TY  - JOUR
A1  - Maurus, K.
A1  - Kosnopfel, C.
A1  - Kneitz, H.
A1  - Appenzeller, S.
A1  - Schrama, D.
A1  - Glutsch, V.
A1  - Roth, S.
A1  - Gerhard-Hartmann, E.
A1  - Rosenfeldt, M.
A1  - Möhrmann, L.
A1  - Fröhlich, M.
A1  - Hübschmann, D.
A1  - Stenzinger, A.
A1  - Glimm, H.
A1  - Fröhling, S.
A1  - Goebeler, M.
A1  - Rosenwald, A.
A1  - Kutzner, H.
A1  - Schilling, B.
T1  - Cutaneous epithelioid haemangiomas show somatic mutations in the mitogen-activated protein kinase pathway
JF  - British Journal of Dermatology
N2  - Background
Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour with marked inflammatory cell infiltration, which exhibits a high tendency to persist and frequently recurs after resection. So far, the underlying pathogenesis is largely elusive.

Objectives
To identify genetic alterations by next-generation sequencing and/or droplet digital polymerase chain reaction (ddPCR) in cutaneous EH.

Methods
DNA and RNA from an EH lesion of an index patient were subjected to whole-genome and RNA sequencing. Multiplex PCR-based panel sequencing of genomic DNA isolated from archival formalin-fixed paraffin-embedded tissue of 18 patients with cutaneous EH was performed. ddPCR was used to confirm mutations.

Results
We identified somatic mutations in genes of the mitogen-activated protein kinase (MAPK) pathway (MAP2K1 and KRAS) in cutaneous EH biopsies. By ddPCR we could confirm the recurrent presence of activating, low-frequency mutations affecting MAP2K1. In total, nine out of 18 patients analysed showed activating MAPK pathway mutations, which were mutually exclusive. Comparative analysis of tissue areas enriched for lymphatic infiltrate or aberrant endothelial cells, respectively, revealed an association of these mutations with the presence of endothelial cells.

Conclusions
Taken together, our data suggest that EH shows somatic mutations in genes of the MAPK pathway which might contribute to the formation of this benign tumour.
KW  - protein kinase pathway
KW  - Background Epithelioid haemangioma
KW  - somatic mutations
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258333
VL  - 186
IS  - 3
ER  - 
TY  - JOUR
A1  - Serfling, S.
A1  - Zhi, Y.
A1  - Schirbel, A.
A1  - Lindner, T.
A1  - Meyer, T.
A1  - Gerhard-Hartmann, E.
A1  - Lappa, C.
A1  - Hagen, R.
A1  - Hackenberg, S.
A1  - Buck, A. K.
A1  - Scherzad, A.
T1  - Improved cancer detection in Waldeyer’s tonsillar ring by \(^{68}\)Ga-FAPI PET/CT imaging
JF  - European Journal of Nuclear Medicine and Molecular Imaging
N2  - Purpose
In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [\(^{18}\)F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [\(^{18}\)F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer’s tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer’s tonsillar ring, the novel PET tracer [\(^{68}\)Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging.

Methods
Eight patients with suspicion of a malignant tumor in Waldeyer’s tonsillar ring or a CUP syndrome were examined. PET/CT scans with [\(^{18}\)F]-FDG and [\(^{68}\)Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings.

Results
Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [\(^{18}\)F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [\(^{68}\)Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUVmax for the primary tumors was 21.29 ± 7.97 for \(^{18}\)F-FDG and 16.06 ± 6.29 for \(^{68}\)Ga-FAPI, respectively (p = 0.2). The mean SUVmax for the healthy contralateral tonsils was 8.38 ± 2.45 for [\(^{18}\)F]FDG and 3.55 ± 0.47 for [\(^{68}\)Ga]FAPI (p < 0.001). The SUVmax ratio of [68Ga]FAPI was significantly different from [\(^{18}\)F] FDG (p = 0.03). Mean TBRmax for the [\(^{68}\)Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [\(^{18}\)F]FDG (10.90 vs. 4.11).

Conclusion
Non-invasive imaging of FAP expression by [\(^{68}\)Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [\(^{18}\)F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [\(^{68}\)Ga]FAPI PET/CT imaging.
KW  - Waldeyer’s tonsillar ring
KW  - cancer of unknown primary (CUP)
KW  - positron emission tomography/computed tomography
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235271
SN  - 1619-7070
VL  - 48
ER  -