Abdominal Wall

This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2021, Case 34, and is desmoid-type fibromatosis in the abdominal wall.

The information provided in this case was accurate and correct at the time of publication in 2021.

Any changes in terminology since the time of publication may not be reflected in this case.

This tumor is an example of desmoid-type fibromatosis. Microscopically it is comprised of sheets and fascicles of neoplastic uniform spindle cells with spindle to oval nuclei within varying amount of collagenous stroma. Some slides may show more sclerotic stroma than others. The tumor cells are seen on some slides to be continuous with the aponeurotic tissue and/or infiltrating skeletal muscle fibers, ostensibly of the rectus abdominis muscle. There are no or exceedingly rare mitoses. Necrosis and nuclear atypia are also absent. By immunohistochemistry, the tumor cells demonstrate nuclear beta catenin staining and are negative for CD34.

Deep fibromatosis, also known as desmoid tumor or desmoid-type fibromatosis (DTF), is a locally aggressive tumor that occurs both sporadically and in syndromic settings. Most of the tumors are sporadic and often affect female patients of child-bearing age, but equal sex incidence is approached beyond the age of 40 years. DTF is usually deep-seated, and the majority affect the abdominal cavity or wall. It is generally painless but can be symptomatic due to its impact on adjacent and involved structures. Cases arising in the mesentery can present with intestinal obstruction, volvulus, or changes in bowel habits. The tumor is generally slow growing, but rapid increase in pregnancy has been reported, as in this case. Resected lesions are usually firm, and occasionally myxoid foci can be seen. Microscopically, the tumor cells can have a range of features within the same tumor and between individual patients, ranging from tissue culture-type hypercellular fibroblasts to densely sclerotic hypocellular foci. Tumor cells typically show an invasive front into adjacent skeletal muscle, adipose tissue, or other structures. The presence of nuclear beta-catenin by immunohistochemistry distinguishes this lesion from potential mimics. Although these tumors have no metastatic potential, they are locally invasive with a high rate of recurrence and therefore require wide local excision when surgically treated.

Patients with familial adenomatous polyposis (FAP), due to a germline mutation in the APC gene, and DTF are said to have Gardner syndrome. DTF in the context of Gardner syndrome has a male predominance. Also, Gardner syndrome-associated DTF occurs at an earlier stage and is most likely to be intra-abdominal or in the abdominal wall. This compares to sporadic tumors in which extra-abdominal locations (eg, inguinal region, chest wall, and shoulder girdle) are more common. Up to one-third of patients with FAP have DTF, and between 15% to 20% of patients with DTF will prove to have Gardner syndrome.

DTF exhibits a mutation in either the CTNNB1 (beta-catenin) gene in sporadic cases or the APC gene in syndromic cases. It appears these mutations are mutually exclusive in DTF. These Wnt/APC/β-catenin pathway alterations are believed to drive the vast majority of DTF. However, other environmental factors clearly play a role, including estrogen and trauma. For example, many FAP patients develop DTF in the surgical scar following prophylactic total colectomy, and even with sporadic cases, the history of preceding trauma at the site of origin is common. Another factor is hormones, as evidenced by sporadic DTF predominance in post-pubertal/pre-menopausal women. Also, when present in pregnant patients, DTF can experience very rapid growth increase (as in the current patient). As a result, hormonal suppression with tamoxifen and other approaches have been advocated as non-surgical treatment options, with some success.

Dermatofibrosarcoma protuberans (DFSP) is a key differential diagnosis for DTF in that it can also present in deep subcutaneous abdominal and other locations, is locally invasive, and is poorly circumscribed. However, unlike DTF, DFSP is a tumor centered on the dermis often with extension to the subcutaneous adipose tissue and not associated with muscular aponeuroses. Therefore, DFSP is essentially a more superficial lesion than DTF. DFSP also appears more storiform, while DTF is more fascicular. When necessary, however, immunohistochemical differentiation from DTF will include negative nuclear beta-catenin and positive CD34. Also, DFSP caries a COL1A1::PDGFB rearrangement not seen in DTF.

Inflammatory myofibroblastic tumor (IMT) can sometimes share overlapping clinical and histological features with DTF. It involves a wider range of anatomic sites and organs, but these include the abdomen, a favored site for DTF. Also, like DTF, it can have variable histological features including a mixture or range of myofibroblastic and fibroblastic spindle cells either resembling nodular fasciitis or with more compact stroma, and/or densely sclerotic stroma with few spindle cells. IMT however commonly contains an inflammatory mixture of lymphocytes, plasma cells, eosinophils, and histiocytes to varying degrees (scant to profuse), and it is more likely than DTF to have a background of prominent blood vessels. Also, unlike DTF, in almost half of cases, IMT stain positively for ALK due to ALK gene rearrangement, either in a t(2,5) (p23;q35) translocation or in alternative rearrangements with non-nucleophosmin (NPM) gene partners.

Keloids are due to excessive production of scar tissue and, like some DTF, follow history of prior trauma or surgery. However, unlike DTF, keloids are non-infiltrative, in general less cellular, and almost always cutaneous and therefore superficial. Also, keloidal fibroblasts do not exhibit beta-catenin nuclear staining.

Patients can rarely develop extrauterine trophoblastic tumors during or after pregnancy, which are sometimes associated with an abdominal wall scar (eg, from prior cesarean section). The lesion seen in this case is neither epithelioid nor trophoblastic and therefore does not match a diagnosis of epithelioid trophoblastic tumor. Overall, epithelioid trophoblastic tumor is unlikely to be mistaken clinically or histologically for DTF.

1. Which of the following is true regarding desmoid-type fibromatosis (DTF)?
   1. A key feature of DTF is the absence of a defining mutation or other gene rearrangements.
   2. DTF contains a rich population of inflammatory cells and ALK rearrangement.
   3. Patients with APC germline gene mutation are at risk of developing DTF.
   4. The likelihood of a DTF patient having Gardner syndrome is practically non-existent.
   5. The presence of CTNNB1 mutation essentially rules out a diagnosis of DTF.
2. Which of the following statements is true in considering a diagnosis of dermatofibrosarcoma protuberans (DFSP)?
   
   
   1. DFSP is expected to express beta-catenin nuclear staining in most cases.
   2. DFSP is well-circumscribed and arises from muscular aponeuroses.
   3. DFSP typically caries a COL1A1::PDGFB rearrangement.
   4. In most cases, DFSP contains a t(2,5) translocation.
   5. Positive staining for CD34 excludes the diagnosis of DFSP.
3. A young woman with a diagnosis of familial adenomatous polyposis syndrome presents with an abdominal mass that turns out to be DTF. Which of the following statements is most appropriate?
   
   
   1. The growth of DTF slows down in pregnant patients because of hormonal suppression.
   2. This patient likely has a scar related DFT following total colectomy.
   3. This patient requires further screening for epithelioid trophoblastic tumor.
   4. This tumor is likely to be subcutaneous, easily palpable, and painful.
   5. This tumor is likely to be well circumscribed and non-infiltrative.

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• Nieuwenhuis MH, Casparie M, Mathus-Vliegen LMH, Dekkers OM, Hogendoorn PCW, Vasen HFA. A nation-wide study comparing sporadic and familial adenomatous polyposis-related desmoid-type fibromatoses. Int J Cancer. 2011;129(1):256-261.
• Penel N, Chibon F, Salas S. Adult desmoid tumors: biology, management and ongoing trials. Curr Opin Oncol. 2017;29(4):268-274.
• Skubitz KM. Biology and treatment of aggressive fibromatosis or desmoid tumor. Mayo Clin Proc. 2017;92(6):947-964.
• Zeng C, Rezai S, Hughes AC, Henderson CE, Liu J. Synchronous choriocarcinoma and epithelioid trophoblastic tumor concurring at the cesarean scar: A case report and review of the literature. Case Rep Obstet Gynecol. 2019;5093938:1-7.

1. Patients with APC germline gene mutation are at risk of developing DTF (c)
2. DFSP typically caries a COL1A1::PDGFB rearrangement (c )
3. This patient likely has a scar related DFT following total colectomy (b)