recurrent epithelial ovarian carcinoma has a poor prognosis and is almost always fatal [ 1 , 2 ] .
the most frequent relapse site involves the peritoneal cavity and the infradiaphragmatic lymph nodes . outside the abdomen ,
the most frequent metastatic sites are the pleura and the mediastinal lymph nodes [ 3 , 4 ] .
although nodal metastases are well known in the course of epithelial ovarian carcinoma , solitary lymph node relapses are rarely described . the cervical , supraclavicular , groin and axillary areas are unusual sites of isolated lymph node involvement . in a retrospective study evaluating 640 ovarian cancer patients ,
prognosis of isolated lymph node relapse seems better than that of metastatic recurrence at other sites and in the event of an asymptomatic relapse , immediate or delayed therapy should be assessed .
recurrence of ovarian carcinoma is commonly suspected when there is a progressive increase of the serum ca-125 level , but it does not allow differentiation between localized and diffuse tumor spread .
ct scan is the imaging technique of choice , but its capability to detect residual tumor is limited in case of small metastases , such as peritoneal , mesenteric and omental recurrences .
f - fdg - pet can detect residual tumor with a higher accuracy than ct and even with a higher sensitivity than the tumor markers ca-125 [ 7 , 8 ] .
recently , we have observed internal mammary lymph node metastases diagnosed by f - fdg - pet / ct as a solitary recurrence site in 3 ovarian cancer patients .
a 65-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy , pelvic lymphadenectomy and omentectomy followed by chemotherapy ( carboplatin and cyclophosphamide ) for ovarian papillary serous adenocarcinoma stage ic in 1997 . at her annual followup , 9 years later ( may 2006 ) , the serum ca-125 level was increased ( 83 u / ml , normal value < 35 u / ml ) .
a pet / ct scan showed increased f - fdg uptakes in the bilateral internal mammary lymph nodes ( fig .
1a , b ) , with suspected infiltration of the right side of the sternum ( fig .
a ct scan confirmed an abnormal left internal mammary lymph node of 1.7 cm in size and a thickening of the right parasternal tissue .
she was treated with 7 courses of chemotherapy ( carboplatin plus gemcitabine ) . at the end of the treatment ,
the serum ca-125 level was stable ( 75 u / ml ) and a ct scan confirmed stable disease .
external radiation therapy was administered to the bilateral internal mammary lymph node chains at a total dose of 4,680 cgy .
pet / tc was performed 4 months after the end of the radiation therapy and showed a reduction of the f - fdg uptake in the right internal mammary lymph node ( suv max .
6 vs. 11 ) and a complete normalization in the contralateral lymph node . in november 2007
, she was retreated with chemotherapy ( 6 courses of carboplatin ) for disease progression in the internal mammary lymph nodes and the sternum . in july 2008
, she developed 2 subcentimetric brain metastases that were treated with stereotaxic radiosurgery , obtaining a complete remission . in september 2008 , an increase of the serum ca-125 level occurred ( 265 u / ml ) and the ffdg - pet / ct scan showed multiple pathological uptakes in the supradiaphragmatic lymph nodes ( bilateral supraclavicular , internal mammary chains and mediastinal ) .
she was treated with 6 courses of carboplatin + paclitaxel and the serum ca-125 level was normalized . during 2010 ,
disease progression was further documented and monochemotherapy with pegylated doxorubicin was started . on december 31 , 2010 , she was still on treatment .
a 47-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and lombo - aortic lymphadenectomy followed by chemotherapy ( cisplatin and cyclophosphamide ) for ovarian papillary serous carcinoma stage iii in 1991 .
subsequently , she first received anterior sigmoid resection for pelvic relapse and adjuvant carboplatin ( 1996 ) , and secondly , chemotherapy with cisplatin + paclitaxel , followed by liver dissections for liver metastases and carboplatin + topotecan chemotherapy ( 1998 ) . during these treatments
, there was no evidence of disease . in 2001 , at a follow - up examination , a right supraclavicular lymph node was palpable . in absence of other signs of localizations ,
the patient experienced partial remission and subsequently , she was submitted for dissection of the right supraclavicular lymph node .
radiation therapy was delivered postoperatively . in december 2002 , a pet / ct carried out during a follow - up examination , showed an increased f - fdg uptake in a left internal mammary lymph node ( fig .
she was operated on and a lymph node metastasis was removed and histologically confirmed ( poorly differentiated adenocarcinoma ) .
no postoperative treatment was administered . in january 2006 , a pet / ct showed an increased f - fdg uptake in 3 supradiaphragmatic nodules located in the right anterior costophrenic sinus .
she was treated with supradiaphragmatic lymphadenectomy and partial diaphragm resection ; 3 out of 14 lymph nodes were massively infiltrated by a poorly differentiated adenocarcinoma of ovarian origin . at the last follow - up examination ( december 2010 ) ,
almost 5 years later , the patient was well and showed no evidence of disease .
a 51-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and omentectomy , followed by chemotherapy ( carboplatin and paclitaxel ) for ovarian papillary serous carcinoma stage iiib in 2002 . at her annual follow - up ,
6 years later , the serum ca-125 level showed an increase above the normal level ( > 35 u / ml ) . a pet / ct scan revealed an increased ffdg uptake in the right internal mammary lymph nodes and the cardiophrenic nodule .
thus , 1 month later , she was submitted for right internal mammarian lymphoadenectomy ; the histological examination confirmed a papillary adenocarcinoma .
from april to july 2009 , she was treated with 6 courses of carboplatin and paclitaxel .
the serum ca-125 level was within the normal range . at the last follow - up visit , in september 2010 , she was well and showed no signs of recurrent disease .
a 65-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy , pelvic lymphadenectomy and omentectomy followed by chemotherapy ( carboplatin and cyclophosphamide ) for ovarian papillary serous adenocarcinoma stage ic in 1997 . at her annual followup , 9 years later ( may 2006 ) , the serum ca-125 level was increased ( 83 u / ml , normal value < 35 u / ml ) .
a pet / ct scan showed increased f - fdg uptakes in the bilateral internal mammary lymph nodes ( fig .
1a , b ) , with suspected infiltration of the right side of the sternum ( fig .
a ct scan confirmed an abnormal left internal mammary lymph node of 1.7 cm in size and a thickening of the right parasternal tissue .
she was treated with 7 courses of chemotherapy ( carboplatin plus gemcitabine ) . at the end of the treatment ,
the serum ca-125 level was stable ( 75 u / ml ) and a ct scan confirmed stable disease .
external radiation therapy was administered to the bilateral internal mammary lymph node chains at a total dose of 4,680 cgy .
pet / tc was performed 4 months after the end of the radiation therapy and showed a reduction of the f - fdg uptake in the right internal mammary lymph node ( suv max .
6 vs. 11 ) and a complete normalization in the contralateral lymph node . in november 2007
, she was retreated with chemotherapy ( 6 courses of carboplatin ) for disease progression in the internal mammary lymph nodes and the sternum . in july 2008
, she developed 2 subcentimetric brain metastases that were treated with stereotaxic radiosurgery , obtaining a complete remission . in september 2008 , an increase of the serum ca-125 level occurred ( 265 u / ml ) and the ffdg - pet / ct scan showed multiple pathological uptakes in the supradiaphragmatic lymph nodes ( bilateral supraclavicular , internal mammary chains and mediastinal ) .
she was treated with 6 courses of carboplatin + paclitaxel and the serum ca-125 level was normalized . during 2010 ,
disease progression was further documented and monochemotherapy with pegylated doxorubicin was started . on december 31 , 2010 , she was still on treatment .
a 47-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and lombo - aortic lymphadenectomy followed by chemotherapy ( cisplatin and cyclophosphamide ) for ovarian papillary serous carcinoma stage iii in 1991 .
subsequently , she first received anterior sigmoid resection for pelvic relapse and adjuvant carboplatin ( 1996 ) , and secondly , chemotherapy with cisplatin + paclitaxel , followed by liver dissections for liver metastases and carboplatin + topotecan chemotherapy ( 1998 ) . during these treatments
, there was no evidence of disease . in 2001 , at a follow - up examination , a right supraclavicular lymph node was palpable .
in absence of other signs of localizations , she was treated with gemcitabine + vinorelbine over a 4-month period .
the patient experienced partial remission and subsequently , she was submitted for dissection of the right supraclavicular lymph node .
radiation therapy was delivered postoperatively . in december 2002 , a pet / ct carried out during a follow - up examination , showed an increased f - fdg uptake in a left internal mammary lymph node ( fig .
she was operated on and a lymph node metastasis was removed and histologically confirmed ( poorly differentiated adenocarcinoma ) .
no postoperative treatment was administered . in january 2006 , a pet / ct showed an increased f - fdg uptake in 3 supradiaphragmatic nodules located in the right anterior costophrenic sinus .
she was treated with supradiaphragmatic lymphadenectomy and partial diaphragm resection ; 3 out of 14 lymph nodes were massively infiltrated by a poorly differentiated adenocarcinoma of ovarian origin . at the last follow - up examination ( december 2010 ) ,
almost 5 years later , the patient was well and showed no evidence of disease .
a 51-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and omentectomy , followed by chemotherapy ( carboplatin and paclitaxel ) for ovarian papillary serous carcinoma stage iiib in 2002 . at her annual follow - up ,
6 years later , the serum ca-125 level showed an increase above the normal level ( > 35 u / ml ) . a pet / ct scan revealed an increased ffdg uptake in the right internal mammary lymph nodes and the cardiophrenic nodule .
thus , 1 month later , she was submitted for right internal mammarian lymphoadenectomy ; the histological examination confirmed a papillary adenocarcinoma .
from april to july 2009 , she was treated with 6 courses of carboplatin and paclitaxel .
the serum ca-125 level was within the normal range . at the last follow - up visit , in september 2010 , she was well and showed no signs of recurrent disease .
we have been unsuccessful in finding reports on internal mammary lymph nodes metastases from ovarian cancer in the recent literature . in this case report , we have presented 3 cases of recurrent ovarian cancer in which pet / ct detected internal mammary lymph node metastases as unique site of disease , 6 , 9 and 11 years after the primary surgical operation , respectively . in the first and third case ,
pet / ct confirmed the recurrence suspected by the increase of the serum ca-125 level ; in the second case , pet / ct was carried out as a follow - up examination in absence of symptoms or increased serum ca-125 levels . in these 3 patients ,
the pet / ct scan has enabled a local therapeutic approach : a surgical treatment in two patients and radiation therapy in 1 patient , permitting a local control of the disease . at , respectively , 4.5 , 8 and 2 years after the diagnosis of internal mammary lymph node metastases our patients are still alive .
to our knowledge , this is the first report on internal mammary lymph nodes as a site of late and very late solitary ovarian cancer recurrence and on the determining role of pet / ct scan for the diagnosis of isolated tumor involvement and therapeutic decisionmaking . surgical dissection or radical radiotherapy
 internal mammary lymph nodes as solitary site of recurrent ovarian cancer have not been previously described . in this case report , 
 3 cases of late and very late isolated recurrence in internal mammary lymph nodes are presented . 
 18f - fdg - pet / ct allowed the diagnosis which was suspected by the increase of the serum ca-125 level in 2 out of 3 cases . 
 local treatment , consisting of surgery ( in 2 patients ) and radiation therapy ( in 1 patient ) , permitted an optimal long - term disease control . 