Yuri Noda

Hepatocyte nuclear factor 4 alpha immunocytochemistry: A useful marker for detecting endocervical glandular lesions in alcohol‐fixed smears

AbstractBackgroundHepatocyte nuclear factor 4 alpha (HNF4α) contributes to tumorigenesis and cancer progression. This study evaluated the diagnostic potential of HNF4α for detecting endocervical glandular lesions (EGLs), including endocervical adenocarcinomas (ECAs), adenocarcinomas in situ (AIS), and lobular endocervical glandular hyperplasias (LEGH) using alcohol‐fixed cytological smears.MethodsHNF4α expression was immunocytochemically assessed in alcohol‐fixed smears and paired formalin‐fixed paraffin‐embedded tissue specimens obtained from 14 patients with histologically confirmed EGLs: eight papillomavirus‐associated (HPVA) ECAs, one non‐NHPVA ECA, two HPVA AIS, and three patients with LEGHs. Three cases of squamous cell carcinomas (SCCs) and two cases of non‐neoplastic lesions were also analyzed as non‐EGL controls. HNF4α positivity was defined as nuclear staining in one or more cell(s)/slide, regardless of intensity.ResultsHistologically confirmed EGL cases were cytologically diagnosed as four adenocarcinomas, eight atypical glandular cells, one misclassified atypical squamous cells of undetermined significance, and one misclassified SCC, with a sensitivity of 85.7% and specificity of 100%. Strong and diffuse nuclear HNF4α expression was observed in atypical glands in both smears and tissue specimens, whereas non‐neoplastic glands and non‐neoplastic/neoplastic squamous epithelium were HNF4α‐negative. HNF4α expression showed 73.7% concordance between tissue and smear samples. Notably, HNF4α immunocytochemistry demonstrated 100% sensitivity and specificity for detecting EGLs, outperforming cytomorphological or immunohistochemical diagnosis (sensitivity, 71.4%; specificity, 100%).ConclusionsHNF4α is a reliable diagnostic marker when using alcohol‐fixed smears, showing enhanced accuracy for EGLs detection regardless of human papillomavirus status. Immunocytochemical analysis of HNF4α in cervical smears can be used for EGL detection and early diagnosis of cervical cancer.

Hepatocyte nuclear factor 4α as a sensitive marker for uterine endocervical adenocarcinomas and their precursors

Hepatocyte nuclear factor (HNF)-4α is a marker of gastrointestinal tumor differentiation; however, its expression in endocervical tumors remains unclear. We aimed to assess the utility of HNF4α expression as a marker for endocervical adenocarcinomas (ECAs) and adenocarcinoma in situs (AISs), and to establish a minimal panel for distinguishing them from nonneoplastic endocervical glandular lesions and metastases. HNF4α expression was analyzed immunohistochemically (positive, H-score ≥10) in 323 tissue samples: 57 endocervical neoplasms including 35 glandular neoplasms and 22 squamous neoplasms, 144 nonneoplastic endocervical lesions, and 122 tumors from other organs. The panel for distinguishing endocervical glandular neoplasms from nonneoplastic glands and from metastases comprised HNF4α, p16, CDX2, and SATB2; staining was assessed. HNF4α was expressed significantly in ECAs and AISs, both HPV-independent and -associated types, but not in nonneoplastic glandular and squamous lesions (p < 0.05). The immunohistochemical detection sensitivity and specificity for endocervical ECA and AIS were 77% and 95%, respectively. For AIS alone, these were 79% and 94%, and for ECA alone, 75% and 94%, respectively. Either HNF4α(+) or p16(+) or double positive identified endocervical gland and squamous neoplasms (sensitivity, 96%; specificity, 76%). HNF4α(+) and SATB2(-) and CDX2(-) profiles suggested ECAs (sensitivity, 69%; specificity, 88%). HNF4α(+) and SATB2(+) or CDX2(+) profiles suggested adenocarcinomas of the gastrointestinal or genital tract (sensitivity, 81%; specificity, 88%). HNF4α is a promising marker for detecting both HPV-independent and -associated ECAs and AIS with high accuracy. Its combination with p16, CDX2, and SATB2 has potential use in diagnostic panels.

Small‐cell neuroendocrine carcinoma of the cervix accompanied by adenocarcinoma and high‐grade squamous intraepithelial lesion

AbstractFew cytological reports have described small‐cell neuroendocrine carcinoma (SCNEC) in the female genital tract. In the present study, we describe a cytological case of SCNEC accompanied by adenocarcinoma, as well as high‐grade squamous intraepithelial lesion (HSIL). A Japanese woman (42 years old) presented with abnormal genital bleeding. A conventional Papanicolaou smear revealed an inflammatory condition with three neoplastic components: SCNEC as irregular aggregates of neoplastic small round cells with nuclear molding and granular chromatin; adenocarcinoma as columnar cell clusters with peripherally located large nuclei, and HSIL as sheets or clusters of dysplastic basal‐type squamous cells with irregular hyperchromatic nuclei. Accordingly, a cytodiagnosis of SCNEC with adenocarcinoma and HSIL was made. Owing to the rarity of cervical SCNEC, cytological diagnosis may be difficult. Due to its aggressive clinical behavior, the presence of an SCNEC component should be verified in any cytodiagnosis of adenocarcinoma or HSIL.