| OCR Text |
Show Signet Ring Cell Adenocarcinoma and Bilateral Leptomeningeal Involvement of Optic Nerve Sheaths Joyce N. Mbekeani, MD, FRCS, FRCOphth, Mohammed Q. Haseeb, MD, FRCS, Asma M. Tulbah, MD, Salem H. Hamed, MD, Selwa A. Al Hazzaa, MD, FRSC, Mohammad A. Dogar, MD Abstract: Signet ring cell adenocarcinoma has a propensity for leptomeningeal carcinomatosis, and although bilateral optic nerve involvement is rare, this may occur with or without obvious signs of diffuse leptomeningeal involve-ment. We describe a 41-year-old woman who presented with a brief history of simultaneous bilateral visual deterioration and a distended abdomen. Examination revealed bilateral no light perception vision and bilateral optic disc edema. Radiologic work-up showed large multiple pelvic masses involving the ovaries, multifocal boney deposits, and wide-spread central nervous system carcinomatosis, involving the optic nerves and the first, fifth, and eighth cranial nerves. Biopsy of an ovarian mass demonstrated islands of signet ring cells. Signet cell adenocarcinomatous infiltration of the leptomeningeal space should be considered in cases of bilateral simultaneous vision loss with signs suggestive of leptomeningeal infiltration of the optic nerve sheath. Journal of Neuro-Ophthalmology 2015;35:162-164 doi: 10.1097/WNO.0000000000000236 © 2015 by North American Neuro-Ophthalmology Society Apreviously health 41-year-old woman was referred with a 2-month history of abdominal distension, intractable vomiting, frontal headaches, and declining vision. She reported bilateral blindness for the previous 6 days. Her medical history was significant for infertility after one successful pregnancy. On examination, the patient was lethargic but oriented. She had no light perception in each eye, and pupils were large and sluggishly reactive to light with no relative afferent pupillary defect. Extraocular movements were normal as were the arterior segments of each eye with intraocular presence of 10 mmHg bilaterally. Ophthalmoscopy revealed bilateral optic disc edema without retinal abnormalities. Systemic examination FIG. 1. Contrast-enhanced fat-suppressed T1 axial magnetic resonance imaging shows optic nerve sheath enhancement posteriorly. Note the demarcation line (arrow) between infiltrated and noninfiltrated optic nerve sheaths and diffuse lep-tomeningeal thickening and enhancement along the folia of cerebellum. Department of Ophthalmology (JNM), North Bronx Health Network; Department of Ophthalmology & Visual Sciences (JNM), Albert Einstein College of Medicine of Yeshiva University, Bronx, New York; Departments of Ophthalmology (MQH, SAAH), Pathology (AMT), Gynecologic Oncology (SHH), and Neuro-radiology (MAD), King Faisal Specialist Hospital, Riyadh, Saudi Arabia; and the Al Faisal University College of Medicine (SAAH), Riyadh, Saudi Arabia. The authors report no conflicts of interest. Address correspondence to Joyce N. Mbekeani, MD, FRCS, FRCOphth, Department of Ophthalmology, 1400 Pelham Parkway, Bronx, NY 10461; E-mail: jnanjinga@yahoo.com 162 Mbekeani et al: J Neuro-Ophthalmol 2015; 35: 162-164 Photo Essay Section Editor: Timothy J. McCulley, MD Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. was significant for a large distended abdomen with discernible pelvis masses. Neurologic, cardiorespiratory, and breast exami-nations were normal. Acute phase reactants were elevated with erythrocyte sedimentation rate of 54 mm/h and C-reactive protein of 120 mg/dL (normal ,10 mg/dL). Tumor marker values were cancer antigen (CA) 125 of 467.1 IU/mL (normal ,35 IU/ mL) while CA 15-3, CA 19-9, and carcinoembryonic anti-gen were normal. Cerebrospinal fluid (CSF) fluid analysis failed to disclose malignant cells but revealed decreased glucose of 0.47 mmol/L (normal: 2.8-44 mmol/L), ele-vated protein of 1.333 mg/dL (normal: 15-50 mg/L), and pleocytosis. The opening pressure was not recorded. Contrast-enhanced MRI of the brain and orbits revealed widespread leptomeningeal thickening and enhancement. This involved the intraorbital optic nerves (Fig. 1), the first, fifth, seventh, and eighth cranial nerves and the brainstem and cerebellum (Fig. 2). In addition, T2 images demon-strated transependymal resorption of CSF indicating intracra-nial hypertension. Postcontrast computed tomography of the abdomen and pelvis revealed bilateral adnexal masses. There was associated ascites, nodular mesenteric and peritoneal deposits, partial small bowel obstruction, and dilated appendix, likely because of peritoneal carcinomatosis (Fig. 3A). Boney metastatic de-posits in the sternum, mandible, clivus, and multiple verte-brae also were present. Biopsy specimen of an abdominal mass revealed multiple islands of signet ring cells within normal ovarian tissue. These cells displayed large deposits of intracytoplasmic mucin displacing hyperchromatic nuclei (Fig. 3B). Confirmatory immunohistochemistry stains with cytokeratin 7 disclosed strong diffuse positivity (Fig. 3C). Ascites fluid cytology re-vealed similar adenocarcinoma. The patient, classified as stage IV malignancy, was deemed too unwell for therapeutic intervention and was offered palliation. Her condition deteriorated rapidly, and she died 2 weeks after admission from multiple organ failure. Once believed to be extremely rare, the incidence of leptomeningeal carcinomatosis (LC) is increasing, primar-ily because of improved patient survival rates and advanced early detection methods. Various neuropathies may occur most often after a detection of a primary cancer and, rarely, as the presenting manifestation. Although the FIG. 2. Multiple cranial nerve involvement (arrows) due to leptomeningeal carcinomatosis. Postcontrast T1 magnetic res-onance imaging reveals enhancement of the first (A), fifth (B), and seventh and eighth (C) cranial nerves. FIG. 3. Pelvic masses. A. Multiple masses are present on postcontrast axial abdominal computed tomography. Biopsy specimen reveals islands of signet ring cells (arrows) with intracytoplasmic mucin and peripherally displaced hyperchromatic nuclei (B) (hematoxylin & eosin, ·200). The cells stain for cytokeratin (C) (immunohistochemistry stain, ·200). Mbekeani et al: J Neuro-Ophthalmol 2015; 35: 162-164 163 Photo Essay Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. primary tumor site was unknown in our case, signet ring cell adenocarcinoma commonly arises from the stomach, colon, breast, prostate, and lungs (1). It can have multiple primary foci and replicate along the natural contours of an organ, such as the stomach, completely encasing it as one sheet of neoplastic tissue, called linitis plastica. Known for rapidly metastasizing, patients often present with wide-spread disease. From the cytopathology and large tumor masses within the abdomen, the most plausible primary site in our patient was the abdomen. Its spread to other intra-abdominal tissues and bones including the spine was likely hematogenous. Tumor cells gained access to the CSF by direct spread from the spine or by penetrating epidural veins (2). Optic nerve infiltration from LC has been reported in several cases of adenocarcinoma from various sources (2- 6). It may lead to severe visual failure, including bilateral blindness (7-10). Along with reports by Suto et al (9) and Hayashi et al (10), our patient experienced simultaneous bilateral optic nerve sheath infiltration, confirmed by contrast-enhanced MRI. The symmetric demarcation from posterior infiltrated and anterior un-infiltrated optic nerves (Fig. 1) lends credence to the possibility that an intracranial sheet of signet ring cells extended into the orbits to encase the optic nerves in a similar fashion to linitis plastica in the abdomen. The mechanism of vision loss in LC has yet to be elucidated and may have been multifactorial in our patient. She had headaches and MRI evidence of increased intracranial presence so the profound vision loss likely resulted from intracranial hypertension and variable con-tributions from meningeal cuffing, parenchymal infiltra-tion, and vascular disruption. The discrepancy between sluggish pupillary light responses and no perception of light vision may have resulted from residual melanopsin ganglion cell activity. Cerebrospinal fluid cytology, the gold standard for diagnosis of LC, was negative in our patient. Detection of malignant cells is only 50%-70% positive in initial speci-mens, increasing to 100% with sequential CSF samples (8,11). Identification of signet ring cells in the abdomen and characteristic neuroimaging findings were deemed ade-quate for diagnosis and staging of LC in our patient. ACKNOWLEDGMENTS Hasan Omairah AAS, COT, OCT-C, CRA, Chief of Photography, Department of Ophthalmology, KFSH&RC, Riyadh, Saudi Arabia. REFERENCES 1. Chu PG, Weiss LM. Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon. Am J Clin Pathol. 2004;121:884-892. 2. DeAngelis LM, Boutros D. Leptomeningeal metastasis. Cancer Invest. 2005;23:145-154. 3. Kim SH, Koh SB, Lee KW. A case of leptomeningeal metastasis presented with bilateral loss of vision. J Korean Neurol Assoc. 1999;17:780-782. 4. Teare JP, Whitehead M, Rake MO, Coker RJ. Rapid onset of blindness due to meningeal carcinomatosis from an oesophageal adenocarcinoma. Postgrad Med J. 1991;67:909-911. 5. Appen RE, de Venecia G, Selliken JH, Giles LT. Meningeal carcinomatosis with blindness. Am J Ophthalmol. 1978;86:661-665. 6. Lisenko Y, Kumar AJ, Yao J, Ajani J, Ho L. Leptomeningeal carcinomatosis originating from gastric cancer: report of eight cases and review of the literature. Am J Clin Oncol. 2003;26:165-170. 7. McCrary JA III, Patrinely JR, Font RL. Progressive blindness caused by metastatic occult signet-ring cell gastric carcinoma. Arch Ophthalmol. 1986;104:410-413. 8. Bruce BB, Tehrani M, Newman NJ, Biousse V. Deafness and blindness as a presentation of colorectal meningeal carcinoamtosis. Clin Adv Hematol Oncol. 2010;8:564-566. 9. Suto C, Oohira A, Funaki C, Kanno S, Mori Y. Pathological findings of optic neuropathy from metastatic leptomeningeal carcinomatosis. Jpn J Ophthalmol. 2007;51:396-398. 10. Hayashi Y, Kato T, Tanaka Y, Yamada M, Koumura A, Kimura A, Hozumi I, Inuzuka T. Markedly ring-enhanced optic nerves due to metastasis of signet-ring cell gastric carcinoma. Intern Med. 2010;49:517. 11. Chamberlain MC. Neoplastic meningitis: a guide to diagnosis and treatment. Curr Opin Neurol. 2001;3:641-648. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: J. N. Mbekeani, M. Q. Haseeb, M. A. Dogar; b. Acquisition of data: J. N. Mbekeani, M. Q. Haseeb, A. M. Tulbah, S. H. Hamed, M. A. Dogar; c. Analysis and interpre-tation of data: J. N. Mbekeani, M. Q. Haseeb, A. M. Tulbah, S. H. Hamed, M. A. Dogar; Category 2: a. Drafting the manuscript: J. N. Mbekeani, M. Q. Haseeb, M. A. Dogar; b. Revising it for intellectual content: J. N. Mbekeani, M. Q.Haseeb,M. A. Dogar, S. A. AlHazzaa; Category 3: a. Final approval of the completed manuscript: J. N. Mbekeani, M. Q. Haseeb, A. M. Tulbah, S. H. Hamed, M. A. Dogar. 164 Mbekeani et al: J Neuro-Ophthalmol 2015; 35: 162-164 Photo Essay Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
