Atypical papillary proliferation in gynecologic patients: a study of 32 pelvic washes.

Papillary clusters in gynecologic pelvic washes frequently cause diagnostic challenges because they can be associated with borderline or malignant ovarian tumors, as well as benign pelvic diseases. The objective of our study was to review all pelvic washes with atypical papillary proliferation (APP) and investigate whether cytomorphology and/or immunohistochemistry on cell block could determine their origin. Thirty-two pelvic washes from 31 patients containing APP were reviewed and correlated with their corresponding gynecologic or pelvic disease. Previously obtained cell blocks with immunohistochemical (IHC) stains were reviewed also. Nine of 32 washes (28%) were overcalled as malignant and were from patients with 5 borderline serous ovarian tumors (BSTO), 1 ovarian follicular cyst, 1 serous cystadenofibroma, and 1 endometrial carcinoma with ovarian seromucinous cystadenoma. BSTO and endometriosis were the most common sources of APP. Cell blocks could not discriminate further the etiology of APP. Immunohistochemistry was performed rarely and not fully contributory. Caution in interpreting papillary groups and cytohistological correlation is recommended to prevent a high false positive rate.

Aspiration biopsy of mammary lesions with abundant extracellular mucinous material. Review of 43 cases with surgical follow-up.

We reviewed 43 fine-needle aspiration biopsy (FNAB) smears with abundant extracellular mucinous material to determine whether accurate classification of mucinous lesions is achievable on FNAB: 26 had carcinoma (pure colloid carcinoma [CCA], 23; mixed CCA/invasive ductal carcinoma [IDC], 3); 17 had benign lesions on follow-up (benign MLL, 6; fibrocystic change [FCC], 6; myxoid fibroadenoma [MFA], 5). All carcinomas were identified correctly as malignant on FNAB. The initial cytologic diagnoses in benign cases were benign in 8, atypical in 8, and "suspicious" for carcinoma in 1. CCAs were moderate to markedly cellular with mild to moderate atypia and lacked oval bare nuclei. Marked nuclear atypia was confined predominantly to cases with mixed CCA/IDC. A distinct feature of CCA was thin-walled capillaries. FCCs and benign MLLs had overlapping cytologic features and showed variable cellularity and no or mild atypia. MFAs were markedly cellular with dyscohesion and variable atypia; stromal fragments and oval bare nuclei were present in every case. Mucinous lesions can be divided into 2 categories by FNAB: those that are adenocarcinomas and those that are not. CCAs have distinctive features that allow a definitive diagnosis on FNAB. Unnecessary surgery can be avoided in MFA by careful evaluation of smear characteristics. Cytologic features of FCC and MLL overlap. Owing to the documented association of MLL with carcinoma, we recommend that lesions that cannot be classified definitively as adenocarcinoma or MFA be considered for conservative excision, even in the absence of atypia.

Distinction of low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions based on quantitative analysis of proliferative activity.

The management of cervical dysplasia is determined by the grade of SIL (LSIL, conservative management; HSIL, ablative/excisional therapy). The grading, however, is subjective and its reproducibility is low. This study evaluates if quantitative differences in mitotic activity and MIB-1 expression (ME) in LSIL and HSIL are helpful in their discrimination. Twenty-seven cervical biopsies with LSIL and 16 with HSIL were immunostained for MIB-1. ME was evaluated in 100 contiguous cells of lesional squamous epithelium in basal layer, lower-third, middle-third, and upper-third, in areas with highest staining. Mitoses were counted in 10 contiguous high power fields in areas with the highest mitotic activity (mitotic index, MI). MI was significantly increased in HSIL (mean 27.5) as compared to LSIL (mean 14.3). MI at cut-off values < or =10 and > or =25, favored a diagnosis of LSIL, and HSIL, respectively. ME, in all four layers, was significantly greater in HSIL vs. LSIL. ME in the basal and the upper-third layer proved useful in grading SIL with equivocal MI: all LSIL cases with MI >10 had <30% of ME in the basal layer; and all, except one, had <30% of ME in the upper-third; all, except one HSIL cases with MI <25 had >30% of ME in either the basal or the upper-third layer. MI and ME (percentage) appear helpful in grading equivocal SIL cases.

Molecular events in the progression of recurrent respiratory papillomatosis to carcinoma.

CONTEXT: Identification of the type of human papillomavirus (HPV) by polymerase chain reaction and sequencing to determine coinfection or superinfection (by more than 1 HPV type) and other molecular events have not been reported in a series of patients exhibiting the morphologic spectrum of recurrent respiratory papillomatosis progressing to carcinoma. DESIGN: Four cases of juvenile-onset recurrent respiratory papillomatosis progressing to carcinoma (no history of smoking or irradiation in 2 cases) were studied. Morphologically distinct foci (squamous papilloma, pulmonary papillomatosis, squamous dysplasia subjacent to carcinoma, and squamous carcinoma) were subjected to laser capture microdissection and polymerase chain reaction amplification using general primers in addition to type-specific primers for HPV types 16 and 18. Direct sequencing of polymerase chain reaction products identified the type of HPV. The tissue sections were immunostained using antibodies to p53, pRb, p21(WAF1), and p16 proteins with a semiquantitative assessment. RESULTS: Human papillomavirus 11 was the only type of HPV identified in all lesions of all cases associated with recurrent respiratory papillomatosis. There was a marked increase in p53 protein expression in foci of dysplasia and carcinoma as compared to squamous papilloma and pulmonary papillomatosis. An inverse correlation between p53 and p21(WAF1) protein expression was noted in all lesions. pRb protein expression increased from the benign to the malignant end of the spectrum. p16 protein was expressed in all lesions. CONCLUSIONS: Infection by HPV-11 may be an early event associated with progression of recurrent respiratory papillomatosis to carcinoma. Increased expression of p53 and pRb proteins and a reduced expression of p21(WAF1) protein appear to be significant subsequent events.

Endometrial adenocarcinoma in situ in complex atypical hyperplasia: correlation with findings in subsequent hysterectomy specimen.

Well-differentiated endometrial adenocarcinoma can be difficult to distinguish from complex atypical hyperplasia (CAH) in a curettage or biopsy specimen. When a focus of back-to-back glands or cribriforming smaller than 2.1 mm is seen in a biopsy, we make a diagnosis of adenocarcinoma in situ (AIS). Whether this diagnosis translates into a more frequent diagnosis of carcinoma on the hysterectomy specimen is unknown. The objective of this study was to compare follow-up hysterectomy findings in biopsies showing AIS in CAH with biopsies showing only CAH without AIS. Twelve biopsy/curettage cases diagnosed as endometrial AIS in CAH and 12 biopsy/curettage cases diagnosed as CAH only were reviewed and correlated with corresponding hysterectomy material. A diagnosis of AIS was designated on biopsy/curettings when a focus of back-to-back glands or cribriforming less than 2.1 mm was present. Hysterectomy specimens showed endometrial carcinoma in 6 (50%) of 12 cases of CAH with AIS, and in 2 (17%) of 12 cases diagnosed as CAH only. Endometrial carcinoma with myometrial invasion was identified in 5 (42%) of the cases showing AIS on biopsy, but in none of the 12 cases diagnosed as CAH only on biopsy. Identification of AIS in CAH cases provides useful prognostic information.