Background: Recent findings strongly promoted the hypothesis that common pelvic gynecological diseases including endometriosis and ovarian neoplasia may develop de novo from ectopic endometrial-like glands and/or embryonic epithelial remnants. To verify the frequency, the anatomical localization and the phenotype of misplaced endometrial tissue along the fetal female reproductive tract, histological and immunohistochemical analyses of uteri, fallopian tubes, and uterosacral ligaments were performed. Methods: Reproductive organs were collected from seven female fetuses at autopsy, five of them from gestational ages between 18 and 26 weeks and two fetuses with gestational ages of 33 and 36 weeks deceased of placental anomalies. Serial sections from areas containing ectopic glands and embryonic duct residues were analyzed by histological and immunohistochemical procedures. Results: Numerous ectopic endometrial glands and stroma were detected in the myometrium in two fetuses with low levels of expression of estrogen receptor-alpha (ER-α) and progesterone receptors (PR). The embryonic ducts were localized in the uterine broad and ovarian ligaments and under the fallopian tube serosa in six fetuses. Low levels of steroid receptors expression were found in the embryonic residues, whereas the carcino-embryonic antigen (CEA) and the tumor marker Ca 125 were not detected. The embryonic residues stromal component strongly expressed the CD 10 and vimentin proteins. Conclusion: The anatomical and the immunohistochemical features of the ectopic organoid structures identified in fetal female reproductive tract suggest that endometriotic as well as neoplastic disease in adult women may develop on the basis of misplaced endometrial glands and/or embryonic cell remnants.

Immune-based anti-cancer strategies combined with radiation therapy (RT) are actively being investigated but many questions remain, such as the ideal treatment scheme and whether a potent immune response can be generated both locally and systemically. In this context, tumor-associated tertiary lymphoid structures (TLS) have become a subject of research. While TLS are present in several types of cancer with strong similarities, they are especially relevant in medullary breast carcinoma (MBC). This suggests that MBC patients are ideally suited for investigating this question and may benefit from adapted therapeutic options. As RT is a corner-stone of MBC treatment, investigating interactions between RT and TLS composition is also clinically relevant. We thus first characterized the lymphoid structures associated with MBC in a patient case report and demonstrated that they closely resemble the TLS observed in a genetical mouse model. In this model, we quantitatively and qualitatively investigated the cellular composition of the tumor-associated TLS. Finally, we investigated TLS regulation after hypo-fractionated RT and showed that RT induced their acute and transient depletion, followed by a restoration phase. This study is the first work to bring a comprehensive and timely characterization of tumor-associated TLS in basal conditions and after RT. It highlights cellular targets (i.e., Tregs) that could be selectively modulated in subsequent studies to optimize anti-tumor immune response. The study of TLS modulation is worth further investigation in the context of RT and personalized medicine.

Endometriosis is a curious pathology that has been the topic of many international publications. Its etiology remains mysterious but seems to have multiple causes. It is a complex disease whose lesions are very heterogeneous in where they can occur (deep endometriosis, superficial, ovarian cyst), extent, associated symptoms, evolution or aggressiveness of the disease, and response to treatments. Furthermore, it evolves in pushes, remains autonomous, and is responsible for both superficial and deep lesions that explain its two most well know challenges: pain and infertility. It has always been classified by the size of its anatomical lesions—Acosta classification ( 1 ), revised by the American fertility society (AFS) ( 2 ), and the American society of reproductive medicine (ASRM) classification with a description of the disease at different stages: minimal (score of 1 to 5), mild ( 3 – 12 ), moderate (16 to 40), and severe (>40) ( 13 ). If this classification provides a complete repertoire of implants (anatomic) ( 10 ), the attribution of points is arbitrary. In fact, the size of the lesions is not synonymous with the difficulty to treat them surgically. Their location, if deep, is larger than the size of ovarian endometriomas. In addition, small anatomical but evaluative lesions will have a larger impact than big fibrous and stable lesions ( Figure 1 ). Thus, attempts to explain their inflammatory side effects have been proposed ( 14 , 15 ). The French classification nodule, ovaries, adhesions, tube, and inflammation (FOATI) ( 10 ) has had the merit of taking this phenomenon into account. In our opinion, we must go much further and propose an amendment in this classification, taking into account the evolution of the lesions and their deep molecular biology because in reality, the lesions are not at the same stage.

Pleomorphic hyalinizing angiectatic tumor, a rare neoplasm of uncertain lineage resembling malignant fibrous histiocytoma and schwannoma, was first described in 1996 by M. E. F. Smith et al. (Am Surg Pathol. 20:21-29). To date, less than 100 cases have been reported in the international literature. It occurs in subcutaneous and intramuscular soft tissues of extremities or trunk in adults without sex predilection. All lesions are composed of sheets and fascicles of spindled and pleomorphic cells associated with clusters of thick-walled ectatic vessels surrounded by a perivascular hyaline material and inflammatory cells such as mast cells. About one-half of these neoplasms express CD34. No patient has developed metastases but occasional local recurrences are possible. This tumor of uncertain lineage is suggested to be an aggressive locally growing low-grade sarcoma. Only 3 cases were previously studied by electron microscopy and appeared to consist of primitive fibroblastic cells. The authors report histological and ultrastructural characteristics of a new case of PHAT excised from the right buttock of a 66-year-old man with the presence of ganglion-like cells, a feature that has not been previously reported, and unusual central ischemic necrosis. The features of this case are suggestive of a fibroblastic origin.

From a review of 2,000 autopsies of children, 16 cases of extensive necrosis and scarring fibrosis of the myocardium were found. These lesions involved mainly the left ventricle and spared the endocardium, the pericardium, and the coronary vessels. These necrotic or fibrotic heart lesions were found to be closely associated with various pancreatic diseases: cystic fibrosis (11 cases), pancreatic lipomatosis (2 cases), extensive small bowel resection (3 cases, 2 of which were associated with acute interstitial pancreatitis). To explain these unexpected associations, two hypotheses can be put forth: (1) The lack of absorption of some presently undetermined substances indispensable for the correct trophicity of the myocardium, and (2) the release in the blood of proteolytic enzymes with consecutive activation of phlogistic substances such as kinins.