Spread of ovarian carcinoma via lymphatic dissemination

Issue: June 10, 2011

ByMunir Ghesani, MD, FACNM

ByGabriel Sara, MD

ByAmit Patel, MD

A 65-year-old woman with a past medical history significant for depression and anxiety disorder presented in 1991 with abdominal distension and increasing girth. Imaging studies revealed bilateral ovarian masses, and she underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy and debulking surgery for a stage IIb ovarian epithelial cell carcinoma.

Adjuvant chemotherapy with carboplatin and cyclophosphamide was given for a total of six cycles. Her disease remained indolent, and she was monitored with surveillance scans and blood work. In 1998, she was found to have an isolated relapse in the spleen. The patient underwent splenectomy. Chemotherapy was not administered after the surgery.

In October 2000, it was noted that her CA-125 started to slowly increase with a negative CT scan. She had no complaints of symptoms. She was again monitored with surveillance scans and blood work. In February 2002, she developed left supraclavicular metastasis as the only site of disease. Treatment with tamoxifen at that time failed. Her lymphadenopathy became painful and enlarged further in early 2003, and she was treated with five cycles of carboplatin and paclitaxel with an excellent response.

Figure 1. (Clockwise from top left – CT image, PET image, whole body maximum intensity projection PET image, CT/PET fusion image). There is progression of lymphadenopathy in the left supraclavicular station (arrow 1).

Photos courtesy of M. Ghesani

She had recurrence of the supraclavicular lymph nodes in December 2005 and received seven doses of doxorubicin. She had a good partial response, but treatment was stopped because of severe skin toxicity. She then received docetaxel/cisplatinum, resulting in a marked decrease in the size of her neck nodes to less than 1 cm and a drop in the CA-125 from 170 in November 2006 to 19 on January 2007.

Her left neck/supraclavicular lymphadenopathy, again, became enlarged and symptomatic with pain. She completed a course of RT to the left neck/supraclavicular area with slow regrowth during 13 months, subsequently. At that time, chemotherapy was restarted with cisplatin and cyclophosphamide in April 2010. She received two cycles in that month, 21 days apart. The third cycle, given in May, was interrupted because of platinum allergic reaction. Repeat CT scan of the neck and the physical examination showed no change in her neck nodes.

She received gemcitabine hydrochloride from June to October. She did not tolerate treatment well, showing abnormal liver function tests and significant fatigue. She did not respond to chemotherapy, and bulky disease progressed in the left neck. Salvage chemotherapy with weekly vinorelbine started last month.

CT/PET fusion image
Figure 2. Display convention, same as Figure 1. There is progression of lymphadenopathy in the left tracheoesophageal groove (arrow 2).

Discussion

Ovarian cancer is one of the most treatable solid tumors; most patients will respond temporarily to surgery and cytotoxic agents. The disease, however, frequently persists and recurs, having the highest fatality-to-case ratio of all the gynecologic cancers. Ovarian cancer represents one-fourth of the malignancies of the female genital tract, but it is the most common cause of death among women who develop cancers of gynecologic origin. Ovarian carcinomas account for 4% of the total cancers in women in the US, ranked behind malignant neoplasms of the lung, breast, colon and uterus. Annually in the US, approximately 21,550 new cases are diagnosed and 14,600 ovarian cancer-related deaths occur. Despite discouraging statistics, improvement in 5-year survival has occurred steadily during the past 3 decades because of more aggressive surgical management and the development of more effective chemotherapy. Five-year survival in the US has improved significantly, from 37% in 1974-1976 to 52% in 1992-1998.

Ovarian carcinoma can spread by local extension, lymphatic invasion, intraperitoneal implantation, hematogenous dissemination and transdiaphragmatic passage. Intraperitoneal dissemination is the most common and recognized characteristic of ovarian cancer. In contrast, hematogenous spread is clinically unusual early on in the disease process, although it is not infrequent in patients with advanced disease. It has been demonstrated that the earliest mode of spread is by exfoliation of cells that implant along the surfaces of the peritoneal cavity. The cells follow the circulatory path of peritoneal fluid, often moving with the forces of respiration from the pelvis, up the paracolic gutters (especially on the right), along the intestinal mesentery, to the right hemidiaphragm. These implanted cells give rise to metastatic foci in the posterior cul-de-sac, the paracolic gutters, on the diaphragmatic surface, the liver capsule, the surface of the intestines, and the omentum. This progressively agglutinates loops of bowel, leading to functional intestinal obstruction, or carcinomatous ileus.

CT/PET fusion image
Figure 3. Display convention, same as Figure 1. New metabolic lymphadenopathy in the left periparotid region (arrow 3); suspicious for metastatic ovarian carcinoma. Note that metastatic disease is limited to the left neck. There was no evidence of metastatic disease in the lungs, abdomen, pelvis or skeleton.

Lymphatic dissemination to the pelvic and para-aortic lymph nodes is most common, particularly in advanced disease. Spread through the lymphatic channels of the retroperitoneal lymph nodes and the diaphragm can lead to dissemination of disease into the supraclavicular lymph nodes and pleural space. Apparent stage I and II tumors have retroperitoneal lymphatic dissemination in about 5% to 10% in most series, whereas lymphatic dissemination in stage III has been reported to be as high as 42% to 78% in carefully explored patients. Most of these lymph nodes are not enlarged but are microscopically positive for malignant cells. Spread through the retroperitoneal and diaphragmatic lymphatics can result in metastasis to the supraclavicular lymph nodes. Hematogenous dissemination at the time of diagnosis is uncommon, with only a small percent of patients who are found to have parenchymal involvement of the lungs or liver. Brain metastases are extremely rare.

Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center, and Beth Israel Medical Center and a HemOnc Today section editor. He is an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons.

Amit Patel, MD, is a fellow in oncology at St. Luke’s-Roosevelt Hospital.

Gabriel Sara, MD, is an oncology attending at St. Luke’s-Roosevelt Hospital.

For more information:

Burghardt E. Am J Obstet Gynecol. 1986;155:315-319.

Cannistra SA. N Engl J Med. 2004;351:2519-2529.

Chen SS. Gynecol Oncol. 1983;16:95-100.

Dauplat J. Cancer. 1987;60:1561-1566.

Jemal A. CA Cancer J Clin. 2009;59:225-249.