Primary malignant mesothelioma of the tunica vaginalis presenting as hydrocele: imaging pitfalls

Summary

A man in his late 70s presented with progressive, painless scrotal swelling. The initial ultrasound was reported as a simple hydrocele, and he was scheduled for surgery. At operation, friable nodules on the tunica vaginalis were biopsied, confirming malignant epithelioid mesothelioma. Staging CT showed no pleural or peritoneal disease, supporting a primary tunica vaginalis origin. As the tunica vaginalis is an embryological continuation of the peritoneum, it is exceptionally rare for mesothelioma to arise here as a true primary rather than as a secondary spread from the peritoneum. This case highlights a rare primary malignant mesothelioma masquerading as a hydrocele, the limitations of ultrasound as a sole diagnostic tool and the importance of maintaining suspicion when operative findings are discordant with imaging.

Background

Malignant mesothelioma is a rare but aggressive neoplasm, most often originating in the pleura or peritoneum. Involvement of the tunica vaginalis testis, an embryological continuation of the peritoneum, accounts for fewer than 3% of all mesotheliomas and is described predominantly in isolated case reports and small series.^1–3 It tends to affect older men and typically presents as painless scrotal enlargement, usually attributed to a hydrocele.^{4 5} Diagnosis is usually made following surgical exploration, and prognosis is poor with high rate of recurrence or nodal metastases.⁶

While asbestos is a well-established risk factor for pleural mesothelioma, its association with tunical disease is inconsistent.⁷ Other proposed contributors include chronic hydrocele, trauma, long-standing inflammation and polyoma virus SV40, though definitive causal relationships remain unproven.⁸

Given its rarity and nonspecific presentation, primary tunical mesothelioma carries major diagnostic and clinical implications. Early recognition is critical, as prompt surgical excision may be curative before local or distant spread.^{2 3 6 9} Awareness among radiologists and urologists can therefore directly influence outcomes.

This case contributes to the limited literature on primary tunica vaginalis mesothelioma and underscores the importance of careful imaging interpretation and early biopsy in atypical cases even if initially appearing benign or risk factors are absent.

Case presentation

A man in his late 70s reported several months of progressive, painless left-sided scrotal swelling. He had no systemic symptoms.

He had worked in a non-industrial office-based job with no known exposure to asbestos or industrial chemicals. There was no history of prior scrotal trauma, chronic hydrocele, radiation, or family history of malignancy. He was a lifelong non-smoker. Examination showed a fluctuant, transilluminable swelling consistent with hydrocele.

Ultrasound was reported as uncomplicated hydrocele and elective hydrocele surgery was arranged. Intraoperatively, multiple red friable nodules were seen on the tunica vaginalis and biopsied (figure 1).

Figure 1. Intraoperative photograph showing multiple red, friable nodules studding the tunica vaginalis, consistent with malignant mesothelioma.

Investigations

1. Ultrasound (initial): Reported as hydrocele on the affected side; retrospective review revealed subtle mural nodularity (figure 2)

2. Histopathology (intraoperative biopsy of tunica vaginalis nodules): The tumour comprised tubulopapillary structures and solid groups of atypical epithelioid cells with irregular hyperchromatic nuclei and nuclear pleomorphism, with focal extension into the epididymis. Moderate nuclear atypia and >5 mitoses per 2 mm² were present (figure 3). Immunohistochemistry showed positivity for AE1/3, calretinin, WT1 and D2-40, with patchy positivity for CK7 and desmin (figure 4); negative for BerEP4, CK5/6, CEA and CK20. Features were consistent with malignant epithelioid mesothelioma. No sarcomatoid component was identified (figure 5).

3. Ancillary molecular testing: BAP1 immunohistochemistry demonstrated preserved nuclear expression. p16 (CDKN2A) fluorescence in situ hybridisation (FISH) showed loss of expression (homozygous deletion), supporting a diagnosis of malignant mesothelioma.

4. Serum tumour markers: alpha-fetoprotein (AFP), human chorionic gonadotrophin (β-HCG) and lactate dehydrogenase (LDH) levels obtained post-operatively were normal.

5. CT of the chest, abdomen and pelvis (contrast-enhanced): No pleural or peritoneal thickening, masses or nodal disease to suggest extratesticular mesothelioma (figure 6).

Figure 2. Scrotal ultrasound of the left hemiscrotum. (A, B) Longitudinal views demonstrating anechoic fluid collection with no mural nodularity (arrows), consistent with a hydrocele. (C) Transverse view with colour Doppler showing no vascularised soft tissue.

Figure 3. Histological sections of the tunica vaginalis lesion showing epithelioid mesothelioma with tubulopapillary and solid architecture, nuclear atypia, brisk mitotic activity and focal epididymal involvement (H&E stain, original magnifications×20, ×100, ×200).

Figure 4. Immunohistochemical staining showing strong diffuse positivity for mesothelial markers (WT1), supporting the diagnosis of malignant epithelioid mesothelioma (H&E counterstain; magnifications ×10–20).

Figure 5. Immunohistochemical section showing absence of staining for carcinoma-associated markers (example: BerEP4), confirming mesothelial rather than epithelial phenotype (H&E counterstain; ×4).

Figure 6. Contrast-enhanced CT abdomen (axial slice) demonstrating no pleural, peritoneal or nodal involvement, consistent with disease confined to the tunica vaginalis.

Differential diagnoses

Hydrocele was the working diagnosis. Other considerations included epididymal cyst, spermatocele, haematocele, inguinal hernia, testicular tumour and paratesticular lesions (eg, adenomatoid tumour). Malignant mesothelioma was only suspected intraoperatively.

Treatment

The patient initially underwent elective surgery for presumed hydrocele, during which the fluid was drained and multiple friable nodules were identified on the tunica vaginalis. These nodules were excised intraoperatively and sent for histopathological analysis, confirming malignant epithelioid mesothelioma.

The case was subsequently discussed at a specialist mesothelioma multidisciplinary team (MDT). Given the absence of radiological metastatic disease, complete macroscopic excision of visible lesions, favourable epithelioid histology and the patient’s clinical status, radical inguinal orchiectomy was not pursued. The patient is currently under active surveillance with six monthly contrast-enhanced CT-CAP and scrotal ultrasound.

Discussion

Malignant mesothelioma of the tunica vaginalis testis is rare, representing <3% of all mesotheliomas and only a minute proportion of paratesticular tumours.¹⁰ While many cases reflect secondary spread from pleural or peritoneal disease, true primary tumours are exceptional but clinically important because aetiology, prognosis and management differ.^{9 11} Unlike pleural or peritoneal mesotheliomas, which are strongly associated with asbestos exposure, primary tunical tumours show weak or inconsistent links.^{10 12} Secondary disease usually requires multimodal therapy, whereas early surgical resection may be sufficient in selected primary cases.^{2 9}

Diagnosis is frequently delayed as the tumour often masquerades as benign hydrocele. Ultrasound remains the first-line investigation for scrotal swelling, but small mural nodules can be missed. In our case, the preoperative scan was reported as a simple hydrocele, with subtle nodularity only appreciated retrospectively. This emphasises the limitations of ultrasound as a sole diagnostic tool and the value of repeat targeted imaging or senior radiologist review when clinical or intraoperative findings are discordant.^13–15 A proposed diagnostic algorithm for painless scrotal swelling in older men is presented in figure 7. Adjunct modalities such as Doppler ultrasound and MRI may better delineate vascularised or papillary lesions, but definitive diagnosis rests on histopathology.^14–17 Staging CT of the chest, abdomen and pelvis is essential to exclude pleural or peritoneal disease; in our patient, the absence of such involvement confirmed a primary origin.

Figure 7. Stepwise diagnostic algorithm for painless scrotal swelling in older men, highlighting the role of ultrasound, intraoperative biopsy, histopathology and staging CT to identify primary malignant mesothelioma of the tunica vaginalis. Abbreviations: AFP, alpha-fetoprotein; β-hCG, beta-human chorionic gonadotropin; IHC, immunohistochemistry; LDH, lactate dehydrogenase; MDT, multidisciplinary team.

Morphologically, this was a high-grade epithelioid malignant tumour with an infiltrative growth pattern, pleomorphic nuclei, frequent mitotic figures and areas of necrosis. Based on morphology, benign entities such as reactive mesothelial hyperplasia and adenomatoid tumour were excluded.

The mesothelial origin was confirmed by strong, diffuse positivity for calretinin, WT1 and D2-40. Patchy desmin positivity was also observed. While reactive mesothelial proliferations often exhibit focal desmin expression, malignant mesotheliomas are usually desmin-negative, though occasional focal staining has been reported.¹⁸ In this case, the morphology and mesothelial marker profile strongly supported malignant mesothelioma, so the patchy desmin positivity was not given significant diagnostic weight.

CK5/6 staining was negative. Although CK5/6 is typically positive in epithelioid mesotheliomas, rare high-grade tumours may lack expression.^{16 19} Positivity for calretinin, WT1 and D2-40, together with the morphological features, confirmed the diagnosis despite this atypical finding.

In diagnostically challenging cases, ancillary molecular studies such as BAP1 immunohistochemistry and p16 (CDKN2A) FISH may confirm mesothelial malignancy.^20–23 In our case, following Regional Mesothelioma MDT referral, BAP1 showed preserved nuclear expression (retained BAP1 has been described in a subset of mesotheliomas),^{20 22} while p16 showed loss of expression (homozygous deletion), supporting malignancy.

Malignant mesothelioma is subclassified into epithelioid, sarcomatoid and biphasic subtypes, with prognostic implications extrapolated primarily from pleural disease. Epithelioid mesothelioma, as seen in our patient, carries the most favourable prognosis, with median survival of 13–20 months in pleural disease, compared with 6–8 months for sarcomatoid or biphasic subtypes.^{24 25} The epithelioid variant is also the most common in tunical disease, accounting for approximately 80% of reported cases.²⁶ Sarcomatoid and biphasic tumours are associated with higher rates of aggressive local recurrence and distant metastasis. Our patient’s pure epithelioid morphology, low-volume disease and negative staging CT may favour a less aggressive course, though evidence specific to tunical disease remains limited.

As a single case report, this study cannot establish causation, identify prognostic factors or demonstrate treatment efficacy. The decision to pursue surveillance rather than radical orchiectomy was based on individual patient factors and MDT consensus; this approach requires validation through larger series. Our findings should be interpreted as hypothesis-generating.

Our case adds to the limited literature by demonstrating a primary tunical mesothelioma with no recognised risk factors and no nodal or distant spread. Epidemiological reviews estimate fewer than 300 cases reported worldwide from 1943 to 2018, most occurring in men in the sixth to eighth decades, with a slight left-sided predominance.¹⁰ Asbestos exposure is documented in only about a quarter of reported cases.¹⁰ More recent reports continue to underline the diagnostic challenge, with many tumours identified only intraoperatively.^27–29

The optimal management remains undefined, with no dedicated NICE or international guidelines. Most published series report radical inguinal orchiectomy as primary treatment, often with adjuvant therapy for high-risk features.² Recurrence rates following orchiectomy alone are substantial (53%),³⁰ and many relapses are distant, suggesting occult micrometastatic disease may be present even with negative staging.³¹

In our patient, the mesothelioma MDT elected active surveillance rather than orchiectomy or adjuvant therapy based on (1) complete macroscopic excision with histologically negative margins; (2) negative staging CT; (3) asymptomatic status, normal tumour markers and ECOG 0; (4) patient preference after shared decision-making; and (5) favourable epithelioid subtype. We acknowledge this deviates from the dominant paradigm. Some clinicians would advocate orchiectomy regardless of intraoperative findings, or adjuvant chemotherapy extrapolated from pleural mesothelioma.⁹ However, evidence for adjuvant therapy in tunical mesothelioma is limited to case reports, and toxicity in an elderly asymptomatic patient may outweigh uncertain benefits.

We recognise that active surveillance risks undertreatment of a biologically aggressive malignancy. Radical inguinal orchiectomy remains the standard of care in most published series; clinicians should not deviate without specialist MDT input and careful patient selection. Our patient is followed with six monthly imaging, and any progression will prompt salvage orchiectomy and/or systemic therapy.

Our case does not establish efficacy of surveillance over orchiectomy but highlights that in carefully selected patients with completely excised, low-volume, epithelioid-only disease and negative staging, surveillance may be a reasonable alternative within a specialist MDT setting. Prospective registry data are urgently needed.

Learning points.

• Hydrocele can conceal significant tunical pathology; careful ultrasound scrutiny of the tunica vaginalis for mural nodularity is essential.

• Primary mesothelioma of the tunica vaginalis should be considered in persistent or atypical scrotal swelling, even when risk factors are absent.

• Intraoperative identification of tunical excrescences warrants biopsy to prevent diagnostic delay.

• Staging CT of the chest, abdomen and pelvis is required to exclude pleural or peritoneal involvement and guide management.

• Histopathological morphology remains the cornerstone of diagnosis; atypical marker expression should be interpreted in balance and in the context of morphological assessment and other markers.