Neuroendocrine differentiation in cervical carcinoma.

Abstract

Aims-To examine neuroendocrine differentiation, as shown by chromogranin A (CGA) expression, in cervical carcinomas. Methods-Sixty seven cervical carcinomas were studied and were classified as adenocarcinomas, adenosquamous carcinomas or squamous cell carcinomas based on the assessment of haematoxylin and eosin staining and stains for mucin. Where features of glandular differentiation were identified, sections were also stained for evidence of intestinal type mucin. CGA immunostaminig was done and the results were graded on a three point scale: 0, + (1-5% of cells positive) and + + (>5% of cells positive). These findings were then analysed with respect to lymph node status, tumour differentiation and clinical outcome. Results-There were 32 adenocarcinomas, 18 adenosquamous carcinomas and 17 squamous cell carcinomas. Positive staining was seen in 14 (20X9%) cases, of which four were strongly positive. All but one case were either adenocarcinomas or adenosquamous carcinomas. There was a trend for CGA positivity to be related to intestinal differentiation but this failed to reach statistical significance. No correlation could be demonstrated between CGA staining and lymph node status, tumour differentiation and clinical outcome. Conclusions-Neuroendocrine differentiation is common in cervical carcinomas where there is evidence of glandular differentiation. Whilst the numbers in this study are relatively small, the presence of neuroendocrine cells in otherwise typical carcinomas does not seem to have any association with clinical behaviour. Neuroendocrine differentiation in carcinomas of the cervix is unusual, but is well recognised. It is seen in neoplasms ranging from well differentiated carcinoid tumours to poorly differentiated small cell carcinomas. These tumours morphologically resemble their counterparts at other sites ofthe body-for example, in the gastrointestinal tract and lung. Isolated neuroendocrine cells are, however, also present in the common types of cervical carcinoma, but are not evident on routine haematoxylin and eosin preparations.'Sixty seven cases of cervical carcinoma were studied to elucidate: (1) the prevalence of Cases showing features of glandular differentiation were also stained with PB/KOH/PAS to identify the presence ofintestinal type mucin.3Immunostaining was performed using a standard avidin biotin complex (Dako, High Wycombe, UK) alkaline phosphatase technique. A rabbit antihuman monoclonal antibody to chromogranin A (Dako) was supplied at a concentration of 3 g/l in a solvent of 0O1 NaCl and 15 mM NaNz and was used at a dilution of 1 in 50 in Tris buffered saline.Incubation was performed for 50 minutes at room temperature. Positive and negative controls were used throughout.The presence of diffuse cytoplasmic staining was assessed. Positivity was graded on a three point scale: 0, + and + + for no positivity, positivity in 1-5% cells and positivity in >5% of cells, respectively. The presence or absence of cytoplasmic staining in the adjacent normal endocervical columnar an...

Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions: a possible link between lobular endocervical glandular hyperplasia/pyloric gland metaplasia and ‘adenoma malignum‘

“…In fact, some reports described CGA-positive cells in intestinal-type adenocarcinomas of the cervix. 15,16 Recent studies have demonstrated that p16 INK4 immunohistochemistry is of diagnostic value for high-risk human papillomavirus (HPV)-related conditions including squamous intraepithelial lesions (SIL). 17 This protein is overexpressed as a consequence of incorporation of E7 derived from high-risk HPV, and it has been shown to be positive in invasive and in situ adenocarcinomas of the cervix, most of which are also considered to be HPV related.…”

Neuroendocrine differentiation in a case of cervical cancer

“…Savargaonkar et al reported that neuroendocrine differentiation was present in 20.9% of his series study of cervical carcinoma [5].…”

“…Almost all neuroendocrine carcinomas of the cervix are associated with HPV 18 or seldom HPV 16 [4]. Neuroendocrine carcinomas most likely develop from neuroendocrine cells occurring in the normal endocervix or from stimulated multipotential reserve cells of the endocervical epithelium undergoing neuroendocrine metaplasia and hyperplasia [5]. Neuroendocrine tumors of uterine cervix are divided into small and large cell type as well as carcinoid and atypical carcinoid [3].…”

A rare variant of carcinoma of the cervix: neuroendocrine tumour

“…9 Savargaonkar et al reported that neuroendocrine differentiation was present in 20.9% of his series study of cervical cancer. 5 Clinically, abnormal vaginal bleeding is the most commonly reported symptom.…”

“…4 It develops from neuroendocrine cells in the normal endocervix or from stimulated multipotent reserve cells of endocervical epithelium undergoing neuroendocrine metaplasia & hyperplasia. 5 Neuroendocrine tumours is divided into well differentiated (carcinoid and atypical carcinoid) and poorly differentiated (small cell & large cell). 3 tumours.…”