Medical maps: Ovarian neoplasms

Ovarian teratoma.

First, the bigger picture: ovarian neoplasms fit into the broader sphere of adnexal masses which can be palpated on pelvic examination.

Adnexal masses

The adnexa refers to the appendages of the uterus – the fallopian tubes, ovaries and ligaments. Ovarian neoplasms are one type of adnexal mass.

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Adnexal masses can be physiological or pathological, and pathological masses can be non-neoplastic or neoplastic. Neoplastic adnexal masses are ovarian neoplasms. Click to enlarge.

Physiological adnexal masses

Physiological adnexal masses arise from the ovaries. They include follicular cysts, corpus luteal cysts and theca lutein cysts. They are by far the most common cystic ovarian lesions.

  • Follicular cyst: when a dominant Graafian follicle grows too large
  • Corpus luteal cyst: when the corpus luteum grows too large
  • Theca-lutein cyst: arising from luteinized theca cells; unknown aetiology but they occur with high levels of B-hCG (therefore, they are associated with gestational trophoblastic disease and ovarian hyperstimulation)

Pathological adnexal masses

Pathological masses can be neoplastic (ovarian neoplasms) or non-neoplastic.

  • Non-neoplastic
    • Ectopic pregnancy
    • Tubo-ovarian abscess
    • TB granuloma
    • Polycystic ovarian syndrome
    • Ovarian torsions
    • Pedunculated fibroids
  • Neoplastic – aka. ovarian neoplasms each of which can be graded based on whether it is benign, borderline or malignant
    • Some ovarian neoplasms will only fall into one of these categories, whereas others can fall into all three

Ovarian neoplasms

Symptoms and signs

Ovarian neoplastic symptoms and signs are notoriously vague. In many cases, there are no early symptoms.

As with all neoplasms, the symptoms and signs can be divided into three groups:

  • Local effects (compression or direct invasion)
    • Increasing abdominal girth (clothes don’t fit the waist)
    • Bloating
    • Changes in bowel habit
    • Abdominal pain
    • Urinary symptoms (urgency, frequency)
  • Systemic effects (metabolic or metastatic)
    • Weight loss
    • Fatigue
  • Paraneoplastic effects
    • Depends on the particular type of neoplasm (see below) – includes the effects of excess oestrogen, androgens, and thyroid hormones

Several of the symptoms like bloating, change in bowel habit, pain or discomfort, can occur during a normal menstrual cycle. However, when symptoms/signs are persistent and unrelated to menstruation, that’s when the warning bells should be sounding.

According to Target Ovarian Cancer, 26% of ovarian neoplasms present to the emergency department as malignant bowel obstruction or ovarian torsion. That’s because ovarian neoplasm symptoms and signs are so frequently missed.

Risk factors

Ovarian neoplasm risk is associated with increased ‘ovulatory age’:

  • Early menarche
  • Late menopause
  • Nulliparity
  • Increasing age
  • Never used combined hormonal contraception

Note: Some sources say polycystic ovarian syndrome (PCOS) increases the risk of ovarian cancer, but several sources suggest the opposite. PCOS is a disease of anovulation, so based on the idea of ‘ovulatory age’, one would expect PCOS to lower the risk.

Other risk factors include a family history, BRCA1/2 mutations, MSH2 mutations (HNPCC) and possibly ovulation induction as part of fertility treatment.

Classification

The ovaries have three basic cell types: epithelial cells, sex-cord/stromal cells (granulosa cells, theca cells and fibroblasts), and gametes aka. germ cells. Tumours can arise from any of these, although epithelial tumours are the commonest.

One point to note – many epithelial ovarian tumours may actually arise from the fallopian tubes, although this isn’t 100% clear.

Ovarian neoplasms can be graded benign (B), borderline (BL) or malignant (M). Some subtypes can fall into all three of these categories, some will only be seen in one.

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Ovarian neoplasms. The most common type is epithelial ovarian cancer, many of which may arise from the fallopian tubes. Germ cell tumours arise from gametes. Sex cord/stromal tumours arise from granulosa cells, theca cells or fibroblasts. Other ovarian neoplasms include lymphomas and metastases. Click to enlarge.

  • Epithelial (~65%)
    • Serous (B/BL/M)
      • B: serous cystadenoma
      • M: serous cystadenocarcinoma
    • Mucinous (B/BL/M)
      • B: mucinous cystadenoma
      • M: mucinous cystadenocarcinoma
    • Endometrioid (B/BL/M)
      • Occur in context of endometriosis
    • Clear cell (B/BL/M)
    • Brenner (B/BL/M)
      • Urothelial tumours of the ovary
      • Usually unilateral
  • Sex-cord/stromal (~10%)
    • Granulosa cell tumours (M)
      • Oestrogen producing, causing precocious puberty, abnormal menstrual bleeding or postmenopausal bleeding depending on menstrual status
    • Theca cell tumours (B)
      • Oestrogen producing, often occurring in older women, association with endometrial cancer
    • Sertoli-Leydig cell tumours (B)
      • Androgen producing, leading to virilisation (acne, hirsutism, voice deepening, breast atrophy, cliteromegaly)
    • Fibromas (tumour of fibroblasts) (B)
      • Meigs syndrome: ascites, pleural effusion and ovarian fibroma
  • Germ cell tumours (~15%)
    • Teratomas (B/BL/M)
      • B: dermoid cyst/mature cystic teratoma
      • B/M: struma ovarii, producing thyroid tissue
      • M: immature teratoma
    • Dysgerminoma (M)
      • Produces LDH
      • Cells have ‘uniform appearance’ under microscope
    • Yolk-sac tumour (M)
      • Produces AFP
      • Schiller-Duval bodies on histology
    • Choriocarcinoma (M)
      • Produces hCG
      • Trophoblast disease that can metastasise to the lungs
  • Other
    • Lymphomas
      • Often occur at ovarian hilum where ovarian lymph drains
    • Metastatic disease
      • Colon/appendiceal (low grade appendiceal mucinous neoplasm, LAMN)
      • Breast
      • Gastric (Krukenberg tumours technically refer to any ovarian tumour with ‘signet-ring’ mucin producing cells on histology)

Diagnostic approach

According to NICE, red flag signs + symptoms for ovarian neoplasms include:

  • Palpable abdominal/pelvic mass on physical examination
  • Persistent abdominal distension esp. >50 yrs old
  • Persistent pelvic/abdominal pain esp. >50 yrs old
  • IBS symptoms in women >50 (as IBS rarely presents at this age)

The first line test is CA125. CA125 is a tumour marker measured in the blood with high sensitivity but low specificity, so it is used as a rule-out test (SN-OUT – sensitivity, rule out).

If serum levels are >35IU/ml, then an ultrasound scan is warranted and the risk of malignancy index (RMI) is calculated:

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The Risk of Malignancy Index (RMI) is a crucial step in evaluating ovarian masses. It takes into account the ultrasound score (U), menopausal status of the patient (M) and the absolute serum CA125 levels (C). Click to enlarge.

NICE suggests an RMI of 250 as its cut-off for further investigation. Further evaluation of a high RMI might include:

  • CT scan of the pelvis
  • Measurement of additional tumour markers such as  hCG, LDH, AFP
  • Generally, a biopsy will be taken to grade and subtype the neoplasm
  • Genetic testing – e.g. BRCA1/2, MSH2… current recommendations suggest genetic testing for women diagnosed with non-mucinous ovarian cancer regardless of their family history

Treatment

Ovarian cancer treatment involves a combination of chemotherapy and surgery. That’s all you need to know!

Summary

Below is a summary of how it all fits together – adnexal masses and ovarian neoplasms. Hope it helps!

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Adnexal masses and ovarian neoplasms medical map. Click to enlarge.

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