Adjuvant treatment of unresectable choroid plexus carcinoma with literature review

Abstract

Choroid plexus carcinomas are rare and arise from the choroid plexus, with invariably poor prognosis. We report an unusual case of an 8-year old male who presented with symptoms of increased intracranial pressure with radiological evidence of brain intraventricular lesion which was proved to be choroid plexus carcinoma on histopathology and immunohistochemistry. Treatment consisted of limited surgery followed by craniospinal irradiation and boost to the local tumor.

Post treatment there was evidence of residual disease with no significant clinical improvement for which patient was managed conservatively with steroids along with chemotherapy with poor outcome.

Hence aggressive surgical resection of the tumor is the most relevant prognostic predictor for survival, and is associated with poor prognosis if not completely excised irrespective of adjuvant treatment.

INTRODUCTION

The choroid plexus carcinomas (CPC) are relatively uncommon neoplasm of the central nervous system in the pediatric population which represents less than 1 percent of all primary brain tumors. Although rarely reported in adults, 80% of CPCs occur in the pediatric population [1].

Choroid plexus carcinomas are believed to arise from the choroid plexus epithelium, commonly from lateral ventricles.

They are usually diagnosed as intraventricular tumor such as astrocytoma, meningioma, papillary variant ependyoma or villous hypertrophy of the choroid plexus, as these are more common with similar presentation [2, 3]. The diagnosis is commonly made after histopathology and immunohistochemistry. The extent of surgery is the most important determinant of treatment outcome. Here we report a case of choroids plexus carcinoma who showed poor outcome with adjuvant treatment following limited surgery.

CASE REPORT

A 8 year old boy presented with headache, decreased vision in both eyes and projectile vomiting for 3 months. The patient had one episode of seizure followed by extension of lower limbs and flexion of upper limbs (decorticate rigidity) and loss of consciousness (Glasgow coma scale 4), on examination pupils showed sluggish light reflex. MRI of the brain showed a large illdefined space-occupying lesion arising from the roof of left lateral ventricle and extending to the left temporoparietal region, interbrain part (thalamic region, corona radiata, posterior part of corpus callosum) and associated with hydrocephalus (Fig 1). The CSF cytology was positive for malignant cells. The boy underwent subtotal excision of the mass due to large size of tumor and involvement of surrounding critical structures with ventriculo-peritoneal shunting. Postoperatively, there was no clinical improvement of the patient (Glasgow coma scale 4) with sluggish pupillary reflex; further the boy also developed difficulty in respiration along with extension of upper and lower limbs (decerebrate rigidity) suggesting progression of disease.

The histopathology and immunohistochemistry of the biopsy was consistent with choroid plexus carcinoma (fig 2). Patient was planned for craniospinal irradiation to the primary lesion (54 Gy/30 fractions in 6 weeks) and to the neuraxis including the spine (24 Gy/13 fractions in 3 weeks). After completion of radiation there was no significant clinical improvement (Glasgow coma scale 7) and pupillary reflex was still sluggish. Radiologically there was evidence of residual contrast-enhancing tumor (Fig 3), for which patient was planned for cisplatin (20 mg/m² day 1-5) and etoposide (100 mg/m² day 1-5) chemotherapy at 3-week interval. The patient survived for about a month only following the first cycle of chemotherapy.

DISCUSSION

The choroid plexus carcinoma is sometimes called an anaplastic choroid plexus papilloma and is associated with poor prognosis if not completely excised.

Figure 1.

T2-weighted coronal MRI (a,b); T1-weighted axial contrast enhanced MRI (c,d) showing heterogeneously enhancing lesion arising from the roof of left lateral ventricle and extending to the left temporo-parietal region, interbrain part( left thalamic region, corona radiata, posterior part of corpus callosum) and associated with hydrocephalus.

Figure 2.

Microphotograph of Choroid plexus carcinoma. (a) Cellular papillary-acinar epithelial lesion (H&E x200 x digital magnification), (b) & (c) Focal GFAP expression, (d) Cytokeratin, (e) Vimentin expression, and (f) Lesion is negative for alpha fetoprotein ( DAB x200 x digital magnification).

Figure 3.

T1, T2-axial contrast enhanced (a, b); T1, T2 coronal contrast enhanced (c,d); T1,T2-sagittal contrast enhanced (e,f) showing post treatment residual disease in left temporo-parietal region.

The diagnosis is seldom made clinically or radiologically, it is usually confirmed by histopathology and immunohistochemistry including a combination of GFAP, cytokeratin and vimentin expression (fig 2). Complete tumor resection is the main factor influencing the survival and overall prognosis, which is often difficult to achieve due to high morbidity associated with younger patient age, widespread tumor dissemination, and tumor vascularity, which puts patients at increased risk (4, 5).

Mounting evidence from literature suggests that aggressive surgical resection of the tumor is the most relevant prognostic predictor for survival (4, 5). The 5-year survival rate is only 58% even after complete tumor resection as compared to 20% after partial resection [6, 7]. Hence almost half of the patients are at risk even after complete resection; this may be due to higher probability of invasion and dissemination. Adjuvant treatment of CPC may therefore be important not only for patients with partially resected CPC but also for patients with completely resected CPC.

Adjuvant radiotherapy improves the survival outcome of patients with CPC for incompletely and completely resected tumors but age seems to be a limiting factor for radiotherapy as children below 3 years have late neurological sequelae of radiotherapy, in this subgroup of patients chemotherapy forms the main adjuvant treatment modality [8].

Adjuvant chemotherapy significantly improves the cumulative overall survival of all patients with CPC irrespective of type of surgery, but due to limited number of cases, larger studies are required to ascertain the role of adjuvant chemotherapy mainly in patients who have undergone complete resection of tumor [9, 10,11]. Furthermore literature also suggests possible role of chemotherapy in the neo adjuvant setting so as to reduce the size and vascularity of tumor, thereby increasing the feasibility of complete surgical resection [5, 12], but adjuvant chemoradiotherapy have shown the best 2 year survival of 63%, as compared to 45% and 32% in patients receiving adjuvant chemotherapy alone and radiotherapy alone respectively. In those without any adjuvant treatment the 2 year survival was a dismal 15% in incompletely resected and 58 % in completely resected patients of CPC [13 ].

Although adjuvant radiotherapy and chemotherapy gives promising response, local control remains the main challenge, and “second look” surgery has to be considered for patients with incomplete resection. There is evidence which suggests that a second surgery after cytoreduction with chemotherapy is beneficial in patients with incomplete resection with an increase in 2-year survival of 69% compared with a survival of 30% for patients with and without second surgery [5].

Conformal techniques such as Proton Stereotactic Radiotherapy (PSRT), Proton Stereotactic Radiosurgery (PSRS) and Gamma knife based radiosurgery, which involves the use of a highly focused beams of radiation to target the cancer cells have gained importance in recent times. [14] Newer advances such as stem cell transplantation and effective chemotherapy as a part of treatment continues to be under study. Recent studies have shown that immunopositivity for gene TP53 is an important prognostic predictor which influences treatment outcome and survival. Studies have shown Immunopositivity for TP53 conferred a 5-year survival of 0% compared to 82% for those that were immunonegative, hence concluding that patients who lack TP53 dysfunction could be treated successfully without radiotherapy [15].

CONCLUSION

Complete surgical resection of the tumor is the most important prognostic predictor for treatment outcome and survival in patients of CPC. Adjuvant chemotherapy should be given to patients with less than completely resected CPC, if possible in combination with radiotherapy. For completely resected CPC, there is a trend towards a better cumulative overall survival, for those patients receiving chemoradiation.

Although chemoradiation forms as effective adjuvant treatment modality there is still significant uncertainty regarding the role of adjuvant treatment in CPC and definitive recommendations can be made only after further larger studies.