Giacomo Caprara

Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma

Androgens and androgen receptors (AR) are involved in the pathogenesis of breast cancer. Epidemiological studies have shown a significant association between the risk of breast cancer and androgens. However, the functional role and clinical value of AR expression in breast carcinoma have still not been clearly defined. The present study was set up to investigate the prevalence of ARs in a series of consecutive invasive breast carcinomas (IBCs) and to evaluate the patterns of AR phenotypes in a series of selected invasive lobular carcinomas (ILCs). Among the 250 consecutive IBCs (consisting of 212 ductal and 38 lobular neoplasms), AR immunoreactivity was observed in 151/250 (60.4%) cases, being expressed in 118/212 (56%) ductal and 33/38 (87%) lobular carcinomas (a statistically significant difference, χ2=11.82). AR expression was frequently associated with ER (65.2%, χ2=14.33) and PR positivity (66.9%, χ2=7.36). Most AR positive cases showed a low proliferative index (63.7%) and a low or intermediate histological grade (G1–G2, 63.9%). Among the 80 selected ILCs, AR expression was observed in 64/80 (80%) cases. Our results confirm that ARs are expressed in most breast cancers. Moreover, we demonstrated that AR positivity is particularly marked in lobular neoplasms. In addition, AR positive carcinomas are frequently characterized by a low or intermediate grade, a low proliferative index and ER and/or PR co-expression.

Segmental bowel resection for colorectal endometriosis: is there a correlation between histological pattern and clinical outcomes?

BACKGROUND Laparoscopic segmental resection as a treatment for intestinal endometriosis can be supported by favorable clinical outcomes, but carries a high risk of major complications. The purpose of this study is to evaluate histopathological patterns of colorectal endometriosis and investigate potential relationships between histological findings and clinical data. METHODS We consecutively included 47 patients treated with laparoscopic segmental resection because of symptomatic colorectal endometriosis. All patients underwent follow-up for a median of 18 months (range: 6-35). We examined the histological patterns of colorectal endometriosis and evaluated the relationships between histological findings (satellite lesions, positive margins and vertical infiltration) and clinical outcomes (incidence of recurrence, quality of life and symptom improvement). Moreover, we observed if satellite lesions could influence preoperative scores of the short form-36 health survey (SF-36) questionnaire and visual analogue score (VAS) for pain symptoms. RESULTS There were no statistically significant differences in terms of anatomical and pain recurrences, pain symptoms and quality of life improvement among patients with or without positive margins, satellite lesions and different degrees of vertical infiltration (P > 0.05). Furthermore, women with or without satellite lesions were no different in terms of preoperative VAS of pain symptoms and SF-36 scores (P > 0.05). CONCLUSIONS The presence of satellite lesions or positive resection margins does not seem to influence clinical outcomes of segmental colorectal resection. Similarly, satellite lesions do not appear to have a major role in determining preoperative clinical presentation. These results may be useful to reconsider the surgical strategy for bowel endometriosis.

Nested stromal-epithelial tumor (NSET) of the liver: a case report of an extremely rare tumor.

Malignant mixed tumors of the liver in adults are extremely rare. To our knowledge, only a few cases have been reported in the literature. Nested stromal-epithelial tumors (NSET) of the liver are characterized by non-hepatocytic, non-biliary tumors with nests of epithelial and spindle cells, an associated myofibroblastic stroma, as well as variable calcifications and ossifications. We report a case of NSET of the liver affecting a young woman and provide detailed histological and clinical follow-up data, adding an additional case of this extremely rare pathology to the literature.

The role of 3D microenvironmental organization in MCF-7 epithelial-mesenchymal transition after 7 culture days.

We present a multi-technique study on in vitro epithelial-mesenchymal transition (EMT) in human MCF-7 cells cultured on electrospun scaffolds of poly(l-lactic acid) (PLA), with random and aligned fiber orientations. Our aim is to investigate the morphological and genetic characteristics induced by extracellular matrix in tumor cells cultured in different 3D environments, and at different time points. Cell vitality was assessed with AlamarBlue at days 1, 3, 5 and 7. Scanning electron microscopy was performed at culture days 3 and 7. Immunohistochemistry (for E-cadherin, β-catenin, cytokeratins, nucleophosmin, tubulin, Ki-67 and vimentin), immunofluorescence (for F-actin) western blot (for E-cadherin, β-catenin and vimentin) and transmission electron microscopy were carried out at day 7. An EMT gene array followed by PCR analysis confirmed the regulation of selected genes. At day 7, scanning electron microscopy on aligned-PLA revealed spindle-shaped cells gathered in buds and ribbon-like structures, with a higher nucleolar/nuclear ratio and a loss in E-cadherin and β-catenin at immunohistochemistry and western blot. An up-regulation of SMAD2, TGF-β2, TFPI2 and SOX10 was found in aligned-PLA compared to random-PLA cultured cells. The topography of the extracellular matrix has a role in tumor EMT, and a more aggressive phenotype characterizes MCF-7 cells cultured on aligned-PLA scaffold.

Question mark form of uterus: a simple sonographic sign associated with the presence of adenomyosis.

Adenomyosis as the presence of ectopic endometrial glands and stroma within the myometrium is an elusive condition that is challenging to diagnose due to the similarity between its clinical symptoms and ultrasound characteristics and those of other frequent benign conditions such as leiomyomatosis1. Over recent years, transvaginal sonography (TVS) has been recommended as an appropriate tool for visualization of adenomyosis, with a sensitivity of 65–81% and a specificity of 65–100%2. We performed a prospective study between January 2012 and January 2014 including 50 symptomatic fertile women who were scheduled to undergo elective hysterectomy because of symptoms of endometriosis/adenomyosis. Adenomyosis was diagnosed on TVS, in accordance with previous studies3,4, in the presence of one or more of the following criteria: heterogeneous myometrium, irregular cystic areas, hypoechoic linear striations, asymmetry of uterine walls and poor definition of the endometrial–myometrial junctional zone (JZ). Moreover, a novel sign, which we called ‘question mark Figure 1 Transvaginal ultrasound image and representative diagram showing the question mark form of the uterus as a marker for adenomyosis.

Histological evaluation of ureteral involvement in women with deep infiltrating endometriosis: analysis of a large series

STUDY QUESTION In women with deeply infiltrating endometriosis (DIE) what is the prevalence of involvement of endometriotic tissue and fibrosis in ureteral endometriosis (UE), as assessed by histological staining? SUMMARY ANSWER In women with DIE, ureteral involvement is more often due to endometriotic tissue rather than fibrosis. WHAT IS KNOWN ALREADY In the current literature, histological evaluation of ureteral endometriosis is mainly based on the degree of wall infiltration by endometriosis instead of the tissue composition. A few studies reported ill-defined and contradictory histological data on the tissue composition of UE. STUDY DESIGN, SIZE, DURATION Retrospective observational study based on clinical records of women affected by DIE, laparoscopically treated for UE at a tertiary referral center, between January 2010 and March 2013. All cases of ureteral nodule excision or ureterectomy with histological examination of the specimens were included. Exclusion criteria were other identified causes of hydroureteronephrosis, medical therapy for a period of at least 3 months before surgery and previous surgery for DIE. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 77 patients were included in the study and among them seven (9%) presented with bilateral ureteral involvement, giving a total of 84 cases of UE available for analysis. All patients had stage IV endometriosis. According, respectively, to the presence of endometrial glands and/or stroma cells or of fibrotic tissue only, the endometriotic UE and fibrotic UE groups were compared with regard to hydroureteronephrosis at pre-operative urinary tract computerized tomography scan, type of surgical procedure performed to treat UE (nodule removal or ureterectomy), association with other locations of the disease and post-operative complications (ureteral fistula or stenosis). MAIN RESULTS AND THE ROLE OF CHANCE For the 84 cases of UE, 65 (77%) and 19 (23%), respectively, showed endometriotic tissue and fibrotic tissue only. Presence of hydroureteronephrosis and endometriotic pattern of UE showed a significant association [endometriotic UE 44/65 (68%) versus fibrotic UE 8/19 (42%); P = 0.04]. Fibrotic pattern of UE and presence of concomitant recto-vaginal endometriosis showed a significant association [endometriotic group: 29/65 (45%) versus fibrotic group 18/19 (95%); P < 0.001]. LIMITATIONS, REASONS FOR CAUTION The retrospective and monocentric (tertiary referral center) study design. WIDER IMPLICATIONS OF THE FINDINGS Besides the distinction between extrinsic and intrinsic UE based on the degree of wall infiltration by endometriosis, a new classification according to the histological pattern of UE could be useful for clinicians, both in the diagnostic and therapeutic fields. STUDY FUNDING/COMPETING INTERESTS None.

Mixed Adenocarcinoma of the Rectovaginal Septum Associated with Endometriosis and Endometrial Carcinoma: A Case Report

Purpose: To present a case of primary mixed (clear cell and endometrioid type) adenocarcinoma of the rectovaginal septum, probably arising from endometriosis and associated with a highly differentiated, early-stage endometrioid endometrial carcinoma. The case was managed by a minimally invasive approach and postoperative adjuvant chemotherapy. Results: The patient underwent clinical/instrumental follow-up and a second-look laparoscopy after the primary surgery as well as adjuvant chemotherapy. No evidence of disease could be observed after the treatment. Conclusion: Surgery with postoperative chemotherapy can be recommended for the treatment of mixed adenocarcinoma of the rectovaginal septum.

Comparison of transvaginal sonography and computed tomography–colonography with contrast media and urographic phase for diagnosing deep infiltrating endometriosis of the posterior compartment of the pelvis: a pilot study

PurposeTo compare the diagnostic accuracy of transvaginal sonography (TVS) and computed tomography–colonography with contrast media and urographic phase (CTCU) in the preoperative detection of deep infiltrating endometriosis (DIE).Materials and methodsForty-seven patients with clinical suspicion of DIE underwent preoperative TVS and CTCU. Imaging data were compared with histopathologic analysis. Sensitivity, specificity, positive and negative predictive values and test accuracies of the two modalities were calculated.ResultsFor diagnosing intestinal DIE, TVS and CTCU had a sensitivity of 98 and 71%, specificity of 33 and 50%, positive predictive value of 91 and 91%, negative predictive value of 67 and 20%, accuracy of 89 and 68%, respectively. For diagnosing ureteral DIE, TVS and CTCU had a sensitivity of 10 and 60%, specificity of 94.8 and 70.2% on the right; sensitivity of 28.5 and 57.1%, specificity of 96.3 and 76.9% on the left, respectively.ConclusionTVS should be regarded as an accurate, radiation-free first-line diagnostic modality for patients with suspicion of posterior endometriosis. CTCU should be regarded as a complementary imaging modality, particularly for sigmoid or ureteral endometriosis.

One-Step Laparoscopic Management of a Female Adnexal Tumor of Wolffian Origin

We report a case of female adnexal tumor of Wolffian origin (FATWO), a rare neoplasm arising from the mesonephric ducts. A 48-year-old woman came first to our center for a recent discovery of a pelvic mass. Transvaginal ultrasonographic findings suggested a solid right para-ovarian mass suspected to be malignant. After thorough counseling, the patient underwent operative laparoscopy for excision of the para-ovarian mass with frozen section (FS) examination resulting in the diagnosis of a poorly differentiated adenocarcinoma. In this case, FS results allowed performing a comprehensive oncological staging, through a totally laparoscopic extrafascial hysterectomy, bilateral adnexectomy, total omentectomy, pelvic wall peritonectomy, and pelvic, parasacral and para-aortic lymphadenectomy. Final pathological and immunohistochemical results confirmed the diagnosis of FATWO. To our knowledge, this is the first case of FATWO managed entirely by a minimally invasive laparoscopic approach in a single surgical session.

Fertility‐Sparing Treatment of Endometrial Cancer with Initial Infiltration of Myometrium by Resectoscopic Surgery: A Pilot Study

Three women with a well-differentiated grade 1 endometrioid adenocarcinoma of the endometrium with minimal myometrial infiltration were treated with hysteroscopic resection and hormone therapy. The presence of myometrial infiltration has often been mentioned as an exclusion criterion for conservative management in young patients because of worsening cancer prognosis. The subsequent 5-year follow-up and the pregnancies achieved may confirm the choice of this temporary treatment and indicate a new option for fertility-sparing treatment in highly motivated patients.