Papillary Immature Metaplasia of the Uterine Cervix - A Histopathological Revisit and Consideration for Cell of Origin

초록

Background: Papillary immature metaplasia (PIM) of uterine cervix is characterized by filiform papillary growth and partial loss of maturation. It has been considered as a variant of LSIL because of frequent association with HPV 6 and 11, but is frequently misdiagnosed as papillary squamous cell carcinoma, condylomatous carcinoma, or HSIL. Since there are only a few literature describing this entity, its clinical and histopathologic features are not well recognized. We had a few questions abut PIM, including HPV status, clinicopathological differences between PIM and conventional LSIL and HSIL, and the cell of origin. Design: To answer the questions, we reviewed clinical and histopathologic findings of 21 PIMs, and compared the results of histochemical and immunohistochemical expressions to those of normal and abnormal cervical epithelial lesions. HPV status were analyzed by HPV DNA chips, which was designed to detect 40 HPV subtypes, and negative cases were confirmed by PCR. Results: Histologically, most cases formed exophytic papillary lesions (81%), but a few cases showed flat topped plaque with downward epithelial proliferation (19%). The cells were composed of variable proportion of basaloid and squamoid cells in all cases, and all contained variable amount of mucin secreting epithelium within the lesion. 52% showed localized koilocytosis. Seven were associated with HSIL; two in the previous conization, and five in the adjacent mucosa. P16 immunostaining showed non-block positivity in all cases, except in the associated HSIL. They were associated with HPV 6 (n=3), 11 (n=7), 16 (n=1), 16/18 (n=1), but nine were HPV negative on HPV DNA chips, which were confirmed by PCR. All the cases showed basal or parabasal expression of CK17 (reserve cel marker) in contrast to uniform negativity in LSIL. 91 % showed top heavy expression pattern (91%) for CK 7 in contrast to the negativity (94%) in LSIL. Conclusions: PIM is basically derived from columnar cells having metaplastic potential in the squamocolumnar junction, which was differentiated into reserve cells, and then toward immature and mature squamous epithelium. In contrast, LSIL appears to be a cellular change occurring in mature squamous epithelium. Cellular proliferation of PIM could be induced by HPV infection of both low and high risk HPV, but it is not necessarily associated with concurrent HPV infection. Association of HSIL in adjacent mucosa of PIM in some cases suggested a potential to progress from PIM to HSIL.