TABLE 2.
Immunophenotype and Differential Diagnosis of Nervous System Tumors Associated With HCSa
| Tumor | Immunophenotype | Important differential diagnosis |
|---|---|---|
| Astrocytoma | GFAP+, S100+, Olig2 + IDH1R132H + and ATRX loss (in IDH1-mutant tumors) | Pilocytic astrocytomaDD varies with location and may rest upon clinical and radiological parametersDiffuse astrocytoma (grade 2)Reactive conditions (clinical and neuroradiological imaging)Oligodendroglioma (monotonous round nuclei, 1p/19q codeletion)Anaplastic astrocytoma (grade 3)Glioblastoma (necrosis and microvascular proliferation)Oligodendroglioma (monotonous round nuclei, 1p/19q codeletion)Glioblastoma (grade 4)Metastatic neoplasm (not infiltrative, cohesive cells)Oligodendroglioma (Monotonous round nuclei, 1p/19q codeletion)PCNSL (CD45+, CD43+) |
| Atypical teratoid/rhabdoid tumor | INI1 loss | Medulloblastoma (synaptophysin+, retained INI1) |
| Choroid plexus carcinoma | No specific IHC, CK+ | Papillary tumor of the pineal regionPapillary endolymphatic sac tumor (component of VHL)AT/RT (INI1 loss)Small blue cell tumors (CK−)Anaplastic ependymoma (GFAP+, CK−)Germ cell tumors (SALL4+, OCT3/4+) |
| Dysplastic cerebellar gangliocytomas | Synaptophysin+, NFTP+, NeuN+ | Conventional gangliocytoma (abrupt interface with white matter)Astrocytoma (synaptophysin−) |
| Ependymoma | GFAP+, S100+, EMA+ (dot-like intracytoplasmic) | Schwannoma (strong S100+, GFAP−)Meningioma (EMA+, GFAP−)Pilocytic astrocytomaDiffuse astrocytomaNeurocytoma (synaptophysin+)Small blue cell tumors (GFAP−) |
| Hemangioblastoma | Inhibin+ | Metastatic clear cell carcinoma (PAX8+, Inhibin−) |
| Malignant peripheral nerve sheath tumor | Diffuse H3K27me3 loss | Synovial Sarcoma (NY-ESO+)Leiomyosarcoma (Desmin+, SMA+)Metastatic spindle cell melanoma (S100+, SOX10+)Neurotrophic melanoma (S100+, SOX10+) |
| Medulloblastoma | Synaptophysin+, contain stellate reactive GFAP + astrocytes | AT/RT (INI1 loss)Ependymoma (GFAP+)Metastatic small cell carcinoma (TTF1+)Neurocytoma (cytologically bland) |
| Meningioma | Membranous EMA+, SSTR2A+, CK+ (secretory subtype), PR+, GFAP− | Schwannoma (diffuse S100+, EMA−)SFT (STAT6+, CD34+, EMA−)Metastatic carcinoma (BerEP4+)Astroblastoma (Intra-axial, GFAP+)Melanocytoma (MelanA+, MiTF+, EMA−) |
| Neuroblastoma | Synaptophysin+, NFTP+ | Glioma (GFAP+)Neurocytoma (cytologically bland) |
| Neurofibroma | Mixed population of S100 + and CD34+ | Schwannoma (more uniform and pronounced S100+, CD34−)Low-grade MPNST (cellular, atypia, mitosis, focal S100 + or S100−)Ganglioneuroma (dysmorphic ganglion cells)DFSP (cellular, storiform growth pattern, S100−, uniform CD34 + involving all cells)NSM (lobulated, hypocellular, no association with nerve)Spindle cell lipoma (posterior neck location, S100−)Perineuroma (GLUT1+) |
| Oligodendroglioma | No specific IHC, Olig2+ | Reactive processesInfiltrating astrocytomaClear cell ependymoma (compact noninfiltrating architecture, EMA+)DNT (seizure history, compatible imaging, nodular architecture, floating neurons)PCNSL (CD45+, CD43+) |
| Retinoblastoma | CRX+, NSE+ | MedulloepitheliomaNematode endophthalmitisPersistent hyperplastic primary vitreousCoat's disease |
| Schwannoma | Diffuse S100+, variable GFAP | Neurofibroma (mixed population of S100 + and CD34+)NSM (lobulated, hypocellular, does not exhibit Antoni A and B pattern)MPNST (invade surrounding tissue, no hyaline vessels, monotonous growth, focal S100 + or S100−)Leiomyoma (no association with nerve, S100−, SMA+)Meningioma (patchy S100+, EMA+, Reticulin−)Pilocytic astrocytoma (Reticulin−) |
| Subependymal giant cell astrocytoma | S100+, focal weakly | Gemistocytic astrocytoma |
| GFAP+ | Tumors with ganglion cells |
aAlthough IHC offers rapid method of confirming the diagnosis of tumors, DNA methylation-based assay could be helpful to decipher the cases when IHC and DNA sequencing for mutations fail to reach a definite diagnosis.103
IHC, Immunohistochemistry.