Thyroid transcription factor-1 distinguishes subependymal giant cell astrocytoma from its mimics and supports its cell origin from the progenitor cells in the medial ganglionic eminence

Abstract

Subependymal giant cell astrocytoma is a benign brain tumor mostly associated with tuberous sclerosis complex. However, it may be misinterpreted as other high-grade brain tumors due to the presence of large tumor cells with conspicuous pleomorphism and occasional atypical features, such as tumor necrosis and endothelial proliferation. In this study, we first investigated thyroid transcription factor-1 (TTF-1) expression in a large series of subependymal giant cell astrocytomas and other histologic and locational mimics to validate the diagnostic utility of this marker. We then examined TTF-1 expression in non-neoplastic brain tissue to determine the cell origin of subependymal giant cell astrocytoma. Twenty-four subependymal giant cell astrocytoma specimens were subjected to tissue microarray construction. For comparison, a selection of tumors, including histologic mimics (21 gemistocytic astrocytomas and 24 gangliogliomas), tumors predominantly occurring at the ventricular system (50 ependymomas, 19 neurocytomas, and 7 subependymomas), and 134 astrocytomas (3 pleomorphic xanthoastrocytomas, 45 diffuse astrocytomas, 46 anaplastic astrocytomas, and 40 glioblastomas) were used. Immunohistochemical stain for TTF-1 was positive in all 24 subependymal giant cell astrocytomas, whereas negative in all astrocytomas, gangliogliomas, ependymomas, and subependymomas. Neurocytomas were positive for TTF-1 in 4/19 (21%) of cases using clone 8G7G3/1 and in 9/19 (47%) of cases using clone SPT24. In the three fetal brains that we examined, TTF-1 expression was seen in the medial ganglionic eminence, a transient fetal structure between the caudate nucleus and the thalami. There was no BRAF mutation identified by direct sequencing in the 20 subependymal giant cell astrocytomas that we studied. In conclusion, TTF-1 is a useful marker in distinguishing subependymal giant cell astrocytoma from its mimics. Expression of TTF-1 in the fetal medial ganglionic eminence indicates that subependymal giant cell astrocytoma may originate from the progenitor cells in this region.

Subependymal giant cell astrocytomas in Tuberous Sclerosis Complex have consistent TSC1/TSC2 biallelic inactivation, and no BRAF mutations

“…The BRAF V600E mutation was reported in a small set (6 of 14 cases) of SEGAs [ 23 ] suggesting that it could explain MAPK/ERK and AKT activation in SEGAs. However, subsequent studies have produced contradictory results, failing to confirm the presence of the BRAF V600E mutation in SEGAs [ 18 , 21 , 23 , 26 , 32 ].…”

Novel case of recurrent intraventricular atypical central neurocytoma with prominent gangliogliomatous differentiation in a 10‐year‐old boy with 10 years of follow up

“…While most of the tumor cells in SEGA display astrocytic features and show patchy immunoreactivity for GFAP, other tumor cells more closely resemble neurons or have intermediate features with astrocytoma‐like cytoplasms and neuronal‐like nuclei; these may show expression for neuronal markers . Recently, some papers suggested that thyroid transcription factor‐1 (TTF‐1) is a good marker that can distinguish SEGA from its mimics and supports its cell origin from the progenitor cells in the medial ganglionic eminence . Although no TTF‐1 was performed in our case, the presence of a cellular CN‐like component with permeative borders and a clinical course of tumor recurrence and absence of tuberous sclerosis make the differential diagnosis of SEGA unlikely.…”

Canine adrenocorticotropic hormone-producing sinusoidal neuroendocrine tumor associated with Cushing’s disease

“…3G) by cross reactivity of this antibody to dog cells. The CDX-2 antibody, which is used for determining human intestinal NETs [6,10], did not react in the tumor cells. Interestingly, antibody against ACTH detected the tumor cells ( Fig.…”

“…In dogs and cats, these tumors occur in the intestines, esophagus, lungs, naso-oral cavity and skin [13-16, 18, 23]. In humans, the most common sites are the gastrointestinal and respiratory tracts [2,6,10,22]. Most of these tumors are malignant and aggressive [13,18,20,23].…”

“…Antibody against thyroid transcription factor-1 (TTF-1), which is used for identifying human respiratory NETs [6,10], labeled the tumor cells ( Fig. 3G) by cross reactivity of this antibody to dog cells.…”