Breast cancer is the most common malignancy in women worldwide. Despite early detection and improved treatment modalities, a considerable number of breast cancer patients experience relapse with distant metastatic disease, most commonly to the bone, liver, lung and brain. Additionally, it has been noted that the metastatic behavior of a given patient's breast cancer is associated with the intrinsic biologic subtype (as determined by either gene expression profile or immunohistochemical biomarkers). While hormone receptor positive Luminal A/B breast cancers have predilection for bone metastasis, triple negative breast cancer (TNBC) show more frequent brain and lung metastasis1.
When dealing with a carcinoma in daily practice, diagnostic (and prognostic) immunohistochemical markers commonly employed to support breast origin include GATA3, mammoglobin, GCDFP-15, ER, PR, and HER2/neu. When presented with malignant cytomorphology, positive staining for the aforementioned immunohistochemical markers, prior cytologic or histologic material available for comparison, and/or a compelling clinical history, metastatic breast carcinoma can be a relatively straightforward diagnosis to make.
However, TNBCs present a unique diagnostic challenge. Representing 10-20% of all breast cancers, TNBCs (as well as related groups like metaplastic carcinoma and basal-like breast cancers) often show limited to absent staining for GCDFP15, mammoglobin, and even GATA34,5; of course, one cannot rely on biomarker staining either as these tumors are negative for ER, PR, and HER2/neu by definition. When TNBC is in the differential diagnosis, one should turn to the neural crest transcription factor, SOX10.
The utility of SOX10 in the diagnosis of neural crest derived lesions such as melanoma and nerve sheath tumors is well known to practicing pathologists. Perhaps less well known is the more recently described utility of SOX10 as arguably one of the most useful marker for TNBC, especially paired with GATA32,4,5. While SOX10 is positive in only half to two thirds of TNBC, SOX10 stains the vast majority of GATA3-negative TNBC, and when positive, typically displays strong and diffuse nuclear staining (as compared to the often weak and patchy cytoplasmic staining of GCDFP15 and mammoglobin). Nearly all (95%) cases of TNBC will show positivity for at least one of these two markers (GATA-3 and/or SOX10) when used in combination5. In the context of a carcinoma in the lung (as in the current case), SOX10 shows 100% specificity for TNBC compared to lung adenocarcinoma irrespective of TTF1 status2. Furthermore, SOX10 has been shown to stain roughly half of metaplastic squamous cell carcinomas of the breast (primary and metastatic), whereas it is consistently negative in squamous cell carcinomas of the lung, skin, cervix, oral mucosa, and esophagus6.