Diagnostic challenges in pathology

Uterine serous papillary carcinoma vs. papillary endometrial carcinoma: In the 1970s there were several papers on papillary carcinomas of the endometrium with psammoma bodies; however, most of these were case reports. The study that identified uterine serous carcinoma as an entity is from Standford et al. Today, we know that there are different types of papillary serous carcinoma of the endometrium. There is a pure papillary serous carcinoma, which is a very aggressive lesion and usually has vascular invasion. There is serous carcinoma mixed with endometrioid carcinoma and currently there are no studies showing what proportion of serous carcinoma is important in the prognosis of this type of lesion; however, it appears that patients with this type of tumor have better prognosis than the ones with pure serous carcinoma. The presence of areas of serous carcinoma in an endometrioid carcinoma reduces the survival by 50%, and very often in these cases the tumor seen in the lymphatics of the myometrium is papillary serous carcinoma. The third type of papillary serous carcinoma is when this type of tumor is seen in endometrial polyps. In general, there is no myometrial invasion and in some cases, there is not even stromal invasion; however, frequently, this type of tumor is associated with very superficial lesions in the fallopian tube epithelium, the surface of the ovary and the peritoneum. These lesions are typical of surface papillary peritoneal carcinoma and we believe they represent multicentric lesions. This has been proven by molecular studies. The most common type of papillary serous carcinomas is the mixed with endometrioid carcinoma. Pure papillary serous carcinoma and papillary serous carcinoma in polyps have a similar frequency. It is extremely important to remember that the recurrence rate of noninvasive uterine serous carcinoma is between 30% and 50%. The differential diagnosis of uterine serous carcinoma is with clear cell carcinoma, papillary metaplasia, adenocarcinoma of the endocervix, and papillary endometrioid carcinoma. Clear cell carcinoma is usually easily recognized because of the clear appearance of the cells; however, it also has different features, which are classical of this tumor. These features are papillae with hyaline material inside and lined by only one layer of cells. The presence of different patterns with hyaline material inside and lined by only one layer of cells. The presence of different patterns in the same tumor including papillary, glandular, and micro cystic, is specific for this type of tumor. In our experience, the prognosis of clear cell carcinoma, when the tumor is detected at a lower stage, is not different from that of endometrioid carcinoma and it is significantly better than that of papillary serous carcinoma. Papillary metaplasia might simulate papillary serous carcinoma at lower power; however, at higher magnification, most of the cells are very uniform, there is no significant cytologic atypia and mitotic figures are absent. Adenocarcinoma of the endocervix. It has been reported that some adenocarcinomas of the endocervix have similar appearance to papillary serous carcinoma; however, in our experience, this happens only on the superficial portions of the tumor. When we examined deeper areas, the tumor has only a glandular component without papillary features. Papillary endometrioid carcinoma. There have been few studies of this type of tumor. In papillary endometrioid carcinoma, the papillae have a smooth border and there are very few cell detachments separated from the main papillae. In addition, frequently areas of squamous differentiation are seen. A very typical feature of this type of endometrioid carcinoma is that in the areas of stromal invasion frequently there are granulomas with multiple inflammatory cells and the epithelium becomes very thin. Papillary endometrioid adenocarcinoma is considered a grade 2 endometrial carcinoma, even without the presence of solid areas, because of the frequency of vascular invasion (71%). The recurrence rate of papillary endometrial carcinoma is also higher than that of typical endometrial carcinoma (13% vs. 5%). Regarding the use of immunostains to identify this tumor, there are no studies evaluating p53 in this type of endometrial adenocarcinoma. Most of the studies of p53 in endometrial carcinoma are in cases without papillary features. Malignant mixed mullerian tumors – carcinosarcoma: Most probably this type of tumor originates from a single multipotential stem cell with divergent differentiation. Usually these are large, extremely aggressive tumors, and it is easy to separate the carcinomatous component from the sarcomatous component which, in general, is spindle. The carcinomatous component often is high-grade, predominantly papillary serous. The sarcomatous component is spindle; however, areas of cartilaginous, and skeletal muscle cells are also seen. In the metastasis of malignant mixed mullerian tumors, usually we see only carcinoma. In approximately 24% of the cases, there are foci of carcinoma and sarcoma. It is rare to see only the sarcomatous component in the metastasis. Malignant mixed mullerian tumors should be differentiated from sarcomatoid carcinoma, mullerian adenosarcoma and dedifferentiated adenocarcinoma. Sarcomatoid carcinoma is a lesion more frequently seen in the cervix and it is difficult to clearly separate the epithelial component from the stromal component. In contrast with malignant mixed mullerian tumors in sarcomatoid carcinomas there is transition from the epithelial component to the stromal component, which close to the epithelium, is still positive for keratin. Mullerian adenosarcoma. Rarely, a mullerian adenosarcoma needs to be differentiated from a malignant mixed mullerian tumor. In most cases of adenosarcoma, the epithelial component is benign; however, sometimes there are significant atypical epithelial areas in one or more foci of a typical adenosarcoma. Some pathologists have suggested to designate these tumors as mullerian adenosarcoma with carcinoma in-situ rather than malignant mixed mullerian tumors because the behavior is that of the adenosarcoma and not the aggressive behavior of the malignant mullerian tumor. Another important issue in the relationship between mullerian adenosarcomas and malignant mixed mullerian tumors is that in approximately 10–15% of the malignant mixed mullerian tumors there are foci of residual adenosarcomas. Therefore, most probably, these malignant mixed mullerian tumors generate from adenosarcomas. Undifferentiated carcinoma of the endometrium. In order to understand the concept of dedifferentiated in adenocarcinoma of the endometrium, which is probably the main differential diagnosis of malignant mixed mullerian tumors, it is important to review the concept of undifferentiated carcinoma of the endometrium. This is an entity not well recognized in the literature. In our opinion, undifferentiated adenocarcinoma of the endometrium is an extremely aggressive lesion characterized by epithelioid type of cells usually forming diffuse sheaths of epithelioid cells. We believe that undifferentiated carcinoma of the endometrium should be separated from grade 3 endometrioid adenocarcinoma because in the undifferentiated carcinoma, there are no residual glands while in the grade 3 adenocarcinoma, there are multiple solid areas; however, unequivocal endometrioid glands are seen. The survival of undifferentiated adenocarcinoma of the endometrium is extremely low compared to adenocarcinomas grade 3. Approximately 73% of patients with undifferentiated carcinoma of the endometrium died of disease in less than 5 years while only 39% of grade 3 endometrioid adenocarcinoma died in 5 years. Dedifferentiated endometrioid adenocarcinoma. We designate the tumor as dedifferentiated endometrioid adenocarcinoma when there are foci of adenocarcinoma, grade 1 or grade 2, next to foci of totally undifferentiated adenocarcinoma. Sometimes the undifferentiated carcinoma has the appearance of rhabdoid cells that can be confused with necrosis. It is very important to recognize this type of tumor as undifferentiated carcinoma and not to designate the entire lesion as a grade 2 endometrial adenocarcinoma because most patients with undifferentiated adenocarcinoma of the endometrium will die of the disease in 1–60 months with a median of 6 months.