What is the most likely diagnosis for a woman presenting with dyspepsia, weight loss, and shortness of breath, with an adnexal mass and a 12 cm irregular uterus?

Ovarian Cancer

The most likely diagnosis is ovarian cancer, given the combination of an adnexal mass, systemic symptoms suggesting metastatic disease (dyspepsia, weight loss, shortness of breath), and an enlarged irregular uterus that may represent either direct extension or a separate uterine pathology. 1, 2

Clinical Reasoning

The constellation of findings strongly points toward advanced ovarian malignancy:

• Adnexal mass with systemic symptoms: The presence of dyspepsia, weight loss, and shortness of breath are classic indicators of metastatic spread, which is characteristic of ovarian cancer rather than other gynecologic malignancies 1, 2

• Ascites and pleural effusions: Shortness of breath in this context likely represents pleural effusion, which the ACR identifies as a key imaging feature in malignant adnexal masses and is one of the five IOTA malignant features (M features) that strongly suggest ovarian cancer 1, 2

• Dyspepsia as a metastatic indicator: This symptom suggests peritoneal or omental metastases, which are hallmark features of advanced ovarian cancer and are specifically highlighted by ACR guidelines as important in evaluating disease extent 1

Why Not the Other Diagnoses

• Uterine sarcoma: While the 12 cm irregular uterus could suggest this diagnosis, uterine sarcomas rarely present with adnexal masses as the primary finding and do not typically cause pleural effusions or ascites as initial manifestations 1

• Endometrial cancer: This malignancy rarely causes pleural effusion or significant ascites, and would not present with an adnexal mass as the primary finding 1

• Cervical cancer: Does not typically present with adnexal masses or pleural effusion as initial manifestations 1

Diagnostic Approach

Immediate imaging evaluation:

• Transvaginal ultrasound with color Doppler is the first-line imaging modality to characterize the adnexal mass 3, 4
• Look for IOTA malignant features: irregular solid tumor, at least 4 papillary structures, irregular multilocular-solid tumor ≥100 mm, very strong blood flow, and ascites 3, 1
• Assess for pleural effusions and ascites on imaging 1, 2

Laboratory evaluation:

• CA-125 should be measured immediately, as it has 98.5% specificity in postmenopausal women and is elevated in 80-90% of serous carcinomas 5
• Critical caveat: CA-125 only detects 50% of stage I ovarian cancers, so a normal level does not exclude malignancy 5
• If CA-125 is not elevated, measure CA 19-9 for mucinous or clear cell tumors 5

Urgent referral:

• All women with evidence of metastatic disease, ascites, or complex adnexal masses should be referred to a gynecologic oncologist 4, 6, 7
• Initial management by a gynecologic oncologist is the second most important prognostic factor after stage for long-term survival 3

Common Pitfalls

• Do not rely on CA-125 alone: It performs best when combined with ultrasound findings and only improves specificity in lesions already suspected to be malignant on imaging 1, 5
• Do not delay referral: Only 33% of women with ovarian cancer are appropriately referred to gynecologic oncologists initially, which negatively impacts outcomes 3
• Recognize the irregular uterus: This may represent direct extension from the ovarian mass, synchronous uterine pathology, or displacement by the adnexal mass—all scenarios require oncologic evaluation 1