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Penile Secondary Lesions www.nature.com/scientificreports OPEN Penile secondary lesions: a rare entity detected by PET/CT Tima Davidson1,2*, Liran Domachevsky1,2, Yogev Giladi2, Eddie Fridman2,3, Zohar Dotan2,4, Barak Rosenzweig2,4, Raya Leibowitz2,5 & Jennifer Ben Shimol2,6 While penile metastases are rare, PET/CT has facilitated their detection. We aimed to describe penile secondary lesions (PSL) identifed by PET/CT. We reviewed 18F-FDG and Ga68-PSMA PET/CT records performed in a single center during May 2012-March 2020, for PSL. Of 16,774 18F-FDG and 1,963 Ga68-PSMA-PET scans, PSL were found in 24(0.13%) men with a mean age of 74. PSMA detected PSL in 12 with prostate cancer; FDG identifed PSL in 4 with lymphoma, 3 with colorectal cancer, 2 with lung cancer, and one each with bladder cancer, pelvic sarcoma, and leukemia. Mean SUVmax of PSL was 7.9 ± 4.2 with focal uptake in 13(54%). Mean lesion size was 16.5 ± 6.8 mm; 8 at the penile root, 4 along the shaft, and 1 at the glans. CT detected loss of the penile texture in 15(63%). PSL were observed only during relapse or follow-up of disseminated disease. Among those with prostate cancer, PSA varied widely. Fifteen (62.5%) died, at a mean 13.3 ± 15.9 months following PSL demonstration, nine had non-prostate malignancies. PET/CT identifed and characterized PSL in a fraction of cancer patients, most commonly those with prostate cancer. PSL universally surfaced in advanced disease, and signaled high mortality, especially in non-prostate cancers. Penile secondary lesions (PSL) appear infrequently among cancer patients; several hundred cases have been reported since Eberth originally described them in 1870 1–5. Most are seen in cancers of the genitourinary and lower gastrointestinal tracts; 29% were reported to originate in the bladder, 28% in the prostate, and 12% in conjunction with rectosigmoid cancer5. Clinical features of PSL include palpable nodules, ulcerations, obstructive or irritative urinary symptoms, hematuria, and priapism, ofen with signifcant morbidity 3. PSL may originate from venous spread, lymphatic invasion, or local infltration. While the rich arterial and venous communication in the penile region typically limits tumor cell seeding, venous or lymphatic occlusion from neighboring cancers may enable implantation5,6. PSL detection is limited in most imaging modalities, and lesions are likely missed when asymptomatic, which occurs in up to 12%, or when the symptoms are attributed to the primary cancer. CT and MRI do not routinely capture the penis. Tese modalities also do not adequately detect occult involvement of normal-sized lymph nodes7–11. With ultrasound, PSL may be obscured by the pubic bone or pubic fat pad, or from attenuation caused by the faccid tunica albuginea12. Te increasing use of PET/CT to stage malignancies, by means of 18F-FDG (18-fuorodeoxyglucose) and Ga 68-PSMA (gallium 68-labeled prostate specifc membrane antigen), facilitates the detection of PSL 13–17. However, to our awareness, there are no published papers describing these PET/CT fndings in a series of patients with multiple types of malignancies. Our objective was to characterize the PET/CT features of PSL in cancer patients at a large tertiary institution. Methods Ethics. Tis single-institution study was approved by the institutional review board of Sheba Medical Center, according to the Declaration of Helsinki (approval no: SMC-20-7097). Informed consent was waived by the institutional review board of Sheba Medical Center due to the retrospective nature of the study. Study design. We searched the computerized database of Sheba Medical Center, a tertiary hospital, for PET/CT imaging reports from May 2012 to March 2020 that included the term “penis” or “penile”. Once identi- fed, relevant reports and images were individually reviewed to confrm the presence of an FDG- or PSMA-avid 1Department of Nuclear Medicine, Sheba Medical Center, Derech Sheba 2, 52621 Ramat Gan, Tel-Hashomer, Israel. 2Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel. 3Department of Pathology, Sheba Medical Center, 52621 Tel Hashomer, Israel. 4Department of Urology, Sheba Medical Center, 52621 Tel Hashomer, Israel. 5Oncology Institute, Shamir Medical Center, 70300 Zerifn, Israel. 6Department of Medicine, E. Wolfson Medical Center, 5822012 Holon, Israel. *email: [email protected] Scientifc Reports | (2021) 11:5912 | https://doi.org/10.1038/s41598-021-85300-8 1 Vol.:(0123456789) www.nature.com/scientificreports/ penile lesion. Imaging data were retrieved from the picture archive and communication system (PACS, Care- stream Health 11.0, Rochester, NY), and clinical data were obtained from the computerized medical records at our hospital. Clinical data, including medical history, laboratory work, and biopsy results were reviewed. Study inclusion criteria were: (1) men aged 18 years and older; (2) a history of a malignancy with a primary site that was non-penile; and (3) fndings consistent with PSL on PET/CT. Exclusion criteria included the pres- ence of abnormal fndings in the genital area on PET/CT. Tese included urinary retention in the penile urethra, without clear demonstration of a suspicious penile lesion, and evidence of radiotracer contamination in the penile area. Tis retrospective study evaluated consecutive patients. During the designated period, a total of 48,731 18-F-FDG PET/CT scans were performed, mainly for assessment of known or suspected oncological diseases; of them, 22,875 scans were performed on 16,774 unique male patients. From 2015 onward, PET/CT using Ga 68-PSMA was performed in men with diagnosed or suspected prostate cancer or with biochemical recurrence. In total, 2,087 Ga 68-PSMA scans were carried out on 1,963 men. From a total of 18,737 unique PET/CT studies, the reports of 57 men mentioned the word “penis” or “penile”, and 24 (0.13%) met the study eligibility criteria. Of the 1963 men with Ga 68-PSMA studies, 12 (0.61%) met the eligibility criteria. Te remaining were excluded due to the absence of fndings compatible with PSL. PET/CT image acquisition. PET/CT scanning was performed using a combined PET-CT protocol with a 16-detector-row helical CT scanner (Gemini GXL, Phillips Healthcare). Tis scanner enables simultaneous acquisition of up to 45 transaxial PET images, with interslice spacing of 5 mm in one bed position; and provides an image from the vertex to the thigh in about 10 bed positions. Te transaxial felds of view and pixel sizes of the PET images reconstructed for fusion were 57.6 cm and 4 mm, respectively, with a matrix size of 144 × 144 mm. Te CT component was performed in accordance with the hospital’s standard protocol, with routine use of both oral and intravenous contrast media unless either was contraindicated. Te following technical parameters were used for CT imaging: pitch 0.8, gantry rotation speed 0.5, 120 kVp, 250 mAs, 3-mm slice thickness, and specifc breath-holding instructions18–20. Depending on the type of PET/CT scan (with FDG or PSMA), the patient received an intravenous injec- tion of 370 MBq 18F-FDG afer 4–6 h of fasting, or an injection of 148 MBq Ga 68-PSMA in the absence of a prerequisite fast. About 60 min later, CT images were obtained from the vertex to the mid-thigh for about 32 s. A contrast-enhanced CT scan was captured 60 s afer injection of 2 mL/kg of non-ionic contrast material (Omnipaque 370 GE Healthcare). An emission PET scan followed in 3D acquisition mode for the same axial image range, 2.0–2.5 min per bed position. Te diagnostic CT images were used for fusion with the PET data and to produce a map for attenuation correction. PET images were generated with CT attenuation correction utilizing a line of response protocol, and the reconstructed images were constructed for review (EWB, Extended Brilliance Workstation, Philips Medical Systems, Cleveland OH, USA)18–20. Image interpretation. All available images were interpreted by experienced specialists in nuclear medicine and radiology, and re-reviewed by one of the study co-authors with 20 years’ experience and dual certifcation in radiology and nuclear medicine. Readers were not blinded to clinical information. Consensus was achieved on interpretation of all of the images. Ga 68-PSMA and 18F-FDG activity were quantifed by calculating a maximum standardized uptake value (SUVmax). Tis was done by manually generating a region of interest over the sites of abnormally increased radioactive material activity. Increased Ga 68-PSMA/ 18F-FDG uptake that was not explained by the normal bio-distribution, or uptake that was higher than the physiological uptake in the surrounding tissue was consid- ered pathological/positive. Positive PET fndings were analyzed with respect to their intensity of uptake (SUV max) and pattern of uptake enhancement (focal or difuse). Cases with more than 2 focal penile fndings were considered difuse. CT images were examined for abnormalities of the penis that corresponded to PET fndings, and classifed as loss of the typically smooth penile texture. Te following descriptions were used: a focal hyperdense sof tis- sue mass, a focal hypodense lesion, a difuse heterogeneous sof tissue mass infltration along the penis, or the absence of detectable CT fndings. For focal lesions, the diameter length was measured and the location within the penis was evaluated, and labeled as: at the root, along the shaf, or at the glans. We also examined the involvement of other structures within the pelvis (prostate, prostatic bed afer prosta- tectomy, seminal vesicles, bladder, pelvic lymph nodes) and organs outside the pelvis. We analyzed penile fndings on ultrasound and MRI when available. For men with more than one PET/CT scan, we assessed the dynamic changes in penile lesions with regard to size and the persistence of increased uptake in all the consecutive imaging studies.
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