Dual-tracer PET/CT imaging to determine tumor heterogeneity in a patient with metastatic ACTH-secreting neuroendocrine neoplasm: A case report and literature review

Abstract

Introduction: We present a case of a patient with disseminated ACTH-secreting neuroendocrine neoplasm with biologic heterogeneity between a primary tumor and metastases. The diagnosis was obtained and multidisciplinary management was conducted with a positron emission tomography/computed tomography (PET/CT) scan with Gallium-68 [68Ga]-labeled dodecanetetraacetic acid-tyrosine-3-octreotate ([68Ga]-DOTA-TATE) and Fluor-18 [18F]-fluorodeoxyglucose ([18F]-FDG).

Case report: A PET/CT scan revealed a difference between [68Ga]-DOTA-TATE and [18F]-FDG uptake in primary tumor and several metastases. PET/CT showed high [18F]-FDG uptake and lack of [68Ga]-DOTA-TATE in the primary tumor, whereas both [68Ga]-DOTA-TATE and [18F]-FDG hyperaccumulation were identified in the majority of metastases. Despite positive [68Ga]-DOTA-TATE PET/CT, which is associated with high affinity with the somatostatin receptor 2 subtype, immunohistochemical examination revealed overexpression of the somatostatin receptor 5 subtype only. Perhaps, this explained the ineffectiveness of the treatment with "cold" somatostatin analogs.

Conclusion: This case had an aggressive clinical course, despite cytoreductive surgical treatment and somatostatin analog therapy. PET/CT imaging with two tracers is a molecular tool that demonstrates a biologic heterogeneity between a primary tumor and metastases and yields additional information that may influence the choice of the patient management strategy.

Keywords: PET/CT; [18F]-FDG; [68Ga]-DOTATATE; ectopic Cushing’s syndrome; ovarian NET.

Figure 1

Positron emission tomography/computed tomography (PET/CT) images with Gallium-68 [68Ga]-labeled dodecanetetraacetic acid-tyrosine-3-octreotate ([68Ga]-DOTA-TATE) and Fluor-18 [18F]-fluorodeoxyglucose ([18F]-FDG). (A) The maximum intensity projection (MIP) images summarize the physiological and pathological distribution of [68Ga]-DOTA-TATE in the body. (B) PET/CT scan showed multiple mediastinal lymphatic nodes (blue dotted arrow) and widespread bone metastases with significant uptake of [68Ga]-DOTA-TATE. (C) [68Ga]-DOTA-TATE-positive bone metastasis in the left iliac wing (white arrow). (D) [68Ga]-DOTA-TATE-negative solid mass in the left ovary (red arrow). (E) The MIP images summarize the physiological and pathological distribution of [18F]-FDG in the body. (F) Multiple [68Ga]-DOTA-TATE-positive metastases in mediastinal lymphatic nodes (blue dotted arrow). (G) The axial PET/CT image demonstrated low [18F]-FDG uptake in the bone metastasis in the left iliac wing (white arrow). (H) The axial slice of [18F]-FDG PET/CT showed high [18F]-FDG uptake in the solid mass in the left ovary (red arrow).

Figure 2

Histological and immunohistochemical examination of primary neuroendocrine tumor of the left ovary. (A) Hematoxylin and eosin staining ×50. (B) CD56 ×50. (C) ACTH ×50. (D) GLUT-1 ×100. (E) SSTR 5 subtype ×200.

Figure 3

PET/CT images with [68Ga]-DOTA-TATE and [18F]-FDG. (A) The maximum intensity projection (MIP) images summarize the physiological and pathological distribution of [68Ga]-DOTA-TATE in the body. PET/CT scan showed an increase in the size of the previously detected metastases and the appearance of a new mediastinal lymph node and bone metastases. (B) [68Ga]-DOTA-TATE. PET/CT revealed an avid metastatic lesion in the upper inner quadrant of the left breast (white arrow). (C) The MIP images of [18F]-FDG PET showed intense tracer uptake in the same area as the [68Ga]-DOTA-TATE PET/CT scan. (D) [18F]-FDG-positive metastatic lesion in the left breast (white arrow).

Figure 4

Histological and immunohistochemical examination of a metastatic lesion in the left breast. (A) Hematoxylin and eosin staining ×200. (B) Synaptophysin ×200. (C) ACTH ×200. (D) GLUT-1 ×200. (E) SSTR 5 subtype ×200. (F) Ki-67 ×200.