Desmoid fibromatosis of the liver: a case report and rare entity with diagnostic resolution by histopathology and immunohistochemistry

Abstract

Background

Desmoid tumors (aggressive fibromatosis) are rare, locally invasive fibroblastic neoplasms with no metastatic potential but a propensity for local recurrence. Primary involvement of the liver is exceptionally uncommon and poses significant diagnostic challenges due to overlapping radiologic features with primary hepatic malignancies and other spindle cell neoplasms. Large mesenchymal tumors may rarely be associated with nonislet cell tumor hypoglycemia.

Case presentation

A 71-year-old woman presented with a five-year history of progressive abdominal swelling and recurrent hypoglycemic episodes. Examination revealed a large, firm, non-tender abdominal mass measuring 30.0 × 28.0 cm. Laboratory investigations, including liver function tests and tumor markers (alpha-fetoprotein, CA 19 − 9, and CA-125), were within normal limits, except for correctable hypokalemia. Cross-sectional imaging demonstrated a large heterogeneous mass arising from segments II and III of the left hepatic lobe with progressive enhancement, favoring a benign or low-grade mesenchymal neoplasm. Differential diagnoses included solitary fibrous tumor, inflammatory myofibroblastic tumor, and desmoid fibromatosis. The patient underwent left lateral hepatectomy. Histopathology revealed a spindle cell proliferation composed of uniform fibroblastic cells arranged in long fascicles within a collagenous stroma, without significant atypia or increased mitotic activity. Immunohistochemistry showed strong nuclear positivity for beta-catenin, while smooth muscle actin (SMA) and CD31 were negative in tumor cells; S100 showed weak positivity. These findings confirmed the diagnosis of desmoid tumor. The postoperative course was uneventful, with resolution of hypoglycemic episodes.

Conclusion

Primary hepatic desmoid tumor is an exceptionally rare entity that may clinically and radiologically mimic malignant hepatic neoplasms. Strong nuclear beta-catenin expression is critical for definitive diagnosis. This case underscores the importance of comprehensive histopathological and immunohistochemical evaluation in atypical hepatic masses and highlights the potential association with paraneoplastic hypoglycemia.

Background

Desmoid-type fibromatosis (DTF) is a rare, locally aggressive fibroblastic neoplasm characterized by clonal proliferation of myofibroblasts within a collagen-rich stroma. It accounts for approximately 0.03% of all neoplasms and 3% of soft tissue tumors, most commonly arising in the abdominal wall and mesentery, and only rarely in the upper and lower extremities [1]. Although histologically benign and lacking metastatic potential, DTF exhibits an infiltrative growth pattern and a marked propensity for local recurrence, placing it within the spectrum of intermediate-grade soft tissue tumors [2].

Only a limited number of cases of primary hepatic desmoid fibromatosis have been reported in the literature [3]. When arising in the liver, these tumors often present a diagnostic challenge, as their imaging features—ranging from well-circumscribed to infiltrative masses with variable enhancement—can mimic more common hepatic lesions, including hepatocellular carcinoma, cholangiocarcinoma, and metastatic disease [4]. Definitive diagnosis typically relies on histopathological evaluation demonstrating a uniform proliferation of spindle cells, with nuclear β-catenin positivity on immunohistochemistry [5]. In Nigeria, desmoid tumors have been reported in the jaw, abdomen, and mesentery; however, to date, there are no reported cases of primary hepatic involvement [6–8].

Case presentation

Herein, we present the case of a 71-year-old woman with a five-year history of progressive abdominal distention and recurrent episodes of profound hypoglycemia. She was otherwise systemically well, with no history of weight loss, fever, or jaundice, and her only comorbidity was hypertension. She had previously been offered surgical intervention in the UK two years prior to presenting to our center in Nigeria but declined at that time. Over the ensuing period, her abdominal distention worsened, accompanied by increasingly frequent hypoglycemic episodes.

On examination, she was alert, well and in no distress. Her abdomen was markedly but surprisingly, not tender. A large mass could be appreciated occupying much of the upper abdomen with extension past to the left lower quadrant. No clinical ascites was present. Her bowel sounds were normoactive. A digital rectal exam was performed There were external hemorrhoids at the 5:00 and 7:00 positions. There was no palpable mass in the rectum.

The full blood count was normal; electrolytes, urea, and creatinine were essentially unremarkable, except for moderate hypokalemia, which was corrected with intravenous potassium. Tumor markers such as carbohydrate antigen-125, carbohydrate antigen 19 − 9, and alpha-fetoprotein, as well as liver function tests, were normal. Viral serology was negative.

Abdominal computed tomography and magnetic resonance imaging were performed as part of her work up. Relevant imaging findings are depicted Figs. 1 and 2.

Fig. 1.

Above are pre-contrast (A), contrast enhanced (B, C) and delayed (D) computed tomographic images of the abdomen showing a huge, well-circumscribed, hypodense mass arising from the left lobe of the liver. The mass demonstrates moderate heterogeneous enhancement on the early contrast phase and progressive, persistent enhancement on the delayed phase. No calcification is identified

Fig. 2.

Above are axial T1-weighted (A), T2-weighted (B), T1 post-contrast (C), diffusion-weighted image (D) and apparent diffusion coefficient map (E) of the abdomen showing a huge, well-circumscribed, heterogeneously enhancing mass arising from the left lobe of the liver. The mass demonstrates heterogeneous signal intensity on T2-weighted images. Areas of high T2 signal with corresponding high signal on both DWI and ADC (T2 shine-through effect) are noted

Radiological impression: Large, heterogeneous left hepatic lobe mass with progressive enhancement. Given the prolonged clinical course without constitutional symptoms and normal biochemical markers, the imaging findings favor a benign or low-grade neoplasm rather than an aggressive malignancy. Differential considerations included mesenchymal neoplasms (solitary fibrous tumors, desmoid fibromatosis, and inflammatory myofibroblastic tumors), benign hepatic neoplasms (hepatic adenoma and focal nodular hyperplasia, although atypical for this size), and, less likely, well-differentiated hepatocellular carcinoma or slow-growing cholangiocarcinoma. The associated hypoglycemia was considered nonislet cell tumor hypoglycemia, classically associated with large mesenchymal tumors. A tissue diagnosis was deemed essential for definitive characterization.

The patient was agreeable and a left lateral hepatectomy was performed. Procedural details are as follows:

A midline incision was made, and a Thompson retractor was secured to facilitate adequate exposure. Intraoperative findings revealed a large, highly vascular mass arising from segments II and III of the liver. The falciform and left triangular ligaments were divided to mobilize the left lobe. A Pringle maneuver was applied for inflow control. Parenchymal transection was performed using a combination of instrument-based fracture techniques, ligatures, vascular staplers, clips, and sutures.

A massive, oval-shaped, light brown specimen measuring 31.0 × 29.5 × 16.0 cm was subsequently resected (Figs. 3 and 4). No lymphadenopathy was identified. Minor bleeding from the raw hepatic surface was controlled with diathermy and Surgicel. The abdomen was closed in layers. Intraoperative glucose levels were managed with a dextrose infusion, and two units of packed red blood cells were transfused following tumor resection.

Fig. 3.

Excised mass

Fig. 4.

Excised mass with residual liver tissue

Postoperatively, the patient was admitted to the intensive care unit for 72 h. Her blood glucose levels were monitored closely. Her need for glucose infusion subsequently decreased. The patient commenced oral intake on postoperative day one. Her postoperative recovery was essentially uneventful.

Histopathology revealed liver tissue with distorted architecture due to proliferating spindle-shaped cells that were diffusely distributed and formed short, intersecting fascicles. Individual tumor cells are elongated, with large, pleomorphic, vesicular nuclei, indistinct nucleoli, irregular nuclear membranes, and scantly clear cytoplasm (Figs. 5). Within the tumor cells, numerous variable-sized vascular spaces are also visible. Mitosis is sparse. The resection margins are positive for tumor cells. The nuclear atypia may be consistent with ancient changes. The mass has been there for five years.

Fig. 5.

a: H&E at x4 magnification. b: H&E at x20 magnification. (Both show proliferating spindled-shaped cells forming short intersecting fascicles)

On hematoxylin and eosin (H&E) staining, a mesenchymal tumor of intermediate grade was diagnosed according to the following differential criteria: solitary fibrous tumor, desmoid fibromatosis, and gastrointestinal stromal tumor. Immunohistochemistry revealed tumor cells that were positive for beta-catenin, nuclear staining (Fig. 6) and S100 show weak staining (Fig. 8) but negative for SMA (Fig. 9), CD31 (Fig.7), CD117 and desmin.

Fig. 6.

a: Beta-catenin at x4 magnification. b: Beta-catenin at x20 magnification. (Both show strong nuclear positivity)

Fig. 8.

a: S100 at x4 magnification. b: S100 at x20 magnification. Figure 8a and 8b show S100 weak positivity for the tumour cells

Fig. 9.

a: SMA at x4 magnification. b: SMA at x20 magnification. Figure 9a and 9b show SMA negativity for the tumour cells, while the blood vessels’ positivity indicates good internal control

Fig. 7.

a: CD 31 at x4 Magnification. b: CD 31 at x20 Magnification. Figure 7a and 7b show negativity for the tumour cells, while we have a positive internal control where the endothelial cells of the blood vessels were stained brown)

A diagnosis of desmoid fibromatosis was made on the basis of the immunohistochemistry results.

Fig. 10.

a: CD 117 at x4 magnification. b: CD 117 at x20 magnification. CD 117, also known as Dog 1, shows negativity for the tumour cells)

Despite positive margins, immediate re-resection was deferred in accordance with the Desmoid Tumor Working Group’s recommendations [9], as margin status alone does not predict progression. Postoperative follow-up included cross-sectional imaging every 3–4 months for the first 2–3 years, every 6 months until 5 years, and annually thereafter if stable. MRI was preferred, with contrast-enhanced CT used as needed [10]. Clinical monitoring was performed concurrently. Intervention was reserved for radiographic progression, symptom development, or threat to vital structures. This strategy reflects the indolent and unpredictable behavior of desmoid tumors and avoids unnecessary morbidity.

More than one year after surgery, she remains clinically disease-free, with no evidence of recurrence or adverse sequelae, and is awaiting scheduled follow-up imaging.

Discussion

Desmoid tumors are benign clonal proliferations of myofibroblasts that exhibit local infiltration but lack metastatic potential [11]. This case represents a rare presentation of primary hepatic desmoid-type fibromatosis (DTF) manifesting with progressive abdominal distention and clinically significant hypoglycemia. Beyond its unusual anatomic location, the case is notable for its metabolic presentation, which is not classically associated with DTF and broadens the clinical spectrum of this disease. The combination of a large hepatic mass and hypoglycemia introduces a complex diagnostic framework, in which both primary hepatic malignancies and paraneoplastic syndromes must be carefully considered. In this context, definitive diagnosis relies on histopathological and immunohistochemical evaluation, particularly in the setting of atypical clinical features.

The development of desmoid fibromatosis is thought to arise from multiple contributing factors, including familial adenomatous polyposis (FAP), previous surgical or traumatic injury, hormonal effects, and mutations in the CTNNB1 gene, which encodes β-catenin [9]. Nonetheless, liver involvement is exceptionally uncommon, even in individuals considered at high risk. Because these tumors are rare, the most effective therapeutic approach is not well established. The most reliable management option in this patient was surgical excision. Watchful waiting is not indicated due to the tumour’s size. Medical treatments such as NSAIDs, antioestrogen agents, and systemic therapies, including tyrosine kinase inhibitors, are also additional management options described in the literature [12].

Desmoid tumors are benign, deep fibromatoses originating from the fascia and muscle aponeurosis, with infiltrative growth. It can affect any part of the body [12].

Why primary hepatic involvement is very rare. It most commonly arises in the mesentery, abdominal wall or retroperitoneum [11, 13]. This rarity warrants careful exclusion of secondary hepatic involvement from more typical extrahepatic primary lesion especially given the known tendency of intraabdominal desmoid tumour to extend into adjacent structures [14].

The index case presents with hypoglycemia. Hypoglycemia has also been recorded in patients with nonpancreatic tumors known as non-islet cell tumor hypoglycemia (NICTH) [15]. This is often associated with large mesenchymal or epithelial tumors that secrete excessive amounts of insulin-like growth factor II (IGF-II), particularly its high–molecular-weight variant (large IGF-II), which can activate insulin receptors, inhibit gluconeogenesis, and suppress counterregulatory hormone responses [15]. Retrospectively, we should have measured the IGH-II in this patient. However, this not routinely done at our institution, and due to limited resources, we are unable to do it elsewhere. We hypothesize, the mechanism of hypoglycemia present in this patient may be established in tumors such as solitary fibrous tumors (as in Doege–Potter syndrome), which provides a valuable framework for understanding hypoglycemia in other nonislet cell neoplasms [16].

For hepatic desmoid tumors, several non-mutually exclusive hypotheses may account for the development of worsening hypoglycemia: first, replacement of normal liver parenchyma, resulting in impaired liver function [17–19]. Second, ectopic production of IGF-II. Increased production of high-molecular-weight IGF-II (“big IGF-II”) could increase peripheral glucose utilization, suppress hepatic glucose release, and blunt counterregulatory hormone responses, such as glucagon and growth hormone, thereby provoking clinically significant hypoglycemia [20–22]. Third, there are cytokine-mediated metabolic effects. Desmoid tumors may induce systemic metabolic disturbances beyond the IGF-II pathway. There are also documented cases of paraneoplastic insulin resistance in patients with desmoid fibromatosis, potentially driven by proinflammatory cytokines, such as interleukin-6 (IL-6), produced by the tumor [23].

In particular, the presence of hypoglycemia in this case raises important considerations regarding tumor-related metabolic effects, which are not typically associated with DTF. While hypoglycemia is more commonly described in the context of large mesenchymal tumors through non-islet cell tumor hypoglycemia (NICTH), mediated by aberrant production of insulin-like growth factor II (IGF-II), its occurrence in DTF is exceptionally uncommon. The substantial tumor burden in this patient may have contributed to increased glucose utilization and/or paraneoplastic IGF-II secretion, although confirmatory biochemical testing was not performed. From a diagnostic standpoint, the overlapping radiologic features with primary and secondary hepatic malignancies underscore the importance of histopathological evaluation, particularly in atypical presentations. Therapeutically, the management of intra-abdominal and hepatic desmoid tumors remains nuanced, with a growing emphasis on individualized, multidisciplinary strategies ranging from active surveillance to systemic therapy. However, in cases such as this—characterized by progressive symptoms, mass effect, and metabolic complications—surgical resection remains a reasonable and effective approach.

Conclusion

This case highlights an uncommon presentation of primary hepatic desmoid-type fibromatosis with associated hypoglycemia, expanding the recognized clinical spectrum of this disease. It underscores the importance of considering rare benign entities in the differential diagnosis of large hepatic masses with atypical systemic features, and reinforces the central role of histopathological and molecular evaluation in establishing the diagnosis. In symptomatic patients, particularly in resource-variable settings, surgical resection remains an effective and pragmatic treatment strategy. Further reporting of similar cases is needed to better characterize the biological behavior and optimize management of this rare entity.

Abbreviations

CA

Carbohydrate antigen

CTNNB

1-Catenin Beta-1

CD

Clusters of Differentiation

CT

Computerized tomography

DFT

Desmoid Type Fibromatosis

FAP

Familiar Adenomatous Polyposis

IGF

Insulin Growth Factor

MRI

Magnetic Resonant Imaging

SMA

Smooth Muscle Actin

NICTH

Non-islet cell Tumor Hypoglyceamia

NSAID

Non-Steroidal Anti-inflammatory Drugs

Authors’ contributions

BO: Conceptualization, Methodology, Investigation, Pathological Diagnosis, Writing – Review & Editing.TO: Management (Anaesthetic)-Review & EditingJO: Investigation (specimen grossing and histopathological evaluation), Writing – Original Draft Preparation.OO: Investigation (diagnostic support and immunohistochemistry antibody selection), Writing – Review & Editing.AO: Investigation (radiological image interpretation), Writing – Original Draft Preparation, Writing – Review & Editing.FL: Supervision– Review & EditingOA: Supervision, Patient selection, Writing – Review & Editing.

Funding

This research did not receive funding.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Ethical approval was not required for this case report in accordance with institutional guidelines. The study was conducted in accordance with the Declaration of Helsinki.

Consent for publication

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

Competing interests

The authors declare no competing interests.