Steven S. Shen, MD, PhD

Mahul B. Amin, MD

Jae Y. Ro, MD, PhD

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.



  • Classic seminoma, typical seminoma

  • Germinoma in extragonadal sites

  • Dysgerminoma in females


  • 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



  • 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


  • 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


  • 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


  • 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


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%)


  • Average 5.0 cm (range 2.0-24 cm)


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



  • Periodic acid-Schiff without diastase

    • Reactivity: Positive

    • Staining pattern

      • Cytoplasmic


  • 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


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


Pathologic Interpretation Pearls

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

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