Hyperparathyroidism revealed by brown tumors of the jaws: a retrospective case series

Abstract

Introduction and importance:

Brown tumors are rare osteolytic lesions resulting from prolonged excess of parathyroid hormone (PTH). Although they typically affect the axial skeleton, jaw involvement is uncommon and may represent the first manifestation of previously undiagnosed hyperparathyroidism. Because these lesions closely mimic other giant cell–rich jaw pathologies, accurate diagnosis requires careful clinicobiochemical correlation.

Methods:

This retrospective single-center case series included three consecutive female patients treated between 2022 and 2023 for expansile giant cell–rich jaw lesions associated with elevated PTH levels. Clinical, radiological, biochemical, therapeutic, and follow-up data were analyzed descriptively.

Results:

Three patients, aged 22–60 years, presented with painless mandibular or maxillary swellings. Imaging showed radiolucent or mixed lesions with cortical expansion, including perforation in two cases. Histopathology revealed multinucleated giant cells within a fibrovascular stroma. Biochemical evaluation confirmed primary hyperparathyroidism in two patients and secondary hyperparathyroidism in one patient on hemodialysis. Parathyroidectomy led to lesion regression in the primary cases, while the secondary case was managed conservatively.

Discussion:

Jaw brown tumors may represent sentinel manifestations of systemic endocrine disease and can be easily misdiagnosed because of their radiological and histological resemblance to other giant cell lesions. Recognition of this association is crucial, as correction of the underlying endocrine disorder frequently leads to spontaneous lesion regression, avoiding unnecessary maxillofacial surgery.

Conclusion:

Brown tumors of the jaws should be considered in the differential diagnosis of giant cell–rich jaw lesions. Early biochemical investigation and multidisciplinary management are essential to identify underlying hyperparathyroidism and ensure appropriate treatment.

Introduction

Brown tumors are rare, benign osteolytic lesions representing a skeletal manifestation of prolonged hyperparathyroidism^[1^]. Persistent elevation of parathyroid hormone (PTH) stimulates osteoclastic bone resorption and replacement of normal bone by fibrovascular tissue^[2^]. Although these lesions typically involve areas of high bone turnover, such as the ribs, pelvis, and long bones, maxillofacial involvement, particularly of the maxilla, remains rare and may pose a diagnostic challenge.

In the jaws, brown tumors frequently mimic other osteolytic entities, particularly central giant cell granuloma, both radiologically and histologically, making clinicobiochemical correlation essential for accurate diagnosis^[3,4^]. Importantly, jaw lesions may precede systemic manifestations and become the initial presentation leading to the detection of previously unrecognized primary or secondary hyperparathyroidism. This diagnostic sequence is especially relevant in settings where routine metabolic screening is limited, and where maxillofacial imaging often represents the first step toward etiological clarification^[4^].

HIGHLIGHTS

• Jaw brown tumors may be the first sign of undiagnosed hyperparathyroidism.

• They closely mimic other giant-cell jaw lesions.

• Treating the endocrine cause often leads to lesion regression without jaw surgery.

• Multifocal jaw lesions should prompt evaluation for systemic metabolic disease.

• Multidisciplinary assessment is key to accurate diagnosis and optimal management.

Here, we report three illustrative cases of jaw brown tumors that served as the presenting manifestation of underlying hyperparathyroidism (primary in two patients and secondary in one). The bimaxillary and multifocal patterns observed in this series are infrequently described and underscore the need to include brown tumors in the differential diagnosis of expansile osteolytic jaw lesions^[5,6^]. This case series was reported according to the PROCESS 2025 guidelines^[7^].

Methods

Participants and recruitment

This retrospective observational case series included three consecutive female patients with expansile giant cell–rich jaw lesions treated at the Department of Oral Surgery, Rabat Dental Consultation and Treatment Center, between January 2022 and December 2023. Consecutive recruitment was employed to minimize selection bias. Inclusion criteria were: (1) histopathological evidence of a giant cell–rich lesion; (2) elevated serum PTH levels; and (3) complete clinical, radiological, biochemical, and follow-up data. Patients were excluded if biochemical confirmation of hyperparathyroidism was absent or if medical records were incomplete. Demographics (age, sex), comorbidities (including chronic renal failure), and clinical findings were recorded. No monetary incentives were provided.

Pre-intervention patient optimization

Preoperative optimization focused on correcting biochemical abnormalities. Patients with hypercalcemia (Cases 1 and 3) received hydration and loop diuretics to lower serum calcium. Routine medication histories were reviewed and managed according to clinical standards, and preoperative education and psychological support were provided when appropriate.

Interventions

All patients received endocrine-directed treatment. Therapeutic interventions comprised surgical parathyroidectomy for those with primary hyperparathyroidism and multidisciplinary conservative management for the patient with secondary hyperparathyroidism due to chronic renal failure. Preoperative parathyroid localization relied on cervical ultrasonography, which identified the culprit gland in the two patients with primary hyperparathyroidism; ^99mTc-sestamibi scintigraphy was not performed, as ultrasonography was conclusive, nuclear-medicine access was limited in our setting, and localization studies are of limited value in secondary hyperparathyroidism, which reflects diffuse four-gland hyperplasia.

Surgical parathyroidectomies were performed under general anesthesia with standard sterile preparation. Patients were positioned supine with neck extension; a cervical incision and dissection were used to expose and excise the diseased gland. Intraoperative PTH monitoring confirmed adequate excision. Standard surgical instruments and absorbable sutures were used. Perioperative analgesia, antibiotics when indicated, and venous thromboembolism prophylaxis, per institutional protocols, were provided.

Operator details

Incisional biopsies were performed under local anesthesia by a team consisting of a Professor of Oral Surgery and a third-year oral surgery resident, ensuring both expert oversight and trainee participation. Definitive parathyroidectomies were conducted independently by board-certified endocrine surgeons with extensive specialized experience (>50 parathyroid procedures annually). Collaboration with endocrinology and nephrology specialists supported comprehensive case management.

Quality control

To ensure diagnostic and procedural consistency, all histopathological slides were reviewed by two experienced oral pathologists, and imaging was interpreted by a maxillofacial radiologist. Standardized clinical and imaging protocols were applied across all cases. No significant procedural or diagnostic discrepancies were noted between cases.

Post-operative care and follow-up

Post-operative care for surgical patients included pain control, hydration, early mobilization, and routine monitoring of serum calcium, phosphate, and PTH. Patients received verbal and written care instructions, including signs of hypocalcemia. Follow-up visits were scheduled at approximately 3 and 6 months, and 1 year post-intervention, and comprised clinical examination, radiological imaging, and biochemical reassessment in the secondary care outpatient setting with the operating surgeon and endocrinologist. No participants were lost to follow-up. Long-term surveillance recommendations were communicated but were outside the reported observation period.

Analysis

Given the small sample size and observational design, data were analyzed narratively without formal statistical testing. Emphasis was placed on describing clinical characteristics, diagnostic pathways, biochemical profiles, intervention details, and short-term outcomes, consistent with established case series reporting expectations.

Results

Participants

Three female patients, aged 22, 45, and 60 years, were included. One patient had chronic renal failure requiring long-term hemodialysis, while the remaining two had no significant medical history. None had a prior diagnosis of hyperparathyroidism at presentation (Table 1).

Table 1.

Clinical and diagnostic characteristics of three cases with Brown tumors secondary to hyperparathyroidism.

Feature	Case 1	Case 2	Case 3
Age / gender	45-year-old female	22-year-old female	60-year-old female
Medical history	No systemic illness	Chronic renal failure on hemodialysis	No systemic illness
Lesion location	Left posterior mandible	Left posterior maxilla and right anterior mandible	Bilateral maxilla (more on left)
Clinical presentation	Firm, painless swelling; buccal and lingual expansion	Bilateral firm swellings; buccal expansion	Painless swelling with vestibular and palatal expansion
Radiological features	Mixed-density expansile lesion; cortical expansion and perforation	Multifocal osteolytic lesions; maxillary perforation; mandibular expansion	Two maxillary lesions; larger ill-defined with perforation; smaller well-defined
Histopathology	Giant cell lesion (CGCG)	Giant cell lesion (CGCG)	Giant cells with hemosiderin (brown tumor features)
Biochemical profile	↑ PTH (914.5 pg/mL), ↑ calcium (12.8 mg/dL), ↓ phosphate	↑ PTH (1070 pg/mL); normocalcemia and normophosphatemia	↑↑ PTH (2062 pg/mL), ↑ calcium (13.3 mg/dL), ↓ phosphate, ↑ ALP (398 U/L)
Parathyroid imaging	Hypoechoic left parathyroid mass	Bilateral retrothyroid nodules	Hypervascularized left parathyroid nodule (54 × 13 mm)
Final diagnosis	Jaw brown tumor due to primary hyperparathyroidism	Jaw brown tumors due to secondary hyperparathyroidism	Jaw brown tumors due to primary hyperparathyroidism
Management and outcome	Focused parathyroidectomy (no jaw surgery); normalisation of serum calcium and PTH; radiological regression at 6 months and marked regression with restored trabecular pattern at 12 months; no complications (Clavien-Dindo 0).	No jaw surgery; medical metabolic management (dietary phosphate restriction, phosphate binders, calcitriol, cinacalcet, dialysis optimisation) coordinated by nephrology and endocrinology; progressive lesion reduction at 6 months and further regression at 12 months; no complications (Clavien-Dindo 0).	Correction of hypercalcemia (hydration + loop diuretics) then focused parathyroidectomy with intraoperative PTH monitoring (no jaw surgery); normalisation of calcium, PTH and ALP; regression of both maxillary lesions at 6 and 12 months; no complications (Clavien-Dindo 0).

Case description

Case 1

A 45-year-old female presented with a slowly enlarging, painless swelling of the left posterior mandible, evolving over approximately 1 year. She had no history of trauma, infection, or systemic disease. Extraoral examination revealed facial asymmetry without lymphadenopathy or sensory deficit.

Intraorally, a firm bony expansion involved both buccal and lingual cortices, extending from the apical region of tooth 34 to the edentulous area of tooth 36. Teeth 34 and 35 were vital and stable (Fig. 1A). Panoramic radiography revealed a poorly defined radiolucent lesion in the left mandibular body (Fig. 1B). Cone-beam computed tomography (CBCT) demonstrated a large mixed-density lesion with marked cortical expansion, thinning, and focal perforation (Fig. 1C). The preserved vitality of adjacent teeth and the absence of inflammatory signs excluded odontogenic or infectious etiologies.

Figure 1.

Case 1. (A) Preoperative intraoral view showing buccal and lingual bony expansion at the edentulous tooth 36 region. (B) Panoramic radiograph showing a poorly defined radiolucent lesion in the left mandibular body (arrows). (C) Cone-beam computed tomography showing a mixed-density lesion with marked cortical expansion, thinning, and focal perforation. (D) Histopathology (hematoxylin and eosin, ×400) showing multinucleated giant cells within a cellular fibrovascular stroma.

An incisional biopsy was performed. Histopathological examination showed multinucleated giant cells within a fibroblastic stroma, consistent with central giant cell granuloma (Fig. 1D). A metabolic evaluation revealed hypercalcemia (12.8 mg/dL), hypophosphatemia (1.95 mg/dL), and markedly elevated PTH (914.5 pg/mL). Cervical ultrasonography identified a hypoechoic mass posterior to the left thyroid lobe, consistent with a parathyroid adenoma. These findings were consistent with primary hyperparathyroidism.

The patient underwent a parathyroidectomy without direct maxillofacial surgery. No deviation from the planned management strategy occurred.

At 6 months post-parathyroidectomy, the patient showed a significant reduction in the mandibular lesion clinically and on imaging, with early signs of bone remineralization. By 12 months, there was marked radiological regression of the lesion, with restoration of normal trabecular patterns. Serial biochemical monitoring demonstrated normalization of serum calcium and PTH levels. Throughout the perioperative and postoperative periods, no complications occurred (Clavien-Dindo Grade 0), and the recovery course was uneventful.

Case 2

A 22-year-old female with chronic renal failure, on hemodialysis for 4 years, was referred for progressive facial deformity caused by swellings in the left posterior maxilla and right anterior mandible. Clinical examination revealed firm, non-tender swellings without lymphadenopathy or sensory disturbance (Fig. 2A).

Figure 2.

Case 2. (A) Extraoral and intraoral views showing facial asymmetry with swelling of the left maxilla and right mandible, as well as intraoral swelling extending from tooth 22 to tooth 26 with normal overlying mucosa. (B) Panoramic radiograph showing multiple radiolucent lesions involving the maxilla and mandible. (C) Three-dimensional CBCT reconstructions showing multiple expansile osteolytic craniofacial lesions, including a maxillary lesion extending toward the orbital floor. (D) Histology (hematoxylin and eosin, ×400) showing a fibrocellular stroma with numerous multinucleated giant cells.

Intraorally, the maxillary lesion extended from teeth 22 to 27, and the mandibular lesion involved from teeth 43 to 45 with buccal cortical expansion (Fig. 2A). Panoramic radiography showed multiple radiolucent lesions (Fig. 2B). CBCT revealed multifocal osteolytic lesions involving the craniofacial skeleton. The maxillary lesion extended superiorly toward the orbital floor with cortical perforation, while the mandibular lesion caused buccal expansion with preservation of the lingual cortex (Fig. 2C). The multifocal pattern and renal history strongly suggested a systemic etiology.

Incisional biopsy confirmed central giant cell granuloma (Fig. 2D). Biochemical evaluation demonstrated elevated PTH (1070 pg/mL) with normal calcium and phosphate levels. Cervical ultrasonography revealed bilateral retrothyroid nodules. Based on clinicopathological and biochemical correlation, a diagnosis of brown tumors secondary to hyperparathyroidism was established.

Management was conservative and directed at the underlying metabolic disorder, comprising dietary phosphate restriction, oral phosphate binders, active vitamin D supplementation (calcitriol), a calcimimetic (cinacalcet), and optimization of the hemodialysis regimen, coordinated jointly by nephrology and endocrinology. No surgical intervention was performed on the jaw lesions. At 3 months, the tumors remained stable. By 6 months, panoramic imaging showed a gradual reduction in lesion size with improved metabolic control. At 12 months, further regression correlated with ongoing endocrinology and nephrology care. The patient experienced no perioperative or postoperative complications (Clavien-Dindo Grade 0) throughout management and follow-up.

Case 3

A 60-year-old female with no known medical history presented with a painless swelling of the left maxilla that had been evolving over 2 years, with accelerated growth over the preceding 6 months (Fig. 3A). Intraoral examination revealed a fully edentulous maxilla with firm vestibular and palatal expansion (Fig. 3B).

Figure 3.

Case 3. (A) Extraoral view showing facial asymmetry with swelling of the left maxilla. (B) Intraoral view showing the edentulous maxilla with firm vestibular and palatal expansion. (C) Coronal CBCT reconstructions showing bilateral maxillary lesions with mixed radiodensity and expansion, infiltrating both maxillary sinuses. (D) Histology (×400) showing numerous multinucleated giant cells dispersed within a spindle-cell stroma with abundant capillaries.

CBCT demonstrated bilateral maxillary lesions (Fig. 3C). The right lesion was well-defined and expansile, whereas the left lesion was larger, ill-defined, and associated with cortical perforation. The bilateral non-odontogenic pattern raised suspicion of systemic disease. Cervical ultrasonography identified a hypervascularized left parathyroid nodule (54 × 13 mm), consistent with a parathyroid adenoma.

Fine-needle aspiration followed by incisional biopsy revealed multinucleated giant cells clustered around hemosiderin deposits within a fibrovascular hemorrhagic stroma, highly suggestive of a brown tumor (Fig. 3D). Subsequent biochemical investigations showed markedly elevated PTH (2062 pg/mL), hypercalcemia (13.3 mg/dL), hypophosphatemia (3.2 mg/dL), and elevated alkaline phosphatase (398 U/L).

The patient underwent medical correction of hypercalcemia, followed by focused parathyroidectomy with intraoperative PTH monitoring confirming successful excision. No maxillofacial surgery was performed. After the focused parathyroidectomy, early follow-up at 6 months revealed a noticeable decrease in the size and expansion of the bilateral maxillary lesions on CBCT, accompanied by improved cortical definition. At 12 months, there was marked radiological regression of both maxillary brown tumors and normalization of serum biochemistry (calcium, PTH, alkaline phosphatase). The patient’s recovery was smooth, with no complications reported (Clavien-Dindo Grade 0) in the perioperative or postoperative periods, and clinical function remained preserved.

Discussion

In this retrospective case series, three female patients aged 22–60 years presented with expansile giant cell–rich jaw lesions that ultimately led to the diagnosis of previously unrecognized hyperparathyroidism – primary in two cases and secondary in one. Multifocal involvement was observed in two patients, and cortical perforation occurred in two lesions. Importantly, definitive endocrine management – parathyroidectomy for primary disease and metabolic optimization for secondary hyperparathyroidism – resulted in progressive radiological regression within 6–12 months in all cases, without the need for direct maxillofacial surgical intervention. These findings reinforce that jaw brown tumors represent reversible metabolic manifestations and highlight the importance of addressing the endocrine etiology rather than performing primary osseous resection.

Brown tumors constitute a skeletal complication of prolonged PTH excess and belong to the spectrum of osteitis fibrosa cystica^[8^]. Sustained elevation of PTH promotes osteoclastic activation and high bone turnover, leading to trabecular destruction, cortical thinning, and replacement of normal bone by fibrovascular tissue rich in multinucleated giant cells and hemorrhagic components^[1,2,4^]. In advanced cases, this exaggerated metabolic remodeling may radiographically simulate aggressive neoplasms or metastatic disease, particularly when lesions are multifocal^[9^]. The cortical perforation and expansile behavior observed in our series reflect this pathophysiological mechanism.

Although brown tumors can affect various skeletal sites, jaw involvement is clinically significant because it may represent the initial manifestation of hyperparathyroidism^[10^]. Epidemiological data suggest that brown tumors occur in approximately 3–5% of primary hyperparathyroidism cases and less frequently in secondary disease^[11^]. Primary hyperparathyroidism most often presents between the fourth and sixth decades of life and shows a marked female predominance (approximately 3:1)^[2,10^]. Brown tumors most frequently involve the ribs, pelvis, clavicles, and long bones, whereas within the craniofacial region, the mandible is affected more often than the maxilla^[1,8^]; the exclusively female and predominantly maxillary pattern observed in our small series is therefore noteworthy. The exclusive female distribution in our cohort corresponds to the recognized demographic predominance of primary hyperparathyroidism^[10,11^]. Secondary hyperparathyroidism, typically associated with chronic kidney disease, results from phosphate retention, hypocalcemia, and impaired vitamin D metabolism, leading to compensatory PTH overproduction and renal osteodystrophy^[12^]. In rare instances, prolonged stimulation may progress to tertiary hyperparathyroidism or be associated with hereditary conditions such as hyperparathyroidism–jaw tumor syndrome^[13,14^].

Radiographically, brown tumors commonly appear as uni- or multilocular osteolytic lesions with cortical expansion and thinning^[8^]. Multifocality, bilateral distribution, and non-odontogenic patterns – as seen in two of our cases – should raise suspicion of systemic metabolic disease. Previous reports describe aggressive maxillary presentations that mimic malignant processes^[15^], and multifocal osteolytic lesions may be misinterpreted as metastases^[9^]. Therefore, imaging findings alone are insufficient for diagnosis and must prompt biochemical evaluation.

Histopathologically, brown tumors are characterized by multinucleated giant cells within a fibrocellular stroma containing hemorrhagic areas^[8^]. However, these features overlap significantly with central giant cell granuloma and other giant cell–rich lesions, rendering histology non-specific^[8,9^]. This diagnostic overlap underscores the critical role of biochemical correlation. Measurement of serum PTH, calcium, and phosphate levels is indispensable for distinguishing brown tumors from primary jaw pathology^[10^]. In our series, endocrine evaluation was decisive in establishing the diagnosis and preventing unnecessary local surgical intervention.

From a clinical management perspective, the central principle is the correction of the underlying endocrine disorder. Parathyroidectomy remains the definitive treatment for primary hyperparathyroidism and has been consistently associated with the gradual regression of brown tumors over several months^[16^]. Systematic analyses report regression intervals typically ranging from 6 to 24 months following hormonal stabilization^[17^]. In our patients, radiological improvement was evident at 6 months and became marked at twelve months, aligning with the lower range of reported timelines. In secondary hyperparathyroidism, medical metabolic optimization remains the first-line therapy^[12^], and regression under conservative management has been documented^[16^]. Our findings support this therapeutic hierarchy. Accurate preoperative localization underpins parathyroid surgery. ^99mTc-sestamibi scintigraphy, often combined with SPECT/CT, is regarded as a reference modality for parathyroid localization and is particularly valuable when cervical ultrasonography is inconclusive, when an ectopic or mediastinal gland is suspected, or when minimally invasive focused parathyroidectomy is planned^[18^]. In secondary hyperparathyroidism, where diffuse four-gland hyperplasia is the rule, such localization imaging is generally unnecessary. In the present series, ultrasonography reliably localized the adenoma in both primary cases.

A key clinical contribution of this series lies in emphasizing a structured diagnostic approach for giant cell–rich jaw lesions. Based on our experience and literature evidence, we propose the following practical framework:

1. Assess lesion distribution and radiologic aggressiveness.

2. Exclude odontogenic and inflammatory causes.

3. In cases of multifocal, bilateral, or atypically aggressive lesions, systematically request serum calcium and PTH.

4. Confirm diagnosis through clinico-biochemical correlation before planning local surgical treatment.

Incorporating routine metabolic screening into this algorithm may substantially reduce misdiagnoses and prevent overtreatment.

Importantly, none of our patients required direct maxillofacial surgical resection. Conservative management aligns with recommendations, reserving local surgery for persistent, symptomatic, or cosmetically deforming residual lesions after endocrine correction^[15,19^]. Avoiding premature curettage or resection reduces operative morbidity and preserves structural integrity, particularly in anatomically complex maxillary regions.

The limitations of this study include its retrospective design and small sample size, inherent to the rarity of jaw brown tumors^[15^]. Although regression was documented within twelve months in all cases, longer-term surveillance would provide further insight into complete bone remodeling and recurrence risk. Additionally, volumetric radiological quantification was not systematically performed, limiting precise measurement of regression kinetics. A further limitation is that parathyroid localization relied solely on cervical ultrasonography; ^99mTc-sestamibi scintigraphy with SPECT/CT was not performed, which may have reduced sensitivity for detecting ectopic or supernumerary glands and represents a methodological constraint of this series. Future prospective multicenter studies with standardized imaging protocols could refine predictive factors for incomplete resolution and optimize follow-up strategies.

Conclusion

Brown tumors of the jaws, although rare, should prompt systematic endocrine and biochemical evaluation for hyperparathyroidism in patients presenting with giant cell–rich jaw lesions. In this series, correction of the underlying metabolic disorder – parathyroidectomy for primary disease and optimized medical therapy for secondary hyperparathyroidism – resulted in lesion regression without the need for direct maxillofacial surgery, emphasizing that management must target the hormonal imbalance rather than the osseous manifestation.

Early recognition, accurate classification, and multidisciplinary collaboration are essential to avoid unnecessary invasive procedures and mitigate systemic complications. Future prospective studies with standardized long-term follow-up are needed to better define regression timelines and identify predictors of incomplete resolution.

Patient perspective

All patients were informed about the nature of their condition, the underlying endocrine cause, and the proposed management strategy. Following treatment, patients with primary hyperparathyroidism reported progressive improvement in facial symmetry and oral comfort as the lesions regressed after parathyroidectomy. The patient with secondary hyperparathyroidism expressed reassurance upon understanding the systemic origin of her jaw lesions and the importance of metabolic control in preventing progression. No patient reported functional impairment during follow-up, and all expressed satisfaction with the multidisciplinary management approach.

Ethical approval

This retrospective case series was conducted in accordance with institutional guidelines and the Declaration of Helsinki. Ethical approval was not required due to the use of anonymized data, in accordance with institutional policy.

Consent

Written informed consent for the publication of clinical data and accompanying images was obtained from all patients. All identifying information has been removed to ensure anonymity. Signed consent forms are retained by the authors and are available for review by the journal upon request.

Sources of funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

Y.S.: conceptualization; investigation; methodology; project administration; writing – original draft; writing – review & editing; O.E.Y.: investigation; writing – original draft; writing – review and editing; L.H.: resources (patient management and clinical data); writing – review & editing; M.S.: data curation; writing – review & editing; B.T.: supervision – project administration, supervision, validation, writing – review & editing.

Conflicts of interest disclosure

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Research registration unique identification number (UIN)

Not applicable.

Guarantor

Sibari Yousra.

Provenance and peer review

Not applicable.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available because they contain information that could compromise the privacy and confidentiality of the patients.

Artificial intelligence statement

No artificial intelligence tools were used in the clinical management of the patient, data acquisition, histopathological analysis, or any component of the research workflow. AI-assisted language editing tools (specifically large language model-based tools) were used exclusively for linguistic improvement of the manuscript text at the drafting and revision stages. All AI-generated linguistic suggestions were reviewed, verified for scientific accuracy, and edited or discarded as appropriate by the corresponding author. The authors take full and sole responsibility for the scientific content, accuracy, and integrity of the published work. No AI-generated figures, data, or clinical decisions are reported.