Pacita Keh

Urogenital sinus origin of mucinous and ciliated cysts of the vulva.

The origin of mucinous and ciliated cells in the vulva and the pathogenesis of cysts lined by these epithelia were investigated. Small mucinous glands numbering from one to more than a hundred were encountered in 9 of 19 vulvas (53%) that were consecutively examined at autopsy. Eleven other cysts were encountered clinically. Six were lined by mucinous epithelium, three by pseudostratified cells with cilia plus small foci of mucinous epithelium, and two by ciliated epithelium only. Four of the cysts with ciliated epithelium were otherwise typical Bartholins gland cysts. It is concluded that glands lined by either mucinous or ciliated epithelia are normal constituents of the vulvar vestibule, are derived from urogenital sinus, and develop into cysts when the neck leading to the vulvar surface becomes inflamed and obstructed.

HMGA2: A Potential Biomarker Complement to P53 for Detection of Early-stage High-grade Papillary Serous Carcinoma in Fallopian Tubes

Before high-grade papillary serous carcinoma (HG-PSC) becomes invasive, it is believed to be a poorly defined short-lived precursor lesion. A recent characterization of serous tubal intraepithelial carcinoma (STIC) and of the p53 signature suggested that HG-PSC may follow a stepwise progression on cellular and molecular levels. High-mobility group AT-hook 2 (HMGA2), an oncofetal protein, is overexpressed in ovarian cancer. To test whether HMGA2 can be another valuable marker for STIC, we examined HMGA2 expression in 3 groups of patients: (1) 24 patients with STIC and its invasive counterpart, HG-PSC of the fallopian tubes, (2) 24 patients with HG-PSC of the ovaries but without STIC (positive control), and (3) 30 patients with cancer and normal fallopian tubes (negative control). We found that HMGA2 was overexpressed in 75% of patients with STIC, was coexpressed with p53 in more than 50% of patients, and was completely negative in the secretory cells of the 30 patients with normal fallopian tubes. Among 7 patients with cells negative for p53 staining, HMGA2 was positive in 5; among 6 patients whose tumor cells were negative for HMGA2 in STIC, 3 were positive for HMGA2 in the invasive component; about 70% of invasive HG-PSC tumor cells were immunoreactive for both HMGA2 and TP53. In invasive carcinoma, HMGA2 overexpression was correlated with p53 (r=0.45), indicating the role of HMGA2 in p53 mediated tumor progression. Our findings of immunoreactivity for HMGA2 may lead to a novel, useful biomarker to complement p53 in the detection of early-stage serous carcinoma.

Signet-Ring Cell Change Versus Signet-Ring Cell Carcinoma: A Comparative Analysis

Signet-ring cell change (SCC) is a nonneoplastic condition that morphologically simulates signet-ring cell carcinoma (SRCA). The few case reports on SCC have focused on morphologic characteristics in distinguishing benign from malignant. In biopsy specimens, however, SCC can be easily confused with SRCA, which often demonstrates innocuous cytologic features. The object of this study is twofold: 1) to report 14 additional cases of SCC, comparing their morphologic and phenotypic features with that of SRCA; and 2) to evaluate the incidence of SCC in pseudomembranous colitis. Paraffin sections of biopsy or resection specimens containing focal or extensive SCC and 5 cases of colonic SRCA were stained with hematoxylin and eosin, periodic-acid Schiff stain with and without diastase digestion, and by standard ABC immunoperoxidase procedure using antibodies to E-cadherin, p53, and Ki-67. Both cells in SCC and SRCA were strongly positive for neutral mucins. Cells in SCC were strongly positive for E-cadherin and negative for p53 and Ki-67. In contrast, cells in SRCA were strongly positive for p53, exhibited high proliferation, and demonstrated absent or weak positivity for E-cadherin. Although SCC is not well recognized in pseudomembranous colitis, the incidence is fairly high: 14 of 50 (28%) cases showed variable numbers of signet-ring cells. Extensive SCC, although rare, can occur in different clinical conditions and can be easily mistaken for SRCA. When in doubt, routine immunohistochemical stains such as p53, Ki-67, and E-cadherin can help to differentiate SCC from SRCA.

Squamous cell dysplasia and carcinoma in situ of the cervix and vagina after prenatal exposure to diethylstilbestrol.

Squamous cell abnormalities of the vagina and cervix were evaluated in 1424 women exposed to diethylstilbestrol (DES) in utero. The prevalence of dysplasia was 2.1% and the incidence 0.85/100 person-years of followup. The dysplastic epithelial changes were almost always mild in women with no prior history of dysplasia and was slightly more frequent in the cervix than the vagina. Severe dysplasia and carcinoma in situ (CIS) were encountered only in those subjects specifically referred because of those abnormalities. The most common problem in the diagnosis of these squamous cell changes was the misinterpretation of mature and immature metaplastic cells for dysplastic squamous cells. Discordance between biopsy and cytology was common-place in the detection and followup of dysplasia, especially when it was mild. There were no instances in the study where cytology and biopsy samples from the vagina were both abnormal concurrently. Colposcopically directed biopsies did not increase the frequency of confirmation of cytologic findings. These data suggest that both cytology and biopsy of abnormal segments of the vagina and cervix remain an integral part of the examination of the DES-exposed female during long-term follow-up studies.

Histologic and immunohistochemical analyses of endometrial carcinomas: experiences from endometrial biopsies in 358 consultation cases.

CONTEXT Uterine serous carcinoma is biologically more aggressive than the endometrioid carcinoma. Because uterine serous carcinoma has a high propensity for lymphovascular invasion and intraperitoneal and extra-abdominal spread, accurate diagnosis of this tumor type in endometrial biopsies/curettings is critical for appropriate clinical management. OBJECTIVE To share our experience in the evaluation of endometrial biopsy specimens in type I and type II endometrial adenocarcinoma. DESIGN We retrospectively reviewed 358 biopsies containing endometrial carcinoma during a recent 3 year period of our consultation records. In cases in which our interpretation differed from the submitting diagnosis, a panel of immunostains was performed. The performance characteristics of each antibody in our panel was calculated in this group of challenging cases. RESULTS Among the endometrial carcinomas we examined, a diagnosis of type I carcinoma accounted for 91% of cases (327 of 358) and type II carcinoma for 9% of cases (31 of 358); 41 cases (11.5%) were ambiguous or discordant (differing from submitted diagnoses and reviewed) based on histology alone. All 41 ambiguous and discordant cases were further evaluated with a battery of immunohistochemical markers. Of the 41 cases, 36 (88%) were ultimately classified (10 cases [24%] were endometrioid carcinoma; 18 cases [44%] were uterine serous carcinoma; 8 cases [20%] resulted in various other outcomes) and 5 cases (12%) remained indeterminate. CONCLUSIONS Making the distinction between type I and II endometrial carcinoma remains a common problem in general practice. Although no one biomarker provides excellent statistical performance, a panel of immunohistochemical markers is often useful in difficult cases.

Diagnostic discrepancies in breast specimens subjected to gross reexamination

To determine the accuracy of gross examination of breast specimens from a large university pathology service, 1120 breast specimens submitted from 1995 to 1997 that had residual tissue after submission of tissue sections were reexamined for diagnostic discrepancies. A total of 520 mastectomies, 143 wire localization excisions, 156 lumpectomies, and 301 mammoplasties were reexamined. Fifty-three (5%) major and 65 (6%) minor diagnostic discrepancies were detected. Major discrepancies included eight additional positive lymph nodes, 37 missed cancers, four upstagings by size, and four skin invasions. Forty-four of the major discrepancies were in mastectomy specimens. First-year residents accounted for slightly more than one half of all discrepancies. In contrast, review of original slides of 733 breast cancer cases revealed only 11 (1.5%) major discrepancies: three changes of margin status, six missed carcinomas, one positive lymph node, and one upstaging by size. Most discrepancies occurred because a specimen was not thoroughly inspected. The second most common cause was failure to recognize lesions. Our findings suggest that gross dissection performed by first-year residents is more prone to error and that such discrepancies are amenable to instruction and supervision.