Molavi Chapter 15 - Ovary Flashcards
Rule of thumb for tumors of the ovary
There’s almost no non-neoplastic pathology. No margins, no depth of invasion, no “reactive lesions” on the differential.
Find the tumor, identify the tumor. It’s malignant.
This is normal old ovarian stroma. Blue, cellular, vaguely fascicular or storiform pattern.
There is a follicle present as well with a central oocyte and a ring of granulosa cells.
Sex cord cells
The hormone-secreting supporting cells of the ovary: theca and granulosa cells.
Theca cells secrete androgens under LH stimulation.
Granulosa cells covert some androgens to estrogen under FSH stimulation.
Histology of a follicle
Halo of theca cells around a ring of granulosa cells, surrounding a germ cell (oocyte).
In developing follicles, the granulosa cells form Call-Exner bodies (rosettes of granulosa cells surrounding pink globules)
Call-Exner bodies
Luteinized
Indicates that ovarian cells hve become plump with abundant pink cytoplasm
Corpus luteum
A newly ovulated follicle
The capsule of luteinized granulosa cells collapses on itself. There is associated hemorrhage.
The result is an undulating body of cells producing progesterone until/if the placenta takes over.
Corpus albicans
When the hemorrhage of the corpus luteum resolves and the walls of the body hyalinize to form pink cloud-like islands
Walthard rests
Benign nests of transitional (urothelial) epithelium in the ovary and fallopian tube
Rete ovarii
Analogous to rete testis
Rudimentary gland spaces in the hlium of the ovary.
Angulated, slit-like, with low cuboidal epithelium.
Ovarian inclusion cyst
Simple cyst lined with cuboidal, columnar, or ciliated epithelium.
Often budding inward from the ovarian surface.
\When small, they are called “surface inclusion cysts.” When large, they are called “serous cystadenomas.”
Surface epithelial-type ovarian tumors
- Serous (~60% benign)
- Mucinous (~80% benign)
- Endometrioid (Almost always malignant)
- Clear cell (Almost always malignant)
- Brenner (almost always benign)
Germ cell-type ovarian tumors
- Teratoma
- Dysgerminoma
- Yolk sac
- Choriocarcinoma
- Embryonal carcinoma
Sex cord stromal-type ovarian tumors
- Fibroma
- Thecoma
- Granulosa cell tumor
- Sertoli cell tumor
- Leydig cell tumor
- Sertoli-Leydig cell tumor
Low-grade serous cell epithelial carcinoma of the ovary (LGSC)
- Progress slowly from adenoma to borderline to carcinoma
- KRAS or BRAF mutations, but not p53 mutations
- Fairly uniform nuclei, unlike high grade
- “Serous” due to watery fluid, as opposed to mucinous
- IS simply a low-grade serous “tumor” until there is evidence of stromal invasion. This invasion is often seen around micropapillary areas.
High-grade serous cell epithelial carcinoma of the ovary (HGSC)
- Genetically distinct from LGSC
- Arise from fallopian tube epithelium
- Present at high stage due to tedency to metastasize even from tiny tumors
- Show p53 mutations and genetic instability. Also associated with inherited BRCA mutations.
- Fallopian tubes are prophylactically removed in BRCA patients to exclude presence of tiny foci of serous tubal intraepithelial carcinoma (STIC), basically LGSC foci of the fallopian tube.
- Characterized by significant nuclear atypia, solid architecture with slit-like spaces. Nuclei are mitotically active, apoptotic, pleomorphic, and dark.
Borderline tumor / Atypical proliferative serous tumor
- Increasingly complex papillary fronds, looking grossly glandular and resembling cauliflower
- They have clear tree-like branching papillae with fibrovascular cores
- Papillary epithelium is usually a thin layer without significant atypia.
- A superimposed micropapillary pattern may develop when secondary mutations are acquired (Medusa’s head appearance)
Micropapillary serous carcinoma of the ovary
May arise from a borderline serous tumor in the presence of a secondary mutation
Medusa’s head / micropapillary pattern is shown in the inset. Over 5 mm of micropapillary pattern upgrades this to a non-invasive low-grade serous carcinoma.
Psammoma bodies are common.
Non-invasive low-grade serous carcinoma of the ovary
Characterized by micropapillary growth pattern of LGSC, but confined to the cystic cavity without stromal invasion.
Psammoma bodies.
“Implants”
Presence of serous tumor foci outside of the ovaries, such as in the omentum
By definition, an implant is NOT a metastasis and should NOT show evidence of stromal invasion
However, the presence of implants increase the stage of the tumor.
Unlike in other organs, mucinous carcinoma of the ovary does not imply. . .
. . . malignant cells in a bed of mucous
As it does in some other organs
Borderline mucinous tumor
A mucinous tumor graduates from cystadenoma to borderline when it acquires a more complex epithelial lining, as in serous epithelial ovarian tumors.
Cells may appear to be gatsric foveolar type, intestinal type, or even Paneth cell type.
The arrow here indicates complexity and epithelial tufting, upgrading this from cystadenoma to borderline mucinous tumor.
Endometrioid tumors of the ovary
Histologically identical to (and use the same FIGO 3 tier grading system as) endometrioid carcinomas of the endometrium.
Unlike endometriosis, there is no endometrial stroma in an endometrioid tumor.
They may arise within endometriosis or be found along with endometriosis, and concurrent endometrial carcinoma is not uncommon.
Nuclei are cleared out and pleomorphic. Distinct glandular spaces are visible, often with some necrosis.
Clear cell tumors of the ovary
- Tend to appear in a monolayer, without the stratification of nuclei seen in other high-grade neoplasms.
- By definition they are high-grade, and like endometrioid carcinoma are also associated with endometriosis.
- Hobnail cells may be present (arrow)
Brenner tumors
- Adenomas with urothelial-type epithelium
- Thought to arise from Walthard rests
- Nests of urothelial-type epithelium in a fibrotic stroma, sometimes forming gland-like spaces with pink secretions.
- Usually benign, as seen here
Malignant Brenner tumor
- Invasive urotheilial or squamous cell carcinomas
- Arise in association with a benign Brenner tumor
Ways that a teratoma can become malignant
- By growing a secondary malignancy from a tumor component (lymphoma, thyroid carcinoma, etc)
- By being associated with a malignant germ cell tumor
- By having an immature component, usually neural
Fibrothecoma
- A spectrum of lesions ranging from pure fibroma to pure thecoma
- Grossly, fibromas look like leiomyomas (but are very rare in the ovary)
- Grossly, thecomas are butter-colored and stand out from gray stroma
- Histologically, both tumors look similar to leiomyomas, but have more of a sheet-like pattern with bland, spindled cells
- These are all benign tumors
Granulosa cell tumors
- Appear similar to normal granulosa cells, but have more distinctive oval folded or angulated nuclei with a longitudinal groove (coffee-bean nucleus)
- Cells can be packed, giving the impression of nuclear molding, but they are not as blue, hyperchromatic, or crowded as SCC
- At low power, cells are arranged in rows with a “zigzag” pattern
- Rarely, the pathognomonic Call-Exner bodies may be present
- These are malignant, but indolent. They tend to recur after many years.
Ovarian tumor markers
Yolk sac tumors are also called. . .
. . . endodermal sinus tumors
Estrogen-producing tumors
Granulosa cell OR fibrothecoma tumors can be estrogen producing
Signet Ring Ovarian Stromal Tumor
Mutation found in 97% of adult granulosa cell tumors
FOXL2
