Introduction
Primary intraosseous cavernous hemangioma (PICH) is a rare bone tumor accounting for 0.7% to 1.0% of all bone tumors [1]. PICHs rarely appear in the skull, being 0.2% of cranial bone tumors, considering both splanchnocranium and neurocranium [2]. Toynbee published the first record of this type of tumor in medical literature in 1845 [3]. A review of the literature reveals approximately 140 published cases. Additionally, we describe our patients. Based on the global distribution of skull PICH-related publications and the analysis of their geolocational data, the countries of origin of the publications are mostly concentrated in Europe, North America, and East Asia. PICH is most frequent in middle-aged men [2]. In the neurocranium, the most frequent site is the frontal bone, followed by the parietal bone, occipital bone, and temporal bone in cases with a single PICH. Other neurocranium bones are rarely involved. Sometimes it is possible to find multiple PICHs in the same person. 
Case Presentation
Case 1 
A 53-year-old woman presented with a swelling on the left side of her forehead. The swelling had rapidly grown for one year. The mass was solid, immobile, and hard in consistency, painless, and adhered to deep planes when palpated beneath normal-looking skin. She denied having a headache, dizziness, or a history of trauma. Other medical history was irrelevant. Routine hematological tests revealed no abnormalities. On the frontal bone, a CT image showed a 20×20×15 mm osteolytic lesion within the diploe (Figure 1). Because of the difficult differential diagnosis, the original radiologist’s impression of the mass was not reported. An MRI revealed a bone mass that was hypointense on T1WI but hyperintense on T2WI. There is evidence of outer table lamellar thickening after gadolinium administration (Figure 2). A left frontal craniectomy and total lesion resection with a margin of surrounding normal bones of 0.5 cm were conducted under general anesthesia. It was rich in blood supply by clusters of small vessels, giving a purplish and hemorrhagic aspect to the underlying lesion (Figure 3). The resulting bone defect was repaired with a cylindrical metametacrylate plasty attached to the surrounding bone with titanium miniplates (Figure 4). The specimen’s histology revealed an intradiploic cavernous hemangioma (Figure 5). The postoperative period was uneventful, and the patient recovered well. There was no recurrence of the lesion after a one-year follow-up.
Case 2
A 70-year-old woman diagnosed with non-Hodgkin lymphoma (NHL) presented with a painless occipital swelling. CT scan showed an osteolytic lesion at an inion point of 5 cm diameter, with intact inner and outer bone layers. Magnetic resonance showed a hypointense T1WI and hyperintense T2WI, with heterogenous enhancement after gadolinium administration. Time of flight angiography (TOF) sequences demonstrated no intracranial invasion and no encasement of torcular Herophili. Lymphoma of the bone was considered the most probable diagnosis. Resection was performed and surprisingly revealed an intraosseous cavernous hemangioma. No long-term follow-up was not possible because the patient died of NHL complications. 
Case 3
A 42-year-old woman appeared with a painless, slow-growing frontal lesion. She suffered from aesthetic deformity with several psychological implications. Skull X-rays showed an osteolytic lesion 2 cm in diameter. A CT scan revealed a diploe lesion with a honeycomb appearance. Resection was performed, and metametacrylate plasty was used to reconstruct the bone defect, resulting in minimal deformity. Histological evidence supported the diagnosis of cavernous hemangioma.
Case 4
A 39-year-old woman suffered from frontal headache and sinusitis for months. No analgesic medical therapy was effective. Transnasal endoscopy did not reveal anything pathologic. CT scan demonstrated an intraosseous lytic lesion extended in the posterior wall of the frontal sinus, obliterating inner mucosa-lined airspace. The resection revealed cavernous hemangioma. 
Discussion 
Toynbee described the first case of cranial cavernous hemangioma in 1845 [3]. Since then, many cases have been described as a single case report. However, some authors collected multiple patients (Table 1).


PICHs of the skull are uncommon vascular tumors, accounting for about 0.2% of all skull tumors. They represent 10% of benign tumors of the skull [4]. They are most common in the spine and rarely occur in the skull. Contrary to our four cases, they are more frequent in men. PICH is classified based on the dominant feeding vessel. Therefore, hemangioma is histologically described and classified as cavernous, capillary, or mixed capillary-cavernous. Only papers in which hemangioma is described as cavernous were considered, and capillary and mixed subtypes were excluded. We report our literature review based on PubMed research from 1845 to August 2022, when the last systematic review focused on this argument was published [5]. Described cases have exponentially grown from the first one in 1985 until now. Of 151 cases of cranial PICH reported in the literature (including four cases of our own), 38.4% were located in the frontal bone, 19.9% in the parietal bone, 13.3% in the occipital bone, 6.9% in the temporal bone, and 13.3% in other neurocranium bones. About 5.3% of cases have more than one PICH, or giant PICH growing in more than one anatomical bone. They arise from the vessels of the diploic space, fed by branches of the external carotid artery. They are made of capillaries widely dilated and separated by fibrous tissue. The pathogenesis is still unknown, but a history of trauma seems to be related in some case reports [6]. No hereditary cases were still described, contrary to intraparenchymal cavernous hereditary disease. Like our four cases, the typical presentation is a slow-growing palpable mass in a certain period of a patient’s life without any significant symptoms or signs. When hemangioma is big enough or quickly increases its size, it could be associated with headache [6]. Radiologic evaluation includes plain skull X-rays, CT scans, and magnetic resonance imaging (MRI). Cranial X-ray is sometimes the first radiographic evaluation, showing a circular lucency with a trabecular or honeycomb pattern. Above all, the gold standard is represented by cranial CT with a bone window since it is more sensitive than simple radiography. MRI is not helpful but can help differential diagnosis from other kind of skull bone lesions. Although the appearance in the CT be different depending on the characteristics of the PICH. Usually CT image consists of a circular osteolytic lesion (hypodense), expansive, and well delimited, with sclerotic spaced trabeculations, giving sometimes an appearance of honeycombing in the axial cuts [7]. It frequently expands the external table respecting the periosteum, and rarely invades it. Because it is a slowing benign lesion reactive hyperostosis, it is never identified at its margins (8 parietally (two cases). MRI images consist of hypo- to iso-intense lesions on T1WI, sometimes with hyperintensity depending on fatty content, and hyperintense on T2WI. Trabecula and spicula should modify the intensity on MRI images, as a highly vascularized lesion enhances diffusely and heterogeneously after gadolinium administration. Sometimes could be hemorrhagic [9]. In some cases, angiography of these lesions can help diagnose, for example, the largest PICH. Angiography demonstrates a hypervascular lesion in the latest arterial phase, without drainage or venous phase. As it is a vascular lesion, and there is a risk of bleeding during surgical removal, preoperative embolization may be useful in some cases [10]. 
The differential diagnosis includes other slow-growing, expanding bone lesions, both benign or malignant, such as dermoid and epidermoid cysts, metastases, low-grade hemangioendothelioma, osteoporosis circumscripta, cephalocele, intradiploic arachnoid cyst, intradiploic meningioma, leptomeningeal cyst, malignant mesenchymal tumor (chondrosarcoma, chordoma, giant cell tumor, and solitary fibrous tumor/hemangiopericytoma), lymphoma, hyperparathyroidism, myeloma, osteomyelitis, osteoma, aneurismal bone cyst, Langerhans histiocytosis (eosinophilic granuloma or histiocytosis X). The radiological and clinical characteristics that help the differential diagnosis are presented in Table 2.




Surgical treatment is recommended for accessible lesions, which may be cured by en-bloc excision, including a circumferential margin of the healthy bone [6, 11]. Curettage is not recommended because an incomplete resection can cause relapse; however, the possibility of recurrence is avoided by including a margin of safety [6]. Total surgical excision is the treatment of choice and the prognosis after complete excision is excellent and recurrence is usually rare. Their surgical treatment must be considered because intraosseous cavernous hemangiomas grow progressively without spontaneous involution. This condition permits avoiding the painful clinical and cosmetic implications and, depending on their first symptoms and anatomical location, avoiding complications such as hemorrhages or nerve damage cranial, although with low frequency [8]. Most authors recommend total surgical excision to treat the mass effect and neurological compromise, improve an esthetic deformity, and obtain a definitive diagnosis [11]. The surgical approach becomes more difficult for those with an extension to the base of the skull. For the lesions considered non-accessible or unresectable, radiation therapy may be considered. Furthermore, radiotherapy should be reserved in the case of recurrent tumors too. However, this therapeutic modality does not reduce or heal the tumor but only stops lesion growth reducing vascularization. 
Conclusion
Cranial cavernous hemangiomas are benign vascular lesions usually surgically treated when another type of bone neoplasm is suspected. The most common clinical feature is a solid tumor in the skull, which can be painful or not. Histopathologic examinations continue to be the gold standard for diagnostic purposes. The preferred treatment is a craniectomy with total resection to safe margins in healthy bone. A good prognosis is associated with complete resection. If the surgery is successful, relapse is uncommon. Case studies are mostly from the Western world and China. Data from emerging nations, such as South America and Africa, are needed to assess the precise statistical prevalence of PICH. The authors believe that PICH is not a rare tumor, but it has become more common in recent decades. 

Ethical Considerations
Compliance with ethical guidelines
All study procedures were in compliance with the ethical guidelines of the Declaration of Helsinki 2013. 

Funding
This research received no financial support for preparing or publishing this paper.

Authors contributions
Conceptualization: Domenico Catapano; Methodology, writing, review, and editing: Antonello Curcio; Investigation: Antonello Curcio, Domenico Catapano, and Lucia Maria Cecilia Dimitri; Writing the original draft: Antonello Curcio, Domenico Catapano, Lucia Maria Cecilia Dimitri, and Chiara Copelli; Supervision: Leonardo Pio Gorgoglione, Antonino Germano; Reading and approval of the published version of the manuscript: All authors.

Conflict of interest
The authors declared no competing interests.

Acknowledgements 
I am grateful to all of those with whom I have had the pleasure to work during my fellowship in Division of Neurosurgery of Hospital Casa Sollievo Della Sofferenza: Gorgoglione Leonardo, Carotenuto Vincenzo, Impusino Antonio; De Bonis Costanzo; Paiano Luigi Maria, Fazzari Elena, Icolaro Nadia, Savarese Luciano and Bonfitto Antonio. 

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