False-Positive Sentinel Lymph Nodes in Breast Cancer Patients Caused by Benign Glandular Inclusions

Abstract

We report 3 cases of sentinel lymph nodes (SLNs) containing benign glandular inclusions (BGIs) in patients with breast carcinoma that were initially misdiagnosed as metastatic carcinoma. The first case had an SLN with glandular elements adjacent to a squamous inclusion cyst, the second had an SLN with a single complex gland showing apocrine features, and the third had 2 SLNs, each containing rare glands lined by bland columnar cells and surrounded by thin, fibrous bands. All glandular elements were distinctly different from the corresponding invasive carcinoma. Immunostains for myoepithelial markers revealed smooth muscle myosin reactivity and scattered p63+ nuclei, indicating the presence of myoepithelial cells. Based on morphologic and immunohistochemical findings, a diagnosis of BGIs was established. Our case series report indicates that comparison with the morphologic features of primary breast carcinoma and using immunohistochemical analysis for myoepithelial markers are important ancillary tools in distinguishing BGIs from metastatic carcinoma.

Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer

“…37 Because the OSNA assay is designed not to recognize tumor cells corresponding to ITCs, this is unlikely to be a source of error in the test. However, benign intranodal epithelial inclusions, such as heterotopic mammary glands, benign glandular inclusions, or benign Mullerian inclusions, are inevitable for the false-positive diagnoses, [38][39][40][41] although their presence is a rare event in axillary lymph nodes. Clinical trials comparing OSNA assay and histopathological examination have demonstrated a high specificity (96% to 97%) after investigating discordant cases.…”

Synchronous ductal carcinoma in situ of the breast and within epithelial inclusions in an ipsilateral sentinel lymph node

“…This is described in association with intraoperative techniques for assessment of SLNs, including frozen section examination [13,14], but it also a potential problem with intraoperative touch imprint cytology and qRT-PCR (quantitative reverse transcriptase-polymerase chain reaction). However, this remains an issue even in a formalin-fixed, paraffin-embedded material; reports of benign inclusions misdiagnosed as metastatic disease are recorded [4,5,14]. Although malignant change in such inclusions is exceptionally rare, this adds a further level of difficulty to reaching the correct diagnosis when epithelial inclusions are present.…”

Absence of ectopic epithelial inclusions in 3,904 axillary lymph nodes examined in sentinel technique

“…Immunohistochemistry was performed on lymph nodes (all levels) of ten male and ten female patients, chosen at random prior to the examination of H&E sections. For that purpose, we applied a pan-cytokeratin antibody (clone MNF116, DAKO, Carpinteria, CA; dilution 1:100), which covers a wide spectrum of cytokeratins (cytokeratins 5,6,8,17,19).…”

“…Not infrequently, salivary gland and thyroid fragments are found in cervical lymph nodes and melanocytic nevus cells in axillary and inguinal nodes [4]. Anatomical pathologists occasionally encounter ectopic breast tissue, embryologic remnants of the milk line, in the axillary fat as well as in the capsule and parenchyma of axillary lymph nodes [5][6][7][8][9]. It stands to reason that these ectopic epithelial elements will be recognized by intraoperative PCR and hence interpreted as metastasis.…”