Hypoglycemia unmasking a giant pulmonary solitary fibrous tumor: a case report

Abstract

Background

Hypoglycemia may result from multiple clinical conditions which are categorized based on clinical status. The first principal step in clinical diagnostic evaluation is measurement of plasma insulin, c-peptide, pro-insulin, and beta-hydroxybutyrate levels. One of the rare causes of hypoglycemia is a group of disorders known as non-islet cell tumor hypoglycemia (NICT), which results from the paraneoplastic secretion of insulin-like growth factor 2 (IGF-2). In rare cases, Solitary fibrous tumors SFTs are associated with recurrent hypoglycemia and represent the most frequent subtype of NICT.

Case presentation

We report a 66-year-old Iranian (Middle Eastern) man who presented with recurrent episodes of hypoglycemia, and significant unintentional weight loss. Laboratory workup revealed low insulin, C-peptide, and IGF-1 levels. Imaging studies identified a massive right thoracic mass with near-complete collapse of the right lung. Histopathological evaluation confirmed the diagnosis of solitary fibrous tumor with positive immunohistochemical staining for STAT6 and CD34. The tumor was surgically resected. Postoperatively, the patient recovered uneventfully, with resolution of hypoglycemic episodes.

Conclusion

This case highlights the importance of considering SFT and NICTH in patients with unexplained hypoglycemia and low insulin/C-peptide levels. Timely imaging and histopathological evaluation are crucial, as surgical resection can be curative.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13256-026-06334-y.

Introduction

Hypoglycemia, defined as a plasma glucose concentration below 3.0 mmol/L (54 mg/dL), can stem from a wide range of clinical conditions. When Whipple’s triad is present, a 72-h supervised fasting test is the recommended as initial diagnostic approach [1]. In patients with no clear etiology despite standard workup, rare causes—such as non-islet cell tumor hypoglycemia (NICT) —should be considered. Mesenchymal tumors are the most common form of NICTs [2, 3].

Solitary fibrous tumors (SFTs) are rare spindle-cell neoplasms of mesenchymal origin, first described in the pleura but now recognized to arise in virtually any anatomic location. They peak in the sixth and seventh decades of life. Symptoms are commonly due to the mass effect but paraneoplastic symptoms can also occur. The majority of SFTs are benign, approximately 10–20% demonstrate malignant behavior including local invasion and distant metastasis [4, 5]. A rare but potentially life-threatening manifestation of SFT is non-islet cell tumor hypoglycemia (NICTH), which results from ectopic secretion of incompletely processed insulin-like growth factor-2 (IGF-2), also known as “big IGF-2” [6].

Here, we present a 66-year-old man with recurrent hypoglycemia ultimately found to have a massive thoracic SFT, emphasizing the diagnostic challenges and therapeutic considerations in such presentations.

This case report was prepared in accordance with the CARE (CAse REport) guidelines. We used the CARE checklist when writing the manuscript to ensure completeness and transparency [Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D; the CARE Group. The CARE Guidelines: Consensus-based Clinical Case Reporting Guideline Development].

Case presentation

A 66-year-old Iranian (Middle Eastern) man with a known history of type 2 diabetes mellitus (DM) and hypertension (HTN) presented with recurrent episodes of hypoglycemia over the past two months. He had been diagnosed with DM three years earlier during a routine check-up and was managed with a combination of metformin 500 mg and sitagliptin 50 mg twice daily. The patient remained stable on this regimen until he began experiencing symptoms including anorexia, paresthesia of the soles, malaise, and exertional dyspnea. These symptoms notably improved following administration of oral glucose.

He reported an unintentional weight loss of 12 kg over the past year. Upon initial evaluation, fasting blood sugar (FBS) was as low as 44 mg/dL. Despite discontinuation of his antidiabetic medications, his hypoglycemic episodes persisted. Laboratory workup revealed low serum insulin (0.1 µU/mL; normal 2.6–24.9), C-peptide (0.07 ng/mL; normal 1.1–4.4), and IGF-1 (33.1 ng/mL; normal 40–225), consistent with non-islet cell tumor hypoglycemia (NICTH). He was referred to a tertiary center for further evaluation.

On admission to Namazi Hospital (located in Shiraz city, Fars province, in southern region of Iran), his vital signs were stable (BP: 140/85 mmHg, HR: 90 bpm, RR: 18, T: 37 °C). Physical examination revealed decreased breath sounds and dullness to percussion on the right hemithorax with increased tactile fremitus. No peripheral edema, clubbing, or signs of infection were noted. Neurological and cardiovascular examinations were within normal limits.

We should notice that the patient didn’t have a remarkable point in his social or familial history. Laboratory Results are presented in Table 1.

• Abdominopelvic ultrasound showed bilateral renal cortical cysts and a mildly enlarged heterogeneous prostate.

• Transthoracic echocardiography (TTE) showed mild left ventricular hypertrophy and mild valvular regurgitations with preserved ejection fraction (EF = 55%).

• The chest CT scan is shown in Fig. 1.

Table 1.

Laboratory results of the patient

Test		Unit	Reference interval
FBS	44	mg/dl	70–100
HbA1C	3.8	%	Non-diabetic: < 5.7% Pre-diabetic: 5.7–6.4% Diabetic: > 5.6%
2Hpp	193	mg/dl
Insulin level	0.1	µU/ml	Adult: 2.6–24.9
C-PEPTIDE	0.07	ng/ml	1.1–4.4
IGF-1	35.3	ng/ml	40–225
ACTH	8.14	pg/ml	7.2–63.6
Cortisol (8AM)	7.5	µgr/dL	3.7–19.4
Cortisol 6h after tetracosactide	33.5	µgr/dL
Urine creatinine (Random)	205	mg/dl	Adult male: 40–278
Urine Potassium (Random)	33.8	mEg/L	Adult: 25–150
TSH	4.08	µIu/ml	0.35–4.94
T4	6.65	µgr/dL	4.8–12
T3	1.31	ng/ml	0.8–2
Anti TPO	437	Iu/ml	Up to 39.2

Test	Result
WBC* /mm3	10.2
Hb gr/dl	12.3
Plt (103/ml)	232
MCV, fl	87.5
BUN (mg/dl)	12
Cr (mg/dl)	0.71
Na (mEq/L)	139
K (mEq/L)	3.1*
PH	7.44
PCO2	37.8
PO2	61.9
HCO3 mmol/L	25.8
BE	1.6
AST, U/L	22
ALT, U/L	18
Alk. Ph., U/L	229
T. Bili., mg/dl	0.76
D. Bilimg/dl	0.36
Protein, gr/dl	6.3
Albumin, gr/dl	3.7
Calcium (mg/dl)	9.4
Mg (mg/dl)	1.7
Ph (mg/dl)	2.8
CRP, mg/l	8
ESR(mm/hours)	33

Fig. 1.

Contrast enhanced computed tomography revealed a large (168 × 200 × 250 mm) heterogeneous soft tissue mass occupying the right hemithorax with collapse of the right lung and involvement of the right main bronchus, pulmonary artery, and vein. (A Coronal view, B, C Axial view)

Histopathological examination of the Tru-Cut biopsy revealed a spindle-cell neoplasm, immunohistochemistry showed diffuse and strong positivity for STAT6 and CD34, confirming the diagnosis of solitary fibrous tumor.

The patient underwent right posterolateral thoracotomy with complete resection of the tumor, right middle lobectomy, partial pleurectomy, and vascular repair due to invasion into the superior vena cava and right pulmonary artery. It should be mentioned that the patient tolerated the procedure well without considerable complications. Surgical findings described a massive posterior mediastinal tumor occupying the entire right hemithorax with extensive adhesions and lung compression.

Figure 2 shows the gross appearance of the resected tumor.

Fig. 2.

The pathological specimen was about 17 cm × 20 cm × 25 cm in size and appeared to be encapsulated

Histopathological and immunohistochemical features are depicted in Figs. 3, 4 and Table 2.

Fig. 3.

Histopathological features of the solitary fibrous tumor (Hematoxylin and Eosin stain). High-power view (× 40), B Intermediate-power view (× 20), C Low-power view (× 10), D Low-power view (× 4)

Fig. 4.

Pathological evaluation of the thoracic mass revealed a spindle-cell neoplasm. Immunohistochemistry showed diffuse and strong positivity for STAT6 and CD34, confirming the diagnosis of solitary fibrous tumor. The tumor was negative for ALK, SMA, CK. The Ki-67 labeling index was 3–4% (assessed by the hot spot method in areas of highest proliferative activity), indicating low proliferative potential

Table 2.

Findings of immunohistochemical analysis:

Marker	Result	Primary antibody source
STAT-6	POSITIVE (diffuse and strong)	Rabbit monoclonal
CD34	POSITIVE (diffuse and strong)	Rabbit polyclonal
ALK—protein	Negative	Rabbit monoclonal
SMA	Negative	Mouse monoclonal
CK	Negative	Mouse monoclonal
Ki-67	Low (3–4%)	Rabbit monoclonal

Image (**) shows margin description: unencapsulated but well-circumscribed tumor, with areas of hemorrhage. Microscopically, the tumor focally approached the resection margin; however, no definitive infiltration into adjacent tissue was identified.

After surgery, he was admitted to the Surgical ICU and later transferred to the Thoracic Surgery ward. His recovery was uneventful, with full resolution of hypoglycemic episodes. The patient himself also expressed great relief and gratitude for the resolution of symptoms and improvement in his quality of life. He was discharged in stable condition with recommendations for endocrinology follow-up and monitoring of serum glucose levels. Figure 5 shows the postoperative chest X-ray.

Fig. 5.

Plain chest radiography after tumor resection

Discussion

This case illustrates a classic presentation of Doege-Potter syndrome, the rare paraneoplastic phenomenon of non–islet cell tumor hypoglycemia (NICTH) caused by IGF-2–secreting solitary fibrous tumors (SFTs). Hypoglycemia results from “big” IGF-2, which increases glucose uptake and suppresses insulin secretion via feedback mechanisms, reflected in the patient's low insulin, C-peptide, and IGF-1 levels [6].

A review of 50 patients in a recent study, which categorized solitary fibrous tumors of the chest (SFTC) into pleural (SFTP) and pulmonary (SFTL) subtypes, revealed that approximately 62% of patients were under 55 years of age, and more than half were female. Most SFTP cases originated from the left side, while among 17 cases of SFTL, 9 were located on the right side. Tumor size ranged from 1.8 to 21.5 cm, with a mean size of 10.56 ± 3.18 cm [7]. In comparison, our patient was a 66-year-old man with a tumor arising from the right hemithorax, measuring 25 cm in its largest dimension—significantly larger than the tumors reported in that study.

SFTs, mesenchymal neoplasms characteristically positive for STAT6 and CD34, are often benign but up to 20% may become malignant and recur many years after initial diagnosis [5, 6]. A literature review of 22 cases of SFT in head and neck revealed that all tumors showed strong and diffuse vimentin, with a majority showing CD34 and all cases tested were negative for S100 protein, cytokeratin, smooth muscle actin, ALK-1 etc. [8]. These findings are compatible with our patient’s tumor IHC.

Based on the literature, there is no single measure of malignant potential as predictor of clinical progression. Although, a variety of parameters, such as greater than four mitoses per 10 high-power fields, tumor size, nuclear atypia, necrosis, and tumor suppressor gene expression, have been identified as being associated with increased risk of malignant potentiality [9].

We evaluated our patient’s risk of metastasis using the prognostic risk stratification models proposed by Demicco et al. According to both the original “three-variable model “and “the modified four-variable model”, the patient falls into the intermediate-risk category. This classification underscores the necessity for close and diligent long-term follow-up [9, 10].

Confirmation of NICTH involves biochemical evidence of suppressed insulin, C-peptide, and GH, with elevated big-IGF-2—which has similar structure and biological features to insulin and is the main cause of hypoglycemia in NICTH [11]—and high IGF-2/IGF-1 ratio. Low beta hydroxybutyrate and hypokalemia also support the diagnosis [12, 13]. Although testing of high-molecular-weight IGF-II secreted by the tumor through Western immunoblot method or gel-filtration is more accurate for establishing the diagnosis, these procedures often are not accessible in many routine clinical settings. Therefore, the diagnosis is frequently made based on patient’s clinical course [14]. It should be mentioned that there are some studies in literature in which IGF-1 level is measured in NICT induced hypoglycemia. In one study that was a report of 5 cases who were diagnosed with NICT, all patients had decreased levels of IGF-1 [15].

As observed in our case, the prolonged course of non-specific symptoms and weight loss, along with low levels of insulin, proinsulin, C-peptide, and IGF-1, led us to consider non-islet cell tumor (NICT) as the possible underlying mechanism of recurrent hypoglycemia. Furthermore, the patient had no other diseases that could have caused hypoglycemia.

Once there is biochemical evidence of NICTH, it is necessary to obtain a cross-sectional imaging of the chest, abdomen, and pelvis to identify a tumor [16].

Of note, based on a literature review done by Mohammed Turab et. Al. the most common paraneoplastic symptom with SFT is the osteoarthropathy. The prevalence of hypoglycemia is seen in less than 5% of patients with SFT [20].

It seems that complete surgical resection is the preferred treatment strategy for SFTPs if possible [17, 20]. In malignant or metastatic cases where complete removal is not feasible, debulking coupled with somatostatin analogs or preoperative embolization has shown benefit in glycemic control and tumor burden reduction. It should be mentioned that SFTs are often resistant to chemotherapy and it is controversial to be used routinely, so it is reserved mainly for metastatic disease and unresectable masses [18, 20]. Our patient’s complete surgical excision via thoracotomy mirrors successful approaches in similarly large thoracic SFTs with optimal control of hypoglycemic episodes in further follow-up.

Late recurrence remains a risk—even a decade post resection—especially in malignant or large-volume NICTH-associated tumors. Therefore, prolonged follow-up is essential even after successful surgical tumor resection. Also, it is recommended to consider Oncologic surveillance as provides opportunity for early detection and treatment of recurrent or metastatic disease. [19]

The review from MD Anderson showed that tumors greater than 15 cm in older patients (greater than 55) with mitotic rates greater than or equal to 4/10 per high power fields were at high risk of metastasis and precluded close surveillance [9]. It is important to mention that Surveillance of each patient should be individualized based on tumor location and other patient factors. Based on evidences Presence of factors including hypoglycemia, area of necrosis and hemorrhage with high mitotic rates and signs of cellular atypia on biopsy have all been noted to be markers of poor prognosis and increase the probability of recurrence in future [19, 20]. Considering that SFT has been diagnosed in many patients later in life, the need for lifetime surveillance for timely diagnosis of recurrence is crucial with some recent studies recommending surveillance for 10–15 years [6]. This is advocated for our patient despite his excellent postoperative course.

Limitations: Several limitations of this case report warrant acknowledgment. First, macroscopic photographs of the tumor cut surface at its maximum dimension were not available due to the time elapsed since initial specimen processing, which limited comprehensive documentation of gross pathological features such as the extent and distribution of intratumoral hemorrhage or necrosis.

Second, immunohistochemical staining for insulin, proinsulin, IGF-1, and IGF-2 could not be performed as these markers were not available in our pathology laboratory at the time of diagnosis. The absence of IGF-2 immunostaining represents a notable limitation, as IGF-2 overexpression is a well-established mechanism underlying non-islet cell tumor hypoglycemia (NICTH) in solitary fibrous tumors. Demonstration of IGF-2 expression would have provided direct pathophysiological confirmation of the hypoglycemic mechanism in this case. Future cases of SFT presenting with hypoglycemia should ideally include IGF-2 immunohistochemistry as part of the diagnostic workup to establish this association definitively.

Despite these limitations, the clinical presentation, biochemical profile, histopathological features, and resolution of hypoglycemia following tumor resection collectively support the diagnosis of solitary fibrous tumor associated with NICTH in this patient.

Conclusion

This case underscores the significance of recognizing recurrent fasting hypoglycemia—especially with suppressed insulin and C-peptide levels—as a potential sign of NICTH secondary to SFT even when the patient does not exhibit prominent or dramatic symptoms of the tumor. The diagnosis hinges on elevated big-IGF-2 if it is feasible to check the levels, imaging confirmation, and STAT6/CD34-positive pathology. Complete surgical resection remains the standard of cure, emphasizing the need for long-term surveillance even in otherwise low-grade histology.

Author contributions

MJ: study concept, design, supervision. SSH: study concept, data collection, writing the paper. SKH: study concept, data collection. MJF: study concept, design.

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and give their approval for this version to be published.

Funding

None to disclose.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The ethical clearance for the case report was waived by the Ethics Committee of shiraz university of medical sciences. Written informed consent was obtained from the patient.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

There is no competing interests in this case report.