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 deposits in the sternum, mandible, clivus, and multiple vertebrae 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 revealed 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, primarily 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 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 widespread 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 contributions from meningeal cuffing, parenchymal infiltration, 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 specimens, increasing to 100% with sequential CSF samples (8,11). Identification of signet ring cells in the abdomen and characteristic neuroimaging findings were deemed adequate for diagnosis and staging of LC in our patient.
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 interpretation 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. Al Hazzaa; Category 3: a. Final approval of the completed manuscript: J. N. Mbekeani, M. Q. Haseeb, A. M. Tulbah, S. H. Hamed, M. A. Dogar.
Hasan Omairah AAS, COT, OCT-C, CRA, Chief of Photography, Department of Ophthalmology, KFSH&RC, Riyadh, Saudi Arabia.
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.
© 2015 by North American Neuro-Ophthalmology Society
11. Chamberlain MC. Neoplastic meningitis: a guide to diagnosis and treatment. Curr Opin Neurol. 2001;3:641–648.