Leptomeningeal metastasis from squamous cell carcinoma of oesophagus with unusual presentation

Abstract

Oesophageal cancer rarely metastasis to the brain but advances in brain imaging and increasing survival of these patients has led to more detection of this condition. Although oesophageal cancer is common in the north of Iran it is less frequent in the central parts such as Yazd. Leptomeningeal metastasis is very uncommon in oesophageal cancer. This paper presents a 73-year-old man with leptomeningeal carcinomatosis from squamous cell carcinoma of oesophagus presented by hoarseness due to true vocal cord plegia.

Background

Oesophageal carcinoma is a common health problem in the north and the west of Iran; however, it is less frequent in other parts.¹ Lung, liver and bone metastasis can be seen in the advanced stages of oesophageal carcinoma, however central nervous system (CNS) involvement is not common.^{2 3} Incidence of brain metastasis from oesophageal carcinoma is approximately 1.5%.⁴ In most of the patients brain metastasis presents with a single lesion.^{4 5} Leptomeningeal carcinomatosis occurs in approximately 5% of cancerous patients, especially those with breast or lung cancer, and it is a clinically important neurological complication.^{3 6} There are very few reports on leptomeningeal metastasis in oesophageal cancer. Presented in this paper is a 73-year-old man with squamous cell carcinoma (SCC) of oesophagus and leptomeningeal metastasis.

Case presentation

A 73-year-old man was referred to our centre for palliative brain radiation therapy due to leptomeningeal metastasis. His new complaints had begun 2 months before with hoarseness and frontal headache. Physical examination had revealed a tender mass in the frontal area and right true vocal cord (TVC) plegia in direct laryngoscopy. Cervicothoracic CT scanning did not show any other findings except right TVC plegia (figure1). Brain MRI showed an infiltrative lesion in the right side frontal bone extending to both frontal sinuses and intracranium and leptomeningium (figure 2A,B). His medical history indicated that the patient had undergone surgical intervention for treatment of SCC of oesophagus (figure 3) 20 months previously. The pathological report showed a 3 cm tumour, moderately differentiated SCC extending to the adventitia (T3) and four from six resected lymph node involvements (N2). The patient had been receiving six courses of platinum-based chemotherapy.

Figure 1.

CT scan shows right true vocal cord plegia.

Figure 2.

(A) Brain MRI shows an infiltrative lesion in the frontal bone extending to both frontal sinuses and intracranium and leptomeningium. (B) Axial view.

Figure 3.

Section shows well differentiated squamous cell carcinoma with prominent keratin pearls.

Differential diagnosis

Although other malignancies such as lymphoma and lung cancer could be listed as differential diagnosis however, they were ruled out by history, physical examination, laboratory test and imaging.

Treatment

In our centre the patient received 3000 cGY whole brain radiation and tolerated the treatment fairly well and his symptoms subsided.

Outcome and follow-up

Four weeks later however, the patient's condition deteriorated. The patient was admitted to the intensive care unit because of a loss of consciousness and respiratory failure and finally he died.

Discussion

Brain metastasis is not common in oesophageal cancer. The incidence rate has been reported to be between 1% and 5%.^{2 4} It is more common in patients in whom the disease is seen in the advanced stages and with large primary tumours.^2–4 In contrast to other solid tumours pulmonary metastasis is not common in these patients.² Rice et al⁵ showed that adjuvant therapy significantly increases the risk of brain metastasis.⁵ In most series, single brain metastasis was seen.⁴ The incidence of leptomeningeal metastasis (leptomeningeal carcinomatosis or meningeal carcinomatosis) in patients with solid tumours ranges from 4% to 15%.^{3 7} It is mostly seen in breast and lung cancers.^{3 7} Leptomeningeal carcinomatosis is very rare in oesophageal cancer. Cancer cells may invade the meninges through different pathways including: haematogenous spread, spread via the endoneural/perineural and perivascular lymphatic routes, direct spread from the CNS and iatrogenic spread.⁷ The most common presenting features of leptomeningeal metastasis are headache, changes in mental status, cranial nerve palsies and neck stiffness.⁸ The diagnosis of leptomeningeal carcinomatosis is done by cytological examination of the cerebrospinal fluid or by neuroradiological confirmation via CT scanning and MRI.³ In our patient, based on obvious MRI findings and the patient's poor general condition on the one hand and on the other hand his clinical and radiological findings being normal cerebrospinal fluid cytology was not performed. The prognosis of these patients is poor as in our patient .It is mostly due to primary lesions and also lack of treatment efficacy.⁸ The median survival is about only 4-6 weeks.^{3 8} The treatment consists of radiation therapy for palliation of symptoms, intrathecal chemotherapy and optimal therapy of the primary disease.⁸ There are few reports of leptomeningeal carcinomatosis in oesophageal cancer in the literature. Okumura et al reported a case of basaloid carcinoma with leptomeningeal carcinomatosis that at presentation showed neither any gross disease in CT scanning and MRI nor tumoural cells in the cerebrospinal fluid. Only quantitative reverse transcription-PCR for CEA mRNA expression and anticytokeratin antibody staining was helpful and led to the diagnosis, although only 4 months later and despite systemic chemotherapy the disease progressed and brain CT scanning showed multiple brain metastasis.³ In another paper Tanaka et al presented a case of moderately differentiated SCC, stage IV in which the patient had received chemotherapy. After treatment, the patient showed complete response to chemotherapy, initially, with no evidence of lesion at the affected part. Three months later, he complained of headache vertigo, and MRI and cytological examination of CSF, showed meningeal carcinomatosis.⁹ Girola et al¹⁰ and Abdo et al⁸ reported in two different papers two cases of oesophageal adenocarcinoma with meningeal carcinomatosis. Our patient similar to most previously reported ones showed an advanced disease (stage IIIb) however, he experienced a longer disease free interval between treatment procedures for primary oesophageal tumour and occurrence of CNS complications. He did not have any evidence of lung metastasis at the time of CNS relapse. Cranial nerve symptoms are an initial complaint in a third of these patients and they intervene during the course of illness in  two-thirds of this population. The commonest symptom is diplopia followed by hearing loss. Other frequent complaints include facial numbness and visual loss. The first complaint rarely is tinnitus, hoarseness, dysphagia, vertigo or decrease of taste sensation.¹¹ In this case hoarseness due to right TVC plegia was seen. TVC plegia was diagnosed via direct laryngoscopy and CT scanning. Another uncommon feature in this patient was the route of leptomeningeal involvement. We think leptomeningium was involved by direct extension from the frontal bone lesion. Radiation therapy could palliate the symptoms for a very short period and finally the disease progressed very fast and the patient died.

Learning points.

• Leptomeningeal involvement in squamous cell carcinoma of oesophagus is rare and presentation with vocal cord plegia is uncommon.

• Leptomeningeal involvement may occur via direct extension from the inner table of the frontal bone.

• It may present without any evidence of local recurrence or lung metastasis.

• Radiation therapy can palliate the symptoms however, survival is poor.