Table 1 Differential diagnosis of multisystem organ diseases with the manifestations of multi-invasive lesions in the CNS.

CNS-LyG

CNS and systemic involvement (i.e., lungs, skin, etc.), respiratory and focal neurological deficits.

Diffuse infiltrative lesions and mass-like lesions in the brain. Linear, patchy, nodular, mass-like, and irregular ring-like lesions on contrast-enhanced CT scans.

Polymorphous lymphoid cell infiltration, lymphocytic vasculitis, lymphocytic invasion of vascular walls, and granulomatous lesions.

CD68 (+), CD3 (+), CD20 (+).

Surgery, observation, steroid hormones, interferon, chemotherapy, radiotherapy, rituximab, stem cell transplantation and bone marrow transplantation.

CNS-ECD

CNS and systemic involvement (i.e., lungs, bone, etc.), bone pain, diabetes insipidus and cerebellar ataxia.

Occupying lesions or massive nodules in the brain,

involving the dura and showing meningioma-like masses with obvious homogeneous enhancement.

Observation of lipid-rich foam cells or eosinophilic cytoplasmic histiocytes and fibroblasts. CD68 (+), CD1a (-), S-100 (+/-) and Birbeck granules (-).

Surgery, observation, steroid hormones, interferon, cytotoxic drugs, radiotherapy and targeted drugs.

CNS-T-LYP

CNS and systemic involvement (i.e., lungs, joints, etc.).

Multiple occupying and diffuse lesions in the brain with punctate, mass-like, and ring-like enhancement; peripheral edema; involvement of both brainstem and cerebellum.

Diffuse infiltration of massive microlymphoidocytes, perivascular lymphoid sheaths, abundant reticular fibers, no obvious mitotic phase. CD3 (+), CD4 (+) and CD8 (+/-).

Surgery, steroid hormones and immunosuppressants.

CNS-IgG4-RD

CNS and systemic involvement (i.e., pancreas, salivary lacrimal glands, kidneys, lungs, etc.).

Orbital pseudotumor, hypophysitis, diffuse thickening or masses in the endocranium/dura mater.

Massive lymphocyte and plasma cell infiltration with fibrosis, IgG-positive plasma cells > 40%.

Steroid hormones, rituximab, azathioprine and other immunosuppressants, imatinib and tocilizumab.

CNS-RDD

Involvement of the CNS, enlargement of surrounding lymph nodes, visual changes, pituitary dysfunction and spinal cord dysfunction.

Multiple occupying, meningioma-like lesions in the brain and the spinal cord with obvious homogeneous enhancement and cystic degeneration, and involvement of the endocranium/dura mater.

Infiltration of various types of cells, massive Russell bodies and emperipolesis. S-100 (+), CD68 (+), CD163 (+) and CD1a (+).

Surgery, observation, steroid hormones, radiotherapy, cytotoxic drugs, rituximab and immunosuppressants.