Leptomeningeal carcinomatosis in a younger patient with signet-ring cell carcinoma

Cumhuriyet Tıp Dergisi Cumhuriyet Medical Journal Cumhuriyet Tıp Derg 2011; 33: 348-352 Cumhuriyet Med J 2011; 33: 348-352 Case report-Olgu sunumu Leptomeningeal carcinomatosis in a patient with signet-ring cell carcinoma younger Taşlı yüzük hücreli karsinomlu genç hastada leptomeningeal karsinomatozis Öztürk Ateş, İrem Kor Ateş, Saadettin Kılıçkap*, Sevgen Önder Departments of Internal Medicine (Ö. Ateş, MD., İ. K. Ateş, MD.), Pathology (Assist. Prof. S. Önder, MD.), Hacettepe University School of Medicine, TR-06100 Ankara, Department of Medical Oncology (Assoc. Prof. S. Kılıçkap, MD.), Cumhuriyet University School of Medicine, TR-58140 Sivas Abstract Leptomeningeal metastasis (LMM) occurs in about 3-8% of patients with systemic cancer. It is very rare in patients with signet-ring cell carcinoma. But, the prognosis is also very poor. We report a case of a younger woman with signet-ring cell carcinoma of primary origin unknown who presented with meningeal carcinomatosis. Keywords: Leptomeningeal metastasis; signet-ring cell carcinoma; prognosis. Özet Leptomenengeal metastazlar, sistemik kanserli hastaların yaklaşık %3-8’inde oluşur. Bu, signetring hücreli karsinomu olan hastalarda çok nadirdir. Ama prognoz da çok kötüdür. Meningeal karsinomatozisi olan ve birincil orjini bilinmeyen signet-ring hücreli karsinomu olan genç bir bayan olguyu bildiriyoruz. Anahtar sözcükler: Leptomeningeal karsinomatozis; taşlı yüzük hücreli karsinom; prognoz. Geliş tarihi/Received: October 28, 2010; Kabul tarihi/Accepted: March 17, 2011 *Corresponding author: Saadettin Kılıçkap, MD., Onkoloji Anabilim Dalı, Cumhuriyet Üniversitesi Tıp Fakültesi, TR58140 Sivas. E-mail: Introduction Leptomeningeal metastasis (LMM), also named as carcinomatous meningitis, is the infiltration of the leptomeninges by malignant cells and occurs in about 3-8% of patients with systemic cancer [1, 2]. The presence of LMM associates with poor prognosis. It also decreases the score of the quality of life because of headache, nausea, vomiting, and neurological complications such as sensorial and motor nerve dysfunction, altered mental status, and seizures. The most common sources of LMM are breast cancer, small cell carcinoma of lung, malignant melanoma, and hematopoietic malignancies such as acute lymphoblastic leukemia and lymphoma [3, 4]. In English literature, there are several case reports developed LMM from signet-ring cell carcinoma. Primary origin of these cases is often gastric carcinoma. We report a case of a younger woman with signet-ring cell carcinoma of primary origin unknown who presented with meningeal carcinomatosis. Case report A 19-year-old woman without previously serious illness was admitted with abdominal 349 and back pain and discomfort in March 2006. On admission, there was also weight loss (10 kg for last 3 months). Her physical examination revealed a pelvic mass. The computed tomography (CT) of pelvis indicated bilateral ovarian mass. Because of suspicion of ovarian cancer, extensive surgery including total abdominal hysterectomy, bilateral salpingo oopherectomy, bilateral paraaortic and pelvic lymph node dissection, and omentectomy was performed. Pathological examination consisted with metastasis of mucinous type signet-ring cell adenocarcinoma. In immunohistochemical examination, neoplastic cells were positive for carcinoembrionic antigen, CK-20, CK-7, but negative for GCDFP-15. Because of the presence of signet-ring cells, her gastrointestinal tract was evaluated to detect the primary origin of the tumor. Endoscopy of upper gastrointestinal tract and double contrast colon imaging was performed, but revealed no abnormality. At 5 days after the admission, diplopia, nausea, and headache developed. She also complained with weakness, and disability. The neurological examination was unremarkable. Magnetic resonance imaging (MRI) of the brain and cervical spine demonstrated contrast enhancement nodular appearance of cerebellar fissures and leptomeningeal. Lomber punction was performed and the cytological examination of cerebrospinal fluid (CSF) revealed malignant epithelial cells with signet-ring morphology (Figure 1). CT of upper and lower abdomen showed peritoneal carcinomatosis and metastases of thoracal vertebreas. Spinal MRI demonstrated widespread metastasis in spinal column, compression fractures at T3, T10, and T11. Figure 1: Malignant epithelial cells with pleomorphic nuclei. The nuclei are located eccentrically due to cytoplasmic mucin, giving the tumor cells signet ring appearance. MGG x1000. The patient was initially treated with intrathecal methotrexate at doses of 15 mg/day. Treatment sessions were repeated twice a week for 3 weeks. The response was assessed by CSF cytology. After 6 cycles, CSF was cleared from malignant cells. The patient also received craniospinal radiotherapy for 10 days after intrathecal methotrexate therapy was completed. Because of signet-cell carcinoma of primary origin unknown, she also received the combined chemotherapy including docetaxel (60 mg/m2, day 1), cisplatin (60 mg/m2, day 1), and fluorouracil (600 mg/m2, 1-5 days) with concomitant granulocyte-stimulating factor prophylaxis for every 3 weeks. After 2 cycles, febril neutropenia developed. Despite of antibacterial therapy, her general condition was Cumhuriyet Tıp Dergisi Cumhuriyet Medical Journal Cumhuriyet Tıp Derg 2011; 33: 348-352 Cumhuriyet Med J 2011; 33: 348-352 350 unimproved. The patient died because of febril neutropenia and sepsis. Discussion Although LMM from solid cancers is uncommon, the prognosis is very poor. Median survival after LMM diagnosis is about 4-6 months [2, 5]. The clinical manifestations of LMM are very variable and include lower motor neuron weakness, headache, radicular pain, and diplopia. The neurological signs are characterized by reflex asymmetry, mental status changes, ocular muscle paresis, and motor neuropathy as well as sensorial loss [2, 6]. Quality of life deteriorates after the diagnosis because of neurological complications. The diagnosis is usually based on cytological examination of the CSF and/or MRI of brain and spinal tract. The detection of malignant cells in the CSF is the gold standard for the diagnosis. But, a positive cytology is demonstrated in only about 50% of cases [4]. Another diagnosis procedure of LMM is MRI. The enhanced contrast involvement of leptomeningeal surface on craniospinal MRI may be useful for diagnosis of LMM. Tumor metastasis to leptomeningeal surface occurs by a few mechanisms. Hematogenous spread is the most common source of LMM [6]. The others include direct extension of extradural tumors and meningeal seeding from brain metastasis. However, Batson’s plexus can take a role in the tumor spread to CNS [6]. Treatment options for patients with LMM include radiotherapy and/or chemotherapy. Intrathecal chemotherapy is usually used for patients with LMM because most chemotherapeutic agents do not penetrate the blo (...truncated)