Dysgerminoma

Tumor cells show ultra structural, histochemical and morphologic similarity to primordial germ cells which has not yet gained the ability for further differentiation
Primordial germ cells migrate from the wall of yolk sac to ovary during the development hence these neoplasms can be seen in the route of migration of these germ cells like
- Mediastinum
- Retroperitoneum
- Posterior abdominal wall
- Para spinal and sacrococcygeal region

Cytogenetic and molecular features

Common genetic alterations include
- Gain on chromosome 12p, 12q, 22q
- Loss from 13q
Small subset exhibits mutation of KIT oncogene

Prevalence

Constitutes 1-2% of primary ovarian neoplasms and accounts for 3-5% of ovarian malignancies

Clinical features

Age: More common in 2^nd and 3^rd decades of life but can occur at any age
Usually asymptomatic and incidental finding
Most common presentation in large tumors – abdominal enlargement and presence of mass in the lower abdomen
Sometimes torsion can cause abdominal pain
Loss of weight may also occur
Dysgerminoma is associated commonly with Gonadoblastoma
Menstrual and endocrine abnormalities are seen in tumor with syncytiotrophoblastic giant cells or when combined with other neoplastic germ cell elements, especially choriocarcinoma (mixed germ cell tumor)

Gross features:

Unilateral in 85% of cases and bilateral in 15% of cases.
Most of the cases involve right ovary (50%) when compared to left (35%)
BIlaterality is seen in patients with dysgerminoma associated with gonadoblastoma.
Pure dysgerminomas – Solid gray white tumors, that are round, oval and lobulated with fibrous capsule.
Size – Varies from few centimetres in diameter to large masses.
Consistency is firm and rubbery in small tumors and soft in large tumors.
Cut surface – Tumor in solid gray pink to tan in colour.
- Areas of hemorrhage and necrosis can be seen in large tumors.
- Presence of cystic areas suggest the possibility of other neoplastic elements (eg. Teratoma).

Microscopic features:

It is composed of islands, aggregates or strands of large uniform cells surrounded by connective tissue stroma containing lymphocytes.
Cells are large round or oval having distinct cytoplasmic borders and measure 15 to 25 μm in diameter.
Cell contain ample amount of pale, clear or slightly granular eosinophilic cytoplasm
Nucleus is large, vesicular and centrally located having granular chromatin and contains one or two prominent eosinophilic nucleoli.
Mitotic activity in slight or brisk.
Cytoplasm of tumor cells contain glycogen which is positive with PAS and is removed by diastase digestion.
Lipid can also be demonstrated in the cytoplasm of tumor cells.
Stroma surrounded tumor cells showing lymphocytic infiltration.
Lymphoid follicles with germinal center, plasma cells, eosinophils and granulomatous reaction can be present in stroma.
Predominant cell type in lymphocytic infiltrate are T cells and macrophage.
Stroma can be loose with free and deilcate fibrovascular network or can be densely hyalinized.
Foci of necrosis, hemorrhage and calcifications can be seen.
Occasional relatively large, oval or round calcified bodies can be present which indicate presence of burnt out gonadoblastoma.
6-8% of tumors may show syncytiotrophoblasts and are associated with increased levels of serum hCG.
Pure dysgerminomas are not associated with elevated serum Alpha-fetoprotein (AFP). Presence of elevated levels of AFP indicates presence of other neoplastic germ cell elements like yolk sac tumor.

Immunohistochemical features and differential diagnosis:

SALL4 – POSITIVE
CD117 (C-KIT) – POSITIVE
OCT-4 – POSITIVE
D2-40 – POSITIVE
Low molecular weight cytokeratin – Negative.

Clinical behaviour and treatment:

Capable of metastatic and local spread
When the tumor is small, capsule is intact, but when the tumor is large, capsule ruptures and produces adhesions to surrounding structures and may lead to direct extension by the tumor
Lymphatic spread occurs to the lymphnodes in the vicinity of common iliac arteries and the terminal part of abdominal aorta
Hematogenous spread occurs to distant organs and most common organs involved are liver, lungs, and bones
The tumors are associated with elevated levels of serum lactic dehydrogenase (LDH) and its isoenzyme-1 (LDH-1). These substances can be used as tumor markers.
Prognosis of pure dysgerminoma and unilateral encapsulated dysgerminoma is favourable.
Unfavourable prognostic factors include
- Presence of metastasis at the time of diagnosis
- Presence of adhesions
- Spread into adjacent structures.
- Bilaterality
- Large size of tumor

Treatment

Unilateral encapsulated pure dysgerminoma with normal other ovary – Unilateral oophorectomy or salpingo-oophorectomy with adjuvant chemotherapy to prevent recurrences and metastasis
In patients with widely disseminated metastases – combination chemotherapy composed of Cisplatin, Etoposide and Bleomycin is successful.
Dysgerminoma arising in the dysgenetic gonad
- Hysterectomy and bilateral salpingo oophorectomy due to the risk of developing tumor in another ovary

Reference

Aleksander Talerman, Russell Vang. Germ cell tumors of the ovary. In:Blausteins Pathology of the female genital tract by Robert J.Kurman, Lora Hedrick Ellenson, Brigitte M.Ronnett. Sixth edition. 847-908

DYSGERMINOMA

Tumor cells show ultra structural, histochemical and morphologic similarity to primordial germ cells which has not yet gained the ability for further differentiation

Primordial germ cells migrate from the wall of yolk sac to ovary during the development hence these neoplasms can be seen in the route of migration of these germ cells like

Mediastinum

Retroperitoneum

Posterior abdominal wall

Para spinal and sacrococcygeal region

Cytogenetic and molecular features

Common genetic alterations include

Gain on chromosome 12p, 12q, 22q

Loss from 13q

Small subset exhibits mutation of KIT oncogene

Prevalence

Constitutes 1-2% of primary ovarian neoplasms and accounts for 3-5% of ovarian malignancies

Clinical features

Age: More common in 2nd and 3rd decades of life but can occur at any age

Usually asymptomatic and incidental finding

Most common presentation in large tumors – abdominal enlargement and presence of mass in the lower abdomen

Sometimes torsion can cause abdominal pain

Loss of weight may also occur

Dysgerminoma is associated commonly with Gonadoblastoma

Menstrual and endocrine abnormalities are seen in tumor with syncytiotrophoblastic giant cells or when combined with other neoplastic germ cell elements, especially choriocarcinoma (mixed germ cell tumor)

Gross features:

Unilateral in 85% of cases and bilateral in 15% of cases.

Most of the cases involve right ovary (50%) when compared to left (35%)

BIlaterality is seen in patients with dysgerminoma associated with gonadoblastoma.

Pure dysgerminomas – Solid gray white tumors, that are round, oval and lobulated with fibrous capsule.

Size – Varies from few centimetres in diameter to large masses.

Consistency is firm and rubbery in small tumors and soft in large tumors.

Cut surface – Tumor in solid gray pink to tan in colour.

Areas of hemorrhage and necrosis can be seen in large tumors.

Presence of cystic areas suggest the possibility of other neoplastic elements (eg. Teratoma).

Microscopic features:

It is composed of islands, aggregates or strands of large uniform cells surrounded by connective tissue stroma containing lymphocytes.

Cells are large round or oval having distinct cytoplasmic borders and measure 15 to 25 μm in diameter.

Cell contain ample amount of pale, clear or slightly granular eosinophilic cytoplasm

Nucleus is large, vesicular and centrally located having granular chromatin and contains one or two prominent eosinophilic nucleoli.

Mitotic activity in slight or brisk.

Cytoplasm of tumor cells contain glycogen which is positive with PAS and is removed by diastase digestion.

Lipid can also be demonstrated in the cytoplasm of tumor cells.

Stroma surrounded tumor cells showing lymphocytic infiltration.

Lymphoid follicles with germinal center, plasma cells, eosinophils and granulomatous reaction can be present in stroma.

Predominant cell type in lymphocytic infiltrate are T cells and macrophage.

Stroma can be loose with free and deilcate fibrovascular network or can be densely hyalinized.

Foci of necrosis, hemorrhage and calcifications can be seen.

Occasional relatively large, oval or round calcified bodies can be present which indicate presence of burnt out gonadoblastoma.

6-8% of tumors may show syncytiotrophoblasts and are associated with increased levels of serum hCG.

Pure dysgerminomas are not associated with elevated serum Alpha-fetoprotein (AFP). Presence of elevated levels of AFP indicates presence of other neoplastic germ cell elements like yolk sac tumor.

Immunohistochemical features and differential diagnosis:

SALL4 – POSITIVE

CD117 (C-KIT) – POSITIVE

OCT-4 – POSITIVE

D2-40 – POSITIVE

Low molecular weight cytokeratin – Negative.

Clinical behaviour and treatment:

Capable of metastatic and local spread

When the tumor is small, capsule is intact, but when the tumor is large, capsule ruptures and produces adhesions to surrounding structures and may lead to direct extension by the tumor

Lymphatic spread occurs to the lymphnodes in the vicinity of common iliac arteries and the terminal part of abdominal aorta

Hematogenous spread occurs to distant organs and most common organs involved are liver, lungs, and bones

The tumors are associated with elevated levels of serum lactic dehydrogenase (LDH) and its isoenzyme-1 (LDH-1). These substances can be used as tumor markers.

Prognosis of pure dysgerminoma and unilateral encapsulated dysgerminoma is favourable.

Unfavourable prognostic factors include

Presence of metastasis at the time of diagnosis

Presence of adhesions

Spread into adjacent structures.

Bilaterality

Large size of tumor

Treatment

Unilateral encapsulated pure dysgerminoma with normal other ovary – Unilateral oophorectomy or salpingo-oophorectomy with adjuvant chemotherapy to prevent recurrences and metastasis

In patients with widely disseminated metastases – combination chemotherapy composed of Cisplatin, Etoposide and Bleomycin is successful.

Dysgerminoma arising in the dysgenetic gonad

Hysterectomy and bilateral salpingo oophorectomy due to the risk of developing tumor in another ovary

Reference

Aleksander Talerman, Russell Vang. Germ cell tumors of the ovary. In:Blausteins Pathology of the female genital tract by Robert J.Kurman, Lora Hedrick Ellenson, Brigitte M.Ronnett. Sixth edition. 847-908

Age: More common in 2^nd and 3^rd decades of life but can occur at any age