with broad-based budding, demonstrating cerebral blastomycosis (magnifications = 40X before enlargement).

Figure 3. CNS Vasculitis

(A, B) Patient 4. (C–H) Patient 5.

Figure 4. Granulomatous, Histiocytic, and Plasma Cell Disorders

(A–D) Patient 6, neurosarcoidosis. (E–H) Patient 7, IgG-4–related disease (IGG4RD). (I–L) Patient 8, Langerhans histiocytosis.

Figure 5. Infections

(A–D) Patient 9, toxoplasmosis. (E–L) Patient 10, blastomycosis.