Imaging features of localized IDH wild-type histologically diffuse astrocytomas: a single-institution case series

Abstract

Isocitrate dehydrogenase wild-type (IDHwt) diffuse astrocytomas feature highly infiltrative patterns, such as a gliomatosis cerebri growth pattern with widespread involvement. Among these tumors, localized IDHwt histologically diffuse astrocytomas are rarer than the infiltrative type. The aim of this study was to assess and describe the clinical, radiographic, histopathological, and molecular characteristics of this rare type of IDHwt histologically diffuse astrocytomas and thereby provide more information on how its features affect clinical prognoses and outcomes. We retrospectively analyzed the records of five patients with localized IDHwt histologically diffuse astrocytomas between July 2017 and January 2020. All patients were female, and their mean age at the time of the initial treatment was 55.0 years. All patients had focal disease that did not include gliomatosis cerebri or multifocal disease. All patients received a histopathological diagnosis of diffuse astrocytomas at the time of the initial treatment. For recurrent tumors, second surgeries were performed at a mean of 12.4 months after the initial surgery. A histopathological diagnosis of glioblastoma was made in four patients and one of gliosarcoma in one patient. The initial status of IDH1, IDH2, H3F3A, HIST1H3B, and BRAF was "wild-type" in all patients. TERT promoter mutations (C250T or C228T) were detected in four patients. No tumors harbored a 1p/19q codeletion, EGFR amplification, or chromosome 7 gain/10 loss (+ 7/ - 10). We assessed clinical cases of localized IDHwt histologically diffuse astrocytomas that resulted in malignant recurrence and a poor clinical prognosis similar to that of glioblastomas. Our case series suggests that even in patients with histologically diffuse astrocytomas and those who present with radiographic imaging findings suggestive of a localized tumor mass, physicians should consider the possibility of IDHwt histologically diffuse astrocytomas.

Figure 1

Preoperative axial T2-weighted MRI, showing a high-intensity area with a well-defined tumor border of the right insular tumor (Case 1) (A), of the precentral gyrus (Case 2) (B), of the left inferior frontal gyrus tumor (Case 3) (C), of the left insular tumor (Case 4) (D) and, of the left insular tumor (Case 5) (E).

Figure 2

Hematoxylin and eosin staining of the initial surgical specimen showing a diffuse astrocytoma. Case 1 (A), Case 2 (B), Case 3 (C), Case 4 (D), and Case 5 (E). The Ki-67 labelling index was approximately 2% in Case 1 (F), 3% in Case 2 (G), 2% in Case 3 (H), 5% in Case 4 (I), and 2% in Case 5 (J). Scale bars: 100 μm.

Figure 3

(A) Preoperative axial T2-weighted and (B) axial T1-weighted MRI with gadolinium enhancement, showing a high-intensity area with no enhancement in the left inferior frontal gyrus forming a localized tumor mass. (C) Postoperative axial T2-weighted MRI showing no tumors due to gross-total resection (first surgery). (D) Axial T1-weighted MRI with gadolinium enhancement performed about 6 months after the first surgery, showing nodular enhancement in the left frontal surgical cavity. (E) Postoperative axial T1-weighted MRI with gadolinium enhancement, showing no tumors due to gross-total resection (second surgery). (F) Axial T1-weighted MRI with gadolinium enhancement performed about 4 months after the second surgery, showing enhancing mass lesion in the surgical cavity again. (G) Postoperative axial T1-weighted MRI with gadolinium enhancement, showing no tumors owing to gross-total resection (third surgery). (H) Axial T1-weighted MRI with gadolinium enhancement at last follow-up, showing recurrent tumor. Tumor progression could not be controlled.

Figure 4

Histologic and immunohistochemical findings. (A) HE staining of initial surgery specimen showing diffuse infiltration of atypical astrocytes without necrosis or micro vascular proliferation. (B) IHC staining of IDH1 R132H of initial surgery specimen showing negative results. (C) HE staining of second surgery specimen showing proliferation of atypical glial cells with mitoses and microvascular proliferation. (D) IHC staining of IDH1 R132H of second surgery specimen showing negative results. Scale bars: 100 μm.