Orbital metastasis diagnosed by ultrasound-guided fine-needle aspiration biopsy: case report of unknown primary site

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ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia

Short communication

Orbital metastasis diagnosed by ultrasound-guided fine-needle aspiration biopsy: case report of unknown primary site夽 D. Cruzado-Sánchez a,∗ , J. Sánchez-Ortiz b , C.I. Peralta c , W.A. Tellez c , G. Maquera-Torres d , S. Serpa-Frías a a

Servicio de Oncología Ocular, Instituto Nacional de Enfermedades Neoplásicas (INEN), Lima, Peru Servicio de Oftalmología, Hospital Nacional Cayetano Heredia, Lima, Peru c Sociedad Científica de Estudiantes de Medicina Villarrealinos (SOCEMVI), Universidad nacional Federico Villarreal, Lima, Peru d Servicio de Patología, Instituto Nacional de Enfermedades Neoplásicas (INEN), Lima, Peru b

a r t i c l e

i n f o

a b s t r a c t

Article history:

Twenty five percent of orbital metastasis is usually of unknown primary origin and it

Received 20 March 2019

requires histopathological and immunohistochemical confirmation. The fine-needle aspi-

Accepted 2 July 2019

ration biopsy (FNAB) of the orbit is an alternative procedure to conventional orbitotomy.

Available online xxx

The case is presented of a 60 year-old woman with a right orbit tumour mass and neoplastic

Keywords:

atrium, and so an orbitotomy procedure was ruled out. An ultrasound-guided FNAB was

lesions in her brain and cranium. As an incidental finding, she had a thrombus in her left Fine-needle biopsy

performed instead with rapid on-site evaluation (ROSE) of biopsy samples. These showed

Image-guided biopsy

malignant cells of a lung adenocarcinoma, which was confirmed with immunohistochem-

Orbital neoplasms

istry and chest diagnostic images. In conclusion, biopsy samples obtained by FNAB, together

Cytology

with cytopathological and immunohistological analysis, enabled orbital metastasis to be identified in the case described, and showed that FNAB is a safe, effective, and minimally invasive alternative. ˜ ˜ S.L.U. All rights © 2019 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana, reserved.

Metástasis de la órbita diagnosticada por biopsia por aspiración con aguja fina guiada por ultrasonido: reporte de caso de sitio primario desconocido r e s u m e n Palabras clave:

El 25% de las metástasis de la órbita suelen ser de origen primario desconocido y requieren

Biopsia por aguja fina

confirmación histopatológica e inmunohistoquímica. La toma de biopsia con aspiración

夽 Please cite this article as: Cruzado-Sánchez D, Sánchez-Ortiz J, Peralta CI, Tellez WA, Maquera-Torres G, Serpa-Frías S. Metástasis de la órbita diagnosticada por biopsia por aspiración con aguja fina guiada por ultrasonido: Reporte de caso de sitio primario desconocido. Arch Soc Esp Oftalmol. 2019. https://doi.org/10.1016/j.oftal.2019.07.002 ∗ Corresponding author. E-mail address: [email protected] (D. Cruzado-Sánchez). ˜ ˜ S.L.U. All rights reserved. 2173-5794/© 2019 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana,

OFTALE-1542; No. of Pages 5

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Biopsia guiada por imágenes

con aguja fina de la órbita (BAAFO) es un procedimiento alternativo a la orbitotomía con-

Neoplasia orbitaria orbitaria

˜ vencional. Describimos el caso de una mujer de 60 anos que presenta una masa tumoral

Citología

en la órbita derecha y lesiones neoformativas en el cerebro y cráneo. Incidentalmente, la paciente presentó un trombo en la aurícula izquierda, por lo que se desestimó la orbitotomía y se realizó la BAAFO guiada por ultrasonido con evaluación rápida in situ de las muestras obtenidas. Se encontraron células malignas de adenocarcinoma pulmonar confirmadas con inmunohistoquímica e imágenes diagnósticas del tórax. En conclusión, las muestras obtenidas por BAAFO, junto al análisis citopatológico e inmunohistológico, permitieron identificar la metástasis orbitaria en el caso mencionado, siendo este procedimiento una alternativa segura, efectiva y mínimamente invasiva. ˜ ˜ S.L.U. Todos de Oftalmolog´ıa. Publicado por Elsevier Espana, © 2019 Sociedad Espanola los derechos reservados.

Introduction Orbital metastases represent approximately 7% of all lesions in this location,1 its presence is uncommon and can be of unknown origin in almost 25% of cases.1,2 The most frequent primary tumors involved are breast, prostate and lung.1 Orbital biopsies are usually performed by orbitotomy; however, postoperative complications can arise and limitations such as anesthesia costs, prolonged surgery time and hospital admissions are involved.2 Alternatively, orbital fine needle aspiration biopsy (OFNAB) is a minimally invasive and effective procedure with lower associated costs and an option to sample tumor lesions, and the option of obtaining tumor tissue due to image guidance such as ultraound increases its accuracy.1 Likewise, several authors, such as Pagni et al.,1 Gupta et al.2 and Agrawal et al., suggest that this procedure improves diagnostic efficiency3 ; other authors describe that the process and analysis of cytopathology and immunohistochemistry samples increases the sensitivity and specificity of results.4–7 However, there are few reports of the use of this technique. We present the case of a patient with orbital metastasis of unknown primary origin that underwent an ultrasoundguided OFNAB, which provided samples of the lesion and further analysis to determine the diagnosis.

Clinical case A 60-year-old woman with no previous pathological history, referred due to right orbit ocular protrusion during 6 weeks and occasional headaches. Ophthalmological examination showed a right eye visual acuity of 20/30 and 20/20 in the left eye. Indirect right axial proptosis was identified with limited eye movements to ipsilateral abduction. In addition, a 10 × 7 mm tumor with hard consistency was partially palpated in the right temporal superior orbital rim. Exophthalmometry in the right eye was: 13,0 ± 1,3 mm and in the left eye: 9,5 ± 1,2 mm. No lesions in biomicroscopy or fundoscopy were found in any of the eyes. Nuclear magnetic resonance imaging of the brain and orbits (Fig. 1A–D) showed an irregular, extraconal and heterogeneous tumor in the right orbital cavity, which induced

protrusion of the ipsilateral eyeball associated with neoformative lesions in the brain. The patient was scheduled for transconjunctival orbitotomy but the procedure was delayed because in the preoperative evaluation a thrombus was found in the left atrium by echocardiography (Fig. 1E), requiring prior anticoagulant treatment. For this reason, it was decided to perform an ambulatory OFNAB supplemented with transpalpebral ultrasound and rapid in situ evaluation of the tissues. The samples obtained were prepared for cytopathological and immunohistochemical analysis (Fig. 2A–H). The procedure was performed using a disposable 25 G needle, a disposable 10 ml syringe and a syringeholding device (Fig. 2C,D). Needle insertion was made through the upper conjunctiva, maintaining a stable needle direction towards the tumor. OFNAB was supplemented by transpalpebral ultrasound to guide the needle through a monitor (Fig. 2A,B). The tumor perforation and suction with the needle inside was carefully performed. The samples quality supervision through the rapid in situ evaluation was carried out by the cytopathologist. Prior to cytopathological analysis, respective smears were made on several slides, which then were fixed and stained with hematoxylin-eosin. An additional fraction was collected for immunostaining. Cytological analysis with hematoxylin-eosin staining revealed small neoplastic cells with hyperchromatic nuclei and moderate cellular atypia indicative of adenocarcinoma. The immunohistochemical evaluation showed positive staining for cytokeratin AE1/AE3 and thyroid-1 transcription factor, and negative desmin, related to the presence of lung adenocarcinoma metastases (Fig. 3A–E). A chest tomography was immediately programmed, identifying a tumor in the left upper lobe (Fig. 1G,H).

Discussion Orbital tumors with solid consistency are usually diagnosed with biopsies mainly taken by orbitotomy under general anesthesia. This is how it is usually done in our institution. With this method, the samples taken are larger and the technique requires the surgeon’s ability to access the lesions; however, this technique involves some surgical com-

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Fig. 1 – (A–D) Axial, coronal and sagittal sections of orbits and brain MRI: the arrows show extraconal irregular tumor masses predominantly in the right hemisphere of the brain. (E) Echocardiographic study showing a thrombus in the patient left atrium. (F) OFNAB guided by tumor ultrasound. (G, H) Axial and coronal sections of chest tomography showing an irregular mass in the apical region of the left upper lobe.

plications. Markowski et al. reported extraocular muscles paralysis, diplopia and blepharoptosis, among other postoperative lesions that represented 28.8% of patients that underwent lateral or medial orbitotomy sampling.8 For the case described, lateral orbitotomy was postponed due to the start of anticoagulant treatment and the potential risk of associated postoperative hemorrhage. Accordingly OFNAB was chosen for diagnostic purposes. To ensure a successful sampling with OFNAB, the tumor size (7,0 mm tall) was taken into account and was consistent with the recommended dimensions for aspirations (≥2,5 mm tall),9 although Pagni et al. recently reported a case with 24 patients where tumor size was not a limiting factor.1 Another variable that should be considered is the location, which favors the monitoring of the needle, since most biopsies performed were easily accessible, palpable and superficial masses.8 In addition, needle tracing during the procedure improved with ultrasound guidance, ensuring its position

and avoiding potential lesions of the adnexal orbital tissue. Diagnostic accuracy of OFNAB improved when supplementing it with other methods. Gupta et al. reported efficacy in 78% of cases when the procedure is guided by ultrasound,2 although cases of OFNAB without guidance by ultrasonography have also been reported5,6 with favorable results, both methods being equally effective.1,7 However, through ultrasonography we were able to avoid patient exposure to high levels of radiation. Likewise, Agrawal et al. reported an accuracy of up to 100% when the samples obtained were analyzed with auxiliary techniques (immunohistochemistry, flow cytometry, electron microscopy and PCR),3 and Pagni et al. attributed the success to the work of the multidisciplinary and coordinated specialist team.1 These advances led to reducing the common limitations of OFNAB and the risks described, such as aspirations, hemorrhages, eye perforations and damage to peripheral orbital tissues.4 Furthermore, rapid

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Fig. 2 – (A–C) Ophthalmologist performing OFNAB guided by ultrasound in the right orbit. The ultrasound image (B) shows: (a) vitreous humor; (b) extraocular muscle; (c) orbital tumor; (d) fine needle inside the tumor. (D–F) The materials used for the biopsy are shown. (G) Rapid in situ evaluation of the quality of the samples by the pathologist.

Fig. 3 – (A–B) Cytological samples in which small tumor cells with hyperchromatic nuclei with moderate variation in shape and size are observed (H&E, ×200). (C) Histological cut showing infiltrating islands of adenocarcinoma (H&E, ×50). Immunohistochemical stains were positive for cytokeratin AE1/AE3 (D) and TTF-1 (E).

in situ evaluation by the cytopathologist was important since it allowed the assessment of biopsy quality for later analysis. Usually, 2 OFNAB techniques are applied. The first is by suction, where the fine needle is placed using a syringe gun in order to aspirate the tumor area by negative pressure. The second is done by capillarity, in which only one needle is used and inserted into the tumor with backward movements in multiple directions to obtain an adequate amount of material. However, no significant differences between the two techniques have been reported.3 In our case, the suction method was used since the tumor lesion had solid consistency upon palpation

and was located in the anterior orbit, as illustrated by nuclear magnetic resonance (Fig. 1A-D). The fine needle aspiration biopsy technique is widely used for the diagnosis of various types of tumors and the most commonly reported complications of this technique are bleeding and infections, among others, in the various organs undergoing this technique.8–10 Seeding tumor cells along the needle path used for biopsy is considered a serious but rare complication.8,9 We have not been able to find reports of complications due to OFNAB in the literature; however, in a previous study of FNAB in uveal melanoma it is mentioned

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that, in addition to being a rare complication, the number of seeded cells is less than the limit necessary to produce viable tumors.8 The immunohistochemical result was positive for cytokeratin AE1/AE3, which defines epithelial lineage. It is a mixture of 2 monoclonal antibodies, and it has been observed to identify the majority of human cytokeratins, being a differentiation marker, especially in squamous and ductal carcinomas from the complex epithelium. The other positive marker in our case was the thyroid-1 transcription factor. This is expressed in more than 90% of small cell lung carcinomas and in 75% of non-small cell lung carcinomas, but it is not expressed in typical pulmonary carcinoids. However, the expression of thyroid-1 transcription factor in papillary, follicular and goitre carcinomas has also been confirmed, but not in anaplastic carcinomas of the thyroid gland. Additionally, the result was negative for desmin, which is a differentiation marker for sarcomas. The conclusion was adenocarcinoma cytology, considering the high possibility of primary lung tumor, which was confirmed with images of a tumor by chest tomography (Fig. 1). Orbital metastases have been described as unusual1 ; however, it should be considered as a differential diagnosis. In our case, it was taken into account since the multiple lesions that appeared in the brain were indicative of neoplastic processes. The approximate age of orbital metastatic tumors onset is 60 years, and despite being infrequent they may be the first manifestation of breast or lung cancer.8 However, 25% of diagnosed orbital metastases do not show evidence of cancer history as in our case, and 10% remain as a tumor of unknown origin, despite thorough evaluation.4 In conclusion, we report the case of a patient with a metastatic orbital tumor of unknown origin, with a high probability of intra-surgery complications, in which a minimally invasive procedure was chosen for the diagnosis of the primary neoplasm, being a rapid and effective method, requiring a multidisciplinary and coordinated teamwork. We consider it an option for the diagnostic approach of tumor lesions in the orbit.

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Conflict of interest The authors are not linked or have any commercial affiliation with the instruments discussed in the work.

references

1. Pagni F, Jaconi M, Smith AJ, Brenna A, Valente MG, Leoni S, et al. The role of fine needle aspiration of orbital lesions: a case series. Acta Cytol. 2016;60:31–8. 2. Gupta S, Sood B, Gulati M, Takhtani D, Bapuraj R, Khandelwal N, et al. Orbital mass lesions: US-guided fine-needle aspiration biopsy–experience in 37 patients. Radiology. 1999;213:568–72. 3. Agrawal P, Dey P, Saikia UN, Gupta N, Radhika S, Nijhawan R, et al. Fine-needle aspiration cytology of orbital meningiomas. Diagn Cytopathol. 2012;40:967–9. 4. Singh AD, Biscotti CV. Fine needle aspiration biopsy of ophthalmic tumors. Saudi J Ophthalmol. 2012;26:117–23. 5. Czerniak B, Woyke S, Daniel B, Krzysztolik Z, Koss LG. Diagnosis of orbital tumors by aspiration biopsy guided by computerized tomography. Cancer. 1984;54:2385–9. 6. Dubois PJ, Kennerdell JS, Rosenbaum AE, Dekker A, Johnson BR, Swink CA. Computed tomographic localization for fine needle aspiration biopsy of orbital tumors. Radiology. 1979;131:149–52. 7. Orlandi D, Sconfienza LM, Lacelli F, Bertolotto M, Sola S, Mauri G, et al. Ultrasound-guided core-needle biopsy of extra-ocular orbital lesions. Eur Radiol. 2013;23:1919–24. 8. Markowski J, Jagosz-Kandziora E, Likus W, Pajak J, Mrukwa-Kominek E, Paluch J, et al. Primary orbital tumors: a review of 122 cases during a 23-year period: a histo-clinical study in material from the ENT Department of the Medical University of Silesia. Med Sci Monit. 2014;20:988–94. 9. Minaga K, Takenaka M, Katanuma A, Kitano M, Yamashita Y, Kamata K, et al. Needle tract seeding: an overlooked rare complication of endoscopic ultrasound-guided fine-needle aspiration. Oncology. 2017;93 Suppl 1:107–12. 10. Cappelli C, Pirola I, Agosti B, Tironi A, Gandossi E, Incardona P, et al. Complications after fine-needle aspiration cytology: a retrospective study of 7449 consecutive thyroid nodules. Br J Oral Maxillofac Surg. 2017;55(3):266–9.