College of American Pathologists
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  Anatomic Abstracts





May 2011

Michael Cibull, MD
Melissa Kesler, MD
Rouzan Karabakhtsian, MD
Megan Zhang, MD

Alternate mucoid and hyalinized stroma in clear cell carcinoma of the ovary Alternate mucoid and hyalinized stroma in clear cell carcinoma of the ovary

The stroma in ovarian clear cell carcinoma often shows alternate mucoid and hyalinized change. The hyalinized stroma is recognized to be an aberrant deposition of basement membrane material produced by tumor cells. The mucoid stroma, on the other hand, has drawn far less attention, and its significance remains unclear. The authors examined 60 ovarian clear cell carcinomas for the distribution and nature of the mucoid stroma. For comparison, they examined 125 other surface epithelial ovarian tumors. Twenty-nine of 60 (48 percent) clear cell carcinomas showed a mucoid stroma, either focally (21 cases) or diffusely (eight cases). The mucoid stroma in clear cell carcinomas was distinct from that in other surface epithelial tumors in that it showed a compact spherule-like appearance. It also exhibited a cribriform pattern resembling that of adenoid cystic carcinoma. It was rarely associated with stromal cells, despite the presence of abundant glycosaminoglycan, including hyaluronan. Alternatively, it was strongly associated with hyalinized stroma. Among 40 clear cell carcinomas that had at least one type of stroma, 26 (65 percent) had both, either concomitantly or separately. The mucoid stroma tended to attenuate if the hyalinized stroma developed. In vitro, a clear cell carcinoma cell line, HAC-2, formed a spherule-like structure containing hyaluronan in the center, and a significant amount of hyaluronan was detected by latex agglutination immunoturbidimetry. This indicates that HAC-2 has the potential to produce hyaluronan. These findings show that the spherule-like mucoid stroma and hyalinized stroma represent different phases of the stromal remodeling process, which is promoted by the deposition of different extracellular matrices produced by clear cell carcinoma cells. The spherule-like mucoid stroma and hyalinized stroma are considered complementary diagnostic signatures of ovarian clear cell carcinoma.

Kato N, Takeda J, Fukase M, et al. Alternate mucoid and hyalinized stroma in clear cell carcinoma of the ovary: manifestation of serial stromal remodeling. Mod Pathol. 2010;23:881–888.

Correspondence: Dr. N. Kato at
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STIC upregulates markers associated with high-grade serous carcinomas STIC upregulates markers associated with high-grade serous carcinomas

Serous tubal intraepithelial carcinoma has been proposed as a precursor for many pelvic high-grade serous carcinomas. The authors’ previous analysis of the ovarian cancer genome identified several genes with oncogenic potential that are amplified or overexpressed, or both, in the majority of high-grade serous carcinomas. Determining whether these genes are upregulated in serous tubal intraepithelial carcinomas (STICs) is important in further elucidating the relationship between STICs and high-grade serous carcinomas. It is also fundamental in understanding the molecular pathogenesis of high-grade serous carcinomas. The authors conducted a study in which they obtained 37 morphologically defined STICs from 23 patients with stage IIIC/IV high-grade serous carcinomas. Both the STICs and the high-grade serous carcinomas were analyzed for expression of Rsf-1 (HBXAP), cyclin E, fatty acid synthase (FASN), and mucin-4. They were also examined for expression of established markers, including p53, Ki-67, and p16. The authors found that diffuse nuclear p53 and p16 immunoreactivity was observed in 27 of 36 (75 percent) and 18 of 33 (55 percent) STICs, respectively, whereas an elevated Ki-67 labeling index (10 percent or greater) was detected in 29 of 37 (78 percent) STICs. Cyclin E nuclear staining was seen in 24 of 35 (77 percent) STICs, whereas normal tubal epithelial cells were all negative. Increased Rsf-1 and FASN immunoreactivity occurred in 63 percent and 62 percent of STICs, respectively. Interestingly, only one STIC showed increased mucin-4 immunoreactivity. Carcinomas, when compared with STICs, overexpressed p16, Rsf-1, cyclin E, and FASN in a higher proportion of cases. The authors concluded that STICs express several markers, including Rsf-1, cyclin E, and FASN, in high-grade serous carcinomas. In contrast, mucin-4 immunoreactivity does not change or is reduced in most STICs. These results suggest that overexpression of Rsf-1, cyclin E, and FASN occurs early in tumor progression.

Sehdev AS, Kurman RJ, Kuhn E, et al. Serous tubal intraepithelial carcinoma upregulates markers associated with high-grade serous carcinomas including Rsf-1 (HBXAP), cyclin E and fatty acid synthase. Mod Pathol. 2010;23:844–855.

Correspondence: Dr. Ie-Ming Shih at
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Warty-basaloid carcinoma: features of a distinctive penile neoplasm Warty-basaloid carcinoma: features of a distinctive penile neoplasm

Most penile cancers are squamous cell carcinomas, but several subtypes have differing clinicopathologic, viral, and outcome features. The authors presented 45 cases of a distinctive morphological variant of penile squamous cell carcinoma composed of mixed features of warty and basaloid carcinomas. This tumor was recognized in a recent viral study and showed a strong association with human papillomavirus infection. However, its clinicopathologic features are not well known. Patients in the authors’ multi-institutional study were a mean age of 62 years. Most tumors (64 percent) invaded multiple anatomical compartments, including glans, coronal sulcus, and particularly, inner foreskin mucosa. Tumor size ranged from 2 to 12 cm (mean, 5.5 cm). Three morphological patterns were recognized. The most common, which was observed in two-thirds of the cases, was that of a typical condylomatous tumor on surface and basaloid features in deep infiltrative nests. In 15 percent of the cases, there were nonpapillomatous invasive carcinoma nests with mixed basaloid and warty features. Less commonly, there were tumors that were predominantly papillomatous. Invasion of penile erectile tissues was frequent and involved either corpus spongiosum or cavernosum (47 percent each). Tumors limited to lamina propria were rare. Most tumors were of high grade (89 percent). Vascular and perineural invasion were found in about one-half and one-quarter of cases, respectively. Associated penile intraepithelial neoplasia was identified in 19 cases and mostly showed basaloid, warty-basaloid, or warty features. Inguinal nodal metastases were found in 11 of 21 patients with groin dissections. Invasion of corpora cavernosa, high histological grade, and presence of vascular/perineural invasion were more prevalent in metastatic cases. In 21 patients who were followed, the cancer-specific mortality rate was 33 percent, with a mean survival time of 2.8 years. The authors concluded that warty-basaloid carcinomas are morphologically distinctive human papillomavirus-related penile neoplasms that, like basaloid carcinomas, are biologically more aggressive than typical warty carcinomas, from which they should be distinguished.

Chaux A, Tamboli P, Ayala A, et al. Warty-basaloid carcinoma: clinicopathological features of a distinctive penile neoplasm. Report of 45 cases. Mod Pathol. 2010;23:896–904.

Correspondence: Dr. A. L. Cubilla at
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.