Appendiceal Endometriosis with Intestinal Metaplasia Mimicking Appendiceal Mucinous Neoplasm - A Case Report and a Concise Review for the Practicing Pathologist.

Appendiceal endometriosis is a rare entity and, when accompanied by intestinal metaplasia, represents a challenging differential diagnosis with low-grade appendiceal mucinous neoplasm (LAMN). We present the case of a 47 years-old woman, with multiple surgical interventions for endometriosis, with persistent symptoms despite chronic hormonal treatment, with imaging showing stage IV endometriosis. Hence, en bloc low rectum resection with total hysterectomy and bilateral adnexectomy was performed, followed by appendectomy. Unexpectedly, despite the gross normal macroscopic appearance of the appendix, microscopy showed multiple endometriosis foci, consisting of endometrial glands embedded in varying amounts of endometrial stroma. As some of these glands were bordered by mucinous-type epithelium containing intestinal cells, Goblet cells, Paneth cells in addition to the presence of mucus-filled microcysts, immunohistochemistry (IHC) was performed in order to differentiate between intestinal-metaplasia and LAMN. IHC showed positivity of the endometrial epithelium for KRT7, estrogen receptor (ER) and progesterone receptor (PR). Both the appendiceal mucosa and the intestinal-type metaplastic epithelium of the glandular structures were positive for KRT20. Additionally, the endometrial stroma enclosing endometrial glands, as well as the stroma surrounding mucinous-type metaplastic epithelium, were positive for CD10, ER and PR. This patient's case draws attention to the rare occurrence of appendiceal endometriosis and the uncommon intestinal metaplasia, which can easily mimic LAMN, emphasizing the paramount importance of the differential diagnosis with this type of neoplasia.

Vulvar and Vaginal Melanomas-The Darker Shades of Gynecological Cancers.

Melanomas of the skin are poorly circumscribed lesions, very frequently asymptomatic but unfortunately with a continuous growing incidence. In this landscape, one can distinguish melanomas originating in the mucous membranes and located in areas not exposed to the sun, namely the vulvo-vaginal melanomas. By contrast with cutaneous melanomas, the incidence of these types of melanomas is constant, being diagnosed in females in their late sixties. While hairy skin and glabrous skin melanomas of the vulva account for 5% of all cancers located in the vulva, melanomas of the vagina and urethra are particularly rare conditions. The location in areas less accessible to periodic inspection determines their diagnosis in advanced stages, often metastatic. Moreover, despite the large number of drugs newly approved in recent decades for the treatment of cutaneous melanoma, especially in the category of biological drugs, the mortality of vulvo-vaginal melanomas has remained almost constant. This, together with the absence of specific treatment guidelines due to the lack of a sufficient number of cases to conduct randomized clinical trials, makes melanomas with this localization a discouraging diagnosis, associated with a very poor prognosis. Our aim is therefore to draw attention to this oftentimes overlooked entity in order to encourage the community to employ various strategies meant to increase research in this area. By highlighting the main risk factors of vulvar and vaginal melanomas, as well as the clinical manifestations and molecular changes underlying these neoplasms, ideally novel therapeutic schemes will, in time, be brought into effect.

Surgical Features after Neoadjuvant Treatment for Breast Cancer.

Introduction: Patients with breast cancer may receive neoadjuvant cancer treatment in order to benefit from radical surgery or to turn an indication for extensive surgery into a conservatory or oncoplastic operation. AIM: To establish the main implications of therapeutic management of the cases of breast cancer treated initially with chemotherapy followed by surgery. MATERIAL AND METHOD: 35 breast cancer patients operated in 2020 after NACT (neoadjuvant chemotherapy) in Surgery Clinic of Coltea Hospital are analyzed, and the response after treatment is pathologicaly evaluated using the Residual Cancer Burden method Results: The results of the analysis of the group of patients showed that most patients presented downstaging of the disease after neoadjuvant treatment with a proportion of 17,14% with complete pathologic response. DISCUSSIONS: We performed clinical and imagistic evaluation of patients before and after NACT and pathologic evaluation of the surgical specimen using residual tumor burden method, taking into account the age of the patients, clinical and pathological staging and the status of hormone receptors and Her 2. Conclusions: Neoadjuvant chemotherapy is currently part of the therapeutic arsenal of breast cancer being followed in most cases by downstaging of tumors and increasing the number of cases that can be operated. 17.1% of cases achieved pathologic complete response, 2 of them being Her 2 positive carcinomas. The use of conservative and oncoplastic surgical techniques is possible after downstaging tumors by NACT.

Ovarian metastases reported after adjuvant laparoscopic oophorectomies in breast cancer.

INTRODUCTION: Ovarian metastases (OM) of breast cancer (BC) can occur with different rates, ranging from 3-30%, being reported after prophylactic, therapeutic ovariectomies or discovered at necropsy. The aim of the study was to review the histopathological aspects of 59 laparoscopic oophorectomies performed in our Department as part of the oncological treatment of premenopausal women with BC. A number of eight (13.55%) patients were histologically confirmed with OM. The initial tumor, node, metastasis (TNM) stage of BC tumors was advanced with no pelvic symptoms or imaging abnormalities associated. Five (62.5%) patients had unilateral ovarian involvement and three (37.5%) bilateral, two of them being associated with primary bilateral BC. The immunohistochemical markers used to confirm the breast origin of metastasis were estrogen receptor (ER), progesterone receptor (PR), gross cystic disease fluid protein 15 (GCDFP15), Wilms' tumor 1 (WT1), cancer antigen-125 (CA-125), cytokeratin 7 (CK7), cytokeratin 20 (CK20). One case showed positive cytoplasmic reaction for thyroid transcription factor-1 (TTF-1). GCDFP15 was positive in all OM and almost all (seven of eight) were noted as non-immunoreactive for WT1. Although six cases of metastatic BC were positive for CK7 and negative for CK20, only four of them retain the same immunoprofile of their primary tumor for the metastatic ovarian lesions. Only one case out of eight showed weak and focal positivity for CA-125. Three cases were positive for mucin 1 (MUC1) and epithelial membrane antigen (EMA). CONCLUSIONS: The differential diagnosis between OM and primary ovarian cancer can be challenging for the pathologist as well and immunostaining is of help. GCFDP15 is the most specific for breast carcinoma. In contrast with the recent papers published in the literature, we detected TTF-1 cytoplasmic expression in invasive breast carcinoma by SPT24 clone.

Large cell neuroendocrine cervical tumor treated by radical surgery and adjuvant chemotherapy: A case report and literature review.

Neuroendocrine carcinomas of the uterine cervix are rare, but extremely aggressive, gynecological malignancies that are associated with an overall poor prognosis. The present study reports the case of a 41-year-old patient diagnosed with large cell neuroendocrine cervical tumor. A radical total hysterectomy with bilateral adnexectomy, pelvic and lymph node dissection was performed. The post-operative course was uneventful, and the patient was discharged on post-operative day 8.

Low-grade appendiceal mucinous neoplasm mimicking an adnexal mass.

We present a rare case of malignant epithelial neoplasm of the appendix, an uncommon disorder encountered in clinical practice, which poses a variety of diagnostic and therapeutic challenges. We report a particular case in which the appendix was abnormally located in the pelvis, mimicking an adnexal mass. Therefore, it was difficult to make the preoperative diagnosis on clinical examination, imaging studies and laboratory tests and we discovered the lesion during the diagnostic laparoscopy. No lymphadenopathy or mucinous ascites were found. The case was completely handled via the laparoscopic approach keeping the appendix intact during the operation. The frozen section, the detailed histopathology overview as well as multiple immunostaining with a complex panel of markers report diagnosed a low-grade appendiceal mucinous neoplasm (LAMN) with no invasion of the wall. No adjuvant therapy was considered needed. At a one-year follow-up oncological assessment, the patient was free of disease. In women with cystic mass in the right iliac fossa an appendiceal mucocele should be considered in the differential diagnosis. Laparoscopic appendectomy can represent an adequate operation for the appendiceal mucinous neoplasm if the histological report is clear and surgical precautionary measures are taken.

Endometrial Carcinoma Associated with Ovarian Granulosa Cell Tumors--A Case Report.

Ovarian granulosa cell tumors represent uncommon neoplasms with estrogen-secreting capacity. Due to their association with persistently increased levels of estrogen, modifications of the endometrial tissue ranging from hyperplasia to malignant degeneration may be encountered. We present the case of a 65-year-old patient who presented for post-menopausal vaginal bleeding. The endometrial biopsy raised the suspicion of an atypical endometrial hyperplasia and the patient was submitted to surgery. Histopathological studies of the specimen of total hysterectomy with bilateral adnexectomy revealed the presence of a well-differentiated endometrial carcinoma associated with a granulosa cell tumor of the ovary. In conclusion whenever a modified aspect of the endometrium is found preoperatively, attention should be given on other possible underlying modifications and a radical approach should be taken in consideration.

Regeneration of the adult thymus is preceded by the expansion of K5+K8+ epithelial cell progenitors and by increased expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma.

Studies of HIV-1-infected individuals on anti-retroviral therapies and of patients receiving lymphoablating treatments indicate that the thymus retains restorative capacity even in adults. The contributions of the thymic epithelial cells (TECs) to the regeneration of the thymus and the identity of epithelial cell progenitors were evaluated in murine models of transient thymic atrophy followed by a complete regeneration. Using microarray approach, we analyzed the pattern of gene expression in TECs sorted from mice that were depleted of thymocytes by steroid treatment or by irradiation. The initial analysis identified significant increases in the mRNA for cMyc, Trp63 and Tcf3 transcription factors known to be expressed in early epithelial cell progenitors in tissues other than the thymus. Immunohistochemistry showed that in involuted thymuses, the cMyc and Trp63 proteins were expressed in a subset of cortical thymic epithelial cells (cTECs) that were keratin 5 positive (K5(+)), typifying cTEC precursors. Importantly, confocal microscopy established that epithelial cells with the phenotype of putative TEC progenitors (i.e. K5(+)K8(+)) expressed the Trp63 protein and confirmed that K5(+)K8(+) TEC progenitors expanded significantly during atrophy and prior to the thymic regeneration. Thus, our data demonstrated for the first time that critical steps in the recovery of the adult thymus include expansion of TEC progenitors and elevated expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma. These results suggest that TEC progenitors could be reactivated in the adult thymus and, therefore, reactivation of TEC progenitors could provide a new approach for thymic reconstitution.

[The sentinel lymph node technique in colorectal cancer using in vivo dye--utility and limits]. / Ganglionul santinela in cancerul colorectal folosind colorant intravital--utilitate, limite.

The aim of this work is to analyze the importance of sentinel lymph node technique in the treatment of colorectal cancer. There are presented data from literature concerning sentinel lymph node, especially papers about the place of sentinel lymph node method in the treatment of colorectal cancer. This work also shows the experience of Surgical Clinical Department of Coltea Hospital in the use of sentinel lymph node method in colorectal cancer (8 patients with colon cancer and 9 with rectal cancer). There are presented the criteria for inclusion in the study group (26 patients initially proposed for the study) and the exclusion criteria, the diagnostic method using an in vivo dye and the pathology study. The study of the literature and our experience leads to the conclusion that the identification of the sentinel lymph node in colorectal cancer doesn't modify the dissection of the lymphatic area. This procedure may change the adjuvant treatment for colorectal cancer. The discussion is still open concerning the importance of lymphatic micro metastases found by RT-PCR and immunohistochemistry methods. More studies are necessary to clarify these problems.

CRM1-dependent function of a cis-acting RNA export element.

Viruses often contain cis-acting RNA elements, which facilitate the posttranscriptional processing and export of their messages. These elements fall into two classes distinguished by the presence of either viral or cellular RNA binding proteins. To date, studies have indicated that the viral proteins utilize the CRM1-dependent export pathway, while the cellular factors generally function in a CRM1-independent manner. The cis-acting element found in the woodchuck hepatitis virus (WHV) (the WHV posttranscriptional regulatory element [WPRE]) has the ability to posttranscriptionally stimulate transgene expression and requires no viral proteins to function. Conventional wisdom suggests that the WPRE would function in a CRM1-independent manner. However, our studies on this element reveal that its efficient function is sensitive to the overexpression of the C terminus of CAN/Nup214 and treatment with the antimicrobial agent leptomycin B. Furthermore, the overexpression of CRM1 stimulates WPRE activity. These results suggest a direct role for CRM1 in the export function of the WPRE. This observation suggests that the WPRE is directing messages into a CRM1-dependent mRNA export pathway in somatic mammalian cells.