Somatostatin receptor expression in lymphomas: a source of false diagnosis of neuroendocrine tumor at 68 Ga-DOTANOC PET/CT imaging

Tiina Ruuska, Yadith Ramírez Escalante, Samuli Vaittinen, Maria Gardberg, Aida Kiviniemi, Päivi Marjamäki, Jukka Kemppainen, Sirkku Jyrkkiö, Heikki Minn
Acta Oncologica 2018, 57 (2): 283-289

BACKGROUND: 68 Ga-DOTANOC PET/CT is routinely used to image neuroendocrine tumors (NETs). A case of lymphoma initially thought to be NET based on a positive 68 Ga-DOTANOC PET/CT was recently seen at our institution. This prompted us to determine prospectively somatostatin receptor (SSTR) status in patients with lymphoma by immunohistochemical analysis of SSTR subtypes 2, 3 and 5 (SSTR2,3,5 ) and 68 Ga-DOTANOC PET/CT imaging.

MATERIAL AND METHODS: Twenty-one patients with newly diagnosed lymphoma were referred to 68 Ga-DOTANOC and FDG PET/CT prior to any treatment. Tracer uptake was evaluated visually by two nuclear medicine specialists. Maximum standardized uptake values (SUVmax) were determined from 14 nodal and two extranodal regions with highest uptake in each patient. Lesions were then graded with Deauville score (1-5) on FDG PET/CT and modified Krenning score (0-4) on 68 Ga-DOTANOC PET/CT, respectively. SSTR2,3,5 status was analyzed from routine biopsies of lymphomatous tissue and matched to corresponding PET/CT findings.

RESULTS: About 20/21 patients had FDG-positive lymphoma (Deauville score ≥3). Uptake of 68 Ga-DOTANOC was regarded as positive if Krenning score was ≥2 and resulted in 13/21 (62%) patients having 68 Ga-DOTANOC-positive lymphomas. The highest uptake of 68 Ga-DOTANOC was seen in Hodgkin's lymphoma of nodular sclerosis subtype and in diffuse large B-cell lymphoma (SUVmax median 9.8 and 9.7, respectively). Both cases showed strong SSTR2 immunopositivity in tumor cells. Some patients had SSTR2 immunopositivity predominantly in endothelial and dendritic cells and follicular centers of lymph nodes contributing to a positive PET/CT with probably low tumor-specific uptake. SSTR3 and SSTR5 were negative in most lymphoma subtypes.

CONCLUSIONS: According to this pilot study, 68 Ga-DOTANOC PET/CT is positive in some lymphoma subtypes which express SSTRs. These tumors present a potential risk of being misinterpreted as NETs if a representative tumor sample is not available. Lymphomas with high expression of SSTRs may be amenable to treatments targeting these receptors.

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