Understanding Ovarian Tumors.

Dr. Zayed | Published: April 11, 2025.

WHY, WHERE AND WHEN OF OVARIAN TUMOR'S: Ovarian tumors, originating from distinct cellular lineages within the ovary due to metaplastic changes or mutation of proto-oncogenic genes. Ovarian Tumors  present as adnexal masses unilateral or bilateral, during premenopausal or postmenopausal period, underscoring the ovary’s complex ontogenetic diversity. Clinically, patients presents with pelvic pain or abdominal distension attributable to mass effect as the tumor grows, with endocrine perturbations due to hormonal dysregulations reflect neoplastic interference with the hypothalamic-pituitary-ovarian axis (HPO Axis), manifesting as aberrant vaginal bleeding from estrogen hypersecretion, or hirsutism and virilization from androgen excess secreted from these tumors. It is often missed but very certainly seen that heavy ovarian tumor masses can result in torsion along its axis to compress infundibulopelvic ligament (suspensory ligament) which carries vessels to ovary resulting in ischemia (arterial obstruction) or edema (venous obstruction) to ovary resulting in Necrosis. Tumor Markers here can be used as monitoring treatment efficacy and tumor resolution rather than as standalone diagnostic tools.

UNDERSTANDING OVARIAN TUMORS CLASSIFICATION: Ovarian neoplasms are categorized based on their histogenetic origins within the ovarian architecture. Surface epithelial tumors derive from the ovarian surface epithelium, a mesodermally derived layer of coelomic ancestry enveloping the gland. Germ cell tumors emerge from primordial germ cells, the progenitor population of the oocyte lineage, prior to their terminal differentiation. Sex cord-stromal tumors originate from the specialized stromal and sex cord derivatives of the gonadal ridge, encompassing granulosa cells, theca cells, Sertoli cells, and Leydig cells, which collectively regulate follicular development and steroidogenesis. Metastatic tumors represent secondary neoplastic deposits within the ovary, frequently arising via hematogenous or transcoelomic spread from primary sites such as the gastrointestinal tract (e.g., Krukenberg tumors) or mammary gland.

PSAMMOMA BODIES IN SEROUS CYSTADENOMA

SURFACE EPITHELIAL TUMORS (SET): Takes births from the coelomic epithelium ,encompass serous, mucinous, endometrioid, and Brenner subtypes due to the metaplastic property of this pluripotent lining, each defined by its unique histologic profiles - serous with watery cystic contents, mucinous with viscid secretions, endometrioid linked to ectopic endometrial tissue, and Brenner characterized by transitional epithelium akin to urothelium (same  epithelium as lining of bladder and ureters). It is now understood from "INCESSANT OVULATION HYPOTHESIS" that, more ovulations leading to more damage-repair cycle resulting in metaplastic changes in this lining which explains why womens on OCP's and Multiparity gives them immunity for Surface epithelial tumors. histology shows Dystrophic calcification aka 'PSAMMOMA BODIES'. the state of benign vs malignant can be known through the anatomy on USG or histology, benign presents as a simple layer of epithelium (vs malignant, which shows as papillary projections and/or shaggy appearance). the Infamous 'BRCA Mutation, Lynch syndrome' association is for SET. CA-125 is the tumor marker associated with SET.

Interesting  to know : Epithelial ovarian tumors, arising from the surface epithelium encasing the ovary, might initially appear detached from ovulation, an internal cortical process where follicles mature and release oocytes, yet their influence emerges as they grow. Small benign lesions, such as serous cystadenomas or Brenner tumors, may start superficially, forming cysts or masses externally without directly blocking follicular development or the rupture site. However, as these tumors enlarge benign or malignant, their effects intensify. Massive mucinous cystadenomas, sometimes exceeding 20 cm, compress the parenchyma, crushing follicles and severing the microvascular and hormonal lifelines (e.g., FSH/LH signaling) critical for ovulation. Malignant forms, like high-grade serous carcinomas, invade the stroma, annihilating functional tissue with neoplastic replacement, while even borderline tumors disrupt through mass effect or inflammation, derailing endocrine harmony. In premenopausal women, this disruption often signals early-irregular cycles or ovulation failure raise suspicion alongside symptoms like bloating. Conversely, in postmenopausal women, where ovulation has naturally ceased, these tumors conceal themselves insidiously; the absence of menstrual or ovulatory clues delays detection, leaving mechanical pressure or late-stage invasion to manifest as vague pelvic discomfort or ascites, often too advanced for early intervention. Thus, while epithelial tumors bridge the ovary’s surface and interior to halt ovulation, their secrecy in postmenopausal silence amplifies their clinical challenge. 

FRIED EGG NUCLEUS IN YOLK SAC TUMORS

GERM CELL TUMORS : GCT originate from the ovary’s primordial germ cells, the progenitors of oocytes, and encompass teratomas, dysgerminomas, yolk sac tumors, and choriocarcinomas, each defined by specific histopathological characteristics. Teratomas, typically benign, exhibit somatic differentiation into tissues like skin, hair, cartilage, or glands, though malignant variants arise with immature variant. Dysgerminomas, analogous to testicular seminomas in Males, are rapidly proliferating neoplasms prevalent in younger premenopausal females including children, marked by radiosensitivity and expression of Tumor markers like PLAP, LDH, B-HCG. The histology characteristically shows "FRIED EGG APPEARANCE". Yolk sac tumors and choriocarcinomas, less common but aggressive, secrete alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), respectively, reflecting their extraembryonic lineage. Yolk sac tumors histologically show a pattern similar to 'PRIMITIVE GLOMERULI' called "SCHILLER DUVAL BODIES". Choriocarcinoma on the flip side shows "SYNCYTIOTROPHOBLAST & CYTOTROPHOBLAST" on histology and can metastasise early through Hematogenous route. as we discussed, the release of B-HCG from this tumor can have all the effects as studied in a typical pregnancy - ranging from hyperemesis Gravidarum to Gestational thyrotoxicosis under the influence of this hormone.

CALL EXNER BODIES IN GRANULOSA CELL TUMOR

SEX CORD TUMORS: Arising from the cells coverings around the oocyte, granulosa and theca cells are the cell of origin for this tumor. As of our understanding of why this tumors are infamously known to release hormone comes from "TWO-CELL-TWO GONADOTROPIN-HYPOTHESIS". granulosa cell tumor and sertoli leydig cell tumor (though are the male reproductive cells, they are formed by metaplastic changes) are the main type of tumors. we also understand as the sex hormones are primarily synthesized from lipids, shall be the very reason to have yellowish appearance on gross section. 

REINKE CRYSTALS IN S-L TUMOR.

on histology they appear to have 'MULTIFOLLICULAR PATTERN (CUBOIDAL CELLS) WITH EOSINOPHILIC MATERIAL' called "CALL EXNER BODIES" (vs "REINKE CRYSTALS" SURROUNDED BY SERTOLI CELLS). Granulosa cell tumor secrets high amounts of oestrogen & inhibin which can cause precocious puberty in premenopausal females and vaginal bleeding in postmenopausal females as the main symptom (vs Hirsutism & virtualization symptoms due to androgen from sertoli cells).

METASTATIC TUMORS: The infamous 'KRUKENBERG TUMOR' comes primarily from 'Gastric Adenocarcinoma' (diffuse type). It is very interesting to notice that they have exactly same cellular appearance where they come from without any change resembling 'SIGNET RING'. second commonly we see breast cancer also have there secondaries spreading transcoelomic to ovaries with exact cellular architecture.

SIGNET RING CELLS