Can We Tell the Site of Origin of Metastatic Squamous Cell Carcinoma? An Immunohistochemical Tissue Microarray Study of 194 Cases
SM Share, TC Pereira, EP Conroy, AV Magalhaes, JF Silverman. Allegheny General Hospital, Pittsburgh, PA; Universidade de Brasilia, Brasilia, Brazil
Background: In the work-up of metastatic squamous cell carcinoma (SCC), commonly used immunohistochemical (IHC) markers such as K903, p63, and CK5/6 help to confirm a squamous malignancy, but the IHC stains do not determine the primary site of origin. Moreover, unlike adenocarcinoma, IHC has not been well studied in the work-up of metastatic SCC of unknown primary. We compared the specificity of commonly used IHC markers known to support specific tissue sites, including TTF-1, CK 7, CK 20, Villin, p16, and CDX-2, to the commonly used squamous IHC markers, K903, CK 5/6, and p63.
Design: Using a tissue microarray, we compared 194 SCC cases from the following sites as follows: 35 lung, 34 skin, 14 cervix, 4 vagina, 16 vulva, 8 penis, 9 anus, 3 rectum, 10 esophagus, 4 bladder/urethra, and 57 head and neck (4 eye/orbit, 2 parotid gland, 19 tongue, 10 tonsil, 5 oral cavity, 4 pharynx, and 13 larynx). All IHC stains were interpreted to be positive if 5% or more of the malignant cells were positive, regardless of the staining intensity.
Results: p63, and K903 stained positively in 100% of cases, and CK 5/6 in nearly 100% of cases of SCC, with the exception of 2 lung SCC. TTF-1 staining was seen only in 2 of 35 lung SCC, and was negative in all other sites. Positive staining for CK 7 ranged from 12.5% in esophagus and anus to 100% in vagina. CK 20 was positive in 3.1% of lung SCC, and was negative in all other sites. CDX-2 was positive in 7.1% of vulva SCC, and was negative in all other sites. Positive staining for p16 ranged from 21.4% in vulva SCC to 75% in vagina and anus, and was negative in lung, penis, bladder/urethra, and head and neck sites other than the oral cavity. Villin was negative in all cases.
Conclusions: Although commonly used SCC markers are very sensitive and specific, they do not help identify the primary site of tumor origin. TTF-1 showed marked specificity for lung SCC, but had very low sensitivity. P16 showed high sensitivity for GYN, anal, and oral cavity primaries, but exhibited low specificity. CDX-2 was found to be positive only in some vulvar SCC, and CK 7 was negative in SCC from the penis and oral cavity. We conclude that the primary site of SCC cannot confidently be determined by IHC alone, but certain site specific IHC markers can help in identifying the primary site in occasional cases.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 258, Monday Morning