Primary seminal vesicle adenocarcinoma: a lethal yet cryptic malignancy with review of literature

Abstract

The rarity of primary seminal vesical adenocarcinoma (PSVA) coupled with mostly late and advanced presentation with high mortality makes it an unanticipated malignancy with poor prognosis. Although there has been sporadic reporting of cases, the dearth of literature makes standardised care a challenge. The detection has incorporated immunohistochemistry for establishing the site of origin as well as the differentiation of primary from metastatic cancer. Surgical management with seminal vesiculectomy continues to be the mainstay of treatment, but difficult anatomy and delayed intervention do lead to an increased chance of residual disease that may warrant further adjuvant chemoradiation. We present a case report where PSVA developed in a patient with Zinner syndrome—an observation that is extremely rare with a literature review of PSVA including the various aspects of management including contemporary diagnosis techniques.

Background

One of the rarest malignancies in urological oncology and therefore a health problem due to uncertainty of diagnosis, with only about 60 reported cases until, primary seminal vesicle adenocarcinoma (PSVA) continues to remain a diagnostic and therapeutic enigma.¹ Although most cases are asymptomatic in the early stages, the more advanced stages do present with haematuria, haematospermia, local and referenced pain, and/or upper tract obstruction due to mass effect. Many cases present with symptoms of metastases specific to the organ involved.

The differentiation between primary and secondary seminal vesicle adenocarcinoma is a challenge and an exercise that proves to be the most important in-effective management. Close collaboration of urology, radiology and pathology teams is often pivotal to arrive at the correct diagnosis.

The treatment modality offering best chance of cure continues to be surgical resection either by open method or minimally invasive techniques including laparoscopic and robot-assisted approaches. Radiation and chemotherapy in the neoadjuvant and adjuvant setting are used in the metastatic setting and locally advanced cases. Androgen deprivation therapy has also been reported effective in some cases of metastatic PSVA.² The dearth of case volume contributes to an often unrecognised diagnosis and snags with management that we have tried to simplify with this case report with literature review. Our attempt is to familiarise the practising urologist with the presentation of PSVA and present standard investigation and treatment practices.

Case presentation

A 28-year-old man presented to the out-patient clinic with worsening symptoms of perineal pain. Physical examination was significant for the right lower quadrant tenderness and a firm large mass palpable above prostate on digital rectal examination. Medical/social/family history was unremarkable and non-contributory to the patient’s current problem. Our working diagnosis based on the history and physical examination was a mass arising possibly from the pelvic or abdominal viscera, possibly benign/malignant or inflammatory.

Investigations

Based on the patient’s physical findings, we performed a CT scan with contrast of the abdomen and pelvis (figures 1 and 2) was to characterise the outline and the extent of the mass. It revealed a right-sided 15.4 cm seminal vesical cyst filling almost the entire pelvis and lower abdomen with extrinsic compression of the bladder and the prostate. The patient was also found to have right renal agenesis and a right ectopic ureter inserting into the seminal vesicle (figure 3). A diagnosis of Zinner syndrome was considered preoperatively.³

Figure 1.

Sagittal imaging of CT pelvis showing large right Seminal Vesicle (SV) cyst compressing bladder and prostate.

Figure 2.

Coronal CT imaging of pelvis showing large Seninal Vesicle (SV) cyst.

Figure 3.

Right renal agenesis supporting the diagnosis of Zinner syndrome.

Basic laboratory tests were within normal limits. No additional serum marker testing was performed.

Differential diagnosis

The relative rarity of large pelvic masses in young males made the initial differential diagnosis both easy and difficult for us. The working diagnosis was that of a pelvic extraperitoneal mass possibly a pelvic lymphangioma, primary pelvic gastrointestinal stromal tumour, congenital arterio-venous malformation and PSVA. The presence of the large (Seminal Vesicle) SV cyst on CT with clear planes of separation from the rest of the viscera with the association of Zinner syndrome made the diagnosis of PSVA the most likely one.

Treatment

In view of a possible PSVA, a robot-assisted laparoscopic resection of seminal vesical cyst was performed along with a right ureterectomy after being counselled regarding the potential morbidity of the procedure including postoperative erectile and ejaculatory dysfunction. The SV cyst was dissected completely free from the surrounding structures and resected with minimal spillage (figure 4). There were minimal adhesions to the rectum noted intraoperatively. The patient tolerated surgery well and had an uneventful recovery.

Figure 4.

Intraoperative photograph of the Seminal Vesicle (SV)cyst.

Final pathology of the specimen revealed a moderate-to-poorly differentiated adenocarcinoma of the seminal vesicle. The epithelial tumour cells were lining the interior seminal vesicle cyst wall. The tumour was composed of high-grade pleomorphic cells with large nuclei and scant clear cytoplasm. Tubular formation was evident (figure 5). The tumour was positive for cancer antigen 125, carcinoembryonic antigen and cytokeratin 7 (figure 6). There was no immunoreactivity with prostate-specific antigen (PSA), NK3 Homeobox 1 (NKX3.1), paired box gene 8 (PAX8) and cytokeratin 20.

Figure 5.

Seminal Vesicle (SV) adenocarcinoma demonstrating high-grade atypical pleomorphic cells with clear cytoplasm forming tubular structure (40×).

Figure 6.

Cancer antigen 125 immunoreactivity in seminal vesicle adenocarcinoma (40×).

The case was discussed in the tumour board and a decision was made to treat it like a tumour arising primarily from the seminal vesicles as there was no clinical, radiological or pathological evidence of any other primary. The rare nature of the disease and the lack of standardised chemotherapy protocols for PSVA was a dilemma and this was discussed as well in the institutional tumour board. The plan to initiate carboplatin/paclitaxel was based on the mullerian origin of the SV cyst which is similar to ovarian adenocarcinoma and the historical favourable response with this regime in treatment of the same. This was supported by Guindalini et al who reported a sustained and durable response to platinum-based chemotherapy.⁴ It was also decided to use the least toxic chemotherapeutic regime at the start in the form of carboplatin, in view of complete resection and negative surgical margins. He underwent six cycles of adjuvant carboplatin and paclitaxel.

Outcome and Follow-up

The patient withstood both the surgery and the adjuvant chemotherapy well. Surveillance imaging was performed at 3-month intervals during the first year. An MRI and Positron emission Tomography - Computerised Tomography (PET-CT) after chemotherapy was read as stable, without any evidence of recurrence. Surveillance with imaging every 6 months during the next 2 years and yearly imaging thereafter was normal. The patient was well with no signs of recurrence till about 6-year post-surgery (November 2018), when he presented with haematuria and nodularity in the prostate measuring 1.9×1.4 cm with enhancement on pelvic MRI. He underwent a cystoscopy that revealed papillary appearing prostatic urethral tumour measuring 3 cm. The tumour was resected entirely transurethrally, which was confirmed pathologically to be a recurrence of the original seminal vesicle adenocarcinoma. There was no evidence of metastases to any other part of the body on FDG PET (FluoroDeoxyGlucose PET) imaging. The patient underwent additional adjuvant chemotherapy with carboplatin and paclitaxel and has been free of recurrence until now and is healthy at present.

Discussion

The unusual presentation poses a diagnostic challenge to the clinician to differentiate it from other retrovesical tumours. The diagnosis is based on a combination of clinical findings, radiological examination and pathological results.

Clinical features

The average age of presentation is not accurately cited in literature. It is most common in men above 50 years (range 19–90 years).² Secondary neoplastic involvement of seminal vesicle is more frequent as compared with PSVA. Diagnosis is unlikely at an early stage due to the absence of symptoms and when the patients become symptomatic, they often suggest locally advanced disease masking the seminal vesicular origin of the tumour.^{3 5 6} It has been suggested that agenesis or dysgenesis of the kidneys with ectopic ureters exposes the epithelium of the seminal vesicles to carcinogens which could lead to PSVA in one or both the glands.⁷

The most common symptoms are non-specific. The patients may present with haematuria, haematospermia, dysuria, painful defecation, or pelvic and perineal pain.⁸ Our patient presented with persistent perineal pain and minimal irritative lower urinary tract symptoms. Digital rectal examination is an essential part of the physical examination to rule out prostate and rectal cancer.

Imaging

In the early stage of the disease, contrast-enhanced CT scan, MRI and ultrasonography may help in localising the tumour to seminal vesicle and exclude tumours of the adjoining organs such as prostate, rectum and urinary bladder. The radiological findings are usually described as a solid or cystic mass between the rectum and prostate or bladder.^9–11 Occasionally, a low-attenuated expansive process on the site of the seminal vesicle is found in CT scan.⁵ The partially cystic appearance on imaging studies can cause a diagnostic dilemma as it is difficult to differentiate from an old haemorrhage or abscess which are more common clinically than PSVA.¹² The usage of CT/MRI imaging can often demonstrate seminal vesicle origin of the tumour in an advanced stage of the disease.¹³ CT chest and abdomen or PET imaging has been described for metastatic workup and to determine response to systemic therapy.^{7 14} Cystoscopy and/or sigmoidoscopy may be considered to rule out tumour origin from either the bladder or the rectum/colon.

Pathology and immunohistochemistry

Despite the extensive usage of vastly improved modalities of CT/MRI for tumour origin and localisation, pathology still remains the gold standard for diagnosis of PSVA. The pathological diagnostic criteria established by Dalgaard and Giertson in 1956 for PSVA are¹⁵:

1. The tumour should be a microscopically verified carcinoma, localised exclusively or mainly to the seminal vesicle.

2. The presence of another simultaneous primary carcinoma should be excluded.

3. The tumour should preferably resemble the architecture of the non-­neoplastic seminal vesicle.

Benson et al added that identification of mucin production may also be considered diagnostically important.¹⁶

These strict criteria can be applied to surgically resected specimens, but are less suitable in evaluating image-guided needle biopsies or transurethral resection specimens in advanced cases. The role of tissue studies for establishing a diagnosis prior to definitive intervention must include immunohistochemical analysis in all cases.

PSVA has two main gross patterns. One of the types has firm, gritty cut surfaces with poorly defined margins 16 and others are mostly cystic and contain turbid red or haemorrhagic brown fluid,^{9 17} clear fluid⁸ or pus and necrotic material.¹⁸ Presence of papillary tumours in the cyst wall has also been described.¹⁰

The most common histology of PSVA is moderate-to-poorly differentiated adenocarcinoma with at least focal papillary architecture and tubular structures.^{2 17} An in situ component may help in establishing seminal vesicle origin in poorly differentiated cases if the tumour has not entirely destroyed the organ.^{11 18} Mucinous differentiation with goblet cells may be present in some patients.¹⁹ Desmoplastic reaction can also be found near the infiltrating glands¹⁶ and perineural and angiolymphatic invasion may also be seen. There have been few reports about primary squamous cell carcinoma (SCC). This histology is extremely rare and the prognosis is poor, with disease presentation usually being metastatic at diagnosis.²⁰ The differential diagnosis of SVC in immunohistochemistry (IHC) is mentioned in table 1.

Table 1.

Differential diagnosis of primary seminal vesicle adenocarcinoma based on immunohistochemistry

Type of cancer	CK-7	CK-20	CA-125	CEA	Prostein (p501s)	NKX3.1	CDX2	PAX8
Primary seminal vesical carcinoma	+	–*	+†	+/–	–	–	–	+/–
Prostate cancer	–‡	–	–	–	+	+	–	–
Rectal cancer	–	+	–	+	–	–	+	–
Urinary bladder adenocarcinoma	+§	-¶	+/–	–	–	–	–¶	–
Mullerian duct adenocarcinoma	+	–	+/–	+/–	–	–	–	NA

*Positive in only one case report 2.

†Negative in poorly differentiated carcinoma.

‡May be positive in ductal type prostate cancers.

§Negative in enteric types.

¶Positive in enteric types.

CA-125, cancer antigen 125; CDX2, caudal type homeobox transcription factor 2 protein; CEA, carcino-embryonic antigen; CK-7, cytokeratin 7; CK-20, cytokeratin 20; PAX8, paired box gene 8.

As there are no stains specific to seminal vesicle epithelium, the main goal of IHC is to rule out tumours originating from adjacent organs or metastatic from elsewhere rather than confirming seminal vesical origin. Poorly differentiated or anaplastic tumours, particularly in biopsy specimens, may not express markers typically seen in better differentiated tumours. Clinicopathological correlations become even more important in such settings.

Treatment

PSVA is a rare disease and standard treatment guidelines are not available. A multidisciplinary team approach is recommended. A recent case series by Guo et al concluded that combinations of radical surgery, radiation therapy, chemotherapy and androgen deprivation therapy benefit patients with PSVA.²¹ Complete surgical excision with pelvic lymphadenectomy has the best prognosis.¹⁶ The surgical approach of local or radical excision depends on the local extension of the disease. Surgical techniques can range from local excision to cystoprostatectomy, prostatectomy with seminal vesicle excision or pelvic exenteration. Primary radiation with curative intent has historically fared poorer than surgery for patients fit for resection.⁹ The approaches to open seminal vesiculectomy have been described via the transabdominal, transperineal and transcoccygeal methods. These approaches have good curative control, but are associated with considerable postoperative pain and morbidity. Surgery may be challenging due to difficult visualisation. Tang et al managed a case of primary SCC of the seminal vesicles with open approach and were able to resect the mixed solid/cystic mass in the right SV free from the surrounding structures without any reported problems.²² Endoscopic resection via the transurethral approach may be associated with less morbidity as compared with open resection, but the oncological outcomes are inferior and incur significantly higher failure and recurrence rates. The familiarity of minimally invasive prostatectomy made Kavoussi undertake laparoscopic seminal vesiculectomy with success in 1993,²³ and many single centre reports of oncologically safe laparoscopic seminal vesiculectomies with reduced blood loss and pain have been reported.^24–26 The advent of robotics in pelvic surgery associated with endowristed instrumentation and 3D magnified vision has made surgery much simpler than before. Minimal blood loss, comparable operative times and early discharge make robotic seminal vesiculectomy an attractive option for the management of PSVA. A case series of six patients with large seminal vesicle cysts revealed operative time of 198±23 min inclusive of cystoscopy time and estimated blood loss of 5–10 mL. Most patients were discharged on postoperative day 1 or 2.²⁷ It is therefore expected to be the treatment of choice in the future for management of these tumours.

Various adjuvant treatment modalities have been described. Adjuvant radiation is used in cases of incomplete resection or positive surgical margins.¹⁹ Hormonal therapy in the form of bilateral orchidectomy⁵ or antiandrogens⁸ has been used either as an adjuvant or palliative treatment. The rationale for antiandrogen therapy is hormone dependency of the seminal vesicles.²⁸ Adjuvant chemotherapy has been used rarely. Campobasso et al described a case with positive surgical margins and lymph node metastasis in which the patient received adjuvant four cycles of cisplatin-gemcitabine along with pelvic intensity-modulated radiotherapy with a radiation dose of 60 Gy. He was recurrence free at 21-month follow-up.¹

Neoadjuvant chemotherapy using six cycles of MVAC dose dense regimen (methotrexate 30 mg/m² D1, cisplatin 80 mg/m² D2; vinblastine 3 mg/m² D2, doxorubicin 30 mg/m² D2) once every 15 days was described by Terrisse et al.²⁹ The patient had partial response at primary site and complete response at pulmonary metastasis.

Chemotherapy is the mainstay of treatment in the metastatic setting. The various regimens used are folinic acid-fluorouracil, oxaliplatin (FOLFOX-6), docetaxel, cisplatin-gemcitabine and carboplatin-paclitaxel. Survival varies from 16 months to 4.5 years.⁴ Lal et al reported a case of metastatic PSVA to the liver managed with multiagent chemotherapy (FOLFOX-6) and androgen deprivation therapy (GnRH analogues).⁷ Terrisse et al also reported complete remission 4 years after pulmonary metastasectomy.⁸ Despite anecdotal cases of short intermediate term survival, most cases of PSVA are rapidly lethal because of the advanced stage at diagnosis with a 3-year mortality rates reported as high as 95%.

A recent review of literature concluded that although the best way of treatment is via the multimodal approach, the prognosis is generally poor and the mean survival is 2 years from diagnosis.³⁰ Our patient presented early with organ confined disease, and with adjuvant chemotherapy had been disease-free for close to 6 years. The recent recurrence appears confined to prostatic urethral mucosa without any involvement of the stroma. He has no urinary symptoms and has been functional sexually with minimal amount of ejaculation volume.

Learning points.

• Primary seminal vesicle adenocarcinoma is a rare yet lethal malignancy with vague symptomatology affecting men of a wide age range. A high suspicion on the part of the treating clinician is required to establish diagnosis.

• A multidisciplinary approach involving the urological and medical oncology specialities is required to treat the tumour.

• New advances in immunohistochemistry are extremely important in establishing the primary source of origin being the seminal vesicles as there are no stains for the seminal vesicle epithelium.

• Minimally invasive approaches like the robotic approach may be beneficial in reducing the blood loss and tumour spillage and at the same time help in faster recovery and better cosmesis.

• Surveillance is paramount as these tumours are known far recurrence and metastases, even after many years. Early intervention helps in effective disease control.