Intratubular Germ Cell Neoplasia

Intratubular Germ Cell Neoplasia

Steven S. Shen, MD, PhD

Mahul B. Amin, MD

Jae Y. Ro, MD, PhD

ITGCN is characterized by large atypical cells located along the periphery of the tubules image. The cells have centrally located nuclei, prominent nucleoli, and abundant clear cytoplasm.

Immunohistochemical stain for Oct3/4 shows strong nuclear immunoreactivity in ITGCN cells image within the seminiferous tubules. Normal germ cells are negative.



  • Intratubular germ cell neoplasia (ITGCN)


  • Carcinoma in situ; ITGCN, unclassified type


  • Proliferation of uncommitted neoplastic germ cells within seminiferous tubules; usually aligned at periphery of tubules



  • Incidence

    • Present in ipsilateral uninvolved testis in 80-95% of patients with malignant germ cell tumors

    • Present in contralateral testis in 5-8% of patients with malignant germ cell tumors


  • In cryptorchid testis or in association with malignant germ cell tumor

  • Risk factors

    • Cryptorchidism

    • Microlithiasis

    • Gonadal dysgenesis with Y chromosome

    • Family history (1st-degree male relative)

    • Androgen insensitivity syndrome


  • Surgical approaches

    • Unilateral ITGCN usually managed by active surveillance or orchiectomy

    • Bilateral ITGCN may be treated by orchiectomy

  • Radiation

    • May be used for bilateral ITGCN


  • May progress to seminomatous or nonseminomatous germ cell tumors in about 50% of cases within 5 years


General Features

  • Usually no abnormalities or microlithiasis on ultrasound


General Features

  • No demonstrable testicular mass; testis size may be normal or smaller


Histologic Features

  • Intratubular proliferation of malignant germ cells distributed along periphery of tubules

  • Seminiferous tubules may be atrophic, decreased in diameter, and may have thickened basement membrane

  • Large atypical cells with prominent cell borders, centrally located nuclei with enlarged nuclei, evenly distributed chromatin, and prominent nucleoli

  • Tumor cells with abundant clear to faintly eosinophilic cytoplasm

  • Tubules with decreased or absent spermatogenesis

  • May be associated with microlithiasis

  • Pagetoid extension of ITGCN into rete testis may be seen; more frequent in nonseminomatous germ cell tumor than in seminoma

Cytologic Features

  • Large atypical cells with abundant clear to faintly eosinophilic cytoplasm; mitoses may be seen

Predominant Pattern/Injury Type

  • Intratubular growth pattern, no mass formation

Predominant Cell/Compartment Type

  • Germ cells, uncommitted atypical germ cells, seminomatous/undifferentiated



  • PAS-diastase

    • Reactivity: Positive but sensitive to diastase

    • Staining pattern

      • Cytoplasmic


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

  • Negative for cytokeratin, α-fetoprotein, and CD30(BerH2)


Normal Spermatogonia

  • Usually accompanied by mixture of spermatogonia, spermatocytes, spermatids, and spermatozoa

  • No tubular atrophy or thickening of peritubular tunica basement membrane

  • Lacks prominent nucleoli

  • Negative for CD117, Podoplanin(D2-40), Oct3/4, and PLAP

Malignant Lymphoma (Intratubular)

  • Usually associated with diffuse interstitial infiltrative growth

  • Positive for CD45(LCA), CD20, and CD3

  • Negative for germ cell tumor markers

Metastatic Carcinoma or Melanoma (Intratubular)

  • Metastatic carcinoma or melanoma may be intratubular; usually more pleomorphic with mitoses

  • Metastatic carcinoma positive for pankeratin, EMA/MUC1, and tissue-specific markers (TTF-1, PSA, etc.)

  • Melanoma positive for S100 and HMB-45

ITGCN with Microscopic Invasive Seminoma

  • Lymphoplasmacytic infiltrate in interstitium

  • Atypical tumor cells may be scattered among lymphocytes

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Intratubular Germ Cell Neoplasia

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