Ovarian cancer was typically reported in the literature to metastasize to the peritoneal cavity. Notably, other rare sites of metastases had been reported either at the primary diagnosis or during the disease course. These sites included the bone, brain, skin, breast, non-regional lymph nodes, and rare intra-abdominal organs (5). In the present study, we retrospectively reviewed the demographics, disease characteristics, and prognosis of this unique cohort of patients from a single centre.
It is crucial to understand the pattern of distant metastasis from ovarian cancer as this impacts the patient's survival. In their study, Deng et al. analysed the prognostic significance of the site of ovarian cancer distant metastasis. They reported the distant lymph node metastatic site to be associated with better survival than the other sites of distant metastasis including liver, bone, brain, and lungs (6). This was previously reported also by Hjerpe et al. where the median overall survival for patients with non-regional lymph node metastases was significantly higher than the other distant metastasis (41.4 vs 25.2- or 26.8-months) (7). Moreover, ovarian cancer patients suffering from distant lymph node metastases experienced a better prognosis when treated by surgery and chemotherapy (6). In our study, non-regional lymph node metastases were the most reported rare metastatic sites (56.3%) and these patients experienced significantly better overall survival from visceral/skeletal metastasis (estimated median OS 39 vs. 13 months. Moreover, they had significantly higher progression-free survival (estimated median 29 vs. 13 months).
Inguinal nodal metastasis from ovarian carcinoma represented the most common site of rare metastasis in our patients (29.2%). This could be explained by altered lymphatic drainage pathway of the ovaries either through the round ligament, or the gubernaculum or due to surgical excision of the primary pathway to the paraaortic and iliac lymph nodes (8).
Axillary and intramammary nodal metastasis from ovarian cancer is very rare and whenever found represents a diagnostic dilemma. Two pathways could explain the spread of ovarian cancer to axillary nodes through the superior diaphragmatic lymph nodes. The first follows an anterior pathway to the prepericardial nodes then the subclavian lymph trunk ending eventually the axillary lymph nodes, while the other one is posteriorly through inferior diaphragmatic nodes to superficial umbilical lymphatics that end in cisterna chyli that is continuous into the thoracic duct which ends at the junction between the left subclavian and internal jugular veins (9). It should be mentioned that thorough clinical, radiological, and pathological interpretation is crucial to differentiate these patients from primary breast carcinomas with ovarian metastasis (10). In our study, axillary and intramammary nodal metastasis was reported in 7 patients (14.6%), 3 patients presented as a recurrent event through their disease course.
Thanks to the recent advances in imaging technology, the incidence of brain metastasis from ovarian cancer had been reportedly increasing in the recent literature (11). Brain metastasis is more commonly reported with breast and lung carcinomas. On the other hand, the incidence of brain metastasis from ovarian cancer in literature ranged from 0.3–12% (12). Surgery, chemotherapy, and radiation therapy were the most commonly used treatment modalities in these patients (5). In the present study, brain metastasis was the second common (12.5%) after non-regional nodal metastasis. This was reported in 6 patients out of them only one patient was presented with this rare metastatic pattern in her first presentation, while the other 5 patients presented with brain metastasis in the form of recurrence. All patients were managed by chemoradiation while one patient performed surgical resection.
Bone metastasis was rarely reported from ovarian carcinoma. Most of the available evidence from the literature is derived from case reports and retrospective studies. The incidence of ovarian cancer patients who developed bone metastasis ranged from 0.82–3.74% (6, 13). This could be explained by either direct, hematogenous, lymphatic, and transperitoneal spread. The vertebral venous system was thought to be the route of the spread of ovarian cancer to the vertebrae in some studies (13). In our study, bone metastasis was reported in six patients (12.5%), three of them were confined to lumbar vertebrae, while one patient had hip bone metastasis and the other two had multiple sites bone metastasis.
Diagnosis of splenic metastasis is a rare event. Interestingly, splenic metastasis from breast, lung, colorectal carcinoma and melanoma were more commonly reported than from ovarian cancer. Moreover, splenic capsular metastasis was more commonly encountered in ovarian cancer as a part of widespread peritoneal carcinomatosis rather than isolated parenchymal metastasis (14). In the present study, three patients were diagnosed with parenchymal splenic metastasis one of them presented as recurrent. All patients were managed by splenectomy.
The treatment strategy of ovarian cancer patients with rare distant site metastasis is still not standardized. The treatment is mainly individualized per each case within the scope of the multimodal approach aiming at improving the patient's survival. Although previous studies reported a better impact of surgery on patient's survival particularly in patients with non-regional lymph node metastasis (6, 7), we found no survival benefit of surgery among the whole cohort of patients with rare distant metastatic sites of ovarian cancer.
It is worth mentioning that this study had some limitations. The retrospective nature and the small sample size along with the variation in clinical presentation and management of the disease might have affected some of the results. The patients included in this study were managed all over nearly seven years in which some advances and changes in the management protocols might have been achieved.