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Malignant Ovarian Neoplasm

Ovarian Cancer

Ovarian cancer (OC) may correspond to distinct types of malignant ovarian neoplasms. The most common type of OC is epithelial ovarian cancer, which accounts for about 90% of all cases. The course of the disease is characterized by a prolonged period of non-specific, mild to moderate gastrointestinal and genitourinary symptoms, which are often ignored the affected women and their physicians. Accordingly, the majority of patients is diagnosed with advanced-stage OC, when distant metastases have formed. Metastatic OC is associated with a poor prognosis, and every possible effort should be made to facilitate the early detection of ovarian malignancies.


Presentation

The clinical presentation does neither allow for the diagnosis of OC, nor the identification of the specific type of neoplasm. What's more, women may be diagnosed incidentally when suspicious findings are noted on preventive examination or imaging. This is due to most patients being free of symptoms for prolonged periods of time.

Symptomatic patients present with non-specific complaints, which are mostly of insidious onset. Women may claim pain in the lower abdomen or pelvic region, and constitutional symptoms such as fever, night sweats, chills, loss of appetite and weight may be reported. Functional OC may induce distinct symptoms, depending on its endocrine profile, the patient’s age and reproductive status. Menstrual disorders and irregular uterine bleeding are the most common [1].

Furthermore, ovarian neoplasms may displace or exert pressure on adjacent structures, thereby provoking digestive disorders and changes in the urinary frequency. Gastrointestinal, genitourinary, and gynecological symptoms may also be produced by metastatic OC. Tumor cells shed from the ovarian surface tend to implant on the serous membranes lining the peritoneal cavity, and additional mass lesions may become palpable. Ascites may occur with metastatic OC or may be present earlier [1].

About 70% of OC patients are only diagnosed when metastases have formed in the upper abdomen or beyond the abdominal cavity. Yet, retrospective studies have shown that most women do present symptoms long before reaching this stage of the disease [2]. It is thus of utmost importance to determine the cause of persistent abdominal or pelvic pain, nausea, early satiety, bloating, urinary urgency, and pollakisuria [3].

Fatigue
  • […] following are often identified by women as some of the signs and symptoms of ovarian cancer: Bloating Pelvic or abdominal pain Trouble eating or feeling full quickly Feeling the need to urinate urgently or often Other symptoms of ovarian cancer can include: Fatigue[ovarian.org]
  • […] increased abdominal size/persistent bloating Eating - difficulty eating or feeling full quickly Pain - in pelvic or abdominal areas Urinary symptoms - urgency or frequency Occasionally there can be other symptoms such as changes in bowel habits, extreme fatigue[ovariancanada.org]
  • Side effects of pelvic radiation therapy may include diarrhea , fatigue, skin irritation, premature menopause, bladder irritation, or a narrowing of the vagina due to the buildup of scar tissue.[britannica.com]
  • Symptoms include abdominal or pelvic pressure or pain, swelling or bloating, nausea, persistent fatigue, urinary urgency or frequency, and abnormal vaginal bleeding.[radiologyinfo.org]
  • […] loss of appetite Pelvic or abdominal pain (that's your tummy and below) Urinary symptoms (needing to wee more urgently or more often than usual) Occasionally there can be other symptoms: Changes in bowel habit (eg diarrhoea or constipation) Extreme fatigue[targetovariancancer.org.uk]
Weight Gain
  • Symptoms may include A heavy feeling in the pelvis Pain in the lower abdomen Bleeding from the vagina Weight gain or loss Abnormal periods Unexplained back pain that gets worse Gas, nausea, vomiting, or loss of appetite To diagnose ovarian cancer, doctors[medlineplus.gov]
  • gain These symptoms can be caused by other conditions but if you are experiencing any of these symptoms, contact your local doctor.[cancer.org.au]
  • gain or loss pain during intercourse vaginal bleeding in post-menopausal women Diagnosis In the best-case scenario a woman is diagnosed with ovarian cancer while it is still contained in just one ovary.[medical-dictionary.thefreedictionary.com]
Leg Swelling
  • swelling and DVT/PE (pressure on pelvic veins) abnormal vaginal bleeding can also be a symptom symptoms of metastatic disease include pleural effusion, ascites, weight loss and fatigue less commonly, sudden torsion, rupture or infection of the tumour[geekymedics.com]
Lymphedema
  • […] addition, exercise will instill you with the motivation and the drive for optimal wellness. [14] Physical therapy also provides: Massage Therapy, which recent studies show can decrease stress, anxiety, depression, and pain, and increase alertness [15] Lymphedema[physio-pedia.com]
Foul Smelling Discharge
  • You have foul-smelling discharge from your vagina. You are sick to your stomach or cannot keep fluids down. You have signs of infection, such as: Increased pain, swelling, warmth, or redness. Red streaks leading from the incision.[northshore.org]
Pleural Effusion
  • Staging investigations for patients with a high RMI score include: blood tests – FBC (for anaemia), U E (for renal function), LFTs (for metastases) imaging – CXR to check for pleural effusion or lung metastases, CT /- MRI abdomen and pelvis to assess[geekymedics.com]
  • Stage 4: Distant metastases other than peritoneal metastases are detected, or the patient is found to suffer from malignant pleural effusion.[symptoma.com]
  • Complications of advanced disease: malnutrition, electrolyte imbalance, small and large bowel obstruction, infection, ascites, pleural effusion.[patient.info]
  • effusion , and mucositis .[en.wikipedia.org]
Malignant Pleural Effusion
  • Stage 4: Distant metastases other than peritoneal metastases are detected, or the patient is found to suffer from malignant pleural effusion.[symptoma.com]
  • Distant metastatic disease Malignant pleural effusion Pulmonary parenchymal metastases Liver or splenic parenchymal metastases (not surface implants) Metastases to the supraclavicular lymph nodes or skin 41.[slideshare.net]
Nausea
  • Common symptoms may include: Abdominal bloating, indigestion or nausea Changes in appetite, such as a loss of appetite or feeling full sooner Pressure in the pelvis or lower back A more frequent or urgent need to urinate and/or constipation Changes in[cancercenter.com]
  • Ovarian Cancer Overview Ovarian cancer warning signs include ongoing pain or cramps in the belly or back, abnormal vaginal bleeding, nausea, and bloating. Depending on the cancer stage, ovarian cancer treatment includes surgery and chemotherapy.[webmd.com]
  • Symptoms may include A heavy feeling in the pelvis Pain in the lower abdomen Bleeding from the vagina Weight gain or loss Abnormal periods Unexplained back pain that gets worse Gas, nausea, vomiting, or loss of appetite To diagnose ovarian cancer, doctors[medlineplus.gov]
  • […] swollen tummy discomfort in your tummy or pelvic area feeling full quickly when eating, or loss of appetite needing to pee more often or more urgently than normal Other symptoms Other symptoms of ovarian cancer can include: persistent indigestion or nausea[nhs.uk]
Abdominal Pain
  • The following are often identified by women as some of the signs and symptoms of ovarian cancer: Bloating Pelvic or abdominal pain Trouble eating or feeling full quickly Feeling the need to urinate urgently or often Other symptoms of ovarian cancer can[ovarian.org]
  • Persistent bloating - not bloating that comes and goes Feeling full quickly and/or loss of appetite Pelvic or abdominal pain (that's your tummy and below) Urinary symptoms (needing to wee more urgently or more often than usual) Occasionally there can[targetovariancancer.org.uk]
  • In these cases symptoms may include: Abdominal pain Trouble urinating or frequent urination Low back pain Pain with sexual intercourse Bad cramps with a woman’s periods Feeling full quickly after eating, or no appetite Nausea or vomiting.[cancer.coloradowomenshealth.com]
  • The symptoms include bloating, pelvic or abdominal pain, difficulty eating or feeling full quickly, and an urgent or frequent need to urinate.[npr.org]
  • And even with malignant tumors, women are more likely to have symptoms like bloating, pelvic or abdominal pain, appetite issues and menstrual changes if the cancer spreads to other body parts.[medicaldaily.com]
Abdominal Distension
  • Early symptoms are often vague, such as abdominal discomfort, abdominal distension or bloating, urinary frequency or dyspepsia. Constitutional symptoms include fatigue, weight loss, anorexia and depression.[patient.info]
  • distension (often misdiagnosed as “middle-aged spread”) increasing tumour size results in pressure effects causing chronic abdominal, pelvic or back pain , urinary frequency/urgency (pressure on bladder), constipation/altered bowel habit/bowel obstruction[geekymedics.com]
  • Symptoms that come later include the following: Pelvic pain or pressure Pain with intercourse Abdominal swelling and bloating Urinary frequency Constipation Ascites : Collection of fluid in the abdomen , contributing to abdominal distension and shortness[emedicinehealth.com]
  • Often these masses are large enough to cause bloating , abdominal distension, constipation , and changes in bladder habits. In the more uncommon ovarian types (stromal and germ cell tumors), symptoms are similar.[medicinenet.com]
  • distension or discomfort, abdominal mass [6] [5] Back pain [6] [7] Feeling full quickly while eating [6] [5] [7] Painful urinination or frequent urges, constipation, or diarrhea [6] [7] Indigestion and acid reflux [5] Shortness of breath (SOB) [5] Weight[physio-pedia.com]
Dyspepsia
  • Early symptoms (eg, dyspepsia, bloating, early satiety, gas pains, backache) are nonspecific. If cancer is being considered, do CT, measure tumor markers (eg, CA 125), and surgically stage tumors.[merckmanuals.com]
  • Early symptoms are often vague, such as abdominal discomfort, abdominal distension or bloating, urinary frequency or dyspepsia. Constitutional symptoms include fatigue, weight loss, anorexia and depression.[patient.info]
  • .  A history of nonspecific gastrointestinal complaints, including : nausea, dyspepsia, and altered bowel habits, is particularly common  abdominal distention as a result of ascites are generally signs of advanced disease.  A change in bowel habits[slideshare.net]
  • Patients with advanced carcinomas usually present with vague abdominal swelling or discomfort, abdominal bloating, dyspepsia and early satiety, lack of appetite, malaise, urinary frequency and weight change (either gain or loss).[atlasgeneticsoncology.org]
Hirsutism
  • It’s also appropriate to code any functional activity, such as one of the following: • other ovarian dysfunction (256.8); • hirsutism (704.1); • hyperestrogenism (256.0); • other ovarian hyperfunction (256.1); • precocious sexual development and puberty[fortherecordmag.com]
  • A case of hirsutism due to bilateral diffuse ovarian Leydig cell hyperplasia in a post-menopausal woman. Eur J Intern Med. 2003;14(7):432-3. Serov SF, Scully RE, Sobin LH. Histological typing of ovarian tumours. Geneva: WHO; 1973.[revistas.pucsp.br]
  • The most common presenting symptom in children and adolescents is abdominal pain, although precocious puberty, irregular menses, or hirsutism may also be present. 18 Patients with ovarian cancer may have abdominal pain, swelling, or nonspecific gastrointestinal[aafp.org]
  • These patients usually have menstrual cycle irregularities and either typical clinical signs of hirsutism, obesity, infertility, acne, male balding pattern or biochemically show increased androgen levels.[radiologyassistant.nl]
  • The presence of polycystic ovaries alone in the absence of clinical signs such as amenorrhea, infertility, obesity, and hirsutism is insufficient for diagnosing this syndrome.[e-ultrasonography.org]
Night Sweats
  • Women may claim pain in the lower abdomen or pelvic region, and constitutional symptoms such as fever, night sweats, chills, loss of appetite and weight may be reported.[symptoma.com]
  • For premenopausal women, surgical removal of the ovaries may cause symptoms of menopause, including hot flashes, vaginal dryness and night sweats. For more information, visit CancerQuest's page on surgery.[cancerquest.org]
Abdominal Pain with Urination
  • In these cases symptoms may include: Abdominal pain Trouble urinating or frequent urination Low back pain Pain with sexual intercourse Bad cramps with a woman’s periods Feeling full quickly after eating, or no appetite Nausea or vomiting.[cancer.coloradowomenshealth.com]

Workup

The patient's medical and family history provide the backbone of OC diagnosis. When obtaining information regarding the occurrence of cancer in family members, it should be kept in mind that those mutations associated with hereditary OC may also predispose to breast cancer, prostate cancer, pancreatic cancer, and melanoma [4]. Notwithstanding, the international standard of care is to offer genetic testing to all women in whom OC is diagnosed, regardless of age, medical and family history [5].

Sonography is the methods of choice to assess ovarian lesions, and it may be complemented by more sophisticated imaging techniques such as computed tomography and magnetic resonance imaging. Diagnostic imaging not only allows for the evaluation of the ovaries but also the fallopian tubes, uterus, adjacent tissues, lymph nodes, and distant organs. It should be kept in mind that the sensitivity of imaging techniques may be insufficient for the detection of early-stage OC. Concurrent measurements of tumor markers may support the tentative diagnosis of OC, with common panels including cancer antigen 125, carcinoembryonic antigen, and carbohydrate antigen 19-9 [3].

Finally, tissue samples have to be obtained to confirm the diagnosis, to determine the tumor's cellular origin, grade, and histotype. Core biopsy specimens are preferred to this end, but fine-needle aspiration samples from mass lesions or ascitic fluid may be used if the former are not feasible [3].

The FIGO staging system is applied to determine the patient's prognosis and to allow for a well-founded decision regarding treatment strategies [1]:

Stage 0: Tumor in situ
Stage 1: OC involves one (1A) or both (1B) ovaries, whose capsule remains intact. There are no tumor cells on the ovarian surface, and peritoneal washings yield negative results. If the capsule is raptured or tumor cells are detected on the ovarian surface or washings are positive, stage 1C has been reached.
Stage 2: Pelvic extension can be confirmed. Metastases have formed in the uterus or fallopian tubes (2A) or other pelvic structures (2B). Positive peritoneal washings warrant the diagnosis of OC stage 2C.
Stage 3: Peritoneal implants are detected outside the pelvis and/or regional lymph nodes are involved. Stages 3A, 3B, and 3C are assigned according to the size of peritoneal metastases.
Stage 4: Distant metastases other than peritoneal metastases are detected, or the patient is found to suffer from malignant pleural effusion.

Laparoscopic assessment may be necessary to define the stage of OC and to determine whether primary resection is feasible.

Pleural Effusion
  • Staging investigations for patients with a high RMI score include: blood tests – FBC (for anaemia), U E (for renal function), LFTs (for metastases) imaging – CXR to check for pleural effusion or lung metastases, CT /- MRI abdomen and pelvis to assess[geekymedics.com]
  • Stage 4: Distant metastases other than peritoneal metastases are detected, or the patient is found to suffer from malignant pleural effusion.[symptoma.com]
  • Complications of advanced disease: malnutrition, electrolyte imbalance, small and large bowel obstruction, infection, ascites, pleural effusion.[patient.info]
  • effusion , and mucositis .[en.wikipedia.org]

Treatment

Debulking surgery, performed as bilateral salpingo-oophorectomy or total hysterectomy, has long since been the foundation of OC management. Unilateral salpingo-oophorectomy may be considered in women who wish to preserve fertility but should be carefully weighed against the risks of recurrence. In any case, surgery aims at the complete resection of degenerated tissues, which is associated with the best outcomes. Subsequently, patients are referred for chemotherapy with carboplatin and paclitaxel. These drugs are administered intravenously every 3 weeks. Paclitaxel may be replaced by pegylated liposomal doxorubicin if taxane-free regimens are required. By derogation to the aforedescribed standard procedure of surgery plus adjuvant chemotherapy, patients may benefit from neoadjuvant chemotherapy if the complete resection of neoplasms cannot be achieved by up-front surgery [5].

In recent years, biological agents have increasingly been used to complement the therapy of OC:

  • Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A, is a potent inhibitor of angiogenesis and has been approved for the treatment of advanced OC [6].
  • Similarly, PARP inhibitors olaparib and rucaparib may be used to treat advanced-stage and recurrent OC [7].
  • Other compounds are currently tested regarding their safety and efficacy in OC therapy. Research currently focuses on combination approaches, antibody-drug conjugates, and immunotherapy [5].

Most patients will achieve remission, but many will eventually experience a recurrence of OC. In order to reduce the risk of relapses, maintenance therapies are often incorporated into the therapeutic paradigm. Maintenance strategies comprise the single use of bevacizumab or PARP inhibitors, although no guidelines have yet been established to this end. As a general rule, patients with poor prognostic factors are most likely to benefit from maintenance [3].

Prognosis

The lack of a premalignant phase and effective strategies for early detection combined with the non-specific presentation of the disease result in detrimental diagnostic delays. Most patients are diagnosed with advanced-stage OC, which is associated with a poor prognosis. The overall five-year survival rate has been estimated at 44% for all stages - the worst prognosis among all types of gynecological malignancies [8]. Favorable outcomes are mainly observed when the tumor is detected during early stages of the disease.

Etiology

The precise causes of OC remain largely unknown and most likely comprise a series of environmental and genetic factors. Concerning the former, estrogen replacement therapy has repeatedly been shown to augment the risk of OC in postmenopausal women, while the prolonged reduction of estrogen levels, namely during pregnancy or under oral contraceptives, is ascribed a protective role in OC. These facts argue in favor of a role of ovulation in the etiology of ovarian malignancies, and it has been hypothesized that repeated damage and trauma to the ovarian epithelium during ovulatory cycles may increase the likelihood of mutations and malignant degeneration [9]. Beyond that, obesity, smoking, and the genital use of talcum powder may predispose to OC [10].

Strong genetic influences are most easily recognized in patients suffering from family cancer syndromes such as BRCA-associated hereditary breast and ovarian cancer syndrome, whose lifetime risk of developing malignancies of the ovaries may be as high as 63% [4]. Other hereditary conditions predisposing to OC include Lynch syndrome, Li-Fraumeni syndrome, and mutations in genes like CHEK2, RAD51C, RAD51D, BRIP1, BARD1, PALB2, MRE11, MLH1, PMS2, MSH2, MSH6, and NBN [5] [11]. In sum, about 20% of OC cases can be related to genetic factors, and three-quarters of these patients carry mutations in the BRCA1 or BRCA2 genes [8].

Epidemiology

OC accounts for about 30% of all malignancies of the female genital system and is the leading cause of death from gynecological cancers. In Western Europe and North America, where age-adjusted incidence rates are highest, 90% of affected women are diagnosed with epithelial OC. Higher shares of germ cell tumors are reported in some Asian countries [1].

In general, the individual risk of developing OC increases with age, and the mean age at the time of diagnosis is 62 years [3]. Notwithstanding, some types of OC preferentially affect younger patients: Germ cell OC tends to occur in teenage girls and young women, and patients developing OC due to hereditary conditions are typically diagnosed in their fourth or fifth decade of life [4].

Sex distribution
Age distribution

Pathophysiology

The pathogenesis of OC is a complex process that has yet to be fully explored. It certainly involves host genetic factors, which serve as a basis for the interplay of hormones, inflammatory mediators, and environmental influences [9]. According to the hypothesis of incessant ovulation, as mentioned above, repetitive injury to the ovarian surface epithelium may predispose to inflammation and is associated with changes in hormone levels, thereby leading to oxidative stress and DNA damage. Then again, epithelium harboring unresolved DNA damage would represent a prime target for neoplastic transformation. This hypothesis has not been unchallenged, though: High-grade serous ovarian carcinoma, the most common type of OC, may not even arise from the ovarian surface epithelium. Fallopian tube secretory cells have been identified as their cells of origin, and they are not subjected to the repetitive trauma associated with ovulation [12].

These observations allow for the following conclusions:

  • Further research is required to shed more light on the pathogenesis of OC, as our understanding of this process is still very limited.
  • OC may develop under different circumstances, may originate from distinct cell types. There is no one pathogenesis of OC.

Prevention

High parity and the prolonged use of oral contraceptives are generally associated with reduced risks of developing epithelial OC [13]. The use of genital talcum powder should be avoided, and medical conditions that may predispose to OC, such as endometriosis and pelvic inflammatory disease, should be treated accordingly [9].

Moreover, the risk of OC can be substantially reduced by bilateral oophorectomy [9]. While this procedure is not routinely carried out, it should seriously be considered in patients known to carry gene defects that are associated with a very high lifetime risk of ovarian malignancies. Alternatively, these women should be included in surveillance programs comprising regular clinical examinations, laboratory analyses for tumor markers, and diagnostic imaging. Such ovarian cancer screenings should be carried out from the age of 35, and all patients should be informed about its limitations: As implied above, the sensitivity of available techniques for detecting early-stage OC may be non-satisfactory [11].

Summary

The current classification of the World Health Organization considers a large number of OC types. There are five main groups of ovarian neoplasms, namely surface epithelial-stromal tumors, sex cord-stromal tumors, germ cell tumors, tumors of the rete ovarii, and miscellaneous tumors. Each group comprises multiple subtypes of neoplasias, which differ with regards to their tissue of origin, histological features, and malignant potential. Additionally, lymphoid and hematopoietic tumors may affect the ovaries [1]. It is beyond the scope of this article to provide a detailed description of all types of OC, which is why it will focus on the general aspects of the more common variants of ovarian malignancies.

Patient Information

Malignant ovarian neoplasm refers to any type of ovarian cancer, a rather common disease in industrialized nations. Women suffering from ovarian cancer may be asymptomatic for prolonged periods of time, or they may experience non-specific gastrointestinal and genitourinary complaints. Lower abdominal or pelvic pain, nausea, early satiety, bloating, and changes in the urinary frequency are most common. In case of persistent discomfort, it is paramount to clarify the causes of these symptoms: If patients are during the early stages of the disease, their prognosis is significantly better than that of women with advanced-stage ovarian cancer. Indeed, the outcome of metastatic ovarian cancer is generally poor.

References

Article

  1. Tavassoli F, Devilee P., eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, France: IARC Press; 2003.
  2. Bast RC, Jr., Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009; 9(6):415-428.
  3. Orr B, Edwards RP. Diagnosis and Treatment of Ovarian Cancer. Hematol Oncol Clin North Am. 2018; 32(6):943-964.
  4. Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  5. Matulonis UA. Management of newly diagnosed or recurrent ovarian cancer. Clin Adv Hematol Oncol. 2018; 16(6):426-437.
  6. Musella A, Vertechy L, Romito A, et al. Bevacizumab in Ovarian Cancer: State of the Art and Unanswered Questions. Chemotherapy. 2017; 62(2):111-120.
  7. Sabatucci I, Maltese G, Lepori S, Tripodi E, Bogani G, Lorusso D. Rucaparib: a new treatment option for ovarian cancer. Expert Opin Pharmacother. 2018; 19(7):765-771.
  8. Toss A, Tomasello C, Razzaboni E, et al. Hereditary ovarian cancer: not only BRCA 1 and 2 genes. Biomed Res Int. 2015; 2015:341723.
  9. Sueblinvong T, Carney ME. Current understanding of risk factors for ovarian cancer. Curr Treat Options Oncol. 2009; 10(1-2):67-81.
  10. Olsen CM, Nagle CM, Whiteman DC, et al. Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium. Endocr Relat Cancer. 2013; 20(2):251-262.
  11. Andrews L, Mutch DG. Hereditary Ovarian Cancer and Risk Reduction. Best Pract Res Clin Obstet Gynaecol. 2017; 41:31-48.
  12. Kroeger PT, Jr., Drapkin R. Pathogenesis and heterogeneity of ovarian cancer. Curr Opin Obstet Gynecol. 2017; 29(1):26-34.
  13. Peres LC, Risch H, Terry KL, et al. Racial/ethnic differences in the epidemiology of ovarian cancer: a pooled analysis of 12 case-control studies. Int J Epidemiol. 2018; 47(2):460-472.

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Last updated: 2019-07-11 20:27