Intratubular germ cell

Germ cell

A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by...

 neoplasia

Neoplasia

Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...

, abbreviated ITGCN or IGCN and also known as testicular intratubular germ cell neoplasia and intratubular germ cell neoplasia of the testis, is considered a precursor lesion for many types of testicular germ cell tumor

Germ cell tumor

A germ cell tumor is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads...

s.

The common, unspecified variant of the entity was once considered to be a carcinoma in situ

Carcinoma in situ

Carcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"...

 although the term "carcinoma in situ" is no longer preferred for ITGCN, unspecified type (ITGCNU) lesions because they are not epithelial lesions.

Classification

The World Health Organisation classification of testicular tumours subdivides ITGCN into (1) a more common, unspecified type (ITGCNU), and (2) other specific subtypes. The most common specific subtypes are intratubular embryonal carcinoma

Embryonal carcinoma

Embryonal carcinoma is a relatively uncommon type of germ cell tumour that occurs in the ovaries and testes.-Ovarian embryonal carcinoma:In the ovary, embryonal carcinoma is quite rare, amounting to approximately three percent of ovarian germ cell tumours. The median age at diagnosis is 15 years...

 and intratubular seminoma.

Cancer risk

ITGCNU is seen in the following settings:

• Almost all invasive germ cell tumours of the testis in adults
• Fifty percent of patients with ITGCNU developed invasive germ cell tumours within five years of initial diagnosis.
• Five percent of contralateral testes in men with a history of prior testicular germ cell tumour.
• Less than five percent of cryptorchid testes.
• Less than one percent of patients with infertility.

Germ cell tumors that do not arise from ITGCNU

Not all germ cell tumors (GCTs) arise from intratubular germ cell neoplasia. The following testicular GCTs do not arise from ITGCN:

• Spermatocytic seminoma
  Spermatocytic seminoma
  Spermatocytic seminoma is a neoplasm of the testis , and classified as a germ cell tumour.The name of the tumour comes from the similarity between the small cells of the tumour and secondary spermatocytes.-Relation to seminoma:Spermatocytic seminoma is not considered a subtype of seminoma and,...
  
  
• Pediatric Yolk sac tumors (endodermal sinus tumour). This is currently an area of controversy as some authors dispute the absence of ITGCN in these cases.
• Teratoma
  Teratoma
  A teratoma is an encapsulated tumor with tissue or organ components resembling normal derivatives of all three germ layers. There are rare occasions when not all three germ layers are identifiable...
  
   (rare exceptions)

Diagnosis

ITGCN is not palpable, and not visible on macroscopic examination of testicular tissue. Microscopic examination of affected testicular tissue most commonly shows germ cells with enlarged hyperchromatic nuclei

Cell nucleus

In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 with prominent nucleoli

Nucleolus

The nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...

 and clear cytoplasm

Cytoplasm

The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

. These cells are typically arranged along the basement membrane

Basement membrane

The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...

 of the tubule, and mitotic

Mitosis

Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 figures are frequently seen. The sertoli cells are pushed toward the lumen by the neoplastic germ cells, and spermatogenesis

Spermatogenesis

Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...

 is almost always absent in the affected tubules. Pagetoid

Pagetoid

Pagetoid is a term used in dermatology to refer to "upward spreading" of melanocytes into the epidermis. It is uncommon and a possible indication of a precancerous or cancerous condition. Cells display pagetoid growth when they invade the upper epidermis from below. Squamous cell carcinoma,...

 spread of ITCGN into the rete testis

Rete testis

Rete testis is an anastomosing network of delicate tubules located in the hilum of the testicle that carries sperm from the seminiferous tubules to the vasa efferentia....

 is common. Immunostaining

Immunostaining

Immunostaining is a general term in biochemistry that applies to any use of an antibody-based method to detect a specific protein in a sample. The term immunostaining was originally used to refer to the immunohistochemical staining of tissue sections, as first described by Albert Coons in 1941...

 with placental alkaline phosphatase (PLAP) highlights ITGCNU cell membranes in 95 percent of cases. OCT3/4 is a sensitive and specific

Sensitivity and specificity

Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

 nuclear stain of ITGCNU.

Treatment

ITGCN is generally treated by radiation therapy and/or orchiectomy. Chemotherapy

Chemotherapy

Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 used for metastatic germ cell tumours may also eradicate ITGCN.

External links

• Intratubular germ cell neoplasia - uptodate.com.
• ITGCN micrographs - gfmer.ch.