Tag Archive for: asbestos

1. Senior House Officer, Department of Urology, South Warwickshire NHS Foundation Trust, Warwick, United Kingdom

2. Consultant Histopathologist, Department of Histopathology, South Warwickshire NHS Foundation Trust, Warwick, United Kingdom

3. Consultant Urologist, Department of Urology, South Warwickshire NHS Foundation Trust, Warwick, United Kingdom

We report two cases of mesothelioma of the tunica vaginalis, one primary and one secondary, both with a history of possible exposure to asbestos and discuss their pathogenesis, diagnosis and management.

The first patient is an 89 year-old man referred with recurrent left scrotal swelling following repeated fluid aspirations. His only exposure to asbestos had been through his son who had died one year previously of asbestosis.  At hydrocoelectomy, a thickened tunica vaginalis and heavily blood stained fluid were noted.  Histopathology and immuno-staining confirmed malignant mesothelioma and urgent radical orchidectomy was performed. The tumour recurred within a month with spread to mediastinal and para-aortic lymph nodes.

The second patient is a 68 year-old man referred with increasing shortness of breath and pain over the left side of his chest. He was a retired brick layer with possible occupational exposure to asbestos. Investigations and biopsy established a diagnosis of pleural mesothelioma.  During evaluation for chemotherapy, he presented with a hard testicular lump and underwent radical orchidectomy. Histology confirmed the presence of mesothelioma involving the tunica vaginalis. Follow-up CT scan showed no abdominal or pelvic disease.

Malignant mesothelioma of the tunica vaginalis is an uncommon, locally aggressive tumour, with over 200 cases reported in the literature to date [1]. The disease usually presents in men over 50 years of age, though, there have been cases reported in younger age groups [2] [3]. Exposure to asbestos has been considered as a risk factor. Patients usually present with a hard testicular lump or scrotal swelling. However, the disease lacks characteristic symptoms and signs so that in most cases the diagnosis is made following surgical exploration.  Mesothelioma of the tunica vaginalis has a poor prognosis and high rate of recurrence and nodal metastases. Here we present two cases of malignant mesothelioma of the tunica vaginalis, one primary and one secondary, both associated with a history of possible exposure to asbestos.

An 89 year old man was referred with a 6-month history of swelling in the left hemi-scrotum. The referring general practitioner, suspecting a hydrocoele, aspirated fluid on two occasions but the swelling soon returned. On examination there was a trans-illuminating large left sided hydrocoele. At elective hydrocoelectomy, we found heavily blood stained fluid and a thickened hydrocoele wall. Microscopic examination of the surgical resection specimen revealed fibrous tissue infiltrated by acinar and papillary structures (Fig. 1).

Figure 1. Microscopic examination of the surgical resection specimen

The differential diagnosis included adenocarcinoma and mesothelioma.  Immunohistochemistry supported a final diagnosis of malignant mesothelioma as follows: positivity for calretinin (Fig 1 inset), epithelial membrane antigen (EMA), cytokeratin (CK)20,  and negative for CK5, CK6, CEA, BerEP4, thyroid transcription factor 1 (TTF1), oestrogen receptor, thyroglobulin and prostate specific antigen.

The patient underwent radical orchidectomy with wide local excision. Pathological examination confirmed mesothelioma of the tunica vaginalis extensively infiltrating the epididymis (Fig. 1A) and the testicular parenchyma with vascular invasion.  Tumor seedlings were also noted in the dermal scar tissue. Following the diagnosis, further questioning revealed no personal history of direct asbestos exposure.  However, the patient had been living with his son who had occupational asbestos exposure and had died of asbestosis one year prior to this presentation.

One month later the patient’s wound broke down and on examination nodules were palpable in the wound. A further biopsy confirmed locally recurrent disease. CT scan of the chest and abdomen showed no evidence of pleural or peritoneal tumour, but identified significant mediastinal and left sided para-aortic lymph node disease without any pelvic lymphadenopathy. He declined further active management and died within a few months.

A 68 year old retired man was referred by the general practitioner to a respiratory physician, with a history of increasing shortness of breath and fatigue for 2 months. The patient also reported left sided lower chest pain and mild cough. There was no history of haemoptysis, weight loss or night sweats. He was an ex-smoker (for 30 years).  There was a possibility of asbestos exposure during his former job as a brick layer. On auscultation, there was decreased air entry on the left side of his chest.  Chest X-ray showed a large left sided pleural effusion. An inter-costal tube was placed which drained 6L of thick haemorrhagic fluid over an 11-day period with a good clinical symptomatic response. CT scan of his thorax initially showed no underlying lung or pleural pathology. Pleural fluid cytology was reported as showing individual, dispersed, reactive mesothelial cells, abundant neutrophils and macrophages, but no malignant cells. Subsequent MRI scan also revealed no suggestion of a neoplastic process. Suspecting infection, he was treated with antibiotics and discharged with close follow-up.

Follow-up chest X-ray 6-months later showed some increased markings present locally in the left lower zone possibly indicating focal inflammatory changes. Within the next 3-months, there was a recurrence of his symptoms and the patient was referred to cardiothoracic surgery.  A video assisted thoracoscopic examination was suspicious of pleural mesothelioma and a biopsy was taken. Histology confirmed the diagnosis of an epithelioid malignant mesothelioma.

During his preparations for chemotherapy, the patient was referred to urology with the recent onset of a swelling in his right testicle. On examination, the left testis was normal, but the right testis was rock hard. An ultrasound scan showed a solid, low echogenicity, 3.5cm mass within the right inguinal canal that appeared to be arising from the right epididymis. A radical orchidectomy was performed. The histopathology revealed malignant mesothelioma of tunica vaginalis (Fig. 2) enveloping the testis, epididymis and spermatic cord up to and including the proximal resection margin.

A follow-up CT scan of the thorax, abdomen and pelvis showed significant deterioration in the pleural lesion but no other extra-thoracic abnormality. The patient died of progressive pleural disease 2 years from the first referral (10 months after his radical orchidectomy).  There is no information regarding local recurrence of the intra-scrotal disease.

Malignant mesothelioma arises from the mesothelial cells lining the pleural, peritoneal, and pericardial cavities and rarely the tunica vaginalis. Pleural mesothelioma is by far the most common form of mesothelioma and has a well-recognised link to asbestos exposure [4].  Mesothelioma of the peritoneum or tunica vaginalis is rare in the absence of pleural disease but peritoneal involvement may present with spread to the tunica vaginalis because the latter develops as a direct extension of the peritoneal mesothelium. During the embryonic period all serous cavities develop from a common coelom and are continuous until partitions separate them. Malignant cells may track down from the pleural cavities via persisting connections between the body cavities or by direct extension of disease through the diaphragm. In our second patient, who developed overt pleural disease and spread to tunica vaginalis without any abdominal lesion, we presume this was the case.

Asbestos exposure, trauma and chronic hydrocoele have all been implicated as risk factors in the development of paratesticular mesothelioma [2] [5]. A few cases have also been reported with no prior associated disease process [6].  Due to the rarity of primary tunica vaginalis mesothelioma, little is known of its pathogenesis. In patients with asbestos exposure, we speculate that the asbestos fibres may collect in the tunica vaginalis via the coelomic connections described earlier. A small number of fibres may also reach the area via the blood stream after being absorbed from the lungs and gastrointestinal tract. Asbestos exposure mainly occurs from breathing in asbestos fibres. When products containing asbestos are disturbed, they release fibres into the air which may be inhaled [7]. Oral and dermal exposures have also been described [8]. Familial occupational exposure may also lead to indirect exposure via contaminants brought home. Plas et al reported in their study that a familial occupational history to asbestos increased the risk of malignant mesothelioma of tunica vaginalis 10-fold [2]. The relationship between asbestos exposure and mesothelioma is well established but the mechanisms underlying tumourogenesis are not fully understood. Chronic irritation leading to a hyperplastic inflammatory response along with oncogenic mutations caused by the asbestos fibres may eventually lead to tumour development [4]. We consider our first case to be a presentation of primary tunica vaginalis mesothelioma without pleural or peritoneal disease.  The mediastinal and para-aortic lymph node disease are compatible with metastases from the scrotal disease.  The potential source of asbestos exposure was his son who had died one year earlier of asbestosis and who could have brought contaminants home through his work clothes thirty years earlier.

Mesothelioma presenting in the tunica vaginalis usually affects men between 50 to 70 years of age. The disease presents as a scrotal swelling or hard testicular mass but is rarely diagnosed pre-operatively [2]. The histopathological diagnosis of malignant mesothelioma can be challenging and should be supported by immunohistochemical studies. Winstanley et al studied the immunohistochemical profile of 20 testicular malignant mesotheliomas finding the following positivity rates: calretinin and EMA 100%; thrombomodulin 89%; CK7 83%: CK5/6 72% but only 11% were positive for BerEp4. All cases were negative for CK20 & CEA [9]. Calretinin is a vitamin D dependent calcium binding protein, detected in most malignant mesotheliomas, and considered one of the most specific markers for epithelioid mesothelioma [10]. The main differential diagnoses for mesotheliomas are rare primary adenocarcinomas of the rete testis and metastatic adenocarcinomas that are calretinin and CK5/6 negative and usually BerEP4 and CEA positive.

In any case of confirmed mesothelioma of the tunica vaginalis, radical orchidectomy remains the treatment of choice. Adjuvant radio- or chemotherapy is advised during initial management but radiotherapy is considered to be more effective [2]. In 1998, Plas et al reviewed 73 cases of testicular mesothelioma and found 37.5% developed tumour recurrence following local resection of the hydrocoele wall while only 10.5% did so after scrotal orchidectomy and 11.5% after inguinal orchidectomy [2]. The median survival of patients was reported to be 23 months. The risks of recurrence following radical treatment is maximal during the first two years and close monitoring and follow-up is therefore required [2]. Malignant mesothelioma is often extensive at presentation with a high incidence of rapid local progression and metastatic spread as in our two patients.

Primary or secondary mesothelioma of the tunica vaginalis is extremely rare in occurrence. Preoperative diagnosis is difficult due to the rarity of the disease and the non-specific clinical presentations. A high index of suspicion is required in all patients with scrotal swellings and known exposure to asbestos. Increased awareness of the condition might help in improving the pre-operative diagnosis. The tumour has a rapidly progressive course with a high recurrence rate and poor prognosis. Early diagnosis, vigorous management and close follow-up may provide a better outcome and may improve disease free survival.

1. Bisceglia M, Dor DB, Carosi I, Vairo M, Pasquinelli G. Paratesticular mesothelioma: Report of a case with comprehensive review of literature. Adv Anat Pathol 2010. 17:53-70.

2. Plas E, Riedl CR, Pflunger H; Malignant mesothelioma of the tunica vaginalis testis: review of the literature and assessment of prognostic parameters. Cancer 1998. 83:2437-2446.

3. De Lima GR, de Oliveira VP, Reis PH, Pinheiro FG, Lima MV, Gonzaga-Silva LF. A rare case of Malignant Hydrocele in a young patient. J Paediatr Urol.  2009 Jun; 5(3):243-5; Epub 2008 Dec 12.

4. Cancer Research UK. Mesothelioma: Risks and Causes. https://cancerhelp.cancerresearchuk.org/type/mesothelioma/about/mesothelioma-risks-and-causes

5. Abe K, Kato N, Miki K, Nimura S, Suzuki M, Kiyota H, Onodera S, Oishi Y. Malignant mesothelioma of testicular tunica vaginalis. International Journal of Urology 2002. 9:602-603.

6. García de Jalón A, Gil P, Azúa-Romeo J, Borque A, Sancho C, Rioja L.A; Malignant mesothelioma of the tunica vaginalis: Report of a case without risk factors and review of the literature. International Urology and Nephrology 2003. 35(1):59-62

7. Agency for Toxic Substances and Disease Registry. What is Asbestos? Retrieved April 10, 2009 from: https://www.atsdr.cdc.gov/asbestos/more_about_asbestos/what_is_asbestos/

8. Agency for Toxic Substances and Disease Registry. Toxicological Profile for Asbestos. September 2001. Retrieved April 10, 2009 from: https://www.atsdr.cdc.gov/toxprofiles/tp61.pdf

9. Winstanley AM, Landon G, Berney D, Minhas S, Fisher C, Parkinson MC. The immunohistochemical profile of malignant mesotheliomas of the tunica vaginalis: a study of 20 cases. Am J Surg Pathol 2006. 30:1-6

10. Candura SM, Canto A, Amatu A, Gerardini M, Stella G, Mensi M, Poggi G. Malignant mesothelioma of the tunica vaginalis testis in a petrochemical worker exposed to asbestos. Anticancer Research 2008 Mar-Apr; 28(2B):1365-68.