Case 5 -

Endometrioid Adenocarcinoma of Endometrium in a Peritoneal Lavage Specimen Terence J. Colgan

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Clinical History A 73 year old woman presented with post-menopausal vaginal bleeding. A pelvic ultrasound revealed a "polyp". A subsequent polypectomy and endometrial curetting was reported as "endometrioid adenocarcinoma, FIGO grade 2/3 for an endometrial primary". Four weeks later, the patient underwent a hysterectomy and bilateral salpingo-oophorectomy. A peritoneal wash was undertaken upon entry into the peritoneal cavity. Case 5 - Figure 1 A mesothelial fragment is evident (center) on a background of mononuclear cells. A dense cellular fragment with a distinctly different morphology is evident to the right of the mesothelial fragment. Case 5 - Figure 2 In contrast to the mesothelial fragment with its regular appearance and low nuclear to cytoplasmic ratio (top), the dense cellular fragment exhibits overlapping of cells (architectural disarray) and an increased nuclear to cytoplasmic ratio. Case 5 - Figure 3 In addition to architectural disorganization, these fragments show a smooth peripheral contour. The nuclei show significant variability in size and chromatin abnormalities. The outline of some of the nuclei is irregular and notched. Cytoplasmic vacuolation is evident. Case 5 - Figure 4 In addition to architectural disorganization, these fragments show a smooth peripheral contour. The nuclei show significant variability in size and chromatin abnormalities. The outline of some of the nuclei is irregular and notched. Cytoplasmic vacuolation is evident. Case 5 - Figure 5 In addition to architectural disorganization, these fragments show a smooth peripheral contour. The nuclei show significant variability in size and chromatin abnormalities. The outline of some of the nuclei is irregular and notched. Cytoplasmic vacuolation is evident. Case 5 - Figure 6 In addition to architectural disorganization, these fragments show a smooth peripheral contour. The nuclei show significant variability in size and chromatin abnormalities. The outline of some of the nuclei is irregular and notched. Cytoplasmic vacuolation is evident. Case 5 - Figure 7 In addition to architectural disorganization, these fragments show a smooth peripheral contour. The nuclei show significant variability in size and chromatin abnormalities. The outline of some of the nuclei is irregular and notched. Cytoplasmic vacuolation is evident. Cytologic Diagnosis: Positive for adenocarcinoma, peritoneal lavage. Histologic Diagnosis: Endometrial adenocarcinoma, endometrioid type, with mucinous differentiation, FIGO grade 1/3. Cytologic Findings: The lavage specimen shows mesothelial sheets, and a second population of cohesive cells presenting as 3D fragments with a distinctively different appearance. These fragments show architectural disorganization, and have a smooth peripheral contour. The nuclei show significant variability in size and chromatin abnormalities. The outline of some of the nuclei is irregular and notched. Cytoplasmic vacuolation is evident. Histologic and Clinical Follow-up: Macroscopic examination of the hysterectomy specimen revealed a 53g uterus with a 2 x 1.1 cm lesion of the posterior endometrium. The fallopian tubes and ovaries were of normal size, although the right ovary showed a granular serosa. Microscopic examination revealed a cortical nodule of metastatic adenocarcinoma in the left ovary. The surgical pathology staging of this case was pT3a. Discussion: Pathological staging in endometrial carcinoma includes peritoneal lavage cytology. The reported prevalence of positive or suspicious cytology for all stages of disease varies from 8.5 to 35%. If the potential of cytology findings with respect to upstaging are disregarded, the prevalence of positive or suspicious cytology in clinical and surgical stage I disease varies from 5 to 21%. The use of immunocytochemistry (ICC) to increase the sensitivity of disease detection in peritoneal lavage specimens has been studied, but is not an established procedure. Nevertheless, the use of antibodies AR-3 and B72.3 to detect malignant cells in peritoneal lavage specimens has been reported to almost double the detection of malignant cells. Furthermore, the disease-free survival of cytology negative-ICC positive patients was intermediate between patients who were both routine cytology and ICC negative, and both cytology and ICC positive. Positive or suspicious cytology is correlated with the stage of disease, and is more commonly found in advance stage disease. FIGO grade, myometrial invasion, and histologic subtype have not been found to be consistently correlated with positive or suspicious cytology. By convention a positive peritoneal cytology in endometrial carcinoma advances the surgical pathology stage to a pT3a, although the upstaging of a patient based merely upon the presence of a positive peritoneal cytology is not without controversy. Stage pT3a is a heterogeneous group of patients, and also includes those patients who have histopathologically demonstrated metastases to the uterine serosa, fallopian tubes, or ovaries. A number of studies have concluded that upstaging to pT3a based upon positive peritoneal cytology alone is not merited, because prognosis and/or recurrence is not affected by this isolated cytologic finding. For example, a study by Fidar concluded that pT3a patients based upon a positive peritoneal wash alone have a similar or identical outcome to stage I and II patients. In addition, this group found that such upstaging is an uncommon occurrence (<5% of all cases). In contrast, a number of other studies have concluded that pT3a cases based upon cytology is an important staging designation. For example, a GOG study found 29% of cytology positive patients otherwise staged as clinical stage I and II (with only selected lymph node sampling), had regional or distant failure compared to <11% of cytology negative patients. Even without any other adverse factor, 19% of these patients recurred regionally or distally. The study concluded that positive cytology is associated with an increased risk for recurrence both regionally and distally. A more recent study also showed a 5 year survival of patients with peritoneal positive cytology of only 87% versus 97% in patients with fully staged node-negative endometriod adenocarcinomas otherwise designated as stage I and II. Recent evidence is now available from fully staged endometrial carcinoma, and this evidence supports a pT3a designation by cytology alone. In this study positive cytology was both predictive of both death and disease recurrence, whereas uterine and adnexal serosal metastases were not. Positive cytology was found to be an independent predictor of prognosis and thus the study concluded that this finding warrants a pT3a designation. The recurrence rate in this group of 23% is similar to histologically occult nodal metastases. In summary, a small proportion of women coming to hysterectomy for endometrial carcinoma will have positive peritoneal pathology. The role of immunocytochemistry in increasing the sensitivity of diagnosis is not yet established. Positive cytology is correlated with other evidence of advanced stage disease, and in this situation indicates a worse prognosis. Positive cytology, by itself, does merit a pT3a designation, and recent evidence suggests that these pT3a patients have a poorer prognosis and that adjuvant therapy should be considered. References: Benevelo M, Mariani L, Vocaturo G, et al. 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