1Resident, Department of General Medicine, Sree Balaji Medical College and Hospital, Chromepet, Chennai. Email: shlawgouri@gmail.com
2Assistant Professor, Department of General Medicine, Sree Balaji Medical College and Hospital, Chromepet, Chennai. Email: Vinathamadhurkar@gmail.com
3Resident, Department of General Medicine, Sree Balaji Medical College and Hospital, Chromepet, Chennai. Email: drgurucardio@gmail.com
4Resident, Department of General Medicine, Sree Balaji Medical College and Hospital, Chromepet, Chennai. Email: dr.shobana2022@gmail.com
Background: Neuroendocrine Neoplasm (NEN) of unknown primary are rare, and presentation with orbital metastasis is exceedingly uncommon. High-grade NENs lacking somatostatin receptor expression pose diagnostic and therapeutic challenges.
Case Presentation: We report a 55-year-old female with no prior comorbidities, presenting with progressive restriction of left sided extraocular movements for four months, followed by one month of periorbital swelling and proptosis. CT Brain showed a homogenous enhancing soft tissue mass centred along the left lateral orbital wall involving the adjacent frontal and sphenoid bones with lytic changes and mild periosteal reaction with posterior and superior intracranial extension.
Investigations: Suspecting neoplastic aetiology, whole body 18F-FDG PET/CT was done and the orbital mass exhibited FDG avidity with SUV max of 12.01. Additionally, the scan revealed FDG avid ill defined heterogeneously enhancing lesion in the segment VII of the liver, measuring about 2.1 x 1.9 cm, along with FDG avid enlarged confluent and discrete lymph nodes in the periportal, portocaval and paraaortic regions, largest measuring 4.1 x 2.7 cm with mild necrotic changes. Notably, whole body imaging revealed no other abnormalities with no lesions or FDG uptake in the lungs, pancreas, gastrointestinal tract or elsewhere in the hepatobiliary system.
Histopathology and Immunohistochemistry: Biopsy of the orbital lesion showed cores of fibrocollagenous and bone fragments infiltrated by tumor clusters, nests, and ribbons of round-to-ovoid moderately pleomorphic nuclei, dispersed chromatin, moderate eosinophilic cytoplasm, and foci of necrosis. Biopsy of the liver lesion showed cores of liver parenchyma infiltrated by morphologically identical cells, confirming common etiological origin. Immunohistochemistry demonstrated strong positivity for synaptophysin, chromogranin, and CK19, weak-to-moderate CK7 expression, and negativity for CK20 and Glypican-3. The Ki-67 proliferation index was >80%, consistent with a high-grade tumor. Serum tumor markers (AFP, CEA, CA 125, CA 15-3, CA 19-9, LDH) were within normal limits. 68Ga-DOTATATE PET/CT showed no uptake in any of the lesions, indicating absence of somatostatin receptor expression. Overall, these imaging and histological findings indicated a metastatic, high grade neuroendocrine neoplasm of undetermined primary site.
Management: The patient is planned for systemic chemotherapy with cisplatin and etoposide. Next-Generation Sequencing (NGS) is underway to identify molecular targets for potential immunotherapy.
Conclusion: This case illustrates a rare high-grade DOTATATE-negative NET presenting with orbital and hepatic metastases. It highlights the diagnostic complexity, need for multimodal evaluation, and the importance of histopathology, immunohistochemistry, and molecular profiling in guiding management when conventional imaging and receptor-directed therapies are uninformative.
Keywords: Neuroendocrine neoplasm, poorly differentiated, metastatic, Somatostatin, Synaptophysin, Chromogranin.
How to cite this article: Gaur G, Vinatha MC, Gurucharan, Shobana. Proptosis as the First Manifestation of a Metastatic High-Grade Neuroendocrine Neoplasm of Unknown Primary: A Case Report. Int J Drug Deliv Technol. 2026;16(2): 761-764. DOI: 10.25258/ijddt.16.2.81
Source of support: Nil.
Conflict of interest: None