Abstract

Background: Intracranial epidermoid cysts are rare benign lesions. Cases of malignant transformation (MT) into squamous cell carcinoma (SCC) have rarely been reported. We present a case of concurrent occurrence of SCC diagnosed during primary resection of epidermoid cyst (EC) and a relevant literature review.

Case Description: A 61-year-old patient was diagnosed with a right cerebellopontine angle (CPA) lesion after suffering from vertigo, diplopia, and right trigeminal (V2) hypoesthesia. Brain magnetic resonance imaging (MRI) showed a lesion consistent with an EC, demonstrating restricted diffusion with rim-enhancing area on the medial side of the cyst. During resection, two different tissue pathologies were observed, one consistent with an epidermoid (which was completely removed) and an additional firm tissue adherent to the brainstem, preventing gross total resection. Pathological evaluation confirmed two separate histologies – epidermoid and SCC. The patient never recurred to complete the recommended radiotherapy. Eleven months following surgical resection, a follow-up MRI showed local massive recurrence of the enhancing lesion. He was, further, treated with radiotherapy and is currently being followed up.

Conclusion: MT of an intracranial EC to SCC is rare and associated with poor prognosis. SCC may be found incidentally at time of primary resection or arise from a remnant of previously operated EC. Thus, aggressive complete resection should be intended, and separate pathological specimens should be sent from any abnormal region of the tumor.

Keywords: Epidermoid cyst, Intracranial, Malignant transformation, Squamous cell carcinoma

INTRODUCTION

Intracranial epidermoid cysts (IECs) are extra-axial, usually congenital lesions that arise from trapped epithelium during gestation.[ 12 ] IECs most commonly present during early adulthood, with a peak incidence in the fourth decade.[ 11 , 12 ] Rarely, IEC may occur as a result of traumatic inoculation from a prior surgical procedure or trauma.[ 8 , 11 ] Congenitally, they are most commonly located in the posterior fossa, with a predilection for the CPA cistern,[ 12 ] representing approximately 7% of tumors in this location, and about 1% of intracranial tumors overall.[ 7 , 9 , 10 ] They are considered to be benign, with linear growth as a result of a progressive epithelium desquamation.[ 8 , 12 ]

IECs typically cause symptoms resulting from local mass effect on surrounding neural structures. In rare cases, the epithelium lining of the cyst can undergo malignant transformation (MT) into squamous cell carcinoma (SCC), which occurs predominantly in the fourth and fifth decades of life.[ 1 - 4 , 7 , 10 , 14 , 15 , 18 ] The reasons for MT are unclear but probably relate to the chronic inflammation caused by the contents of the IEC, which leads to cellular dysplasia and eventually neoplasia.[ 1 , 10 ] The concurrent occurrence of SCC has also been described in epidermoid cysts (ECs) located extracranially.[ 6 ] MT presents with rapid clinical or radiological progression.[ 10 ] In addition, MT should be considered in patients who show rapid recurrence of tumor or when the tumor demonstrates enhancement.[ 10 ] We present the case of a 61-year-old male diagnosed with a concurrent CPA IEC and SCC.

CASE PRESENTATION

A 61-year-old male patient presented to our clinic with several weeks of episodic vertigo, diplopia, and right trigeminal (CN V2) hypoesthesia. A magnetic resonance imaging (MRI) examination showed an extra-axial lobulated mass, measuring 22 × 25 × 35 mm, in the right CPA, causing significant pressure on the adjacent cerebellar lobe and brainstem, although, without hydrocephalus. The lesion demonstrated characteristic radiological features consistent with an EC, including hypointensity on T1-weighted image (T1WI), hyperintensity on T2-weighted image (T2WI) with some T2 hypointensities areas in the anterior-medial periphery, correlating with keratin, and restriction on diffusion-weighted image (DWI). A small enhancing region was present on the medial side of the lesion [ Figure 1 ]. Due to typical and characteristic location and radiological features, with only small partial patchy enhancement, the differential diagnoses of infective lesion or other cellular malignancy were possible, although small, and the probability of EC with MT was high on the differential diagnosis list.

Figure 1:

Preoperative magnetic resonance imaging (MRI) T1 + c – coronal (upper left) and axial (upper right) view – demonstrating hypointense T1 right cerebellopontine angle lesion, with a small enhanced area on the medial side of the lesion. Preoperative MRI T2 demonstrating hyperintensity on T2-weighted image with focal areas of hypointensities in the periphery (lower left), correlating with keratin. Restricted diffusion is seen on diffusion-weighted image (lower right).

A right retrosigmoid suboccipital craniotomy was done with electrophysiological monitoring including electromyography of CN 5, 7, as well as brainstem auditory-evoked response, in addition to transcranial motor-evoked potential monitoring and somatosensory-evoked potentials. During surgery, two different tissue pathologies were observed, one consistent with a typical epidermoid tumor, for which a near gross total resection (GTR) was achieved, which could be evident on a postoperative MRI. In addition, a different tissue with firm consistency was recognized that was adherent to the brainstem, preventing GTR, leaving the small enhancing region on the medial side of the lesion as seen on the postoperative MRI.

The pathological evaluation confirmed the presence of two separate histologies. The first specimen demonstrated areas of simple squamous epithelial cyst with mounds of layered keratin, typical of EC [ Figure 2 ]. The other specimen contained thickened, proliferating squamous epithelium creating finger-like projections, and containing dyskeratotic and acantholytic cells and foci of necrosis, compatible with SCC [ Figure 3 ]. Beta-catenin and BRAF V600E were negative, ruling out a craniopharyngioma.

Figure 2:

Demonstrating areas of a simple squamous epithelial cyst with mounds of layered keratin, typical of an epidermoid cyst (H&E stained, ×50).

Figure 3:

Demonstrating areas of proliferating squamous epithelium with thick projections (upper; H&E stained, ×50); and areas of MT demonstrating dyskeratotic cells, few mitotic figures (red circled), and necrosis (lower; H&E stained, ×100).

The patient was recommended radiotherapy, yet for unknown reasons, he never showed up for treatment. Eleven months following surgical resection, a follow-up MRI showed a local massive recurrence of the enhancing lesion [ Figure 4 ]. After a multidisciplinary discussion, and understanding that the tumor was not amendable for GTR without significant morbidity, the patient was re-referred to radiation therapy. An MRI scan done 2 months after radiation therapy showed a decrease in the size of the recurring lesion [ Figure 4 ]. At present, he is being followed up and is expected to continue periodical clinical and radiological investigations.

Figure 4:

Magnetic resonance imaging (MRI) T1 + c – axial view – postoperative MRI 11 months following surgical resection demonstrating local massive recurrence (left); and MRI 2 months following radiation therapy (right) demonstrating a decrease in the size of the lesion.

DISCUSSION

The occurrence of SCC intracranially is usually a result of metastases or direct extension from a primary location outside the central nervous system (CNS)⁴. The primary SCC is extremely rare and is usually the result of MT of benign IEC.[ 13 ] Originally, Garcia et al. published four criteria that should be fulfilled to define a true intracranial MT into SCC.[ 7 ] Later, Hamlat et al. added two more criteria,[ 10 ] providing six criteria that need to be satisfied before diagnosing primary intracranial SCC [ Table 1 ]. Hamlat et al., further, subclassified intracranial SCC into five different types, including (1) initial MT of an IEC; (2) MT from a remnant IEC; (3) MT with leptomeningeal carcinomatosis; (4) SCC arising from other benign cysts; and (5) other malignancies arising from benign cysts.[ 10 ] Accordingly, our case is classified as an initial MT of an IEC (Type 1). A systematic review conducted by Hamlat et al. who described that the first form of MT was the most frequent, with 28 cases reported by the time of the publication (2005).[ 10 ] Since then, several other reports have been published.[ 5 , 14 ]

Table 1:

Criteria for diagnosis of primary squamous cell carcinoma.

Preoperative diagnosis of MT of an IEC, based on radiological features, is challenging, and ultimately, a definite diagnosis depends on histopathological examination. IECs typically have characteristic radiological features, specifically low-signal intensity on T1WI and high-signal intensity on T2WI, as well as strong restriction on DWI.[ 8 , 12 , 14 ] Rarely, they can present with high signal on T1WI imaging, either due to hemorrhage into the lesion cavity or as a result of high protein or lipid content (known as “white IEC”).[ 8 , 12 ] Typically, IECs are not enhancing lesions or only rarely demonstrate any enhancement of the wall. In cases of MT, enhancement becomes more vividly pronounced.[ 8 ] In our case, the lesion had a small enhancing area adjacent to the brainstem that was seen on the preoperative MRI and that was later shown to be the SCC component of the tumor.

There is a surgical advantage to preoperatively acknowledging that these two pathologies can coexist, for two main reasons – the first for biopsy, as in our case, where there were two different tissue consistencies, and the second, for the intended extent of resection. While extensive surgical resection aiming for GTR is currently the gold standard for the treatment of IECs, there is no defined standard of care for IECs undergoing MT.[ 3 , 4 , 16 , 17 ] Surgery alone is not curative and is most often limited due to the firmly adherent nature of the malignant component to vital neurovascular structures, as was in our case. The addition of adjuvant radiation therapy offers some improvement in short-term survival, with Gamma-Knife radiosurgery showing the most promising results.[ 16 , 17 ] However, the exact radiotherapy protocol has yet to be determined, and a large analysis done by Nagasawa et al. who showed no significant correlation between the dose of radiation and survival outcome.[ 16 ]

CONCLUSION

Intracranial SCCs are rare and aggressive tumors. The possibility of MT of an IEC should be always be considered and kept in the surgeon’s mind when approaching to resect such lesions. Preoperatively, MT should be suspected by rapid deterioration of symptoms and signs and aggressive radiological course. The co-occurrence of SCC and IEC is a rare and devastating event, changing the course of the disease. Separate pathological specimens should be sent from any visually distinguishing pathological tissue. Radiotherapy should be supplemented in cases of SCC. In addition, surgical resection should strive for GTR of IEC whenever possible, without compromising vital neurological functions. Postoperatively, a close clinical and imaging follow-up is recommended for any subtotally resected IEC.

Declaration of patient consent

Patient’s consent not required as patient’s identity is not disclosed or compromised.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

References

1. Abramson RC, Morawetz RB, Schlitt M. Multiple complications from an intracranial epidermoid cyst: Case report and literature review. Neurosurgery. 1989. 24: 574-8

2. Agarwal S, Rishi A, Suri V, Sharma MC, Satyarthi GD, Garg A. Primary intracranial squamous cell carcinoma arising in an epidermoid cyst--a case report and review of literature. Clin Neurol Neurosurg. 2007. 109: 888-91

3. Chon KH, Lee JM, Koh EJ, Choi HY. Malignant transformation of an epidermoid cyst in the cerebellopontine angle. J Korean Neurosurg Soc. 2012. 52: 148-51

4. Cuoco JA, Rogers CM, Busch CM, Apfel LS, Entwistle JJ, Marvin EA. Intracranial squamous cell carcinoma arising from a cerebellopontine angle epidermoid cyst remnant four decades after partial resection. Front Oncol. 2019. 9: 694

5. Ding S, Jin Y, Jiang J. Malignant transformation of an epidermoid cyst in the temporal and prepontine region: Report of a case and differential diagnosis. Oncol Lett. 2016. 11: 3097-100

6. Frank E, Macias D, Hondorp B, Kerstetter J, Inman JC. Incidental squamous cell carcinoma in an epidermal inclusion cyst: A case report and review of the literature. Case Rep Dermatol. 2018. 10: 61-8

7. Garcia CA, McGarry PA, Rodriguez F. Primary intracranial squamous cell carcinoma of the right cerebellopontine angle. J Neurosurg. 1981. 54: 824-8

8. Green AJ, Roberts DR, Swanson RA. Post-traumatic epidermoid cyst presenting with headache. Neurology. 2005. 64: 1657

9. Guidetti B, Gagliardi FM. Epidermoid and dermoid cysts. Clinical evaluation and late surgical results. J Neurosurg. 1977. 47: 12-8

10. Hamlat A, Hua ZF, Saikali S, Laurent JF, Gedouin D, Guegan Y. Malignant transformation of intra-cranial epithelial cysts: Systematic article review. J Neurooncol. 2005. 74: 187-94

11. Haouimi A, Gaillard F, editors. Intracranial epidermoid cyst. Radiopaedia.Org. Victoria, Australia: Radiopaedia.Org; 2008. p.

12. Jamjoom DZ, Alamer A, Tampieri D. Correlation of radiological features of white epidermoid cysts with histopathological findings. Sci Rep. 2022. 12: 2314

13. Kim MS, Kim OL. Primary intracranial squamous cell carcinoma in the brain stem with a cerebellopontine angle epidermoid cyst. J Korean Neurosurg Soc. 2008. 44: 401-4

14. Lee CW, Park JE, Lee JH, Kim HS, Kim SJ. Coexistence of intracranial squamous cell carcinoma and epidermoid cyst: A case with consecutive imaging findings. Invest Magn Reson Imag. 2018. 22: 172-6

15. Michael LM, Moss T, Madhu T, Coakham HB. Malignant transformation of posterior fossa epidermoid cyst. Br J Neurosurg. 2005. 19: 505-10

16. Nagasawa D, Yew A, Spasic M, Choy W, Gopen Q, Yang I. Survival outcomes for radiotherapy treatment of epidermoid tumors with malignant transformation. J Clin Neurosci. 2012. 19: 21-6

17. Tamura K, Aoyagi M, Wakimoto H, Tamaki M, Yamamoto K, Yamamoto M. Malignant transformation eight years after removal of a benign epidermoid cyst: A case report. J Neurooncol. 2006. 79: 67-72

18. Vellutini EA, De Oliveira MF, Ribeiro AP, Rotta JM. Malignant transformation of intracranial epidermoid cyst. Br J Neurosurg. 2014. 28: 507-9