Non-epithelial ovarian tumors (Gonadal tumors (Granulosa-Stroma cell…
Non-epithelial ovarian tumors
rare ovarian malignancies: 5% of all ovarian tumors and for about 7% of malignant tumors of the ovary, occure >50 y.o.
They originate from a female components (granular and thecal cells) and male gonads (Leydig and Sertoli cells), stromal cells and fibroblasts
Granulosa-Stroma cell tumors
granulosa cell tumor=FOLLICULOMA!,
Sertoli-Leydig tumors with annular tubules
Granulosa-Stroma cell tumors
Granulosa Cell Tumor (GTC)
70% of all malignant gonadal tumors and for 2-5% of all tumors of the ovary
95% of these tumors are unilateral
80% are diagnosed at FIGO stage I
They may rupture and cause intra-abdominal bleeding, resulting in acute pain and require an emergency surgical treatment
Granulosa cell tumors are classified into mature and juvenile types (95% and 5%, respectively).
The mature form develops most often at perimenopausal age, between 50 and 54 years
The predominating sign is abnormal uterine bleeding, as a result of hormones – mainly estrogens – produced by malignant cells
Hormonal stimulation leads to endometrial atypical hyperplasia (30-55%) even adenocarcinoma (5-10%)
In about 50% of the cases juvenile type of granulosa cell tumor is diagnosed in girls under10 and in 80% – under 20 years of age.
Symptoms: are premature puberty and associated with production of sex hormones:
increased breasts, appearance of axillary and pubic hair, vaginal mucous discharge and irregular menses
Virilization (result of androgen production and secretion)
Treatment similar as in case of epithelial ovarian cancer (hysterectomy with bilateral salpingooophorectomy, omentectomy, complete staging: peritoneal biopsy and lavage
Lymphadenectomy may be omitted
histopathology speciment folliculoma consist Call-Exner bodies, which are pathognomonic for that type of malignancy. CEB are mimic mature ovarian follicule, fulfilled with proteoglycans and hialuronic acid.
clinical stage and patient’s age
tumor size over 10-15 cm. and tumor rupture
Lymph and vascular space invasion (LVSI)
High proliferation index Ki-67>25%
Mitotic index >20 visible mitosis in 20HPF
Prognosis: excellent in early clinical stages (FIGO I)- 5y survival 75-90%
late reccurence can appear over 5-7 years after initial surgery!!
Follow up- inhibinB serum concentration is used in prediction
Prognostic factors in advanced stages (FIGO II-IV, FIGI IA G-3, high-grade)
Adiuvant therapy is crucial to prolonged survival !!!
First-line based on BEP scheme (bleomycin, etoposide, cisplatin- 4 cycles)
Second-line PVB protocols (cisplatin, vinblastine, bleomycin
Sometimes platines with addition of taxanes- reccurent or persistent disease)
Role of bevacizumab (VEGF inhibitor)- phase II clinical trials- promising!
Serum markers in follow up- indicating possible reccurence
Estradiol- secreted by 70% of these tumors, therefore the value of this marker is limited.
Inhibins (subunits A and B) are glycopeptide hormones produced in granular cells of the ovary. secretion is stimulated by follicle-stimulating hormone (FSH).
TUMORS OF THE THECOMA-FIBROMA GROUP
account for only 0.5-1% of ovarian tumors.
affected postmenopausal women in mean age of 59
In 90% of the cases they are unilateral and
very rarely malignant.
They are usually unilateral solid tumors and there are mostly benign
In women of procreative age to preserve fertility unilateral adnexectomy is recommended
due to hormonal activity resulting in endometrial hyperplasia, hysterectomy with bilateral adnexectomy is warranted in premenopausal and postmenopausal woman
When sparing treatment is considered endometrial biopsy
is mandatory to exclude endometrial cancer- risk ratio up to 25%
the commonest solid ovarian tumors. They are benign in nature and usually develop in postmenopausal women.
Their size varies from 3 to even 24 cm and may occur bilaterally
Fibromas of the ovary may coexist with ascites and hydrothorax (the Meigs syndrome) which resolve after excision
US: may mimic pedunculated uterine myomas
„pure” FIBROMA is hormonally inactive!!
Fibrosarcoma of the ovary extremely rare ovarian tumor
They may develop as primary tumor or evolve from a preexisting fibroma
They usually affect postmenopausal women >58
Characterized with rapid growth and abundant vascularization
Immunohistochemically ( studies assessing Ki-67 and PCNA mutations as well as high proliferation and mitotic index)
Radical treatment with possible debulking surgery
no standard adjuvant chemiotherapy: epirubicin + ifosfamide + dacarbazine and paclitaxel + cisplatin
LEYDIG AND SERTOLLI CELL TUMORS
account for 0.5% of ovarian tumors and less than 0.2% of ovarian cancers
detected in young women under 30.
in 98% of the unilateral, of about 5-15 cm in diameter(18).
Symptoms: virilization due to androgenes production (70-85%)
At diagnosis: 90% of the patients are at FIGO stage I.
20% of these tumors manifest clinical malignancy
Prognosis is good, with a 5-years’ survival rate of 70-90%.
Late-stage cases carry a poor prognosis with a mortality rate of nearly 100%
SERTOLLI-LEYDIG WITH ANNULAR TUBULES TUMOR
Consist of granulosa and sertolli-leydig cells
15-times more frequent in patients with Peutz-Jeghers Syndrome
in 98% of the unilateral, of about 5-15 cm in diameter
More agressive biology (lymphatic spread and metastatical disease)
Hormonal activity- Progesteron sectetion
worst prognosis then ”pure” Sertoli-Leydig tumors
EXTREMLY RARE NEOPLASM
Frequently small and unilateral
Consist of mixed granulosa and Sertoli-Leydig cells
Surgery -Unilateral resection of tumor
Occurance- 30 years old young woman
Primitive germ cel tumors:
dysgerminoma (30-40%), yolk sac tumor (14%), Embrional carcinoma (4%), Polyembryoma, Nongestational choriocarcinoma (2%), Mixed germ-cel tumors (5%)
Bi and triphasics teratomas:
mmature teratoma (35%)- malignant!!, teratoma maturum- benign!!
Monodermal teratomas and tumors made of somatic cells coexist with dermoid cysts:
Struma ovarii- tumor made of thyroid cells, mostly benign, Carcinoid (various forms), Primitive neuroendocrine tumors, Glioblastoma, Melanoma
Comprise 20-25% all tumors and almost 58% of all tumors before 20 y.o.
They arised from primitive germ cell of embryonic gonad and look-like an testicular malignant tumors.
Adiuvant chemotherapy is based on testicular germ cancers, they are 10 times less common
Most frequent types (dysgerminoma, immature teratoma, yolk sac tumor, mixed germ tumor, chorioncarcinoma)
Mostly rapid growth (SYMPTOMS: abdominal pain, possible torsion of tumor, rupture of the capsule, sanguination into peritoneal cavity);
Pre-puberty early onset symptoms (bhCG and estrogen depending tumors)
Almost 70% of all cases early manifestation, stages I-II FIGO , unilateral solid components.
Good prognosis- ovar 90% individuals 5y survival !!
derived from 3 germ layers contain immature and embryonal structures, comprising<1% teratomas,
occurs in all ages, but mostly first two decade of lives, usually unilateral, up to 30 cm,
differentiate from mixed mullerian tumor (only mesodermal).
good prognosis if reccurence don`t occur in first 12-18 months after initial surgery.
Prognostic facors: FIGO stage, percentage of immature elments (tissue), mitotic activity.
Chth: BEP, VBP
lactate dehydrogenase, AFP, B-hCG
Dysgerminoma (seminoma)- first described in 1931,tumor composed of primordial germ cells, is not associated with endocrine manifestation „pure dysgerminoma” if contain syncythiotrophoblast may produce bhCG
Uncommon tumor accounting 1-2% of ovarian neoplasms, 3-5% of ovarian malignancies
Tumor can arise from dysgenetic gonads so kariotyping is crucial in further managment
If chromosome Y occure bilateral resection of dysgenetic ovaries in mandatory!!!
Rapidly growth neoplasm , unilateral, solid
Highly radiosensitive tumor
Favorable prognosis, 5-y survival 75-90%
Reccurence rate- after USO- 18-52% but treated succesfuly by subsequent radiation therapy
80% reccurences occur in first 2 years after surgery
Disseminated metastases: BEP scheme
Specific markers : AFP, BhcG, LDH
Yolk sac tumor ↑AFP
Embryonal carcinoma ↑AFP, ↑BhcG
Nongestational choriocarcinoma ↑BhcG