Inflammatory myofibroblastic tumor (IMT) is a distinctive neoplasm that frequently arises in the lung and accounts for ~1% of lung tumors. Distant metastatic IMT is extremely rare and has been poorly investigated. This analysis was specifically performed to explore the clinicopathological and genetic features of early distant metastatic IMT. Two typical patients with distant metastatic IMTs were selected, which accounted for 1.13% of all diagnosed IMTs in the last 5 years. One patient was a 55 year-old male, and the other patient was a 56 year-old female. Both primary tumors arose from the lung, and the initial clinical symptoms of the two patients involved coughing. Both of the imaging examinations showed low-density nodular shadows in the lungs with enhancement around the mass. Microscopically, dense arranged tumor cells, prominent cellular atypia, and high mitotic activity with atypical form were more prominent in the metastatic lesions than in the primary lesions. All of the primary and metastatic tumors in both cases showed positive anaplastic lymphoma kinase (ALK) immunostaining and ALK rearrangement via fluorescence in situ hybridization. The EML4 (exon 6)-ALK (exon 20) fusion variant (v3a/b) was identified by using next-generation sequencing (NGS) and was verified by using reverse transcription polymerase chain reaction (RT-PCR). Furthermore, intronic variants of NOTCH1 and synonymous variants of ARAF were also detected via NGS in one IMT for the first time and were verified in all of the primary and metastatic lesions via PCR. Distant metastasis occurred during a short period of time (1 and 2 months) after the first surgery. One patient presented with multiple metastases to the subcutaneous tissue and bone that responded to ALK inhibitor alectinib therapy, and the tumor was observed to regress 10 months after the initial ALK inhibitor therapy. In contrast, the other patient presented with subcutaneous neck metastasis without ALK inhibitor treatment and succumbed to the disease within 3 months after the surgery. This study demonstrated the possible role of EML4-ALKv3a/b in the malignant progression of IMT and proposed certain therapeutic effects of ALK inhibitors on multiple metastatic IMTs.

Summary Background Dermatofibrosarcoma protuberans (DFSP) is one of the most common dermal sarcomas, but facial DFSP is rare. Patients and Methods The clinicopathological characteristics of 34 facial DFSPs were reviewed. Additional immunostaining (CD34) and PDGFB/COL1A1‐PDGFB fluorescence in situ hybridization (FISH) detection were performed. Results Patients were aged from 24 to 64 years (mean 42.9 years), with a male‐to‐female ratio of 4.7 : 1. Morphologically, classic DFSP (25/34, 73.5 %), pigmented DFSP (2/34, 5.9 %), DFSP with myoid differentiation (1/34, 2.9 %) and fibrosarcomatous DFSP (FS‐DFSP) (6/34, 17.6 %) were found. Moreover, myxoid degeneration was observed in three FS‐DFSP cases (3/6, 50.0 %). All 29 cases that underwent CD34 immunohistochemistry exhibited positive staining (100 %). Genetically, PDGFB rearrangement/COL1A1‐PDGFB fusion was detected in 94.1 % (16/17) of patients. Regarding prognosis, the recurrence (83.3 % vs. 59.1 %) and metastasis (33.3 % vs. 0 %) rates were higher in FS‐DFSPs than that in ordinary DFSPs. All available surgical margins were positive before DFSPs recurrence. All patients with negative excision or re‐excision margins were alive without evidence of disease (mean, 81.8 months; median, 81 months). Conclusions Facial DFSP occurs predominantly in males, while FS‐DFSPs are more likely to exhibit myxoid degeneration and a worse prognosis. Notably, negative surgical margin status determined a satisfactory prognosis.

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Hintergrund: Dermatofibrosarcoma protuberans (DFSP) ist eines der häufigsten dermalen Sarkome, kommt aber im Gesicht nur selten vor.Patienten und Methoden: Die klinisch-pathologischen Charakteristika von insgesamt 34 fazialen DFSP wurden näher untersucht. Hierzu wurden zusätzlich eine Immunmarkierung (CD34) sowie eine PDGFB/COL1A1-PDGFB Fluoreszenz-in situ-Hybridisierung (FISH) durchgeführt.Ergebnisse: Die untersuchten Patienten waren zwischen 24 und 64 Jahre alt (im Mittel 42,9 Jahre), das Verhältnis Mäner zu Frauen betrug 4,7 : 1. Morphologisch fanden sich "klassische" DFSP (25/34; 73,5 %), pigmentierte DFSP (2/34; 5,9 %), DFSP mit myoider Differenzierung (1/34; 2,9 %) und fibrosarkomatös transformierte DFSP (DFSP-FS) (6/34; 17,6 %). Zusätzlich zeigte sich bei drei Fällen mit DFSP-FS eine myxoide Degeneration (3/6; 50,0 %). In allen 29 Fällen mit CD34-Immunhistochemie-Untersuchung fand sich eine positive Anfärbung (100 %). In der genetischen Untersuchung wiesen 94,1 % (16/17) der Patienten eine PDGFB-Rearrangement/COL1A1-PDGFB-Fusion auf. Die Raten an Rezidiven (83,3 % vs. 59,1 %) und Metastasierung (33,3 % vs. 0) lagen bei den DFSP-FS deutlich höher als bei den gewöhnlichen DFSP. In allen Fällen von Rezidiven waren die Schnittränder vorher als positiv eingestuft worden. Umgekehrt waren alle Patienten mit negativen Schnitträndern (bei der Exzision oder Re-Exzision) noch am Leben, ohne weitere Krankheitszeichen aufzuweisen (Mittel 81,8 Monate, Median 81 Monate).Schlussfolgerung: DFSP tritt vor allem bei Männern auf. Bei DFSP-FS besteht eine höhere Wahrscheinlichkeit für myxoide Degeneration bei insgesamt schlechterer Prognose. Ein negativer Status der chirurgischen Schnittränder zeigte eine gute Prognose an.