Aggressive fibromatosis-associated with papillary thyroid cancer: two cases and a brief review

Herein, we report two cases of aggressive fibromatosis (AF) arising in the neck that were associated with papillary thyroid cancer. One is a 31-year-old male patient who was diagnosed with AF 9 months after his thyroid cancer operation; there has been no recurrence after surgical resection and postoperative radiotherapy. The other is a 53-year-old female patient who was diagnosed with thyroid cancer and AF simultaneously. There is still no recurrence after surgical resection, endocrine therapy and thyroid-stimulating hormone (TSH) suppression treatment. Both cases showed beta-catenin positivity upon further immunohistochemistry (IHC) examination. The treatment strategy in this situation includes surgical excision combination with radiotherapy and endocrine therapy to reduce the recurrence rate.

Although complications associated with pazopanib, a multitarget tyrosine kinase inhibitor, are known, periosteal reaction as a side effect has never been reported. We present a case involving a male pediatric patient with desmoid tumors treated for 6 months with pazopanib who presented with pain and periosteal reaction in the ilium and scapula. Three months after termination of pazopanib therapy, the periosteal reaction in the scapula resolved and that in the ilium improved. Children receiving pazopanib presenting with focal pain should be examined for the periosteal reaction; this knowledge may facilitate correct diagnosis of symptoms as a drug-associated finding.

In this issue, experts at Royal Marsden Hospital report the outcomes for a large cohort of patients with desmoid tumor (DT) who did not undergo intervention at the time of their initial diagnosis. In this vein, the current report describes 584 DT patients during an 18-year period, 168 of whom were managed with active surveillance. Most of these patients did not need any form of additional treatment during the follow-up period. The main indications in those treated were tumor progression, pain, or both, which occurred within 2.5 years after diagnosis. Active surveillance dominated this large series, especially in the latter part of the study period. Indications for upfront surveillance in this series included: no/limited symptoms, slowly growing tumor, no involvement of relevant structures, and/or patient preference. The Royal Marsden cohort was composed of young patients (median age, 42.2 years; range, 11–86 years) with a median tumor size of 5.9 cm and included all disease sites [abdominal wall (36%), extremity (30%), chest wall (18%), intrabdominal (9%), and other (6%)]. Overall, 36% of the patients progressed (most commonly in the upper extremity and chest wall), 36% remained stable, and 27% had partial or complete regression, in keeping with outcomes of initial observation in other institutional series. The only variable that univariate analysis identified with disease progression was age younger than 50 years at diagnosis. In contrast, variables associated with intervention after a period of observation shown by multivariable analysis were: size (??7 cm; p?<?0.05; hazard ratio [HR], 1.8; range, 1.1–2.8), pain (p?<?0.01; HR, 2.1; range, 1.3–3.3), stable disease (p?<?0.01; HR, 2.1; range, 1.3–3.3), and most strikingly, tumor progression (p?<?0.01; HR, 10.5; 4.1–26.7). Although site also was not statistically significant for intervention, the majority of upper-extremity (58%) and chest wall (57%) patients required treatment, consistent with their clinically appreciated aggressive biology. Following methotrexate plus vinca agent chemotherapy, 8 systemic therapy for DT has remained enigmatic, but possibly more sophisticated and convenient. Pazopanib, sorafenib, and possibly gamma-secretase inhibitors offer patients oral therapy with excellent opportunity for disease control. However, one wonders about the emotional impact on patients to continue returning on a regular basis to a (cancer) center for ongoing CT or MRI scans and follow-up assessment with an oncologic provider. Recently, we reported higher levels of anxiety in individuals with DT even compared with sarcoma, which in fact did not ease with treatment, and continued throughout surveillance. At our center, we have the tools to offer routine distress and symptom screening for all patients—however screening falls short unless resources are available to aid in treating patient anxiety. In a culture of active surveillance, treatment for anxiety, distress, and symptoms still needs to be addressed.

The diagnosis of desmoid fibromatosis or other spindle cell tumors in the sinonasal region is very rare in children and needs to be thoroughly confirmed with immunohistochemical and/or molecular tests. We report 2 patients with such rare tumors and describe the use of next-generation sequencing in their evaluation. A 3-year-old female had a 4.4-cm midline nasal cavity mass involving the bony septum and extending into the base of the skull bilaterally. The moderate cellular fibroblastic proliferation revealed areas of thick keloid-like collagen bands and other areas with myxoid edematous stroma. Deep targeted sequencing identified a novel G34V mutation in the CTNNB1 gene consistent with desmoid fibromatosis. An 11-month-old male infant presented with a right nasal mass that extended through the cribriform plate into the anterior cranial fossa and involved the right ethmoid sinus and adjacent right orbit. Histology revealed an infiltrative atypical fibrous proliferation with focal calcifications that was negative for CTNNB1 and GNAS mutations. A novel RET E511K variant was identified in the tumor and later was also found in the germline and hence rendered of unknown significance. Both cases highlight the utility of next-generation sequencing in the evaluation of pediatric sinonasal spindle cell tumors that may have overlapping pathologic features.

During a follow-up study after the treatment of T cell lymphoma, a 21-year-old man reported an intra-abdominal mass in his right lower abdomen, which was then confirmed using abdominal CT. Therefore, recurrence was suspected due to his medical history. To perform a biopsy, laparoscopic surgery was scheduled, which located the tumor in the mesentery of the terminal ileum, involving the cecum. For this, laparoscopic ileocecal resection was performed. After 7 days, the patient was discharged without complications. Histopathologically, the mass was diagnosed as a desmoid tumor via immunostaining. We herein report a case of an intra-abdominal desmoid tumor, which was successfully treated using laparoscopic surgery.

Characterization of the tumor immune microenvironment (TME) and immune checkpoints can possibly help identify new immunotherapeutic targets for Desmoid tumors (DTs). We performed immunohistochemistry (IHC) on 33 formalin-fixed paraffin-embedded (FFPE) tissue sections from DT samples to characterize the TME and the immune checkpoint expression profile. We stained for CD3, CD4, CD8, CD20, FoxP3, CD45RO, CD56, CD68, NKp46, granzyme B, CD27, CD70, PD1 and PD-L1. We found that most of the tumors showed organization of lymphocytes into lymphoid aggregates at the periphery of the tumor, strongly resembling tertiary lymphoid organs (TLOs). The tumor expressed a significant number of memory T cells, both at the periphery and in the tumoral stroma. In the lymphoid aggregates, we also recognized a significant proportion of regulatory T cells. The immune checkpoint ligand PD-L1 was negative on the tumor cells in almost all samples. On the other hand, PD1 was partially expressed in lymphocytes at the periphery of the tumor. To conclude, we are the first to show that DTs display a strong immune infiltration at the tumor margins, with formation of lymphoid aggregates. Moreover, we demonstrated that there is no PD-L1-driven immune suppression present in the tumor cells.