Should tissue diagnosis of lung and thyroid lesions be obtained before proceeding with hysterectomy and surgical staging in a patient with confirmed low-grade endometrial carcinoma and PET-avid (Positron Emission Tomography-avid) lung and thyroid lesions?

Management Sequencing for Concurrent Endometrial Carcinoma and PET-Avid Lung/Thyroid Lesions

Obtain tissue diagnosis of the lung nodule before proceeding with hysterectomy, as the presence of a second primary malignancy or metastatic disease would fundamentally alter the entire treatment paradigm and surgical approach for this patient.

Rationale for Lung Nodule Biopsy First

Critical Diagnostic Principle

• Tissue-based diagnosis is crucial before any radical treatment, and reasonable attempts at pre-surgical diagnosis should be pursued, particularly when the diagnosis would alter management 1.
• The 1.2 cm perihilar nodule with SUV 7.1 represents an indeterminate solitary pulmonary nodule that requires multidisciplinary assessment considering patient factors, epidemiological risk, and radiologic characteristics 1.
• A pre-surgical pathological diagnosis is recommended for clinical stage I/II lung lesions, though high likelihood of malignancy (>65%) assessed by experienced multidisciplinary groups may be sufficient to proceed without biopsy in select cases 1.

Why This Changes Everything

• If the lung nodule represents primary lung cancer, this patient has two separate primary malignancies requiring coordinated but distinct treatment plans—the endometrial cancer management would proceed, but timing and sequencing must account for lung cancer treatment 1.
• If the lung nodule represents metastatic endometrial cancer (though unusual for grade 1 endometrioid), this upstages the endometrial cancer to stage IVB, fundamentally changing from curative surgical intent to systemic therapy considerations 2, 3.
• If the lung nodule is benign, you avoid unnecessary delay or modification of straightforward hysterectomy for what is otherwise low-grade, early-stage endometrial disease 1.

Practical Biopsy Approach

• CT-guided transthoracic needle biopsy is appropriate for this 1.2 cm perihilar lesion, though complications occur in up to 15% of cases, particularly in elderly patients and smokers 1.
• For peripheral lung nodules, EBUS (endobronchial ultrasound) or EUS (endoscopic ultrasound) guidance should be considered first as minimally invasive options if the lesion is accessible 1.
• The location, size, and solid component of the nodule should guide the most favorable biopsy approach 1.

Thyroid Nodule Management

Lower Priority for Immediate Biopsy

• The thyroid nodules can be addressed after the lung nodule is characterized, as thyroid malignancy—even if present—typically has an indolent course that allows sequential management 1, 4.
• FDG-avid thyroid nodules with SUV up to 10.9 warrant evaluation, but thyroid ultrasound supplemented by fine needle aspiration cytology should be the first-line diagnostic procedure 1.
• If bilateral papillary thyroid carcinoma is ultimately diagnosed, total thyroidectomy would be indicated, but this can be coordinated after addressing the more immediately pressing lung and endometrial issues 4.

Thyroid-Specific Considerations

• The calcified cervical lymph node with high FDG uptake (SUV 10.9) raises concern for thyroid malignancy with nodal involvement, but this still represents potentially curable disease that can be addressed in a staged fashion 1, 4.
• Preoperative vocal cord assessment and neck ultrasound mapping would be necessary before any thyroid surgery, but these can be deferred until the lung situation is clarified 4.

Endometrial Cancer Staging Considerations

Current Disease Status

• Complex atypical hyperplasia bordering on FIGO grade 1 endometrioid adenocarcinoma represents low-grade, hormone-responsive disease with generally favorable prognosis 2, 5.
• The ER/PR positive, p53 wild-type, MMR-intact profile confirms type I (estrogen-related) endometrial cancer with better prognosis than type II disease 2, 5.
• The hypermetabolic fundal uterine lesion on PET correlates with known endometrial pathology and does not necessarily indicate advanced disease 3.

Impact of Lung Findings on Endometrial Staging

• Preoperative imaging with PET/CT can detect distant metastatic disease that would alter surgical management from comprehensive staging to palliative or systemic therapy approaches 3.
• If the lung nodules represent metastatic endometrial cancer, total hysterectomy with bilateral salpingo-oophorectomy would still be considered for source control, but comprehensive lymphadenectomy might be omitted in favor of systemic therapy 2, 3.
• The multiple subcentimeter bilateral pulmonary nodules further complicate the picture and strengthen the argument for tissue diagnosis before committing to major surgery 3.

Recommended Management Algorithm

Step 1: Multidisciplinary Tumor Board Review

• Present this case to an expert multidisciplinary tumor board with representation from gynecologic oncology, thoracic surgery/pulmonology, endocrinology, and medical oncology 1.
• The board should assess the likelihood of malignancy for the lung nodule using validated algorithms that incorporate medical history, smoking status, and radiologic characteristics 1.

Step 2: Lung Nodule Tissue Diagnosis

• Proceed with CT-guided biopsy or EBUS/EUS-guided sampling of the 1.2 cm perihilar nodule 1.
• If lung adenocarcinoma is diagnosed, perform immunohistochemistry including TTF-1, CK7, CK20 to distinguish primary lung cancer from metastatic endometrial cancer 1, 6.
• Primary lung adenocarcinoma typically shows TTF-1+, CK7+, CK20- pattern, while endometrial adenocarcinoma would show different staining patterns 1, 6.

Step 3: Proceed Based on Lung Biopsy Results

If benign lung nodule:

• Proceed directly with total hysterectomy and bilateral salpingo-oophorectomy with surgical staging for endometrial cancer 2.
• Address thyroid nodules with FNA after recovery from hysterectomy 1.

If primary lung cancer:

• Stage the lung cancer completely with brain MRI and comprehensive mediastinal staging 1.
• Coordinate treatment sequencing with multidisciplinary team—likely hysterectomy first given the low-grade endometrial cancer, followed by lung cancer treatment 1.

If metastatic endometrial cancer to lung:

• Reconsider surgical approach—may still perform hysterectomy for source control but comprehensive staging less critical 2, 3.
• Initiate systemic therapy discussions and consider clinical trial enrollment 2.

Critical Pitfalls to Avoid

• Do not assume the lung nodule is benign based solely on the presence of confirmed endometrial cancer—63-year-old patients can have multiple primary malignancies 1, 6.
• Do not proceed with major surgery without tissue diagnosis when the result would fundamentally change the treatment plan 1.
• Do not delay lung biopsy for thyroid evaluation—the lung finding has more immediate implications for the endometrial cancer surgical plan 1.
• Do not assume FDG-avid lung nodules are automatically malignant—inflammatory conditions can cause false positives, though SUV 7.1 is concerning 1.