The eye of the beholder: orbital metastases from midgut neuroendocrine tumors, a two institution experience

Abstract

BackgroundMetastases to the orbit occur rarely in midgut neuroendocrine tumor (NET) patients with only 20 cases reported to date. Patients typically present with bilateral involvement of the recti muscles and experience symptoms such as diplopia, proptosis, and decreased vision. Although orbital MRI remains the gold standard for imaging orbital disease, many orbital lesions are now detected on somatostatin-receptor (SSTR) based imaging such as 68Ga-DOTATATE PET-CT.Case presentationsPatient 1 is a 72 year-old female with a well-differentiated G3 ileal NET who was incidentally diagnosed with orbital metastases during a hospitalization for pre-septal cellulitis in 2018. Her disease has been controlled with capecitabine rather than local therapy.Patient 2 is a 68 year-old male with a G2 ileal NET who was diagnosed with orbital involvement after developing left peri-orbital swelling in 2017. He was found to have bilateral rectus muscle involvement and was treated with image-guided radiation therapy (IGRT) to both orbits and achieved disease control.Patient 3 is a 63 year-old female with a well-differentiated G3 ileal NET who was incidentally diagnosed with bilateral orbital masses in her recti after undergoing a 68Ga-DOTATATE PET-CT in 2015. She was asymptomatic initially however has now developed diplopia. She will be starting 177Lu-DOTATATE peptide radionuclide receptor therapy (PRRT) shortly.Patient 4 is a 72 year-old male with a grade 2 ileal NET who was incidentally diagnosed with a left lateral rectus metastasis in 2007. This was monitored via surveillance MRI until it began to grow and became symptomatic in 2015. The patient received stereotactic radiation to the site and has been asymptomatic since.Patient 5 is a 61 year-old female with a grade 2 ileal NET who developed progressive diplopia in 2016. Bilateral orbital metastases were noted on orbital MRI and she completed IGRT to the sites shortly thereafter. In the setting of continued growth of the masses she was switched to chemotherapy with capecitabine which has controlled her orbital disease.ConclusionsNETs can metastasize to the orbits. Orbital disease now often is detected on SSTR-based imaging rather than orbital MRI; when found, it changes treatment approach and surveillance for patients.

Midgut neuroendocrine tumour presenting as orbital metastases

“…The absence of clinical fatigability and negative acetylcholine receptor antibody in the index case, coupled with extensive infiltration of the periorbital muscles, made a neuromuscular junctional abnormality unlikely. 6,13 Focal nodular enlargement of the periorbital muscles on CT/MRI, without invasion of the orbital fat or adjacent osseous structures, indicative of metastases to the extraocular muscle, has been proposed to be specific for metastatic midgut NETs. Das and coauthors propose that a tissue diagnosis and orbital biopsy is unnecessary in this setting.…”

“…Das and coauthors propose that a tissue diagnosis and orbital biopsy is unnecessary in this setting. 13 The case presented was not known with a NET and the biopsy findings were invaluable in determining the underlying aetiology by allowing immunological staining and appropriately directed further investigations.…”

“…According to the 2017 Wold Health Organization (WHO) statement, NETs are classified as either well differentiated or poorly differentiated based on their morphological growth pattern and proliferation indices, namely Ki-67 and mitotic rate (MR). Well-differentiated tumours are classified as Grade 1 (Ki-67 < 3% and MR < 2), Grade 2 (Ki-67 3-20% and MR [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] or Grade 3 (Ki-67 > 20% and MR > 20). 3 Poorly differentiated NETs, also referred to as neuroendocrine carcinomas, have a Ki-67 index > 20% and a MR exceeding 20/10 per high power field (HPF).…”

PET/CT and PET/MRI in ophthalmic oncology (Review)

“…Patients with orbital metastases usually present with diplopia, pain, palpable mass, proptosis, strabismus and visual loss. Breast, lung and prostatic cancer, together with cutaneous melanoma and neuroblastomas in children are the commonest tumors metastasizing to the orbit (36,99,101). Orbital metastases exhibit 18 F-FDG avidity and therefore, 18 F-FDG PET/CT is a valuable diagnostic tool for these patients, enabling detection of the primary tumor, accurate disease staging and effective assessment of therapeutic response (99).…”

“…Orbital metastases exhibit 18 F-FDG avidity and therefore, 18 F-FDG PET/CT is a valuable diagnostic tool for these patients, enabling detection of the primary tumor, accurate disease staging and effective assessment of therapeutic response (99). Furthermore, orbital metastases originating from NETs can be successfully detected on SSTRs imaging with PET using 68 Ga-DOTA-conjugated compounds (18,101). Both ocular and orbital metastases harbor histological features identical to the primary malignancy, and therefore, immunohistochemistry should be employed in challenging cases, where imaging with advanced hybrid techniques fails to detect the primary disease site.…”