Hyperostosis Frontalis Interna in a Breast Cancer Survivor: A Case-Based Nuclear Medicine Perspective

Introduction

Hyperostosis frontalis interna (HFI) is a benign, often incidental radiological finding characterized by excessive bone formation along the inner table of the frontal bone. Though it typically carries no clinical consequence, its radiologic features can mimic serious pathology, particularly in patients with a history of malignancy. In this case, a 43-year-old woman with a history of breast cancer, BRCA2 germline mutation, and prior chemotherapy presented with bilateral hip pain. Bone scintigraphy revealed findings consistent with HFI, raising important considerations in differential diagnosis and imaging interpretation.

This blog post presents the full clinical and imaging analysis, diagnostic reasoning, key features of HFI, and concludes with a 10-question quiz to test your understanding, backed by references from SCI-grade literature.

Case Summary

Patient: 43-year-old female
History: Treated for breast cancer with 4 cycles of Taxotere (docetaxel) and Cytoxan (cyclophosphamide)
Symptoms: Bilateral hip pain
Genetics: Positive for germline BRCA2 mutation
Imaging: Whole-body 99mTc-MDP bone scintigraphy

Key Findings

No abnormal radiotracer uptake in the spine, hips, or long bones
Diffuse radiotracer uptake in the skull, especially involving bilateral frontal and parietal bones
No hot spots suggestive of metastasis

Diagnosis: Hyperostosis frontalis interna (HFI)

Pathophysiology of Hyperostosis Frontalis Interna

HFI is characterized by thickening of the inner table of the frontal bone, usually in a bilateral, symmetric distribution. Though its exact etiology remains unclear, proposed contributing factors include:

Hormonal stimulation (especially estrogens)
Aging
Genetic predisposition
Endocrine abnormalities
Obesity and dietary factors

Histologically, the process involves benign, non-malignant osteoblastic activity and does not typically cross the midline sagittal sinus.

Epidemiology

Prevalence: Up to 12% in the general population
Most common in: Women over 65
Frequently found incidentally on head CT or skull X-rays
Rarely associated with clinical symptoms unless hypertrophy becomes extreme

Clinical Presentation

Most cases of HFI are asymptomatic and discovered incidentally during evaluation for unrelated neurological complaints or trauma. However, in rare cases, extensive thickening may cause:

Cognitive dysfunction
Headaches
Seizures
Neuropsychiatric symptoms (e.g., apathy, irritability)

These symptoms, when present, are likely secondary to intracranial mass effect or brain atrophy.

Imaging Characteristics

A. X-ray and CT

Bilateral symmetric cortical thickening
Primarily affects frontal bones, may extend to parietal bones
Appears as flat or nodular hyperdensities
Does not cross the midline

B. 99mTc-MDP Bone Scan

Increased symmetric radiotracer uptake in frontal/parietal regions
Can be mistaken for metastases, especially in oncology patients
Confirmed via SPECT/CT for anatomic correlation

C. SPECT/CT

Delineates the anatomic bone change
Rules out underlying neoplasm, hemorrhage, or cortical invasion

Differential Diagnosis

Condition	Key Differentiators
Metastatic Disease	Focal, irregular uptake; often asymmetric
Paget’s Disease	Typically involves occipital/skull base areas
Fibrous Dysplasia	"Ground-glass" appearance on CT; younger patients
HFI	Symmetrical, confined to the frontal bones, benign

Quiz

1. What is the photon energy of 99mTc used in bone scintigraphy?

A. 240 keV
B. 140 keV
C. 511 keV
D. 70 keV

Explanation: 99m-Technetium emits gamma rays at 140 keV, ideal for SPECT imaging.

2. What is the physical half-life of 99mTc?

A. 3 hours
B. 6 hours
C. 12 hours
D. 24 hours

Explanation: The half-life of 99mTc is approximately 6 hours, balancing image quality with radiation exposure.

3. What is the primary excretory organ for 99mTc-MDP?

A. Liver
B. Spleen
C. Bladder
D. Colon

Explanation: Radiotracer is excreted via the kidneys and accumulates in the bladder.

4. Which of the following is the most likely diagnosis given symmetric skull uptake?

A. Brain metastasis
B. Fibrous dysplasia
C. Paget’s disease
D. Hyperostosis frontalis interna

Explanation: Symmetrical uptake in frontal bones is characteristic of HFI.

5. What distinguishes HFI from metastatic disease on bone scan?

A. Uptake in long bones
B. Asymmetry
C. Midline crossing
D. Symmetry and location

Explanation: HFI typically shows symmetric frontal bone uptake, unlike the random pattern of metastases.

6. What is the most definitive imaging modality to confirm HFI?

A. Chest X-ray
B. Head CT
C. MRI Brain
D. DEXA scan

Explanation: Head CT clearly shows inner table thickening of the frontal bone.

7. Which syndrome is NOT associated with HFI?

A. Morgagni-Stewart-Morel syndrome
B. Cowden syndrome
C. Alzheimer’s disease
D. Turner syndrome

Explanation: Turner syndrome has no known link with HFI.

8. What symptom is least likely to be associated with HFI?

A. Seizure
B. Headache
C. Syncope
D. Cognitive impairment

Explanation: Syncope is not commonly linked to HFI.

9. Does HFI commonly cross the sagittal midline?

A. Yes
B. No

Explanation: It characteristically spares the sagittal sinus.

10. What is the recommended treatment for asymptomatic HFI?

A. Radiotherapy
B. Chemotherapy
C. Observation
D. Craniotomy

Explanation: No intervention is needed unless symptoms arise.

References

Gaillard F, Thakur A. Hyperostosis frontalis interna. Radiopaedia.org (2022).
Kang SR, et al. Brain metastases mimicking HFI on bone scintigraphy. Clin Nucl Med. 2016;41(10):789–791.
Tripathi M, et al. HFI mimicking skull metastasis. Indian J Nucl Med. 2012;27(4):272–273.
Venkatesh M, El-Feky M. Technetium 99m-methyl diphosphonate. Radiopaedia.org (2022).
Verdy M, et al. Prevalence of HFI in relation to body weight. Am J Clin Nutr. 1978;31(11):2002–2004.
Herhskovitz I, et al. Morphological grading of HFI. Am J Phys Anthropol. 1999;109(3):303–313.
Eisenberg RL. Skull thickening. In: Clinical Imaging. Elsevier Saunders; 2011.

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