In a 40‑year‑old woman with cyclic pelvic, low‑back, and breast pain that worsens during her menstrual cycle, and with negative pelvic MRI and ultrasound except for a resolving right ovarian cyst, what differential diagnoses should be considered?

Differential Diagnosis for Cyclic Pelvic, Breast, and Low Back Pain in a 40-Year-Old Woman

In this 40-year-old woman with cyclic symptoms and negative imaging, the differential diagnosis should prioritize endometriosis as the leading consideration, followed by adenomyosis, pelvic congestion syndrome, musculoskeletal causes, and cyclical mastalgia as distinct entities rather than manifestations of a single process.

Primary Gynecologic Considerations

Endometriosis

• Endometriosis remains the most likely diagnosis despite negative MRI, as imaging has poor sensitivity for detecting peritoneal disease 1
• MRI correctly identifies only 56% of women with structural gynecologic causes of chronic pelvic pain and misses 46% of those with true pathology 1
• Laparoscopy is significantly more accurate than MRI for diagnosing superficial peritoneal endometriosis (p < 0.0001) and deep-infiltrating endometriosis (p < 0.0001) 1
• Women who fail empiric therapy with NSAIDs, oral contraceptives, or antibiotics should be considered highly likely to have endometriosis or adenomyosis 2
• The cyclic nature of symptoms strongly supports an estrogen-dependent process 3

Adenomyosis

• Adenomyosis should be considered alongside endometriosis in women with cyclic pelvic pain who fail empiric therapy 2
• MRI may have limited sensitivity for adenomyosis, particularly in early or focal disease 1
• This diagnosis often coexists with endometriosis and presents with similar cyclic symptomatology 4

Pelvic Congestion Syndrome

• Pelvic congestion syndrome is a recognized cause of chronic pelvic pain localized to the deep pelvis 5
• This condition may not be adequately visualized on standard MRI protocols without specific venous phase imaging 5
• Symptoms typically worsen with prolonged standing and may have hormonal variation 5

Breast Pain as a Separate Entity

Cyclical Mastalgia

• The breast pain represents cyclical mastalgia, which accounts for 70% of breast pain cases and is bilateral or diffuse, related to hormonal fluctuations, worsening in the luteal phase 3, 6
• Cyclical breast pain follows a predictable pattern with the menstrual cycle, worsening during the luteal phase and improving with menstruation 3
• This pain is directly related to hormonal fluctuations rather than structural breast pathology 3
• The risk of cancer with cyclical pain alone in the absence of other signs is extremely low 6, 7
• For cyclical breast pain, imaging is not necessary beyond routine age-appropriate screening, as cyclical pain alone does not require imaging 3

Musculoskeletal and Extramammary Causes

Musculoskeletal Low Back Pain

• Low back pain may represent referred pain from spinal nerve root syndrome (cervical or thoracic) that can manifest as both back and breast discomfort 5
• Costochondritis (Tietze syndrome) can cause chest wall pain that radiates to the breast and may have cyclic exacerbation 5, 7
• Pelvic myofascial pain can present with deep pelvic discomfort and may be hormonally modulated 5
• Fibromyalgia should be considered when multiple pain sites are present without clear structural pathology 5

Nerve Entrapment

• Entrapment of the lateral cutaneous branch of the third intercostal nerve can cause breast and chest wall pain 5
• Irritation of anterolateral and anteromedial branches of intercostal nerves from T3 to T5 can lead to breast or nipple pain 5, 3

Less Common but Important Considerations

Ovarian Pathology

• While the resolving ovarian cyst was noted, functional cysts can be linked with irregular vaginal bleeding, menorrhagia, and cyclic pain 8
• Functional cysts less than 5 cm usually resolve spontaneously, but larger cysts (≥5 cm) are less likely to resolve and may require annual ultrasound assessment 8
• The risk of malignancy in a symptomatic ovarian cyst in a 40-year-old is approximately 1:1,000 8

Intraperitoneal Adhesions

• Adhesions are a potential cause of deep pelvic pain but may not be visible on MRI 5
• Previous surgery, infection, or endometriosis can lead to adhesive disease 5

Hydrosalpinx or Chronic Inflammatory Disease

• Chronic pelvic inflammatory disease can present with persistent pelvic pain 5
• Hydrosalpinx may be subtle on imaging and requires specific ultrasound features (endosalpingeal folds) for diagnosis 5

Diagnostic Algorithm

Immediate Next Steps

1. Maintain a pain diary for 2-3 menstrual cycles to document the precise relationship between symptoms and cycle phase 3, 6
2. Trial empiric therapy with NSAIDs and continuous or cyclic oral contraceptives for 3 months 2
3. No additional breast imaging is indicated given the cyclical nature and absence of focal findings 3, 6

If Empiric Therapy Fails

1. Consider diagnostic laparoscopy as the gold standard for identifying endometriosis, adhesions, and other peritoneal pathology that MRI cannot detect 1
2. GnRH agonist trial may serve both diagnostic and therapeutic purposes if laparoscopy is declined or delayed 2
3. Evaluate for musculoskeletal causes with physical examination focusing on chest wall tenderness, trigger points, and spinal pathology 5, 7

Critical Pitfalls to Avoid

• Do not dismiss endometriosis based on negative MRI alone, as MRI has poor sensitivity for peritoneal disease and misses nearly half of structural gynecologic causes 1
• Do not order breast imaging for diffuse cyclical breast pain when clinical examination is normal, as this increases healthcare utilization without improving cancer detection 5, 3
• Do not fail to consider that these may be three separate conditions (endometriosis causing pelvic pain, cyclical mastalgia causing breast pain, and musculoskeletal pathology causing low back pain) rather than a single unifying diagnosis 5, 3, 4
• Do not delay laparoscopy indefinitely in women who fail empiric therapy, as this is the only definitive way to diagnose or exclude peritoneal endometriosis 1