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Revision as of 15:22, 22 May 2019

Testicular cancer Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gertrude Djouka, M.D.[2], Shanshan Cen, M.D. [3]

Overview

The pathophysiology of testicular cancer depends on the histological cell subtypes and findings. Most testicular cancers derived from the lack of differentiation of primordial germ cell into spermatogonia. On microscopic histopathological analysis of testicular cancer, fried-egg appearance is the characteristic finding of seminoma; marked nuclear atypia is the characteristic finding of embryonal carcinoma; blander cytomorphology, hyaline-type globules, and Schiller-Duval bodies are characteristic findings of yolk sac tumor  ; syncytiotrophoblasts and cytotrophoblast cells are the characteristic findings of choriocarcinoma.

Pathogenesis

Normal process of testicular germ cells

  • Primordial germ cell mass leads to gonocytes through cell proliferation
  • Gonocytes differentiate into spermatogonia

Normal process of testicular sex cord stromal

Leydig cells

Germ cells tumors

Germ cell tumors derived from germ cell neoplasia in situ

  • Lack of primordial germ cell to differentiate into spermatogonia leads to germ cell neoplasia in Situ[2]
  • Germ cell neoplasia in Situ may gain some abnormal chromosome(12), then it leads to seminomas and nonseminomas cancers.
  • Seminomas and non seminotous germ cell tumors have similar pathogenesis[5][6]
  • Aneuploid
  • Loss of chromosomes 4,5,11,13,18, and Y
  • Gain of chromosomes 7,8,12, and X
  • More than 90% of all testicular cancers are germ cell tumors. This type of cancer starts in germ cells, which are the cells that develop into sperms.
  • About 50% of all germ cell tumors are seminomas, or seminomatous germ cell tumours. They grow slower than non-seminomas.
  • Overrepresentation of short arm of chromosomes 12p may be related to invasive growth of seminomas and nonseminomatous testicular cancer.[7]
  • Seminomas tumors may have both genetic and immune components due to lymphocytes infiltration in HIV patients.[8]
  • Histological of seminomas tumor in HIV patients: tumor infiltrated by lymphocytes which may lead to weak immune system response.[8]
  • familial contribution:[9]
    • Gene on chromosome Xq27 may be related to testicular germ cell tumors
  • Some proteins such as C-kit (receptor) and placental-like alkaline phosphatase (PLAP) may be excessively expressed[10]

Germ cell tumors unrelated to germ cell neoplasia in situ

  • Mutations from the proteins that may be involved in the maturation of the spermatogonia.[11]
  • Mostly located in the testis and rarely metastases
  • Mutated proteins invovloved:SAGE1 and SSX2-4
  • Hypothesis of gain of chromosome 9 may be involved in the process.[12]

Testicular sex cord stromal tumors

Leydig cells tumor

Sertoli cell tumor

Granulosa cell tumor

Gross and Microscopic Pathology

The gross and microscopic features of the most common tumors are described below:[14][15][16][17][18][19][20][17][21][22][23][24][25][3][26][27][28]

Types Gross pathology Microscopic pathology Images
Germ cell neoplasia in situ
  • Solid, fleshy nodules
  • Similar to seminoma in appearance
  • Well-circumscribed with hemorraghic and necrotic areas
  • Hyperchromatic nuclei
  • Prominent nucleoli and clear cytoplasm
  • Thickened basement menbrane
  • Proliferation of tumor germ cell in the seminiferous tubules
Contributed by Nephron in wikimedia.commons
Seminoma
  • Solid, firm without cross section
  • Solid fleshy tan to yellow mass in homogeneous appearance
  • Well-circumscribed with small hemorraghic and necrotic areas
  • Large nucleoli with clear to pale to eosinophilic cytoplasm due to the presence of glycogen
  • Clonal proliferation of neoplastic germ cells
  • Fried-egg appearance
  • Prominent mitotic figures
  • Nests and sheets of cancer cells with "squared-off" nuclei
  • Granulomatous inflammation
Contributed by Nephron in wikimedia.commons
Embryonal carcinoma
  • Poorly demarcated mass
  • Soft gray on cut surface
  • Large hemorraghic and necrotic foci.
Contributed by Nephron in wikimedia.commons
Yolk sac tumor
  • Solid, lobulated, soft, mucinous on cut surface
  • Gray and grayish yellow mass
  • May have small hemorrhagic and necrotic foci
  • Heterogenous mass
  • Hyaline-type globules
  • Schiller-Duval bodies
  • Multiple histological patterns such as recticular, microcystic, glandular, papillary, hepatoid, and solid
  • Associated with myxoid stroma
  • Variable cytologic atypia
Contributed by EDDAOUALLINE Hanane in wikimedia.commons
Choriocarcinoma
  • Hemorrhagic and necrotic nodules
  • May appear more cystic and calcified in homogeneous
  • More Hemorrhagic and necrotic
  • Made up of mononucleated trophoblast and multinucleated syncytiotrophoblast cells
  • Hyperchomatic cytoplasm
Contributed by Nephron in wikimedia.commons
Teratoma, postpubertal-type
  • Hetereogenous, cystic and irregular calcification on appearance
  • Solid, firm mass
  • Arrange in disorder fashion
  • Cytologic atypia
  • High mitotic activities
  • Presence of 3 germ cells layers
  • Presence of immature elements with primitive nuclei
Contributed by Nephron in wikimedia.commons
Mixed germ cell tumors
  • Solid and cystic mass
  • More hemorhragic and necrotic.
  • Microscopic findings are variable depending on the tumor type
  • May have the component of yolk salk and choriocarcinoma
Contributed by Nephron in wikimedia.commons
Spermatocytic tumor
  • Soft, gray, and gelatinous mass
  • Well circumscribed with small hemorrhagic and necrotic foci.
  • Atyical mitoses activiyies
  • Eosinophilic cytoplasm without glycogen
  • Tumors cells with three different sizes (small, intermediate, and large)
  • Polymorphism with"spirene" chromatin find in the giant cells
  • Frequent apoptosis
Contributed by Nephron in wikimedia.commons
Teratoma, prepubertal-type,

Desmoid cyst

Epidermoid cyst

  • Solid and firm mass
  • Lack of cytologic atypia
  • No mitotic activities
  • Absence of immature elements
  • Desmoid cyst has polosebaceous cells
  • Epidermoist cyst is surrounded with squamous epithelial cells
Contributed by Nephron in wikimedia.commons
Testicular lymphoma
  • Soft, gray, and gelatinous mass
  • Well circumscribed with small hemorrhagic and necrotic foci.
Contributed by Nephron in wikimedia.commons
Leydig cells tumor
  • Homogeneous and well circumscribed mass
  • Solitary and unilateral mass
  • White to brown to yellow on cut surface
  • Cells are arranged in nest, sheets polygonal fahsion
  • Cytoplasm is eosinophilic with round nuclei and prominent nucleoli
  • Presence of lipofuscin pigment and reinke crystal intracytoplasmic
Contributed by Nephron in wikimedia.commons
Sertoli tumor
  • Homogeneous and well circumscribed mass
  • White to grey on cut surface
  • Cells are arranged in cords, nests and lobulated tubules
  • Fibrous stroma ans septa with lymphocytes
  • Elongated spaces and microscysts
  • Pale lipid- rich cytoplasm
  • No prominent nucleoli
Contributed by Nephron in wikimedia.commons
Granulosa tumor

Adult type

  • No distint feature

Juvenile type

  • Solid, nodule yellow-orange and cystic mass

Adult type

  • Cells are arranged in elongated, microfollicular "call-Exner bodies"

Juvenile type

  • Cells are presented in solid sheets and nodules and form the estatic space
  • Eosinophilic cytoplasm
  • Hyperchromatic, round to oval nuclei
  • High mitotic activities
  • Follicles are located on the periphery
Contributed by Nephron in wikimedia.commons

Genetics

These are genes involved in the pathogenesis of testicular cancer:[29][30]

  • Chromosome 12p
  • 12q22.2

Immunohistochemical Markers

  • Germ cell Neoplastic in situ:
    • +PLAP (Placenta like-alkaline phosphatase)[31]
  • Seminomas:[19][32][33]
    • OCT3/4 transcription factors[34]
    • C-kit
    • CD30
    • D2-40 monoclonal antibody
    • PLAP
    • NANOG transcription factor
  • Spermatocytic tumor:[12]
    • +Sall4
    • +/-C-kit

References

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  2. 2.0 2.1 Kraggerud SM, Hoei-Hansen CE, Alagaratnam S, Skotheim RI, Abeler VM, Rajpert-De Meyts E, Lothe RA (June 2013). "Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis". Endocr. Rev. 34 (3): 339–76. doi:10.1210/er.2012-1045. PMC 3787935. PMID 23575763.
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