18F-FDG PET/CT findings in nevoid basal cell carcinoma syndrome: a systematic review and a new case report – BMC Women’s Health

NBCCS is a rare autosomal dominantly inherited disorder and presents as multisystem abnormalities. This disease has the estimated prevalence of 1/57000 to 1/256000 and both sexes are equally affected [8]. The patched-1 (PTCH1) gene, an onco-suppressor gene that maps at 9q22.3 region, is the major causative gene of NBCCS, which involves in the hedgehog signaling pathway [9, 10]. The mutation is transmitted in an autosomal dominant inheritance from parents to their children. However, 35% to 50% of NBCCS are spontaneous mutations and without family history [10].

The diagnostic criteria for NBCCS were first proposed by Evans et al. in 1993 [11]. After the reviewed and revised by Kimonis et al. in 1997 [12], Kimonis et al. [13] in 2004 and Bree et al. in 2011 [14]. A positive diagnosis was established by the presence of one major criterion and genetic confirmation or by two major criteria or by one major and two minor criteria. The major diagnostic criteria would include multiple basal cell carcinomas, odontogenic keratocyst of the jaw, palmar pitting, calcification of the falx cerebri, medulloblastoma and first-degree relatives with NBCCS. And the minor diagnostic criteria would include rib abnormalities, other skeletal malformations and radiologic changes, macrocephaly, lip palate, cardiac or ovarian fibroma, lymphomesenteric cysts and ocular abnormalities. Although the patient in our report denied family history of NBCCS and did not get PICH1 genetic testing, she had multiple basal cell carcinomas, ectopic calcifications and bilateral rib anomalies, which met the diagnostic criteria for NBCCS.

In previously published articles, the authors mostly reported the clinical presentations and conventional imaging manifestations [4, 15,16,17,18,19,20]. Figueira et al. [21] emphasized that it is essential for dental surgeons and dermatologists to know the signs and symptoms of NBCCS, which is important for patients to get early diagnosis and more rational approach to the treatment. Compared to conventional imaging, PET/CT, as a whole-body examination, had the advantage to find more multisystem abnormalities to support the diagnosis of NBCCS. However, there were only three case reports based on PET/CT scans. Additionally, we were the first to report that breast cancer patient with NBCCS on PET/CT.

Basal cell carcinoma is a relatively inert primary cutaneous neoplasm, which usually invades the local skin and adjacent structures but rarely metastasizes far away. It has also been associated with certain syndromes, the NBCCS being the most common [22]. Ayala et al. [23] held the view that ¹⁸F-FDG PET/CT may be helpful in the management of patients with advanced basal cell carcinoma. Because it not only could assess the location and extent of skin lesions, but also early detect metastases [23, 24]. PET/CT be able to provide more information to clinicians to make therapeutic decisions. The patient in our report had the history of multiple basal cell carcinomas and left invasive breast cancer. If radiologists were aware of the link between various diseases, they would make the correct diagnosis of NBCCS and provide reasonable advice to clinicians. From a prognostic standpoint, early diagnosis and appropriate treatment are critical. If diagnosed, lifelong care with interdisciplinary medical collaboration is necessary [25].

In the case of presenting skin lesions, identification of cutaneous metastases originating from breast cancer and primary basal cell carcinomas was important for the patient’s therapeutic choices. Metastasis from internal malignant tumors to the skin was rare, with an incidence of 0.7–10%. Of all malignant tumors, breast cancer had the highest incidence of cutaneous metastases [26, 27]. Lookingbill et al. [28] reported that 237of 992 breast cancer patients (23.8%) had cutaneous metastases, which could occur via lymphatic or bloodstream transmission and were most common in the head, neck and trunk. We should be vigilant for non-healing ulcers, persistently hardening erythema and newly developed skin nodules [28, 29]. Previous studies suggested that these cutaneous metastatic lesions exhibit varying degrees of increased ¹⁸F-FDG metabolism [26, 27, 30]. In our case, the level of ¹⁸F-FDG metabolism in the treated breast cancer was lower than skin lesions, and no definite metastatic lesion was found at other site. Clinically, the levels of tumor markers (CEA, CA153 and CA125) were within the normal range. Therefore, we suspected that the skin lesions were the other primary tumors. Of course, pathological examination is necessary to identify primary and metastatic lesions. In addition, we also need to identify skin changes associated with breast cancer treatment. Skin toxicity changes associated with immunotherapy for renal cancer have been reported in the past, which closely correlate with the treatment history. The associated skin and subcutaneous lesions would subside after discontinuation of the drug [31].

In conclusion, NBCCS is a relatively rare syndrome, which have the features of developmental abnormalities and tumor susceptibility. Compared to conventional imaging, ¹⁸F-FDG PET/CT has more advantages in diagnosing of NBCCS. It is important to recognize this syndrome on ¹⁸FDG PET/CT because of different diagnoses and therapeutic consequences.