L4 (T3) Pathology of the Testis.pptx
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Pathology of the Testis Catherine Chinyama Consultant Pathologist, Guernsey Honorary Clinical Professor [email protected] 17th February 2023 1 Learning Objectives 1. 2. 3. 4. 5. 6. 7. 8. 9. The presentation of epididymo-orchitis and torsion with illustrative clinical cases The predisposing...
Pathology of the Testis Catherine Chinyama Consultant Pathologist, Guernsey Honorary Clinical Professor [email protected] 17th February 2023 1 Learning Objectives 1. 2. 3. 4. 5. 6. 7. 8. 9. The presentation of epididymo-orchitis and torsion with illustrative clinical cases The predisposing factors of testicular cancer The classification of testicular cancer into seminomatous and non-seminomatous germ cell tumours The clinical presentation of testicular cancer The biochemical and radiological investigations for testicular cancer The radiological, gross and histological features of seminoma, teratoma and other germ cell tumours with illustrative clinical cases Basic understanding of staging and prognosis of testicular cancer Basic understanding of treatment of testicular cancer Refer to 104 interactive session for pathology of prostate 2 ‘Normal Testis’ with associated epididymal cyst Tunica Vaginalis Seminiferou Tubules 3 Acute Epididymo-orchitis • Most cases of acute epididymo-orchitis occur in men aged 20 – 39 years • Associated with sexually transmitted diseases such as Chlamydia trachomatis and Neisseria gonorrhoea • In older men over 40 years the most common cause is E.coli infection • Initially the inflammation is confined to the epididymis and later spreads to the testis 4 Presentation, Management of Acute Epididymo-orchitis • Pain and swollen epididymis due to inflammation with a predominance of neutrophils • Culture and sensitivity of urethral secretions to identify causative bacteria • Raised C-Reactive Protein (CRP) • Ultrasound scan may differentiate epididymoorchitis from torsion • Treat with antibiotics, pain relief and supportive care (scrotal elevation) • If not resolved may require inpatient care • May heal with scarring leading to sterility 5 Illustrative Case of Epididymo-orchitis • 41 year old man with Type 1 diabetes mellitus presented with painful swollen left testis for one week • USS showed epididymo-orchitis with poor vascularity • Tumour markers were normal • Did not respond to antibiotics • Declined hospital treatment due to work commitments • Had left orchidectomy 5 weeks after presentation 6 Pathology of E-orchitis • Excision included adherent scrotal skin • Testis was covered in fibrous adhesions • The cut surface was necrotic • Histology showed abscess formation • Died years later due to complications of diabetes mellitus 7 Torsion • Manage as a urological emergency • Torsion occurs due to twisting of the spermatic cord which cuts off the venous drainage from the testis • If untreated leads to infarction of the testis • Presents with sudden onset of testicular pain which may or may not be related to trauma • If ‘untwisted’ within 6 hours there is a chance that the testis will remain viable • The contralateral testis should be fixed to the scrotum (orchidopexy) to risk reduce risk of torsion 9 Illustrative Case of Torsion • 74 year old man experienced pain in the left testis following drainage of hydrocoele • Hydrocoele is the collection of fluid around the testis surrounded by the tunica vaginalis • The main differential diagnosis was epididymoorchitis • Was treated with antibiotics but did not get better • He underwent an orchidectomy 5 days later • The testis showed haemorrhagic infarction + polymorph infiltrate 10 TORSION: COMPLETE HAEMORRAGIC INFARCTION OF THE TESTIS Torsion in a younger man (18years old) 12 Epidemiology of Testicular Cancer • Most common solid malignant tumour in men 3034 years of age • Incidence of testicular cancer higher in caucasian men than black men • Prostate cancer more common black men than caucasians • Testicular cancer accounts for less1% of all new cancers in the UK with 28% increase since the early 1990s (Cancer Research UK) 13 Causes of Testicular Cancer 1. Cryptorchidism/undescended testis increases the risk of cancer 4 – 8 times 2. History of previous testicular cancer 3. Genetic abnormality: Klinefelter’s syndrome (47XXY) & Down’s syndrome (trisomy 21) 4. FH of testicular cancer – First degree relatives have a higher risk than the general population 5. Men with infertility problems are more likely to develop testicular cancer 6. Exposure to oestrogens (diethylstilbestrol) in utero → cryptorchidism→ increases the risk of testicular cancer 14 Atrophic Undescended Testis: Increased risk of testicular cancer 15 Classification of Testicular Tumours GERM CELL TUMOURS Seminomatous tumours • Classical seminoma • Spermatocytic seminoma Non-seminomatous tumours • Embryonal carcinoma • Yolk sac tumour • Choriocarcinoma • Teratoma SEX CORD/STROMAL TUMOURS • Leydig cell tumour • Sertoli cell tumour • Less than 5% of testicular tumours 16 Germ Cell Tumours • More than 90% of cancers of the testis arise in germ cells • Germ cells produce the sperm • Germ cell tumours are divided into seminomas and non-seminomatous • Mixed germ cell tumours consists of seminoma and non-seminomatous components • Germ cell carcinoma in situ or intra-tubular germ cell neoplasia is the precursor lesion 17 Seminomas • Seminomas tend to grow and spread more slowly than non-seminomatous tumours • There are two main sub-types: classical seminoma and spermatocytic seminoma/tumour • Classical Seminoma: • Constitutes more than 95% of seminomas • Affect men between 25 and 45 years of age • Tumours markers can be normal or raised • Spermatocytic Seminoma/Tumour: • Rare tumour; affects older men; average age of 65yrs • Grow more slowly than classical seminomas and are less likely to spread to other parts of the body 18 Non-seminomatous Germ Cell Tumours (GCTs) • These germ cell tumours usually occur in men in their late teens and early 30s • Four main types of non-seminomatous germ cell tumours – Embryonal carcinoma – Yolk sac carcinoma/tumour – Choriocarcinoma – Teratoma 19 Embryonal Carcinoma Present in about 40% of testicular tumours • Pure embryonal carcinoma occurs in only 3% to 4% of cases • Microscopically, looks like tissues of very early embryos • Tends to grow rapidly and spread outside the testis 20 Yolk Sac Carcinoma/Tumour • The cells look like the yolk sac of an early embryo • The most common form of testicular cancer in children • Pure yolk sac tumours are rare in adults • Have better prognosis in children than adults 21 Choriocarcinoma • A very rare and fast-growing testicular cancer in adults • Pure choriocarcinoma tends to spread rapidly to other parts of the body, including the lungs, bones, and brain • Usually present in mixed germ cell tumours with associated haemorrhage 22 Teratoma Derived from 3 germ cell layers of the embryo – Endoderm (innermost layer) – Mesoderm (middle layer) – Ectoderm (outer layer) • Pure teratomas of the testicles are rare • Most teratomas are components of mixed germ cell tumours 23 Types of Teratomas • Mature teratomas • Tumours are formed by cells similar to adult tissues • They rarely spread, can usually be cured with surgery, but may recur after treatment • Immature teratomas • Are less well-developed cancers with cells that resemble those of an early embryo • More likely than mature teratomas to invade nearby tissues, metastasise outside the testis and recur years after treatment. N.B. Dermoid cyst/mature cystic teratomas of the ovary are benign; testicular teratomas are always malignant 24 Clinical Presentation of Testicular Cancer •Any painless swelling or nodule in the testis is cancer until proved otherwise •Mass or nodule not separate from the testis •Dull ache or heavy sensation in the lower abdomen •Advanced cancer + mets may present with: - Back pain due to enlarged para-aortic L nodes - Supraclavicular lymphadenopathy - Cough, chest pain, haemoptysis and shortness of breath due to metastases to the lungs - Marked gynaecomastia in patients with tumours secreting beta HCG as in choriocarcinoma 25 Imaging in Testicular Cancer Ultrasound scan (USS) will distinguish between: • A tumour in the testis and external to the testis • A complex cyst, most likely malignant and a simple cyst, most likely benign • A solid tumour and a cyst • CT scan: chest, abdomen and pelvis to assess for metastases in the lymph nodes, liver and lungs • MRI of brain and bone if metastases suspected • PET scan for recurrent disease after treatment lesions appear ‘hot’ when there is viable cancer 26 Tumour Markers in Testicular Cancer • Testicular tumours produce tumour markers (TMs) not normally present in the blood • Positive TMs aid in making a diagnosis of cancer in the presence of a testicular mass • Different tumours secrete specific TMs • Alpha-fetoprotein (AFP) - yolk sac tumour, embryonal carcinoma • Human chorionic gonadotropin (HCG) Choriocarcinoma, embryonal carcinoma • Lactate dehydrogenase (LDH) - seminoma • All TMs are raised in a mixed germ cell tumour • TMs used for follow-up of patients after therapy 27 Case Report: Seminoma • 33 year old man presented with enlarged right testis with associated dull ache • Ultra Sound Scan - Normal epididymis - Large homogeneous lobulated mass with increased vascularity - Probable seminoma • Tumour Markers - Slightly ↑ Lactate Dehydrogenase 28 USS OF SEMINOMA: well circumscribed tumour with increase in vascularity Macroscopic Appearance Seminoma - He had right orchidectomy - Testis had lobulated tumour with a ‘potato-like’ appearance - No haemorrhage or necrosis - No normal residual testicular tissue 30 MACROSCOPIC APPERANCE OF SEMINOMA Microscopic Appearance Of Seminoma Seminoma cells are large with prominent lymphocytic infiltrate Vascular invasion present: Cancer cells admixed with RBCs in a venule ADVANCED SEMINOMA 95 x 55 x 35mm;106.5g; note the solid ‘potato-like’ appearance EARLY SEMINOMA Central white tumour surrounded brown seminiferous tubules Case Report: Teratoma • 22 year old student ; left painless testicular mass • USS - Focal lesion ,15 x 15 x 11 mm with partly cystic partly solid appearances • Tumour markers were normal • He underwent left orchidectomy 34 USS TERATOMA: Partly cystic partly solid irregular tumour MACROSCOPIC APPEARANCE EARLY TERATOMA Irregular tumour 15mm with cystic cut surface and mucin secretion On low power there is an area of scarring/fibrosis surrounding cystic spaces with seminiferous tubules in the background MICROSCOPIC APPEARNCE OF EARLY TERATOMA On higher power the cystic teratoma is lined by mucin secreting large bowel epithelium 37 Case Report: Mixed Germ Cell Tumour • 32 year old man presented to A&E with a 6 month of testicular swelling; the right testis had ruptured and was bleeding • USS: - Heterogeneous bilateral testicular tumours - Mixed cystic and solid components - No normal testis identified • CT Scan: - Huge scrotal mass 18 x 17cm + enlarged inguinal lymph nodes 38 CT SCAN: huge scrotal mass with enlarged lymph nodes Mixed Germ Cell Tumour • A & E doctor thought it was an infected abscess • Incisional and drainage of right testis • 60 x 50 x 20 mm of tissue removed Histology: Undifferentiated carcinoma Tumour markers: • Alpha fetoprotein = 29,124 ( 0-6) • Beta HCG = 6.6 ( <2.6) Subsequent orchidectomy: • Bilateral testicular tumours fused together • Right testis tissue partly removed 40 Macroscopic Appearances Mixed Germ Cell Tumour • • • • • • Previously opened mass 180 x 100 x 75 mm weighing 805grams Cavity 140 x 80 x 40 mm Prominent vessels on the surface No normal testicular tissue Left tumour intact; right tumour partly removed 41 MIXED GERM CELL TUMOUR: Lt testis and part of residual right testis RT LT Mixed Germ Cell Tumour •Choriocarcinoma (A) - raised HCG •Seminoma (B) •Embryonal carcinoma (C ) - raised AFP B A C Choriocarcinoma in a Mixed Germ Cell Tumour • An early stage mixed germ cell tumour • The area of haemorrhage showed choriocarcinoma cells Prognostic Factors • • • • • Type of tumour e.g. seminona has a good prognosis TNM stage = Tumour , Node, Metastasis Size of tumour (T stage) Extension outside the testis (T stage) Presence of vascular invasion – enables spread to LN and other organs • Lymph node metastasis ( N stage) • Distant metastases to liver or lung ( M stage) • High levels of tumour markers in the blood indicates high tumour load 45 Treatment • Radical orchidectomy with isolated testicular mass followed by adjuvant chemotherapy • If metastases are present at the time of presentation patients receive neo-adjuvant chemotherapy then orchidectomy • There maybe no tumour in the removed testis on pathological examination which is termed complete pathologic response to chemotherapy • Patients are offered sperm banking prior to orchidectomy • Patients are offered a prosthesis after orchidectomy 46 FEMALE & MALE 83-year old with a 26-year oldTERATOMAS an testicular tumour + ovarian cyst ; tumour markers normal raised alpha-feto protein and LDH FEMALE & MALE TERATOMAS Mostly cystic Mostly solid Ectodermal Elements Skin + sebaceous glands and hair follicles Epidermal cyst; No sebaceous glands or hair follicles Immature Mesodermal Tissue cartilage; bone Mature bone and and smooth cartilage; skeletal muscle were muscle present in present in other another field slides Take Home Message • Distinguish between acute epididymo-orchitis and torsion • Painless testicular lump is cancer until proved otherwise • Testicular tumours classified as germ cell and non-germ cell • Seminoma is the most common germ cell tumour • Tumour markers important for diagnosis and monitoring testicular cancers • Mature cystic teratoma of the ovary are benign whereas the testicular mature teratomas are always malignant 51 THE END 52
