Kenneth R. Lee

Mucinous ovarian neoplasms other than cystadenomas and adenofibromas have been classified as either borderline tumors or carcinomas for many years. Borderline tumors have been subdivided more recently into endocervical-like (mullerian) and intestinal forms. Such a distinction is rarely made in the mucinous carcinoma category. We did not encounter a pure endocervical-like carcinoma in the present series. Criteria for distinguishing an intestinal-type mucinous borderline tumor from a mucinous carcinoma have been controversial. In this study of 164 mucinous borderline tumors of intestinal type and 32 mucinous carcinomas, the former were further subdivided into 74 cases with epithelial atypia only and 90 with focal intraepithelial carcinoma. Of the 67 stage I tumors in the borderline (with atypia) category, all 49 with follow-up data were clinically benign; in the seven cases that had been designated stage III, the intraoperative appearance was that of "pseudomyxoma peritonei," which was fatal in four cases. Most of these tumors, however, were probably metastatic to the ovary rather than truly primary borderline tumors, although failure to examine the appendix in six cases compromised their interpretation. All 90 mucinous borderline tumors that had foci of intraepithelial carcinoma were recorded as stage I, but two of the 69 patients with follow-up data (3%) had fatal recurrences. Both of these tumors were incompletely staged, however, and one had ruptured intraoperatively. Thirty-two invasive carcinomas were subdivided into 12 expansile and 20 infiltrative subtypes; within the latter category seven tumors were only microinvasive. All 12 carcinomas with only expansile invasion were stage I; none of the 10 with follow-up data recurred. All seven microinvasive infiltrative carcinomas were stage I; none of the five with follow-up data recurred. One of five patients with stage I infiltrative carcinomas that were more than microinvasive and were adequately followed had a fatal recurrence, but staging had been incomplete in that case. Seven of the remaining eight infiltrative carcinomas were higher than stage I: five of the six (83%) with follow-up data persisted or recurred and were fatal. Considering all stages, increasing tumor grade in the carcinoma category correlated with an unfavorable outcome. However, grade did not influence prognosis in stage I carcinomas. Among 13 stage I cases in all categories with either preoperative or intraoperative tumor rupture and follow-up data, one recurred, a tumor in the borderline with intraepithelial carcinoma category. "Pseudomyxoma peritonei" is an ill-defined term and should not be used as a pathologic diagnosis. The presence of mucin in the abdominal cavity requires careful histologic evaluation to characterize it for prognostic purposes. Adequate and sometimes extensive sampling of mucinous ovarian tumors, the appendix and the peritoneum in cases of "pseudomyxoma peritonei" is necessary to achieve an accurate diagnosis and prognosis.

The gross and routine microscopic features of 25 stage I primary mucinous ovarian carcinomas without clinical evidence of recurrence and 25 mucinous carcinomas metastatic to the ovaries were compared. Findings that were frequent in the latter and strongly favored a metastasis were: 1) bilaterality, 2) microscopic surface involvement by epithelial cells (surface implants), and 3) an infiltrative pattern of stromal invasion. Findings that were less frequent but present exclusively or almost exclusively in metastatic carcinomas were: 1) a nodular invasive pattern, 2) ovarian hilar involvement, 3) single cell invasion, 4) signet-ring cells, 5) vascular invasion, and 6) microscopic surface mucin. Findings that were frequent in, and strongly favored, primary ovarian carcinoma were: 1) an "expansile" pattern of invasion and 2) a complex papillary pattern. Findings that were less frequent but also favored a primary tumor were: 1) size >10 cm, 2) a smooth external surface, 3) benign-appearing and borderline-appearing areas, 4) microscopic cystic glands, and 5) necrotic luminal debris. Findings that did not distinguish the tumors were: 1) a cystic gross appearance, 2) gross solid, papillary, necrotic, or hemorrhagic areas, 3) nature of cyst contents (mucinous vs nonmucinous), 4) stromal mucin (pseudomyxoma ovarii), 5) cribriform, villous, or solid growth patterns, 6) focal area resembling typical colonic carcinoma, 7) goblet cells, or 8) tumor grade. Primary and metastatic mucinous ovarian carcinomas can be distinguished from each other in the great majority of cases based solely on their conventional histopathologic findings. Careful gross evaluation is also important with special attention paid to the external surface of the ovarian tumor(s) to detect abnormalities that have the features of surface implants on microscopic evaluation.

We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.

Five panelists independently reviewed 135 consecutive conventional cervical smears (CPs) originally classified as atypical glandular cells of undetermined significance (AGUS). A thin-layer slide (TP), prepared from the residual material, also was reviewed in each case. All patients underwent colposcopy that yielded at least 1 histologic specimen. Three or more of 5 reviewers retained the AGUS interpretation for 29% of CPs and 12% of the corresponding TPs. Interobserver variability infrequency of use of AGUS was marked, and interobserver agreement was poor. Agreement was improved for cases cytologically interpreted as a high-grade lesion, especially in TPs. Four of 5 reviewers retained the AGUS classification in CPs for all 7 biopsy-proven neoplastic glandular lesions. Of 95 CP interpretations made by 5 reviewers in the 19 histologically diagnosed high-grade lesions, 8 were "negative/reactive" and 6 were AGUS "favor reactive." AGUS is a poorly reproducible cytologic interpretation. Although most neoplastic glandular lesions may be distinguished by cytopathologists experienced in this area from mimics originally considered AGUS, attempts to increase the diagnostic specificity of AGUS may diminish sensitivity for an underlying high-grade precursor. Interobserver agreement was better for TPs than for the corresponding CPs. However, the split-sample TP slides may not have been fully comparable to the CPs.