Mullerian adenosarcomas: an immunophenotypic analysis of 35 cases.

Mullerian adenosarcomas (MAs) are rare mixed mesenchymal and epithelial neoplasms that occur most commonly in the uterus. Although the epithelial component is typically benign, the mesenchymal component of most adenosarcomas morphologically resembles that observed in endometrial stromal tumors and is responsible for their clinical behavior. Thus, the differential diagnosis usually includes not only low-grade endometrial stromal tumors, but also adenofibroma, carcinosarcoma, and embryonal rhabdomyosarcoma especially in small samples. The objective of this study was to ascertain the immunophenotypic profile of the epithelial and mesenchymal components of MAs and delineate possible differences between conventional mesenchymal areas and areas of sarcomatous overgrowth. Representative sections from 35 MAs, 28 of them without sarcomatous overgrowth (MA-NSO) and 7 with sarcomatous overgrowth (MA-SO), were included in the study. Thirty tumors arose in the uterus, 4 were pelvic, and 1 originated in the colon. Adequate blocks were selected and immunostained for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), CD10, WT1, smooth muscle actin, desmin, AE1/3 cytokeratin, CD34, calretinin, inhibin, c-kit, and Ki-67. The mesenchymal component expressed ER in 21/27 MA-NSOs but in only 1/7 MA-SOs (65% overall). PR was expressed in 21/26 MA-NSOs and 4/7 MA-SOs (76% overall), whereas AR was positive in 10/27 MA-NSOs and 5/7 MA-SOs (35% overall). CD10 was expressed in 23/28 MA-NSOs but in only 2/7 MA-SOs (71% overall), and WT1 positivity was seen in 22/27 MA-NSOs and 6/7 MA-SOs (79% overall). Sixty-seven percent of MAs expressed smooth muscle actin, 32% desmin, including both examples of MA-SOs with rhabdomyoblastic differentiation, and 25% expressed AE1/3 cytokeratin. CD34 expression was found in 35% of the tumors, but it was almost always patchy in distribution and weak in intensity, as was calretinin expression, seen only in 12% of the cases. Expression of c-kit and inhibin in greater than 5% of the tumor cells was not encountered. The median and mean Ki-67 labeling indices were 10% and 12%, respectively (range, <5% to 40%). The median and mean Ki-67 indices were both 5% in MA-NSOs compared with 30% and 28%, respectively, in MA-SOs. The epithelial compartment demonstrated expression for ER (24/32), PR (23/31), and AE1/3 cytokeratin (33/33); rare cases expressed CD10 (4 cases) and AR (1 case). In summary, the immunophenotype of most MAs resembled that of endometrial stromal tumors (positive for ER, PR, WT1, and CD10, with variable expression of muscle markers, AR and cytokeratin). The proliferative rate in the stromal component was strongly related to the presence of sarcomatous overgrowth. ER, PR, and CD10 expression was lost in MA-SOs relative to conventional low-grade stromal areas of mullerian/mesodermal adenosarcomas, reflecting the "dedifferentiation" of this component.

Difficulties in assessing the depth of myometrial invasion in endometrial carcinoma.

The depth of myometrial invasion (DMI) is one of the most important prognostic indicators and determinants of therapy in endometrial cancer. There are well-documented problems in recognizing DMI. We examined 100 previously diagnosed endometrioid endometrial carcinomas in hysterectomy specimens, reassessed DMI, and explored morphological features that complicated appraisal of myometrial invasion. The DMI was different from the original measurement in 29% of cases. Twelve percent of all cases (40% of cases with measurement discrepancies) involved differences in the assignment of invasion categories (noninvasive, < or =50% myometrial invasion, and >50% myometrial invasion). Nearly all endometrial cancers originally diagnosed as invasive were considered noninvasive on review. We examined whether the distribution of stromal metaplasia, noninvasive patterns (exophytic tumors, irregular endomyometrial junctions, and adenomyosis), and myometrial invasion patterns were different in cases with and without measurement discrepancies. Irregular endomyometrial junctions, exophytic tumors, and adenomyosis tended to coexist and were more common in the cases with DMI discrepancies. Although there seemed to be a relationship between smooth muscle metaplasia and exophytic tumors, it did not appear that smooth muscle metaplasia was significantly more common in cases with measurement difficulties. However, cases with extensive smooth muscle metaplasia posed problems with assessment of myometrial invasion. Patterns of myometrial invasion other than the conventional destructive pattern were sufficiently uncommon as to not impact on DMI measurement in large numbers of cases. Measuring the DMI is usually uncomplicated, but additional scrutiny should be paid to cases involving exophytic tumors, irregular endomyometrial junctions, adenomyosis, and extensive stromal smooth muscle metaplasia.

Criteria for the diagnosis of fibroepithelial lesions of the breast with liquid-based cytology.

OBJECTIVE: To establish diagnostic criteria for diagnosing and differentiating fibroepithelial lesions of the breast on ThinPrep (Cytyc Corp., Boxborough, Massachusetts, U.S.A.). STUDY DESIGN: Eighty-four fibroepithelial lesions were sampled by ultrasound-guided aspiration biopsy. Based on smears and histologic correlates, there were 55 fibroadenomas, 26 papillary neoplasms and 3 phyllodes tumors. The ThinPrep slides for each sample were reviewed retrospectively and evaluated for specific morphologic and cytologic features. RESULTS: On ThinPrep slides, 95% of the fibroadenomas had a predominance of single myoepithelial nuclei, 89% had staghorn clusters, and 47% had myxoid stroma. Among the papillary neoplasms, 8% had a predominance of single columnar ductal cells, 31% had papillary groups, 23% had vessels, and 27% had collagenous spherulosis. The ThinPrep preparations of the phyllodes tumors showed that 67% had single myoepithelial nuclei, 33% had a predominance of single ductal cells, 67% had staghorn clusters, and 0% had myxoid stroma. A majority of the fibroadenomas and the papillary neoplasms showed mild to moderate ductal epithelial hyperplasia. A majority of the phyllodes tumors showed moderate ductal epithelial hyperplasia. CONCLUSION: Fibroepithelial lesions of the breast can be accurately differentiated using ThinPrep samples based on the evaluation of specific cytologic and morphologic features, including the presence of staghorn clusters, fibromyxoid stroma, vessels, collagenous spherulosis, papillary clusters and predominance of myoepithelial nuclei or columnar cells in the background. However, the degree of ductal epithelial hyperplasia does not aid in the diagnosis.