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Signet Ring Cell Adenocarcinoma and Bilateral Leptomeningeal Involvement of Optic Nerve Sheaths

Mbekeani, Joyce N. MD, FRCS, FRCOphth; Haseeb, Mohammed Q. MD, FRCS; Tulbah, Asma M. MD; Hamed, Salem H. MD; Al Hazzaa, Selwa A. MD, FRSC; Dogar, Mohammad A. MD

Section Editor(s): McCulley, Timothy J. MD

Journal of Neuro-Ophthalmology: June 2015 - Volume 35 - Issue 2 - p 162–164
doi: 10.1097/WNO.0000000000000236
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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 involvement. 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 widespread 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.

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.

Address correspondence to Joyce N. Mbekeani, MD, FRCS, FRCOphth, Department of Ophthalmology, 1400 Pelham Parkway, Bronx, NY 10461; E-mail: jnanjinga@yahoo.com

The authors report no conflicts of interest.

A previously 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 was significant for a large distended abdomen with discernible pelvis masses. Neurologic, cardiorespiratory, and breast examinations 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 antigen 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), elevated 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 demonstrated transependymal resorption of CSF indicating intracranial hypertension.

FIG. 1

FIG. 1

FIG. 2

FIG. 2

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.

FIG. 3

FIG. 3

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.

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ACKNOWLEDGMENTS

Hasan Omairah AAS, COT, OCT-C, CRA, Chief of Photography, Department of Ophthalmology, KFSH&RC, Riyadh, Saudi Arabia.

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