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Exophthalmos

Exophthalmos is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Grave's Disease) or unilateral (as is often seen in an orbital tumor). Measurement of the degree of exophthalmos is performed using an exophthalmometer. Complete or partial dislocation from the orbit is also possible from trauma or swelling of surrounding tissue resulting from trauma. more...

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In the case of Graves Disease, the displacement of the eye is due to abnormal connective tissue deposition in the orbit and extraocular muscles (Epstein et al, 2003) which can be visualized by CT or MRI.

If left untreated, exophthalmos can causes the eye lids to fail to close during sleep leading to corneal damage. The process that is causing the displacement of the eye may also compress the optic nerve or ophthalmic artery leading to blindness.

Exophthalmos vs. proptosis

Some sources define "exophthalmos" as a protrusion of the globe greater than 18mm and "proptosis" as a protusion equal to or less than 18mm. (Epstein et al, 2003). Others define "exophthalmos" as protusion secondary to endocrine dysfunction and "proptosis" as any non-endocrine-mediated protusion .

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Paraneoplastic bilateral proptosis in a case of non-small cell lung cancer - selected reports
From CHEST, 2/1/03 by Andreas H. Diacon

We report the case of a 51-year-old woman with a large cell bronchial carcinoma with neuroendocrine differentiation (T3N0M0, stage IIB) and bilateral exophthalmos. A CT of the orbitae was compatible with Graves ophthalmopathy, but neither abnormalities in thyroid function nor thyroid antibodies could be found. The proptosis normalized 10 days after tumor resection. We conclude that the most likely cause of the reversible proptosis in this patient is paraneoplastic, a condition not previously described in the English-language literature.

Key words: lung cancer; neuroendocrine tumors; paraneoplastic syndrome; proptosis

Abbreviations: SVCS = superior vena cava syndrome; TSH = thyroid-stimulating hormone

We present a case of large cell bronchial carcinoma and bilateral exophthalmos, which normalized 10 days after tumor resection. In absence of an alternative explanation, we conclude that the most likely cause is paraneoplastic.

CASE REPORT

A 51-year-old female active smoker (30 pack-years) presented with increasing dyspnea, dry cough, and right-sided chest pain. The chest radiograph revealed a large, right-sided thoracic mass. On examination, marked bilateral proptosis was noted that had gradually developed over at least the last 12 months (Fig 1, top). The patient had no signs or symptoms of hyperthyroidism. Signs of consolidation were found over the right lung. The jugular veins were slightly distended, and mild bilateral ankle edema was present. Graves disease and a lung malignancy with possible superior vena cava syndrome (SVCS) were initially suspected.

[FIGURE 1 OMITTED]

On contrast-enhanced CT, a well-circumscribed, spherical pulmonary mass extended from the right anterolateral chest wall to the heart. The superior vena cava was not affected (Fig 2). Subsequently, right atrial and ventricular dyskinesia due to a mass encroaching on the right heart were found on echocardiography. A compressed right bronchial system was seen on bronchoscopy, and transbronchial needle aspiration showed cells of non-small cell lung cancer. Metastases to the brain or the orbitae were excluded by CT (Fig 3). Thyroid-stimulating hormone (TSH) was slightly above reference value, and free thyroxine was within normal range, as well as TSH receptor-stimulating antibodies, antimicrosomal antibodies, and antithyroglobulin antibodies. Serum calcium was not raised.

[FIGURES 2-3 OMITTED]

Lung function testing revealed a restrictive pattern, and the predicted postpneumonectomy FE[V.sub.1] was 0.96 L (34% predicted) on the basis of a quantitative radionuclide lung perfusion scan. The patient was deemed operable at a clearly elevated risk due to borderline lung function. A right-sided pneumonectomy with partial resection of the chest wall was performed. Macroscopically, the tumor involved all three lung lobes and the lateral chest wall, while the diaphragm, hilum, and hilar lymph nodes were microscopically free of tumor. On histology, the tumor consisted of large cells with abundant cytoplasm, growing in solid sheets and islands with no neuroendocrine morphology such as organoid nesting, palisading, a trabecular pattern, or rosette-like structures. Positive immunostaining for neuron specific enolase, synaptophysin, and chromogranin indicated neuroendocrine differentiation. Epithelial markers were negative. The final oncologic diagnosis was a large cell bronchial carcinoma with neuroendocrine differentiation, T3N0M0, stage IIB, completely resected.

The patient tolerated the operation well, and a considerable reduction of the proptosis could be documented within 10 days (Fig 1, bottom). Shortly after discharge, however, a bronchial fistula developed with subsequent infection of the pneumonectomy cavity with Staphylococcus aureus. Despite surgical repair of the leakage and prolonged intensive care, the patient died of septic shock.

DISCUSSION

This 51-year-old female patient with stage IIB nonsmall cell lung cancer presented with unexplained bilateral exophthalmos that had gradually appeared over at least 12 months. Orbital metastases as a possible cause were excluded with CT. Neck vein distension, proptosis, and chemosis are symptoms of SVCS, but this condition was ruled out by the patent superior vena cava on CT. In addition, other signs of SVCS such as facial edema and collateral veins were absent, and the mild neck vein distension could be explained by compromised right heart function on echocardiography.

The paraneoplastic character of our patient's bilateral proptosis is most strikingly demonstrated by its rapid regression after tumor removal (Fig 1). This condition seems to be very rare, since we could only find one previous report, published in Japanese. (1) Bilateral proptosis is most usually seen in Graves disease, but our patient had neither clinical nor biochemical signs of hyperthyroidism, and antibodies diagnostic of Graves disease could not be found. It is generally accepted that TSH receptor antibodies play a major role in the pathogenesis of the proptosis in Graves disease. A variety of autoantibodies with either stimulating or blocking properties have been described, and retro-orbital fibroblasts seem to share common antigenic structures with the TSH receptor. (2,3) It is therefore likely that the bilateral proptosis in our patient was caused by a paraneoplastic antibody with affinity to orbital antigens.

Pulmonary large cell carcinomas with neuroendocrine differentiation are closely related to large cell neuroendocrine carcinomas, and both types seem to be more aggressive than classical large cell carcinoma. (4,5) Many paraneoplastic syndromes have been described in lung tumors with neuroendocrine features, especially small cell carcinoma, due to the production of biologically active substances either by the tumor or in response to the tumor. (6) Bilateral proptosis imitating Graves disease may be added to the list.

REFERENCES

(1) Fukushima M, Hatanaka R, Tsushima T, et al. A case of squamous cell carcinoma of the lung associated with exophthalmos and hypercalcemia [in Japanese]. Kyobu Geka 1998; 51:168-173

(2) Stadlmayr W, Spitzweg C, Bichlmair AM, et al. TSH receptor transcripts and TSH receptor-like immunoreactivity in orbital and pretibial fibroblasts of patients with Graves' ophthalmopathy and pretibial myxedema. Thyroid 1997; 7:3-12

(3) Gerding MN, van der Meer JW, Broenink M, et al. Association of thyrotrophin receptor antibodies with the clinical features of Graves' ophthalmopathy. Clin Endocrinol (Oxf) 2000; 52:267-271

(4) Travis WD, Linnoila RI, Tsokos MG, et al. Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma: an ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 1991; 15:529-553

(5) Iyoda A, Hiroshima K, Toyozaki T, et al. Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology. Cancer 2001; 91:1992-2000

(6) Patel AM, Jett JR. Clinical presentation and staging of lung cancer. In: Aisner J, Arrigada R, Green MR, et al, eds. Comprehensive textbook of thoracic oncology. Baltimore, MD: Williams & Wilkins, 1996; 293

Andreas H. Diacon, MD; Mace M. Schuurmans, MD; Frans J. Colesky, MD; and Chris T. Bolliger, MD, FCCP

* From the Departments of Internal Medicine (Drs. Diacon, Schuurmans, and Bolliger) and Pathology (Dr. Colesky), Tygerberg Hospital, University of Stellenbosch, Cape Town, South Africa.

Manuscript received December 17, 2001; revision accepted July 25, 2002.

Correspondence to: Andreas H. Diacon, MD, Department of Internal Medicine, Tygerberg Hospital, University of Stellenbosch, PO Box 19063, 7505 Tygerberg, South Africa; e-mail: ahd@sun.ac.za

COPYRIGHT 2003 American College of Chest Physicians
COPYRIGHT 2003 Gale Group

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