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DOI:10.2214/AJR.05.1483
AJR 2006; 187:W285-W289
© American Roentgen Ray Society

Case Report

18F-FDG PET/CT in a Patient with Lymph Node Metastasis from Ovarian Adenocarcinoma

Eric Gontier1, Myriam Wartski1, Jean-Marc Guinebretiere2 and Jean-Louis Alberini1

1 Nuclear Medicine Department, Cancer Research Center René Huguenin, 35 rue Dailly, 92210 Saint-Cloud, France.
2 Pathology Department, Cancer Research Center René Huguenin, 92210 Saint-Cloud, France.

Received August 23, 2005; accepted after revision December 19, 2005.

 
Address correspondence to J.-L. Alberini (jl.alberini{at}stcloud-huguenin.org).

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Keywords: calcification • 18F-FDG • lymph node • metastasis • PET/CT • oncologic imaging • ovarian cancer • women's imaging


Introduction
Top
 Introduction
Case Report
 Discussion
 References
 
Ovarian carcinoma is the third most common cancer of the female genital tract. It is the first cause of death from gynecologic malignancy, essentially because most patients present with advanced disease [1]. Serous adenocarcinoma is the most common histologic subtype of epithelial ovarian cancers ({approx} 40%) [2]. Serous adenocarcinoma can contain microcalcifications, mainly in the primary tumor or in peritoneal metastases. More rarely, these calcifications occur in lymph node metastases and can be detected on radiologic imaging. Lymph node metastases must not be confused with old granulomatous disease or calcifications due to previous treatment.

The diagnosis of calcified metastasis of ovarian papillary serous adenocarcinoma can be difficult in the supradiaphragmatic area, where such metastases are unusual. This case illustrates the usefulness of PET/CT using 18F-FDG for the detection of residual viable tumoral tissue in calcified cervical lymph nodes in a woman treated 16 years earlier for a papillary serous ovarian adenocarcinoma and presenting no clinical evidence of infradiaphragmatic tumor recurrence.


Case Report
Top
 Introduction
 Case Report
Discussion
 References
 
A 72-year-old woman had been treated earlier by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy, followed by chemotherapy, for an ovarian papillary serous adenocarcinoma. At her annual follow-up 16 years later, she presented with a palpable lesion in the left inferior cervical area. The tumor marker CA (cancer antigen) 125 was normal. CT did not show any abnormal lesions in the left cervical area but revealed calcified right supraclavicular and inferior internal jugular lymph nodes.

PET/CT was performed using a combined PET/CT system (Discovery LS, GEMS). The acquisition parameters for CT were 140 kVp; 80 mA; reconstructed slice thickness, 5 mm. Imaging was performed 60 minutes after the IV injection of 250 MBq of 18F-FDG. Scanning was performed from the inguinal regions to the neck. Six steps were performed with 5 minutes per step. Attenuation correction was performed using transmission data from CT. This PET/CT showed a mildly increased 18F-FDG uptake in the calcified right inferior internal jugular node (260 H) that was considered to be suspicious for lymph node metastasis (Figs. 1A and 1B). Close follow-up was decided on because of the absence of other clinical or biologic abnormalities. It was decided not to perform biopsy because of the calcified nature of the lymph node, which was considered to indicate a benign origin. The 18F-FDG uptake focus was considered by the clinician to be an inflammatory reaction because of its mild intensity.


Figure 1
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  		Fig. 1A —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. PET scan (anterior view, maximum intensity projection) at presentation shows mildly increased 18F-FDG uptake in right basicervical area (arrow).

 

Figure 2
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  		Fig. 1B —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. From left to right, axial low-dose CT, PET, and fused PET/CT views of neck show mildly increased 18F-FDG uptake (maximum standardized uptake value [SUVmax], 2.3) in calcified right inferior internal jugular node (260 H) (solid arrows), and two other calcified nodes in supraclavicular fossa with no increased uptake (arrowheads and open arrows).

 


Figure 3
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  		Fig. 1C —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. One year later, second PET scan (anterior view, maximum intensity projection) reveals two foci of increased activity in right basicervical and supraclavicular areas (respectively, black and white arrows).

 


Figure 4
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  		Fig. 1D —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. Axial low-dose CT, PET, and fused PET/CT views of neck show increased uptake in inferior internal jugular lymph node (SUVmax, 5.2) associated with more numerous and more intense calcifications (426 H) (solid arrows) than in B. New uptake focus is seen in calcified medial supraclavicular node (SUVmax, 3); increased calcifications (open arrows) are also seen. Calcified lateral supraclavicular node showed no significant increased uptake (arrowheads).

 
One year later, the patient's CA 125 remained normal, but she had a nodule in the right supraclavicular area. A second PET/CT showed an increase of the 18-F-FDG uptake intensity in the right inferior internal jugular lymph node (maximum standardized uptake value [SUVmax]: 5.2 [2.3 previously]) (Fig. 1C), which was associated with more numerous and intense calcifications (426 H) (Fig. 1D). Another 18F-FDG uptake focus was observed that corresponded to a calcified right medial supraclavicular lymph node (Fig. 1C). A calcified right lateral supraclavicular lymph node was seen but it did not take up 18F-FDG (Fig. 1D). These calcified nodes were surgically removed, and histopathologic findings revealed metastatic lymph nodes of a papillary serous adenocarcinoma extending through the capsula and invading adjacent muscles, with numerous psammoma body formations (Figs. 1E and 1F). Positive immunoreactivity for CA 125 was found on immunohistochemistry, indicating an ovarian origin.


Figure 5
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  		Fig. 1E —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. Photomicrograph of specimen from metastatic lymph node shows normal sinus and lymph node structures at right of image. Lesion was associated with multiple psammoma bodies larger than 1 mm (arrow). Tumor cells constituted micropapillary formations. (H and E, x25)

 

Figure 6
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  		Fig. 1F —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. Photomicrograph of specimen from extracapsular extension of basicervical metastatic lymph node shows serous carcinoma with multiple psammomas (arrow) has invaded skeletal muscle (right portion of image). (H and E, x25)

 


Figure 7
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  		Fig. 1G —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. Two years after first PET, three new 18F-FDG foci were found on third PET scan (anterior, maximum intensity projection). Foci were located in right supraclavicular, mediastinal, and pelvic areas (respectively, black arrowhead, black arrow, and white arrow).

 
External radiation therapy was discussed but not administered because of the risk of progression of neurologic side effects after surgery. Another year later, because of a mild increase in the level of CA 125, which was 38 IU (for a cutoff of 35 IU/mL) and the patient's complaints of pelvic pain, PET/CT was performed again. Three additional increased foci of 18F-FDG were shown in the right supraclavicular fossa, the left parasternal area, and the right external iliac area (Figs. 1G, 1H, 1I, and 1J). These foci corresponded to calcified lymph nodes on CT. These lesions were interpreted as a multifocal recurrence of the ovarian papillary serous adenocarcinoma. The patient is still alive 2 years after the third PET/CT examination, after which chemotherapy was administered.


Figure 8
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  		Fig. 1H —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. Axial low-dose CT, PET, and fused PET/CT views of neck, chest, and pelvis reveal three new foci of 18F-FDG uptake: one (SUVmax, 6.4) in lateral right supraclavicular fossa (arrowheads, H), another (SUVmax, 4.3) in left parasternal area (arrows, I), and third (SUVmax, 6.5) in right external iliac area (arrows, J). These foci correspond to calcified lymph nodes on CT. Density values were, respectively, 243, 366, and 404 H.

 

Figure 9
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  		Fig. 1I —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. Axial low-dose CT, PET, and fused PET/CT views of neck, chest, and pelvis reveal three new foci of 18F-FDG uptake: one (SUVmax, 6.4) in lateral right supraclavicular fossa (arrowheads, H), another (SUVmax, 4.3) in left parasternal area (arrows, I), and third (SUVmax, 6.5) in right external iliac area (arrows, J). These foci correspond to calcified lymph nodes on CT. Density values were, respectively, 243, 366, and 404 H.

 

Figure 10
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  		Fig. 1J —72-year-old woman treated 16 years earlier for ovarian papillary serous adenocarcinoma. Axial low-dose CT, PET, and fused PET/CT views of neck, chest, and pelvis reveal three new foci of 18F-FDG uptake: one (SUVmax, 6.4) in lateral right supraclavicular fossa (arrowheads, H), another (SUVmax, 4.3) in left parasternal area (arrows, I), and third (SUVmax, 6.5) in right external iliac area (arrows, J). These foci correspond to calcified lymph nodes on CT. Density values were, respectively, 243, 366, and 404 H.

 


Discussion
Top
 Introduction
 Case Report
 Discussion
References
 
A recurrence of ovarian carcinoma is commonly suspected when there is a progressive increase in the level of serum CA 125, which does not allow differentiation between localized and diffuse tumor spread. CT is the imaging technique of choice, but its capability for detecting residual tumor is limited in cases of small metastases. CT is also limited in differentiating residual malignant lesions from benign postoperative changes with fibrotic tissue.

Several studies have shown that 18F-FDG PET can detect residual tumor in patients suspected of having a recurrence of ovarian carcinoma with or without equivocal CT findings [3, 4]. Because PET using 18F-FDG yields metabolic information, it may be helpful in the differentiation of benign and malignant lesions when morphologic abnormalities are found on CT. The sensitivity of PET is especially greater than that of CT (87% vs 53%, respectively) when recurrence is suspected because of an increasing level of CA 125 [4]. The sensitivity and positive predictive value of PET/CT for lesions larger than 1 cm were, respectively, 83% and 93% in a prospective study of 22 patients suspected of having recurrence because of an increasing CA 125 level but who had normal or equivocal findings on CT [5]. These results were systematically confirmed by histology. However, PET is limited in its ability to detect small lesions (< 8 mm), and the presence of physiologic urinary and colonic 18F-FDG uptake can make analysis of abdominal and pelvic images difficult.

Microcalcifications called "psammoma bodies" are observed in 15-30% of serous adenocarcinoma patients. They can be present in the primary tumor and, more rarely, in metastases [2, 6, 7]. Psammoma bodies are microscopic, concentric, laminated, calcified, and extracellular. The mechanism of their formation remains controversial, but these concentric deposits of apatite always occur in viable tissue. On the contrary, dystrophic calcifications, which are the most frequent cause of calcified nodes, result from the deposition of calcium in damaged or necrotic tissue. Coagulative, caseous, and liquefactive tissue necrosis leads to a localized metabolic disturbance that enhances calcium and phosphate salt precipitations [8]. These dystrophic calcifications usually occur after infection, but they also occur in malignant diseases, where they are induced by radiation therapy or chemotherapy.

The psammoma bodies, which are a specific histologic entity, are commonly encountered in tumors, most often those of thyroid, ovarian (which express a papillary component), or meningeal origin. Less commonly, psammoma bodies can be observed in gastrointestinal tumors such as duodenal carcinoid, gastric, and colonic adenocarcinomas; in metastases from breast adenocarcinoma; and in bronchioloalveolar tumors [8, 9]. The prognostic significance of psammoma bodies in serous carcinoma of the ovary is unclear. However, some authors have noted that the ovarian tumors containing numerous psammoma bodies have a better prognosis [10]. When psammoma bodies are numerous and large, they can be visible on CT in both primary tumors and metastases [10]. When they are located in lymph nodes, psammoma bodies cannot be differentiated on CT from dystrophic calcification resulting from granulomatous disease or previous radiation therapy.

Psammoma bodies raise the issue of the differential diagnosis of calcified lymph nodes. In our patient, this diagnosis was difficult because the nodal calcifications were cervical. In the head and neck area, approximately 40% of nodal calcifications are due to benign inflammatory or infectious diseases and 60% are associated with an untreated or treated malignancy such as head and neck primary tumors (thyroid, pharynx, tonsil, or tongue) [11]. In our patient, the clinical history of ovarian cancer treated 16 years earlier could have led one to suspect calcified metastases on CT. But at the time of discovery of the first calcified node, the patient had no biologic evidence of relapse. Moreover, in the spread of serous ovarian carcinoma, distant lymph nodes are involved in only approximately 7% of cases. The cervical, supraclavicular, groin, and axillary areas are unusual sites of lymph node involvement [12].

In our patient, PET/CT showed an increased 18F-FDG uptake, suggesting a metastatic lymph node, with no other abnormality, especially in the peritoneum. Thyroid cancer was excluded by sonography and biologic samples. A recurrence was definitively suggested because of the presence of another calcified node in the supraclavicular area and increasing 18F-FDG uptake on the second PET/CT scans. Surgical excision was recommended. Recurrence was confirmed by histopathologic findings of specific features of psammoma body formations observed in papillary serous adenocarcinoma lesions and high positive immunoreactivity for CA 125 on immunohistochemistry. One year later, the increase of blood CA 125 level and the appearance of new foci of uptake on PET/CT in the supradiaphragmatic and pelvic areas confirmed disease progression.

This case shows the possibility of apparently isolated supradiaphragmatic relapse, which has been previously described in patients with papillary serous ovarian cancer and which may occur many years after complete remission of the original disease [12, 13]. Thus, calcification in nodes in patients with previous papillary serous adenocarcinoma should not be assumed to be an unrelated finding: metastatic disease must be considered. Currently, PET/CT allows localizing increased 18F-FDG uptake with improved anatomic specificity. The presence of 18F-FDG uptake in calcified nodes is an argument for recurrence and must be confirmed by histology.


Acknowledgments
 
We thank Gerard Auclerc of the Centre Charlebourg, La Garenne Colombes, for his contribution.


References
Top
 Introduction
 Case Report
 Discussion
 References
 

  1. Koonings P, Campbell K, Mishell D, Grimes D. Relative frequency of primary ovarian neoplasms: a 10-year review. Obstet Gynecol 1989; 74:921 -926[Medline]
  2. Seidman JD, Russel P, Kurman RJ. Surface epithelial tumors of the ovary. In: Kurman RJ, ed. Blaustein's pathology of the female genital tract, 5th ed. New York, NY: Springer-Verlag,2001 : 791-904
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  6. Ferretti G, Ranchoup Y, Bost C, Coulomb M. CT demonstration of supra-diaphragmatic calcified metastatic nodes from ovarian carcinoma. Clin Radiol 1997;52 : 956-958[CrossRef][Medline]
  7. Mitchell DG, Hill MC, Hill S, Zaloudek C. Serous carcinoma of the ovary: CT identification of metastatic calcified implants. Radiology 1986;158 : 649-652[Abstract/Free Full Text]
  8. Sweeney DJ, Low VHS, Robbins PD, Yu SF. Calcified lymph node metastases in adenocarcinoma of the colon. Australas Radiol 1994; 38:233 -234[Medline]
  9. Giordano G, Gnetti L, Milione M, Piccolo D, Soliani P. Serous psammocarcinoma of the ovary: a case report and review of literature. Gynecol Oncol 2005;96 : 259-262[CrossRef][Medline]
  10. Eisenkraft BL, Som PM. The spectrum of benign and malignant etiologies of cervical node calcification. AJR1999; 172:1433 -1437[Abstract/Free Full Text]
  11. Gormly K, Glastonbury CM. Calcified nodal metastasis from squamous cell carcinoma of the head and neck. Australas Radiol2004; 48:240 -242[CrossRef][Medline]
  12. Patel SV, Spencer JA, Wilkinson N, Perren TJ. Supradiaphragmatic manifestations of papillary serous adenocarcinoma of the ovary. Clin Radiol 1999;54 : 748-754[CrossRef][Medline]
  13. Bamias A, Efstathiou E, Vassilakopoulou M, et al. Late relapse of epithelial ovarian cancer: a single institution experience. Eur J Gynaecol Oncol 2005; 26:439 -442[Medline]

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