Archivio Italiano di Urologia e Andrologia 2021; 93, 164 CASE REPORT No conflict of interest declared. DOI: 10.4081/aiua.2021.1.64 World Health Organization (WHO) classification distin- guishes testicular neoplasms into germ cell-derived (95%) and non-germ cell neoplasms (2). The most fre- quent germ-cell tumours (GCTs) are seminoma (40-50% of cases). In about 80% of the cases, seminoma presents in a typical form (4). TTs are often localized (68%) and confined to the testis. Locally advanced tumours usually remain confined to the scrotum. Although rare, extension of the primary tumour to the inguinal canal can be observed, mostly among non-germ cell TTs (NGCTTs) (5). To the best of our knowledge, no previous case of large seminoma spreading in the retroperitoneum through inguinal canal has been described. In this study we report the first case of testicular cancer presenting as a voluminous ulcerat- ed testicular mass. CASE REPORT A 44-year-old man self-referred to the emergency room of our hospital because of a voluminous scrotal mass associated to abdominal and pelvic pain. The patient had no fever, poor nutritional conditions and pale skin. Clinical history included smoke and thyroid goitre. Physical examination showed a voluminous scrotal mass likely with colliquative necrotic phenomena and abdom- inal extension (Figure 1A). The abdomen was tense and slightly painful on deep palpation. Laboratory tests showed an anaemia with reduction in red blood cell (RBC) count (3.1 × 106 mm3; normal range 4.5- 5.3 × 106 mm3), haemoglobin (Hgb) of 6.9 g/dl (normal range 13-16 g/dl), Hct of 24 % (normal value 37-49%). Tumour markers were elevated, in particular b-HGC was 4873 mIU/ml (normal range between 0-5 mUI/ml), a-fetoprotein was 33.4 ng/ml (normal values less than 6 ng/ml were evaluated) and LDH was 9047 U/L (normal range 313-618 U/L). Complete blood tests are shown in the Table 1. The patient underwent an abdominal CT scan, showing a voluminous scrotal sac (28 x 13 x 12 cm) with solid tissue sized 16 x 16 cm, occupying the scrotum with extension to the left inguinal canal and to the retroperi- Introduction: Testicular cancers represent about 5% of all urological malignancies and 1-1.5% of all male neoplasms. Most of the testicular cancers are localized (68%) at diagnosis. Bulky masses in the scrotum are rare. We present a rare case of bulky testicular cancer with retroperitoneal spread through the inguinal canal. Case report: A 44-year-old man came to the emergency department referring weakness and the presence of a scrotal mass. At physical examination, a voluminous mass was found, with necrotic phenomena within the scrotum. Abdomen was tense and sore. Abdominal CT scan revealed a bulky testicular mass spreading to the retroperitoneal space through the inguinal canal with node enlargement. Patient underwent orchiectomy with excision of infiltrated scrotum skin. Histologic diagnosis confirmed a typical form seminoma. The patient was then treated with a cisplatin-based chemotherapy, with a partial response. The patient recently relapsed and he is being treated with a new line of chemother- apy and subsequent surgery with or without radiotherapy. Conclusions: We described a rare presentation of testicular cancer. This case highlights the importance of a multidiscipli- nary approach to rare testis tumour presentation and early diagnosis for testicular cancers. KEY WORDS: Testicular cancer; Large seminoma; Retroperitoneal space; Inguinal lymph nodes. Submitted 2 June 2020; Accepted 6 July 2020 INTRODUCTION Testicular tumours (TTs) represent about 5% of all uro- logical malignancies and 1-1.5% of all male neoplasms (1). The incidence of testicular cancers is 3-6 new cases per 100.000 males in Western countries, with an increase observed in the past 30 years (2), probably as a consequence of pollution. These rare tumours are more frequent between 18 and 35 years and in Scandinavian countries (1, 3). Risk factors include the presence of a tumour in the con- tralateral testicle, Germ Cell Neoplasia in Situ (GCNIS), Klinefelter's syndrome, cryptorchidism or undescended testicle, family history of testicular cancer (2). Retroperitoneal extension of massive ulcerated testicular seminoma through the inguinal canal: A case report Summary Alessio Antonaci 1, Daniela Fasanella 1, Vikiela Galica 2, Nicola Tinari 3, Jamara Giampietro 4, Pietro Di Marino 4, Andrea Delli Pizzi 5, Raffaella Basilico 5, Luigi Schips 1, Michele Marchioni 1 1 Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University of Chieti, Urology Unit, SS. Annunziata Hospital, Chieti, Italy; 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila “San Salvatore” Hospital, L’Aquila, Italy; 3 Department of Medical, Oral and Biotechnological Sciences and Center for Advance Studies and Technology (CAST), G. D'Annunzio University of Chieti, Italy; 4 Clinical Oncology Unit, SS Annunziata Hospital, Chieti, Italy; 5 Department of Neuroscience, Imaging and Clinical Sciences, G. d'Annunzio University of Chieti, Chieti, Italy. 65Archivio Italiano di Urologia e Andrologia 2021; 93, 1 Retroperitoneal seminoma toneal space. Moreover, there was a pathological involvement of the left inguinal (11 x 7 cm) and iliac-obturator (10 x 6 cm) lymph nodes infiltrating the external iliac vein. In addition, pathologic retroperitoneal lymphatic tissue was documented along the abdominal aorta for a longitudinal extension of about 20 cm, resulting in compression of the inferior vena cava and infiltration of the external iliac vein, left renal vein and left ureter with signs of post-renal obstructive uropathy. No distant lesions to parenchymal organs were detected (Figure 1D-F). In the context of reduced Hgb, the patient underwent a transfusion and was hospitalized in the urology department. Unilateral orchiectomy with lymph node dissection was performed (Figure 1B). First, an inguinal incision was made and the enlarged nodes of left inguinal chain were identified. There was no clear dis- tinction between metastatic lymph nodes and the testicular mass. After cau- tious isolation left inguinal nodes were dissected. Subsequently the inguinal portion of the tumour was also isolated and, after incision enlargement to the scrotum, was removed. Finally, scrotal portion of the mass was resected alongside with the sur- facing necrotic skin (Figure 1C). The right testis and penile shaft were preserved (Figure 2). Histological examination showed a typical seminoma. The neoplasm infiltrated the skin up to ulcerating it and involved lymph nodes (pT4, pN3, pM1, S3). The pres- ence of an intra-tumour phlogistic infiltrate was also revealed. Molecular morphology investigations with immunohistochemical characterization of the tumour showed positivity for Octamer-binding transcription factor (OCT) 3/4, Placental alkaline phosphatase (PLAP), b-HGC, CD117, Leukocyte common antigen (LCA, in the intra tumour inflammatory component) and CD30. Following surgery, the patient received four three-week- ly cycles of standard BEP (Bleomycin 30 UI IV weekly on days 1.8 and 15; Etoposide 100 mg/m² IV on days 1-5; Cisplatin 20 mg/m² IV on days 1-5 (6). CT scan taken one month after the completion of chemotherapy showed a great deal of reduction in the retroperitoneal lymph node masses (6 x 4 cm current vs 17 x 12 cm prior). Serum level of tumour markers was also decreased (Table 2). Subsequently, the patient underwent CT-scan at 3-month intervals. Abdominal and chest imaging showed a stable disease (SD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) (7) with no parenchymal metas- tases for one year and half. A progressive disease (PD) was documented after 18 months. CT-scan showed a new dimensional increase in the left periaortic lymph node tis- sue (55 x 35 mm current vs 50 x 25 mm prior), along the left external iliac chains (57 x 44 cm current vs 47 x 37 cm prior) and the appearance of infiltration of the left iliac and Table 1. Blood tests. Result Reference values Haemoglobin (g/dl) 6.9 13.0-16.0 Red blood cells (mmc) 3.1 4.5-5.3 x 10˄6 Hematocrit (%) 24 37.0-49.0 MCH (pg) 21.8 25.0-35.0 MCHC (g/dl) 28 32.0-36.0 White blood cells (u/L) 8.97 4.00-10.0 x 10˄3 Platelets (mmc) 479 150-450 x 10˄ Fibrinogen (mg/dl) 542 189-400 Glucose (mg/dl) 117 74-106 Creatinine (mg/dl) 0.90 0.66-1.25 Urea (mg/dl) 20.0 9.0-20.0 Albumin (g/dl) 2.6 2.5-5.2 Sodium (mmol/L) 138 136-146 Potassium (mmol/L) 5.40 3.50-5.10 Calcium (mmol/L) 2.3 2.1-2.55 AST (U/L) 35 15-46 ALT (U/L) 21 11-66 Amylase (U/L) 73 30-110 Lipase (U/L) 157 313-618 CPK (U/L) 21 55-170 Total Bilirubin (mg/dl) 0.60 0.20-1.30 LDH (U/L) 9047 313-618 Beta-HCG (mUI/ml) 4873 0-5 Alpha-fetoprotein (ng/ml) 33.4 < 6 MCH: Mean Cell Hemoglobin, MCHC: Mean Cell Hemoglobin Concentration, AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, CPK: Creatin phosphokinase, LDH: Lactate Dehydrogenase, HCG: Human Chorionic Gonadotropin. Figure 1. (A) Voluminous and necrotic scrotum at the diagnosis. (B) Intra-operative photograph. (C) Post-operative photograph of resected scrotal mass. (D-F) Computed tomography shows extensive abdominal diffusion of tumour. Archivio Italiano di Urologia e Andrologia 2021; 93, 1 A. Antonaci, D. Fasanella, V. Galica, et al. 66 psoas muscles by the pathological lymph node tissue (7). Moreover, the patient underwent a PET-CT scan that showed an intense metabolic activity corresponding to a voluminous lymph node masses (10 x 13 cm) in the left iliac region, infiltrating the left ileo-psoas muscle. After considering the disease progression, we had a multi-disciplinary meeting. As salvage chemotherapy the patient is being treated with four three-weekly cycles of standard TIP (Paclitaxel 175 mg/m² IV on day 1; Cisplatin 20 mg/m² IV on days 1-5; Ifosfamide 1000 mg/m² IV on days 1-5). In case of mass reduction, a combined surgi- cal retroperitoneal lymph node dissection (RPLND) and radiotherapeutic approach will be evaluated. DISCUSSION In this report, we described a rare case of large semino- ma extending to the inguinal canal with diffuse retroperi- toneal spreading and skin ulceration. Presentation at advanced stage or even metastatic at diagnosis is more common for NGCTTs (5). Our case is paradigmatic for several reasons. First of all, the age of diagnosis. Our patient presented a primary tes- ticular cancer in the absence of risk factors and at an age older than usual. This highlights the importance of gen- ital examination at every age, even when the probability of a testicular tumour is low. Moreover, our patient had a very unusual presentation. Indeed, while most of testis cancers are diagnosed as localized tumours of few cen- timeters in diameter, in our case the patient turned to physicians only when symptomatic. When investigating the reasons why the patient delayed the primary inter- vention, a complex mix of personal, familiar and social causes emerged. Several studies have shown a detrimen- tal effect of low socio-economic and familiar status on cancer awareness and intervention timing (8, 9). In a recent analysis Macload et al. showed that socio-econom- ic status was associated with poorer oncological out- comes and a more difficult access to primary treatment in patients with testicular cancer (10). Our case corrobo- rates these evidences and suggests the importance of a social tissue that could led to prompt access to primary care and early diagnosis. It is of note that the Italian one is a single payer healthcare system. In consequence, cure costs are not one of the major barriers to early diagnosis and treatment. However, even in this context weaker social strata still exist. Within this strata population could be more susceptible to experiment worse oncolog- ical outcomes. In fact, even after a wide surgical excision and associated chemotherapy, as recommended by inter- national guidelines (11), we obtained only a partial response with a subsequent relapse of the disease. Furthermore, in our case is evident how, even if cis- platin-based regimen is effective on testis cancer, a mul- tidisciplinary approach should be warranted. Early diagnosis, a multidisciplinary approach and a close follow-up remain mandatory to improve prognosis of testicular cancer (12, 13). After relapse, our patient will undergo four cycles of TIP (14). Surgery and radiotherapy should be considered in the case of mass reduction and resectable masses with small residual tumour (15). Moreover, a close follow-up of all psychological aspects was planned in consideration of the high psychological burden of testis cancer. CONCLUSIONS In conclusion, we reported an extremely rare presenta- tion of locally advanced testis cancer, resulting from the combination of cancer and patient related conditions. Early diagnosis is fundamental to guarantee a good onco- logical prognosis for testis cancer. Moreover, a multidis- ciplinary approach is important to guarantee a good oncological outcome. REFERENCES 1. Chia VM, Quraishi SM, Devesa SS, et al. International trends in the incidence of testicular cancer, 1973-2002. Cancer Epidemiol Biomark Prev. 2010; 19:1151-9. 2. Huyghe E, Matsuda T, Thonneau P. Increasing incidence of testic- ular cancer worldwide: a review. J Urol. 2003; 170:5-11. 3. Shanmugalingam T, Soultati A, Chowdhury S, et al. Global inci- dence and outcome of testicular cancer. Clin Epidemiol. 2013; 5:417-27. 4. Moch H, Cubilla AL, Humphrey PA, et al. The 2016 WHO clas- sification of tumours of the urinary system and male genital organs- Part A: Renal, penile, and testicular tumours. 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Correspondence Alessio Antonaci, MD Luigi Schips, MD Michele Marchioni, MD Daniela Fasanella, MD (Corresponding Author) danielafasanella@libero.it Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University of Chieti, Urology Unit, SS Annunziata Hospital Via dei Vestini, 66100, Chieti (Italy) Vikiela Galica, MD Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila “San Salvatore” Hospital, L’Aquila (Italy) Nicola Tinari, MD Department of Medical, Oral and Biotechnological Sciences and Center for Advance Studies and Technology (CAST), G. D'Annunzio University of Chieti, Chieti (Italy) Jamara Giampietro, MD Pietro Di Marino, MD Clinical Oncology Unit, SS Annunziata Hospital, Chieti (Italy) Andrea Delli Pizzi, MD Raffaella Basilico, MD Department of Neuroscience, Imaging and Clinical Sciences, G. D'Annunzio University of Chieti, Chieti (Italy)