Typical Medullary Carcinoma Research Articles

Medullary Carcinoma of the Breast

We reviewed 30 cases of breast cancer originally diagnosed as medullary carcinoma during a 10-year period. Of the 30, only 9 proved to be "typical medullary carcinoma" with the associated favorable prognosis. Seven of the remaining 21 cancers were reclassified as "atypical medullary carcinoma," and the remaining 14 were nonmedullary cancers. Overdiagnosis of medullary carcinoma could lead to inappropriately conservative therapy, since medullary carcinoma is a prognostically favorable neoplasm. Those involved with diagnosis and treatment of patients with breast cancer should be aware of this potential problem.

Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast, and its prognostic implications.

One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977-1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfi et al. and Fisher et al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfi et al. need to be sharpened and simplified in order to reduce inter- and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.

Medullary carcinoma of the breast: a clinicopathologic study with appraisal of current diagnostic criteria.

Fifty-three cases of mammary carcinoma originally diagnosed as medullary carcinoma (MC) or infiltrating duct carcinoma (IDC) with medullary features were reviewed and reclassified using the strictly defined histologic criteria applied a decade ago by Ridolfi et al. Our study interval (1961 to 1982) allowed for a minimum follow-up of 5 years for each patient, with a mean follow-up period of 7.2 years. When reclassified, 24 tumors fulfilled the criteria for MC, 16 tumors were determined to be atypical MC, and ten tumors were found to be IDC; the observed 5-year survival rates were 95%, 80%, and 70%, respectively. These findings confirmed those of other investigators, that when specific criteria are applied, MC proves to be a form of mammary carcinoma with a favorable prognosis. However, we also found that when tumors were excluded from the MC category solely on the basis of in situ carcinoma, focal marginal infiltration, or a sparse mononuclear infiltrate, the survival rate of these patients was similar to that of patients in the medullary category. Thus, we propose that one of these criteria alone should not suffice to exclude the diagnosis of MC. On the other hand, tumors with two or more of these atypical features, or with extensive marginal infiltration, no mononuclear cellular infiltrate, and/or less than 75% syncytial growth, should be classified as IDC with medullary features. Typical MC with bland nuclei or a focal microglandular growth pattern only were not observed in this series; however, these findings should probably also cause a tumor to be classified in the IDC category. By dividing our cases into two rather than three groups, we found a statistically significant difference between the survival rates of 94% and 64% for MC (34 tumors) and IDC (14 tumors), respectively. Although the latter figure probably exceeds the survival rate for IDC without medullary features, the difference does not appear great enough to warrant a separate diagnostic category.

Medullary breast carcinoma. A reevaluation of 95 cases of breast cancer with inflammatory stroma.

The hallmarks of diagnosis of medullary breast cancer (MedBC) used by the authors since 1977 have been that the tumor is well circumscribed, has syncytial architecture in greater than 75% of its surface, contains diffuse inflammatory infiltrate, has atypical nuclei, and forms no glandular pattern. In order to assess the clinical utility of these criteria, we studied a series of 95 previously untreated, surgically operable patients with breast carcinoma at the Institut Gustave-Roussy (IGR) between 1960 and 1979. A diagnosis of MedBC was initially made for these patients or suspected based on abundant inflammatory stroma observed in a histologic evaluation. Using these criteria, 26 cases were identified as typical medullary carcinoma (TMC), 23 cases as atypical medullary carcinoma (AMC), and 46 cases as nonmedullary carcinoma (NMC). The 26 cases of TMC represent a very small fraction of the total infiltrating operable breast carcinomas diagnosed at IGR during the same time period. The prognosis for these 26 patients was much more favorable than for the other groups. They had a 10-year disease-free survival of 92% compared with 53% for the AMC group and 51% for the NMC group. Neither distant metastasis nor secondary primaries of the same histology were seen. Therefore, it is possible with the use of strict histologic criteria to distinguish a group of patients with a much more favorable prognosis. This histologic diagnosis alone renders a most favorable prognosis for the patient even if other factors such as large tumor size and lymph node involvement are present and, by inference, the only therapy needed is the removal of all tumor. In contrast, atypical forms have a prognosis no different from other atypical types of breast carcinomas without inflammatory stroma, and adjuvant therapy appears to be justified if other factors warrant it.

The ultrastructure of medullary carcinoma of the breast.

Three cases of medullary carcinoma complying with strictly defined criteria have been examined by electron microscopy. These carcinomas are characterised by the presence of light and dark tumour cells which exhibit prominent organelles and well-developed Golgi complexes but lack secretory activity. The essential stromal cellular infiltrate of macrophages, lymphocytes and plasma cells contains macrophage-lymphocyte clusters suggesting the existence of an immune response. Also present in the stroma are blood vessels lined by high-endothelial cells of the type said to facilitate lymphocyte migration. It is suggested that light and dark tumour cells with well-developed organelles but absent secretory activity, macrophage-lymphocyte clusters and stromal high-endothelial venules represent specific ultrastructure features of typical medullary carcinoma associated with good prognosis.