testicular tumors

TESTICULAR TUMORS:

TESTICULAR TUMORS

TESTICULAR TUMORS:

TESTICULAR TUMORS CLASSIFICATION W.H.O. CLASSIFICATION

TESTICULAR TUMORS:

TESTICULAR TUMORS GERM CELL TUMORS Seminoma Spermatocytic Seminoma Embryonal carcinoma Yolk sac tumor Polyembryoma Choriocarcinoma Teratomas Mixed germ cell tumors SEX CORD STROMAL TUMORS Leydig cell tumor Sertoli cell tumor Granulosa cell tumor Mixed forms

TESTICULAR TUMORS:

TESTICULAR TUMORS COMBINED GERM CELL – SEX CORD TUMORS Gonadoblastoma OTHER TUMORS Malignant lymphoma Rare tumors

INTRA TUBULAR GERM CELL NEOPLASIA, unclassified:

INTRA TUBULAR GERM CELL NEOPLASIA, unclassified CLINICAL : Intra tubular germ cell neoplasia is a putative precursor lesion for invasive germ cell tumors Identified in almost all testis with invasive germ cell tumors, except testis with spermatocytic seminoma Most patients (> 70 % ) with IGCNU develop invasive germ cell tumor within 7 years Involvement is patchy, & 40 % cases are bilateral T/t is orchiectomy in U/L cases & B/L orchiectomy or radiation in B/L cases.

INTRA TUBULAR GERM CELL NEOPLASIA, unclassified:

INTRA TUBULAR GERM CELL NEOPLASIA, unclassified MACROSCOPIC : No alterations MICROSCOPIC : Seminiferous tubules contain seminoma cells that are large with oval nuclei, prominent nucleoli, & clear cytoplasm Cells are confined to basal aspect of tubules Spermatogenesis is absent in involved tubules

SEMINOMA:

SEMINOMA CLINICAL : Most common germ cell tumor Mean age is 40 yrs Very rare in children Patients present with painless testicular mass 30 % have metastases at presentation, but only 3% have symptoms related to metastases Serum alpha fetoprotein is normal Beta HCG is elevated in 10 – 20 % of patients with stage I Seminoma

SEMINOMA:

SEMINOMA MACROSCOPIC : Characterized by a circumscribed lobular gray white fleshy tumor that have areas of necrosis & hemorrhage

SEMINOMA:

SEMINOMA MICROSCOPIC : Cells have round to oval nuclei with one to several nucleoli & clear to eosinophillic cytoplasm Cell borders are well defined Arranged in solid nests separated by fibrous septa Interstitial gth with preservation of tubules at the periphery of the tumor Granulomatous infiltrate in 50 % cases

SEMINOMA Strong reactivity for PLAP:

SEMINOMA Strong reactivity for PLAP

SEMINOMA:

SEMINOMA IMMUNOHISTO CHEMISTRY Cells are OCT4+ve, PLAP +ve, & c-kit +ve Contains cytokeratin, although only 36 % cases are +ve EMA -ve

SPERMATOCYTIC SEMINOMA:

SPERMATOCYTIC SEMINOMA CLINICAL : Unique tumor with distinct morphological & clinical features Occurs only in testis & represents 2 % of germ cell tumors Patients are in 50s & present with testicular mass Very rarely metastasize Usually cured by orchiedectomy

SPERMATOCYTIC SEMINOMA:

SPERMATOCYTIC SEMINOMA MACROSCOPIC : Tumors are multinodular & have a yellow edematous appearance Hemorrhage & cystic change can be present

SPERMATOCYTIC SEMINOMA:

SPERMATOCYTIC SEMINOMA MICROSCOPIC : Characterized by polymorphous cell population composed of small cells to multinucleate giant cells Cells are arranged in sheets & microcysts are present Nests & pseudo glandular structures are also identified Mitotic figures can be numerous Lymphoid & granulomatous infiltrate are absent

SPERMATOCYTIC SEMINOMA:

SPERMATOCYTIC SEMINOMA IMMUNOHISTO CHEMISTRY Cells are PLAP –ve, vimentin –ve, muscle marker –ve, cytokeratin –ve, AFP –ve, HCG –ve, EMA -ve

EMBRYONAL CARCINOMA:

EMBRYONAL CARCINOMA CLINICAL : 2 nd most common germ cell tumor, comprising approx. 20 % cases Present in majority of mixed germ cell tumors Most men present in their 20s to 30s with a testicular mass Very rare in children & older men More than 2/3rds of patients have metastases, but only 10 % have symptom related to metastases Serum AFP is normal , & beta HCG is elevated in 60 % of cases

EMBRYONAL CARCINOMA:

EMBRYONAL CARCINOMA MACROSCOPIC : Fleshy gray white tumor with prominent necrosis & hemorrhage

EMBRYONAL CARCINOMA:

EMBRYONAL CARCINOMA MICROSCOPIC : Cells are large with vesicular nuclei, prominent nucleoli, & indistinct cell borders Tumor cells are arranged in sheets, cords & glandular structures Necrosis & hemorrhage may be prominent May be intimately admixed with a yolk sac tumor

EMBRYONAL CARCINOMA:

EMBRYONAL CARCINOMA IMMUNOHISTO CHEMISTRY Tumor cells are CD 30 +ve , a finding unique to Embryonal carcinoma, and useful in ruling out solid patte4rn of Embryonal carcinoma, which can simulate Seminoma OCT 4 +ve, PLAP +ve, cytokeratin +ve, c-kit –ve, and EMA -ve

YOLK SAC TUMOR:

YOLK SAC TUMOR CLINICAL : Most common germ cell tumor ( & most common testicular tumor ) in children, where it occurs in its pure form In children, majority of cases are diagnosed before 24 months In adults, it is unusual in pure form, but is found approx. 50 % of mixed germ cell tumors Both children & adults have elevated serum AFP In children, orchiectomy alone results in a cure rate of 90 % Most adults & children present with a testicular mass

YOLK SAC TUMOR:

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

YOLK SAC TUMOR:

YOLK SAC TUMOR MICROSCOPIC : MANY HISTOLOGIC PATTERNS Endodermal sinus pattern Reticular Solid Papillary Microcystic ( most common ) Macrocystic Alveolar Myxomatous Sarcomatoid Polyvesicular – vitelline Hepatoid parietal

YOLK SAC TUMOR:

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, MICROCYSTIC PATTERN:

YOLK SAC TUMOR, MICROCYSTIC PATTERN

YOLK SAC TUMOR:

YOLK SAC TUMOR IMMUNOHISTO CHEMISTRY AFP + ( focal or patchy ), cytokeratin +ve, PLAP variable, EMA –ve, CD 30 -ve

TERATOMA:

TERATOMA CLINICAL : Adults & children present with testicular mass In children, 2 nd most common germ cell tumor Occurs in its pure form with a mean age of diagnosis at 20 months In children, metastases do not occur In adults, occur as a component of mixed germ cell tumor & is identified in > 50 % of mixed tumors In adults, Teratomas are treated like nonseminomatous germ cell tumor In adults, metastases occur even in pure teratomas

TERATOMA:

TERATOMA MACROSCOPIC : in mixed germ cell tumors, teratomatous component is solid & contain multiple cysts

TERATOMA:

TERATOMA MICROSCOPIC : Composed of somatic type of tissues that include enteric type glands, respiratory epithelium, cartilage, muscles etc. Immature Teratomas contain immature neuroepithelium, blastema or cellular stroma Can give rise to carcinoma, such as adenocarcinoma , or sarcoma, such as rhabdomyosarcoma, Wilm's like tumor, or PNET Two monodermal forms : Carcinoid tumor PNET

IMMATURE TERATOMA:

IMMATURE TERATOMA

LEYDIG CELL TUMOR:

LEYDIG CELL TUMOR CLINICAL : Leydig cell tumors comprises 3 to 5 % of testicular neoplasms Occur in adults ( majority : 80 % ) & children Children present with endocrinologic symptoms & adults present with testicular mass & some 10-30 % have gynaecomastia In children, are benign In adults, 10-17% are malignant Unilateral with rare exceptions

LEYDIG CELL TUMOR:

LEYDIG CELL TUMOR MACROSCOPIC : Leydig cells impart a yellow to yellow tan color; tumor is solid & lobulated Malignant tumors tend to be larger ( > 5 cm ) than benign tumors Necrosis can be seen in malignant tumors

LEYDIG CELL TUMOR in child:

LEYDIG CELL TUMOR in child

LEYDIG CELL TUMOR:

LEYDIG CELL TUMOR MICROSCOPIC : Leydig cells vary in size but usually have round nuclei, single prominent nucleoli & abundant eosinophillic cytoplasm or clear cytoplasm Reinke’s crystals are present in 40 to 70 % cases & lipochrome can be abundant in some cases Electron microscopy shows mitochondria with tubular cristae Rarely, adipose differentiation or spindle cell growth are noted

LEYDIG CELL TUMOR:

LEYDIG CELL TUMOR IMMUNOHISTO CHEMISTRY Inhibin – alpha +ve, and tumor shows variable reactivity with cytokeratins, S-100 proteins, synaptophysin, and estrogens & progesterone receptors

SERTOLI CELL TUMOR:

SERTOLI CELL TUMOR CLINICAL : Account for < 1 % of testicular tumors Occur both in children (15 %) & in middle aged adults, & can be malignant ( 10 % cases ) in both Patients present with testicular mass, & estrogen production by tumor can result in gynaecomastia & impotence Treatment is orchiectomy

SERTOLI CELL TUMOR:

SERTOLI CELL TUMOR MACROSCOPIC : Tumors are well circumscribed, solid pale yellow, or white to gray masses Large size & necrosis are worrisome features for malignancy

SERTOLI CELL TUMOR:

SERTOLI CELL TUMOR MICROSCOPIC : Typically composed of solid tubules containing Sertoli cells Cells may be arranged in cords, solid nests & sheets Tubules can contain Lumina Malignant behavior can be difficult to predict Features worrisome for malignancy are identical to those seen in Leydig cell tumors

SERTOLI CELL TUMOR:

SERTOLI CELL TUMOR IMMUNOHISTO CHEMISTRY Inhibin – alpha +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 % cases

SCLEROSING SERTOLI CELL TUMOR:

SCLEROSING SERTOLI CELL TUMOR CLINICAL : Rare variant of Sertoli cell tumor Patients present with a testicular mass & without endocrinologic problems No malignant cases have been reported

SCLEROSING SERTOLI CELL TUMOR:

SCLEROSING SERTOLI CELL TUMOR MACROSCOPIC : similar to Sertoli cell tumor MICROSCOPIC : Cords, nests & tubules of Sertoli cells are present within a fibrotic stroma

LARGE CELL CALCIFYING SERTOLI CELL TUMOR:

LARGE CELL CALCIFYING SERTOLI CELL TUMOR CLINICAL : Rare variant of Sertoli cell tumor Patients are young, with age at diagnosis ranging from 16 to 37 years Occurs as a part of Carney’s complex & in patients with Peutz jegher’s syndrome Malignant tumors ( 17 % cases ) occur, & usually sporadic type

LARGE CELL CALCIFYING SERTOLI CELL TUMOR:

LARGE CELL CALCIFYING SERTOLI 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 CALCIFYING SERTOLI CELL TUMOR:

LARGE CELL CALCIFYING SERTOLI CELL TUMOR MICROSCOPIC : Neoplastic cells are arranged in sheets, small nests & cords & are present in a myxoid to fibrous stroma Dystrophic calcifications, including psammomatous calcifications , are present Malignant tumors are large & exhibit extra testicular spread, increased mitotic activity, necrosis, and angiolymphatic invasion

LARGE CELL CALCIFYING SERTOLI CELL TUMOR:

LARGE CELL CALCIFYING SERTOLI CELL TUMOR IMMUNOHISTO CHEMISTRY : S-100 +ve, EMA –ve, & cytokeratin variable

GRANULOSA CELL TUMOR, adult type:

GRANULOSA CELL TUMOR, adult type CLINICAL : Much less common than in adult female ovary Average age = 42 years Often ( 20 % ) associated with Gynaecomastia Four patients had metastasis & two died

GRANULOSA CELL TUMOR, adult type:

GRANULOSA CELL TUMOR, adult type MACROSCOPIC : lobulated, firm & uniformly yellow gray mass MICROSCOPIC : Micro follicular with a few larger cysts Call – exner bodies may be seen Cells have scant cytoplasm & angular nuclei May have nuclear grooves

GRANULOSA CELL TUMOR, juvenile type:

GRANULOSA CELL TUMOR, juvenile type CLINICAL : Rare sex cord stromal tumor that occurs in males in first few months of life May occur in setting of gonadal dysgenesis Infants present with a testicular mass No malignant cases have been reported May be of Sertoli cell origin

GRANULOSA CELL TUMOR, juvenile type:

GRANULOSA CELL TUMOR, juvenile type MACROSCOPIC : tumors are small & solid & contain multiple small cysts

GRANULOSA CELL TUMOR, juvenile type:

GRANULOSA CELL TUMOR, juvenile type MICROSCOPIC : Sheets of spindle cells with abundant cytoplasm intermixed with follicle like cystic spaces Hyalinized collagenous stroma is also a feature in cellular areas

GONADOBLASTOMA:

GONADOBLASTOMA CLINICAL : Composed of a mixture of Seminoma cells & Sertoli cells Occur in dysgenetic gonads in patients with intersex syndrome ( 80 % phenotypically female ; 20 % phenotypically male ) May have ambiguous genitalia Patient karyotype 46 XY or 45X/XY most commonly Invasive germ cell tumors, usually Seminoma arise in Gonadoblastoma Treatment is removal of gonads

GONADOBLASTOMA:

GONADOBLASTOMA MACROSCOPIC : Solid yellow to tan tumors in dysgenetic gonads; in males, testis are cryptoorchid, & contain female components

GONADOBLASTOMA:

GONADOBLASTOMA MICROSCOPIC : Tumor composed of mainly Seminoma like cells , with admixed sex cord stromal cells Tumor cells form nests with central germ cells & peripheral stromal cells Globules of eosinophillic basement membrane material with peripheral pallisading stromal cells may be present in nests Hyaline globules bear resemblance to those in tubular adenoma, also called Sertoli cell adenoma, but tubules in the latter have no germ cells

LYMPHOMA:

LYMPHOMA CLINICAL : Lymphoma most often result of secondary spread; occasionally , primary lymphoma may occur Most men are in their 60s Involvement is bilateral in 20 % of all cases Survival is stage dependent

LYMPHOMA:

LYMPHOMA MACROSCOPIC : white to tan fleshy tumor

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MICROSCOPIC : In adults, most lymphomas are diffuse large cell types with a B cell phenotype May have immunoblastic features In children, small non cleaved lymphoma is most common Has an interstitial growth pattern with sparing of seminiferous tubules

IHC OF TESTICULAR GERM CELL TUMORS:

IHC OF TESTICULAR GERM CELL TUMORS Seminoma Spermato. Seminoma Embryonal carcinoma Yolk sac tumor Teratoma Choriocarcinoma OCT-4 + - + - - - CD117 + -/+ - - - - CK -/+ - + + + + VIMENTIN + - - + + - PLAP + - + + + + AFP - - + + + + HCG + - + - + + CD30 + - + - - - PAS + - - + - -

TESTICULAR TUMORS - staging:

TESTICULAR TUMORS - staging Primary tumor ( T ) Tx : unknown status of testis T0 : no apparent primary Tis : intra tubular neoplasia T1 : tumor confined to testicle T2 : tumor extending thru tunica albuginea with involvement of tunica vaginalis or the presence of angiolymphatic invasion T3 :spermatic cord involvement T4 : scortal involvement

TESTICULAR TUMORS - staging:

TESTICULAR TUMORS - staging REGIONAL LYMPH NODESD Nx : nodal status unknown N1 : single lymph node involved, < 2 cm N2 : single node, 2-5 cm or multiple nodes < 5 cm N3 : any nodes > 5 cm

TESTICULAR TUMORS - staging:

TESTICULAR TUMORS - staging DISTANT METASTASIS : Mx : status of metastases unknown M0 : no distant metastases M1 : distant metastases

TESTICULAR TUMORS - staging:

TESTICULAR TUMORS - staging SERUM MARKERS Sx : marker studies not performed S1 : LDH 1.5 times “normal” & hCG < 5000 mU/mL, & AFP < 1000uG/mL S2 : LDH 1.5-10 times ”normal” or hCG 5000-50,000 mU/mL, or AFP 1000-10,000 uG/mL S3 : LDH 10 times “normal” or hCG > 50,000 mU/mL or AFP > 10,000 uG/mL

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THANK YOU BY: DR RAVI JAIN