Pediatric Desmoid Tumor of the Head and Neck: A Systematic Review and Modified Framework for Management by Age Group

Background: Unlike in adults, pediatric head and neck desmoid tumors (DTs) have greater capacity to interfere with normal anatomical development. Therefore, adequate interventions and management must be defined. We aimed to provide the most comprehensive systematic review on pediatric head and neck DTs to date, including assessment of lesion location predominance, intervention, and management, and examination of any associations between age and outcomes like surgical margin status, recurrence, and complications.

Methods: A systematic literature review was conducted between January 1990 and December 2023 using PubMed, Scopus, and MEDLINE databases following the Preferred Reporting Items for Systematic Review and Meta-Analyses 2020 guidelines. We aimed to elucidate intervention and management strategies by studying various outcomes in 0-11 and 12-21 year olds.

Results: The literature search yielded 44 studies, totaling 121 patients. Most head and neck DTs localized to the mandible, cranium, and neck; occurred early (P = 4.18 years); and underwent local resection with positive margins. Older and younger patients shared no difference in complication or recurrence rates.

Conclusions: We found recurrence is likely to occur with positive margins. Because standard treatment of DTs is surgical resection with negative margins, if technically feasible with reasonable associated morbidity, we suggest additional resection of the tumor to achieve negative margins. We also recommend more robust follow-up data collection, not only due to desmoid’s high recurrence and data paucity in patients older than 12 years, but also, to better establish best management practices.

Classical and mixed congenital mesoblastic nephroma (CMN) are characterized by an internal tandem duplication (ITD) of the EGFR gene, in contrast to cellular CMN that usually harbors an ETV6::NTRK3 gene fusion. This same fusion occurs in infantile fibrosarcoma, and this tumor can be considered as the soft tissue equivalent of cellular CMN. A soft tissue equivalent of classic/mixed CMN remains undefined at the genetic level. Since classical CMN resembles fibromatosis of soft tissue histologically, we asked whether fibromatosis in children might show EGFR ITD. ITD was investigated using the polymerase chain reaction and primers for exons 18 and 25 of the EGFR gene. Seven of the eight cases of classical or mixed CMN were positive by this approach, but none of the five cellular CMNs. Of 11 cases of fibromatosis (six plantar, two digital, and three desmoid), none were positive for EGFR ITD. Within the limits of this small study, we conclude that pediatric fibromatosis is likely not characterized by EGFR ITD. There are isolated reports of pediatric soft tissue tumors that harbor EGFR ITD, but these have the appearance of infantile fibrosarcoma or mixed CMN rather than fibromatosis. We did not find any such cases, since all 14 cases of infantile fibrosarcoma in our study had an ETV6::NTRK3 fusion. The soft tissue tumors with EGFR ITD are not a morphologic match for the low-grade histology of classical CMN. Whether they have a similar favorable biology or behave more like fibrosarcoma with an ETV6::NTRK3 fusion or an alternative fusion involving other kinases remains to be determined.

Background: Solitary fibrous tumor (SFT) is a remarkably uncommon mesenchymal tumor. STAT6 level and a combination of clinical, pathological, and molecular features are required to arrive at a proper diagnosis.

Case summary: In this report, we present an intriguing case involving a 43-year-old woman who initially exhibited symptoms of a bleeding retroperitoneal tumor, initially resembling a gastrointestinal stromal tumor, but later confirmed as an SFT. However, a year later, what was initially believed to be a recurrence of her SFT was instead identified as a desmoid tumor.

Conclusion: Distinguishing SFT from other tumors was pivotal. Correcting misdiagnoses of tumor type initially and of recurrence later was necessary for appropriate treatment of the correct desmoid type.

Background: Sporadic desmoid fibromatosis (DF) is a rare locally aggressive tumor characterized by mutation in exon 3 of CTNNB1 (T41A, S45F, and S45P). Standard of care is active surveillance (AS), but 30% require treatment. DF clinical course is unpredictable and identification of prognostic markers is needed to tailor strategy. In this prospective study, we investigated the consistency between mutation detected in tumor biopsies with that detected in plasma by digital droplet PCR (ddPCR) and the association between circulating tumor DNA (ctDNA) abundancy with clinical outcome.

Patients and methods: A total of 56 patients and 10 healthy donors were included. CTNNB1 mutation status of DF biopsies was determined by Sanger and in case of WT CTNNB1 with NGS. In matched plasma samples at enrollment and during AS at specific timepoints, we evaluated cfDNA quantity and ctDNA.

Results: ctDNA levels were measured in 46 patients with CTNNB1 mutation. Detection rate for T41A, S45F and S45P was 68%, 42% and 100%, respectively. S45P variant has been detected in all patients with S45P mutation. Longitudinal assessment of ctDNA during AS in nine patients (four with regression and five with progression as first event according to RECIST) showed a concordance between the event and ctDNA level change in six out of nine patients tested (4/5 with progression and 2/4 with regression).

Conclusions: Results of ctDNA analysis support its potential clinical implementation as diagnostic tool in specific clinical scenarios where biopsy can be challenging. A prospective clinical trial needs to be performed to evaluate the potential role of ctDNA as predictive biomarker.

Background: Desmoid tumors, also known as aggressive fibromatosis, are rare benign tumors originating from the musculoaponeurotic stroma. While desmoid tumors in the head and neck region are documented, those located in the nasopharynx are exceptionally rare.

Case presentation: A 26-year-old male presented with a three-year history of left nasal obstruction. A CT scan revealed a mass measuring 5.9 × 4.6 × 3.2 cm occupying the left nasal cavity and nasopharynx, with invasion into the maxillary sinus wall. A biopsy confirmed the presence of a nasopharyngeal desmoid tumor. The patient subsequently underwent endoscopic resection followed by radiotherapy.

Discussion: Nasopharyngeal desmoid tumors pose a significant diagnostic challenge due to their rarity. The use of MRI and CT scans is crucial for accurate diagnosis, despite their histologically benign nature. It is important to note that these tumors can mimic malignant lesions, emphasizing the necessity for a thorough and meticulous evaluation during the diagnostic process.

Conclusion: This case underscores the diagnostic and therapeutic complexities associated with nasopharyngeal desmoid tumors. Increased reporting and documentation of such cases are essential to enhance the understanding and management of this rare condition.