HNPGLs usually demonstrate marked enhancement of intra-tumoral vessels following contrast administration on CT, a low signal on T1-weighted images, and an intermediate to high signal on T2-weighted MRI images. They also often enhance intensely after gadolinium injection on MRI. Flow signal voids in the tumor are typical of PGL, with a “salt and pepper” appearance on spin-echo sequences. These flow voids correspond to intra-tumoral arterial vessels on MR angiography [15–19]. These MR angiography sequences can be achieved without gadolinium (3D time of flight) or with gadolinium injection (3D time-resolved gadolinium). These sequences have been shown to be highly informative, with sensitivities and specificities of 90 % and 94 % [16] and 100 % and 94 % [17], respectively. There is a recent trend of using time-resolved 4D gadolinium MR angiography [19]. The 4D time-resolved imaging of contrast kinetics (TRICKS) technique enables evaluation of both intra-tumoral vessels (early arterial phase) and tumor perfusion, including capillary permeability. Fusion images between 3D volumetric interpolated fat-saturated (FATSAT) T1-weighted (VIBE) and 4D MR angiography are particularly informative. Diffusion-weighted imaging (DWI), which is dependent on tissue cellularity, may be useful in preoperative characterization and prognosis assessment of PGL, but further evaluation is needed [20].

Radionuclide imaging techniques now play a crucial role in the evaluation of HNPGLs. Several excellent studies have demonstrated the superiority of Octreoscan for HNPGLs compared to metaiodobenzylguanidine (^123/131I-MIBG), with sensitivities of 89–100 % and 18–50 %, respectively [21–26]. However, the sensitivity of this imaging modality needs to be revised downward, because some lesions are only a few millimeters in size, and are therefore not detectable by available cameras [27]. The recently introduced hybrid SPECT/CT cameras have increased diagnostic confidence in image interpretation and enhanced sensitivity, but practical constraints such as long imaging times remain important limitations. PET imaging is a highly sensitive functional imaging technique for HNPGLs.

HNPGLs can be sporadic or can occur as components of hereditary syndromes in up to 30–40 % with variable penetrance and increased risk for recurrent behavior and tumor multiplicity. Of all the known genetic mutations, mutations in SDHD are currently the leading cause of hereditary HNPGLs (>50 %), followed by SDHB (20–35 %) and SDHC (15 %) mutations [44–46]. Some correlations between the gene(s) involved and tumor location have been found. SDHD-linked patients have a 75 % risk of developing HNPGLs throughout their life, with concomitant thoracoabdominal PGLs in about 10 % of cases [27]. SDHB-linked PGL syndrome is characterized by a high rate of retroperitoneal PGL or HNPGLs, but a combination of sympathetic and parasympathetic PGLs is found less frequently [27]. Furthermore, it should be noted that multiple PGLs at a very young age found in several family members may be related to SDHAF2 mutations [47]. So far, only HNPGLs have been reported in these rare families. The inheritance pattern of the SDHB and SDHC genes is autosomal dominant, whereas for SDHD and SDHAF2 genes, the disease occurs only when the mutations are inherited from the father, which is consistent with maternal imprinting [48]. Until present, mutations in SDHA have been described in several isolated cases. Major predictors for hereditary HNPGLs are a family history of PGL (especially those related to SDHD mutations), a previous personal history of HNPGLs or sympathetic PGL, and multifocality or a characteristic syndromic presentation [5, 46]. Currently, a well-characterized syndromic presentation includes the existence of other tumor types associated with the presence of a PGL (e.g., renal cell carcinoma, gastrointestinal stromal tumor, and pituitary adenomas can also be related to SDHx mutations) [49, 50].

Imaging phenotypes may vary across genotypes. Although ¹⁸F-FDG is not specific, this imaging modality has clearly shown a higher sensitivity over CT/MRI, ^123/131I-MIBG, ¹⁸F-FDA, and ¹⁸F-FDOPA [32, 51, 52]. More recently, ⁶⁸Ga-DOTATATE PET/CT detected more SDHx-associated PGLs than ¹⁸F-FDOPA PET/CT [39–41, 43]. It is expected that ⁶⁸Ga-DOTA-SSA PET/CT will become the preferred functional imaging modality for HNPGLs in the near future.

There are several potential causes to consider in the differential diagnosis (Tables 13.2 and 13.3).

The aim of pre-therapeutic imaging is to provide the most complete staging of the disease. In this way, treatment can be tailored to each specific situation. The initial staging of a HNPGL is currently based on the use of anatomical and functional imaging approaches in order to determine the tumor extension into the bone and surrounding soft tissue; to determine tumor multiplicity, not only in the head and neck area but elsewhere in the body; and finally to exclude any metastases.