Ovarian cancer metastasis to axillary node without breast involvement: a rare case

Abstract

Background

Ovarian cancer is the most lethal gynaecological cancer globally. Despite advanced multimodality treatment 5year survival is around 50% and its only 31% in stage IV cancers. There is no clearly defined precursor lesion. The events which led to metastasis is not clearly understood. Epithelial ovarian cancers (EOC) are the most common type of ovarian malignancy. Stage IV ovarian cancer incidence are raising day by day. Peritoneum is the most common site of recurrence followed by nodes and intra-abdominal metastasis. Distant metastasis outside abdomen is rare. Moreover, ovarian cancer with metastasis to axillary lymph node is very rare presentation specially when breast is not involved.

Case presentation

We like to report a case of 54year old lady, who was admitted with persistent Right axillary lymph nodal mass. She had a history of High grade serous ovarian cancer stage IVB which was detected and treated 3 years back with neoadjuvant chemo followed by interval cytoreductive surgery followed by Adjuvant multiple line of chemo and maintenance bevacizumab. During follow up, patient had increased Ca-125, and PET CT suggestive of persisting right axillary LN with retroperitoneal LN and right external iliac node. The axillary node was biopsied and found to be metastatic High-grade Serous Ovarian Carcinoma, but mammography showed no abnormality in bilateral breasts. Patient received 2nd line chemotherapy. Secondary Cytoreductive Surgery and HIPEC (cisplatin) and Right Level I ALND done in Department of Surgical Oncology AIIMS, New Delhi. Intraoperatively 3 × 3 cm Right axillary level I single node found. Excision of metastatic axillary node shows excellent result.

Conclusion

This case highlights the importance of meticulous evaluation of patient presenting with axillary lymphadenopathy to rule out possibility of ovarian cancer. Additionally, axilla should also be considered as a possible site of metastasis in a known case of carcinoma ovary for effective treatment planning.

Background

Ovarian Cancer is second most common Gynaecological malignancy worldwide and most common cause of mortality among Gynaecological malignancy in resource abundant countries [1]. Ovarian cancer is sixth leading cause of cancer death in female [2]. Lifetime risk of developing it is 1.3%. 5 year survival of localised Epithelial Ovarian Cancer (EOC) 93%, for Regional cancer is 75%, for Distant metastasis is 31% and for combined stage is 50% [3]. EOC is diagnosed mainly in advanced stages. 70% patients are diagnosed in FIGO stage IIIC or stage IV [4]. The incidence of FIGO stage IV ovarian cancer raised over the past decades, being reported as 12.7% in the nineties, over 15.4% around the turn of the millennium and up to 28.3% between 2005–2011 [4]. Autopsy series showed distant or visceral metastases in clinical stage I&II in up to two-thirds of the cases [5]. The commonest sites of extra-peritoneal disease for stage FIGO IV are malignant pleural effusion in 33–53%, liver in 14–26%, subcutaneous/abdominal wall metastasis in 10–41%, and extra-abdominal lymph nodal metastasis in 5–44% [6], brain metastases (0.3–2.2%)and bone metastases(< 2%)are uncommon [4]. After Multimodality treatment recurrence noted around 20% of stage I, IIA patients and 62.1% of stage IIB-IV patients. In advanced diseased group peritoneal metastasis is the most common site, involved in 75% patients at recurrence and 30% are only confined to peritoneum. Nodal metastasis at recurrence seen at 38% patients and 13% are only confined to nodes. Distant metastasis (Other than Supradiaphragmatic nodes) observed in 47% and only confined to Distant metastasis seen in 8% patients [7]. Isolated Axillary LN metastasis without involvement of breast is rare presentation in ovarian cancer.

Case presentation

54Year Old lady, known hypertensive, para 2, with family history of carcinoma breast and carcinoma Ovary, with no history of substance abuse, was diagnosed with carcinoma ovary in April 2022. Patient evaluated with Ca125, PET-CT. On PET CT there were bilateral FDG avid adnexal cystic mass with septations, bilateral FDG avid external iliac nodes, omental and mesenteric and peritoneal FDG small deposits and sub-centimetric retroperitoneal nodes, and right axillary avid 2.4 × 1.2 cm node. Ca 125 was 2563 on diagnosis. Initially, patient received neo-adjuvant Chemotherapy (Carboplatin & Paclitaxel) followed by Interval Cytoreductive Surgery (TAH + BSO + bilateral Pelvic LN dissection + Omentectomy) in July 2022 followed by Adjuvant Chemotherapy (Carboplatin & Paclitaxel) since September 2022. Patient received maintenance Bevacizumab. Patient was detected with borderline increased ca. 125 after completion of Adjuvant chemotherapy, since December 2022. During maintenance Bevacizumab, Ca 125 was between 90 and 120 range. And PET-CT suggested persistent uptake in Sub centimetric Retroperitoneal nodes and Right Axillary nodes. Patient treated with 2nd line chemotherapy (Lipo-dox). Right Axillary LN biopsy done for evaluation of persisting Lymphadenopathy. On HPE it was metastatic High Grade Serous Ovarian Carcinoma. Genetic test for BRCA-1/BRCA-2 carrier status was reported negative. Mammogram showed no breast lesion but 1.76 cm right level I axillary Lymph-nodal mass. Further, patient received multiple lines of chemotherapy with Oral Etoposide, Cyclophosphamide and Pazopanib.

Patient presented to our Department of Surgical oncology, AIIMS, New Delhi for Surgical Management of persistent disease. Patient treated with Secondary Cytoreductive Surgery (Bilateral PLND + Retroperitoneal LN dissection + Umbilical nodule excision + Pelvic Peritonectomy) with HIPEC (cisplatin) and Right Level I axillary LN dissection on 07th April 2025.

Intraoperatively, multiple enlarged hard nodes, largest around 2 × 2 cm were seen in bilateral Pelvic nodal region, multiple enlarged Retroperitoneal nodes were seen, largest 2 × 2 cm in inter-aortocaval region, multiple presacral nodes were enlarged, single 2 × 2 cm umbilical nodule in the parietal peritoneum was seen. PCI 2/39. In Right axilla 3 × 3 cm large node was present in level 1. CC-0 was achieved in this Cyto-reductive surgery. Cisplatin 75 mg/Square meter BSA for 60 min at 42 ° c done in HIPEC. Patient was discharged uneventfully.

Discussion

Ovarian Cancer is second most common Gynaecological malignancy worldwide and most common cause of mortality among Gynaecological malignancy in resource abundant countries. Mostly, (> 75%) patients present with advanced disease stage III and above.

Majority of ovarian malignancies are epithelial types. High-grade serous ovarian carcinomas are most common type among epithelial ovarian cancers, other subtypes of epithelial ovarian cancers are low grade serous, mucinous, clear cell type, endometroid type. 75% Among all epithelial cancers are serous type. Origin of serous, clear cell type, endometroid type epithelial cancers are from tissue not normally present in ovary, such as the fallopian tube, mullerian inclusion cyst, endometriosis, endo-salpingiosis. The origin of mucinous epithelial cancer is not known.

It commonly spreads intraperitoneally, while local invasion, hematogenous and lymphatic invasions are less common. Most common sites of metastasis is liver, colon, spleen, lung, pleura and very rarely to CNS, bone, skin, breast. Most common site of LN metastasis is in abdomen − 47% to para aortic nodes, 29% to mediastinal nodes and 17% to pelvic nodes [8].

Axillary LNs metastasis from ovarian cancers are often present with breast metastasis and only occasionally seen without involvement of breast. Serous ovarian cancer is the most common type of ovarian cancer to metastasise to the breast [9]. In a case of axillary LN metastasis without breast involvement our first suspect is occult primary breast cancer and thus role of IHC and PET CT comes in. However isolated axillary LN metastasis without breast involvement were reported in only few case reports [10] and all those reports include patients with Stage III and IV serous Ovarian cancer. In one case report the ovarian cancer was grade 2 endometroid carcinoma [11].

The goal is detection and treatment of advanced disease at earliest. Cure rates of this disease are double for patients in whom optimal cytoreduction (< 1 cm gross residual disease following surgery) was performed, compared to those who did not have optimal cytoreduction (30–40% vs. 15–20%) [12]. The standard treatment for ca. ovary is with Cytoreductive surgery and Platinum based chemotherapy. Bevacizumab for maintenance therapy may be used. Despite initial therapy, majority (>70%) of patients with advanced cancer relapses and requires additional treatment.

After multimodality treatment recurrence noted around 20% of stage I, IIA patients and 62.1% of stage IIB-IV patients. In advanced diseased group peritoneal metastasis is the most common site, involved in 75% patients at recurrence and 30% are only confined to peritoneum. Nodal metastasis at recurrence seen at 38% patients and 13% are only confined to nodes. Distant metastasis (Other than Supradiaphragmatic nodes) observed in 47% and only confined to Distant metastasis seen in 8% patients [7].

In our case, Patient from initial presentation had Cancer ovary Stage IV disease with Right axillary level I LN metastasis (Size – 2.4 × 1.2 cm) of but not evaluated and only received treatment for carcinoma ovary with Platinum based neoadjuvant chemotherapy followed by cyto-reductive surgery followed by adjuvant platinum-based chemotherapy followed by maintenance bevacizumab. After Biochemical recurrence patient evaluated with PET and found to have persistent FDG uptake in Right axillary LN (size- 3 × 1.8 cm) along with Right pelvic and Retroperitoneal nodes without any peritoneal disease as shown in Fig. 1. Patient evaluated with Biopsy of right axillary nodes which was positive for high grade serous ovarian cancer and Mammogram showed no abnormalities in bilateral breasts. Genetic test for BRCA 1/BRCA 2 carrier status was negative. Patient received further line of Second line chemotherapy with lipo-dox. Patient treated with secondary CRS and HIPEC with Right level I axillary LN dissection.

Fig. 1.

PET image showing avid right axillary lymph node

Axillary nodal metastasis can mimic primary breast cancer metastasis specially when breast is also involved. Cases where there is axillary nodal metastasis without breast involvement in a ca. ovary or cases where Carcinoma of unknown primary presented with axillary metastasis, role of radiological breast evaluation (with mammography or MRI) and HPE with IHC plays important role. In our case the Right axillary LN biopsy is reported as high grade serous ovarian carcinoma and it is positive for PAX-8 and WT1 and immune-expression of p53 is mutant (where, breast Primary are usually positive for GATA-3 expression) as shown in Fig. 2.

Fig. 2.

a, b Hematoxylin and Eosin stained image on HPE showing axillary nodal metastasis. c, d Axillary nodal metastasis on IHC showing positivity for PAX8 and WT1

In a systematic review paper by Koufopoulos et al. [13], they reviewed 21 articles reporting total 25 patients. 13 patients have axillary LN metastasis at the presentation where 12 patients presented with axillary LN metastasis during recurrence. The cancer was serous ovarian carcinoma in 24 out of 25 cases. They showed no significant difference in survival between two groups (Axillary LN metastasis at initial presentation vs. at recurrence). The sole difference was the higher CA-125 level in the cases that present as initial diagnosis.

Conclusion

Ovarian cancer with metastasis to axillary LN is very rare presentation specially when breast is not involved by metastasis. Second primary breast cancer is to be ruled out by biopsy and imaging with mammography or MRI of breast. Tissue diagnosis with IHC for confirmation, followed by “excision of metastatic axillary lymph nodal mass” along with multidisciplinary management of carcinoma ovary may be a curative option.

This case highlights the importance of meticulous evaluation of patient presenting with axillary lymphadenopathy to rule out possibility of ovarian cancer. Additionally, axilla should also be considered as a possible site of metastasis in a known case of ca. ovary for effective treatment planning.

Abbreviations

EOC

Epithelial Ovarian Cancer

FIGO

International Federation of Gynecology and Obstetrics

LN

Lymph Node

PET

Positron Emission Tomography

CT

Computed Tomography

FDG

Fluorodeoxyglucose

cm

Centimeter

PLND

Pelvic lymph node dissection

TAH

Total Abdominal Hysterectomy

BSO

Bilateral salpingo-oopherectomy

Lipo

Dox-Liposomal Doxorubicin

HIPEC

Hyperthermic Intraperitoneal Chemotherapy

PCI

Peritoneal Cancer Index

CC

Completeness of Cytoreduction

mg

Milligram

BSA

Body surface area

CNS

Central Nervous System

IHC

Immunohistochemistry

CRS

Cytoreductive Surgery

MRI

Magnetic Resonance Imaging

HPE

Histopathological Examination

BRCA

Breast cancer gene

Authors’ contributions

Dr. Shaon Das and Dr. M. D. Ray have written the main manuscript text.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

Not applicable.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient’s relative for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare no competing interests.