Epithelioid Hemangioendothelioma of the Mastoid: Resection for Recurrence and Adjuvant Radiation with 8-Year Followup

Epithelioid hemangioendothelioma (EH) is a rare, vascular neoplasm that can affect any age group and has been reported previously in sites including bone, liver, lung, breast, and brain. We describe a case of EH located in the mastoid, which appears to be the first report of EH in this site. The patient was 62 years old when they presented with dizziness and nausea. A suboccipital surgical approach was utilized to resect the tumor. After 18-month followup, the patient was symptom-free; however, imaging demonstrated a recurrence and the patient was taken back to the operating room for a resection. There is no evidence of recurrence after 8 years of followup. This paper aims to reinforce the need for a timely radical excision and aggressive clinical followup as the best hope for cure. Here, we describe an illustrative case and review the pertinent literature.


Introduction
Weiss and Enzinger �rst de�ned a unique so tissue vascular tumor as an epithelioid hemangioendothelioma (EH) in 1982 [1]. Subsequently, there have been hundreds of cases reported in the literature at sites including the liver, bone, lung, and brain [2][3][4][5]. ese tumors are rare, representing less than 1% of all vascular tumors but can affect any age group [6]. Intracranial EH has been reported in the parenchyma, along the cavernous sinus, infundibulum, clivus and at the cerebellopontine angle [7][8][9][10]. We report the rare case of an epithelioid hemangioendothelioma invading the mastoid bone and adjacent so tissues in a 62-year-old man.

History.
A 62-year-old patient presented with a onemonth history of progressive dizziness and nausea. e patient complained of persistent positional vertigo and increasing hearing loss in the le ear. e past medical history was nonsigni�cant. Neurological examination revealed mild auricular tenderness and decreased hearing, however; the rest of the exam was unremarkable.

Radiographic Evaluation.
Bone windows on computed tomography (CT) demonstrated an osteolytic mass expanding into the epidural space (Figure 1(a)). e mass extended from the mastoid air cell complex to the occipital condyle. e vestibular aqueduct was in proximity but not affected by the mass. Magnetic resonance imaging (MRI) demonstrated the mass to be hyperintense on T1 weighted with cystic changes and heterogeneously enhancing with gadolinium, and measured 4.5 cm by 3.0 cm by 5.0 cm (Figures 1(b) and 1(c)). e mass compressed the cerebellar hemisphere creating mild mass effect upon the fourth ventricle. Cerebral angiography demonstrated minimal tumor blush supplied by the ascending pharyngeal artery and some from the occipital artery (Figures 2(a) and 2(b)). Embolization of the small feeding vessels was not performed because the feeding vessels were small and would not have a signi�cant impact for the subsequent surgery.
2.3. Surgery. e patient underwent tumor resection through a le retromastoid approach utilizing motor evoked potentials, cranial nerve monitoring, and neuronavigation. Aer careful dissection into the suboccipital triangle, a suboccipital craniectomy extending into the occipital condyle was performed along the dural margin. Special precautions were taken to avoid injuring the underlying dura. e tumor was moderately vascular, but so, and was resected carefully off the dura and surrounding neural elements. Once we identi�ed the sigmoid sinus, it was carefully skeletonized and we proceeded to the presigmoid region. e VII cranial nerve was identi�ed and skeletonized. �e skeletonized the jugular foramen and identi�ed the I�th, �th, and �Ith nerves. e involved mastoid air cells were resected. e semicircular canals were visualized and were uninvolved with tumor. Multiple specimens were sent for frozen section as well as permanent. Once all visible tumor was resected and hemostasis was obtained, an abdominal fat gra was placed and the incision was closed primarily. e patient tolerated the procedure well without any complications.

Histopathological, Immunohistochemical, and Molecular
Study. Both specimens showed similar histopathology. ere were cords and sheets of epitheloid cells in the background of �bromyxoid stroma (Figure 3(b)). e cells had abundant eosinophilic cytoplasm with cytoplasmic vacuoles representing primitive lumina formation (blister cells), with red blood cells present in some of them (Figure 3(c)). e nuclei were round to elongated, with moderate hyperchromasia and pleomorphism; however, no mitotic activity was present. e neoplastic process involved the mastoid bone (Figure 3(a)) and adjacent so tissues. Immunohistochemical analysis showed diffuse positivity for endothelial markers, CD31 and CD34 (Figure 3(d)). e neoplastic cells were negative for cytokeratin AE1/AE3 and S100, with low staining with proliferation marker Ki67 (approximately 5%). is morphologic and immunophenotypic picture was that of an epithelioid hemangioendothelioma.
Case Reports in Surgery

Discussion
EH is a rare vascular tumor that has been reclassi�ed as a fully malignant tumor by the World Health Organization [11]. ey have been best described in the liver, lung, breast, and bone [2][3][4][5]. Intracranial involvement has been described in 36 cases and only 4 other cases of posterior fossa EHs [9,10,12,13]. e risk of malignancy, recurrence, and mestastases and a variable clinical course led to appropriate pathological identi�cation and rigorous follow-up paramount. e most common reported location is intra-axial with evidence of mass effect causing headache, seizure, or acute neurological deterioration [7]. e variable radiological appearances of these tumors mimic other primary or secondary parenchymal lesions [14]. e CT scan �ndings range from isodense to hyperdense. e MRI �ndings are more variable with T1-weighted sequencing ranging from isointense to hyperintense with the most common being heterogeneous [15]. e T2-weighted images are hyperintense or heterogenous. ere is usually intense peritumoral vasogenic edema and hetergenous enhancement with gadolinium. e dural-based lesions may mimic meningiomas; however, the cystic conversion and hetergenous enhancement make meningioma less likely [16]. As in our case, the other cases involving the bone were expansile osteolytic masses with intense enhancement [17,18].
e pathomorphology of EH is very characteristic with cords of epithelioid cells in myxohyaline stroma forming primitive lumina that points towards the endothelial differentiation. e differential diagnosis includes metastatic carcinoma, melanoma, and epithelioid angiosarcoma. e cytoplasmic vacuoles can be confused with gland formation by adenocarcinoma or signet ring cell morphology. However, metastatic neoplasms usually present pronounced nuclear atypia and mitotic activity. Although EH can show some expression of epithelial markers, which is usually focal, adenocarcinoma would be diffusely positive for cytokeratin, as well as mucicarmine [19]. Melanoma, a great mimicker of other tumors, oen demonstrates presence of melanin pigment and characteristically strongly expresses S100 protein. Another entity that can look similar is angiosarcoma, especially its epithelioid variant. Some authors believe that there is a continuum between EH and angiosarcoma, with EH being a vascular neoplasm of intermediate malignant potential and angiosarcoma being in the malignant category of vascular tumors [19]. Indeed, angiosarcoma is a more aggressive tumor with a propensity for extensive local growth and metastatic spread to distant organs; it shows a high degree of nuclear atypia and pleomorphism, with high mitotic activity, as opposed to the bland morphology of EH. Also, it  About 25% of EH demonstrates "atypical features" of cellular atypia, >1 mitotic �gure per 10 hpf, necrosis and spindle morphology� such tumors were historically de�ned as malignant EH [1]. However, Deyrup et al. [19] in a recent study of 49 EH cases showed that only tumor size and Case Reports in Surgery 5 mitotic activity were associated with decreased survival (5year disease-speci�c survival of 59%), with tumors with >3 mitotic �gures per 50 hpf and size >3.0 cm having the worst prognosis.
e risk of recurrence and metastasis makes treatment complex. Including the current report, there have been six cases of local recurrence, progression, and seeding of the neuraxis [2,3,16,20,21]. Four of the six cases with progression of disease were reported in cases aer a total resection. One of the six cases was given adjuvant radiation and one was given IFN treatment [2,16]. Complete resection is the treatment of choice when possible and has been associated with a favorable outcome [14]. It is difficult to determine the prognosis based on the histopathology. Parajon and Vaquero [22] reviewed 34 cases of intracranial EH and concluded that if complete surgical resection is achieved, no adjuvant radiotherapy is necessary. However, when presented with clinically aggressive lesions, adjuvant therapy with radiation and Interferon-Alpha has been attempted [17,20,[22][23][24][25][26]. e rarity of reports makes determining the clinical course of this tumor difficult and therefore, careful clinical followup is warranted.

Conclusion
e present case describes the clinical and pathologic features of a epithelioid hemangioendothelioma involving the mastoid in a 62-year-old male. To our knowledge, this is the �rst reported case of EH in this site. Complete surgical resection is the initial treatment of choice, but timely and aggressive clinical followup is necessary to monitor for recurrence.