Ground-Glass Opacities in Prostate Cancer: Metastatic Presentation
Lung metastases from prostate cancer can rarely present as ground-glass opacities (GGOs), but this is an extremely uncommon radiographic pattern that requires tissue diagnosis to confirm. 1, 2
Typical Metastatic Pattern vs. GGO Presentation
Prostate cancer lung metastases typically appear as solid nodules, not ground-glass opacities. The classic metastatic pattern shows small round solid nodules predominantly in the peripheral lung and lower lobes. 3 However, case reports document rare instances where prostate cancer metastases present as focal GGOs with minimal solid components. 1, 2
Documented GGO Cases in Prostate Cancer
A 75-year-old man with metachronous prostate and gastric cancers developed an 11mm focal GGO in the right upper lobe that proved to be metastatic prostate adenocarcinoma on biopsy. 2
An 83-year-old man with treated prostate cancer developed an enlarging GGN (from 1 to 2.1 cm) that was initially suspected to be primary lung adenocarcinoma but ultimately represented metastatic disease. 1
Both cases showed normal or non-elevated PSA levels at presentation, demonstrating that biochemical markers cannot exclude metastatic disease. 1, 2
Critical Diagnostic Algorithm
Step 1: Radiographic Assessment
Multiple bilateral GGNs or part-solid nodules of similar size without mediastinal adenopathy strongly suggest separate primary lung adenocarcinomas rather than metastases. 3 In contrast, a solitary GGO in a patient with known prostate cancer requires tissue diagnosis to distinguish primary lung cancer from the rare metastatic presentation. 1, 2
Step 2: Tissue Confirmation is Mandatory
CT-guided percutaneous needle biopsy or surgical resection is required—imaging characteristics alone cannot distinguish metastatic prostate cancer from primary lung adenocarcinoma when GGO is present. 1, 2 Even experienced radiologists cannot reliably differentiate these entities based on imaging alone. 3
Step 3: Immunohistochemistry Panel
The definitive diagnosis requires immunostaining showing PSA and P504S positivity with negativity for CK7, CK20, TTF-1, and napsin A. 1, 2 This immunoprofile confirms prostatic origin and excludes primary lung adenocarcinoma.
Key Clinical Pitfalls
Do not assume GGOs represent primary lung cancer simply because this is the most common etiology—metastatic prostate cancer must be excluded in patients with known prostatic malignancy. 1, 2 The following features increase suspicion for metastatic disease:
- History of treated prostate cancer, even with long disease-free intervals exceeding 5-7 years 1
- Normal PSA levels do not exclude metastatic disease, particularly in patients with indolent biology or after definitive radiotherapy 1, 2
- Enlarging GGO on serial imaging warrants biopsy regardless of PSA status 1
Alternative Diagnoses to Consider
Ground-glass opacities have extensive differential diagnoses that must be systematically excluded. 4, 5
Drug-Related Pneumonitis
Patients receiving androgen deprivation therapy or other systemic treatments may develop drug-related pneumonitis presenting as GGOs. 3 Organizing pneumonia and hypersensitivity pneumonitis patterns commonly show patchy ground-glass opacities and small nodular lesions. 3
Multifocal Primary Lung Adenocarcinoma
Multiple pure ground-glass or part-solid nodules typically represent separate primary lung cancers (SPLCs) rather than metastases, particularly in women and never-smokers. 3 These patients have better prognosis with less lymph node involvement and systemic spread compared to solid metastatic nodules. 3
Early Interstitial Lung Disease
Extensive ground-glass opacity (>30% of lung involvement) suggests nonspecific interstitial pneumonia (NSIP) or organizing pneumonia rather than metastatic disease. 3, 4 The presence of traction bronchiectasis or honeycombing indicates fibrotic lung disease, not malignancy. 3, 5
Management Approach
For solitary or focal GGOs in patients with prostate cancer history, proceed directly to tissue sampling via CT-guided biopsy or surgical resection. 1, 2 Observation is inappropriate when the differential includes both treatable primary lung cancer and metastatic disease requiring systemic therapy.
If multiple bilateral GGNs are present without solid components or adenopathy, these likely represent multifocal primary lung adenocarcinomas and should be staged as separate primary lung cancers (SPLCs) with the T category determined by the highest T lesion. 3
Obtain comprehensive immunohistochemistry on all biopsied tissue including PSA, P504S, CK7, CK20, TTF-1, and napsin A to definitively establish the primary site. 1, 2 This is particularly critical in patients with metachronous multiple cancers where the primary site cannot be assumed based on clinical history alone.