Seminoma



Seminoma


Steven S. Shen, MD, PhD

Mahul B. Amin, MD

Jae Y. Ro, MD, PhD





Key Facts


Terminology



  • Most common pure germ cell tumor composed of relatively uniform cells with abundant clear cytoplasm, well-defined cell borders, and nuclei with 1 or more prominent nucleoli


Clinical Issues



  • 30-45% of testicular germ cell tumors


Macroscopic Features



  • Well circumscribed and homogeneous ± lobulation


  • Gray-white, tan, creamy, fleshy or firm, often bulging cut surface


Microscopic Pathology



  • Fibrous septae divide sheets or nests of tumor cells into lobules


  • Tumor cells are evenly spread without nuclear overlap in well-fixed tissues


  • Prominent cytoplasmic membranes (distinct cell boundary)


  • Large round-polygonal tumor cells with abundant clear cytoplasm


  • Lymphoplasmacytic infiltrate, occasionally extensive with germinal centers in fibrous septae


  • Granulomatous inflammation in approximately 30%; can be extensive, which can create diagnostic difficulty in recognizing tumor cells


Ancillary Tests



  • PAS positive with diastase sensitive


  • (+) for Oct3/4 (nuclear), Podoplanin(D2-40), & PLAP


  • (-) for cytokeratin (may be focal or weak), CD30(BerH2), & α-fetoprotein







Low-power photomicrograph shows a well-defined classic seminoma surrounded by nonneoplastic seminiferous tubules image. Fibrovascular septae with small lymphocytic infiltrate divide the tumor into lobules.






High-power photomicrograph of classic seminoma shows tumor cells with large nuclei, prominent nucleoli, abundant clear cytoplasm, distinct cell membranes, and even distribution of tumor cells.


TERMINOLOGY


Synonyms



  • Classic seminoma, typical seminoma


  • Germinoma in extragonadal sites


  • Dysgerminoma in females


Definitions



  • Most common pure germ cell tumor composed of relatively uniform cells with abundant clear cytoplasm, well-defined cell borders, and nuclei with 1 or more prominent nucleoli


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 30-45% of testicular germ cell tumors


  • Age



    • Most commonly in men 35-45 years old


    • Uncommon in men over 50 years and rare in children


    • Mean age 5-10 years older than nonseminomatous germ cell tumors


Presentation



  • Most commonly painless testicular mass (70%)


  • Other presentations



    • Scrotal pain (10%)


    • Symptoms of metastasis (10%)


    • Asymptomatic (4%)


    • Gynecomastia and exophthalmos (rare)


  • Mostly unilateral and rarely bilateral (about 2%); bilaterality more common than in nonseminomatous germ cell tumors


  • Spermatic cord involvement (rarer than in nonseminomatous germ cell tumors; < 5%)


Laboratory Tests



  • Serum markers may be elevated



    • Serum lactate dehydrogenase (LDH)


    • Human chorionic gonadotropin (hCG)


  • α-fetoprotein (AFP) should be normal for pure seminoma



    • AFP elevation in patient with pure seminoma is clinically treated as nonseminomatous germ cell tumor


Treatment



  • For patients with stage I seminoma, 3 options are available



    • Radical inguinal orchiectomy and surveillance with measurement of serum markers, chest x-ray, and CT


    • Radical inguinal orchiectomy with single dose carboplatin adjuvant therapy


    • Radical inguinal orchiectomy with radiation therapy


  • For patients with stage II seminoma



    • Radical inguinal orchiectomy followed by radiation therapy to retroperitoneal and ipsilateral pelvic lymph nodes, or combination chemotherapy


  • For patients with stage III seminoma



    • Radical inguinal orchiectomy followed by multidrug (bleomycin, etoposide, and cisplatin) chemotherapy


Prognosis



  • Excellent prognosis with 98% cure rate for stage I or II seminoma


  • Associated with pathologic stage, tumor size, rete testis invasion, and intertubular growth > 3 high-power fields


  • Lymphovascular invasion is important prognostic factor in univariate analysis but not independent prognostic factor


  • Concept of “anaplastic” seminoma (> 3 mitoses per high-power field) is not accepted as separate entity and not adverse prognostic factor



MACROSCOPIC FEATURES


General Features



  • Well circumscribed and homogeneous ± lobulation; 90% confined to testis


  • Gray-white, tan, creamy, fleshy or firm, often bulging cut surface; usually no hemorrhage or necrosis



    • Tumors with hemorrhage and necrosis often indicate nonseminomatous germ cell components


  • May have geographic infarct-type necrosis (usually large tumors)


  • Punctate hemorrhage (usually in areas of syncytiotrophoblasts)


  • Rare spermatic cord invasion (< 5%)


Size



  • Average 5.0 cm (range 2.0-24 cm)


MICROSCOPIC PATHOLOGY


Histologic Features



  • Main architectural growth patterns



    • Solid sheets or nests (most common)


    • Interstitial (in between seminiferous tubules; rare)


    • Tubular, alveolar, or pseudoglandular (rare)


    • Trabecular (rare)


    • Sclerotic (very rare)


  • Fibrous septae divide sheets or nests of tumor cells into lobules


  • Tumor cells are evenly spread without nuclear overlap in well-fixed tissues


  • Lymphoplasmacytic infiltrate, occasionally extensive, with germinal centers in fibrous septae


  • Granulomatous inflammation in approximately 30%; may be extensive, which can create diagnostic difficulty in recognizing tumor cells


  • Fibrosis and sclerosis may be prominent (burnt-out seminoma when no tumor cells present)


  • Hemorrhage and necrosis are rarely seen


  • Syncytiotrophoblastic giant cells may be seen in areas of hemorrhage


  • Intratubular germ cell neoplasia (ITGCN) in surrounding seminiferous tubules or pagetoid spread to rete testis


Cytologic Features



  • Large round-polygonal tumor cells with abundant clear cytoplasm


  • Prominent cytoplasmic membranes (distinct cell boundary)


  • Relatively uniform, large central nuclei with 1-2 prominent nucleoli


  • Mitotic figures range from rare to frequent


  • Some tumors can have larger cells, high N:C ratio, and more mitoses (> 3/high-power field); known as “anaplastic seminoma”


  • Rarely, tumor cells can have rhabdoid appearance with abundant eosinophilic cytoplasm and eccentrically located nuclei; often occurs in poorly fixed specimens


Predominant Pattern/Injury Type



  • Neoplastic


Predominant Cell/Compartment Type



  • Uncommitted large atypical malignant germ cells


ANCILLARY TESTS


Histochemistry



  • Periodic acid-Schiff without diastase



    • Reactivity: Positive


    • Staining pattern



      • Cytoplasmic


Immunohistochemistry



  • Positive for PLAP, Oct3/4, CD117, Podoplanin(D2-40), vimentin, SALL4


  • Negative for cytokeratin (may be focal or weak), α-fetoprotein, HCG, inhibin-α, CD30, glypican-3



DIFFERENTIAL DIAGNOSIS


Embryonal Carcinoma, Solid Pattern



  • Usually admixed with glandular, papillary, and solid growth patterns


  • Marked cellular pleomorphism, vesicular nuclei, nuclear crowding with overlapping and indistinct cell border, irregularly shaped nucleoli, frequent mitoses or apoptoses


  • Positive for cytokeratin and CD30(BerH2)


Yolk Sac Tumor, Solid Pattern



  • Variable growth patterns, most commonly microcystic and reticular


  • Schiller-Duval bodies, basement membrane deposition, and hyaline globules are characteristic, if present


  • Positive for cytokeratin, α-fetoprotein, and glypican-3


Malignant Lymphoma



  • Usually older age group, history of lymphoma, and frequent bilateral involvement


  • Predominantly interstitial pattern of tumor cells between seminiferous tubules


  • Cytokeratin and germ cell markers negative; CD45(LCA) and B- or T-cell markers positive (depending on type, B more common than T)


  • Frequent spermatic cord involvement (> 40%)


Spermatocytic Seminoma



  • Older age group (average: 56 years)


  • No association with ITGCN; intratubular growth may be seen


  • Presence of 3 distinct types of tumor cells


  • Lack of lymphocytic infiltration or granulomatous inflammation; no fibrous septa


  • PAS stain negative


  • Negative for germ cell tumor markers (PLAP, Oct3/4, Podoplanin[D2-40]); CD117 may be positive


Monophasic Choriocarcinoma



  • Extremely rare; primary or metastatic foci postchemotherapy


  • Mononucleated tumor cells of variable sizes


  • More frequent hemorrhage and necrosis


  • Positive for HCG and human placental lactogen (HPL)


Nonspecific Granulomatous Orchitis



  • Mixed population of inflammatory cells


  • Predominantly involves seminiferous tubules


  • Need to differentiate from burnt out seminoma


Sertoli Cell Tumor



  • Usually more prominent tubular or cystic growth


  • Particularly for those with solid or sheets of clear cells


  • Usually lack fibrous septae with lymphoplasmacytic and granulomatous inflammation


  • Usually positive for α-inhibin and cytokeratin, negative for PLAP, Podoplanin(D2-40), and Oct3/4


DIAGNOSTIC CHECKLIST


Pathologic Interpretation Pearls

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Seminoma

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