PET-CT in Clinical Adult Oncology-IV. Gynecologic and Genitourinary Malignancies

Abstract

Concurrently acquired positron emission tomography and computed tomography (PET-CT) is an advanced imaging modality with diverse oncologic applications, including staging, therapeutic assessment, restaging and longitudinal surveillance. This series of six review articles focuses on providing practical information to providers and imaging professionals regarding the best use and interpretative strategies of PET-CT for oncologic indications in adult patients. In this fourth article of the series, the more common gynecological and adult genitourinary malignancies encountered in clinical practice are addressed, with an emphasis on Food and Drug Administration (FDA)-approved and clinically available radiopharmaceuticals. The advent of new FDA-approved radiopharmaceuticals for prostate cancer imaging has revolutionized PET-CT imaging in this important disease, and these are addressed in this report. However, [¹⁸F]F-fluoro-2-deoxy-d-glucose (FDG) remains the mainstay for PET-CT imaging of gynecologic and many other genitourinary malignancies. This information will serve as a guide for the appropriate role of PET-CT in the clinical management of gynecologic and genitourinary cancer patients for health care professionals caring for adult cancer patients. It also addresses the nuances and provides guidance in the accurate interpretation of FDG PET-CT in gynecological and genitourinary malignancies for imaging providers, including radiologists, nuclear medicine physicians and their trainees.

Keywords: PET; [18F]-fluorodeoxyglucose; fluciclovine; gynecologic malignancy; penile cancer; prostate cancer; prostate specific membrane antigen (PSMA); renal cell carcinoma; testicular cancer; urothelial carcinoma.

Figure 1

Physiologic hypermetabolism in the endometrium and in a scar endometrioma in a woman who underwent a prior Caesarian-section. FDG-PET-CT images of the pelvis. (a) Normal endometrial hypermetabolism (white arrow) occurs during the first 4 days of the menstrual cycle and during mid-cycle. An endometrial implant on the anterior abdominal wall also shows similar physiologic uptake; (b) A second FDG PET-CT scan performed off-cycle shows resolution of the metabolic activity both in the endometrium and in the scar endometrioma (subsequently biopsy proven).

Figure 2

Benign leiomyoma (uterine fibroid). (a) Axial contrast-enhanced CT of the pelvis shows vague enhancement of a uterine nodule (white arrowhead); (b) Axial FDG PET-CT images of the pelvis at the same level shows a hypermetabolic uterine nodule, which was felt by additional imaging and stability over time to be a benign uterine leiomyoma. Metabolic activity within uterine leiomyomas can be extremely variable. Some are hypermetabolic for unknown reasons, as is shown here (white arrowhead).

Figure 3

Post-partum uterus. (a) Coronal and (b) axial FDG-CT images of the pelvis show an enlarged uterus with a thickened rind of metabolically active endometrium (white arrow). Note that it is the endometrium, not the myometrium, that is hypermetabolic.

Figure 4

Physiologic [¹⁸F]F-fluoro-2-deoxy-d-glucose (FDG) uptake in fallopian tubes. (a,b) Axial FDG-CT images of the pelvis show increased metabolic activity in the fallopian tubes (white arrows). This typically occurs during the mid-cycle and during ovulation and can be unilateral or bilateral.

Figure 5

Normal functional ovarian metabolic activity on axial FDG PET-CT images of the pelvis. (a) Maturing ovarium follicle with a homogeneous nodular focus of increased metabolic activity (white arrow); (b) Corpus luteum cyst with a ring enhancing, hypermetabolic nodule (white arrowhead).

Figure 6

Pelvic inflammatory disease (PID shown on axial FDG PET-CT images of the pelvis. (a) For a few weeks following placement of an intrauterine contraceptive device (IUD), patients are at increased risk of developing pelvic inflammatory disease (PID), shown here as increased metabolic activity in the endometrium and myometrium on FDG PET-CT (white arrow). (b) A later FDG PET-CT scan shows that the PID and metabolic activity have resolved.

Figure 7

Vesicovaginal fistula on axial FDG PET_CT images of the pelvis. The patient complained of severe incontinence to urine. A vesicovaginal fistula resulted from prior pelvic radiation. Findings on sequential axial FDG PET-CT image of the pelvis include: (a–e) The vagina is diffusely filled with radioactive urine (white arrows); (c) The urinary bladder is empty and contains air (white arrowhead); (f) Radioactive urine is soaking the sanitary pad (white arrowhead).

Figure 8

Seeding of the peritoneum with ovarian cancer with laparoscopic removal. Laparoscopic removal of ovarian cancer carries a higher risk of seeding the peritoneum with tumor, seen here on an axial FDG PET-CT image of the abdomen, with a small hypermetabolic tumor nodule (white arrowhead) near a laparoscopic port site (white arrowhead).

Figure 9

Mucinous cystadenocarcinoma of the ovary with peritoneal spread. (a–e) Axial FDG PET-CT images of the abdomen. (a) Small peritoneal implant (white arrow); (b,c) large mixed attenuation ovarian mass (white arrowheads). The solid components are hypermetabolic. (c–e) Areas of subtly metabolically active mucinous ascites (white arrows).

Figure 10

Gastric carcinoma with a Krukenberg tumor of the ovary shown on axial FDG PET-CT images of the abdomen and pelvis. (a) Axial FDG PET-CT images of the upper abdomen show the stomach to be only mildly metabolically active in this patient with a signet-ring adenocarcinoma of the stomach (white arrow). It would be difficult to distinguish this tumor on PET-CT from normal gastric activity. (b) Axial FDG PET-CT of the pelvis reveals a mildly metabolically active right ovarian mass (white arrowhead) which was a Krukenberg tumor (metastatic from gastric cancer). Krukenberg tumors account for 1–2% of ovarian tumors.

Figure 11

Mucinous adenocarcinoma of the colon metastatic to the ovary shown on axial FDG PET-CT images of the pelvis. (a–c) Axial FDG PET-CT images of the pelvis. There is a hypermetabolic, centrally cystic tumor in the pelvis (white arrowheads), which at surgery was a large metastasis to the ovary from a colon cancer. The ovaries represent a common site for metastatic disease for many tumors, including from colon cancer. This mucinous adenocarcinoma metastasis to the ovary is very similar in appearance on FDG PET-CT to primary ovarian mucinous carcinomas.

Figure 12

Endometrial carcinoma show on axial FDG PET-CT images of the pelvis. (a,b) Axial contrast-enhanced CT images of the pelvis show an endometrial mass that is very low in attenuation (black arrows). (c,d) Although low in attenuation, the mass is intensely hypermetabolic on FDG PET-CT (white arrowheads) and is typical in appearance for endometrial carcinoma.

Figure 13

Endometrial polyp shown by axial FDG-PET_CT images of the pelvis in a 54-year-old woman with a long history of tamoxifen use for breast cancer. (a,b) Axial contrast enhanced CT of the pelvis shows a fluid-filled endometrial cavity containing a low-attenuating polypoid mass (white arrowheads). (c,d) Axial FDG PET-CT shows that the low attenuating polypoid lesion is intensely hypermetabolic (white arrow), a histologically proven to be benign hyperplasic polyp. A small endometrial carcinoma would have a similar appearance.

Figure 14

Endometrial stromal sarcoma on axial FDG PET-CT images of the pelvis. (a,b) A hypermetabolic endometrial mass fills the endometrial cavity (white arrowheads) and is centrally necrotic. (c,d) There are multiple areas of myometrial invasion (white arrows). Histologically, this was a high-grade endometrial stromal sarcoma.

Figure 15

Stage IB1 cervical cancer shown on axial FDG PET-CT images of the pelvis. (a) Small cervical cancer (1.8 cm diameter, white arrowhead); (b) post radiation with persistent metabolic activity in the endocervix consistent with post-treatment inflammation vs. persistent tumor (white arrowhead); (c) 2 years later, cervical cancer recurred with a larger tumor (white arrowhead).

Figure 16

Stage IIA cervical cancer shown by FDG PET-CT images of the pelvis. (a,b) Axial FDF PET-CT of the pelvis shows a hypermetabolic tumor involving the entire cervix (white arrowhead); (c,d) Tumor extends into the vagina on the right (white arrowhead). (e) Sagittal view shows cervical cancer with extension into the upper third of the vagina (white arrow), a normal appearing lower two-thirds of the vagina (dashed white arrows) and normal rectum (curved white arrows).

Figure 17

Stage IIIA cervical cancer by FDG PET-CT and MRI. (a–d) Axial FDG PET-CT demonstrates extension of cervical cancer throughout the entire vagina (white arrowheads). (b,e) Sagittal views of the pelvis shows cervical cancer spread throughout the entire vagina by FDG PET-CT ((e), white arrows) and MRI ((f), black arrows).

Figure 18

Stage IIIB cervical cancer by axial FDG PET-CT images of the pelvis (a) Hydronephrosis (white dashed arrow); (b) hydroureter (white curved arrow); (c) hypermetabolic cervical cancer (white arrowhead; (d) involvement of the right vaginal apex near the expected location of the right ureterovesicle junction (white arrow).

Figure 19

Primary vaginal squamous cell carcinoma on axial FDG PET-CT images of the pelvis. (a) shows normal upper pelvic structures; (b–d) moderately hypermetabolic mass in the left vaginal apex (white arrowheads).

Figure 20

Vulvar squamous cell carcinoma on axial FDG PET-CT images of the pelvis. (a) Axial FDG PET-CT demonstrates bilateral inguinal lymph node involvement (white dashed arrows); (b,c) the vulvar carcinoma is markedly hypermetabolic on FDG PET-CT (white arrowhead); (c,d) there is spread of the vulvar carcinoma into the adjacent subcutaneous tissue on the right, as well as the skin of the right medial thigh (white arrows).

Figure 21

Two patients with prostate cancer on axial MRI and FDG PET-CT images of the pelvis. Case 1: (a) Well-differentiated prostate cancer (Grade group 2) shows typical low signal on T2 MRI in the peripheral zone of the left lobe of the prostate (white arrow); (b) FDG PET-CT in this patient is negative in the region of tumor (white arrow) but shows mild diffuse uptake typical for benign prostatic hypertrophy (BPH); Case 2: (c) T2 MRI in a patient with more poorly differentiated prostate cancer (Grade group 4) shows typical low signal intensity in a tumor in the peripheral zone of the left lobe of the prostate (white arrow); (d) DWI MRI shows increased signal intensity in the prostate cancer (white arrowhead); (e) FDG PET-CT shows increased metabolic activity in the prostate cancer (white arrowhead).

Figure 22

Two patients with prostate cancer recurrence in the post-surgical prostatic fossa, clearly delineated by [¹⁸F]-fluciclovine PET-CT. (a,b) The prostate cancer recurrence is intensely PET-positive in both cases (white arrowheads).

Figure 23

Benign prostatic hypertrophy on axial [¹⁸F]-fluciclovine PET-CT images of the pelvis. (a–d) The prostate is diffusely enlarged and heterogeneously hypermetabolic (white arrowheads). The detection of a site of prostate cancer within this prostate would be difficult. (a,b) White arrows identify the urinary bladder.

Figure 24

Prostate cancer in a patient with benign prostatic hypertrophy (BPH), compared by multiparametric (mp) MRI (a,b) and [¹⁸F]-DCFPyL PET-CT (c). (a) T2 MRI fails to clearly delineate the prostate cancer (site shown by white arrowhead) with the background of benign prostatic hypertrophy (PBH) nodules; (b) DWI MRI shows high signal intensity due to prostate cancer (white arrowhead); (c) the prostate cancer is best shown on the [¹⁸F]-DCFPyL PET-CT (white arrowhead). The background of BPH is low in activity on [¹⁸F]-DCFPyL PET-CT, which offers an advantage over [¹⁸F]-fluciclovine PET-CT, which typically shows diffuse heterogeneous uptake of tracer in BPH.

Figure 25

[¹⁸F]-Fluciclovine-negative PET-CT scans in a patient with metastatic bone disease to an upper cervical vertebra. (a–c) There is progressive sclerosis of the vertebra in 3 successive CT scans performed with [¹⁸F]-Fluciclovine PET-CT scans over a two-year interval (left to right); (d–f) the last ¹⁸F-fluciclovine PET-CT scan shows no increased uptake in the bone metastasis over that of normal background marrow.

Figure 26

Comparison of [¹⁸F]-fluciclovine negative but [¹⁸F]-PSMA-positive PET-CT scans in a prostate cancer patient with a bone metastasis. (a) [¹⁸F]-fluciclovine PET-CT scan is negative; (b) [¹⁸F]-PSMA scan is positive in a metastatic lesion of a lower thoracic vertebral body (white arrowhead) vertebral metastasis.

Figure 27

Diagnostic value of PSMA PET-CT detecting extra-prostatic recurrence in the face of metal artifact. (a,b) There is prostate cancer recurrence in the right seminal vesicle (white arrows), identified despite the presence of bilateral total hip prostheses. A metal artifact reduction algorithm was utilized for the CT; (c) Multiple brachytherapy seeds are present (white arrowheads) without obvious recurrence within the prostate.

Figure 28

Discordant uptake between primary tumor and metastatic prostate cancer on [¹⁸F]-DCFPyL (PSMA) PET-CT. (a) The primary tumor was Grade Group 3 in the transitional zone of both lobes of the prostate, corresponding to the regions of mild uptake on PMSA PET-CT (white arrowheads). There is less activity on PMSA PET-CT than would normally be expected for unknown reasons. The patient had not received ADT; (b) a metastasis to the right pubic bone (white arrow) is intensely PET positive, in comparison to the primary tumor.

Figure 29

A patient with prior brachytherapy with recurrent prostate cancer in the left lobe of the prostate, shown on PSMA PET-CT. The site of tumor is very small but clearly delineated (white arrowhead). MRI would have had limited utility in this patient because of metal artifact created by the brachytherapy seeds.

Figure 30

Subtle extra-prostatic spread of prostate cancer on PSMA PET-CT. (a,b) Axial PSMA PET-CT images demonstrate moderately PET-positive tumor in the posterior peripheral and transitional zones of both lobes of the prostate. The posterior capsule of the prostate is indistinct and shows stranding soft tissue that is PET avid (white arrows), supporting extracapsular spread of disease. The patient had bilateral transitional and peripheral zone tumor by biopsy.

Figure 31

Extensive extra-prostatic spread of prostate cancer on PSMA PET-CT. Areas of tumor include (a,b) spread into the urinary bladder (white arrows); (b) involvement of both seminal vesicles (solid white arrowheads); (c,d) extensive involvement of the prostate; (e) encasement of the proximal urethra (open white arrowhead); (f) MIP PSMA PET mage of the pelvis shows the extensive extra-prostatic involvement and two small involved bilateral pelvic lymph nodes.

Figure 32

Gross extra-prostatic spread of prostate cancer to vas deferens and seminal vesicles on [¹⁸F]-Fluciclovine PET-CT. (a,b) There is PET-positive tumor extending along the right vas deferens (white arrows); (c) tumor also involves both seminal vesicles (white arrowheads).

Figure 33

Tumor involving the left neurovascular pedicle by PSMA PET-CT (a,b). This patient had a radical prostatectomy and seminal vesicles were removed. Involvement of the left neurovascular pedicle (white arrowhead) could be confused with seminal vesicle without knowledge of the surgery performed.

Figure 34

[¹⁸F]-fluciclovine PET-CT in a post prostatectomy patient showing recurrent tumor in the right neurovascular pedicle ((c), white arrowhead), extending along the right mesorectal fascia ((a,b), white arrows), representing a path of perineural spread along the hypogastric plexus.

Figure 35

[¹⁸F]-Fluciclovine PET-CT showing mild uptake in the sympathetic ganglia (white arrowheads). (a) Stellate ganglia; (b) lumbar ganglia; (c,d) sacral ganglia. PSMA PET-CT shows a similar pattern of uptake in the sympathetic ganglia. Celiac ganglia are similarly seen (not shown here).

Figure 36

[¹⁸F]-PSMA PET-CT demonstrates tiny focus of intense activity in the wall of the stomach (a,b, white arrows), shown by subsequent endoscopic biopsy to be a small GIST tumor.

Figure 37

[¹⁸F]-Fluciclovine PET-CT demonstrates PET-positive left-sided bladder wall thickening (a,b, white arrowheads), biopsy-proven urothelial carcinoma.

Figure 38

Upper track urothelial carcinoma shown on FDG PET-CT images of the pelvis. (a) Intensely hypermetabolic mass on an axial FDG PET-CT image of the upper abdomen involving the left kidney (white arrowhead); (b) corresponding contrast-enhanced CT scan shows a soft tissue mass filling the left renal pelvis with parenchymal invasion (white arrowhead).

Figure 39

Lower tract urothelial carcinoma. (a) Axial non-contrast enhanced CT image shows a mass arising from the right posterior aspect of the urinary bladder with a lobular component extending into the bladder (white arrows); (b) Axial FDG PET-CT image shows that the mass in the bladder is hypermetabolic (white arrows), but lower in activity than the surrounding urine (white arrowheads).

Figure 40

Lower tract urothelial cancer with metastatic disease shown on axial FDG PET-CT images. (a) The primary tumor is hypermetabolic (white arrowhead). (b) There is diffuse infiltrative spread into the seminal vesicles and mesorectal fascia (dashed white arrows). (c) There are multiple hypermetabolic nodes in the pelvis and mesentery (white arrows). (d) There are multiple hypermetabolic mediastinal lymph nodes (biopsy proven metastatic, white arrows).

Figure 41

Upper tract urothelial carcinoma pre- and post chemotherapy on FDG PET-CT. (a) There is a large hypermetabolic renal pelvic mass prior to treatment (white arrowheads). (b) Following chemotherapy, there is a persistent mass that is centrally necrotic but shows a peripheral rim of metabolic activity suggesting persistent viable tumor (white arrows). There is a percutaneous nephrostomy tube.

Figure 42

Two cases of large pure seminoma demonstrating variability in metabolic activity in retroperitoneal masses on FDG PET-CT. (a) An axial FDG PET-CT image shows a large tumor with relatively mild uptake (white arrow), relative to background muscle and other tissues; (b) Another large retroperitoneal site of seminoma with more intense metabolic activity is shown on FDG PET-CT (white arrowhead).

Figure 43

Pre- (a) and post-treatment (b) FDG PET-CT scans in a mixed germ cell tumor (white arrows) show a reduction in size following treatment but residual metabolic activity in the left inguinal mass. Subsequent stability in size over a long interval supported that no residual viable tissue was present post-treatment, despite residual metabolic activity.

Figure 44

A pure seminoma with retroperitoneal metastases showing a variable response to treatment is shown on a pre-treatment CT (left, a,c) and a post-treatment FDG PET-CT (right, b,d). Pretreatment CT (a) shows a sizable retroperitoneal mass (white arrow) that undergoes a decrease in size and attenuation, as well as an absence of metabolic activity on post treatment FDG PET-CT (b), white arrow); However, a more inferior additional left periaortic nodule (c, white arrowhead) on the pre-treatment CT shows an interval increase in size as well as significant metabolic on the post-treatment FDG PET-CT (d, white arrowhead), consistent with tumor progression.

Figure 45

Intensely hypermetabolic metastatic embryonal germ cell tumor of the testis on FDG PET-CT to lymph nodes in the left supraclavicular region (a, white arrow) and the retroperitoneum (b, white arrow).

Figure 46

Renal cell carcinoma. FDG PET-CT coronal (a) and axial (b) images. An exophytic mass (white arrows) arising from the inferior pole of the left kidney is slightly higher in metabolic activity than normal renal parenchyma. This is typical for renal cell carcinoma, which can also be similar in metabolic activity to the renal parenchyma.

Figure 47

Renal oncocytoma on contrast enhanced FDG PET-CT. (a,c) Contrast-enhanced CT shows a heterogeneously enhancing mass (black arrows) in the left kidney; (b,d) On FDG PET-CT, the oncocytoma would be difficult to appreciate without the concurrent contrast enhanced CT and is similar in metabolic activity to the remainder of the normal renal parenchyma (white arrows). This was an oncocytoma, but a renal cell carcinoma can have a similar in appearance.

Figure 48

Sarcomatoid cell carcinoma on FDG PET-CT. (c) A large, hypermetabolic invasive mass arising from the left kidney extends into the pararenal space (white arrowhead); (a,b) The hypermetabolic renal mass extends into the left pleural space, with an accompanying pleural effusion (white arrowheads). This was a sarcomatoid renal cell carcinoma, but the main differential would also include lymphoma.

Figure 49

Renal lymphoma on FDG PET-CT. (a,b) Numerous hypermetabolic renal nodules are present in both kidneys, as shown on axial (a) and coronal (b) FDG PET-CT images (white arrowheads); (c) Multiple hypermetabolic nodules are present within the lungs (also lymphoma), as shown on coronal FDG PET-CT image (white arrows). This was diffuse large B-cell lymphoma with renal and lung involvement.

Figure 50

Metastases to the kidneys. (a,b) Contrast-enhanced axial CT images of the abdomen show multiple hypoattenuating soft tissue nodules in both kidneys (white arrows); (c,d) on corresponding axial FDG PET-CT images, the hypoattenuating lesions are hypermetabolic. These lesions were metastatic from an ovarian primary malignancy.

Figure 51

Large renal cell carcinoma with renal vein invasion. FDG PET-CT (a,b) shows a large left renal mass extending into the pararenal space (white arrowhead) and invading the left renal vein (white arrow).

Figure 52

Squamous cell carcinoma of the prepuce of the penis on FDG PET-CT. Axial (a) and sagittal (b) FDG PET-CT images of the penis demonstrate intensely hypermetabolic tissue at the dorsal penile prepuce (white arrows). (c) Axial FDG PET-CT of the pelvis shows involvement of an enlarged hypermetabolic right inguinal lymph node (white arrowhead).

Figure 53

Large squamous cell carcinoma of the penis with fungating right inguinal lymph node shown on FDG PET-CT. (a) Axial FDG PET-CT image shows very large penile hypermetabolic mass (white arrowhead). (b) Photograph of the tumor shows large lobular, erythematous mass involving the glans penis (white arrowhead) extending into the penile shaft. (c) Photograph of the right inguinal lymph node shows a large, fungating, ulcerated right inguinal nodal mass that has extended through the skin (white arrowhead). (d) Axial FDG PET-CT of the right inguinal lymph node mass shows a large, lobular hypermetabolic mass in the right inguinal region.

Figure 54

Squamous cell carcinoma of the base of the penis, spread from a cutaneous perineal squamous cell carcinoma. (a) Axial FDG PET-CT at left shows intrapelvic tumor deposits (white arrows). (b) Hypermetabolic tumor involves the base of the penis (white arrowhead). A Foley catheter is in place.

Figure 55

Metastases to the penis. Axial (a) and sagittal (b) FDG PET-CT images demonstrate multiple hypermetabolic masses involving the penis (white arrowheads). The primary tumor was a sinonasal undifferentiated carcinoma (SNUC).