The study analyzes the treatment data of surgical measures of patients with FPNF. The study applies an overlay technique to describe the frequency of tumor localization. The study results provide an overview of facial regions in particular need of treatment. Furthermore, clinical treatment data are analyzed to specify inpatient treatment needs. The presented quantitative analyses of treatment data provide a guide for planning facial surgical procedures in patients with FPNF. However, in individual cases, clinical treatment data may differ from the values presented here if unusual tumor manifestations are included in the treatment calculation. The complication rate is just under 20% and justifies the inpatient care of the patients as well as the length of stay in the hospital individually adapted to the course of treatment. The correlation analysis shows the relationship between the number of dermatomes affected and the number of surgeries and hospital days of stay after surgery.

Topographic analysis of craniofacial PNF tumor spreads is an important contribution to assessing the treatment needs of these patients. Among NF1-associated PNF, craniofacial PNF requires the most surgical treatment [3, 13]. Both classifications of the facial surface used for topographic evaluation show PNST frequency symmetry illustrated by the tumor-affected regions marked with the same intensity of color on both sides, namely eyes/orbits, temples, cheeks, and lateral forehead. The distribution pattern confirms the assumption that there is no side predilection for the tumor type. The need for surgical treatment focuses on the orbital and periorbital regions and face lifting procedures in cases with extensive tumor spread. However, it must be considered that the determination of tumor topography was performed using predominantly surgical photographs, and therefore the exact tumor spread may be more extensive than the external visual appearance or data evaluation suggests. Classification of tumor locations according to anatomical regions identifies tumor growth extending beyond single regions. According to the present study, the association of tumors with anatomical regions is an uncertain indicator of tumor spread and load, both because tumor spread does not respect these boundaries and because tumor infiltration can destroy these landmarks. However, this finding should not be generalized to the entirety of FPNF. A bias in the NF1-associated size of facial tumor extensions in favor of more advanced and extensive manifestations in a reference center for the treatment of NF1 patients is very likely. In other words, smaller, circumscribed tumors of this type can be reliably assigned to an anatomic region. Superimposing the affected region with anatomical landmarks, e.g., by mirroring the unaffected side of the face onto the diseased side, is a practical step in the assessment of tumor-associated changes in hard and soft tissues. This procedure is based on the fact that the neural territories of tumor-altered facial regions do not cross the anatomical boundary, i.e., the median-sagittal plane [14]. The classification of the facial skin surface according to dermatomes shows that in individual cases, the tumors can be assigned very variably to the defined areas. There are cases in which the tumors infiltrate the dermatome only partially or grow beyond the borders according to visual inspection. On the other hand, overlapping of tumor-invaded facial dermatomes is frequent, so classification must be based on combinations of adjacent dermatomes with tumor-related skin changes. Nevertheless, orientation to the dermatomes is an essential and reliable clue in defining facial tumor spread and associated skeletal lesions [8, 15]. In this respect, there is a difference between the assignment of the FPNF spread of NF1 patients to the extremities and dermatomes. In these regions, the segmental distribution of tumors across body regions was obvious [9, 10]. The two-dimensional evaluation method chosen here is suitable for assessing the individual course of the disease (e.g., to objectify disproportional tumor growth) and planning surgical interventions in the facial regions.

The evaluation of histological findings illustrates consensus between clinical assessment and tissue findings in many cases [16]. However, a review of tissue findings reveals that clinical assessment of misshapen, often large skin tumor regions according to histologic criteria encompasses different subtypes of PNST. The difference between the clinical assessment of a large PNST as "plexiform" and histological diagnosis of these tumors mainly concerns the distinction between PNF, diffuse neurofibroma, and diffuse PNF (Table 2). In a recent Japanese study, the distribution of PNF on the body surface was mapped [17]. A total of 19.2% of diffuse PNF were in the head and neck region. However, the cartography of the tumors was not classified according to dermatomes. Likewise, the diagnosis of PNF was not further specified. Other studies suggest that craniofacial PNF is among the most common tumor sites in NF1 patients requiring surgical intervention [3, 13]. However, from clinical judgment, the differences between PNF and diffuse neurofibroma appear to be gradual (Table 2).

Postoperative bleeding must be considered in the reduction of plexiform neurofibroma. Bleeding can already influence the extent and duration of the measures during the surgical intervention [18]. However, the wound healing results are aesthetically satisfactory [19].

The superimposition of facial findings on digital schematics with the outlines of the head or face is currently a widely used diagnostic tool for illustrating local, visible findings (e.g., tumors or malformations of the facial skin), including the assessment of their progression [20, 21]. Furthermore, digital facial images are used to study myocutaneous functions [22] and the expressive behavior of defined examination groups based on the automated recognition of facial landmarks [23]. Determining the frequency of nosologically defined facial findings concerning anatomical regions can support the characterization of predilection sites for a disease [20].

The approach was employed in the current investigation to identify the therapy requirements for a group of individuals with a tumor predisposition syndrome. Tumors of the face that are distinctive and frequently deforming may manifest in NF1. The selection criterion allows for an assessment of which regions are particularly commonly examined by patients needing treatment, but it does not allow for safe conclusions to be taken regarding the incidence of certain regions of the face acquiring PNF in the community of NF1 patients.

Individual color-coded overlays of the frequency distribution of PNF-related craniofacial skeletal dysmorphology [24] and soft tissue abnormalities [21] should aid in a better understanding of the complicated pathology of the area, possible treatments, and outcomes.

Additionally, the simultaneous surface representation of bone and skin in a projection should be useful for planning combined skeletal-soft tissue surgeries on the craniofacial region in NF1-affected patients.

The study has several limitations. On the one hand, the borders of the tumor that are visible or defined by tools (imaging, surgical documentation, and histology) were accepted as the true extent of the tumor and transferred to the diagram. Inaccuracies in the registration and in the transmission may have had an impact on the outline of the registered area in individual cases. However, this inaccuracy mainly affects the edges of the tumor and therefore probably has little effect on displaying main fields of tumor spread visible as the superimpositions of the individual tumor extensions. A systematic limitation of the procedure is the fundamental uncertainty of the extent of the tumor in the individual case. However, this criticism applies to every clinical study on the subject. Because many tumors could not be completely removed, histologic confirmation of tumor margins determined by visual assessment of the situs and evaluation of imaging is lacking. Furthermore, diffuse PNF in particular disperse very thinly in the edge areas of the lesion, so that only the histological examination can confirm the quality of the resection edge. However, such thin and subcutaneously infiltrating, inconspicuous tumors are less often the target of surgical interventions. Furthermore, this is a cross-sectional study on a nosologically defined collective. NF1 is a chronic progressive disease. Although facial PNF are regarded as congenitally manifest tumors, in our own experience the potential for growth and infiltration does not end at the end of the growth period. The visual definition of the tumor boundaries of the cross-sectional study reflects only the graphically simplified current extent of tumor spread at a certain point in time. In individual cases, a follow-up study using this graphic technique would offer an abstract assessment of tumor growth and derived from this in clinical studies on larger patient groups, information on the preferred direction of growth and the expected tumor volume.