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Diagnosis & Discussion

Diagnosis

Primary Lung Adenocarcinoma and Primary Type I Papillary Renal Cell Carcinoma

Discussion

This patient presented with a primary lung tumor and during initial work-up was found to have a mass in the kidney. Immunohistochemistry was used to differentiate between a metastatic lesion or a second primary tumor. Cell markers used in this case include TTF-1 and PAX-8, which aid in diagnosing lung adenocarcinoma and renal cell carcinoma, respectively.

Tissue specific gene expression is mediated in part by transcription factors, which are used as cell markers. Thyroid transcription factor (TTF-1) plays a role in normal lung function and development, and it is uniformly expressed in the terminal respiratory unit. TTF-1 expression is increased in lung adenocarcinoma, thus making TTF-1 a sensitive marker for lung adenocarcinomas. Similarly, PAX-8, a member of the paired box transcription factor family, is used to aid in the diagnosis of renal cell carcinoma. PAX-8 is involved in normal kidney function and development and its expression is increased in renal cell carcinomas.

In this case, the immunohistochemistry stains identified that the patient had a TTF-1-positive primary lung adenocarcinoma. The immunohistochemistry stains of the kidney biopsy demonstrated positive PAX-8 staining without TTF-1 staining. Given the negative TTF-1, metastasis of the lung was ruled out, while the positive PAX-8 expression supported a diagnosis of a primary renal cell carcinoma.

As seen in this case, most patients with stage IV lung adenocarcinoma are assessed for the tyrosine kinase anaplastic lymphoma kinase (ALK) gene rearrangements, which are detected using fluorescence in situ hybridization (FISH). Tyrosine kinases are key regulators of many signaling pathways and influence cell growth and differentiation. Chromosomal rearrangements involving ALK occur in certain cancers, including non-small cell lung cancer. An inversion within chromosome 2 joins the 3’ end of the ALK gene with the 5’ end of the echinoderm microtubule-associated protein-like 4 gene (EML4). The resulting fusion oncogene EML4-ALK is found in approximately 5% of non-small cell lung cancer patients, which leads to overexpression of ALK. ALK positive lung cancers are associated with certain clinical features, including a lack of smoking history, younger age at onset, and adenocarcinoma histology.

References

  1. Barr ML, Jilaveanu LB, Camp RL, et al. PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma? Journal of Clinical Pathology. 2015; 68(1): 12-17.

  2. Pikor LA, Ramnarine VR, Lam S, et al. Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung Cancer. 2013; 82(2): 179-189.

  3. Shaw AT, Solomon B. Targeting anaplastic lymphoma kinase in lung cancer. Clinical Cancer Research. 2011; 17(8): 2081-2086.

  4. Takahashi T, Sonobe M, Kobayashi M, et al. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene. Annals of Surgical Oncology. 2010; 17(3): 889-897.

  5. Yatabe Y, Mitsudomi T, Takahashi T. TTF-1 expression in pulmonary adenocarcinomas. The American Journal of Surgical Pathology. 2002; 26(6): 767-773.

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