TESTICULAR TUMOUR

TESTICULAR TUMORSWHO CLASSIFICATION

GERM CELL TUMORS

SeminomaSpermatocytic seminoma

Embryonal carcinomaPolyembryoma

Embryonal carcinoma and teratoma (‘teratocarcinoma’)

TeratomaMatureImmatureWith malignant transformation

Choriocarcinoma Yolk sac tumour

SEX CORD STROMAL TUMORS

1. Leydig cell tumor

2. Sertoli cell tumor

3. Granulosa cell tumor

4. Mixed forms

TESTICULAR TUMORS

COMBINED GERM CELL – SEX CORD TUMORS

1. Gonadoblastoma

OTHER TUMORS

1. Malignant lymphoma

2. Rare tumors

Predisposing and accompanying factors

Heredity and genetics. A few cases of testicular germ cell tumor have occurred in a familial setting,suggesting a genetic background. Specifically, trisomy 21 is associated with an increased risk.

Elevated estrogens in utero. Gonadal dysgenetic lesions. HIV-infected patients. Environmental factors More common in white than black Klinefelter syndrome.

Age

1. . The peak is 30-40 years - classic seminoma,

2. 60 -65 years - spermatocytic seminoma,

3. The majority of pure yolk sac tumors occur in infants under 2 years of age.

Presentation

Most testicular germ cell tumors present with progressive, painless enlargement of the testis.

They may grow slowly or with appalling speed. Sometimes, the initial presentation is in the form of a

metastatic deposit in the retroperitoneum, lung, or mediastinum.

A small tumor may be found in a testis by palpation or ultrasonography.

The patient may have gynecomastia, large mediastinal and/or pulmonary metastases.

Cutaneous atypical nevi. It has been claimed that multiple cutaneous atypical nevi occur with increased frequency in patients with testicular germ cell tumors and that they could represent a marker for this disease.

Bilaterality

Bilateral testicular involvement by germ cell tumors is seen in 1.0–2.7% of the cases according to the different series.

The risk of bilaterality rises to 15% if both testes are undescended.

The most common situation is bilateral spermatocytic or classic seminoma.

In the presence of bilateral testicular tumors in an elderly individual, the most likely diagnosis is malignant lymphoma

Telomerase activity is present in all types of testicular germ cell tumors except for mature teratomas.

Spermatocytic seminoma shows completely different genetic features. Isochromosome 12p is not found.

Numerical chromosomal aberrations are common, and gain of chromosome 9 is characteristic.

SEMINOMA

1. Most common germ cell tumor

2. Mean age is 40 yrs

3. Very rare in children

4. Patients present with painless testicular mass

5. 30 % have metastases at presentation, but only 3% have symptoms related to metastases.

Diagram showing relationships between various types of germ cell tumors

Gross appearance of seminoma. The tumor in A is very small, whereas that in B has replaced most of the testis

Gross appearance of combined tumor of testis. In both instances, the solid homogeneous gray areas correspond to the seminoma, and the variegated foci with

hemorrhage to the nonseminomatous component

SEMINOMA

MICROSCOPIC :1. Cells have round to oval

nuclei with one to several nucleoli & clear to eosinophillic cytoplasm

2. Cell borders are well defined3. Arranged in solid nests

separated by fibrous septa4. Granulomatous infiltrate in

50 % cases

Seminoma associated with marked granulomatous reaction. Only a few tumor cells are visible in this field

This seminoma has increased nuclear pleomorphism and a plasmacytoid appearance

Seminoma with trophoblastic giant cells. (A, Hematoxylin and eosin; B, hCG immunostain

SEMINOMA

IMMUNOHISTO CHEMISTRYCells are OCT4+ve, PLAP +ve, & c-kit +veContains cytokeratins, although only

36 % cases are +veEMA -ve

SEMINOMA Strong reactivity for PLAP

strong nuclear and weaker cytoplasmic reactivity for OCT3/4 in this seminoma

SPERMATOCYTIC SEMINOMA

1. Occurs only in testis & represents 2 % of germ cell tumors

2. Patients are in 50s & present with testicular mass

3. Very rarely metastasize.

SPERMATOCYTIC SEMINOMA

MACROSCOPIC

1. Tumors are multinodular & have a yellow edematous appearance

2. Hemorrhage & cystic change can be present

spermatocytic seminoma shows fleshy, gelatinous, and hemorrhagic nodules

SPERMATOCYTIC SEMINOMAMICROSCOPIC :1. Characterized by

polymorphous cell population composed of small cells to multinucleate giant cells

2. Cells are arranged in sheets & microcysts are present

3. Nests & pseudo glandular structures are also identified

4. Mitotic figures can be numerous

5. Lymphoid & granulomatous infiltrates are absent

Spermatocytic seminoma showing admixture of medium-sized cells (predominating), giant cells, and small lymphocyte-like cells

Typical chromatin pattern of spermatocytic seminoma

SPERMATOCYTIC SEMINOMA

IMMUNOHISTO CHEMISTRYCells are PLAP –ve, vimentin –ve, muscle marker –ve, cytokeratin –ve, AFP –ve, HCG –ve, EMA –veNY-ESO 1 +veSCP-1 +ve

Classic seminoma SPERMATOCYTIC SEMINOMA

EMBRYONAL CARCINOMA

1. 2nd most common germ cell tumor, comprising approx. 20 % cases

2. Present in majority of mixed germ cell tumors

3. Most men present in their 20s to 30s with a testicular mass

4. More than 2/3rds of patients have metastases, but only 10 % have symptom related to metastases.

EMBRYONAL CARCINOMA

MACROSCOPIC :

1. Fleshy gray white tumor with prominent necrosis & hemorrhage

EMBRYONAL CARCINOMAMICROSCOPIC :1. Cells are large with vesicular nuclei, prominent nucleoli, &

indistinct cell borders

2. Tumor cells are arranged in sheets, cords & glandular structure

3. Necrosis & hemorrhage may be prominent

4. May be intimately admixed with a yolk sac tumor

Embryonal carcinoma. The pattern of growth is diffuse , The high-power view shows the typical large, irregularly shaped,

overlapping nuclei with multiple prominent nucleoli

EMBRYONAL CARCINOMA

IMMUNOHISTO CHEMISTRYTumor cells are CD 30 +ve, a finding unique to

Embryonal carcinoma, and useful in ruling out solid pattern of Embryonal carcinoma, which can simulate Seminoma .

OCT 4 +ve, PLAP +ve, cytokeratin +ve, c-kit –ve, and EMA -ve

CD30 highlights the cytoplasmic membranes of an embryonal carcinoma

YOLK SAC TUMOR CLINICAL :

1. Most common germ cell tumor ( & most common testicular tumor ) in children, where it occurs in its pure form

2. In children, majority of cases are diagnosed before 24 months

3. In adults, it is unusual in pure form, but is found approx. 50 % of mixed germ cell tumors

4. Most adults & children present with a testicular mass

YOLK SAC TUMOR

MACROSCOPIC : white to tan masses, with myxoid & cystic changes

pediatric yolk sac tumor appears as a solid, yellow, myxoid nodule

The cut surface of this adult yolk sac tumor shows areas of hemorrhage and cystic change.

YOLK SAC TUMOR

MICROSCOPIC :Deposition of basement membrane material &

SCHILLER – DUVAL bodies ( central vessel rimmed by loose connective tissue that in turn is lined by malignant epithelium, all within a cystic space ), are characteristic.

YOLK SAC TUMOR

Pleomorphism and hyaline globules in yolk sac tumor of testis.

an embryonal carcinoma may produce structures resembling the endodermal sinus-like formations seen in yolk sac tumor.

YOLK SAC TUMOR, MICROCYSTIC PATTERN

A myxomatous pattern yolk sac tumor has thin cords of cells in an extensively mucoid stroma.

YOLK SAC TUMOR

IMMUNOHISTO CHEMISTRYAFP + ( focal or patchy ), cytokeratin +ve, PLAP variable, EMA –ve, CD 30 -ve

characteristic patchy distribution of alpha-fetoprotein positivity in this yolk sac tumor

TERATOMA

CLINICAL :

1. Adults & children present with testicular mass

2. In children, 2nd most common germ cell tumor

3. Occurs in its pure form with a mean age of diagnosis at 20 months

4. In adults, occur as a component of mixed germ cell tumor & is identified in > 50 % of mixed tumors

TERATOMA

MACROSCOPIC :

TERATOMA

MICROSCOPIC :1. Composed of somatic type of tissues that include enteric type

glands, respiratory epithelium, cartilage, muscles etc.2. Immature Teratomas contain immature neuroepithelium,

blastema or cellular stroma

Large islands of cartilage are seen surrounding well-differentiated glandular structures

IMMATURE TERATOMA, Microscopic appearance. Hypercellular stroma is seen growing in a concentric fashion around glandular formations

TeratocarcinomaThe solid granular areas , pearly nodules

Chorio carcinoma

Microscopic appearance of testicular choriocarcinoma. There is close

intermingling of cytotrophoblast and syncytiotrophoblast.

LEYDIG CELL TUMOR

CLINICAL :

1. Leydig cell tumors comprises 3 to 5 % of testicular neoplasms

2. Occur in both adults ( majority : 80 % ) & children

3. Children present with endocrinologic symptoms & adults present with testicular mass & some 10-30 % have gynaecomastia

LEYDIG CELL TUMOR

MACROSCOPIC :

1. Leydig cells impart a golden brown colour. tumor is solid & lobulated

2. Malignant tumors tend to be larger ( > 5 cm ) than benign tumors

3. Necrosis can be seen in malignant tumors

LEYDIG CELL TUMOR

MICROSCOPIC :1. Leydig cells vary in size

but usually have round nuclei, single prominent nucleoli & abundant eosinophillic cytoplasm or clear cytoplasm

2. Reinke’s crystals are present in 40 to 70 % cases & lipochrome can be abundant in some cases

The neoplasm is characterized by solid growth of polygonal cells with abundant granular acidophilic cytoplasm

The tumor cells have a cytoplasmic clear quality

LEYDIG CELL TUMOR

IMMUNOHISTO CHEMISTRYInhibin –+ve, Mart -1

Tumor shows variable reactivity withcytokeratins, S-100 proteins, synaptophysin, and estrogens & progesterone receptors

SERTOLI CELL TUMOR

CLINICAL :

1. Account for < 1 % of testicular tumors

2. Occur both in children (15 %) & in middle aged adults, & can be malignant ( 10 % cases ) in both

3. Patients present with testicular mass, & estrogen production by tumor can result in gynaecomastia & impotence

SERTOLI CELL TUMOR

MACROSCOPIC :

1. Tumors are well circumscribed, solid pale yellow, or white to gray masses

2. Large size & necrosis are worrisome features for malignancy

SERTOLI CELL TUMOR

MICROSCOPIC :1. Typically composed of solid

tubules containing Sertoli cells

2. Cells may be arranged in cords, solid nests & sheets

3. Tubules can contain Lumina

SERTOLI CELL TUMOR

IMMUNOHISTO CHEMISTRYInhibin –+ve, but less consistently than in leydig cell

tumor & can be +ve with chromogranin, S-100 proteins, synaptophysin, and cytokeratin AE1/3 &

CAM 5.2 in 64-100 % casesMIS & CD99 +ve

SCLEROSING SERTOLI CELL TUMOR

CLINICAL :

1. Rare variant of Sertoli cell tumor

2. Patients present with a testicular mass & without endocrinologic problems

3. No malignant cases have been reported

SCLEROSING SERTOLI CELL TUMOR

Cords, nests & tubules of Sertoli cells are present within a fibrotic stroma

LARGE CELL CALCIFYINGSERTOLI CELL TUMOR

CLINICAL :

1. Rare variant of sertoli cell tumor

2. Patients are young, with age at diagnosis ranging from 16 to 37 years

3. Occurs as a part of Carney’s complex & in patients with Peutz jegher’s syndrome

4. Malignant tumors ( 17 % cases ) occur, & usually sporadic type

LARGE CELL CALCIFYINGSERTOLI CELL TUMOR

MACROSCOPIC : Benign tumors are small

( usually < 2 cm ) yellow tan or white nodules confined to the testicle

Malignant tumors are larger & may have areas of necrosis

LARGE CELL CALCIFYINGSERTOLI CELL TUMOR

MICROSCOPIC :

1. Neoplastic cells are arranged in sheets, small nests & cords & are present in a myxoid to fibrous stroma

2. Dystrophic calcifications are present

3. Malignant tumors are large & exhibit extra testicular spread, increased mitotic activity, necrosis, and angiolymphatic invasion

GRANULOSA CELL TUMOR,

CLINICAL :

1. Much less common than in adult female ovary

2. Average age = 42 years

3. Often ( 20 % ) associated with Gynaecomastia

GRANULOSA CELL TUMOR,

MICROSCOPIC :

1. Micro follicular with a few larger cysts

2. Call – exner bodies may be seen

3. Cells have scant cytoplasm & angular nuclei

4. May have nuclear grooves

GONADOBLASTOMA

CLINICAL :

1. Composed of a mixture of Seminoma cells & Sertoli cells

2. Occur in dysgenetic gonads in patients with intersex syndrome

3. Patient karyotype 46 XY or 45X/XY most commonly

4. Invasive germ cell tumors, usually Seminoma arise in Gonadoblastoma

GONADOBLASTOMA

MACROSCOPIC :

Solid yellow to tan tumors in males, testis are cryptoorchid.

GONADOBLASTOMA MICROSCOPIC : 1. Tumor composed of

mainly Seminoma like cells , with admixed sex cord stromal cells

2. Tumor cells form nests with central germ cells & peripheral stromal cells

3. Globules of eosinophillic basement membrane material with peripheral pallisading stromal cells may be present in nests

LYMPHOMA

CLINICAL :

1. Lymphoma most often result of secondary spread; occasionally , primary lymphoma may occur

2. Most men are in their 60s

3. Involvement is bilateral in 20 % of all cases

LYMPHOMA

MACROSCOPIC : white to tan fleshy tumor

LYMPHOMAMICROSCOPIC : 1. In adults, most lymphomas

are diffuse large cell types with a B cell phenotype

2. May have immunoblastic features

3. In children, small non cleaved lymphoma is most common

4. Has an interstitial growth pattern with sparing of seminiferous tubules

INTRA TUBULAR GERM CELL NEOPLASIA

1. Intra tubular germ cell neoplasia is a precursor lesion for invasive germ cell tumors

2. Identified in almost all testis with invasive germ cell tumors, except testis with spermatocytic seminoma

3. Most patients (> 70 % ) with IGCNU develop invasive germ cell tumor within 7 years

4. Involvement is patchy, & 40 % cases are bilateral

INTRA TUBULAR GERM CELL NEOPLASIA

MACROSCOPIC :

1. No alterations MICROSCOPIC :

1. Seminiferous tubules contain seminoma cells that are large with oval nuclei, prominent nucleoli, & clear cytoplasm

2. Cells are confined to basal aspect of tubules

3. Spermatogenesis is absent in involved tubules

Other primary tumors

Carcinoid tumors HemangiomaJuvenile xanthogranuloma and

myofibroma.LipomatosisPrimary sarcoma

Metastatic tumors

Arise for the most part in the lung, prostate, kidney, stomach, or skin (melanoma).

Malignant melanoma metastatic to testis

IHC OF TESTICULAR GERM CELL TUMORSSeminoma Spermato.

SeminomaEmbryonal carcinoma

Yolk sac tumor

Teratoma Choriocarcinoma

OCT-4 + - + - - -CD117 + -/+ - - - -CK -/+ - + + + +VIMENTIN + - - + + -PLAP + - + + + +AFP - - + + + +HCG + - + - + +CD30 + - + - - -PAS + - - + - -

Thank you

Speaker

DR. Narmada Prasad Tiwari