Intracranial epidermoid cysts (ECs) are rare, benign tumor of central nervous system that appear from maintain ectodermal implants. Malignant transformation of an EC to squamous-cell carcinoma (SCC) is rarely reported. We present the case of a 43-years old male presenting with left hemianopia and severe headache 6 months after total resection of an epidermoid cyst of right frontal, whose pathological report disclose to be a malignant transformation of previous epidermoid tumor. Optimal total resection in addition adjuvant radiotherapy is the management of choice, although the patient’s general survival of this condition is poor.

Intracranial epidermoid cysts comprising for approximately 0.2-1% of brain tumors.[1] They originally develop from aberrant ectodermal embryonic tissue in the neural groove at 4 or 5 weeks of fetal development.[2] Intracranial epidermoid cysts are benign and slow-growing tumors. early presenting symptoms depending on the sites of the tumor. Epidermoid cysts are commonly known to be benign and totally curable by surgery. [3] Malignant transformation of an epidermoid cyst to squamous cell carcinoma (SCC) is very rare in literature. [4] The most prevalent location of occurrence of carcinoma are in cerebellopontine angle (CPA) and in para-pituitary area. [5] As hamlet mentioned, primary squamous cell carcinoma (PSCC) was categorized into five groups: 1) primary malignant transformation of a benign cyst, 2) malignant transformation from a remnant cyst, 3) malignant transformation of a dermoid and epithelial cyst, 4) malignant transformation with leptomeningeal carcinomatosis, and 5) other malignancies arising from benign cysts. [6] We will describe a case of malignant transformation of epidermoid cyst origination as large suprasellar cystic lesion extended to right frontal lobe in first surgery to recurrent brain mass which was pathology approved as SCC after 11 months. 

A 45-year-old male patient presented to the outpatient department of neurosurgery with complaints of severe headache of 3-months duration. He was apparently well before this episode. On examination, there was right hemi-anopia. The rest of general physical examination and neurological examination was normal. Hematological assessment and serum markers revealed no abnormality. Non-Contrast CT scan revealed a homogenous right parasellar and frontal cyst with peripheral rim of calcification. This mass was found to be compressing over the lateral and fourth ventricle resulting (Figure. 1). The tumor was removed via the sub frontal approach in the supine position, and surgery revealed on gross inspection a large cyst with a thin layer of white capsule containing yellowish-white, firm in consistency, and cheesy material. The cyst including the capsule and contents was removed completely. The patient recovered without incident, and the histological diagnosis was epidermoid cyst. ( Figure-2)

Six months after the initial surgery, he again manifested severe intermittent headache, right eye blindness and intracranial pressure (ICP). MRI demonstrated a large heterogeneous mass isointense on T1-weighted image, hyperintense on T2- weighted image, strongly enhanced after gadolinium, expanding from upper-Sella to right frontal and unusual edema (Figure 3). Rapid neurological deterioration associated with the site of the enhanced lesion in MRI suggests malignant transformation of EC. He underwent followed by second total brain resection of the recurrent tumor, and histological biopsy assessment of the specimen showed a cystic lesion lined by bland squamous epithelium and filled with laminated keratin which gathered with several small scattered islands of severely atypical squamous epithelium. These locations of typical epidermal cyst were collocated with zones that displayed marked nuclear irregularity with mitotic activity and an infiltrative growth pattern (Figure 4-5). Immunohistochemistry (IHC) showed positivity of the tumor cells for P53 protein. Based on these findings, the diagnosis of squamous cell carcinoma (SCC) approved in an EC was made.

The authors provided a 43 years old male patient with two malignant transformation of epidermoid cyst tumor to SCC in secondary surgery. Malignant transformation of an epidermoid cyst tumor to SCC has been seldomly described in the reports.  [7] Based on our current research, The patient’s age ranged from 40 to 85 years (mean age 53 years) and female was more reported. The mechanism of malignant transformation of a remnant benign EC to SCC is still imprecise. [8]

It has been described that long term inflammation prompt from spillage of materials comprising within the EC due to either perused cyst rupture and perhaps come up with by intra-operative introduction of foreign materials may lead to cellular atypia to neoplasia. [9] Another hypothesis assigns malignant transformation of benign EC to carcinoma in situ formation.  [10]

Progression of clinical symptoms is the most important indicator of malignant transformation of EC. Previous reports described malignant interval time were highly variable ranged from 2 months to 33 years with average presenting time within 2 years of primary diagnosis. [11] consequently, in a stable patient after total or subtotal resection of an intracranial epidermoid cyst tumor, clinical and image follow-up every 6 months for 2 years and annually thereafter is necessary. besides, supposing developing clinical worsening in a formerly stable patient emergent brain MRI must be evaluated. [12] Although, past researches reported malignant transformation of EC to SCC in brain parenchyma, Somasundaram described this phenomenon in spinal cord. [5]

Malignant transformation of intracranial epidermoid cysts appears as 

predominant enhanced by contrast imaging. Benign intracranial epidermoid cyst tumor commonly demonstrated on imaging low signal intensity on T1-weighted MRI, high signal intensity on T2-weighted MRI and restricted diffusion on diffusion weighted MRI. after contrast, minimal rim enhancement may be seen in 25% of the patients. [7] Malignant transformation exhibits on image by the edema, tissue invasion, rapid growth, and new enhancement following contrast. accordingly, new contrast enhancement of a residue intracranial EC need tissue diagnosis before adjuvant therapy for malignant transformation is considered.[13] In addition, Macmahon et al, reported malignant transformation of epidermoid cyst to glioblastoma. [14]

The maximum management of an epidermoid cyst tumor is total surgical resection of both cyst and inside components. However, total gross resection is possible in only 70-80% of the patients. [10] treatment of intracranial SCC arising in a residual EC is controversial and poor prognosis is reported. [1] We have known, patients’ mortality period ranged from 3 months to 5 years. consequently, Nagasawa et al., reported an overall survival of 6.6 months for patients with malignant transformation of a benign EC to SCC treated with surgery only and a significant growing in survival to 12.7 months when adjuvant radiotherapy was used. [12]  The average survival time for patients’ management with surgery alone was only 1 month, for those treated with surgery plus external-beam radiation was 18 months, and the median survival time for those managed with surgery plus stereotactic radiosurgery was 44 months. [12] we recommend that stereotactic radiosurgery offers the optimistic survival rate. We review past reports about malignant transformation of EC to SCC. (Table 1).

Table 1. Reports about malignant transformation of EC to SCC.

Finally, malignant transformation of a residual epidermoid cyst tumor is a rarely occurrence with controversial management and poor prognosis. The results of our case the optimal method for treating malignantly transformed ECs is resection with adjuvant radiotherapy. Attentive clinical observation of patients should be performed after resection of brain ECs, given that this report suggests that malignant transformation can occur even months after resection of an EC. Prospective studies are required to define optimal management of patients presenting with squamous cell transformation of a remnant benign EC.