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Pathology of Testes (Testicular Neoplasm)

Anatomy Classification
Primary Neoplasm of Testis Primary Neoplasm of Testis
Seminomatous Tumour Germ Cell Tumour
Non-Seminomatous Tumour Non-Germ Cell Tumour
Secondary Neoplasms Secondary Neoplasms
Paratesticular Tumours Paratesticular Tumours

Germ Cell Tumour

Classification by WHO
Intratubular germ cell neoplasia, unclassified
Malignant Pure Germ Cell Tumor (showing a single cell type)
• Seminoma
• Embryonal carcinoma
Epidemiology
• Teratoma
Incidence of Testicular Cancer by Race
• Choriocarcinoma
Race/ Ethnicity Annual Rate per 100,00 men
• Yolk sac tumor
All Races 5.4
Malignant Mixed Germ Cell Tumor (showing ≥ 1 histologic pattern)
White 6.3
• Embryonal carcinoma, Teratoma (with/ without Seminoma)
Black 1.3
• Embryonal carcinoma, Yolk sac tumor (with/ without Seminoma)
Asian/ Pacific Islander 1.7
• Embryonal carcinoma, Seminoma
American Indian/ Alaska Native 4.6
• Yolk sac tumor, Teratoma (with/ without Seminoma)
Hispanic 4.0
• Choriocarcinoma, any other element
10 Most Frequent Cancers in Males, Peni nsular Malaysia Polyembryoma

Histogenesis of Testicular Neoplasms (Peak Incide nce)

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1° Neoplasms of Testis Seminoma (= Ovarian Dysgerminoma)

Germ Cell Neoplasms (90-95%) Most common type
Seminomas (40%) 2 Peaks
• Classic Typical Seminoma 15-35 y/o
• Anaplastic Seminoma > 60 y/o
• Spermatocytic Seminoma Rarely arise elsewhere
Embryonal Carcinoma (20-25% ) Mediastinum
Teratoma (25-35%) Pineal
• Mature Retroperitoneum
• Immature Can Metastasise
Choriocarcinoma (1%) Nodes
Yolk Sac Tumour Bones
Non-Germ Cell Tumour Radiosensitive (95% cure in early stages)
Sex Cord/ Gonadal Stromal Tumors (5-10%) Pathology
• Specialized Gonadal Stromal Tumor Pale Homogenous Tumour
o Leydig Cell Tumor Big Cells, Lymphocytes, Few Mitoses
o Sertoli Cell Tumor Contain PLAP (Placental Alkaline Phosphatase)
• Gonadoblastoma
Miscellaneous Neoplasms
• Carcinoid Tumor
• Tumors of Ovarian Epithelial Subtypes

Intratubular Germ Cell Neoplasia

Like CIS in other organs
Seen Adjacent to Most Tumours
Often seen where Germ Cell Tumours may arise
Cryptochidism Seminoma of Testis
Klinefelter’s syndrome Fairly Well Circumscribed
Progresses to Invasive Tumour 50% cases over 5 years Pale
May be Bilateral Fleshy
Important to Follow up/ Treat (eg. Radiotherapy) Homogenous Mass
Histological Types (Seminoma)
Classical

Large Large
Intratubular Well-Demarcated Cells Well-Demarcated Cells
Dysplasia Distinct Borders Distinct Borders
Basement Membrane Intact, Thickened Clear Cytoplasm (glycogen rich) Clear Cytoplasm (glycogen rich)
Focal Calcifications Round Nu clei Round Nu clei
Spermatogenesis is almost always absent Prominent Nucleoli Prominent Nucleoli
Lymphocytes Predominant

Non-Seminomas

Spermatocytic
Pleomorphic
Numerous Mitotic Figures
Round, Pyknotic Nuclei
Pink Cytoplasm
Embryonal Carcinoma Large, Bizarre Cells
(Dark, Vacuolated Nuclei)
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Clinical Features Clinical Staging of Testicular Tumour

Painless Swelling of One Gonad Stage I Stage II Stage III
Dull Ache, Heaviness in Lower Abdomen Tumour Spread to Spread beyond
Acute Scrotal Pain (10%) confined to Regional Nodes Retroperitoneal Nodes
Recent Testicular Trauma (10%) Testis IIA IIB IIC Above Diaphragm
Metastasis (10%) Size Size Size Visceral Disease
Neck Mass < 2cm 2-5cm 5-10cm
Cough < 6 +ve > 6 +ve Large
Anorexia Nodes Nodes Bulky
Vomiting Abd. mass
Back Ache
Lower Limb Swelling TNM Staging of Testicular Tumour
Gynecomastia (5%) Tc No Evidence of Tumour
Infertility (Rarely) T1S Intratubular, pre Invasive
Seminomas Non-Seminomas T1 Confined to Testis
Mainly Stage I Mainly Stage II, III T2 Invades beyond Tunica Albuginea or into Epididymis
Aggressive chemotherapy can cure most T3 Invades Spermatic Cord
T4 Invades Scrotum

N1 Single <2cm
N2 Multiple >5cm / Single 2-5cm
N3 Any node > 5cm

Mc No Evidence of Mass
M1 Metastasis

Requirements for Staging (To properly Stage Testicular Tumours)

Pathology of Tumour Specimen
History
Clinical Examination
Radiological procedure – USG/ CT/ MRI/ Bone Scan
Tumour Markers – β HCG, AFP

All patients with a Solid, Firm Intratesticular Mass

(that cannot be Transilluminated) should be regarded as Malignant

Possible Risk Factors

20-35 y/o (↑ Risk Group)
Cryptorchidism (Failure of Testicles to Descend into Scrotum)
Previous cancer in other testicle
History of
Mumps Orchitis
Inguinal Hernia
Hydrocele in childhood
↑ Socioeconomic Status
Maternal Hormone ingestion during Pregnancy (eg. Diethylstilbestrol)
Exposure to ↑ Levels of Circulating Maternal Endogenous Hormones
(especially Estrogen) during Early Pregnancy (during Testicular Development)
↑ Maternal Age at Pregnancy
↑ Maternal BMI at time of conception
Mother experiencing Hyperemesis Gravidarum
Infertile Male

Cryptorchidism, Testicular Tumour

Risk of Developing Carcinoma in Undescended Testis
14-48X the normal expected inci dence
Causes for Malignancy
Abnormal Germ Cell Morphology
↑ Temperature in Abdomen, Inguinal Region (as opposed to Scrotum)
Endocrinal disturbances
Gonadal Dysgenesis

Proto-Oncogene sis in Germ Cell Tumours (Shuin et al)

Seminoma, N-myc expressi on
Embryonal
Carcinoma c-Ki-ras expres sion
Seminoma
Immature c-erb B-1 e xpression
Teratomas
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Investigation Role of Tumour Markers

Ultrasound – Hypoechoic area Diagnosis
Chest X-Ray – PA, Lateral views Testicular Tumours have +ve Markers (80-85%)
CT Scan Non-Seminomas
Tumour Markers Raised Markers (Most)
AFP Normal Marker Level (10-15%)
β HCG After Orchidectomy, if Markers ↑ After Lymphadenectomy, if Markers ↑
LDH Residual Disease Stage III Disease
PLAP Stage II, III Disease
Degree of Marker ↑ appears to be Directly Proportional to Tumour Burden
Tumour Markers Markers indicate Histology of Tumour
Onco-Fetal Substances Cellular Enyzmes If AFP ↑ in Seminoma, means Tumour has Non -Seminomatous Elements
AFP (Trophoblastic Cells) LDH -ve Tumour Markers becoming +ve on follow up indicates
HCG (Syncytiotrophoblastic Cells) PLAP Recurrence of Tumour
Markers become +ve earlier than X-Ray Studies
Serum AFP (Alpha-Fetoprotein)
Secretion is restricted to Nonseminoma Principles of Treatment
Normal < 10ng/mL Advanced Disease,
Orchde ctomy Radiotherapy
Serum Half-Life – 4-5 days Metastasis
Germ Cell Tumor, Hepatocellular Carcinoma (seen exclusively) Seminomas Non-Seminomas Chemotherapy
Concentration > 10,000 ng/mL Radio-Sensitive Radio-Resistant
↑ in Patients with
Hepatic Dysfunction Prognosis
Hepatitis Seminoma Non-Seminoma
Cirrhosis Stage I 99% 95-99%
Drug, Alcohol Abuse Stage II 70-92% 90%
For Testicular Malignancies, ↑ AFP Stage III 80-85% 70-80%
Pure Embryonal Carcinoma
Teratocarcinoma
Yolk Sac Tumour
Combined Tu mour

β HCG (Human Chorionic Gonad otropin)

↑ Level can be found in either
Seminoma
Nonseminoma
Serum Half-Life – 18-36 h ours (24-3 6 hours)
Normal < 1ng/mL
Patients with ↑ β-HCG may experience
Nipple tenderness
Gynecomastia
Germ Cell Tumour (exclusively)
Serum β-HCG con centrations > 10,000 mIU/mL
↑ seen in paƟents with
Trophoblastic Differentiation of a Lung
Gastric Primary Cancer
Hypogonadism
False +ve Elevations
Marijuana use
↑ β-HCG
Choriocarcinoma (100%)
Embryonal Carcinoma (60%)
Teratocarcinoma (55%)
Yolk Cell Tumour (25%)
Seminomas (7%)

LDH (Lactate Dehydrogenase)

Has Independent Prognostic significance
↑ Levels Reflect
Tumour Burden
Growth Rate
Cellular Proliferation
Levels are ↑ in
Pure Seminoma (30-80% Patients)
Nonseminomatous Tumours (60% Patients)
Not a sensitive, specific indicator of disease recurrence
Not useful serum marker for post-treatment surveillance