Tumors of the lateral skull base and infratemporal fossa are an enormously rare enties with many different histologies including the recently described “calcified chondroid mesenchymal neoplasm” (CCMN) [1,2,3]. Most patients have symptoms such as a mass, swelling or pain [11]. Because of overlapping radiological and especially histopathological findings, correct diagnosis and managing is still challenging [10, 13]. Other possible diagnoses would be chondroma, tophaceous pseudogout, tenosynovial giant cell tumors, chordomas, chondrosarcoma, chondroblastoma or phosphaturic mesenchymal tumors (PMTs) [5, 9, 10, 13, 15, 16].

Classifying tumors of the skull base preoperatively would be essential, as the entity determines the extent of the surgery to spare the patient unnecessary radical therapy. For example recurrence and survival rates are worse for chordoma than for the rarer chondrosarcoma and benign chondromas do not have to be radically resected [17, 18]. Chordoma and chondrosarcoma cannot be reliably distinguished from each other in CT or MRI scans [17, 19]. The morphologic aspects of the CCMN described here are similar to those of chordoma and chondrosarcoma and a preoperative diagnosis is not possible based on imaging. Because of the infiltrating and destructive growth a malignant diagnoses could have been possible in our case. In contrast to the CCMN in our case the CCMNs in the case report by Kallen et al. mostly had indolent or benign radiologic features. Proposed diagnosis (sorted from frequent to rare) were benign and malignant entities such as soft tissue chondroma, PMT, sarcoma or chondrosarcoma variant, tenosynovial giant cell tumor, ossifying fibromyxoid tumor, osteochondromatous proliferation chondrobastoma or calcifying aponeurotic fibroma. In imaging the reported CCMNs showed a soft tissue mass hyperintense in T2 and hypointense in T1 like in our case as well as internal calcifications [11]. In summary the diagnosis cannot be made on the basis of imaging alone and a histological clarification is required for diagnosis.

There are also overlaps at the molecular level. FN1 fusions with the RTK FGFR1 and FGFR2 can be also observed in soft tissue chondroma and fusions with the RTK FGFR1 in PMTs [16]. PMTs are rare FN1-fusion-associated neoplasms of uncertain histogenesis and typically induce osteomalacia and hypophosphatemia due to FGFR1 induced secretion of Fibroblast growth factor 23 (FGF23) [10, 20]. Due to all these aspects, correct diagnosis is a challenge even when a histological preparation is available and it is possible that CCMNs are underdiagnosed due to the challenging diagnosis.

Due to the challenging diagnostics, preoperative sampling for histological assessment prior to radical resection was not performed. Firstly, imaging led to the strong suspicion of a malignant tumor. Secondly, we expected a complex histological diagnosis combined with the high probability of not being able to determine this reliably in advance by taking a preoperative sample. Of note, even in the first histological assessment, it was not possible to confirm the diagnosis. Only molecular analysis of the tumor via the TruSight-RNA-Fusion panel yielded the final histological diagnosis. In this regard, frozen sections would not allow for a reliable diagnosis intraoperatively. Noteworthy sampling-errors are well-known in enchondromas and atypical chondrogenic tumours due to well differentiated tumour parts [21]. Furthermore due to the recent first description of CCMNs no statement about a possible malignant transformation within the tumor like in other cartilaginous neoplasms had been possible [21].

Recurrence and survival rates of CCMNs cannot be defined precisely since long term results are missing due to the first description of this entity in 2021 [10]. Although there is no documented overtly malignant biological behavior until now [11], no precise statement of the biology and consequently the radio sensitivity can be made due to the low number of cases. There is one reported case of local recurrence after incomplete excision [11]. Because of this and the infiltrating and destructive growth in our case, locally aggressive growth of CCMNs is possible and complete surgical resection is recommended as the treatment of choice including a close follow-up care including imaging.

A partial resection with better facial nerve results in our case is not recommended based on the current state of research. Should CCMNs prove to be benign with little or no risk of malignant degeneration, tumor reduction could be considered as a treatment option.

Further follow-up of CCMNs is needed to understand the biology of CCMNs in terms of local recurrence, metastasis and local growth. In general, further research is needed to better differentiate between the various neoplasms of the skull base preoperatively.

The external therapy attempt with a tympanostomy tube was inadequate. The tumor was subsequently visible on the external CT image and should have been detected.

In contrast to PMTs, no osteomalacia has been described in CCMNs [11]. This is consistent with the unremarkable blood values of the calcium phosphate homeostasis and the clinically irrelevant slightly low calcidiol and calcitriol in our case.

To summarize, the presented tumor is a CCMNs with involvement of the TMJ region and FN1::FGFR2 fusion. At the time of diagnosis, the tumor showed infiltrating and osteo-destructive growth.