Non Germ cell tumours

Hong Kong 2021

Sex cord stromal tumours

• Leydig Cell Tumour – Malignant Leydig cell tumour • Sertoli Cell Tumour – Malignant Sertoli cell tumour – Large cell calcifying Sertoli cell tumour – Intratubular large cell hyalinising Sertoli cell tumour • Granulosa Cell Tumour – Adult – Juvenile • Tumours of Fibroma/thecoma group • Mixed/Unclassified • Tumours with both sex cord and germ cell elements Sex cord stromal lesions

Leydig Sertoli Granulosa Sertoli/Leydig Fibroma thecoma

Coelomic mesothelium = Sex cords = Sertoli cells

Mesenchyme = Stroma = Leydig cells Leydig cell tumours

• Typical appearance • Oncocytic • Reinke Crystalloids • Lack of GCNIS • 30% have endocrinopathy • Children 20% – German Zoologist 1821-1908

REINKE, F . 1896 . Beiträge zur Histologie des Menschen. Arch . Mikroskop . Anat. 47 :34 German anatomist, 1862-1919 Increase in incidental lesions in the testis.

• Victim Of Modern Imaging Technology • VOMIT • Brainless Application of Radiological Findings • BARF

Leydig cell Malignancy Criteria • Size • Invasiveness • Mitoses • Necrosis • RPLND??

Leydig cell hyperplasia and variants • High hCG • Klinefelter’s syndrome • Bilateral nodularity • Not a reason for Orchidectomy • Cord and tunica involvement • Congenital Adrenal Hyperplasia – Testicular Adrenal Rest Tumours (TART)

Testicular tumor of adrenogenital syndrome (Testicular adrenal rest tumor)

• Congenital adrenal hyperplasia • Florid hyperplasia of Leydig like cells • Responsive to high dose steroids • Mediacl treatment sufficient!

Sertoli Cell Tumors

• Sometimes oestrogens • Variable pattern • Distict nucleoli usually. • Tubules, retiform, solid, clear cells • Charcot-Böttcher filaments • Any tubular component • Enrico Sertoli 1865 Italian Physiologist • Arthur Bottcher 1813-89 Baltic Pathologist • Jean-Martin Charcott 1825-1893 French neurologist

Kao CS, Kum JB, Idrees MT, Ulbright TM. Sclerosing Sertoli cell tumor of the testis: a clinicopathologic study of 20 cases. Am J Surg Pathol. 2014 Apr;38(4):510-7. Henley JD, Young RH, Ulbright TM. Malignant Sertoli cell tumors of the testis: a study of 13 examples of a neoplasm frequently misinterpreted as seminoma. Am J Surg Pathol. 2002 May;26(5):541-50.

Contacted clinicians

• Further investigations • Goitre • Nodular adrenals • Previous myxoma • Lip pigmentation • Acromegaly Diagnosis

• Multiple Large cell calcifying Sertoli cell tumors secondary to Carney complex Large cell calcifying SCTs • Carney complex: myxomas, lentigines, blue naevi, Cushing's 2ary to PANH, PRKAR1A germ line mutation • pituitary adenomas. • Younger age Peutz Jeghers Syndrome

• STK11germ line mutations on chromosome 17 • Autosomal dominant • Muco-cutaneous lesions • Hamatomatous polyps • Testicular lesions… Intratubular large cell Hyalinising Sertoli cell tumours • Peutz-Jeghers Syndrome • Intra tubular growth • Less calcification • Largely in paediatric population

2 Sertoli cell adenoma/hyperplasia • Cryptorchidism • ‘Pick’s’ adenoma • Androgen insensitivity Granulosa cell tumours • Usual type – Rare in pure form: morphology. – Usually benign • Juvenile – Commonest testis tumour in infants – XX/XY mosaicism – Invariably benign • Fibroma/thecomas very rare on own. Cornejo KM, Young RH. Adult granulosa cell tumors of the testis: a report of 32 cases. Am J Surg Pathol. 2014 Sep;38(9):1242-50. Kao CS, Cornejo KM, Ulbright TM, Young RH. Juvenile granulosa cell tumors of the testis: a clinicopathologic study of 70 cases with emphasis on its wide morphologic spectrum. Am J Surg Pathol. 2015 Sep;39(9):1159-69.

Mixed sex cord stromal tumours • More common. • Benign under 10 • Malignancy reported in older group

Immunochemistry

• Germ cell markers negative • Inhibin variable • Calretinin variable • Actin spindle elements • CD99 variable • S100

Tumour containing both germ cell and sex cord-stromal elements

• Gonadoblastoma • 20% phenotypically male • Most <20 years of age • Cryptorchidism, hypospadias and gynecomastia • May present in children under age 2 • Failure of involution of müllerian ducts Tips for diagnosis

• Think of hyperplasia. • Syndromes. • Always look for GCNIS. • Check nuclear morphology. • Immunochemistry. Tumour containing both germ cell and sex cord-stromal elements

• Gonadoblastoma • 20% phenotypically male • Most <20 years of age • Cryptorchidism, hypospadias and gynecomastia • May present in children under age 2 • Failure of involution of Müllerian ducts

Presentation

• Usually young males with feminizing symptoms. • Often persistent mullerian duct structures • Karyotype can be normal but always a Y chromosome.

Newly added 2016 WHO Entities • Hemangioma • Juvenile Xanthogranuloma Hemangioma

• Rare • Well circumscribed • IHC CD31, FLI1 and ERG. • Benign Juvenile Xanthogranuloma

• Neoplastic ? • May progress to multiple sites • Children (<13 months) • mononuclear histiocyte like cells • diffuse infiltrative pattern Other Tumours of the Testicular Adnexa and Paratesticular Tissue

• Rete Testis – Hyperplasia/adenoma – Adenocarcinoma • Epididymis – Clear cell papillary hyperplasia – Papillary cystadenoma and carcinoma • Lesions of mesothelial origin – Papillary hyperplasia – Adenomatoid tumor – Mesothelioma • Tumors of mullerian type epithelium • Desmoplastic small round cell tumour Rete Testis Benign Lesions

• Hyperplasia • Adenomatous hyperplasia • Adenoma – Adenoma of usual type – Sertoliform cystadenoma – Adenofibroma • Morphologic criteria – Circumscribed – Cystic or solid – Cytologically bland Rete hyperplasia and metaplasia Sertoliform cystadenoma Rete Testis Adenocarcinoma

Clinical Features Morphology • Adult males • Grossly solid or cystic • Tubulopapillary • Unilateral hilar mass • Solid, spindle, retiform • Painless testicular • Cuboidal to columnar cells swelling • Eosinophilic to basophilic cytoplasm • Hydrocele • Moderate to marked • Poor survival pleomorphism Diagnostic Criteria

• Hilar location • Normal to malignant transition • No other primary • Morphology incompatible with other intrascrotal primary • Immunohistochemical studies

Nochomovitz and Orenstein; AJSP 1984 Ulbright and Young; AFIP series 4, 2013

Immunoprofile

• Positive: CK7, AE1/AE3, WT1 CKBE312, and calretinin focal • Negative: CK20, CD15, p63, OCT4, CEA, inhibin, and CD30 CKBE312 CK7

CK32B AE1/AE3AE1/AE3 E12 WT1WT1 Treatment and Prognosis

• Radical orchiectomy • RPLND ? • No proven benefit for chemotherapy and radiation • Overall prognosis is poor (5 year at 15%) • Larger size – worse prognosis Papillary cystadenoma of epididymis Serous borderline tumor Adenomatoid Tumour Adenomatoid Tumour

Malignant mesothelioma of tunica vaginalis

• Occur from childhood elderly. • Mean age of 60 year • Some associated with asbestos exposure • Hydrocele • Tunica is thickened and often studded by papillary tumor and coats the TV • Pattern is usually purely epithelioid • Cytologic atypia, mitotic activity, and necrosis are variably prominent.

Calretinin Malignant mesothelioma of tunica vaginalis

• 20 cases : IHC was similar to that of malignant mesothelioma in the pleura • CK5/6 staining could be patchy in some tumors • Radical orchidectomy is the usual treatment • Some patients possibly benefiting from RPLND. • After a median follow-up of 22 months, 50% of 30 patients were disease free after treatment . • Division of malignant mesotheliomas into high-grade and low- grade categories based on pathologic and clinical evaluation may aid in prognostication • Versus mesothelial hyperplasia: gross mass, complex arborizing papillae with fibrovascular cores, invasive growth, and a less frequent inflammatory background. Well-differentiated Papillary Mesothelioma • No longer termed “benign” • Identical tumors have shown invasive foci or progression in other sites

– Gallateau-Salle et al. Am J Surg Pathol 2004;28:534 – Churg et al. Am J Surg Pathol 2014;38:990 Well-differentiated Papillary Mesothelioma

Well-differentiated Papillary Mesothelioma Well-differentiated Papillary Mesothelioma Papillary serous v Mesothelioma

• Thinner papillae • Less cellular budding and stratification • Fewer psammoma bodies • Immunohistochemistry: papillary serous tumors typically being positive with B72.3, PLAP, Leu- M1, CA125, and sometimes CEA Rhabdomyosarcoma • Most common malignant tumor of the spermatic cord • Peak incidence at 9 yrs but also teens • Generally conventional embryonal rhabdomyosarcomas • Many have spindle cell morphology A small % are of the alveolar or pleomorphic • IHC; MyoD1, myogenin, desmin, and muscle- specific actin. Myoglobin stains poorly sensitive but specific. Rhabdomyosarcoma Rhabdomyosarcoma • Radical orchiectomy with RPLND is the usual treatment, with chemotherapy and radiation therapy • Overall survival rate of approximately 80% can be expected Spindle cell subtype has a better outcome. • Complete local resectability and an absence of parenchymal metastases are important favorable prognostic features. • Wraps around testicular structures • Differentiate from transformation of GCT Deep (Aggressive) angiomyxoma

• More common in vulva • Locally aggressive • V rare in men • HMGA2 more specific (gene) • ER/PR • Local recurrence common • WLE recommended Deep (Aggressive) angiomyxoma Cellular Angiofibroma Angiomyofibroblastoma-like tumor

• Benign paratesticular/spermatic cord • circumscription • More superficial location, • mixture of spindle and plump cells, • zonal cellularity, • vessels with hyalinized or fibrinoid change • different from the similarly named vulvar tumor • cellular angiofibroma