Role of immunohistochemistry in problematic cervical biopsies

Abstract

Cervical histopathology remains the gold standard for final diagnosis of cervical pathology. A wide variety of benign and malignant tumours, as well as non-neoplastic tumour-like conditions, can be diagnosed by light microscopic examination. In recent years, immunohistochemical techniques have been found useful to assist in the differential diagnosis of cervical lesions. For histological typing of cervical tumours, certain lineage markers are useful in the differential diagnosis of lesions of epithelial, stromal, smooth muscle, lymphoid, melanocyte or trophoblastic origins. Immunohistochemistry is particularly valuable in distinguishing metastatic and primary carcinomas in the uterine cervix and ascertaining origin of metastatic carcinoma in difficult clinical scenarios involving the uterine cervix. Immunohistochemical markers, such as oestrogen receptor, carcinoembryonic antigen and p16, help distinguish between a cervical adenocarcinoma and an endometrial adenocarcinoma of endometrioid type. The distinction between a large cell neuroendocrine carcinoma and a poorly differentiated squamous or adenocarcinoma may be problematic. Markers for neuroendocrine differentiation, such as chromogranin, synaptophysin, and CD56 may be useful. On the other hand, p63 is useful in distinguishing small cell neuroendocrine carcinoma from small cell squamous carcinoma and in confirming that a poorly differentiated carcinoma is squamous in type. The diagnostic and prognostic value of protein products of oncogenes and tumour suppressor genes, as well as proliferation and apoptosis markers is also gaining importance. MIB1 and p16 are particularly useful in the assessment of pre-invasive cervical squamous and glandular lesions. CD10 is suggested to be a marker of mesonephric lesions. Since molecular targeted therapy of cervical cancer is relatively less established compared with other gynaecological cancers, the role of immunohistochemistry in such clinical application is less explored. On the other hand, diagnosis of an infectious disease in the uterine cervix is also important. Besides special histochemical stains, antibodies against viral protein including human papilloma virus and cytomegalovirus have been found useful to assist diagnosis. Such information will permit greater diagnostic accuracy and tailoring of treatment regimens in an individual patient. Pathologists and gynaecologists should bear in mind that no marker is specific and interpretation of any findings derived from adjunct laboratory techniques must be employed in conjunction with the morphologic and clinical findings.