the american cancer society has estimated 22,280 new cases of ovarian cancer and 14,240 deaths in 2016 ( siegel et al . , 2016 ) .
amongst the types of ovarian cancer , epithelial ovarian carcinoma represents greater than 90% of cases .
has helped stratify two different subsets of disease ( malpica et al . , 2004 ) .
greater than eighty - percent of serous adenocarcinomas of the ovary are high - grade lesions with numerous mitotic figures and high - grade nuclei .
low - grade histology constitutes the remaining cases and is typically diagnosed at earlier stages .
furthermore , they have an indolent disease course with a series of stepwise mutations from borderline tumors with low malignant potential progressing to a well - differentiated carcinoma ( vang et al . , 2009 ) .
high - grade serous carcinomas , on the other hand , are genetically unstable leading to rapid progression and diagnosis at advanced stages .
modalities of serous ovarian cancer metastases are direct tumor invasion into the peritoneal cavity followed by lymphatic and hematogenous spread .
malignant pleural effusions and intraparenchymal liver metastases are the most common sites that upstage the disease ( bonnefoi et al . , 1999 ) .
cardiophrenic lymph node ( cpln ) metastases also upstage the disease to iv - b .
references six total case reports describing mediastinal metastases from high - grade carcinoma ( mayadagli et al . , 2012 ) .
there are currently no case reports that document cpln metastases in low - grade serous carcinomas or borderline tumors . when noted on computed tomography ( ct ) imaging , surgical planning can accommodate resection of cardiophrenic lymph nodes by either gynecologic oncology or cardiothoracic surgery to help achieve complete cytoreduction .
currently , an abdominal ct and a chest x - ray are used to assess for thoracic and pleural metastases . a study done by hynninen et al . found that preoperative f - fluorodeoxyglucose ( fdg ) positron emission tomography / computed tomography ( pet / ct ) diagnosed cpln metastases in 67% of advanced stage epithelial ovarian cancer patients ( n  =  30 ) , which was significantly higher than conventional imaging ( 33% ) ( hynninen et al . , 2012 ) .
whether resection of these cardiophrenic lymph nodes truly results in no residual disease is patient dependent .
a study done in 2007 found that 65% of patients with advanced staged ovarian cancer and moderate to large pleural effusions had macroscopic intrathoracic lesions .
they went on to propose using video - assessed thoracic surgery ( vats ) prior to primary cytoreductive surgery to help stratify patients to neoadjuvant chemotherapy versus a complete cytoreductive operation ( juretzka et al . , 2007 ) .
this raises the importance of appropriate patient selection for cardiophrenic lymph node resection to ensure the benefits outweigh the risks .
the purpose of this report is to describe , to our knowledge , the first two cases of low - grade serous ovarian carcinoma with cardiophrenic lymph node metastasis .
furthermore , by presenting these cases , we strive to improve awareness of this rare disease pattern and optimize surgical cytoreduction in this chemotherapeutic resistant population . a 42  year - old woman presented to her gynecologist with a history of pelvic pressure , bloating , constipation , notable left lower quadrant mass and abnormal uterine bleeding .
transvaginal ultrasound ( tvus ) revealed a uterus measuring 10.8    6.8    5.3  cm with a complex right ovarian mass measuring 11.1    7.4    6.2  cm .
computed tomographic ( ct ) imaging showed a complex cystic right adnexal mass measuring 10.9    8.6    8.5  cm , a complex left ovary measuring 4.7    4.2    3.6  cm , a solid appearing mass in the anterior pelvis measuring 5.4    6.6    7.5  cm , trace ascites , and multiple calcified omental nodules .
she underwent a robotically assisted - total laparoscopic hysterectomy , bilateral salpingo - oophorectomy , omentectomy , appendectomy , and peritoneal biopsies and washings at an outside hospital in august of 2014 .
intra - operative frozen section revealed a mucinous borderline tumor with no area of invasive disease however final pathology showed a mixed mucinous and grade i serous papillary ovarian adenocarcinoma with involvement of the omentum , anterior pelvic peritoneum , right pelvic sidewall , and right posterior cul - de - sac .
two months after her primary surgery , the patient complained of diffuse upper abdominal discomfort .
repeat ct imaging of her chest , abdomen , and pelvis showed shotty retroperitoneal lymphadenopathy and enlarged right cardiophrenic angle lymph nodes measuring up to 7  mm .
she underwent a second cytoreductive surgery with complete debulking for stage iiic low - grade serous and mucinous ovarian carcinoma .
this included a right diaphragm peritonectomy with resection of 100% of the right diaphragmatic surface area and full - thickness resection of the right diaphragm muscle ( 2    1  cm ) with transdiaphragmatic resection of clinically enlarged four right cardiophrenic lymph nodes .
she also had hyperthermic intraperitoneal chemotherapy with carboplatin at a dose of 800  mg / m at 41 to 42  c for 60  min .
her final pathology was consistent with stage iv - b low grade mixed mucinous and papillary serous histology with 4/4 positive cardiophrenic lymph nodes .
she underwent six cycles of intravenous carboplatin , paclitaxel , and bevacizumab with normalization of her ca-125 .
she continues on maintenance bevacizumab without evidence of recurrent disease radiologically or serologically 27  months after initial diagnosis .
a 53  year - old woman presented to the emergency department with worsening abdominal pain for 6  months associated with nausea and vomiting .
ct imaging of her abdomen / pelvis revealed a large 12.7    13    13.3  cm large lobulated heterogeneous partially calcified pelvic mass encasing the uterus and causing moderate right hydroureteronephrosis , scattered omental , mesenteric , and serosal nodular implants with calcifications suspicious for diffuse carcinomatosis .
a chest ct showed a 7.4  mm cardiophrenic lymph node possibly reactive in nature versus metastasis ( fig .
, she underwent an exploratory laparotomy , type 2 radical oophorectomy , right pelvic and paraaortic lymphadenectomy , total omentectomy , en block distal ileectomy , appendectomy , and resection of cecum and subtotal right colectomy , morison 's pouch peritonectomy , right diaphragm peritonectomy ( 100% surface area ) , transdiaphragmatic resection of right cardiophrenic lymph node with primary closure and transdiaphragmatic evacuation of pneumothorax , nonanatomic wedge resection of the liver segment 6 with associated tumor , resection of round ligament of liver and falciform ligament , resection of anterior abdominal wall tumor and umbilectomy ( 5    2.5  cm segment of the anterior abdominal wall fascia and associated soft tissue ) , takedown of splenic flexure , stapled 33  mm circular end - to - end descending colon to rectum anastomosis , and stapled functional end - to - end ileo to ascending colon anastomosis ( enterocolostomy ) her post - operative course was complicated by a small pulmonary embolism , for which she was treated with lovenox .
her final pathology was consistent with stage iv - b low - grade serous adenocarcinoma of the ovary ( fig .
she completed six cycles of intravenous carboplatin and paclitaxel and is without evidence of disease 6  months after diagnosis .
a 42  year - old woman presented to her gynecologist with a history of pelvic pressure , bloating , constipation , notable left lower quadrant mass and abnormal uterine bleeding .
transvaginal ultrasound ( tvus ) revealed a uterus measuring 10.8    6.8    5.3  cm with a complex right ovarian mass measuring 11.1    7.4    6.2  cm .
computed tomographic ( ct ) imaging showed a complex cystic right adnexal mass measuring 10.9    8.6    8.5  cm , a complex left ovary measuring 4.7    4.2    3.6  cm , a solid appearing mass in the anterior pelvis measuring 5.4    6.6    7.5  cm , trace ascites , and multiple calcified omental nodules .
she underwent a robotically assisted - total laparoscopic hysterectomy , bilateral salpingo - oophorectomy , omentectomy , appendectomy , and peritoneal biopsies and washings at an outside hospital in august of 2014 .
intra - operative frozen section revealed a mucinous borderline tumor with no area of invasive disease however final pathology showed a mixed mucinous and grade i serous papillary ovarian adenocarcinoma with involvement of the omentum , anterior pelvic peritoneum , right pelvic sidewall , and right posterior cul - de - sac .
two months after her primary surgery , the patient complained of diffuse upper abdominal discomfort .
repeat ct imaging of her chest , abdomen , and pelvis showed shotty retroperitoneal lymphadenopathy and enlarged right cardiophrenic angle lymph nodes measuring up to 7  mm .
she underwent a second cytoreductive surgery with complete debulking for stage iiic low - grade serous and mucinous ovarian carcinoma .
this included a right diaphragm peritonectomy with resection of 100% of the right diaphragmatic surface area and full - thickness resection of the right diaphragm muscle ( 2    1  cm ) with transdiaphragmatic resection of clinically enlarged four right cardiophrenic lymph nodes .
she also had hyperthermic intraperitoneal chemotherapy with carboplatin at a dose of 800  mg / m at 41 to 42  c for 60  min .
her final pathology was consistent with stage iv - b low grade mixed mucinous and papillary serous histology with 4/4 positive cardiophrenic lymph nodes .
she underwent six cycles of intravenous carboplatin , paclitaxel , and bevacizumab with normalization of her ca-125 .
she continues on maintenance bevacizumab without evidence of recurrent disease radiologically or serologically 27  months after initial diagnosis .
a 53  year - old woman presented to the emergency department with worsening abdominal pain for 6  months associated with nausea and vomiting .
ct imaging of her abdomen / pelvis revealed a large 12.7    13    13.3  cm large lobulated heterogeneous partially calcified pelvic mass encasing the uterus and causing moderate right hydroureteronephrosis , scattered omental , mesenteric , and serosal nodular implants with calcifications suspicious for diffuse carcinomatosis .
a chest ct showed a 7.4  mm cardiophrenic lymph node possibly reactive in nature versus metastasis ( fig .
, she underwent an exploratory laparotomy , type 2 radical oophorectomy , right pelvic and paraaortic lymphadenectomy , total omentectomy , en block distal ileectomy , appendectomy , and resection of cecum and subtotal right colectomy , morison 's pouch peritonectomy , right diaphragm peritonectomy ( 100% surface area ) , transdiaphragmatic resection of right cardiophrenic lymph node with primary closure and transdiaphragmatic evacuation of pneumothorax , nonanatomic wedge resection of the liver segment 6 with associated tumor , resection of round ligament of liver and falciform ligament , resection of anterior abdominal wall tumor and umbilectomy ( 5    2.5  cm segment of the anterior abdominal wall fascia and associated soft tissue ) , takedown of splenic flexure , stapled 33  mm circular end - to - end descending colon to rectum anastomosis , and stapled functional end - to - end ileo to ascending colon anastomosis ( enterocolostomy ) her post - operative course was complicated by a small pulmonary embolism , for which she was treated with lovenox .
her final pathology was consistent with stage iv - b low - grade serous adenocarcinoma of the ovary ( fig .
she completed six cycles of intravenous carboplatin and paclitaxel and is without evidence of disease 6  months after diagnosis .
they show low - grade serous histology with stage iv - b disease by cardiophrenic lymph node metastasis . from a diagnostic standpoint , being able to recognize this pattern of spread where chemotherapeutic resistance is high , can dictate a more targeted surgical strategy .
identifying these cardiophrenic lymph node metastases gives the surgeon a much higher probability of performing a complete tumor debulking . in 2004 , chi et al .
found that incorporating these invasive upper abdominal and lower mediastinal procedures substantially increases the rate of successful cytoreduction ( chi et al . , 2004 ) .
their follow up study in 2010 showed that of the common postoperative complications seen ( pleural effusion , pancreatic leak , intra - abdominal fluid collection ) , two - thirds of them were managed with percutaneous drainage of fluid collections .
overall , there was a 22% rate of major morbidity and 1.4% rate of mortality that was seems acceptable ( chi et al . , 2010 ) .
there is a paucity of data evaluating the prognostic impact of cardiophrenic lymph node metastasis in epithelial ovarian cancer .
genetic and molecular profiling can also be a helpful tool in finding optimal chemotherapeutic agents in low - grade disease , as some evidence suggests a higher likelihood of resistance to standard platinum - taxane based therapy .
evidence suggests high resistance to platinum and taxane based chemotherapeutic agents though they do remain first line with close surveillance . in the setting of persistent disease ,
given higher estrogen and progesterone receptor expression in low - grade disease , hormonal therapy is a reasonable option . whether thoracic surgery influences the chemotherapeutic regimen is unknown . in conclusion , cardiophrenic lymph node metastasis ,
defining stage iv - b ovarian cancer , is extremely rare in low - grade serous ovarian carcinoma .
we have presented two cases that bring to light the importance of pre - operative imaging and astute physician awareness to this unique disease pattern . given high chemotherapy resistance , surgical cytoreduction for patients with low - grade serous carcinoma will remain the mainstay of treatment . by improving awareness of this topic ,
the authors whose names are listed on this manuscript have no affiliations with or involvement in any organization or entity with any financial interest ( such as honoraria ; educational grants ; participation in speakers ' bureaus ; membership , employment , consultancies , stock ownership , or other equity interest ; and expert testimony or patent - licensing arrangements ) , or non - financial interest ( such as personal or professional relationships , affiliations , knowledge or beliefs ) in the subject matter or materials discussed in this manuscript .
 highlightscardiophrenic lymph node metastasis in low - grade ovarian carcinoma is rare.two cases presented here identify clinical strategies needing further attention.low-grade disease is treated with surgery given high chemotherapeutic resistance.preoperative awareness of lymph node metastasis allows for optimal debulking.identifying radiologic evidence of distant metastasis improves patient outcomes . 