Papillary Immature Metaplasia of the Uterine Cervix: a Report of 5 Cases with an Emphasis on the Differential Diagnosis from Reactive Squamous Metaplasia, High-Grade Squamous Intraepithelial Lesion and Papillary Squamous Cell Carcinoma

Abstract

Papillary immature metaplasia (PIM) is a distinctive exophytic lesion of the uterine cervix and shares some histologic and cytologic features with ordinary squamous metaplasia (SM), atypical immature squamous metaplasia (AIM), high-grade squamous intraepithelial neoplasia (HSIL) and papillary squamous cell carcinoma (PSC). PIM has been suggested to be a subset of condyloma associated with low-risk type human papilloma virus (HPV), however, the etiologic role of HPV and biologic behavior of the disease are still elusive. We compared the clinical and histopathological findings, immunohistochemical expression of Ki-67 and p53 protein, and HPV typing of 5 cases of PIM with SM (n=9), HSIL (n=6), and PSC (n=4) to know the helpful features for the differential diagnosis. Histologically, all 5 cases showed a papillary proliferation of immature metaplastic cells involving the proximal transformation zone and endocervix. On HPV typing by polymerase chain reaction-restriction fragment length polymorphism, 2 out of 5 PIM were confirmed to have HPV 6 or HPV 11, while 2 out of 4 PSC were proved having HPV 31 and HPV 16 each. Ki-67 labeling index and mitotic index of PIM were significantly lower than those of HSIL or PSC. There were no significant differences of Ki-67 labeling index and mitotic index between PIM and SM. The expression of p53 varied among the groups and thus it was not helpful for the differential diagnosis.

Thin-Layer Cytology Findings of Papillary Adenosquamous Carcinoma of the Cervix

“…[17][18][19][20]22,23 As for papillary squamotransitional cell carcinoma, studies so far have demonstrated a strong association with HPV type 16. [25][26][27][28] The identification of HPV type 16 DNA in the present example may also suggest further histogenetic links with papillary squamotransitional cell carcinoma. Molecular analysis of a larger collection of cases is needed in order to verify this postulate.…”

Papillary squamous intraepithelial lesions of the uterine cervix: human papillomavirus-dependent changes in cell cycle expression and cytologic features

“…In other studies, the HPV DNA detection rate in such "immature-looking" papillary lesions ranged from 40% to 83% [1,2,5,13]. The variation in HPV detection rate has been interpreted to be the result of a reduction in viral replication and assembly in immature epithelium [2,5], because in lowrisk HPVs, DNA replication has a close relationship to keratinocytic differentiation [4].…”

“…The formerly accepted method was to rely on some universal morphological features, such as uniform nuclear size and spacing, minimal nuclear overlap, low mitotic index, and the preservation of overlying columnar cell layers (for lowgrade lesions) and disorganized epithelial alignment against the basement membrane (for high-grade lesions) [2][3][4]. For lesions with equivocal histologic features, several studies showed that HPV typing and Ki-67 labeling index (LI) are helpful [2,4,5]. However, most of these studies were based on a morphology-and-then-HPV sequence; we know that morphology per se is somewhat subjective, and we have learned from flat lesions that the morphology of an SIL does not correspond perfectly to its HPV type.…”

Papillary Squamous Cell Carcinoma of the Uterine Cervix, High-Risk Human Papilloma Virus Infection and p16INK4a Expression

“…3,4 On the other hand, in 4 cases, a study observed DNA HPV type 31 50% of the time and observed the p53 not to be of great utility in distinguishing from other lesions, including benign ones. 9,10 However, the Ki-67 cellular proliferation marker seems to have greater expression in cases of papillary carcinoma than in condylomas, 11 as do p63 and p16 markers. 12 The high-risk HPV present in this case report adds to the findings of other authors in demonstrating its importance in the oncogenesis of this tumor, as well as that the expression of p16 INK4a can be linked to the role of the virus and its oncogenetic path.…”