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Year : 2021  |  Volume : 1  |  Issue : 3  |  Page : 593-595

The diagnostic challenge of ptosis and diplopia: Cavernous sinus syndrome as the sole sign of unknown pancreatic cancer

Department of Neurology, Bagcilar Training and Research Hospital, Istanbul, Turkey

Date of Submission18-Jan-2021
Date of Acceptance03-Mar-2021
Date of Web Publication02-Jul-2021

Correspondence Address:
Dr. Nurhan K Tutar
Bagcilar Training and Research Hospital, Bagcilar Merkez Mah, Dr. Sadık Ahmet Cd, Istanbul 34100
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_140_21

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Cavernous sinus syndrome (CSS) is a rare condition that presents with clinical signs and symptoms due to the involvement of the cranial nerves (CN) III, IV, VI, V1, and V2. Various causes such as vascular, inflammatory, infectious, or neoplastic pathologies are involved in the etiology. CSS is rarely the first sign of cancer. In this report, we would like to describe a unique patient who manifested with CSS in which the etiological factor behind the clinic was a metastatic pancreatic adenocarcinoma previously unknown.

Keywords: Anisocoria, cavernous sinus syndrome, pancreas cancer, ptosis

How to cite this article:
Tutar NK, Omerhoca S, Kale N. The diagnostic challenge of ptosis and diplopia: Cavernous sinus syndrome as the sole sign of unknown pancreatic cancer. Indian J Ophthalmol Case Rep 2021;1:593-5

How to cite this URL:
Tutar NK, Omerhoca S, Kale N. The diagnostic challenge of ptosis and diplopia: Cavernous sinus syndrome as the sole sign of unknown pancreatic cancer. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Jul 26];1:593-5. Available from: https://www.ijoreports.in/text.asp?2021/1/3/593/319980

Cavernous sinus syndrome (CSS) is a rare entity that manifests by clinical signs and symptoms associated with multiple cranial neuropathies, including any combination of the following; ophthalmoplegia, loss of facial sensation, and Horner's syndrome due to the involvement of the cranial nerves (CN) III, IV, VI, V1, and V2 located in the cavernous sinus. Pain may also accompany, especially with inflammatory processes. Although neuroimaging techniques are advanced, the etiological diagnosis of CSS is a challenging process. Various causes such as vascular, inflammatory, infectious, or neoplastic pathologies are involved in the etiology.[1] Here, we report a patient who presented with cavernous sinus involvement and was diagnosed with metastatic pancreatic cancer after further investigations.

  Case Report Top

A 61-year-old male patient was admitted to our hospital with a 3-week history of droopy eyelid, binocular diplopia, and chemosis in the left eye accompanied by a left-sided headache. The patient's past medical history was unremarkable until he had deep vein thrombosis 3 months ago and started 300 mg of dabigatran daily with regular use. On examination, palpebral aperture measured 8 mm in the right eye and 4.5 mm in the left eye, compatible with left ptosis. Anisocoria with a pupil diameter of 3.5 mm in the right eye and 7 mm in the left eye was detected in an illuminated room [Figure 1]a and [Figure 1]b. Responses to light and near were sluggish in the left eye. There was also restriction of abduction in the left eye, which was compatible with concurrent left CN III and CN VI palsy [Fig. 1c and d]. Corneal sensation was normal, and the corneal reflex was brisk in both eyes. Visual acuity and fundoscopic examination were normal. There was no other focal neurological deficit.
Figure 1: Patients photo; ptosis (a), anisocoria (b), and restriction of abduction in the left eye (c) but no restriction of adduction (d)

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Given the high likelihood of left cavernous sinus involvement, laboratory tests including complete blood count, liver function, renal function test, thyroid function test, sedimentation, C-reactive protein, serum angiotensin-converting enzyme (ACE), autoimmune panel, and chest X-ray were performed, revealing all normal. Serological tests for tuberculosis, Lyme disease, syphilis, and HIV remained negative. Cranial magnetic resonance imaging (MRI) revealed millimetric nodular lesions on the right cerebellum and occipital lobe with ring-contrast enhancement which were considered suspicious for metastasis [Figure 2]a,[Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e, [Figure 2]f. Orbital MRI showed bilateral cavernous sinus infiltration, more prominent on the left side [Figure 2]g, [Figure 2]h. MR angiography showed normal cerebral circulation with no evidence of aneurysm or cavernous sinus thrombosis. Tumor marker studies showed an elevated cancer antigen (CA) 125 of 876 U/mL (normal <35), and CA 19-9 of >1972 U/mL (normal <35). Cerebrospinal fluid (CSF) analysis showed 2-lymphocyte cells, normal biochemistry and cytology revealed no evidence of malignant cells. As brain parenchymal lesions accompanying cavernous sinus infiltration and elevated tumor markers suggest the possibility of metastasis, an abdominal CT was performed and revealed multiple hypodense lesions at the distal corpus and tail of the pancreas with hepatic multiple metastatic infiltrations [Fig. 2i]. Fine needle aspiration biopsy was performed from liver lesions and resulted in pancreatic adenocarcinoma with immunohistochemistry positive for CK7, CK 19, CDX2, CEA, MUC5AC, and CK 20.
Figure 2: Brain MRI shows right cerebellar (a), occipital (b), and parietal (c) nodular lesion on axial FLAIR image. Axial T1-weighted, gadolinium-enhanced images show a ring contrast enhancement pattern (d-f). Orbita MRI shows bilateral cavernous sinus hyperintensity on gadolinium-enhanced axial T1-weighted images (g) and coronal T1-weighted images (h). Abdomen CT shows hypodense lesions at the pancreas with hepatic multiple metastatic infiltrations (i)

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Patient was started on dexamethasone 24 mg/day and palliative radiation was administered to the whole brain and after then he received palliative chemotherapy. Despite thentreatments, there was no significant improvement in the patient's symptoms and neurological deficits. Unfortunately, the patient died after 4 months following treatment.

  Discussion Top

The involvement of the cavernous sinus presents a complex clinical picture due to the various vital structures it contains. In our patient, unilateral headache with multiple cranial neuropathies in the form of simultaneous involvement of CN 3 and CN 6 was compatible with CSS. Aneurysm or space-occupying lesions should be excluded promptly in cases of CN 3 palsy accompanied by pupil involvement, even if it is isolated or together with other CN, which resulted negatively in our patient. In orbital MRI, bilateral cavernous sinus infiltration was clearly observed. In cases where both cavernous sinuses are involved, with the almost symmetrical appearance on radiological imaging, both sides can be interpreted as normal and the diagnosis may be overlooked. The extended laboratory and imaging methods performed in our patient excluded possible vascular, inflammatory, and infectious processes that could cause this infiltration. Concomitant parenchymal brain involvement in cranial MRI raised the suspicion of metastasis due to a possible underlying primary malignancy. The patient had no history of cancer, which required us to screen for a primary tumor. Tumor markers, abdominal CT, and biopsy together revealed the pancreatic origin.

In a series of 126 patients with CSS, Fernández et al. showed that the most common cause of CCS is tumor.[2] Spell et al. reviewed cavernous sinus metastases from distant sites and revealed that breast carcinoma was the most common primary site, accounting for 33% of the cases detected, and other common sources were lymphoma, lung, and prostate cancer.[3]

Pancreatic cancer extremely rarely metastasises to brain (0.33%) and have been mainly described as focal lesions within the brain parenchyma in only limited cases.[4],[5] In terms of CN involvement, Pecen et al. reported a case in which only CN III was affected by metastasis to the orbital apex due to an unknown pancreatic cancer.[6] In the case of brain involvement, metastatic pancreatic cancer treatment is mostly palliative, and the median survival is only 4–5 months after the onset of CN involvement.[7] Unfortunately, although the survival of our patient was very short as in the literature, early diagnosis is invaluable to have the opportunity to improve the patient's quality of life, given the relentless prognosis of cavernous sinus metastases.

  Conclusion Top

Multiple cranial neuropathies requires evaluation of CSS. Diagnostic approaches in CSS should be completed by investigating systemic causes including malignancy, even if there is no history, as in our patient. Ultimately, only neurophthalmologic finding may reveal the underlying cause.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Nadarajah J, Madhusudhan KS, Yadav AK, Chandrashekhara SH, Kumar A, Gupta AK. MR imaging of cavernous sinus lesions: Pictorial review. J Neuroradiol 2015;42:305-19.  Back to cited text no. 1
Fernández S, Godino O, Martínez-Yélamos S, Mesa E, Arruga J, Ramón JM, et al. Cavernous sinus syndrome: A series of 126 patients. Medicine (Baltimore) 2007;86:278-81.  Back to cited text no. 2
Spell DW, Gervais DS Jr, Ellis JK, Vial RH. Cavernous sinus syndrome due to metastatic renal cell carcinoma. South Med J 1998;91:576-9.  Back to cited text no. 3
Go PH, Klaassen Z, Meadows MC, Chamberlain RS. Gastrointestinal cancer and brain metastasis: A rare and ominous sign. Cancer 2011;117:3630-40.  Back to cited text no. 4
Kuratsu J, Murakami M, Uemura S, Ushio Y. Brain and skull metastases of hepatic or pancreatic cancer--Report of six cases. Neurol Med Chir (Tokyo) 1990;30:476-82.  Back to cited text no. 5
Pecen PE, Ramey NA, Richard MJ, Bhatti MT. Metastatic pancreatic carcinoma to the orbital apex presenting as a superior divisional third cranial nerve palsy. Clin Ophthalmol 2012;6:1941-3.  Back to cited text no. 6
Oweira H, Petrausch U, Helbling D, Schmidt J, Mannhart M, Mehrabi A, et al. Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis. World J Gastroenterol 2017;23:1872-80.  Back to cited text no. 7


  [Figure 1], [Figure 2]


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