A large intra-abdominal desmoid tumor in a young male: A case report

DOI: https://doi.org/10.21203/rs.3.rs-2301826/v1

Abstract

Desmoid tumor is a mesenchymal originating fibroblastic proliferation, with no metastasizing potential but is locally aggressive. Although recent consensus merge into observation and active surveillance for desmoid tumor, symptomatic tumors, tumors with persistent growth, and intra-abdominal or abdominal wall desmoid tumors may need prompt surgical treatment. Here we report a patient with 38cm-sized intra-abdominal desmoid tumor who were successfully treated with surgical resection due to nonresponsiveness of chemotherapy and progression of symptoms. The patient is recurrence-free for two years, and further follow up is expected. Surgical treatment still resides as an optimal treatment modality for large intra-abdominal desmoid tumors.

Background

Desmoid tumor, also called as desmoid-type fibrosis or aggressive fibromatosis, is a mesenchymal originating fibroblastic proliferation, with no metastasizing potential but is locally aggressive. Its entity is rare, where the incidence is reported 5 to 6 cases in 1 million people per annum in 2016 (1), and its peak incidence resides in 30 to 40 years-old, slightly inclined to female predominance (2). It arises from a deep soft tissue that is practically anywhere in the body, including abdominal wall, intra-abdominal cavity, mesentery, gastrointestinal tract, extremities, chest wall, breast, head, and neck, etc. Surgical resection of the tumor was primary management undertaken for several decades along with systemic therapy or radiotherapy, but recent consensus merged into active surveillance of the tumor after the initial diagnosis due to its indolent course and possibility for spontaneous regression (SR). Indications for active treatment includes symptomatic tumors or evidence of tumor progressions (3). However, intra-abdominal or abdominal wall desmoid tumor may cause local or obstructive symptoms if the tumor is of substantial size or on progression. Herein, we report a young patient with 38cm intra-abdominal desmoid tumor, who were eventually treated with surgical resection after attempting chemotherapy and had not been recurred since two years ago in tertiary academic medical center.

Case Presentation

An 18-year-old Asian male patient with no known medical history was referred to our institution via outpatient clinic due to huge abdominal mass. He had been having upper abdominal discomfort for several weeks, which aggravated over times. As the patient was obese on the first visit (height 166cm, weight 88kg, and body mass index 31.9kg/m2), the mass did not stand out at the sight but was firmly palpable. Abdominal sonography, abdomino-pelvic computed tomography (CT), and positron emission tomography- CT revealed 26cm-long heterogeneously enhanced and lobulated mass with necrotic components (Fig. 1). Whole body bone scan showed no evident metastasis to bones. The mass seemed to originate from omentomesentery, and though the large portion of small bowel were lateralized to the left, there were no obvious signs of organ invasions. On sonography-assisted biopsy, pathology reported spindle cell proliferative lesion in myxoid background and immunohistochemical stains were negative on α-SMA, CD34, MUC-4, S-100, and ALK, and was positive on β-catenin, indicating high possibility of desmoid-type fibromatosis. No genetic analysis was performed for CTNNB1 or adenomatous polyposis coli (APC) gene mutations.

The upfront surgical resection seemed challenging due to its high occupancy in the abdominal cavity, so the patient was first offered being treated with chemotherapy with the regimen of doxorubicin (20mg/m2 infusion for 1 hour in day 1–3) and dacarbazine (300mg/m2 infusion for 1 hour in day 1–3) by pediatric oncologist. Sperm banking was carried out prior to the chemotherapy. After infusing two cycles with 3-week interval, the tumor size had increased into 32cm of diameter in a month from the first visit, causing heavier abdominal discomfort and pain in the patient. Thus, the chemotherapy regimen had changed to etoposide (100mg/m2 infusion for 3 hours in day 1–5), carboplatin (200mg/m2 infusion for 3 hours in day 1–2), and ifosfamide (1,800mg/m2 infusion for 3 hours in day 1–5). However, nonresponsiveness of the tumor and side effects such as neutropenic fever and general weakness of chemotherapy leading to admission via emergency room made it hard to postpone the surgical resection of the tumor. Preparing for the operation, the patient was injected with antibiotics for the neutropenic fever, transfused with platelet concentrations (PCs) for thrombocytopenia, and total parenteral nutrition. Preoperative consults were made with upper gastrointestinal, hepatobiliary, and vascular surgeons for possible cooperation. At the day before the surgery, percutaneous angiographic embolization was performed for the feeding vessel of the tumor, which branched from the superior mesenteric artery. The operation was conducted two months from the first visit.

The surgeon in charge is specialized in colorectal surgery with more than 10 years of clinical experiences in tertiary academic medical center. At the operating field, long midline incision was insufficient for the complete exposure of the mass, leading to crossed incision with additional transverse upper midline incisions (Fig. 2). Tumor dissection was performed by peeling off the adjoined bowel, mesentery, and retroperitoneum. Ileocecectomy was inevitably carried out due to vascular involvement, and vascular team engaged in dissecting superior mesenteric vessel and its angioplasty. The total operation time was 311 minutes, and estimated blood loss was 3000ml while blood transfusions of 10 packed red blood cells, 6 PCs, and 6 fresh frozen plasma were done. After admitting to the surgical intensive care unit postoperatively, the patient was moved to the general surgical ward two days later and was discharged at postoperative day-15 uneventfully after the slow build-up of the diet. The final surgical pathology revealed 38cm-long desmoid type fibrosis and clear resection margin, with the same results of immunohistochemical staining with the initial findings (Fig. 3). The patient has been followed up in the outpatient clinic since for two years, where either CT or magnetic resonance imaging (MRI) scans was achieved with 3-to-6-month intervals. He had been admitted a year after the surgery due to small bowel obstruction for 5 days, but has stayed stable with no recurrence so far.

Discussion

Desmoid tumor is a tumor officially defined as “clonal fibroblastic proliferations that arise in the deep soft tissues and are characterized by infiltrative growth and a tendency toward local recurrence but an inability to metastasize” by World Health Organization (4). While 10 ~ 15% of desmoid tumor derive from germline mutation of APC gene presenting familial adenomatous polyposis (FAP), most desmoid tumors are sporadic and are associated with somatic mutations of CTNNB1 gene. The mutation of either genes leads to alterations in the Wnt–β-catenin signalling pathway and eventually uncontrolled fibroblastic proliferations (5). These genes are known to be mutually exclusive, and mutational analysis of the biopsied specimen is recommended in the initial diagnostic phase (3). The etiologies of desmoid tumor other than hereditary syndromes include previous trauma history or hormonal effects of estrogen presented in pregnancy (6, 7). Although our young male patient did not have family history of FAP nor previous traumatic history, the mutational analysis would have been useful in the course of the diagnosis.

Despite its high tendency for local recurrence, quite a few proportions of desmoid tumor are likely to stay dormant or even found to spontaneously regress in 20 to 30% (8, 9). Penel et al. claimed in their prospective study that 2-year event-free survival based on the recurrence after surgery or progressive disease during observation were not significantly difference between surgical and non-surgical group in all locations (53% vs 58%, p = 0.415) and in favorable locations such as abdominal wall, intra-abdominal, breast, digestive viscera and lower limb (70% vs 63%, p = 0.413) (10). In their observational study, Burtenshaw et al. demonstrated that of 58 intra-abdominal and abdominal wall desmoid tumor patients who were initially observed, 28 patients showed stable disease, 23 patients exhibited SR, where majority of SR patients had abdominal wall desmoid tumors (73%) (73%)(11). Accordingly, initial management of desmoid tumor has evolved more into observation and active surveillance with CT or MRI scans.

However, symptomatic tumors and tumors with persistent growth may be considered into surgical or medical intervention. Particularly, FAP-associated desmoid tumors are usually managed more actively due to their more aggressive tumor course (3). Medical management includes anti-hormonal therapy, tyrosine kinase inhibitors (TKI) and chemotherapy. The only TKI proved in randomized trials are sorafenib and pazopanib, where sorafenib showed higher overall response rate (ORR) of SR (33% vs 20%) and longer 2-year progression-free survival (81% vs 36%, hazard ratio for progression or death, 0.13, p < 0.001) than the placebo group (12). Available chemotherapy regimens include methotrexate plus vinblastine or vinorelbine, oral vinorelbine, doxorubicin plus dacarbazine, methotrexate with vinca alkaloids, anthracycline based regimens, and pegylated liposomal doxorubicin. Above all, methotrexate with vinblastine regimen were compared in two phase II trials, showing 67% of 5-year progression-free survival and 69% of stable disease or SR in assessable patients in each study (13, 14). In this case, the patient was first managed with doxorubicin plus dacarbazine regimen. As the tumor bulk was massive and the patient had already begun to present symptoms, the surgical management was a pressing matter with tumor progressing gradually.

After the surgery, the assessment of treatment effects and tumor follow-ups are usually implemented with radiologic assessments of CT or MRI scans. There are no standardized and validated response criteria of desmoid tumor, but most studies used Response Evaluation Criteria in Solid Tumors response criteria (3).

Conclusion

We report a patient with 38cm intra-abdominal desmoid tumor who were treated with chemotherapy then surgical resection due to nonresponsiveness and progression of symptoms. The patient is recurrence-free for two years, and further follow up is expected. Although active surveillance is gaining popularity in the management of desmoid tumor, prompt surgical resection is needed if circumstances require.

Abbreviations

SR

spontaneous regression

CT

computed tomography

APC

adenomatous polyposis coli

PC

platelet concentrations

MRI

magnetic resonance imaging

FAP

familial adenomatous polyposis

TKI

tyrosine kinase inhibitors

Declarations

Ethics approval and consent to participate

Not applicable

Consent for publication

Written consent was obtained from the patient for publication of this case report and accompanying images.

Availability of data and materials

All data generated or analyzed during this study are included in this published article [and its supplementary information files]

Competing interests

The authors declare that they have no competing interests

Funding

There is no funding in our research.

Authors' contributions

Sung Jung Kim contributed to writing, medical record review, and literature research.

Jung Woo Han contributed to conceptualization and review of this paper.

Yoon Dae Han contributed to conceptualization, review, and supervision of this paper

Acknowledgements
Not applicable

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