Another relatively rare disease, reported in a 3-year-old child, is alveolar rhabdomyosarcoma (ARMS) (Zhang et al.), which is characterized by its aggressive behavior, poor prognosis, and unfavorable outcome. ARMS may be present in critical organs and can invade the spinal canal that leads to the central nervous system; nevertheless, clinical symptoms can be variable, depending on the size and site of the retroperitoneal mass and distant metastases. In this patient, a post-operative biopsy and FKHR gene rupture confirmed ARMS, while PET imaging helped to reveal retroperitoneal lymphatic metastases, which was not detected by CT imaging or ultrasound. The authors also emphasized that retroperitoneal ARMS requires careful differentiation, potentially being misdiagnosed as neuroblastoma, which is a very common pediatric extra-cranial, solid tumor. The advantage of using 18F-FDG PET/CT for pediatric patients lies in the possibility to evaluate disease activity and therefore guide therapy and prognostication, as is the case for Kaposiform hemangioendothelioma (KHE), a rare vascular neoplasm mostly appearing in infancy or early childhood. A 13-month-old girl with KHE presented with limited movement of the lower extremity caused by spinal involvement and a normal platelet count (Qiu et al.). 18F-FDG PET/CT allowed documentation of mild hypermetabolism in the lesion, consistent with a low-grade tumor, as subsequently confirmed by KHE bioptical diagnosis. Treatment with 6-month sirolimus monotherapy reduced the retroperitoneal lesion's size, alleviating clinical symptoms.
As the diagnosis of occult cancers with unknown primary sites is very complicated and challenging, a biopsy is essential for a confident diagnosis; nevertheless, PET/CT or PET/MRI imaging can contribute, in most cases, to the planning of personalized treatment, precise staging, and improved risk-estimation. Zeng et al. reported a case of rare retroperitoneal clear-cell carcinoma with an unknown primary focus. Although no obvious abnormality was observed in either kidney, via imaging (PET/CT and MRI) or surgical exploration, interestingly, immunohistochemistry results confirmed a renal origin of the carcinoma. PET/CT revealed enormous 18F-FDG activity in the retroperitoneal clear-cell carcinoma (as observed in high-grade renal clear-cell carcinomas), likely due to its pathological grade, suggesting that high 18F-FDG uptake could be related to low tumor differentiation.
Besides its widespread oncological application, 18F-FDG PET/CT also plays a key role in inflammatory and infectious settings, where its ability to quantify disease extent, evaluate treatment response, and identify inflammatory occult sites, which remain undetermined after clinical and/or conventional imaging assessment, are exploited. In this regard, Tsai et al. demonstrated the additional diagnostic value of 18F-FDG PET imaging for resolving a challenging case of right-sided persistent lower-back pain after an L5-S1 laminectomy, refractory to several different therapies. When initial spinal root MRI imaging was considered inconclusive to support a surgical intervention, a subsequent 18F-FDG PET/MRI revealed increased tracer uptake exclusively along the right S1 root, consistent with the clinical presentation; this metabolic finding allowed the final diagnosis and localization of an inflammatory neuropathy, secondary to epidural fibrosis, with sacral root entrapment. This case highlights the diagnostic value of simultaneous PET/MRI imaging for soft-tissue and spinal cord abnormalities, by combining metabolic and anatomic information.
As stated above, since most tumors demonstrate an increased 18F-FDG uptake (greater than background tissues and benign lesions), metabolic information provided by 18F-FDG PET imaging often plays a crucial role in correctly differentiating malignant and benign diseases. However, the chance of misinterpreting a hypermetabolic benign finding as malignant requires extreme caution from PET readers, particularly in cases of rare diseases or uncommon presentations, which can potentially lead to unnecessary diagnostic or therapeutic procedures, thereby negatively affecting patients' care. In this regard, the occurrence of a benign lesion mimicking malignancy was reported in a patient with fast-growing soft tissue nodules confined to the left groin. This was initially suspected as malignant due to conventional imaging features and an increased 18F-FDG uptake at PET/CT (Hu et al.). Unexpectedly, subsequent surgical excision revealed an uncommon localization of Kimura's disease, a rare benign chronic lympho-granulomatous disease. Based on the overall patient history, as well as clinical, laboratory, and imaging data, this case highlights the need to consider differential diagnoses for 18F-FDG-avid lymph nodes, ranging from malignant to inflammatory or infectious diseases, such as lymphoma, nodal metastases, active tuberculosis, sarcoidosis, or benign lympho-proliferative disorders, all of which can show a similar degree of tracer uptake. Similarly, Bore et al. reported a paramediastinal hypermetabolic lesion detected by 18F-FDG PET/CT, initially performed for staging in a patient with ovarian cancer and suspected for metastasis or synchronous primitive tumor. After a subsequent biopsy, mediastinal Schwannoma was instead diagnosed, allowing the patient to undergo chemotherapy and ovarian surgery, as initially planned. This case represents a warning for the risk of PET false positives that, particularly in oncological patients, may result in incorrect upstaging, in turn potentially leading to changes in the planned therapeutic management and consequently, exposing patients to overtreatment and associated toxicity risks. Conversely, the chance of misinterpreting a low 18F-FDG-avid tumor as a benign lesion requires careful consideration, with low metabolic activity in malignant lesions mainly related to low glucose metabolism (reflecting histologically and clinically less-aggressive tumor behavior), low cellularity, or small size. For example, oligo-vertebral plasma cell myeloma localizations, characterized by the coexistence of mild 18F-FDG uptake and morpho-structural changes, may overlap with the morpho-functional features of a vertebral hemangioma, potentially delaying tumor diagnosis and treatment (Hu et al.).