The usefulness of [18F]FDG-PET/CT in detecting and managing cancers with unknown primary site depends on histological subtype

We assessed the role of [18F]FDG-PET/CT in identifying and managing cancer of unknown primary site (CUP syndrome). We reviewed [18F]FDG-PET/CT scans of individuals with CUP syndrome recorded in clinical referral letters from 2012 to 2019. We evaluated the identification of primary tumor (PT) by [18F]FDG-PET/CT, according to histological subtype, and the impact on clinical management. The median age was 65 years, 36/64 males (56%). PTs were detected in 28/64 (44%) patients. Detection was significantly lower in patients with squamous cell carcinoma (SCC) than with other histologies combined, p = 0.034. Mean age, mean SUVmax (10.6 ± 6.0) and organ involvement were similar between patients with and without discovered PTs; and between patients with SCC and with other histologies combined. However, those with SCC were less likely than the others to present with multi-lesion involvement, p < 0.001. [18F]FDG-PET/CT interpretations apparently affected treatment of 8/28 (29%) patients with PT detected, and in none of the 35 whose PT was not discovered, p < 0.001. [18F]FDG-PET/CT appeared helpful in detecting PT in almost half the patients with CUP syndrome; the lowest rate was for patients with SCC pathology. PET/CT showed limited overall value in guiding clinical management, however benefited those with discovered PT.

Improved cancer detection in Waldeyer’s tonsillar ring by 68Ga-FAPI PET/CT imaging

Purpose In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [18F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [18F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer’s tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer’s tonsillar ring, the novel PET tracer [68Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging. Methods Eight patients with suspicion of a malignant tumor in Waldeyer’s tonsillar ring or a CUP syndrome were examined. PET/CT scans with [18F]-FDG and [68Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings. Results Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [18F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [68Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUVmax for the primary tumors was 21.29 ± 7.97 for 18F-FDG and 16.06 ± 6.29 for 68Ga-FAPI, respectively (p = 0.2). The mean SUVmax for the healthy contralateral tonsils was 8.38 ± 2.45 for [18F]FDG and 3.55 ± 0.47 for [68Ga]FAPI (p < 0.001). The SUVmax ratio of [68Ga]FAPI was significantly different from [18F] FDG (p = 0.03). Mean TBRmax for the [68Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [18F]FDG (10.90 vs. 4.11). Conclusion Non-invasive imaging of FAP expression by [68Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [18F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [68Ga]FAPI PET/CT imaging.

Homöopathisierte Misteltherapie beim CUP-Syndrom

ZusammenfassungCUP-Syndrome sind schwierig in der Therapie und in der Regel nur palliativ behandelbar. Die Gabe von potenzierten Misteln kann die Lebensqualität und auch die Lebensquantität häufig wesentlich verbessern. Der Autor stellt drei Kasuistiken vor.

Metastases from Occult Breast Cancer: A Case Report of Carcinoma of Unknown Primary Syndrome

Carcinoma of unknown primary (CUP) syndrome occurs when metastases from an unknown primary site spread to multiple organs. Occult breast cancer (OBC) is defined as a clinically recognizable metastatic carcinoma from an undetectable primary breast tumor. It accounts for 0.3–1% of all breast cancers, often presenting with lymph node, bone, and skin metastases. Clinical and radiological examinations represent the first steps in the diagnostic algorithm for CUP syndrome from OBC. However, histological and immunohistochemical analyses, multidisciplinary team evaluation, and a multidisciplinary therapy are essential in the diagnosis and treatment of CUP syndrome from OBC. We report the case of a 52-year-old woman who underwent the removal of a parietal skin lesion. The histological and immunohistochemical analyses suggested a breast cancer origin. Clinical assessment and laboratory and radiological examinations did not locate the primary tumor. Hormone therapy was offered to the patient; however, she refused it. After 28 months, the patient reported a right cervical lump, and a total-body positron emission tomography showed dissemination of the disease to the lymph nodes and bone. A CUP syndrome from OBC was diagnosed. A multimodality approach with radiotherapy and hormone and biological therapy was started. At present, 5 years from the first presentation, the patient is asymptomatic despite the disseminated disease.

Bone and lymph node metastases from occult mammary carcinoma: a case report of carcinoma of unknown primary (CUP) Syndrome

Cancer of unknown provenance is a rare disease, accounting approximately for up to 1% of all breast cancers. A 68-year-old female was admitted to the Medical Oncology Unit of Policlinico Universitario G.Martino because of diffused bone-involvement, with mixed (osteolytic/osteoblastic) features, which interested almost every skeletal structure of the body (vertebral bodies of the entire column, costal skeleton, sternum, proximal third of both humeri, scapulae, clavicles, pelvis and femurs), suspicious for metastatic disease.