Cytopathology of Sister Mary Joseph nodules: the Johns Hopkins experience

More than a century after Sister Mary Joseph first recognized the clinical significance of umbilical nodule, the umbilicus remains a diagnostic window into occult malignancy. Although prior studies demonstrate that most Sister Mary Joseph nodules (SMJNs) represent metastatic adenocarcinoma, our institutional review spanning February 2019 through October 2025 additionally identified rare presentations including melanoma, mesothelioma, and lymphoma. Fine-needle aspiration continues to provide a rapid, minimally invasive link between this superficial clinical finding and its association with underlying visceral primary.

We performed a retrospective review of cytopathology and surgical pathology archives from February 2019 through October 2025 in the Epic Beaker database. All cases were retrieved and reviewed for cytopathologic and histopathologic features, and immunohistochemical (IHC) profiles. Additionally, clinical and imaging data were extracted from electronic records and correlated with the pathologic findings.

Twenty-one patients with umbilical lesions were identified. Median age was 72 years (44-92), and 67% of the patients were female. Adenocarcinoma predominated (14/21, 67%), with primary origins confirmed as gastrointestinal (48%), gynecologic (24%), genitourinary (10%), and other (19%). IHC studies, available in 14 cases, supported primary site attribution using CK7, CK20, PAX8, WT1, GATA3, ER, CDX2, and other antibodies. The median interval from primary tumor diagnosis to presentation of SMJN was 8 months. In 4 patients, SMJN was the initial presentation. Six patients had documented survival data.

SMJN in current practice remains predominantly metastatic adenocarcinoma, most often gastrointestinal or gynecologic in origin. However, rare entities-including mesothelioma, melanoma, and lymphoma-underscore the need for a broad diagnostic differential. Fine-needle aspiration offers a rapid, minimally invasive diagnostic bridge and reinforces that the umbilicus remains a valuable clinical marker of an often occult malignancy.