The utility of PAX8 and IMP3 immunohistochemical stains in the differential diagnosis of benign, premalignant, and malignant endocervical glandular lesions.

UNLABELLED: Glandular lesions of the endocervix can be diagnostically challenging and occasionally the differential diagnosis includes endocervical adenocarcinoma in situ (EC AIS) and well-differentiated endocervical adenocarcinoma (ECA). PAX8 and IMP3 are two markers which have not been well studied in the endocervix. Our aim was to evaluate their immunohistochemical (IHC) expression in benign and malignant endocervical glandular lesions as well as to compare them to the traditionally used panel (Ki-67, p16, CEA). DESIGN: We searched our surgical pathology files for a cohort of benign endocervical glandular lesions as well as premalignant and malignant groups including EC AIS and ECA. An IHC panel consisting of PAX8, IMP3, Ki-67, p16, and CEA was performed on all cases. Immunoreactivity was scored on a degree of positivity (S0=no immunoreactivity, S1=up to 10% cells, S2=between 10 and 50% cells, S3=>50% cells) and intensity (Int0 - absent, Int1 - mild/faint, Int2 - moderate, Int3 - strong). RESULTS: PAX8 showed diffuse positivity (S3) with at least a moderate intensity of staining (Int2) in the benign group. PAX8 was focal (S1) in ECA and faint (Int1), compared to EC AIS, which was moderate (S2) and faint (Int1). IMP3 expression was focal in the benign group (S1), moderate (S2) in EC AIS and moderate-to-diffuse (S2-3) in ECA. IMP3 intensity was faint (Int1) in benign lesions, moderate (Int2) in EC AIS, and strong (Int3) in ECA. Significant Ki-67, p16, and CEA expression was noted in the premalignant/malignant cohort. CONCLUSION: PAX8 and IMP3 can be helpful in the differential diagnosis of benign vs. malignant endocervical glandular lesions. Our study, however, shows that there is some degree of overlap of staining in both the benign and malignant group. As such, PAX8 and IMP3 should always be interpreted with caution and in combination with the histomorphology.

Utility and Limitations of Albumin mRNA In Situ Hybridization Detection in the Diagnosis of Hepatobiliary Lesions and Metastatic Carcinoma to the Liver.

Albumin messenger RNA (mRNA) in situ hybridization is a sensitive and specific biomarker for hepatocellular carcinoma (HCC). Intrahepatic cholangiocarcinoma (ICC) shows variable sensitivity, whereas extrahepatic cholangiocarcinoma (ECC) and metastatic carcinoma are generally negative. We studied the clinical utility and limitations of albumin mRNA detection in a cohort of HCCs, ICCs, ECCs, bile duct adenomas, bile duct hamartomas, and metastatic carcinomas to the liver; and investigated the variability in sensitivity observed for this biomarker in ICCs. We identified 122 cases of hepatobiliary lesions and metastatic carcinomas. Albumin mRNA detection was performed using RNAscope run on formalin-fixed, paraffin-embedded tissue sections. ICCs were categorized according to the classification proposed by Hayashi and colleagues into the small duct, large duct, and indeterminate subtypes. Albumin mRNA was detected in all 17 HCCs and focally in 6/8 (75%) of bile duct adenomas. All 28 nonhepatic carcinomas, 13 bile duct hamartomas, and 9 ECCs were negative. Albumin mRNA was found in 38/47 (80.9%) of ICC with 35/37 (94.6%) in the small duct subtype, 2/3 (66.7%) in the indeterminate subtype, and 1/7 (14.3%) of the large duct subtype (P<0.003). Albumin mRNA detection is a sensitive and specific biomarker for HCCs. It is highly sensitive and moderately specific in the diagnosis of ICC with small gland morphology, but not ICCs with large duct morphology and in metastatic carcinoma. The variability in the sensitivity of albumin mRNA expression in ICCs may depend on the subtypes of ICC.

Expression and utility of IMP3 in the differential diagnosis of atypical glandular cells and adenocarcinoma in liquid-based cervical cytology.

BACKGROUND: Atypical glandular cell (AGC) interpretation in gynecological cytopathology presents many diagnostic challenges. We evaluated the expression of IMP3 in liquid-based cervical cytology and its utility in differentiating premalignant/malignant glandular lesions from benign/reactive processes. Additionally, we tried to determine whether IMP3 may be useful in differentiating among the types of uterine adenocarcinomas. DESIGN: Our cohort included 82 cases; 59 diagnosed with AGC and 23 with adenocarcinoma (Ac). IMP3 immunocytochemical stain was performed on ThinPrep slides and the results correlated with subsequent biopsy findings. IMP3 positivity was assessed by strong (2+ and 3+) granular cytoplasmic staining in at least one group of three epithelial cells. RESULTS: In the AGC group, IMP3 was positive in 14 (73.7%) of 19 cases that on histologic follow-up were confirmed Ac, and 39 (98.6%) of 40 non-glandular lesions/benign cases were negative. In the Ac group, IMP3 was expressed in 16 (69.6%) of 23 cases, of which 16 (72.2%) of 21 were uterine Ac. By combining the two groups, and excluding the 2 extrauterine carcinomas, IMP3 was positive in 30 (75%) of 40 uterine Ac, most of which (86.7%) were in situ/invasive endocervical Ac, and type II endometrial Ac (Papillary Serous and Clear Cell Carcinoma), and only 40% endometrioid Ac. CONCLUSION: In ThinPrep slides with AGC, IMP3 positivity predicts the presence of a significant endocervical or endometrial lesion on subsequent histology, and may also be a potential diagnostic tool useful in differentiating among the types of adenocarcinomas of the female lower genital tract.