Download MBBS Pathology PPT 14 Testis Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Pathology PPT 14 Testis Lecture Notes

Testis

Must know

1-Classification of testicular tumor
2-Tumor markers in diagnosis
3-Morphology of
a)

Seminoma

b)

Embryonal carcinoma

c)

Yolk sac tumor

4-Cryptorchidism


Testicular lesion

? CongenitalAnomalies
? RegressiveChanges
? Inflammation (Nonspecific , Specific Inflammations, Granulomatous

(Autoimmune) Orchitis)

? VascularDisorders(torsion)
? SpermaticCordandParatesticularTumors
? TesticularTumors
INFLAMMATIONS-
? Inflammation of the testis is termed as orchitis and of epididymis is

called as epididymitis; the latter being more common

1-Non-specific Epididymitis and Orchitis-
? may be acute or chronic
? common routes of spread are via the vas deferens, or lymphatic and

haematogenous routes

? caused by urethritis, cystitis, prostatitis and seminal vesiculitis
? common infecting organisms in Neisseria gonorrhoeae and Chlamydia

trachomatis
Grossly,
? acute stage- firm, tense, swollen and congested
may be multiple abscesses, especially in gonorrhoeal

infection

? chronic stage- variable degree of atrophy and fibrosis

Histological y,
? acute- congestion, oedema and diffuse infiltration by neutrophils, or formation of

neutrophilic abscesses

? Chronic- focal or diffuse chronic inflammation, disappearance of seminiferous

tubules, fibrous scarring and destruction of interstitial Leydig cells
2-Granulomatous (Autoimmune) Orchitis -
Non-tuberculous granulomatous orchitis-
? unilateral, painless testicular enlargement
? may resemble a testicular tumour clinically
? autoimmune basis is suspected

Gross- enlarged
? Cut section of the testicle is greyish-white to tan-brown
? Histological y, granulomatous reaction(non caseating) is present diffusely

throughout the testis and is confined to the seminiferous tubules

? Peritubular fibrosis
? interstitial lymphocytes and plasma cells
3-Tuberculous Epididymo-orchitis-
? invariably begins in the epididymis and spreads to the testis

? May spread via -tuberculous seminal vesiculitis, prostatitis and renal tuberculosis
? haematogenous spread- from tuberculosis of the lungs

Grossly, discrete, yellowish, caseous necrotic areas
? Microscopical y, numerous tubercles which may coalesce to form large caseous

mass

? Characteristics of typical tubercles such as epithelioid cells, peripheral mantle of

lymphocytes, occasional multinucleate giant cells and central areas of caseation

necrosis are seen

? AFB positive


4-Spermatic Granuloma(epididymitis nodosa)
? Spermatic granuloma is the term used for development of

inflammatory lesions due to invasion of spermatozoa into the stroma
MORPHOLOGIC FEATURES-
Grossly,
? a small nodule, 3 mm to 3 cm in diameter in head of epididymis

? firm, white to yellowish-brown

? Histological y, it consists of a granuloma composed of histiocytes,

epithelioid cells, lymphocytes and some neutrophils

? Characteristical y, the centre of spermatic granuloma contains

spermatozoa and necrotic debris
Vascular disorder

Torsion of Testis
? Twisting of the spermatic cord
? sudden cessation of venous drainage and arterial supply
? usually followed by sudden muscular effort or physical trauma
? Trauma may occure in either in a fully-descended testis or in an

undescended testis

1-Neonatal torsion-
? occurs either in utero or shortly after birth

? It lacks any associated anatomic defect in testis

2-"Adult" torsion-
? is typically seen in adolescence and presents with the sudden onset of testicular

pain

? bel -clapper abnormality -bilateral anatomic defect that leads to increased

mobility of the testes (bel -clapper abnormality)
? Viable- manually untwisted within approximately 6 hours of the

onset of torsion

MORPHOLOGIC FEATURES-
duration and severity of vascular occlusion
? may be coagulative necrosis of the testis and epididymis
? may be haemorrhagic infarction
Spermatic Cord and Paratesticular Tumors

1-Lipomas
? common lesions involving the proximal spermatic cord, identified at

the time of inguinal hernia repair

? represent retroperitoneal adipose tissue that has been pulled into the

inguinal canal along with the hernia sac, rather than a true neoplasm

2-Adenomatoid tumor-
? most common benign paratesticular tumor
?
? typically occurring near the upper pole of the epididymis
? grossly , well circumscribed small nodules
? Microscopically- Proliferation of glandular structures, irregularly lined by cuboidal

to flattened epithelial cell

? Treatmet- local excision

Malignant tumor

? rhabdomyosarcomas -children
? liposarcomas- adults


CLASSIFICATION OF TESTICULAR TUMOR

? most useful classification of tumors is histogenetic
? Named according to from which tissue they arise and of which they consist


WHO histological classification of testis tumours

? Germ cell tumours
? Tumours of one histological type (pure forms)
? Tumours of more than one histological type (mixed forms)
? Sex cord/gonadal stromal tumours Pure forms
? Miscellaneous tumours of the testis
? Haematopoietic tumours
? Tumours of collecting ducts and rete
? Tumours of paratesticular structures
? Mesenchymal tumours of the spermatic cord and testicular adnexae
? Secondary tumours of the testis


Testicular cancer is staged using the TNM system created by the American Joint

Committee on Cancer (AJCC)
It's based on 4 key pieces of information:
? T refers to how much the main (primary) tumor has spread to tissues next to the

testicle

? N describes how much the cancer has spread to regional (nearby) lymph nodes
? M indicates whether the cancer has metastasized (spread to distant lymph nodes

or other organs of the body)

? S indicates the serum (blood) levels of tumor markers that are made by some

testicular cancers

? Letters or numbers appear after T, N, M, and S to provide more details about

each piece of information.

? The numbers 0 through 4 indicate increasing severity
? The letters "IS" after the T stand for in situ, which means the tumor is contained

in one place and has not yet penetrated to a deeper layer of tissue.

? The letter X after T, N, M, or S means "cannot be assessed" because the

information is not known
TNM classification of germ cel tumours of the testis

pTNM pathological classification
? pTx ?Primary tumour cannot be assessed
? pT0 No evidence of primary tumour (e.g. histologic scar in testis)
? pTis Intratubular germ cell neoplasia (carcinoma in situ)
? pT1 Tumour limited to testis and epididymis without vascular/lymphatic

invasion; tumour may invade tunica albuginea but not tunica vaginalis

? pT2 Tumour pT1 + involvement of tunica vaginalis
? pT3 Tumour invades spermatic cord with or without vascular/lymphatic invasion
? pT4 Tumour invades scrotum with or without vascular/lymphatic invasion

pN ? Regional lymph nodes

? pNX Regional lymph nodes cannot be assessed
? N0 No regional lymph node metastasis
? pN1 <2 cm or less in greatest dimension and 5 or fewer positive nodes
? pN2 2 to 5 cm in greatest dimension; or more than 5 nodes positive, none more

than 5 cm; or evidence of extranodal extension of tumour

? pN3 Metastasis with a lymph node mass more than 5 cm in greatest dimension
S ? Serum tumour markers
? SX Serum marker studies not available or not performed
? S0 Serum marker study levels within normal limits
? LDH, hCG (mIU/ml) ,AFP (ng/ml)

Serum tumor markers (S)

For staging, serum (blood) levels of tumor markers are measured after the testicle

containing the cancer has been removed with surgery

LDH

HCG

AFP (ng/ml)

(U/liter)

(mIU/ml)

SX Marker studies not available or not done.

S0 Normal

Normal

Normal

S1 <1.5 x

<5,000

<1,000

*

Normal

S2 1.5 - 10 x

5,000 -

1,000 -

+

Normal

50,000

10,000

S3 >10 x

>50,000

>10,000

+

Normal
Cryptorchidism
? Cryptorchidism is a complete or partial failure of the intra-abdominal testes to

descend into the scrotal sac

associated with
? testicular dysfunction
? an increased risk of testicular cancer

? In 70% of cases, the undescended testis lies in the inguinal ring
? in 25% in the abdomen
ETIOLOGY. exact etiology is not known in majority of cases
1. Mechanical factors-
? short spermatic cord
? narrow inguinal canal
? adhesions to the peritoneum
? problems with development of the gubernaculum
? a patent processus vaginalis, or impaired intra-abdominal pressure have also

been hypothesized to contribute to cryptorchidism

2. Genetic factors-
? up to 23% of cases suggesting an underlying genetic mutation
? Mutations in insulin-like factor 3 and its receptor, LGR8, have been

demonstrated in a small number of cases

? trisomy 13
3. Hormonal factor- cryptorchidism is only rarely associated with a well-defined

hormonal disorder
? deficient androgenic secretions
? mullerian inhibiting substance
? insulin-like 3 hormone
4. Neuromuscular- abnormalities of the genitofemoral nerve's calcitonin gene-

related peptide or the cremasteric nucleus have been postulated to cause

cryptorchidism

Miscellaneous-
? Maternal alcohol consumption, analgesic consumption, and smoking have also

been associated with an increased risk

? Gestational diabetes has been shown to be related to the development of

cryptorchidism
MORPHOLOGIC FEATURES. Cryptorchidism is unilateral in 80% cases

Grossly, the cryptorchid testis is small in size, firm and fibrotic

Histology-
1-Seminiferous tubules
? tubular basement membrane is thickened
? hyalinised tubules with a few Sertoli cells
? foci of spermatogenesis are discernible in 10% of cases
2. Interstitial stroma: usual y increase in the interstitial fibrovascular stroma and

conspicuous presence of Leydig cells, seen singly or in small clusters



? CLINICAL FEATURES. asymptomatic and is discovered only on physical

examination

1. Sterility-infertility. Bilateral cryptorchidism is associated with sterility while

unilateral disease may result in infertility
2. Inguinal hernia. A concomitant inguinal hernia is frequently present along with

cryptorchidism

3-Malignancy. Cryptorchid testis is at 30-50 times increased risk of developing

testicular malignancy
? most commonly seminoma and embryonal carcinoma, than a normally

descended testis

? risk of malignancy is greater in intraabdominal testis than in testis in the inguinal

canal
? current recommendations are for correction at 6 to 12 months of age
? carcinoma arises from foci of intratubular germ cell neoplasia within the atrophic

tubules

? Orchiopexy reduces the risk of sterility and cancer

Tumour marker

Tumour markers- Germ cell tumours of the testis secrete polypeptide hormones

and certain enzymes which can be detected in the blood
There are two principal serum tumour markers
? alpha fetoprotein (AFP) and
? beta subunit of human chorionic gonadotropin (shCG)

? In addition, carcinoembryonic antigen (CEA), human placental lactogen (HPL),

placental alkaline phosphatase, testosterone, oestrogen and luteinising hormone

may also be elevated
AFP-
? synthesized by fetal yolk sac and also the liver and intestine
? elevated in 50-70% of testicular germ cell tumours
? Markedly elevated in yolk sac tumor
? a serum half life of 4.5 days
? However, elevated serum AFP levels are also found in liver cell carcinoma

hCG-
? secreted by placental trophoblastic cells
? elevated in non-seminomatous germ cell tumours of the testis (e.g. in

choriocarcinoma, yolk sac tumour and embryonal carcinoma)

? elevated in 50% of patients with germ cell tumours
? elevation in seminoma in 10-25% of cases

Lactate dehydrogenase (LDH)-
? may also be elevated
? direct relationship between LDH and tumour burden
? However, this test is nonspecific although its degree of elevation correlates with

bulk of disease
Applications-
? In the evaluation of testicular masses
? In the staging of testicular germ cell tumors. For example, after orchiectomy,

persistent elevation of HCG or AFP concentrations indicates stage II disease even

if the lymph nodes appear of normal size by imaging studies

? In assessing tumor burden
? In monitoring the respons to therapy. After eradication of tumors there is a

rapid fall in serum AFP and HCG. With serial measurements it is often possible to

predict recurrence before the patients become symptomatic or develop any other

clinical signs of relapse

TESTICULAR TUMOR
Testicular tumor

? Most germ cell tumours occur between the ages of 20 and 50 years
? Before puberty, seminoma is extremely uncommon
? usual germ cell tumours , yolk sac tumour and the better differentiated types of

teratoma

? Spermatocytic seminoma and malignant lymphoma usually occur in older

patients

? incidence increases shortly after the onset of puberty and reaches a maximum in

men in the late twenties and thirties

ETIOLOGIC FACTORS
? Cryptorchidism
? Other developmental disorders- Dysgenetic gonads associated with endocrine

abnormalities such as androgen insensitivity syndrome

? Genetic factors-high incidence in first-degree family members, twins
? Other factors. A few less common factors
?Orchitis
?Trauma
?Carcinogens. LSD, hormonal therapy for sterility, copper, zinc etc
Prenatal risk factors ?
? consistent associations of testicular cancer with low birth weight
Exposures in adulthood
? Possible etiological clues, however, include a low level of physical activity and

high socioeconomic class

qPATHOGENESIS-vast majority of these tumours originate from germ cells
1-Developmental disorders- contribute to the pathogenesis
2-Molecular genetic features-common molecular pathogenesis of all germ cell

tumours:
? Hyperdiploidy is almost a constant feature
? isochromosome of short arm of chromosome 12
? Telomerase activity is present in all germ cell tumours of the testis
? Other mutations include p53, cyclin E and FAS gene
3-Intratubular germ cel neoplasia (ITGCN) or carcinoma insitu-
Most testicular germ cell tumors originate from a precursor lesion called

intratubular germ cell neoplasia (ITGCN)exceptions to this rule are
? pediatric yolk sac tumors
? Teratomas
? adult spermatocytic seminoma

4-Three hit' process. Germ cells in seminiferous tubules undergo
a. first hit-activate the cell
b. second hit- occure in CIS cell and further activate
c. third hit- via some epigenetic phenomena cell become invasive
this sequential tumorigenesis explains the development of seminomatous tumours


CLINICAL FEATURES AND DIAGNOSIS

? gradual gonadal enlargement and a dragging sensation in the testis
? secondary symptoms such as pain, lymphadenopathy, haemoptsis and urinary

obstruction (Metastatic involvement )

SPREAD-
? Lymphatic spread- retroperitoneal para-aortic lymph nodes, mediastinal lymph

nodes and supraclavicular lymph nodes

? Haematogenous spread -primarily occurs to the lungs, liver, brain and bones
1-Intratubular germ cel neoplasia, unclassified type (IGCNU)
? Also called carcinoma in situ (CIS) stage of germ cell tumours
? preinvasive stage of germ cell tumours
? intratubular seminoma and intratubular embryonal carcinoma are common
? 2-4% of cryptorchidism pt show
? Clinical features - atrophic testis, infertility, maldescended testis, and intersex

features

? gross- no grossly visible lesion
? Histopathology - Germ cells with abundant vacuolated cytoplasm, large, irregular

nuclei and prominent nucleoli located within the seminiferous tubules

? restricted to the seminiferous tubules without evident invasion into the

interstitium

? Immunoprofile- PLAP can be demonstrated in 83-99% of intratubular germ cell

neoplasia of the unclassified type (IGCNU) cases and is widely used for diagnosis


Comparison of morphological features of normal seminiferous tubules (left part) and intratubular

germ cel neoplasia (IGCNU) in seminiferous tubules (right part).

Seminoma
? Seminomas are the most common type of germ cell tumor, making up about

(50%)

? peak incidence is the third decade and they almost never occur in infants
? An identical tumor arises in the ovary, where it is called dysgerminoma


.

MORPHOLOGY- cut surface has a homogeneous, graywhite, lobulated, usually

devoid of hemorrhage or necrosis
Generally the tunica albuginea is not penetrated
but occasionally extension to the epididymis, spermatic cord, or scrotal sac occurs
Microscopy- typical seminoma is composed of sheets of uniform cells divided

into poorly demarcated lobules by delicate fibrous septa containing a lymphocytic

infiltrate
Tumor cell-
cell is large and round to polyhedral and has a distinct cell membrane; clear or

watery-appearing cytoplasm; and a large, central nucleus with one or two

prominent nucleoli

Stroma-
? delicate fibrous tissue which divides the tumour into lobules
? characteristic lymphocytic infiltration, indicative of immunologic response of the

host to the tumour

Variable features-
? tumor giant cells and greater mitotic activity
? 15% of seminomas contain syncytiotrophoblasts
? ill-defined granulomatous reaction (20%)


Special stain-Cytoplasm contains variable amount of glycogen that stains positively

with PAS reaction

IHC- seminoma cells stain positively for KIT, (regardless of KIT mutational status),

OCT4, and placental alkaline phosphatase (PLAP)
Prognosis-
? better than other germ cell tumours
? tumour is highly radiosensitive

Spermatocytic Seminoma-
? Spermatocytic seminoma is both clinically and morphologically a distinctive

tumour from classic seminoma

? Incidence of about 5% of all germ cell tumours
? older patients
? generally in 6th decade of life
? bilateral in 10% of patients
? Grossly, spermatocytic seminoma is homogeneous, larger, softer and

more yellowish and gelatinous than the classic seminoma

? Histological y, the distinctive features are as under:
1. Tumour cells. lymphocyte-like to huge mononucleate or multinucleate giant

cells. Majority of cells are, however, of intermediate size. Mitoses are often

frequent.
2. Stroma. stroma lacks lymphocytic and granulomatous reaction seen in classic

seminoma.
? prognosis of spermatocytic seminoma is excellent
? slow-growing and rarely metastasises
? tumour is radiosensitive

Embryonal Carcinoma-
? 30% of germ cell tumours more common
? 2nd to 3rd decades of life
? 90% cases are associated with elevation of AFP or hCG or both


Grossly,- a small tumour in the testis
? distorts the contour of the testis as it frequently invades the tunica and the

epididymis

? Cut surface- greywhite, soft with areas of haemorrhages and necrosis


Microscopy-
1. tumour cells are arranged in a variety of patterns-- glandular, tubular, papillary

and solid
2.tumour cells are highly anaplastic carcinomatous cells having large size, indistinct

cell borders, amphophilic cytoplasm and prominent hyperchromatic nuclei
Yolk Sac Tumour (Synonyms: Endodermal Sinus Tumour,

Orchioblastoma, Infantile Embryonal Carcinoma)
? most common testicular tumour of infants and young children upto the age of 4

year

? may be present as the major component in 40% of germ cell tumours
? AFP levels are elevated in 100% cases of yolk sac tumours

? Grossly, the tumour is generally soft, yellow-white, mucoid with areas of necrosis

and haemorrhages

Microscopical y, yolk sac tumour has the following features
1. patterns--loose reticular network, papil ary, tubular and solid arrangement
2. flattened to cuboid epithelial cells with clear vacuolated cytoplasm
3.A pathognomonic feature is Schil er -Duvel body
a central vessel surrounded by tumor cells in a cystic space often lined by flattened

tumor cells
4. presence of both intracellular and extracellular PAS-positive hyaline globules


Choriocarcinoma
? highly malignant tumour composed of syncytiotrophoblast and cytotrophoblast
? 2nd decade of life
? serum and urinary levels of hCG are greatly elevated in 100% cases


? Grossly, the tumour is usually small and may appear as a soft, haemorrhagic

and necrotic mass

? Microscopical y, the characteristic feature is syncytiotrophoblast and

cytotrophoblast without formation of definite placental-type vil i
Teratoma-
? Teratomas are complex tumours composed of tissues derived from more than

one of the three germ cell layers--endoderm, mesoderm and ectoderm

? more common in infants and children and constitute ( 40%)
? in adults they comprise 5% of all germ cell tumours

MORPHOLOGIC FEATURES. Testicular teratomas are classified into 3 types:
1. Mature (differentiated) teratoma
2. Immature teratoma
3. Teratoma with malignant transformation


Gross-
? large, grey-white masses enlarging testis

? Cut surface shows characteristic variegated appearance--grey-white solid areas,

cystic and honey-combed areas, and foci of cartilage and bone

Germ cell layer derivatives
Microscopicy-
? three categories of teratomas show different appearances:
1-Mature (differentiated) teratoma. Well differentiated structures such as

cartilage, smooth muscle, intestinal and respiratory epithelium, mucus glands, cysts

lined by squamous and transitional epithelium, neural tissue, fat and bone

2-Immature teratoma.
? incompletely differentiated and primitive or embryonic tissues
? along with some mature elements present are poorly-formed cartilage,

mesenchyme, neural tissues, abortive eye, intestinal and respiratory tissue

elements etc

? Mitoses are usual y frequent




Immature stroma
3-Teratoma with malignant transformation-
? extremely rare form of teratoma
? one or more of the tissue elements show malignant transformation
? Transformation may take the form of a squamous cell carcinoma, mucin-

secreting adenocarcinoma, sarcoma, or other cancers.

? importance of recognizing a non?germ cell malignancy arising in a teratoma is

that these secondary tumors are chemoresistant

Mixed Germ Cell Tumours
? About 60% of germ cel tumours have more than one of the above

histologic types (except spermatocytic seminoma) and are cal ed mixed

germ cel tumours

most common combinations of mixed germ cel tumours are as under:
1. Teratoma, embryonal carcinoma, yolk sac tumour and syncytiotrophoblast
2. Embryonal carcinoma and teratoma (teratocarcinoma)
3. Seminoma and embryonal carcinoma
? SEX CORD-STROMAL TUMOURS-Tumours arising from specialised gonadal

stroma

primitive mesenchyme>>>
? specialised stroma of gonads in either sex gives rise to theca, granulosa and lutein

cells in the female

? Sertoli and interstitial Leydig cells in the male

vLeydig (Interstitial) Cell Tumour-
? 20 to 50 yr,
? secrete androgen, or both androgen and oestrogen
Grossly, as a small, well-demarcated and lobulated nodule. Cut surface is

homogeneously yellowish or brown
Histological y, the tumour is composed of sheets and cords of normal-looking

Leydig cells
These cells contain abundant eosinophilic cytoplasm and Reinke's crystals and a

small central nucleus
vSertoli Cell Tumours (Androblastoma)-
? infants and children
? Oestrogen or androgen
? gynaecomastia in an adult
? precocious sexual development in a child

? Grossly, the tumour is large, firm, round, and well circumscribed. Cut surface is

yellowish or yellow-grey

? Microscopical y, Sertoli cell tumour is composed of benign Sertoli cells arranged

in well-defined tubules
MIXED GERM CELL-SEX CORD STROMAL TUMOURS-
? Gonadoblastoma- secrete androgen
? Grossly, the tumour is of variable size, yellowish-white and soft
? Microscopical y, gonadoblastoma is composed of 2 principal cell types--large

germ cells resembling seminoma cells, and small cells resembling immature

Sertoli, Leydig and granulosa cells

OTHER TUMOURS
Malignant Lymphoma-
? comprises 5% of testicular malignancies
? most common testicular tumour in the elderly
? Bilaterality is seen in half the cases
? Most common are large cell non-Hodgkin's lymphoma of B cell type
Must know

1-classification
2-Tumor markers in diagnosis
3-Morphology of
a)

Seminoma

b)

Embryonal carcinoma

c)

Yolk sac tumor

4-Cryporchidism