Ga-68 Chemokine Receptor-4 PET/CT Imaging in Schminke Type of Nasopharyngeal Carcinoma

A 43 years old woman presented with a lump in the left breast for ten months, gradually progressive in size with no associated symptoms. Fine needle aspiration cytology revealed features suggestive of malignancy which was followed with a core needle biopsy. The histopathological report revealed an invasive ductal carcinoma grade III, ER 2+, PR -ve, HER2/neu 3+ with Ki 67 index of 30%. She underwent F-18 FDG PET/CT for initial staging [Figure 1]. As part of an ongoing project for evaluating CXCR4 receptor expression in newly diagnosed breast cancer, she underwent Ga-68 CXCR-4 PET/CT imaging [Figure 2].

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Figure 1 FDG PET/CT demonstrated multiple FDG avid lesions on the maximum intensity projection (MIP) image (a). Transaxial CT, fused PET/CT, and PET images localized the increased FDG avidity in the left breast lesion (b-d, SUVmax 7.8 with left axillary lymph nodes and skeleton; e-g, sternum) suggestive of metastatic breast cancer. Apart from these lesions, increased FDG uptake is also noted in the nasopharynx, which on transaxial images (h-j) is localized to an infiltrative soft tissue mass in the nasal cavity and nasopharynx predominantly on the left side. The mass is seen to involve the adjacent maxillary, sphenoid, and ethmoidal air sinuses with infiltration of surrounding structures with a SUVmax of 15.1

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Figure 2 MIP image of CXCR-4 PET/CT demonstrated multiple tracer avid lesions. On transaxial images, mild increased tracer is localized to the left breast lesion (b-d) and left axillary and sternal lesion (e-g). In addition, intense CXCR-4 expression was noted in the nasopharyngeal lesion (h-j) and had a SUVmax value of 12.2. In view of clinical and imaging suspicion of a synchronous second primary in the nasopharynx, she underwent pathological confirmation, which demonstrated lymphoepithelial nasopharyngeal carcinoma (Schminke type)

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Nasopharyngeal carcinoma is a rare malignancy arising from the epithelial cells of the nasopharynx. It is endemic to certain parts of Asia and Africa and has more incidence in males and smokers.[1] The chemokine receptor overexpression has been reported as an adverse prognostic factor in various malignancies. Among these, CXCR-4 is the most widely expressed receptor on malignant tumors, and its role in tumor angiogenesis and lymphatic vasculature has been studied extensively.[23]

Chemokine imaging was found to be more sensitive for in vivo quantification of CXCR-4.[4] Lympholucin is a synthetic analog of CXCL12/SDF-1, the only known natural ligand of CXCR-4. Moderate CXCR-4 expression is noted in many solid tumors such as neuroendocrine tumors, cholangiocarcinoma, pancreatic carcinoma, and hepatocellular carcinoma.[5] CXCR-4 imaging also demonstrated chemokine receptor expression in primary and recurrent breast carcinoma and plasmacytoma.[67] However, its role in nasopharyngeal cancer is yet to be studied. In the present case, we highlight the CXCR-4 expression in a synchronous second primary of the nasopharynx in a known case of breast cancer. This case also gives insight into possible treatment strategies with CXCR-4 targeted therapy.