Germ Cell Tumours & Teratomas

Germ cell tumours (GCTs) arise from totipotent primordial germ cells and are the great mimics of pathology — capable of recapitulating embryonic (somatic) tissues, extra-embryonic structures (yolk sac, trophoblast), or remaining undifferentiated. They are a NEET PG favourite because each subtype carries a signature serum marker and a near-pathognomonic histology, making them ideal single-best-answer material.

Definition & origin

A germ cell tumour is a neoplasm derived from the primordial germ cell. These cells originate in the wall of the yolk sac, migrate along the dorsal mesentery to the gonadal ridge, and finally colonise the gonad. Because the germ cell is totipotent, its neoplasms can differentiate along three pathways:

1. No differentiation / germ cell phenotype → seminoma (testis) / dysgerminoma (ovary) / germinoma (CNS, mediastinum).
2. Embryonic somatic differentiation (ecto-, meso-, endoderm) → teratoma.
3. Extra-embryonic differentiation → yolk sac tumour (endodermal sinus) and choriocarcinoma (trophoblast).

A common pluripotent precursor that can give rise to all of these is embryonal carcinoma, regarded as the most primitive and the "stem cell" lesion of mixed GCTs.

High-yield: GCTs occur predominantly along the midline because of the migratory path of primordial germ cells — gonads (testis, ovary), mediastinum (anterior), retroperitoneum, pineal/suprasellar region, and sacrococcygeum. An anterior mediastinal mass in a young adult (one of the classic "terrible Ts") is most often a teratoma/GCT.

Classification

GCTs are broadly split into seminomatous and non-seminomatous (the latter being more aggressive and AFP/β-hCG producing). The female counterparts mirror the male ones.

Tumour	Differentiation	Male (testis)	Female (ovary)	Key marker
Germinomatous	Germ cell, undifferentiated	Seminoma	Dysgerminoma	LDH, PLAP; β-hCG ±
Embryonal carcinoma	Pluripotent primitive	Embryonal carcinoma	(rare)	AFP/β-hCG (mixed)
Yolk sac tumour	Extra-embryonic endoderm	Yolk sac tumour	Yolk sac tumour	AFP
Choriocarcinoma	Trophoblast	Choriocarcinoma	Choriocarcinoma	β-hCG (very high)
Teratoma	Somatic (3 layers)	Teratoma	Mature/immature teratoma	usually none

High-yield: In the testis, pure teratoma in an adult is malignant (regardless of "mature" histology), whereas in children testicular teratoma is benign. In the ovary, mature cystic teratoma (dermoid) is benign. This testis-vs-ovary behaviour reversal is heavily tested.

Teratomas

A teratoma contains tissues from all three germ layers (ectoderm, mesoderm, endoderm). They are subclassified by maturity.

Mature teratoma / Dermoid cyst

• Most common benign ovarian tumour and the most common ovarian neoplasm overall in young women (20–30 yrs).
• Composed of mature, differentiated adult-type tissue. Because ectodermal elements predominate, the cyst is lined by skin with hair, sebaceous glands, and teeth — hence "dermoid."
• Gross: unilocular cyst with a Rokitansky protuberance (mamillary nodule) projecting into the lumen, packed with hair, sebum, teeth, and cartilage.
• Karyotype is classically 46,XX (parthenogenetic — arises from a single ovum after meiosis I).

High-yield: Mature cystic teratoma is the most common ovarian tumour to undergo torsion and is the classic cause of ovarian dermoid. A pelvic radiograph showing teeth/bone within a cyst is the tell-tale image. Malignant transformation (~1–2%) is usually to squamous cell carcinoma in older women.

Monodermal / specialised teratomas

• Struma ovarii — teratoma composed predominantly (or entirely) of mature thyroid tissue. May cause hyperthyroidism; rarely undergoes malignant change to papillary thyroid carcinoma.
• Carcinoid — arising from intestinal/respiratory epithelium; can secrete serotonin and cause carcinoid syndrome without liver metastasis (because venous drainage bypasses the portal system).

High-yield: Struma ovarii = ovarian teratoma made of thyroid follicular tissue → can present as thyrotoxicosis with a pelvic mass. A frequently asked one-liner.

Immature teratoma

• Contains immature/embryonic tissue, most importantly immature neuroepithelium (primitive neural tubes and rosettes).
• Malignant; occurs in younger patients (first two decades), usually solid (vs cystic mature teratoma).
• Grading (Norris/Robboy) is by the amount of immature neuroepithelium, the single most important prognostic factor:

Grade	Immature neuroepithelium per slide (×40 LPF)	Behaviour
Grade 1	< 1 low-power field	Low malignant potential
Grade 2	1–3 low-power fields	Intermediate
Grade 3	> 3 low-power fields	High grade, aggressive

High-yield: The grade of an immature teratoma depends on the quantity of immature (primitive) neuroepithelium, not on other tissues. Glial implants on peritoneum that are mature (gliomatosis peritonei) do not worsen prognosis.

Dysgerminoma (ovary) / Seminoma (testis)

• Female counterpart of the testicular seminoma; the most common malignant ovarian germ cell tumour.
• Histology: sheets/nests of large uniform cells with clear cytoplasm (glycogen-rich) and central nuclei, separated by fibrous septa infiltrated by lymphocytes; granulomas may be seen.
• Markers: LDH (bulk/turnover), PLAP (placental alkaline phosphatase); modest β-hCG if syncytiotrophoblast giant cells present. OCT3/4 and c-KIT (CD117) positive.
• Most radiosensitive and chemosensitive germ cell tumour → excellent prognosis.
• Associations: dysgenetic gonads — Turner syndrome with Y material, androgen insensitivity, and pure gonadal dysgenesis (Swyer). Arises from gonadoblastoma.

High-yield: Dysgerminoma = "lymphocyte-rich, fried-egg cells in nests with fibrous septa." It is the GCT most associated with dysgenetic/streak gonads and is exquisitely radiosensitive.

Yolk sac tumour (endodermal sinus tumour)

• The most common testicular tumour in children < 3 years (infantile testis); in the ovary it is the second most common malignant GCT.
• Recapitulates the yolk sac / extra-embryonic mesenchyme.
• Schiller–Duval bodies — the pathognomonic histological lesion: a central blood vessel surrounded by a cuff of tumour cells, sitting within a cystic space, resembling a glomerulus (perivascular formations). Also seen are eosinophilic hyaline globules (PAS-positive, diastase-resistant) containing AFP.
• Marker: alpha-fetoprotein (AFP) — the single best serum marker.

High-yield: Schiller–Duval bodies (glomerulus-like perivascular structures) + raised AFP = yolk sac tumour. This is one of the single most repeated histology questions in NEET PG. Remember: AFP → Yolk sac (mnemonic "A for AFP, A for yolk sAc / endodermAl sinus").

Choriocarcinoma

• Malignant tumour of trophoblast — composed of both cytotrophoblast and syncytiotrophoblast (no chorionic villi). Highly haemorrhagic.
• Marker: β-hCG, characteristically very high (syncytiotrophoblast secretes it).
• Haematogenous spread, early and widespread → lungs (commonest), liver, brain, vagina. Can cause haemorrhagic metastases.
• Gestational choriocarcinoma (post molar pregnancy) is chemosensitive (methotrexate) with excellent cure; non-gestational/germ-cell choriocarcinoma is more chemoresistant.

High-yield: Very high β-hCG + syncytiotrophoblasts (no villi) + early lung mets = choriocarcinoma. Elevated β-hCG can cause thyrotoxicosis (β-hCG α-subunit cross-reacts with TSH receptor) and gynaecomastia in males.

Embryonal carcinoma

• Aggressive; sheets/glands of large primitive anaplastic cells with indistinct borders, marked pleomorphism, and necrosis.
• Markers: variable AFP and β-hCG; CD30 positive, OCT3/4 positive, c-KIT negative (distinguishing it from seminoma).
• Often a component of mixed germ cell tumours (the commonest pattern in testis), and considered the pluripotent stem-cell element.

Serum tumour markers — the exam's favourite grid

Marker	Positive in	Notes
AFP	Yolk sac tumour, embryonal Ca, mixed	NOT raised in pure seminoma/dysgerminoma or pure choriocarcinoma
β-hCG	Choriocarcinoma (very high), embryonal, ~10% seminomas	From syncytiotrophoblast
LDH	Seminoma/dysgerminoma	Reflects tumour bulk, non-specific
PLAP	Seminoma/dysgerminoma	Membrane stain
CD30	Embryonal carcinoma	OCT3/4 also +
c-KIT/CD117, OCT3/4	Seminoma/dysgerminoma	c-KIT negative in embryonal

High-yield: Pure seminoma does NOT raise AFP. If AFP is elevated in a "seminoma," there is an occult non-seminomatous (yolk sac/embryonal) component, and it must be treated as a non-seminomatous GCT. This single fact is examined repeatedly.

Mnemonic for markers: "AFP = Yolk; hCG = Chorio; pure seminoma stays clean (only LDH/PLAP)."

Diagnostic approach (stepwise)

Young patient with gonadal/midline mass → serum AFP + β-hCG + LDH → imaging (USS pelvis / scrotal Doppler / CT chest-abdomen-pelvis for staging) → surgical excision (orchidectomy via inguinal route / oophorectomy) → histopathology + IHC (OCT3/4, CD30, c-KIT, AFP, hCG) → classify & grade → adjuvant therapy decision based on stage + markers.

High-yield: Testicular masses are biopsied by high inguinal orchidectomy, NEVER trans-scrotal biopsy (risk of scrotal/lymphatic seeding altering nodal drainage).

Management / drug of choice

• Seminoma/dysgerminoma: highly radiosensitive; early stage cured with surgery ± radiotherapy; advanced with BEP chemotherapy (Bleomycin, Etoposide, cisPlatin).
• Non-seminomatous GCT (yolk sac, embryonal, choriocarcinoma, mixed): surgery + BEP chemotherapy; markers (AFP/β-hCG) used to monitor response and detect relapse.
• Mature cystic teratoma (dermoid): cystectomy (ovary-sparing) — benign.
• Immature teratoma: surgery + chemotherapy for grade 2–3.
• Gestational choriocarcinoma: methotrexate (single-agent) or EMA-CO; among the most chemo-curable solid tumours.

High-yield: BEP is the backbone regimen for malignant GCTs. Bleomycin → pulmonary fibrosis, cisplatin → nephrotoxicity & ototoxicity, etoposide → secondary leukaemia. Serum tumour markers are the principal tool for monitoring treatment response.

Complications

• Torsion / rupture of dermoid cyst → acute abdomen; rupture may cause chemical (granulomatous) peritonitis from sebaceous contents.
• Malignant transformation of mature teratoma → SCC (most common).
• Struma ovarii → thyrotoxicosis; rare malignant struma.
• Carcinoid syndrome from monodermal carcinoid.
• Paraneoplastic & marker effects: β-hCG-induced thyrotoxicosis/gynaecomastia.
• Anti-NMDA receptor encephalitis — classically associated with ovarian teratoma in young women (psychiatric symptoms, seizures, autonomic instability; resolves after tumour removal).
• Treatment toxicities: bleomycin lung, cisplatin renal/ototoxicity.

High-yield: A young woman with new-onset psychosis, seizures and dyskinesias — think anti-NMDA receptor encephalitis and look for an ovarian teratoma.

Key differentials

• Seminoma vs Embryonal carcinoma: both large cells, but seminoma has fibrous septa with lymphocytes and is c-KIT+/CD30−, whereas embryonal carcinoma is pleomorphic, necrotic, CD30+/c-KIT−.
• Yolk sac tumour vs clear cell carcinoma (ovary): both have hyaline globules; yolk sac shows Schiller–Duval bodies and raised AFP, younger age; clear cell shows hobnail cells, older age, linked to endometriosis.
• Dysgerminoma vs lymphoma/granulomatous oophoritis: dysgerminoma cells are PLAP+/OCT3-4+ with glycogen.
• Mature vs immature teratoma: presence of immature neuroepithelium defines immature; mature is purely adult-type tissue.
• Granulosa cell tumour / Sertoli–Leydig (sex-cord stromal): hormone-producing, NOT germ cell origin — distinguished by inhibin positivity, Call–Exner bodies (granulosa).

Eponyms & named entities to remember

• Schiller–Duval body — yolk sac tumour (glomeruloid perivascular structure).
• Rokitansky protuberance (dermoid plug) — mature cystic teratoma.
• Call–Exner bodies — granulosa cell tumour (a sex-cord differential, not GCT).
• Reinke crystals — Leydig cell tumour (differential).
• Norris–Robboy grading — immature teratoma.

Recently asked / exam angle

• "Schiller–Duval bodies are seen in?" → Yolk sac tumour (the single most repeated GCT histology MCQ).
• "Most common benign ovarian tumour?" → Mature cystic teratoma (dermoid).
• "Tumour marker not raised in pure seminoma?" → AFP.
• "Ovarian tumour causing hyperthyroidism?" → Struma ovarii.
• "Most common testicular tumour in a child < 3 yrs?" → Yolk sac tumour.
• "Very high β-hCG with lung metastases in a germ cell tumour?" → Choriocarcinoma.
• "Grading of immature teratoma is based on?" → Amount of immature neuroepithelium.
• "Most radiosensitive GCT?" → Seminoma/Dysgerminoma.
• "Ovarian teratoma associated paraneoplastic encephalitis?" → Anti-NMDA receptor encephalitis.
• Image-based: pelvic X-ray with tooth in cyst → dermoid; histology of glomeruloid structure → yolk sac.

Rapid revision

• Germ cell tumours are midline (gonad → mediastinum → retroperitoneum → pineal/sacrococcygeal).
• Mature cystic teratoma (dermoid) = most common benign ovarian tumour; 46,XX; Rokitansky protuberance; risk of torsion.
• Immature teratoma graded by immature neuroepithelium; malignant, solid, young patients.
• Struma ovarii = thyroid-tissue teratoma → may cause thyrotoxicosis.
• Schiller–Duval bodies + AFP = yolk sac tumour; commonest testicular tumour in infants.
• Choriocarcinoma = cyto + syncytiotrophoblast, no villi, very high β-hCG, early haematogenous lung mets.
• Dysgerminoma/seminoma = lymphocyte-rich nests, PLAP/OCT3-4/c-KIT positive, most radiosensitive, linked to dysgenetic gonads.
• Embryonal carcinoma = pluripotent, CD30+, c-KIT−, primitive anaplastic cells.
• Pure seminoma never raises AFP — if it does, treat as non-seminomatous.
• BEP (Bleomycin–Etoposide–cisPlatin) is the chemo backbone; bleomycin → lung fibrosis.
• Testicular teratoma: malignant in adults, benign in children; ovarian dermoid: benign.
• Gestational choriocarcinoma is highly chemocurable with methotrexate.
• High inguinal orchidectomy — never trans-scrotal biopsy.
• Anti-NMDA receptor encephalitis → look for ovarian teratoma.