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ALK-associated pulmonary carcinoma

Tuesday 14 June 2011

ALK-rearranged lung carcinomas, ALK-associated lung cancer

A subset (1% to 5%) of non-small-cell lung carcinomas harbors the EML4-ALK fusion gene.

All cases show at least a focal adenocarcinoma component, and rare cases had additional squamous and sarcomatoid differentiation, respectively.

Solid or acinar growth pattern, cribriform structure, presence of mucous cells (signet-ring cells or goblet cells), abundant extracellular mucus, lack of lepidic growth, and lack of significant nuclear pleomorphism are more common in ALK-positive cancers.

Two recognizable constellations of findings, a solid signet-ring cell pattern and a mucinous cribriform pattern, are present at least focally in the majority (78%) of ALK-positive tumors, but are rare (1%) in ALK-negative tumors.

Characteristic histologies are present both in primary sites and in metastases. Thus, histologic findings may help to identify cases for ALK testing.

ALK-positive cancers commonly showed coexpression of thyroid transcription factor-1 and p63, and its significance is currently unclear.

Chromosomal rearrangements leading to constitutive activation of anaplastic lymphoma receptor tyrosine kinase (ALK) define a category of lung adenocarcinomas that may be amenable to targeted therapy with the ALK inhibitor crizotinib.

ALK+ lung adenocarcinomas have distinctive morphologic features, with signet ring cells showing a significant association with ALK rearrangements irrespective of tumor site (primary vs metastatic) or specimen type.

Primary ALK+ lung adenocarcinomas showed a significant association with solid, micropapillary, and papillary-predominant histologic patterns and tumor cells with a signet ring or hepatoid cytomorphology. (22743652)

Among metastatic lung tumors and small biopsy/cytology specimens, the only distinguishing morphologic feature of ALK+ tumors was the presence of signet ring cells. (22743652)

References

- Histologic and cytomorphologic features of ALK-rearranged lung adenocarcinomas. Nishino M, Klepeis VE, Yeap BY, Bergethon K, Morales-Oyarvide V, Dias-Santagata D, Yagi Y, Mark EJ, Iafrate AJ, Mino-Kenudson M. Mod Pathol. 2012 Jun 29. PMID: 22743652

- Comprehensive Histologic Analysis of ALK-Rearranged Lung Carcinomas. Yoshida A, Tsuta K, Nakamura H, Kohno T, Takahashi F, Asamura H, Sekine I, Fukayama M, Shibata T, Furuta K, Tsuda H. Am J Surg Pathol. 2011 Aug;35(8):1226-34. PMID: 21753699

- EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset. Inamura K, Takeuchi K, Togashi Y, Hatano S, Ninomiya H, Motoi N, Mun MY, Sakao Y, Okumura S, Nakagawa K, Soda M, Choi YL, Mano H, Ishikawa Y. Mod Pathol. 2009 Apr;22(4):508-15. PMID: 19234440 [Free]