Case presentation: Mesothelioma of the tunica vaginalis. Dr Ben Shepherd Pathology Queensland Princess Alexandra Hospital Brisbane

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1 Case presentation: Mesothelioma of the tunica vaginalis Dr Ben Shepherd Pathology Queensland Princess Alexandra Hospital Brisbane

2 A 76 year old man presented June 2011 with a 6 month history of painless left testicular enlargement No constitutional symptoms Ex-smoker, no other known significant exposures Chronic hypertensive kidney disease Early dementia

3 Chronic hydrocoele repaired 2007 Reviewed months post repair with a scrotal lump, clinically thought benign, resolved with observation O/E (2011) A hard irregular intrascrotal mass palpably fixed to the testis No regional adenopathy Scrotal skin mobile

4 Inguinal orchidectomy performed The tunica were thickened and nodular on the posterior aspect of the inferior testicular pole Tunica adherent A solid grey white tumour 35mm based on the tunica involving testis and epididymis

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11 CK5/6 Calretinin EMA

12 Immunohistochemistry Positive: Calretinin, CK5/6 (focal), EMA, CK7, D240 Negative: S100, Melan A, inhibin, P63, TTF-1, PSA, CEA, CK20, CD30, PLAP, CD117

13 Diagnosis Malignant mesothelioma of the tunica vaginalis, epithelial type Post operative staging negative No additional treatment; remains disease free after 4 years

14 Discussion Mesothelial lesions of the paratestis 1. Reactive hyperplasia Occurs in the context of hydrocoele, haematocoele and hernia Combination of surface hyperplasia with underlying reactive fibrosis and entrapment of surface mesothelium may simulate a malignant process

15 Papillae, tubules, nests and cords may be seen within the fibrosis Reactive cytologic atypia common Architecturally complex proliferations with tissue destruction, infiltrative growth and marked cytologic atypia argue for malignancy A gross mass lesion excludes hyperplasia

16 A low power impression of a linear arrangement of nests/tubules (often widely spaced) as opposed to haphazard random arrangement is a useful finding FISH for 9p21 lesion may have an adjunct role in difficult cases but has low sensitivity

17 Reference 2

18 2. Adenomatoid tumour Common benign lesion of paratestis, often head of epididymis but also commonly involving tunica albuginea May involve adjacent testis, occasionally extensively Usually small (~2cm) but occasionally up to 7cm Asymtomatic, solitary, unilateral

19 Grossly circumscribed and pale Microscopically a variable admixture of tubules, cords, small nests of cuboidal cells with eosinophilic, amphophilic or vacuolated cytoplasm Fibrous stromal component, sometimes containing smooth muscle, is present to a variable degree Interstitial pattern of infiltration is common if parenchyma involved

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22 Typical examples are a spot diagnosis but because of the numerous variations on the morphologic themes, a variety of other neoplasms may be simulated; infarction may also cause diagnostic difficulty Lymphoid aggregates are useful clues Keratins and mesothelial markers positive Focal areas of malignant mesotheliomas (and rarely more extensively) may simulate adenomatoid tumour

23 3. Mesothelioma Benign variants- a small subset of what is already a rare tumour type at this site a. Multicystic and b. well differentiated papillary mesothelioma Multicystic mesothelioma mimics hydrocoele and represents a tumour composed of cystic spaces lined by a single layer of non-atypical mesothelium Vanishingly rare, apparently indolent

24 Pathology Outlines

25 Well differentiated papillary mesothelioma most commonly occurs in the peritoneum of young women Most commonly defined as a localised solitary tumour with an exclusively papillary architecture; papillae are lined by a single layer of bland cuboidal cells Despite very low numbers of reported cases (<15) meeting strict criteria, a benign course is expectedcomplete resection is necessary however Some authors prefer to regard these as favourable variants of mesothelioma rather than truly benign tumours

26 Wikipedia- user Nephron

27 Mesothelioma of uncertain malignant potential per Brimo, Illei and Epstein Difficulties encountered in classifying very rare lesions in which there is a prominent well differentiated papillary architecture but with the addition of any of: 1. Multifocality 2. Moderate nuclear atypia 3. Increased mitotic activity 4. More complex growth including tubules, cribriform, condensed growth Series of 8 cases, only 5 with follow-up beyond a year but no documented recurrence/ progression. Authors argue the need for an additional diagnostic category.

28 Malignant mesothelioma: Of mesotheliomas overall, around 1% occur in this site. ~250 cases reported in literature to date as short series and single cases Age range 7-87 yrs, most in sixth to eighth decades Most commonly presents as scrotal enlargement with hydrocoele (55%) or a mass (30%)

29 35-40% have a documented history of asbestos exposure Clinical diagnosis most frequently testicular tumour or hydrocoele Most arise in the tunica vaginalis, rarely the cord or epididymis Gross- variable: diffuse tunica thickening +/- multiple nodules +/- infiltration of intrascrotal structures Most (60-70%) are epithelial (epithelioid) type, less often mixed, only very rarely pure sarcomatoid (incl desmoplastic)

30 LM, IHC and EM features similar to mesothelioma at other sites Spectrum of differentiation: papillary (simple to complex, single lining layer to stratified) to tubular (simple vs slit like anastamosing vs large gland pattern/ cysts/ intracystic proliferation) to more poorly differentiated with cords, nests, sheets +/- necrosis Interface sections may show a transition from normal mesothelium to hyperplastic appearances to frank malignancy

31 Immunohistochemistry: positive pancytokeratins, CK7, CK5/6 (variable), EMA (membranous), thrombomodulin, D2-40, calretinin, WT-1 Negative (or weak focal) CK20, BerEP4, B72.3, MOC-31, Leu-M1

32 Prognosis Aggressive malignancy- both local invasion and metastases, lymphatic or haematogenous Local recurrence in up to 60% within 2 years Lethal in around 30%, median survival 24 months Better prognosis than mesothelioma at other sites, most likely because of superior surgical options

33 Other considerations- malignant epithelial lesions of paratestis 1. Mullerian type carcinoma especially serous carcinoma Centred in the epididymo-testicular groove Morphology as seen in gynae tract; benign, borderline, malignant Serous papillae tend to be broader with nuclear stratification, budding +/- cilia Psammoma bodies may be seen in mesothelioma or serous carcinoma but generally more frequent in serous carcinoma CA-125 and WT-1 coexpression useful for serous carcinoma, also CEA, BerEP4

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35 2. Rete testis carcinoma Very rare Strict criteria recommended 1. Absence of histologically similar primary extra-scrotal tumour as an alternative plausible primary 2. Hilar centred mass 3. Morphology incompatible with other alternatives 4. IHC to exclude mesothelioma, serous carcinoma

36 Transition from normal rete epithelium to malignant epithelium useful if present A slit like glandular architecture is characteristic CD10 frequently positive, calretinin may be positive

37 Ref 2

38 3. Epididymal carcinoma Vanishing rarity Often widely invasive, occasionally more localised Variety of architectures seen but tubular common, especially with columnar morphology and prominent clear cells

39 4. Metastatic adenocarcinoma More commonly bilateral or multifocal with cord, epididymis and testis involvement Vascular/lymphatic invasion Interstitial pattern of growth History of primary carcinoma IHC positive adeno markers, negative meso

40 5. Testicular tumour extending into the paratestis An embryonal carcinoma or malignant sex cord stromal tumour may be considered in the DDx but careful attention to the predominant location and morphology will almost always resolve the issue; IHC if necessary

41 Conclusion Mesothelioma is an uncommon tumour and distinctly rare at this site; it commonly presents as a testicular tumour or hydrocoele There is a spectrum of intrascrotal mesothelial lesions presenting different diagnostic challenges A number of other (also rare) epithelial neoplasms need consideration in the differential diagnosis

42 Acknowledgements Dr John Dooley- NH Diagnostics Dr Hema Samaratunga- Aquesta Pathology/ Princess Alexandra Hospital Dr Scott McClintock- Urology

43 References 1. Bisceglia M, Ben Dor D, Carosi I et al. Paratesticular mesothelioma. Report of a case with comprehensive review of literature. Adv Anat Pathol 2010, 17 (1) Amin MB. Selected other problematic testicular and paratesticular lesions: rete testis neoplasms and pseudotumors, mesothelial lesions and secondary tumors. Mod Pathol 2005, 18, S Chen X, Sheng W, Wang J. Well differentiated papillary mesothelioma: a clinicopathological and immunohistochemical study of 18 cases with additional observation. Histopathology 2013, 62, Lee S, Illei PB, Han JS, Epstein JI. Florid mesothelial hyperplasia of the tunica vaginalis mimicking malignant mesothelioma. Am J Surg Pathol 2014, 38 (1), Jones MA, Young RH, Scully RE. Malignant mesothelioma of the tunica vaginalis. Am J Surg Pathol 1995, 19 (7), Trpkov K, Barr R, Kulaga A, Yilmaz A. Mesothelioma of tunica vaginalis of uncertain malignant potential - an evolving concept: case report and review of the literature. Diagnostic Pathology 2011, 6:78 7. Brimo F, Illei PB, Epstein JI. Mesothelioma of the tunica vaginalis: a series of eight cases with uncertain malignant potential. Mod Pathol 2010, 23,

44 8. Chekol SS, Sun C-C. Malignant mesothelioma of the tunica vaginalis testis. Diagnostic studies and differential diagnosis. Arch Pathol Lab Med. 2012, 136, Winstanley AM, Landon G, Berney D et al. The immunohistochemical profile of malignant mesotheliomas of the tunica vaginalis. Am J Surg Pathol. 2006, 30 (1), Mensi C, Pellegatta M, Sieno C et al. Mesothelioma of the tunica vaginalis and asbestos exposure. BJUI. 2012, 110, Eble JN, Sauter G, Epstein JI, Sesterhenn IA, editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press, 2004;

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