Desmoid Fibromatosis of the Anterior Abdominal Wall in Pregnancy: A Case Report and Review of the Literature

Pavol Zubor; Caroline Marie Henriksen; Maren Elvenes Økstad; Erika Cerskuviene; Jozef Visnovsky; Karol Kajo; Kristen Olav Lind

doi:10.20944/preprints202310.0633.v1

Submitted:

10 October 2023

Posted:

10 October 2023

You are already at the latest version

Abstract

Introduction: Desmoid tumor (DT) is a rare benign neoplasm rising from muscle aponeurosis, having been associated mostly with trauma or pregnancy. DT has an infiltrative and locally aggressive growth pattern and usually does not metastasize. However, it has a high recurrence and complication rate. When they occur in pregnancy, are all pregnancies and deliveries taken as individual case for optimal management by the physicians and midwifes, who need to be cautious in finding the optimal delivery mode for patients, which depends on tumor size, location, behavior and past history. Study Objectives: We present a case report of a large desmoid tumor of the anterior abdominal wall in a 29-year-old woman in pregnancy, presenting a delivery problem, which resolved in surgical management. Moreover, we are bringing a systematic review of the literature to provide an overview on pathomechanism, symptoms, diagnostics and treatment management of the pregnant women affected by DT. Results: The authors report a case of pregnant women who underwent systemic oncological treatment for abdominal wall desmoid tumor and have been pregnant afterwards. The observational conservative management was chosen with an elective cesarean section at the 38+4 pregnancy week with uncomplicated postpartum follow-up. Conclusion: Pregnancy-associated desmoid tumors are very rare and optimal management of this tumor is not well established, despite some guidelines for non-pregnant patients. The authors reviewed the literature focusing on the actual modern management of desmoid tumors at all, including patients during the pregnancy, as well.

Keywords:

benign neoplasm

;

desmoid tumors

;

chemotherapy

;

high-risk pregnancy

;

delivery

;

uncommon complications

;

abdominal discomfort

;

management

Subject:

Medicine and Pharmacology - Obstetrics and Gynaecology

Introduction

Desmoid fibromatosis (DF) or sporadicall named as desmoid tumors (DT) represents rare type of tumors, accounting for 0.03% of all neoplasms and less than 3% of tumors arrising from soft tissue (1). DF according to WHO (2020) is defined as a locally aggressive but non-metastasizing deep-seated (myo)fibroblastic monoclonal neoplasm with infiltrative growth pattern and tendency for local recurrence (2). In the International Classification of Diseases (ICD) it is classified as D48.1 diagnosis (3).

Incidence of DF is 2.4 to 5 per one million population per year. DTs predominantly affect young females, mostly between age of 30 to 40 years and occurs more than twice as often in female than male patients. However, in older patients, the incidence do not depend on gender (4-6). Reflecting the age it can be described as follow: the "juvenile" type of DT, which ocusrs predominantly as extra-abdominal desmoid tumor mostly in women; "fertile" DT, that is exclusively abdominal localized DT in women in fertile age; "menopausal" DT, a predominantly abdominal tumor where the sex ratio approaches 1:1; and "senescent" type of DT, where abdominal and extra-abdominal varieties are equally frequent among female and male population (5).

Reflecting their location can be desmoid tumors classified as extra-abdominal and abdominal. Abdominal DTs are either superficial (abdominal wall) or intra-abdominal. These tumors shows a high recurrence rate even if there are og benign feature on microscopic histological assessment. Their biologic behavior often indicates patterns of the "malignant" disease because severe progression and local infiltration to vital organs leads to their impairment and sometimes to the patients death. Intraabdominal DTs can affect surrounding organs and vessels, what may greatly complicate their surgical treatment (7,8). As for the topical anatomic location are DT present in extra-abdominal locations (49%), abdominal wall (40%), and intra-abdominal areas including retroperitoneal space (8%) (6).

The extra-abdominal lesions mostly occur in the neck, shoulder, chest wall, breast, back, arm, buttock, thigh and leg. Multicentric extra-abdominal desmoids are very rare and thay have specific clinical presentation (9,10).

Historically, these tumors were first described by MacFarland in 1832. Etymologically, the word “desmoid” was first time used by professor Johannes Müller (1801–1858, chairman of the Department of Anatomy, Physiology and Pathology at the University of Berlin) in his monograph on cancer (11), published in Berlin in 1838, where he done the detailed analysis of the microscopic features of benign and malignant neoplasms in humans. The name is derived from the Greek word «Desmos», which means band or tendon-like (12). In 1951, Gardner first described the often presence of desmoid tumors in patients with Familial adenomatous polyposis (FAP).

The detailed pathogenesis and factors affecting clinical behavior of DTs are still uncertain. However, most cases of DTs were described in patients with previous abdominal trauma or surgery (either laparoscopic, robotic or open) (13-16).

DT is histologically arising from connective tissues of muscle (the result of abnormal monoclonal, fibroblastic proliferation or proliferation of myofibroblasts), the fascia or the aponeurosis. Recently, studies showed the important role of impairments in the Wnt/β-catenin signaling pathway or mutations in APC and CTNNB1 genes as a 'key' trigger for the development of desmoid tumors (17,18).

Although histology is the gold standard to sett the diagnosis, imaging modalities represents the basic tool in the diagnostic process of these tumors. To establish an adequate therapeutic approach, the proper diagnosis is necessary. Multimodal imaging tools, including computed tomography (CT), ultrasound (US) and Magnetic Resonance Imaging (MRI), are helpful tools in the assessment process. These techniques can be also used to guide the minimally invasive interventions and monitor their effectiveness in the treatment (19).

The management is multidisciplinary and often repetitive as DTs growth locally invasive and prone to the high local recurrence after resection.

Since their clinical behavior is heterogeneous and unpredictable where outcome is impacted by anatomic area, nearness to crucial organs, affiliation with FAP, and natural behavior, the treatment ought be individualized in aim to decrease the risk for treatment failure with subsequent tumor recurrence and achieving the acceptable morbidity with highets possible quality of life (20). Numerous issues with respect to ideal treatment of desmoids stay disputable. In any case, wide surgical extraction remains the treatment of choice, except when it is mutilating or is associated with significant organ function impairment and morbidity. Involvement of surgical margins is likely related with an increased risk of local recurrence. In this case, surgical re-resection, adjuvant radiation, systemic therapy or close clinical follow-up might all be appropriate alternatives (21).

Apart of this approach, there is in the last years increasing evidence proving significant progression in the systemic, biological or focused technological treatment possibilities for these patients.

In this paper, we report a case of young female who was diagnosed with desmoid tumor before pregnancy, underwent oncological treatment and has been pregnant with a residual desmoid tumor in anterior abdominal wall, thus leading to a special obstetric problem requiring individual management. Moreover, we are presenting an overview of the current local or systemic therapeutic possibilities for patients affected by desmoid fibromatosis with special attention to DTs in pregnancy.

Case report

A 29-year old primiparous woman with physiological pregnancy was refered to a primary care hospital for follow-up during pregnancy and planning of delivery with the first check in 12+4 week of pregnancy. She has underwent one legal abortion in the past history.

She was non-smoker, denied drinking alcohol or using illicit drugs, her pregravid body mass index was 20.2, and her past medical history was significant for FAP for which she underwent laparoscopic total proctocolectomy with ileoanal reservoir, with transient right-sided relieving colostomy at the age of nineteen. This due to papillous tubulovillious adenoma with low grade intraepithelial (LB-IEN) neoplasia. Subsequently regullarly (regularly) followed by colonoscopic examinations finding sporadic tubular adenomas with LG-IEN on excisional biopsies. Colostomy was closed back 8 months after the primary surgery.

When the patient turned 26 (6 years after the surgery) she developed a desmoid tumor sized 12 x 4.6 x 6.6 cm on abdominal ultrasound scan (Figure 1) and 8.8 x 4.8 x 15.3 cm on MRI scan (Figure 2) in anterior abdominal wall on the right side close to previous troacar point of incision after laparoscopic surgery for FAP and transient relieving stomy. Primarily suspected from sarcoma or desmoid tumor. A core-cutt biopsy was performed confirming the diagnosis desmoid fibromatos tumor, estrogene receptor positive (ER+). The tumor-board considered the situation as stable, with the possibility for partial spontaneous regression. As the risk for recurrence was assessed on to be 50%, no surgery was performed and she was referred for follow-up with new MRI control in about 3 months. During this follow up period she got pregnant and underwent a provoked medical legal abortion in week 6.

The 3-months MRI control (Figure 3) showed stable tumor size, however MRI check after six months showed significant tumor growth progression (Figure 4), sized 10.5 x 6.2 x 17.5 cm in cranio-caudal diameter located in musculus rectus abdominis on the right side. She was recommended to cut-of oral contraceptives and preventive devices (IUD) containing estrogene and/or progesterone and was referred to the National Oncology Center for further treatment. Here, the local Tumor-board concluded with the administration of chemotherapy, where treatment started with 3 cycles of Caelyx (doxorubicin hydrochloride), 40mg/m2 every 4th week with MRI control afterwards. The chemotherapy was administred at our local hospital. The patient suffered side effects in form of skin rashes, allergic respiratory problems and mucositis. She received every cyclus 60 mg of Caelyx i.v. Control MRI scan showed no effect of the treatment, furthermore slightly progression in the cranio-caudal tumor size (12 x 6.6 x 20 cm), (Figure 5). As the oncologist awaited the late response on chemotherapy, the further plan was to continue in the same treatment options (Caelyx, however in reduced dosage, set to 30mg/m2) due to previous side effects. Patient underwent 3 further cycles with total dose of 47 mg doxorubicin at each cycle. MRI scan after 6 cycles showed partial regression of the tumor, now sized 11.2 x 5.4 x 19.1 cm (Figure 6). She was continuously monitored by surgeon and radiologist with MR scans every 4 months and the 12 month-s scan after chemotherapy the tumor showed significant regress, sized only 1.2 x 3.7 x 8.7 cm (Figure 7). Five weeks later the patient became pregnant and was referred from the midwife for gynecological controls, starting on week 12+4.

All the prenatal controls showed no respiratory or bowels conditions worsening even in the tumor size/growth. All medical checks showed normal fetal growth charts and physiologic findings in maternal-fetal flow circulation, placenta morphology and amniotic fluid indexes out over the pregnancy.

Due to the previous total colectomy for FAP, chemotherapy and location of the tumor with size progression, the conclusion for an elective cesarean section (CS) were done and she delivered at 38+4 week of pregnancy through uncomplicated CS with Pfannenstiel incision and low transverse corporal incision on the uterus. She delivered the healthy baby weighing 3435 g, length 48 cm with Apgar score 10-10-10. Normal peroperative expulsion of placenta, bleeding estimated for 450 ml. The postpartum period followed uncomplicatedly, the patient was treated for anemia by i.v. iron substitution (Ferinject - ferric carboxymaltose; 500 IU), and was discharged home on 4th day postpartum without any clinical problems, advised to avoid hard physical activity in 4 weeks post partum.

Follow-up correspondence was done at 4 months post partum and the patient had recovered well, with a normal physical activity in life, DT is stable in size and the patient is followed-up by regular checks by gastric surgeons for desmoid tumor and FAP with regular colonoscopies and MR scans.

Discussion

The studies of patomechanism in desmoid tumors showed that 90% of them are sporadic, and the remaining 5-10% display a genetic link to FAP (Gardner syndrome). Patients with this syndrome have a 800-1000 times greater risk of developing DTs than in the general population (18,22). Sporadic DTs create most commonly in extra-abdominal areas, but those related with FAP are generally found within the small bowel mesentery and/or in the abdominal wall, predominantly arising in soft tissue (23-26) causing bowel obstruction or ulceration and ureter stenosis. Patients with FAP often develop intra-abdominal tumors after abdominal trauma or surgery (2). Moreover, the risk of DTs in FAP is increased by also certain pathologies in APC variants (27).

Etiology

The etiology of desmoid fibromatosis is multifactorial and incorporates hereditary components (most commonly sporadic somatic CTNNB1 mutations and less frequently germline APC mutations in Gardner syndrome), physical factors (surgery, injury), and hormonal factors as pregnancy or contraception (28-29). Surgery and trauma increases the risk of tumour development via its recovery process where proliferative phase of wound healing exhibit high β-catenin expression (30).

Desmoid tumors are associated with germline variations in APC involving codons 1310–2011 within the mid- to C-terminal parcel of the encoded protein (31). FAP-associated desmoid tumours are caused by APC rather than CTNNB1 variant, the latter being more common in sporadic counterparts; nevertheless, they also show nuclear beta-catenin immunoreactivity secondary to Wnt pathway activation (32).

Pathogenesis

In the pathomechanism of DTs, two mutually exclusive mechanisms have been described. The majority (85-90%) of sporadic DTs results from somatic mutation pathway of CTNNB1 gene. It act on three different point mutations in codons 41 and 45 of exon 3 of the CTNNB1 gene that encodes β-catenin, a protooncogene: p.Thr41Ala, p.Ser45Phe and p.Ser45Pro (33-37). The p.Thr41Ala (55%) and p.Ser45Phe (35%) are the most frequent mutations giving p.Ser45Phe only approximately 10% frequency (33,34,36,38).

A smaller percentage (10-15% of cases) of desmoid tumours (germline APC mutation associated pathway) emerge within the Gardner syndrome. These patients harbor germline mutations in the APC tumour suppressor gene, specifically are changes located at or beyond codon 1444, what lead to loss of heterozygosity of the wildtype allele, however, rare cases of DTs with sporadic APC mutations have been described, as well (39-46). The activating mutations in CTNNB1 or inactivating mutations in APC (where a truncated APC protein with low affinity to β-catenin is created) interfere with β-catenin proteasomal degradation. These processes results in abnormal accumulation of β-catenin within cell nuclei (47,48).

Because β-catenin functions are a part of the transcription apparatus in the nucleus, this increased activation of the WNT/β-catenin pathway is thought to drive tumorigenesis of DT through advance cell transcription, proliferation, adhesion and survival (49-51).

When simplified, this complex integration can be described as a process where DT pathogenesis is strongly connected to Wnt/ β-catenin cascade, and where β-catenin dysregulation plays a crucial part through binding to transducin β-like protein 1 (TBL1/TBLR1), and this complex stimulates the expression of several Wnt/APC/β-catenin pathway target genes, including some proliferative components, such as S100A4 or CTHRC1 (52). The APC genes plays a central part within the phosphorylation and proteosomal degradation of β-catenin and the Wnt pathway, in turn, restrains APC-dependent phosphorylation (53,54).

On grow macroscopy DT resemble scar tissue with firm consistence and gray or whitish color. Under the light microscopy they are displayed by a heterogeneous, poorly characterized and uniform proliferation of spindle cells that resembles myofibroblasts wrapped inside a stroma of abundant collagen and a vascular network missing capsule. No necrosis, cellular atypia or increased mitosis is noted. Inside the nuclei there may be detected euchromatin or heterochromatin. There is no histological difference between sporadic DT and FAP-related, however their molecular profile can be different.

On immunohistochemistry are DTs characterized by nuclear positivity for smooth muscle actin, muscle spocific actin, vimentin, β-catenin, PDGFRb, Cox-2, androgen and β-estrogen receptors. They are negative for S-100, h-caldesmon, desmin, CKIT and CD34 (2,18,55).

Prognosis, prediction and clinical behavior

The biological course of desmoid fibromatosis in certain patients varies a lot. Presentation may vary from asymptomatic lesions to impairing tumors with unpredictable growth, stabilization, and ev. regression. The variety of symptoms is directly associated with the size, location and progression speed of DTs. The intra-abdominal DTs grow asymptomatic until they reach large dimension, leading to intestinal, urinary, vessel obstruction, tissue ischemic dammage with possible perforations or bleeding (56-57). Although tumour-related deaths are rare, they are more common reported in patients with FAP (58). In spite of the fact that up-front surgery with negative surgical margins is considered as the standard of care, local recurrence may not absolutely correlate with status of tumor margins (32,59). Roughly 25-60% of patients show recurrence after resection; extensive surgery can be morbid causing significant loss of function or disabling chronic symptoms (18). Moreover, a subset of tumours may exhibit spontaneous regression (60). Rarely is complete remission seen also despite the recurrent feature of DTs after only simple observation. (61).

When considering surgery, it is extra-abdominal location, younger age, larger tumour size, and mutation status of DT what gives higher rates of local recurrence in patients (59,62,63). The most affecting mutation giving a high risk for local recurrence is p.Ser45Phe in CTNNB1 gene (34,36,64,65), linking this mutation with unfavorable prognostic factors but not a prognostic factor for event-free survival (progression, relapse, or death) (66).

For all these reasons, a watchful waiting approach with a individual period of initial observation has been refered for asymptomatic patients (28).

Point by point physical examination, imaging by ultrasound, CT and MRI, and if not previously done, biopsy should be performed in accordance to the recommendations for soft tissue sarcomas as it was adapted at consensus meeting in Milan (Italy, June 2018) (3). Following this consensus, the current strategy for management of DT advocates for an «active surveillance» period. This approach does not show up to impact the efficacy of ensuing treatment when required, but permits the clinician to arrange the following step in the therapeutic management. Hence, being cautious and maintaining a strategic distance from potential hurt is considered the best option in the first management approaches after setting the diagnosis in many patients. In this period, neither surgery nor other treatment forms are proposed. Any aggressive attempts for total eradication of the tumor may be more awful than the illness itself. It is important to comprehend that even a recurrent desmoid tumor can undergo spontaneous regression (61). Considering the disease biology with unpredictable course, active treatment should be indicated in cases with continuously growth progression of DTs. Tumor size progression at a single evaluation, particularly in the absence of severe clinical symptoms and in non-critical anatomic areas, should not be considered as an sign to begin an active treatment quickly. The active surveillance implies that patients ought to be checked with first MRI or CT inside 1-2 months and afterward in 3-6 months intervals until the fifth year, and yearly afterwards. The later occurrence of severe tumor progression with symptom burden is considered as a indication for active treatment after initial postponed decision for that (3).

Here, when active approach for DT is required, clinician should consider surgery as an up-front therapy. The achievement of R0 margins is the primary aim, but sporadic presence of positive (R1) microscopic margins can be also accepted. In these cases, the following radiation therapy or systemic treatment can be offered to the patients. Thus, a multidisciplinary approach in DT patients therapy is clearly required (3).

The last evidence for surgical management of abdominal desmoid tumours in terms of success, recurrence and morbidity was brought by Moore et. al. (2023). Authors have conducted a large systematic mata-analytical search for 20-yrs period, since November 2000, and concluded that the surgical resection for abdominal desmoids remains a valid treatment option in highly selective cases where negative margins can be obtained, with low morbidity (4.4%) and/or mortality (2% within 30 days after operation) (67).

As DTs shows localy infiltrative growth and may often exhibit relapses, most of R1 cases were treated with subsequent radiotherapy. Moreover, evolution in therapeutic options brought the shift from primary surgeries to less invasive approaches. The wide attention has gained the image-guided ablations with low morbidity as e.g. cryoablation and high-intensity focused ultrasound.

Adjuvant radiotherapy (RT) known for its significant reduced risk of local recurrence rate when applied in patients with incomplete surgical resection or in recurrent tumours is ofently indicated as second step in the manegament (68). However, due to side effects, it can be applied only in patients where anatomic conditions restrict complete resection and therapy is not giving high toxicity. Risk most common factors for local treatment failure include young age, large tumor size, recurrent disease feature, limb, girdle or intra-abdominal location, positive surgical margins, omission of RT, radiation dose < 50 Gy and inappropriate radiation field extention. The recommended dose is 50-56 Gy in 28 once-daily fractions of 2 Gy (69,70). The doses > 56 Gy have failed to demonstrate improvement in local disease control and are associated with greater toxicity including fibrosis, soft tissue necrosis, edema, pathological fractures or vascular complications as well as radio-induced neoplasms (71).

To the others local treatment approaches belongs a noninvasive high-intensity focused ultrasound (HIFU). Here, the low-power cumulative HIFU therapy may lead to significant efficacy and long-term control mostly in recurrent DTs. Zhong et all. (2022) has reported the mean ablation proportion of the HIFU treatment at 69.5%, the objective response rate 47.3% and the 5-year progression-free survival (PFS) rate at 69.3% (72).

The promising results for local approaches showed also study from Schmitz et al. (2016) pointing on the percutaneous cryoablation of extraabdominal DTs (73), which were recently confirmed by Vora et al. (2021). Authors in this meta-analysis study showed that the proportion of stable disease rate was 85.8%, and the progression free survival rate at 1 year was 84.5% and 78.0% at 3 years, with only 4.2% of major/minor complications. Moreover, the 37.5% to 96.9% of patients showed partial or complete symptom relief (74).

In patients that have anatomic barriers to effective surgery, radiotherapy, HIFU or cryoablation, the systemic treatment may be indicated. This option currently include nonsteroidal anti-inflammatory drugs (NSAID), anti-hormonal agents, tyrosine kinase inhibitors (TKI), «low-dose» chemotherapeutic regiments, and conventional chemotherapy as anthracycline-based regimens, mostly liposomal doxorubicin.

NSAID have shown the ability to block the Wnt/β-catetin signaling pathway mediated by COX-2 or prostaglandines which induces an objective size response and lowers pain perception in patients (75,76).

Anti-hormonal therapy is based on often ER+ immunohistochemical status of DTs and its linkage to pregnancy. The most used agents are tamoxifen and toremifene (77,78). They are used alone or in combination with NSAIDs. The therapeutic effect of these two drugs is thought to be involved in the affection of transforming growth factor-β (TGF-β) and its receptors, known as an important pathway regulating fibroblasts proliferation (75,76).

One of the first reports on tamoxifen use in DTs was a study from Sportiello et al. (1991) who reported a case of recurrent retroperitoneal desmoid tumor successfully treated with tamoxifen (Nolvadex tablets) in patient presented late in her second pregnancy with a large retroperitoneal pelvic DT what resulted in a complete tumor regression remaining stable for 27 months (79).

Despite the initial encouragement, later studies have shown that hormonal agents and nonsteroidal anti-inflammatory drugs have limited efficacy. Thus, they did not gain the wide clinical acceptance and clinicians have turned the focus on standard and low-dose chemotherapy. Here, the most often used are anthracycline-based therapies given for 6-8 cycles achieving the tumor shrinking or disease stabilization in 80% of the cases, and a lasting response in 45-50 % of patients (80,81). However, clinical usage is limited by the risk of cardiomyopathy and secondary malignancies. Nevertheless, pegylated liposomal doxorubicin has been reported to have significant effect with quite well tolerated toxicity profile for its lower cardiac toxicity than conventional doxorubicin (82). In trying to overcome the toxicity of antracyclines, the low-dose chemotherapy regiments based on the metotrexate and a vinca alkaloid (vinblastine or vinorelbine) have been also investigated and represent a preferable choice to full-dose chemotherapy (83).

The last and very promising systemic therapy is a biological treatment where the therapeutic agents targets concrete signaling pathways in DTs patomechanism. Here, the tyrosine kinase inhibitors (imatinib, nilotinib, sorafenib, sunitinib, and pazopanib) are well studied (84), and sorafenib is now one of the most utilized therapies, though limited by its side effect profile. Among patients with refractory, progressive or symptomatic DTs, use of sorafenib (400-mg tablet once daily) led to significant prolongation in progression-free survival and initiated durable responses, where the 2-year PFS rate was 81% (85).

The promising effect of targeted biological therapy started the wide spectra of ongoing clinical trials focusing on the Notch pathway by using of gamma-secretase inhibitors (Nirogacestat, PF-0308401) showed efficacy in phase 1 and 2/3 trials (86,87), selective inhibitor of nuclear β-catenin acting through binding TBL-1 (Tegavivint, BC-2059) (88), or immune checkpoints inhibitors (PD-L1) (89), tumor microenvironment (matrix metalloproteinases), platelet-derived growth factor receptor (PDGFR), angiogenesis (vascular endhothelial growth factor, VEGF), cell-cycle regulatory proteins (RB1, CDKN2A and TP53), cell-cell adhesions (N-cadherin and α-catenin) or cell proliferation/survival by blocking the mTOR pathway (90) which can present multiple potential novel therapeutic targets (76).

The serious advancement showed the use of Nirogacestat in adults with growing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors (RECIST). In a study from Gounder et al. (2023) DTs patients received the oral γ-secretase inhibitor nirogacestat (150 mg) showed significant progression-free survival benefit at 2 years at 76%. Nirogacestat was associated with significant benefits with respect to PFS, objective response, symptom burden, role and physical functioning, pain, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly (95%) of low grade 1 or 2 (91).

There have been reported around 100-120 cases of DTs in pregnancy worldwide so far published on Pubmed, however only a few cases with systemic therapy for DT. The common sign of these reports was strong biological variability of DTs depending on hormonal background and mostly watch-&-see management with close follow-up and operative delivery. Moreover, the reports describing DTs in pregnancy showed that clinical picture of DTs can be unpredictable, especially when they develop before delivery or in post-partum period. Most of these cases initially diagnosed in pregnancy were bioptised (core biopsy) and if malignity was excluded, they were managed conservatively by follow-up with ev. precise MRI scans for assessment of the DT size and location where pregnancy was ended by CS with DT resection during CS or in the postpartum period, (Table 1) (57,61,92-102).

For decades, DF has been thought as a conceivable hormone-dependent malignancy based on these arguments: estrogen receptors positivity on imunnohistological assessment, the predominance of female patients with high incidence in the fertile age, studies reporting diagnosis or relapse of desmoid tumor in and/or after pregnancy, and watched tumor shrinkage with the administration of anti-estrogen drugs or in post-partum period.

One of the first multicentric study focusing on DTs behavior and pregnancy was published from Italy by Fiore et al., (2014) on ninety-two women with DT who analyzed long-term data linked to disease presentation during and after pregnancy. They showed that the initial treatment of DT in pregnant women was resection (52%), watchful waiting (43%) with later progression at 63% and only 4% of patients received medical therapy. Only 13% of patients relapsed after surgery. After pregnancy, 46% underwent treatment of DT, whereas 54% were managed with watchful waiting. Only 17% showed further progression after treatment. Spontaneous regression occurred in 14%. After further pregnancies, only 27% of patients progressed. The only advers obstetric event was a higher rate of cesarean sections (60). The linkage to pregnancy and postpartum events was even more strengthened by the report from Hanna et al. (2016), who reported a case of rapidly progressing DT in the post-partum period (95), and recently also confirmed by Debaudringhien et al. (2022) who showed that history of pregnancy was associated with an increased risk of progression/relapse in patients with newly diagnosed DF, whereas hormonal contraception did not showed an connestion with disease progression or relapse (29).

The important knowledge in the management of DTs in pregnancy was brought by Cates et al. (2015), who found that pregnancy itself does not increase the risk for local recurrence after surgical resection of desmoid tumors (103). Based on these findings, it seems that pregnancy can be taken as a risk factor for promoting growth and progression of desmoid-type fibromatosis in ongoing pregnancy and post-partum because of the estrogenenic stimulation of desmoid growth, however, it has of low impact on recurrence of DTs after its surgical resection. Thus, subsequent pregnancy should not be discouraged for women in fertile age after surgical resection of desmoid tumors.

Conclusion

Pregnancy-associated DTs are rare and optimal management of these tumors is yet to be established. Nowadays, controversy points on the follow-up approach or proper timing of surgical resection, which may be influenced by the increased potential for tumor growth and the negative reactions of a gravid uterus. Surgical resection of these tumors has been performed successfully both during and early after delivery, where the postpartum radiotherapy, chemotherapy and other medical intervention showed its effectiveness. Risk for disease progression during pregnancy is high, but it can be safely managed. Pregnancy-related DF has good outcomes. As desmoid tumors does not significantly increase obstetric risk, thay can not be a contraindication to future pregnancies.

The management of desmoid tumors, especially when diagnosed during pregnancy is complex and requires multidisciplinary expertise by an experienced team where treatment has to be individualized. We must identificate the reliable prognostic/predictive factors is they are the key for assessing the efficacy of local or systemic treatment. The better understanding of genetics and molecular alterations in signaling pathways enriched this attitude and led to the development of the tailored interventions for DT, which could revolutionize its therapy and management strategies.

Disclosure and Contributorship

The article or part of it has not been published in any other journal. PZ, KK, JV participated in writting of the article, EC, PZ and KOL was involved in clinical management of the patient, CMH, MEØ, PZ contributed in manuscript preparation and review, KOL and PZ participated in the final reviewing of the manuscript and post-surgical clinical management of the patient.

Funding and financial support

None.

Acknowledgments

Authors thank to Petra Zuborova for technical help with managing this paper and to the pasient who approved the content of the paper and signed the consent for the publishing of this case.

Conflict o finterests

The authors declare no conflicts o finterests regarding the publication of this manuscript.

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Figure 1. Abdominal ultrasound (A – transverse view; B – longitudinal view) picture of desmoid tumor sized 12 x 4.6 x 6.6 cm on the first diagnosis.

Figure 2. MRI scan (A – axiall plane; B – sagital plane) asessment of fibromatosis lesion at the first diagnostic scan sizing 8.8 x 4.8 x 15.3 cm.

Figure 3. The 3-months MRI controll scan (A – axiall plane; B – sagital plane) after initial diagnosis showing stable tumor size.

Figure 4. MRI scan (A – axiall plane; B – sagital plane) on 6-month follow-up check showing significant tumor growth progression, sized 10.5 x 6.2 x 17.5 cm in cranio-caudal diameter located in musculus rectus abdominis on the right side.

Figure 5. MRI scan (A – axiall plane; B – sagital plane) after 3 cycles chemotherapy showing no effect of the treatment and slightly progression in the cranio-caudal tumor size (12 x 6.6 x 20 cm).

Figure 6. MRI scan (A – axiall plane; B – sagital plane) after 6 cycles chemotherapy showing partial regression of the tumor, now sized 11.2 x 5.4 x 19.1 cm.

Figure 7. MRI scan (A – axiall plane; B – sagital plane; C – coronal plane) 12 months after chemotherapy showing significant tumor regress, sized only 1.2 x 3.7 x 8.7 cm.

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