Download MBBS Pathology PPT 14 Testis Lecture Notes

Testis

Must know

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

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Seminoma

b)

Embryonal carcinoma

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c)

Yolk sac tumor

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4-Cryptorchidism


Testicular lesion

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

(Autoimmune) Orchitis)

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? VascularDisorders(torsion)
? SpermaticCordandParatesticularTumors
? TesticularTumors
INFLAMMATIONS-

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? 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-

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? may be acute or chronic
? common routes of spread are via the vas deferens, or lymphatic and

haematogenous routes

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

trachomatis
Grossly,

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

infection

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? chronic stage- variable degree of atrophy and fibrosis

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

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neutrophilic abscesses

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

tubules, fibrous scarring and destruction of interstitial Leydig cells

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2-Granulomatous (Autoimmune) Orchitis -
Non-tuberculous granulomatous orchitis-
? unilateral, painless testicular enlargement
? may resemble a testicular tumour clinically
? autoimmune basis is suspected

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

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throughout the testis and is confined to the seminiferous tubules

? Peritubular fibrosis
? interstitial lymphocytes and plasma cells
3-Tuberculous Epididymo-orchitis-

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? 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

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

mass

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

lymphocytes, occasional multinucleate giant cells and central areas of caseation

necrosis are seen

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? AFB positive


4-Spermatic Granuloma(epididymitis nodosa)

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? Spermatic granuloma is the term used for development of

inflammatory lesions due to invasion of spermatozoa into the stroma
MORPHOLOGIC FEATURES-
Grossly,

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? 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,

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epithelioid cells, lymphocytes and some neutrophils

? Characteristical y, the centre of spermatic granuloma contains

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spermatozoa and necrotic debris
Vascular disorder

Torsion of Testis
? Twisting of the spermatic cord

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? 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

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

? It lacks any associated anatomic defect in testis

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

pain

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? 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

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onset of torsion

MORPHOLOGIC FEATURES-
duration and severity of vascular occlusion

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? may be coagulative necrosis of the testis and epididymis
? may be haemorrhagic infarction
Spermatic Cord and Paratesticular Tumors

1-Lipomas

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? 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

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

2-Adenomatoid tumor-
? most common benign paratesticular tumor

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?
? typically occurring near the upper pole of the epididymis
? grossly , well circumscribed small nodules
? Microscopically- Proliferation of glandular structures, irregularly lined by cuboidal

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to flattened epithelial cell

? Treatmet- local excision

Malignant tumor

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? rhabdomyosarcomas -children
? liposarcomas- adults

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CLASSIFICATION OF TESTICULAR TUMOR

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

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WHO histological classification of testis tumours

? Germ cell tumours
? Tumours of one histological type (pure forms)

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? 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

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? Tumours of paratesticular structures
? Mesenchymal tumours of the spermatic cord and testicular adnexae
? Secondary tumours of the testis

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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

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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

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or other organs of the body)

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

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testicular cancers

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

each piece of information.

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? 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.

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? 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

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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)

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? 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

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? 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

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? 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

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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

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? S0 Serum marker study levels within normal limits
? LDH, hCG (mIU/ml) ,AFP (ng/ml)

Serum tumor markers (S)

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

containing the cancer has been removed with surgery

LDH

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HCG

AFP (ng/ml)

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(U/liter)

(mIU/ml)

SX Marker studies not available or not done.

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S0 Normal

Normal

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Normal

S1 <1.5 x

<5,000

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<1,000

*

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Normal

S2 1.5 - 10 x

5,000 -

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1,000 -

+

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Normal

50,000

10,000

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S3 >10 x

>50,000

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>10,000

+

Normal

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

descend into the scrotal sac

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

? In 70% of cases, the undescended testis lies in the inguinal ring

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? in 25% in the abdomen
ETIOLOGY. exact etiology is not known in majority of cases
1. Mechanical factors-
? short spermatic cord
? narrow inguinal canal

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? 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

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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

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demonstrated in a small number of cases

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

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

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related peptide or the cremasteric nucleus have been postulated to cause

cryptorchidism

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

been associated with an increased risk

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

cryptorchidism
MORPHOLOGIC FEATURES. Cryptorchidism is unilateral in 80% cases

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

Histology-
1-Seminiferous tubules
? tubular basement membrane is thickened

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? 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

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? CLINICAL FEATURES. asymptomatic and is discovered only on physical

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examination

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

unilateral disease may result in infertility

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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

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

descended testis

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? 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

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? carcinoma arises from foci of intratubular germ cell neoplasia within the atrophic

tubules

? Orchiopexy reduces the risk of sterility and cancer

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Tumour marker

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

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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)

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

placental alkaline phosphatase, testosterone, oestrogen and luteinising hormone

may also be elevated

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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

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? 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

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choriocarcinoma, yolk sac tumour and embryonal carcinoma)

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

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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

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

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

if the lymph nodes appear of normal size by imaging studies

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? 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

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predict recurrence before the patients become symptomatic or develop any other

clinical signs of relapse

TESTICULAR TUMOR

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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

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teratoma

? Spermatocytic seminoma and malignant lymphoma usually occur in older

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patients

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

men in the late twenties and thirties

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

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abnormalities such as androgen insensitivity syndrome

? Genetic factors-high incidence in first-degree family members, twins
? Other factors. A few less common factors
?Orchitis

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?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

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? 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

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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

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? 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

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

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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

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this sequential tumorigenesis explains the development of seminomatous tumours


CLINICAL FEATURES AND DIAGNOSIS

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

obstruction (Metastatic involvement )

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

nodes and supraclavicular lymph nodes

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? 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

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? 2-4% of cryptorchidism pt show
? Clinical features - atrophic testis, infertility, maldescended testis, and intersex

features

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

nuclei and prominent nucleoli located within the seminiferous tubules

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? restricted to the seminiferous tubules without evident invasion into the

interstitium

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

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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

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

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

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(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

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.

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

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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

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into poorly demarcated lobules by delicate fibrous septa containing a lymphocytic

infiltrate
Tumor cell-

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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

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

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host to the tumour

Variable features-
? tumor giant cells and greater mitotic activity
? 15% of seminomas contain syncytiotrophoblasts

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? ill-defined granulomatous reaction (20%)


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

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with PAS reaction

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

OCT4, and placental alkaline phosphatase (PLAP)

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Prognosis-
? better than other germ cell tumours
? tumour is highly radiosensitive

Spermatocytic Seminoma-

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? Spermatocytic seminoma is both clinically and morphologically a distinctive

tumour from classic seminoma

? Incidence of about 5% of all germ cell tumours

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? older patients
? generally in 6th decade of life
? bilateral in 10% of patients
? Grossly, spermatocytic seminoma is homogeneous, larger, softer and

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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

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

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

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

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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

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

epididymis

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


Microscopy-

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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

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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

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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

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

and haemorrhages

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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

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

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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

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

and necrotic mass

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? 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

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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

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

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Gross-
? large, grey-white masses enlarging testis

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? 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

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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

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

2-Immature teratoma.
? incompletely differentiated and primitive or embryonic tissues

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? along with some mature elements present are poorly-formed cartilage,

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

elements etc

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? Mitoses are usual y frequent

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Immature stroma
3-Teratoma with malignant transformation-
? extremely rare form of teratoma
? one or more of the tissue elements show malignant transformation

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? 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

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that these secondary tumors are chemoresistant

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

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

germ cel tumours

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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

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stroma

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

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cells in the female

? Sertoli and interstitial Leydig cells in the male

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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

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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

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small central nucleus
vSertoli Cell Tumours (Androblastoma)-
? infants and children
? Oestrogen or androgen

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? gynaecomastia in an adult
? precocious sexual development in a child

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

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yellowish or yellow-grey

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

in well-defined tubules

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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

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germ cells resembling seminoma cells, and small cells resembling immature

Sertoli, Leydig and granulosa cells

OTHER TUMOURS

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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

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Must know

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

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a)

Seminoma

b)

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Embryonal carcinoma

c)

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Yolk sac tumor

4-Cryporchidism