Germ cell tumor pathophysiology: Difference between revisions

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* Germ cells are the cells that develop in the embryo and become they make up the reproductive system in males and females.
*[[Germ cells]] are the cells that develop in the [[embryo]] and they make up the [[reproductive system]] in [[males]] and [[Females|females.]]
* After the development of germ cells, they follow the body midline path and descend into the pelvis as ovarian cells or into the scrotal sac as testicular cells.
* After the development of [[germ cells]], they follow the body midline path and descend into the [[pelvis]] as [[ovarian]] cells or into the [[Scrotum|scrotal]] sac as [[testicular]] cells.
* Th [[ovaries]] and [[testes]] are called [[gonads]] and many [[ovarian]] and [[testicular]] [[tumors]] have [[germ cell]] origin.
*The [[pathophysiology]] of [[germ cell tumors]] is different based on the [[classification]] of [[germ cell tumors]]
*Each of the distinct entities of [[germ cell tumor]] has a different [[pathogenesis]]
 
== '''Dysgerminoma''' ==
 
* It is understood that [[ovarian]] [[germ cell]] [[tumors]] are the result of the [[Pathology|pathologic]] [[transformation]] of [[primordial germ cells]] during different stages of the development.
* The [[pathophysiology]] of [[ovarian]] [[germ cell]] [[tumors]] depends on the [[histological]] subtype.
* Their common origin is believed to be from the [[primordial germ cells]] that [[Transformation|transformed]] [[Pathology|pathologically]] in different stages of development.
*[[Dysgerminoma]] arises from [[primordial germ cells]], which are [[gonadal]] [[cells]] that are normally involved in the [[gametogenesis]].
*The majority of [[Dysgerminoma|dysgerminomas]] in women present in the stage 1A.
*[[Bilateral]] invovlement occurs in 10% to 15% of the cases.
*In < 15% of the affected cases, elements of other [[germ cell]] [[tumors]] can also be found.
* It is difficult to distinguish subtypes of ovarian germ cell tumor on gross [[pathology]] alone.
*<nowiki/>The majority of [[ovarian]] [[germ cell]] [[tumors]] have a [[solid]] and [[cystic]]<nowiki/>appearance with areas of [[hemorrhage]] and [[necrosis]]
*On microscopic [[pathology]], [[ovarian]] [[germ cell]] [[tumors]] may be charac<nowiki/>terized by a uniform “fried egg” appearance ([[dysgerminoma]]), presence of Schiller-Duval bodies ([[yolk sac tumor]]), presence of embryonic-like neural, [[gastrointestinal]], and/or cartilaginous tissue ([[teratoma]]), or mixed histopathological features (embryonal cell carcinoma).
 
== '''Testicular Seminoma''' ==
 
* Accounts for about a third of all [[testicular]] [[Germ cell neoplasm|germ cell]] [[malignancies]] and is one of the most treatable [[cancers]] with a survival rate of 98% to 99% in early-stage disease
* Originates in the [[germinal epithelium]] of the [[seminiferous tubules]] as a result from the proliferation of immature [[spermatogonia]]   
*On gross [[pathology]], [[seminoma]] is characterized by pale gray to yellow [[nodules]] that are uniform or slightly lobulated and often bulge from the cut surface
*[[Microscopic]] [[Pathology]]:
** On [[microscopic]] [[pathology]], [[seminoma]] is characterized by
*:* Cells with [[fried egg]] appearance - '''key feature'''
*::* Clear [[cytoplasm]]
*::* Central [[nucleus]], with prominent [[nucleolus]]. Nucleus may have "corners", i.e. it is not round.
*:*[[Lymphocytes]] - interspersed (common)
*:*[[Syncytiotrophoblast|Syncytiotrophoblasts]], present in 10-20% of [[seminoma]]
*::* Large, [[irregular]], [[vesicular]] [[nuclei]]
*::*[[Eosinophilic]] [[vacuolated]] [[cytoplasm]] (contains [[hCG]])
*:* Florid [[granulomatous]] reaction
** Approximately 24% of Stage I [[seminomas]] have ''[[lymphovascular]] invasion'' for stage I (Tx, N0, M0)<ref name="pathologyofseminoma1" />
** Intertubular [[seminoma]] may not form a discrete [[mass]] and mimic a benign [[testis]]<ref name="pathologyofseminoma1" />
**
 
== '''Germinoma''' ==
 
* On microscopic histopathological analysis, uniform cells that resemble [[primordial germ cells]], consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic are characteristic findings of germinoma.
* Pure germinomas are composed of large polygonal undifferentiated cells with abundant cytoplasm arranged in nests separated by bands of connective tissue
* The histologic appearance of NGGCTs varies depending upon the specific cell types present<ref name="pmid17618441" />
 
*Infiltrating small lymphocytes are often present and can obscure the diagnosis, especially in small biopsy specimens<ref name="pmid17618441" />
* Genes involved in the pathogenesis of germinoma include gains of 1p, 8p, and 12q and losses of 13q and 18q, duplication of the short arm of chromosome 12, loss of 1p and 6q, alterations in sex chromosomes in children, alterations of the ''p14'' gene, mutations of the ''c-kit'' gene, aberrations of ''CCND2'' (12P13), and ''RB1'', and gain-of-function mutations of ''KIT''.
* The progression to germinoma usually involves the mutations of the ''KIT/RAS'' signalling or ''AKT1''/mtor pathways and cyclin/''CDK-RB-E2F'' pathway if ''CCND2''(12P13) and ''RB1'' genes are aberrated
== '''Yolk sac tumors''' ==
*The hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor has been associated with the development of endodermal sinus tumor.
*On gross pathology, solid gray-white with a gelatinous, myxoid, or mucoid appearance, necrosis, cystic changes, and hemorrhage are characteristic findings of endodermal sinus tumor.
*On microscopic histopathological analysis, Schiller-Duval bodies is a characteristic finding of endodermal sinus tumor.
 
== '''Embryonal carcinoma''' ==
*Pineal embryonal carcinoma is a relatively rare malignant neoplasm and accounts for a small proportion of all intracranial germ cell tumors.
*It is an aggressive tumor and has a propensity to metastasize systemically
*the most aggressive component has a component of embryonal carcinoma that is often found in mixed germ-cell tumors
*On microscopic histopathological analysis, pineal embryonal carcinoma is characterized by:
**Poorly differentiated, pleomorphic cells in cords, sheets, or papillary formation
**Indistinct cell borders
**Nucleoli - key feature
**Vesicular nuclei (clear, empty appearing nuclei) - key feature
**Necrosis - common
**Mitoses - common
**Variable architecture:
**Solid (predominant in ~55% of cases)
**Glandular (predominant in ~17% of cases)
**Papillary (predominant in ~11% of cases)
**Nested
**Micropapillary
**Anastomosing glandular
**Sieve-like glandular
**Pseudopapillary
**Blastocyst-like
**Embryoid bodies - ball of cells in surrounded by empty space on three sides
 
== '''Teratomas''' ==
'''Pineal teratoma:'''
 
* Mature teratomas are benign, mature, well-differentiated cystic lesions; whereas immature teratomas are poorly differentiated lesions with solid components and malignant transformation
* On other occasions, mature teratomas contain elements that undergo malignant transformation (most commonly squamous components).
* Fat
* Cystic spaces due to mucus production or other exocrine products
* Soft-tissue from any part of the body Calcification, including teeth
* On microscopic histopathological analysis, pineal teratoma is characterized by cells originating from at least two and usually all three embryonic layers (ectoderm, mesoderm, and endoderm).
* The histological subtype may not necessarily determine the biological behavior
 
'''Sacrococcygeal teratoma'''
 
Microscopic Pathology of sacrococcygeal teratoma can be divided into following two types depending on the [[microscopic]] [[pathology]]:
 
'''Mature Teratoma'''
 
* [[Benign]]
* Consists of fully differentiated [[somatic]] [[Tissue (biology)|tissue]]
 
'''Immature Teratoma'''
 
* [[Malignant]]
* Consists of small fraction of incompletely differentiated [[Tissue (biology)|tissue]]
* They have elevated [[Tumor marker|tumor markers]] including [[yolk sac]] component secreting [[alpha fetoprotein]] or [[Primitive neuroectodermal tumor|primitive neuroectodermal tumor (PNET)]].
 
=='''Polyembryoma'''==
*Polyembryoma is a rare, very aggressive, and usually found in the ovaries
*It has features of both yolk sac tumor and undifferentiated teratoma/embryonal carcinoma
*A characteristic finding of embryoid bodies lying in a loose mesenchymal stroma can be found
*It can be seen in association with Klinefelter syndrome
 
=='''Gonadoblastoma'''==
*Gonadoblastoma is a benign tumor that almost exclusively involves individuals suspected of intersex disorders. This tumor comprised of underdeveloped germ cells and sex-cord stromal cells which defines the term gonadoblastoma.
*The exact pathogenesis of gonadoblastoma is not fully understood. Gonadal development starts at 5 weeks of gestation and continues according to sex chromosomes. Any defects in this complicated process lead to defective gonadal development and gonadal dysgenesis and subsequently, it may be converted to gonadoblastoma in 20% to 30% of the cases.
 
== '''References''' ==
<references />

Latest revision as of 15:59, 15 August 2019

Dysgerminoma

Testicular Seminoma

Germinoma

  • On microscopic histopathological analysis, uniform cells that resemble primordial germ cells, consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic are characteristic findings of germinoma.
  • Pure germinomas are composed of large polygonal undifferentiated cells with abundant cytoplasm arranged in nests separated by bands of connective tissue
  • The histologic appearance of NGGCTs varies depending upon the specific cell types present[2]
  • Infiltrating small lymphocytes are often present and can obscure the diagnosis, especially in small biopsy specimens[2]
  • Genes involved in the pathogenesis of germinoma include gains of 1p, 8p, and 12q and losses of 13q and 18q, duplication of the short arm of chromosome 12, loss of 1p and 6q, alterations in sex chromosomes in children, alterations of the p14 gene, mutations of the c-kit gene, aberrations of CCND2 (12P13), and RB1, and gain-of-function mutations of KIT.
  • The progression to germinoma usually involves the mutations of the KIT/RAS signalling or AKT1/mtor pathways and cyclin/CDK-RB-E2F pathway if CCND2(12P13) and RB1 genes are aberrated

Yolk sac tumors

  • The hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor has been associated with the development of endodermal sinus tumor.
  • On gross pathology, solid gray-white with a gelatinous, myxoid, or mucoid appearance, necrosis, cystic changes, and hemorrhage are characteristic findings of endodermal sinus tumor.
  • On microscopic histopathological analysis, Schiller-Duval bodies is a characteristic finding of endodermal sinus tumor.

Embryonal carcinoma

  • Pineal embryonal carcinoma is a relatively rare malignant neoplasm and accounts for a small proportion of all intracranial germ cell tumors.
  • It is an aggressive tumor and has a propensity to metastasize systemically
  • the most aggressive component has a component of embryonal carcinoma that is often found in mixed germ-cell tumors
  • On microscopic histopathological analysis, pineal embryonal carcinoma is characterized by:
    • Poorly differentiated, pleomorphic cells in cords, sheets, or papillary formation
    • Indistinct cell borders
    • Nucleoli - key feature
    • Vesicular nuclei (clear, empty appearing nuclei) - key feature
    • Necrosis - common
    • Mitoses - common
    • Variable architecture:
    • Solid (predominant in ~55% of cases)
    • Glandular (predominant in ~17% of cases)
    • Papillary (predominant in ~11% of cases)
    • Nested
    • Micropapillary
    • Anastomosing glandular
    • Sieve-like glandular
    • Pseudopapillary
    • Blastocyst-like
    • Embryoid bodies - ball of cells in surrounded by empty space on three sides

Teratomas

Pineal teratoma:

  • Mature teratomas are benign, mature, well-differentiated cystic lesions; whereas immature teratomas are poorly differentiated lesions with solid components and malignant transformation
  • On other occasions, mature teratomas contain elements that undergo malignant transformation (most commonly squamous components).
  • Fat
  • Cystic spaces due to mucus production or other exocrine products
  • Soft-tissue from any part of the body Calcification, including teeth
  • On microscopic histopathological analysis, pineal teratoma is characterized by cells originating from at least two and usually all three embryonic layers (ectoderm, mesoderm, and endoderm).
  • The histological subtype may not necessarily determine the biological behavior

Sacrococcygeal teratoma

Microscopic Pathology of sacrococcygeal teratoma can be divided into following two types depending on the microscopic pathology:

Mature Teratoma

Immature Teratoma

Polyembryoma

  • Polyembryoma is a rare, very aggressive, and usually found in the ovaries
  • It has features of both yolk sac tumor and undifferentiated teratoma/embryonal carcinoma
  • A characteristic finding of embryoid bodies lying in a loose mesenchymal stroma can be found
  • It can be seen in association with Klinefelter syndrome

Gonadoblastoma

  • Gonadoblastoma is a benign tumor that almost exclusively involves individuals suspected of intersex disorders. This tumor comprised of underdeveloped germ cells and sex-cord stromal cells which defines the term gonadoblastoma.
  • The exact pathogenesis of gonadoblastoma is not fully understood. Gonadal development starts at 5 weeks of gestation and continues according to sex chromosomes. Any defects in this complicated process lead to defective gonadal development and gonadal dysgenesis and subsequently, it may be converted to gonadoblastoma in 20% to 30% of the cases.

References

  1. 1.0 1.1
  2. 2.0 2.1