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2019 NPA-07

This case was originally published in 2019. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.

Clinical History

A 59-year-old woman was found unresponsive by her spouse and was pronounced dead at the scene. She had a past medical history significant for obesity, type II diabetes mellitus, hyperlipidemia, hypertension, and coronary artery disease. Autopsy revealed cardiomegaly, complete stenosis of the left anterior descending artery, and acute ischemic myocardial changes. A standard skull and brain examination was performed.

Tissue Site
Skull

Questions

  1. Which of the following is the most likely diagnosis?

    1. Fibrous dysplasia

    2. Giant cell tumor of the bone

    3. Hyperostosis frontalis interna

    4. Meningioma

    5. Osteoma

  2. Which gross description best fits with this entity?

    1. Bilateral inner table thickening with nodularity

    2. Expansile lesion(s) eroding and expanding the bone

    3. Polypoid or sessile mass with smooth, bosselated surface

    4. Sheet-like growth along the dural surface

    5. Well-circumscribed, firm mass with expansion of cortical bone

  3. Which of the following is most likely to be included in the differential diagnosis for this entity?

    1. Aneurysmal bone cyst

    2. Cholesterol granuloma

    3. Fibrous dysplasia

    4. Giant cell tumor of bone

    5. Paget disease of the bone

View Answer Key

Discussion and Diagnosis

Morgagni and Santorini first described obesity and virilism/hirsutism associated with thickening of the internal table of the frontal bone in the 1700s and named it hyperostosis frontalis interna (HFI). Throughout the 1930s to 1950s, many reports described patients with HFI and a variety of coexisting endocrine abnormalities including diabetes, acromegaly, and galactorrhea with more recent population studies reporting a higher incidence in obese women and men with androgen abnormalities. Additional reports have found associations with multiple other endocrine pathway abnormalities.

HFI is considered an incidental neuroimaging or autopsy finding most commonly seen in middle-aged, postmenopausal women. HFI has also been described in men, but less commonly, and the majority of those described in the literature had hypogonadism or testicular atrophy. In fact, Farinelli, the famous castrated Italian singer from the 18th century, was found to have HFI when his remains were exhumed in 2006 for research purposes. Reports are varied, but it is estimated that up to 5% to 12% of the general population has HFI. The etiology is still largely unknown, but it is favored to relate to endocrine imbalances resulting in increased bone growth. Some studies have postulated altered blood supply may contribute to the frontal bone predilection. Cases with multiple sequential imaging studies have confirmed that HFI is slowly progressive.

X-ray, CT scan, and MR images all show moderate to severe bilateral thickening of the inner table of the frontal skull, sometimes with prominent lobulations (Image A and Image B). Rarely, underlying brain parenchyma will show compression and atrophy.

Image A: CT Scan (from prior hospitalization).

Image A: CT Scan (from prior hospitalization).

Image B: T1-weighted MRI, postcontrast (from prior hospitalization).

Image B: T1-weighted MRI, postcontrast (from prior hospitalization).

Gross examination of HFI reveals symmetric thickening of the inner table of the frontal bone of the skull with midline sparing (Image C). The surface of the internal frontal skull often shows numerous irregular nodules bilaterally (Image D). Hyperostosis can extend to adjacent bone, involve underlying dura, or lead to calcification of the falx; however, the diploë and outer table of the bone are typically spared. Underlying brain parenchyma can be compressed when the bony nodules become too large and result in parenchymal atrophy. Neurosurgical intervention has been performed in rare cases where symptoms of headache or seizures are present.

Image C: Gross image.

Image C: Gross image.

Image D: Gross image.

Image D: Gross image.

Histologic sections of HFI are rarely taken at the time of autopsy because of the characteristic gross appearance. However, microscopy can show remodeling of the endocranial plate with thickened cancellous bone. The bony lamellae are variably organized and mostly concentric. Nodules have been described as having numerous thin-walled blood vessels of varying diameter separated by thin, bony septae. Later involvement of periosteal dura has been noted.

The differential diagnosis for HFI includes other skull base lesions such as Paget disease, rickets, or leontiasis ossea. Selective involvement of the inner table of the skull and lack of involvement of the outer table assist in differentiating HFI from the previously mentioned entities. Other bony lesions such as osteoma or osteosarcoma are not typically bilateral and multifocal. Also to be considered, but much less likely, would be an en plaque meningioma or metastasis, in which case involvement of the dura and histologic sections would confirm the diagnosis.

Diagnosis
Hyperostosis frontalis interna

Take Home Points

  • Hyperostosis frontalis interna (HFI) is an incidental neuroradiologic and gross finding, often found at autopsy.
  • HFI is most commonly seen in middle-aged, postmenopausal women.
  • The etiopathogenesis underlying hyperostosis frontalis interna is unknown but postulated to involve endocrine abnormalities.
  • Neuroimaging and gross examination of the skull in HFI show bilateral inner table thickening with irregular, protruding nodules of bone and sparing of the diploë and outer table of the bone.
  • The most relevant differential diagnoses for HFI that need to be ruled out include Paget disease of the bone, rickets, osteoma, meningioma, and metastasis.

References

  1. Belcastro MG, Todero A, Fornaciari G, et al. Hyperostosis frontalis interna (HFI) and castration: the case of the famous singer Farinelli (1705-1782). J Anat. 2011;219:632-7.
  2. De Lehoczky T, Orban A. Hyperostosis frontalis interna. Br Med J. 1938 May;1(4036):1049-62.
  3. Hershkovitz I, Greenwald C, Rothschild BM, et al. Hyperostosis frontalis interna: an anthropological perspective. Am J Phys Anthropol. 1999;109:303-25.
  4. Raikos A, Paraskevas GK, Yusuf F, et al. Etiopathogenesis of hyperostosis frontalis interna: a mystery still. Ann Anat. 2011 Oct;193(5):453-8.
  5. She R, Szakacs J. Hyperostosis frontalis interna: case report and review of literature. Ann Clin Lab Sci. 2004;34(2):206-8.

Answer Key

  1. Which of the following is the most likely diagnosis?
    A. Fibrous dysplasia
    B. Giant cell tumor of the bone
    C. Hyperostosis frontalis interna
    D. Meningioma
    E. Osteoma
  2. Which gross description best fits with this entity?
    A. Bilateral inner table thickening with nodularity
    B. Expansile lesion(s) eroding and expanding the bone
    C. Polypoid or sessile mass with smooth, bosselated surface
    D. Sheet-like growth along the dural surface
    E. Well-circumscribed, firm mass with expansion of cortical bone
  3. Which of the following is most likely to be included in the differential diagnosis for this entity?
    A. Aneurysmal bone cyst
    B. Cholesterol granuloma
    C. Fibrous dysplasia
    D. Giant cell tumor of bone
    E. Paget disease of the bone
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