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=Testicular sex cord stromal tumors=
=Testicular sex cord stromal tumors=
===Leydig cells tumor===
===Leydig cells tumor===
*The pathogenesis of leydig cells tumors is not well understood.<ref name="pmid17284120">{{cite journal |vauthors=Al-Agha OM, Axiotis CA |title=An in-depth look at Leydig cell tumor of the testis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=2 |pages=311–7 |date=February 2007 |pmid=17284120 |doi=10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2 |url=}}</ref><ref name="pmid17284120">{{cite journal |vauthors=Al-Agha OM, Axiotis CA |title=An in-depth look at Leydig cell tumor of the testis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=2 |pages=311–7 |date=February 2007 |pmid=17284120 |doi=10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2 |url=}}</ref><ref name="pmid16097561">{{cite journal |vauthors=Conkey DS, Howard GC, Grigor KM, McLaren DB, Kerr GR |title=Testicular sex cord-stromal tumours: the Edinburgh experience 1988-2002, and a review of the literature |journal=Clin Oncol (R Coll Radiol) |volume=17 |issue=5 |pages=322–7 |date=August 2005 |pmid=16097561 |doi= |url=}}</ref>
*The pathogenesis of leydig cells tumors is not well understood.<ref name="pmid17284120">{{cite journal |vauthors=Al-Agha OM, Axiotis CA |title=An in-depth look at Leydig cell tumor of the testis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=2 |pages=311–7 |date=February 2007 |pmid=17284120 |doi=10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2 |url=}}</ref><ref name="pmid16097561">{{cite journal |vauthors=Conkey DS, Howard GC, Grigor KM, McLaren DB, Kerr GR |title=Testicular sex cord-stromal tumours: the Edinburgh experience 1988-2002, and a review of the literature |journal=Clin Oncol (R Coll Radiol) |volume=17 |issue=5 |pages=322–7 |date=August 2005 |pmid=16097561 |doi= |url=}}</ref>
*It is hypothesized that there is a disturbance of hypothalamic-pituitary-testicular axis which lead to excess of hormone productions.
*It is hypothesized that there is a disturbance of hypothalamic-pituitary-testicular axis which lead to excess of hormone productions.
*The G proteins in the leydig cells and the structure alteration of Lutheinizing hormone receptors may play role in leydig cells tumors.
*The G proteins in the leydig cells and the structure alteration of Lutheinizing hormone receptors may play role in leydig cells tumors.


==Gross and Microscopic Pathology==
==Gross and Microscopic Pathology==

Revision as of 15:45, 10 May 2019

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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

  • Normal inner cell mass leads to primordial germ cell mass[1][2]
  • Primordial germ cell mass leads to gonocytes through cell proliferation
  • Gonocytes differentiate into spermatogonia

Normal process of testicular sex cord stromal

Leydig cells

  • Leydig cells are found in the seminiferous tubules of the testis.[3][4]
  • Leydig cells secrete testosterone hormone under the signal of luteinizing hormone
  • Leydig cells are involved in the development of male secondary sexual characteristics and spermatogenesis

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

  • The pathogenesis of leydig cells tumors is not well understood.[3][13]
  • It is hypothesized that there is a disturbance of hypothalamic-pituitary-testicular axis which lead to excess of hormone productions.
  • The G proteins in the leydig cells and the structure alteration of Lutheinizing hormone receptors may play role in leydig cells tumors.

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]

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.
  • Presents with mixed histological features (solid, papular, glandular)
  • Marked nuclear atypia
  • Marked epithelial cells with polymorphism
  • Large nuclei with abundant amphophilic cytoplasm
  • Prominent mitotic activities
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 york 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.
  • Vascular invasion
  • Pleomorphic tumor cells
  • Large irregular nuclei
Contributed by Nephron in wikimedia.commons

Genetics

These are genes involved in the pathogenesis of testicular cancer:[26][27]

  • Isochromosome 12p
  • 12q22.2

Immunohistochemical Markers

Germ cell Neoplastic in situ:

  • +PLAP (Placenta like-alkaline phosphatase)[28]

Seminomas

Stain positively for:[19][29][30]

  • OCT3/4 transcription factors[31]
  • C-kit
  • CD30
  • D2-40 monoclonal antibody
  • PLAP
  • NANOG transcription factor

Embryonal carcinoma

Stain positively for:[29][30]

  • PLAP
  • OCT3/4[31]
  • SOX2
  • CD30
  • +/-GpC3,keratin

Yolk sac tumor:[12][32]

  • +SALL4
  • +AFP
  • +GATA3
  • +Glypican3
  • +Keratin
  • +/-C-kit

Choriocarcinoma:[12]

  • +Ck7
  • +GATA3
  • +HCG
  • +/-Sall4

Spermatocytic tumor:[12]

  • +Sall4
  • +/-C-kit

Teratoma:[21][33][12]

  • +Sall4
  • +Cytokeratin
  • +HCG
  • +/-GATA3,SOX2,OCT4

Testicular lymphoma:[12]

  • +CD3
  • +CD20
  • +CD45

References

  1. Miyai, Kosuke; Ito, Keiichi; Nakanishi, Kuniaki; Tsuda, Hitoshi (2019). "Seminoma component of mixed testicular germ cell tumor shows a higher incidence of loss of heterozygosity than pure-type seminoma". Human Pathology. 84: 71–80. doi:10.1016/j.humpath.2018.09.007. ISSN 0046-8177.
  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.
  3. 3.0 3.1 3.2 Al-Agha OM, Axiotis CA (February 2007). "An in-depth look at Leydig cell tumor of the testis". Arch. Pathol. Lab. Med. 131 (2): 311–7. doi:10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2. PMID 17284120.
  4. Neaves WB (May 1975). "Leydig cells". Contraception. 11 (5): 571–606. PMID 1095296.
  5. Bray F, Richiardi L, Ekbom A, Forman D, Pukkala E, Cuninkova M, Møller H (April 2006). "Do testicular seminoma and nonseminoma share the same etiology? Evidence from an age-period-cohort analysis of incidence trends in eight European countries". Cancer Epidemiol. Biomarkers Prev. 15 (4): 652–8. doi:10.1158/1055-9965.EPI-05-0565. PMID 16614105.
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