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Unveiling the Hidden Culprit: Subcutaneous Inguinal Phosphaturic Mesenchymal Tumour Causing Tumour-Induced Osteomalacia
*Corresponding author: Dr. Manish Ora, Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPIMS), Lucknow, Uttar Pradesh, 226014, India. drmanishora@yahoo.com
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Received: ,
Accepted: ,
How to cite this article: Kaur J, Sharma S, Jagannath S, Mayilvaganan S, Ora M. Unveiling the Hidden Culprit: Subcutaneous Inguinal Phosphaturic Mesenchymal Tumour Causing Tumour-Induced Osteomalacia. Indian J Nucl Med. 2026;41:379-81. doi: 10.25259/IJNM_186_25
Abstract
Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excess fibroblast growth factor-23 (FGF23), leading to renal phosphate wasting and hypophosphatemia. Patients present with nonspecific bone pain, muscle weakness, and fractures, resulting in significant diagnostic delays. Benign phosphaturic mesenchymal tumours are causative and are commonly located in the bones and soft tissues of the lower limbs and the head and neck. Complete surgical excision is curative, emphasising the need for lesion localisation. We present a rare case of a subcutaneously located lesion in the uncommonly reported inguinal region. Functional imaging utilising 68Ga-DOTANOC PET/CT offers unparalleled detection rates in this pathology.
Keywords
68Ga-DOTANOC PET/CT
Osteomalacia
Phosphaturic tumour
Tumour induced osteomalacia
TIO
INTRODUCTION
Tumour-induced osteomalacia (TIO) is a rare paraneoplastic disorder caused by excess secretion of fibroblast growth factor-23 (FGF23) from small, slow-growing tumours. The resulting renal phosphate wasting and decreased synthesis of 1,25-dihydroxyvitamin D led to chronic hypophosphatemia and impaired osteoblastic activity. Classically, patients present with vague, prolonged symptoms, such as diffuse bone pain, muscle weakness, and recurrent fractures, leading to diagnostic delay.[1,2] Laboratory evaluation demonstrates a characteristic hypophosphatemia, elevated alkaline phosphatase, and inappropriately low 1,25-dihydroxyvitamin D, while serum calcium levels are usually normal. The tumours responsible for TIO are most often benign phosphaturic mesenchymal tumours, typically located in the bones and soft tissues of the lower limbs and the head and neck region. Unusual sites, such as the inguinal region and subcutaneous location, are reported only sporadically.[2-4] Advances in functional imaging, particularly 68GaDOTA-based PET/CT, have greatly improved detection and localisation, enabling curative resection and guiding management for recurrent diseases.
CASE REPORT
A 58-year-old male patient, known case of type 2 diabetes mellitus for 6 years on lifestyle management, presented with generalised weakness and difficulty in walking following severe COVID -19 infection in April 2022. He had back pain radiating to the thighs and progressive lower limb weakness with restricted mobility and support for movement. The patient underwent left inferior parathyroidectomy for suspected hyperparathyroidism in August 2022, yet symptoms did not resolve. On clinical examination, neurological assessment revealed proximal lower limb weakness (power hip-3/5, knee-4/5). Upper limb motor system and upper-lower limbs sensory examination were preserved. Reflexes were brisk in the lower limbs. Investigations revealed severe hypophosphatemia (1.8 mg/dL; reference range: 2.5–4.5 mg/dL), raised alkaline phosphatase (430 U/L; reference range: 44–147 U/L), and normal serum calcium levels (9.0 mg/dL; reference range: 8.5–10.5 mg/dL). Osteoporosis was noted on bone densitometry, PTH was mildly raised (8.96 pmol/L), and 25-hydroxy vitamin D was in the normal range (115.5 ng/mL; reference range: 30 – 100 ng/mL). FGF 23 was markedly elevated. Magnetic resonance imaging (MRI) showed metabolic bone disease. Serum FGF 23 was 800 (normal range: 44–215 pg/mL). In view of suspected tumour-induced osteomalacia, the patient underwent Ga-68 DOTANOC PET/CT scan. It revealed a soft-tissue lesion in the left inguinal region with a maximum standardised uptake value (SUVmax) of 16.8, suggestive of a somatostatin receptor– expressing tumour. The surgeon performed an intraoperative ultrasound [Fig 1], which confirmed the presence of the lesion. A grey-brown soft-tissue lesion measuring 3.8 x 3 x 2 cm was excised. Histopathology was suggestive of hypercellular areas of oval/spindle cells with eosinophilic cytoplasm, and some foci of calcified matrix, consistent with a phosphaturic mesenchymal tumour. The patient recovered uneventfully and was discharged in stable condition after curative surgery. He had normal serum phosphate (4.1mg/dL) and calcium (9.2 mg/dL) levels, and a reduced serum alkaline phosphatase (335 U/L) in the postoperative period. Serum alkaline phosphatase was normalised to 159 u/L at 6-month follow-up.
DISCUSSION
TIO is a rare paraneoplastic syndrome characterised by defective bone mineralisation. Tumours secrete FGF23, which reduces renal tubular phosphate reabsorption and decreases 1,25-dihydroxyvitamin D synthesis. This leads to hypophosphatemia and osteomalacia.[1,2] Clinical manifestations include bone pain, muscle weakness, and recurrent fractures. Most cases are reported in adults, with prolonged diagnostic delay typically exceeding four years.[1,2,5] Small benign tumours cause TIO, located most commonly in the lower limbs (49.5%), followed by the head and neck (27.0%), upper extremities (7.4%), thorax and abdomen (4.9%), and spinal region (4.6%). Tumours are commonly located in the bones (44.5 %), soft tissues (38.4 %), craniofacial bones or paranasal sinuses (17.0 %).[2,3] However, reports of a subcutaneous tumour in the inguinal region are sporadic. Tonello et al. described a 40-year-old man with a progressive 3-year history of bone pain, pathological fractures, and skeletal deformities. He had hypophosphatemia with hyperphosphaturia. Whole-body MRI and fluorodeoxyglucose (FDG) positron emission tomography/computed tomogrpahy (PET/CT) localised a small left inguinoscrotal soft-tissue nodule, confirmed as a phosphaturic mesenchymal tumour.[4] The diagnostic evaluation of suspected TIO involves confirming phosphaturia in the presence of hypophosphatemia and elevated FGF23 levels. Conventional imaging modalities, such as CT or MRI, may fail to detect small peripheral lesions. The rarity of these tumours, their small size, and their locations may partially explain diagnostic delay. Detecting somatostatin receptors expression with 68Ga-DOTA-based PET/CT has excellent detection rates (98.9 %), followed by Tc99m-HYNIC-octreotide scan (95.3 %) and 18F-FDG PET/CT (74.8 %).[2] Benign phosphaturic mesenchymal tumour (PMT) is the most common histological diagnosis (81.2%). Other less common histologies include haemangiopericytoma, giant cell tumour, glomangiopericytoma, and odontogenic tumour. Malignant PMT and bone sarcomas are rare (~2.5%). Most tumours (96.6%) express FGF23.[2] Complete surgical resection of the tumour is curative, with clinical response in 97.6% and normalisation of serum phosphorus and FGF23 in 91.5% and 81.4% of patients, respectively. In case of recurrent disease or incomplete resections, adjunctive therapies such as radiotherapy, chemotherapy, octreotide, or embolisation may be done.[2,6] The anti-FGF23 monoclonal antibody burosumab is now an approved option for unresectable or unlocalisable TIO, demonstrating both biochemical and clinical responses.[7] This case highlights the importance of considering TIO in patients’ classical biochemical presentation. 68Ga-DOTANOC PET/CT plays a pivotal role in localising small mesenchymal tumours, particularly in unusual anatomical sites, enabling curative surgical resection.
CONCLUSION
Tumour-induced osteomalacia is sometimes difficult to diagnose because of its vague symptoms and occult tumour location. This case highlights the value of accurate clinical diagnosis in patients with unexplained hypophosphatemia and bone pain. Gallium-68 DOTANOC PET/CT played a pivot role in localising a rare and unexpected subcutaneous inguinal phosphaturic mesenchymal tumour, allowing curative surgical excision and clinical recovery.
Author contributions:
MO and SM: Conceptualisation; SM and SJ: Case identification and clinical management; JK, SS and MO: Imaging acquisition and interpretation; JK and SS: Data curation; JK and SJ: Literature review; JK and SS: Manuscript drafting; MO and SM: Critical revision of manuscript; MO: Supervision. All authors reviewed and approved the final manuscript.
Ethical approval:
Institutional Review Board approval is not required.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for their images and other clinical information to be reported in the journal. The patient understand that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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