Prediction of lung cancer metastasis relies on post-resection assessment of tumor histology, which is a severe limitation since only a minority of lung cancer patients are diagnosed with resectable disease. Therefore, characterization of metastasis-predicting biomarkers in pre-resection small biopsy specimens is urgently needed. Here we report a biomarker consisting of the phosphorylation of the retinoblastoma protein (Rb) on serine 249 combined with elevated p39 expression. This biomarker correlates with epithelial-to-mesenchymal transition traits in non-small cell lung carcinoma (NSCLC) cells. Immunohistochemistry staining of NSCLC tumor microarrays showed that strong phospho-Rb S249 staining positively correlated with tumor grade specifically in the squamous cell carcinoma (SCC) subtype. Strong immunoreactivity for p39 positively correlated with tumor stage, lymph node invasion, and distant metastases, also in SCC. Linear regression analyses showed that the combined scoring for phospho-Rb S249, p39 and E-cadherin in SCC is even more accurate at predicting tumor staging, relative to each score individually. We propose that combined immunohistochemistry staining of NSCLC samples for Rb phosphorylation on S249, p39, and E-cadherin protein expression could aid in the assessment of tumor staging and metastatic potential when tested in small primary tumor biopsies. The intense staining for phospho-Rb S249 that we observed in high grade SCC could also aid in the precise sub-classification of poorly differentiated SCCs.

Chronic lymphocytic leukemia (CLL) is a malignant proliferation of monoclonal mature B-cells in peripheral blood. Leukemia cells can commonly spread from the blood to other sites such as the lymph nodes, liver, and spleen. However, contrary to T-cell lymphomas that can involve the skin, CLL metastasis to the skin is unusual and is rarely the first manifestation of systemic disease. When leukemia cells invade the skin, it is termed leukemia cutis. Furthermore, multiple skin morphologies can be present in leukemia cutis making diagnosis challenging. Likewise, it can be mistaken for other common etiologies such as drug or substance allergy, infection, and scabies, among others. We herein present a case of CLL with leukemia cutis as the initial manifestation of systemic disease. The initial punch biopsy results were non-specific for inflammatory changes, but a subsequent biopsy revealed findings confirming leukemia cutis. This case not only demonstrates that identifying malignant skin manifestations in a timely manner and treating them is essential, as it improves the quality of life and survival, but also demonstrates that leukemia cutis can be a dynamic disease where multiple biopsies may be needed to confirm the diagnosis, as histopathology can change over time.

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