Testicular metastasis of prostate adenocarcinoma: the other side of orchiepididymitis| Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology
Vol. 116: Issue 1 - February 2024
DOI: 10.32074/1591-951X-940
Case reports
Published: 2024-03-08
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Testicular metastasis of prostate adenocarcinoma: the other side of orchiepididymitis

Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy
Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy
Urology Division, University Hospital of Parma, Parma, Italy
Urology Division, University Hospital of Parma, Parma, Italy
Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy
Oncology Division, University Hospital of Parma, Parma, Italy
Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy
Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy

Abstract

Background. Metastatic prostate adenocarcinoma is a rare event and there are few references to this topic. We report an unusual case of prostate cancer metastasis and review of contemporary literature. Moreover, we discuss the pathogenesis and the clinical aspects of this event.
Case presentation. A 70-year-old patient was admitted to the hospital for right scrotal pain. The ultrasound examination described an increase in testicular size, suggesting the possibility of orchiepididymitis. Past medical history reported a previous prostate adenocarcinoma. Inflammatory blood tests were normal. Importantly, PSA was 3.3 ng/ml. PET scan positivity in the scrotum raised suspicion of a relapse. Therefore, he underwent right orchiectomy.
Conclusion. Although metastatic prostate adenocarcinoma is rare, a correct diagnosis is of paramount importance because the therapy changes accordingly. Patients who complain of scrotal pain need to be examined accurately. Although the most common cause behind this symptom is infectious, the patient’s past medical history should be reviewed to exclude previous malignancies.

Background

Scrotal pain is a common reason for visits to the emergency room in adults. This symptom may be due to orchiepididymitis, testicular torsion, inguinal hernia or testicular neoplasm 1.

Metastases to the testis are rare events. The most common metastatic neoplasm is leukemia; reported solid neoplasms are less frequent and include melanoma, prostate, lung and kidney adenocarcinomas. However, the incidence of this latter group is below 1% 2,3.

We report the case of a man who was admitted to the hospital for scrotal pain; ultrasound examination showed an increase in testis size, and thus the patient underwent right orchiectomy. Surprisingly, the histology report revealed the presence of prostate adenocarcinoma.

Case presentation

A 70-year-old patient was admitted to the emergency room of our hospital for right scrotal pain. He had no significant past medical history except for a previous transurethral resection of the prostate (TURP) that led to the diagnosis of prostate adenocarcinoma (Gleason Score 9, Grade Group 5) six years earlier. The patient was treated with androgen deprivation therapy (leuprorelin) and radiotherapy.

After hospital admission an ultrasound examination of the pelvic region was performed. It reported an increase in right testis size (46 x 22 mm), hydrocele, heterogenous echotexture and enhanced vascularity. Physical examination of the right testis showed swelling, hardness and soreness. Abdominal examination was unremarkable. The clinical presentation was suggestive of orchiepididimitis.

Blood tests were normal, except for PSA which was 3.3 ng/ml. Therefore, disease restaging was performed using positron emission tomography/computed tomography (PET/CT) with 68Ga-PSMA. The radiopharmaceutical was prepared in the local radiopharmacy as previously described 4.

PSMA PET/CT revealed increased tracer accumulation in the right scrotum (SUVmax = 5.6) suggesting prostate cancer recurrence (Fig. 1).

The patient underwent right orchiectomy. The gross description reported that the testis measured 5 x 3 x 2 cm, featured an area of induration and was diffusely gray on cut sections (Fig. 2A). The histology report described that most testis and epididymis were replaced by a glandular neoplasm with nests of plasmacytoid cells (Fig. 2B). Previous prostate adenocarcinoma was comparable to the testicular neoplasm (Fig. 2C). Immunohistochemistry showed that the tumor in the biopsy was positive to ERG (Fig. 2D), PSA (Fig. 2E) and AR (Fig. 2F), negative to inhibin, p63 and ER. The lesion in the testis was positive to PSMA (Fig. 2G), thereby suggesting metastatic prostate adenocarcinoma in the testis. To confirm the primary site, NKX3.1 was performed on the metastasis because it is considered both a sensitive and specific marker for prostate adenocarcinoma 5. Figure 2H shows positivity in tumor cells.

Discussion

A metastasis in the testis is a rare event. The incidence is below 1% except for leukemia and lymphoma 2. The likely explanation is that scrotal temperature prevents tumor cell proliferation. The risk of metastasis might also be reduced by the presence of Sertoli cells tight junctions, which constitute the blood-testis barrier 6,7.

A palpable unilateral nodule is the clinical presentation of metastasis to the testis. However, testicular metastasis is often an incidental finding during specimen processing or autopsy. Both testes might be involved, but it is usually unilateral 6,8. The interval between the event and the metastasis may range from six months to some years 9. Metastatic prostate cancer usually has a high Gleason score which matches the primitive neoplasm 6. Table I shows literature cases of prostate adenocarcinoma metastatic to the testis.

Metastatic high grade prostate adenocarcinoma should be differentiated from primary tumors of the testis. The International Society of Urological Pathology (ISUP) suggests performing the following antibodies: SALL4, OCT4 and EMA; alternatively, OCT4, Glypican 3, EMA and cytokeratin 7 might be used 10.

Patient survival is limited to one year, despite reports of longer periods. Prognostic significance is uncertain. Both increase in PSA levels and PSMA PET/CT positivity should improve surveillance in hormone-treated patients, especially to detect isolated metastases as in our patient 9.

The best treatment following surgery is still a matter of debate. A single testicular metastasis might have a low risk of spreading to other organs, but this cannot be excluded. Therefore, orchiectomy may be followed by adjuvant therapy, which is based on radiotherapy or hormone therapy 9. The latter includes androgen pathway inhibitors such as abiraterone and androgen receptor antagonists such as apalutamide and enzalutamide 11.

Olaparib, a poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitor, may be used in case of progression with hormonal agents on condition that patients have alterations in BRCA1 or BRCA2. For this reason, we suggest that metastatic prostate cancer be screened for these two mutations 12.

Conclusion

Patients who complain about scrotal pain need to be examined accurately. Although the most common cause behind this symptom is infectious, the patient’s past medical history should be reviewed to exclude previous malignancies.

CONFLICTING OF INTEREST STATEMENT

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

FUNDING

The authors received no financial support for the research, authorship, and/or publication of this article.

AUTHORS’ CONTRIBUTION

EMS, FPP and LG conceived the idea of this case report. UM, LR and DG provided clinical and radiological data. GDR and AT wrote the manuscript. LG, GDR and AT reviewed the manuscript. All authors contributed to the article and approved the submitted version.

ETHICAL CONSIDERATION

We confirm that the local Ethics Committee has been consulted and that ethical approval is not necessary for the report of a single case.

Figures and tables

Figure 1.68Ga-PSMA PET/CT in the restaging of prostate adenocarcinoma. MIP images (A); CT and fused PET/CT axial sections (B, C); CT and fused PET/CT coronal sections (D, E). PSMA PET/CT showed increased uptake in the right scrotum (black and light blue arrows) with SUVmax value of 5.6.

Figure 2.Transurethral resection of the prostate (TURP) specimen and testis with prostate adenocarcinoma. Gross photograph of the testis (A); whole slide image of testicular metastasis at 4x (B); TURP specimen with prostate adenocarcinoma at 10x (C); ERG expression in the TURP specimen at 10x (D); PSA expression in the TURP specimen at 10x (E); androgen receptor expression in the TURP specimen at 10x (F); PSMA expression in the testicular metastasis at 4x (G); NKX3.1 expression in the testicular metastasis at 4x (H).

Year Authors Age PSA (ng/ml) at diagnosis Histological type GS Time between diagnosis and metastasis in the testis (months) Presentation in the testis Involvement Sides PSA (ng/ml) at metastasis in the testis Orchiectomy ADT RT CT
2018 Su et al. 13 72 129 Acinar 9 6 Swelling Bilateral Both 6.2 Yes Yes No No
2016 Hsieh et al. 14 62 NA NA NA 84 Induration Unilateral Right NA Yes Yes Yes No
2021 Olorunsola et al. 6 71 6.8 Acinar 10 0 None Bilateral Both NA Yes Yes No No
2006 Manikandan et al. 15 56 1100 Acinar 6 30 Swelling Bilateral Both 60 Yes Yes No No
2017 Santos-Lopes et al. 16 69 NA Acinar 8 60 Nodule Unilateral Left 20 Yes No Yes No
2015 Sampathrajan et al. 17 63 225.5 Acinar 8 0 None Unilateral Right NA Yes No No No
2019 Bilal et al. 18 55 100 NA NA 0 None Unilateral Left NA Yes No No No
2019 Dahiru et al. 19 82 25.8 Acinar 5 0 None Unilateral Left NA Yes No No No
2023 Kato et al. 20 73 4.3 Acinar 8 28 Swelling Unilateral Left 1.5 Yes Yes No Yes
1997 Baykal et al. 21 64 80 Acinar 5 0 None Unilateral Right NA Yes No No No
2015 Aydogmus et al. 22 69 33.1 Acinar 9 0 Swelling Unilateral Left NA Yes No No No
2016 Campara et al. 23 48 597 Acinar 7 108 Swelling Unilateral Left 23.1 Yes Yes Yes No
2009 Haupt et al. 24 71 NA Acinar 9 48 Nodule Unilateral NA NA Yes Yes Yes No
2022 DiMarco et al. 25 67 3.3 Acinar 6 144 Swelling Unilateral Right 0.3 Yes No No No
2023 Hermi et al. 26 55 100 Acinar 10 6 Induration Unilateral Left 3.2 Yes Yes No No
2018 Gao et al. 27 69 100 Acinar 8 24 Swelling Unilateral Left 19.2 Yes Yes No No
2011 Kim et al. 28 73 10.8 Acinar 6 96 None Bilateral Both 9.3 Yes Yes No No
2016 Zhang et al. 29 69 100 Acinar 6 0 Swelling Unilateral Right NA Yes Yes Yes No
2010 Janssen et al. 30 71 7.7 Acinar 6 30 Swelling Unilateral Left 2.1 Yes Yes Yes No
2013 Upchurch et al. 31 78 1240 NA NA 30 Swelling Bilateral Both NA Yes Yes No No
2010 Rahardjo et al. 32 66 40 NA NA 0 Swelling Unilateral Left NA Yes No No No
2007 Menchini-Fabris et al. 33 67 15.5 Acinar 9 6 Pain Unilateral Left NA Yes No No No
2014 Kusaka et al. 34 56 137 Acinar 9 64 Swelling Unilateral Right 4.9 Yes Yes Yes Yes
2022 Fortier et al. 35 64 150 Ductal 8 264 Induration Unilateral Right 40 Yes Yes Yes No
PSA = prostate specific antigen; GS = Gleason Score; ADT = androgen deprivation therapy; RT = radiotherapy; CT = chemotherapy; NA = not available.
 Table I.Literature cases of prostate adenocarcinoma metastatic to the testis.

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Affiliations

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Gianluca Di Rienzo

Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy
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Alessandro Tafuni

Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy
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Umberto Maestroni

Urology Division, University Hospital of Parma, Parma, Italy
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Livia Ruffini

Urology Division, University Hospital of Parma, Parma, Italy
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Enrico Maria Silini

Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy
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$authorString->getFullName() => Donatella Gasparro

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Donatella Gasparro

Oncology Division, University Hospital of Parma, Parma, Italy
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$authorString->getFullName() => Francesco Paolo Pilato

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Francesco Paolo Pilato

Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy
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$authorString->getOrcid() =>

$authorString->getFullName() => Letizia Gnetti

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Letizia Gnetti

Anatomic Pathology Unit, University Hospital of Parma, Parma, Italy
non esiste orcidID ""https://orcid.org/0000-0002-6982-5188

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright

© Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology , 2024

How to Cite

[1]
Di Rienzo, G., Tafuni, A., Maestroni, U., Ruffini, L., Silini, E.M., Gasparro, D., Pilato, F.P. and Gnetti, L. 2024. Testicular metastasis of prostate adenocarcinoma: the other side of orchiepididymitis. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology. 116, 1 (Mar. 2024), 69-74. DOI:https://doi.org/10.32074/1591-951X-940.
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