Uncommon Hematogenous Metastasis: Orbital Involvement in Uterine Cervical Cancer

Background

Uterine cervical cancer (UCC) is the fourth leading cause of cancer in women after breast, lung, and colorectal cancer [1]. UCC often presents as squamous cell carcinomas that arise from infection with human papillomavirus (HPV) [2], which is easily prevented by HPV vaccination and cervical cancer screening. For locally advanced UCC (FIGO stage IB3, stage II, stage III, and stage IVA), chemoradiation is recommended (weekly cisplatin, 40 mg/m2), followed by radiation therapy (RT) after positron emission tomography-computed tomography (PET-CT) scan for determination of nodal metastases and design of radiation fields [3]. Metastatic UCC is often diagnosed by PET-CT scan. Its treatment depends on metastatic site (local or not), history of RT, age, and general state of health [3]. There are 2 types of metastases related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Hematogenous metastasis is relatively unusual, and most commonly involves the lungs (36.3%), bone (16.3%), and other anatomic locations [4]. Orbital metastasis is rare in patients with UCC. To date, only 23 cases have been reported [5–27]. The present report is of a 70-year-old woman with advanced UCC involving the orbit, which was reduced solely by local RT.

Case Report

A 70-year-old woman receiving dialysis presented to a local hospital due to general fatigue for 5 months. She had not received UCC screening for 30 years, and had not received the HPV vaccine. She was referred to our hospital with a large uterine mass. She had been diagnosed with diabetes mellitus 17 years prior and had been on dialysis for diabetic renal failure a year before. A vaginal speculum examination showed a bulky mass at the site of the cervix with a bad odor (Figure 1A). Magnetic resonance imaging (MRI) showed a mass lesion measuring 12.1×8.9 cm in size in the uterine cervix with infiltration to the parametrium (Figure 1B, 1C). CT scan and PET-CT scan revealed right hydronephrosis and pelvic lymphadenopathy (Figure 1D, 1E). No distant metastasis was detected by PET-CT. Pathological examination revealed squamous cell carcinoma (SCC), and infection with high-risk human papilloma-virus (HR-HPV) (Figure 2A, 2B). HR-HPV includes HPV strains 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. Based on these examinations, we diagnosed the patient with locally advanced UCC. Considering the patient’s renal insufficiency, only RT was performed, for 42 days. A total of 50 Gy in 25 fractions irradiated the whole pelvis using image-guided RT. Boost irradiation (6 Gy in 3 fractions) to the pelvic lymph nodes was performed using the 3-fields technique external beam RT, and 3 fractions of intracavitary brachytherapy of 6 Gy each were performed using a remote afterloading system. At 20 days after RT, dozens of subcutaneous painless masses in the chest were observed, and a biopsy revealed SCC and infection with HR-HPV (Figure 2C, 2D). At 34 days after RT, the patient became aware of right-side loss of vision and exophthalmos, and CT showed a 3.1-cm diameter mass in the right orbital area (Figure 3A–3C). Although it was too difficult to perform a biopsy safely because of the location, it was diagnosed as a metastasis of UCC from the clinical course; that is, almost simultaneous occurrence of the subcutaneous masses and the orbital mass. At 44 days after RT to the pelvis, 2-dimensional RT (total of 30 Gy in 10 fractions) of the right orbital area was performed to reduce the exophthalmos and recover her vision (Figure 4). Starting at 13 days after RT to her right eye, chemotherapy (docetaxel, 70 mg/m2, day 1; and carboplatin, AUC=5, day 1; both repeated every 21 days) was performed for 2 cycles. After RT to her right eye, the orbital tumor shrank (Figure 3D–3F), and the symptoms improved without adverse effect. Regrettably, she died of cancer 7 months after orbital RT and 11 months after diagnosis of UCC. No eye symptoms recurred until her death.

Discussion

UCC is one of the most common cancers among women, and is the fourth most common cancer after breast, colorectal, and lung cancers, in this group. The Global Cancer Observatory (GLOBOCAN) 2020 estimated that, globally, there were approximately 604 000 new cases of UCC, with 342 000 deaths annually [28]. In Japan, the number of both patients and deaths has gradually increased since the 1990s. UCC affects approximately 10 000 people and kills about 2800 women annually [29].

UCC commonly metastasizes to lymph nodes, bones, and lungs. Ocular metastases from UCC are extremely rare. To the best of our knowledge, 23 cases of ocular metastasis from uterine UCC have been reported in the literature [5–27] (Table 1). In these 23 cases, the most common site of ocular metastasis was the orbit (13 cases, 56%), followed by the choroid (6 cases, 26%). Similar to our case, in which ocular metastasis appeared after treatment for UCC, in 16 previous cases (69%) of ocular metastasis, the ocular metastasis appeared after treatment. As in our case, sight loss was the most common symptom of ocular metastasis (11 cases, 47%), and exophthalmos was the third most common symptom (7 cases, 30%). We diagnosed the ocular mass as a case of metastasis without any biopsy. Likewise, 6 previous cases (26%) were diagnosed from the clinical course without biopsy. Pathology results from these cases included 15 cases (65%) of SCC of the cervix. The approach to ocular metastasis from UCC is not standardized, given its rare nature. The treatment is palliative for symptom control and may consist of RT, chemotherapy, and/ or surgery. Among the 23 previous cases, we identified 5 cases similar to our case, in which orbital metastasis was diagnosed after squamous cell cervical cancer diagnosis and treatment [9,13,15,21,24]. Of these, 1 patient received only RT to the orbit, without surgery or chemotherapy. However, the orbital mass nearly doubled in size over the following month [15]. In contrast, 3 patients received RT to the orbit, and improved their ocular symptoms [19,21,24]. Our case and other reports suggest that local orbital radiotherapy may result in a partial or complete response in over half of the patients. Thus, local orbital radiotherapy may be considered for orbital metastasis of UCC. Surgical excision may lead to poor quality of life; however, it can be considered if RT fails to control symptoms.

Conclusions

This report has highlighted that cervical cancer may still present at an advanced stage, particularly in older women, and has described a rare presentation with metastasis to the orbit. In this case, RT to the orbital metastasis from UCC was effective and contributed to the patient’s quality of life.