Stromal Reaction is a Feature of Diffusely Infiltrating Endometrial Adenocarcinoma: Reply
Dr. Mittal correctly points out that the inclusion criteria in the study by Longacre and Hendrickson (1) consisted of both a diffuse pattern of invasion and absent to minimal stromal reaction. The study by Mittal and Barwick (2) required a diffuse pattern of growth (in > 50% of tumor) with no inclusion or exclusion based on stromal reaction. Lee et al. (3) used a definition of diffuse infiltration similar to that of Longacre and Hendrickson. Our study did not analyze a diffuse pattern of myometrial invasion but did analyze the type of host stromal reaction and morphologic changes within the invasive component of the tumor. Although the number of cases was small, Mittal and Barwick found an overall mortality for cases possessing a diffusely infiltrating pattern of invasion to be 40% (2 of 5 patients). These cases were all associated with some lymphocytic infiltrate in the stroma, which was marked in two cases. Although these findings may suggest a relationship between a lymphocytic stromal reaction, a diffusely infiltrating pattern of invasion, and a poor prognosis, we think this is unlikely but would require analyzing their control cases, as they do not report the frequency of a lymphocytic stromal reaction in the control group or its association with prognosis. We found that a lymphocytic host stromal reaction was not associated with a statistically significant different mortality when compared with cases with other types of stromal reaction or those with no reaction. Additionally we found a lymphocytic host stromal reaction was associated with a better overall outcome due to a lower rate of recurrence than those cases associated with a prominent edematous or fibromyxoid stromal reaction (P = 0.038). Similar to our findings, Lee et al. (3) also found a stromal lymphocytic response to be associated with a decreased rate of recurrence. Furthermore, our study demonstrated a strong association between the presence of a host stromal reaction and distinctive morphologic changes within the invasive glands, denoted as MELF (microcystic, elongated, fragmented), which in some cases are associated with deceptively deep myoinvasion that may be overlooked, resulting in an underestimation of the extent of myometrial invasion.
Shawn K. Murray, M.D.
Robert H. Young, M.D.
Robert E. Scully, M.D.
1. Longacre TA, Hendrickson MR. Diffusely infiltrative endometrial adenocarcinoma. An adenoma malignum pattern of myoinvasion. Am J Surg Pathol 1999; 23:69–78.
2. Mittal KR, Barwick KW. Diffusely infiltrating adenocarcinoma of the endometrium. A subtype with poor prognosis. Am J Surg Pathol 1988; 12:754–8.
©2004International Society of Gynecological Pathologists
3. Lee KR, Vacek PM, Belinson JL. Traditional and nontraditional histopathologic predictors of recurrence in uterine endometrioid adenocarcinoma. Gynecol Oncol 1994; 54:10–18.