Doege-Potter syndrome in a patient with solitary fibrous tumor of the pleura: a rare cause of refractory hypoglycemia—a case report

Introduction

Solitary fibrous tumors (SFTs) are uncommon mesenchymal neoplasms that may arise in various anatomical locations, with the pleura being among the most frequently reported sites (1). Historically termed “localized fibrous mesothelioma”, these tumors are now recognized to originate from the submesothelial connective tissue rather than from mesothelial cells, reflecting their distinct histogenesis (2). Clinically, they most often present as well-circumscribed, slow-growing masses and only rarely manifest with paraneoplastic syndromes, including hypoglycemia (3). Although the majority of solitary fibrous tumors of the pleura (SFTPs) follow a benign clinical course with excellent prognosis after complete surgical excision, a subset exhibits aggressive behavior with malignant transformation, local recurrence, and metastatic potential (4).

Doege-Potter syndrome (DPS) is a rare paraneoplastic manifestation of SFTP characterized by recurrent non-insulin-mediated hypoglycemia, occurring in less than 5% of cases, with approximately 100 cases reported in the literature worldwide (3). The pathophysiological mechanism involves excessive secretion of incompletely processed insulin-like growth factor (IGF) II (big IGF-II), which increases peripheral glucose utilization and suppresses endogenous insulin and growth hormone secretion, resulting in persistent and potentially life-threatening hypoglycemia (5). Accurate differentiation between benign and malignant SFTP is essential for therapeutic planning and prognostic stratification. Histopathological features indicative of malignancy includes increased cellularity, nuclear pleomorphism and atypia, elevated mitotic activity (typically >4 mitoses per 10 high-power fields), and areas of necrosis or hemorrhage (6).

We report a case of malignant SFT of the pleura arising from the right hemithorax and presenting with refractory, non-insulin-mediated hypoglycemia in a patient with pre-existing diabetes mellitus. Complete surgical excision with negative margins achieved immediate postoperative resolution of hypoglycemia, and the patient remains disease-free at 3-year follow-up. This case reinforces the pivotal role of radical resection in managing malignant SFTs and associated DPS, and adds meaningful evidence to the limited literature on this rare clinical entity. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0007/rc).

Case presentation

A 65-year-old man with a medical history of cerebrovascular accident, type 2 diabetes mellitus treated with oral hypoglycemic agents, hypertension, and dyslipidemia presented to a local emergency department with recurrent hypoglycemia and progressive dyspnea. On arrival, his blood pressure was 150/90 mmHg, heart rate 90 beats per minute, and oxygen saturation 95% on room air. Chest radiography revealed a large opacity occupying the right hemithorax (Figure 1). Contrast-enhanced computed tomography (CT) of the chest demonstrated a well-circumscribed, mildly heterogeneous soft-tissue mass measuring approximately 18.8 cm × 15.1 cm × 18.2 cm in the right mid-to-lower hemithorax, causing significant compression of the right lung and cardiac structures with contralateral mediastinal shift (Figure 2). Additional findings included patchy ground-glass opacity in the posterior segment of the right upper lobe, centrilobular and paraseptal emphysema in both lungs, and a few small nodules in the left lower lobe measuring up to 0.4 cm. The patient was subsequently referred to the Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand, for further evaluation and management.

Figure 1 Chest X-ray shows a homogeneous opacity indicating a large pleural mass in the right chest cavity.

Figure 2 Axial computed tomography demonstrates well-circumscribed, mildly heterogeneous soft-tissue mass measuring approximately 18.8 cm × 15.1 cm × 18.2 cm in the right mid-to-lower hemithorax, causing significant compression of the right lung and cardiac structures with contralateral mediastinal shift.

Ultrasound-guided core needle biopsy revealed a spindle cell neoplasm. Immunohistochemical analysis showed strong positivity for CD34 and STAT6, with additional positivity for β-catenin and S100, while desmin, CD117, DOG1, and cytokeratin AE1/AE3 were negative. Biochemical evaluation demonstrated suppressed insulin (<0.4) and C-peptide levels (0.15) with altered insulin-like growth factor parameters (IGF-1 low and IGF-2 levels normal respectively), consistent with non-insulin-mediated hypoglycemia. A benign peripheral nerve sheath tumor was initially considered in the differential diagnosis. After multidisciplinary team discussion, surgical resection was recommended given the tumor size, compressive symptoms, and limited role of systemic therapy.

Following informed consent, the patient underwent urgent right anterolateral thoracotomy under general anesthesia with left-sided double-lumen endotracheal intubation for right lung isolation. The thoracic cavity was entered through the sixth intercostal space. Intraoperatively, a large, well-encapsulated mass with loose adhesions and no pleural effusion was identified. The adhesions were carefully divided using a LigaSure^TM device, and complete tumor excision was achieved without evidence of invasion into adjacent lung parenchyma or cardiac structures. The postoperative course was uneventful. The patient was monitored in the intensive care unit, chest drains were removed on postoperative day 5, and he was discharged home on postoperative day 10 in stable condition.

Final histopathological examination demonstrated spindle cells arranged within a collagenous stroma. Immunohistochemistry confirmed strong nuclear STAT6 and diffuse CD34 positivity, consistent with SFT. At follow-up, the patient experienced complete resolution of hypoglycemia and dyspnea, with only mild incisional discomfort. Surveillance imaging at 6 months and 3 years showed no evidence of recurrence (Figure 3). All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Figure 3 Timeline of presentation, diagnosis, surgical resection, and 3-year disease-free follow-up in a patient with malignant solitary fibrous tumor of the pleura presenting with Doege-Potter syndrome. CT, computed tomography.

Discussion

Malignant solitary fibrous tumor of the pleura (MSFTP) associated with DPS is exceptionally rare, with existing evidence largely derived from isolated case reports and small series (4-7). Most published cases describe large pleural tumors often exceeding 10–15 cm presenting with recurrent, non-insulin-mediated hypoglycemia secondary to overproduction of incompletely processed “big” IGF-II (4). Biochemical profiles typically reveal suppressed insulin and C-peptide levels, and rapid postoperative resolution of hypoglycemia following complete tumor excision is consistently reported (5,6). The immediate and sustained normalization of blood glucose levels following complete tumor resection in our patient strongly confirms a tumor-induced (paraneoplastic) etiology of hypoglycemia. Notably, however, many hypoglycemia-associated SFTs are ultimately classified as benign or borderline, and clearly malignant cases with pronounced histopathological aggressiveness remain uncommon (5).

Diagnosis is established through combined biochemical, radiological, and histopathological evaluation. Biochemically, patients exhibit hypoinsulinemic hypoglycemia with suppressed insulin and C-peptide levels, low IGF-1, and elevated “big” IGF-II (3,6). Imaging-CT and magnetic resonance imaging defines tumor extent and local invasion (8). Histopathology demonstrates spindle cells in a patternless architecture, with malignancy suggested by hypercellularity, nuclear atypia, increased mitotic activity (>4/10 high-power fields), and necrosis (6,7). CD34 and nuclear STAT6 positivity confirm the diagnosis (8,9). In the present case, the combination of refractory hypoinsulinemic hypoglycemia, a large pleural mass, and confirmatory histopathology established the diagnosis of malignant SFT with DPS. Malignant SFTs having unpredictable behavior, and features such as large size, high mitotic index, necrosis, and infiltrative growth are associated with recurrence or metastasis (7,9). Long-term surveillance is therefore recommended even after complete resection.

Complete surgical excision with histologically negative margins (R0 resection) remains the cornerstone of management for malignant SFT of the pleura and offers the greatest likelihood of durable remission, including definitive resolution of associated DPS (7,8). Incomplete resection is a well-established risk factor for local recurrence and adverse long-term outcomes (4,5,9). In the present case, despite the large tumor burden and significant intrathoracic compression, complete tumor excision was successfully achieved through an anterolateral thoracotomy with clear surgical margins, thereby optimizing oncologic control and postoperative recovery.

The role of adjuvant therapy remains uncertain. Radiotherapy may be considered in cases with adverse histopathological features or incomplete resection to improve local control, whereas systemic chemotherapy is generally reserved for unresectable, recurrent, or metastatic disease, with variable therapeutic response (4,7). Our patient did not receive adjuvant therapy and remains recurrence-free at 3-year follow-up, emphasizes the importance of complete surgical resection and vigilant postoperative monitoring.

The present case differs in several important respects. First, it demonstrates unequivocal malignant histopathological features, including high mitotic activity and necrosis, in conjunction with refractory hypoglycemia, an infrequent combination in the literature (3,5). Second, the occurrence of persistent hypoglycemia in a patient with pre-existing type 2 diabetes mellitus presents a unique diagnostic challenge, as hypoglycemic episodes may initially be attributed to antidiabetic therapy rather than a paraneoplastic process (6-8). Third, although postoperative normalization of glucose levels is well documented, extended oncologic follow-up is less commonly reported. Finally, the sustained 3-year disease-free survival observed in this case, achieved without adjuvant therapy, provides meaningful evidence supporting the durability of complete surgical resection even in malignant variants (3,5).

Conclusions

A systematic approach is essential in the management of DPS, a rare but potentially aggressive paraneoplastic condition. Complete surgical resection remains the treatment of choice and typically results in rapid metabolic resolution. As the role of adjuvant therapy is not yet well established, accurate histopathological evaluation, appropriate risk stratification, and long-term surveillance are crucial to optimize outcomes and detect recurrence early.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0007/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0007/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0007/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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