Complex surgical management of extensive chest-wall desmoid fibromatosis

Desmoid fibromatosis (DF) is a rare tumor that arises from fibroblasts and myofibroblasts and typically presents on the trunk and limbs. While metastasis of fibromatosis is exceedingly uncommon, DF can spread rapidly to adjacent tissue. Its aggressive nature and frequent recurrence pose challenges for treatment, often requiring a multidisciplinary approach. This case represents the multidisciplinary workup for the identification and management of a rare presentation of desmoid fibromatosis involving the breast. It also discusses the post-surgical follow-up of the patient after a complex resection and reconstruction. We report a case of a patient treated at George Washington University Hospital, Washington, DC. A 26-year-old woman presented with left chest pain. Physical examination revealed an approximately 12-13 cm, ill-defined, immobile mass arising from the left breast. An MRI demonstrated a 9.5 cm spiculated mass involving the left pectoralis major muscle and underlying costal cartilage junctions. The tumor extended deep to the rib margin and along the anterior margin of the pleura. The mass was resected en bloc in a joint case with thoracic and general surgery and reconstructed with a bilateral bi-pedicled, muscle-sparing, transverse rectus abdominis myocutaneous free flap with plastic surgery. Pathology demonstrated desmoid fibromatosis. In conclusion, desmoid tumors of the breast represent a very rare breast neoplasm that can imitate other breast masses, both benign and malignant. Surgery remains an important treatment option and may require coordination and complex surgical planning between various surgical subspecialties.

Desmoid-type fibromatosis (DTF) is a benign but locally aggressive neoplasm characterized by persistent fibroblast activation, unlike reactive fibrosis (RF), where fibroblast activation is transient. Although the Wnt/β-catenin signaling pathway is known to play a role in DTF pathogenesis, the specific genetic drivers contributing to this abnormal fibroblast activation are not fully understood. To identify additional driver genes that underlie the persistent activation of fibroblasts in DTF, we conducted a comparative transcriptome analysis between 29 DTF and 14 RF tissue samples, identifying 4267 differentially expressed genes (DEGs) specific to DTF. These DTF-specific DEGs were significantly associated with pathways involved in embryonic limb morphogenesis and muscle contraction, whereas RF-specific DEGs were linked to immune response and apoptosis. Using weighted gene coexpression network analysis to further elucidate the key regulatory circuits associated with persistent activation of DTF fibroblasts, we identified a highly DTF-specific gene module comprising 120 genes. This module was also significantly enriched in other fibroproliferative conditions showing persistent fibroblast activation, such as keloid disease and idiopathic pulmonary fibrosis. Subsequent analyses identified 7 driver transcription factors (ZNF536, IRX5, TWIST2, NKD2, PAX9, SHOX2, and SALL4) within this DTF-specific module that may contribute to the sustained activation of DTF fibroblasts. We further assessed the utility of 5 key genes from this module (TWIST2, LRRC15, CTHRC1, SHOX2, and SALL4) as potential biomarkers to distinguish DTF from RF using immunohistochemistry. All markers demonstrated excellent diagnostic performance, with TWIST2 showing exceptionally high sensitivity and specificity, surpassing β-catenin, the current standard biomarker for DTF. In conclusion, our study identifies gene modules and driver transcription factors that are highly specific to DTF, offering new insights into the genetic underpinnings of abnormal fibroblast activation in DTF. We also propose novel biomarkers that could improve the diagnostic accuracy and clinical management of DTF.

Pancreatic DTF is a mass formed by fibroblast overgrowth, which is locally invasive but cannot metastasize remotely.DTF is classified into three types according to the location of its occurrence, namely abdominal wall (about 60 %), extra-abdominal (about 25 %), and intra-abdominal (about 15 %).1 Pancreatic DTF, although located in the retroperitoneum, is generally classified as the third type. It is mostly a solid mass, 2 but in this case, the lesion was clearly cystic-solid, and its cystic portion may be related to the involvement of the lesion in the proximal branch pancreatic ducts, which in turn caused cystic dilatation of the corresponding pancreatic ducts.

Aggressive fibromatosis is a rare, benign proliferative disease with unknown aetiology and high recurrence rate. To date, there are only eight reported cases affecting the larynx. Four were managed with total laryngectomy, whilst spontaneous regression happened in one case. Spindle cell carcinoma is a rare but highly aggressive biphasic tumour which often arises in the head and neck. Diagnosed with laryngeal fibromatosis more than 10 years ago, our patient had undergone six trans-oral laser debulking procedures. On this occasion, he presented with a two-week history of severe worsening dyspnoea and hoarseness of voice, requiring urgent debulking. Final pathology results revealed spindle cell carcinoma of the larynx. In this report, we describe the case of laryngeal fibromatosis which progressed to spindle cell carcinoma. To our knowledge, no such case has been described previously. This case highlights an important complication of laryngeal fibromatosis and emphasises the importance of regular follow-ups.

BACKGROUND: Radiotherapy is considered an alternative treatment for unresectable or pharmacologically resistant desmoid-type fibromatosis. While it results in relatively good local control, the risk of secondary malignancy remains a concern. CASE: We present a case of secondary osteosarcoma after carbon-ion radiation therapy (CIRT). A 31-year-old male patient presented with left thigh pain. The tumor was located between the left gluteus maximus and gluteus medius and extended to the vastus lateralis and biceps femoris. It was diagnosed as desmoid-type fibromatosis after needle biopsy. The patient was treated with several medications, including a cyclooxygenase 2 inhibitor and tamoxifen; however, his left thigh pain did not improve. He was treated with CIRT 1 year after diagnosis (67.2 Gy [relative biological effectiveness] 16fr/4wks). He developed osteosarcoma of the left femur 8 years later. He underwent chemotherapy and tumor excision with disarticulation of the left hip. Pulmonary metastasis was detected 6 and 17 months after the definitive surgery and excised using metastasectomy. However, he died due to the recurrence of multiple pulmonary metastases 29 months after the definitive surgery. CONCLUSIONS: In this case, we believe that the low radiation dose to the femur may have caused secondary malignancy.

A new lump in patients with a history of gastrointestinal stromal tumor (GIST) may indicate resistance to medication and recurrence. It is important to monitor for recurrence or metastasis after surgery for GIST, especially in cases of high-risk GIST, as it determines the subsequent treatment. However, it is difficult to differentiate between GIST and DF by imaging. Tissue biopsy and final diagnosis through pathological analysis are usually required. Here, we report 2 cases of primary diagnosis with high-risk GIST and suspected tumor recurrence during Imatinib treatment. The mass was not located where the previous GIST lesion had been. After the complete excision of the mass through laparoscopic surgery, the pathological findings revealed that it was not a recurrence of GIST, but a desmoid-type fibromatosis.