Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumours): A Review with Special Emphasis on the Controversies in Management

Uterine carcinosarcomas (MMMT—malignant mixed Müllerian tumours) are highly aggressive, rare, biphasic tumours composed of epithelial and mesenchymal elements believed to arise from a monoclonal origin. While hysterectomy with bilateral salpingo-oophorectomy remains the mainstay treatment, high rates of recurrence and metastases suggest a need for lymphadenectomy and postoperative adjuvant treatment. There are no established consensus guidelines for therapeutic patient management. Though well recognized that it improves locoregional control, the role of radiation in improving overall survival outcomes remains undecided. Although various combinations of chemotherapy have been explored, an optimal therapeutic modality is yet to be determined. As overall survival rates have not improved in thirty years, it is suggested that targeted chemotherapy and/or a multimodality approach may yield better outcomes. This paper provides a summary of the aetiopathogenesis of carcinosarcomas (MMMT) limited to the uterus with special emphasis on the controversies in the management of these patients

Small fibre neuropathy in sarcoidosis

Sarcoidosis is characterized by multisystem granulomatous formation particularly in the chest. In this case report, we present an uncommon case highlighting significant peripheral nerve involvement, a phenomenon that is not well recognized  in sarcoidosis. The patient presented with severe incapacitating pain. Sarcoidosis as being the underlying cause was only established after extensive investigations. This case highlights the importance of recognizing small fibre peripheral polyneuropathy as a possible presentation of sarcoidosis. This could help to direct appropriate  medical intervention

A review of duodenal metastases from squamous cell carcinoma of the cervix presenting as an upper gastrointestinal bleed

Upper gastrointestinal bleeding due to duodenal metastases is extremely uncommon. Extra-pelvic spread of squamous cell carcinoma (SCC) of the cervix to the small bowel is rare with only 6 reported cases in the English literature since 1981(PubMed, Medline)

An appraisal of students' awareness of "self-reflection" in a first-year pathology course of undergraduate medical/dental education

<p>Abstract</p> <p>Background</p> <p>Self-reflection and reflective practice are increasingly considered as essential attributes of competent professionals functioning in complex and ever-changing healthcare systems of the 21^stcentury. The aim of this study was to determine the extent of students' awareness and understanding of the reflective process and the meaning of 'self-reflection' within the contextual framework of their learning environment in the first-year of their medical/dental education. We endorse that the introduction of such explicit educational tasks at this early stage enhances and promotes students' awareness, understanding, and proficiency of this skill in their continuing life-long health professional learning.</p> <p>Methods</p> <p>Over two years, students registered in first-year pathology at the University of Saskatchewan were introduced to a self-reflection assignment which comprised in the submission of a one-page reflective document to a template of reflective questions provided in the given context of their learning environment. This was a mandatory but ungraded component at the midterm and final examinations. These documents were individually analyzed and thematically categorized to a "5 levels-of-reflection-awareness" scale using a specially-designed rubric based on the accepted major theories of reflection that included students' identification of: 1) personal abilities, 2) personal learning styles 3) relationships between course material and student history 4) emotional responses and 5) future applications.</p> <p>Results</p> <p>410 self-reflection documents were analyzed. The student self-awareness on personal learning style (72.7% level 3+) and course content (55.2% level 3+) were well-reflected. Reflections at a level 1 awareness included identification of a) specific teaching strategies utilized to enhance learning (58.4%), b) personal strengths/weaknesses (53%), and c) emotional responses, values, and beliefs (71.5%). Students' abilities to connect information to life experiences and to future events with understanding were more evenly distributed across all 5 levels of reflection-awareness.</p> <p>Conclusions</p> <p>Exposure to self-reflection assignments in the early years of undergraduate medical education increases student awareness and promotes the creation of personal meaning of one's reactions, values, and premises in the context of student learning environments. Early introduction with repetition to such cognitive processes as practice tools increases engagement in reflection that may facilitate proficiency in mastering this competency leading to the creation of future reflective health professionals.</p

Expression of cell cycle proteins in male breast carcinoma

<p>Abstract</p> <p>Introduction</p> <p>Male breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints.</p> <p>Methods</p> <p>75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS).</p> <p>Results</p> <p>Decreased DFS was observed in the majority of tumors that overexpressed PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p = 0.04) and were associated with increased DFS of >150 months (p = 0.04). Overexpression of c-myc (90%) was linked with a higher incidence of node negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression was associated with decreased lymph node metastasis (p = 0.04). P21 and p57 positive tumors were related to decreased DFS (p = 0.04). Though p16 was overexpressed in 76.6%, this did not reach statistical significance with DFS (p = 0.06) or nodal status (p = 0.07).</p> <p>Conclusion</p> <p>Aberrant cell cycle protein expression supports our view that these are important pathways involved in the etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA with significantly worse outcomes. P27 appears to be a predictive marker for lymph nodal status. Such observation strongly suggests that dysregulation of cell cycle proteins may play a unique role in the initiation and progression of disease in male breast cancer. Such findings open up new avenues for the treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies in the future.</p

Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins

<p>Abstract</p> <p>Aim</p> <p>The aim of our study was to evaluate survival outcomes in malignant mixed Mullerian tumors (MMMT) of the uterus with respect to the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components.</p> <p>Methods</p> <p>23 cases of uterine MMMT identified from the Saskatchewan Cancer Agency (1970-1999) were evaluated. Immunohistochemical expression of Bad, Mcl-1, bcl-x, bak, mdm2, bax, p16, p21, p53, p27, EMA, Bcl-2, Ki67 and PCNA was correlated with clinico-pathological data including survival outcomes.</p> <p>Results</p> <p>Histopathological examination confirmed malignant epithelial component with homologous (12 cases) and heterologous (11 cases) sarcomatous elements. P53 was strongly expressed (70-95%) in 15 cases and negative in 5 cases. The average survival in the p53+ve cases was 3.56 years as opposed to 8.94 years in p53-ve cases. Overexpression of p16 and Mcl-1 were observed in patients with longer survival outcomes (> 2 years). P16 and p21 were overexpressed in the carcinomatous and sarcomatous elements respectively. Cyclin-D1 was focally expressed only in the carcinomatous elements.</p> <p>Conclusions</p> <p>Our study supports that a) cell cycle and apoptotic regulatory protein dysregulation is an important pathway for tumorigenesis and b) p53 is an important immunoprognostic marker in MMMT of the uterus.</p

The Evolution of Dieulafoy's Lesion Since 1897: Then and Now—A Journey through the Lens of a Pediatric Lesion with Literature Review

Background. In 1897, Dieulafoy was the first to characterize a gaping arteriole within the gastric mucosa causing massive hematemesis, designating it as “exulceratio simplex.” A hundred years later, this vascular abnormality, now commonly referred to as a “Dieulafoy lesion,” has been identified through the entire gastrointestinal tract and the bronchus. Objectives and Methods. As the original findings have been subjected to revisions and modifications by modern authors, Dieulafoy's original paper was reviewed and analyzed. The evolution of the current usage of “Dieulafoy's lesion” in the literature has been summarized with comparisons to the original report. Additionally, an index case of a 10-year-old female with a gastric “exulceratio simplex” is reported with a review of previously reported paediatric Dieulafoy lesions. Conclusions. The term “Dieulafoy lesion” in modern literature no longer adheres to the initial conclusions with regards to its origin, demographics, and presenting symptoms. Dieulafoy lesions remain a rare cause of gastrointestinal bleeding that can cause life-threatening haemorrhages in children

JL Uterine carcinosarcomas (malignant mixed müllerian tumours): a review with special emphasis on the controversies in management. Obstet Gynecol Int

Uterine carcinosarcomas (MMMT-malignant mixed Müllerian tumours) are highly aggressive, rare, biphasic tumours composed of epithelial and mesenchymal elements believed to arise from a monoclonal origin. While hysterectomy with bilateral salpingooophorectomy remains the mainstay treatment, high rates of recurrence and metastases suggest a need for lymphadenectomy and postoperative adjuvant treatment. There are no established consensus guidelines for therapeutic patient management. Though well recognized that it improves locoregional control, the role of radiation in improving overall survival outcomes remains undecided. Although various combinations of chemotherapy have been explored, an optimal therapeutic modality is yet to be determined. As overall survival rates have not improved in thirty years, it is suggested that targeted chemotherapy and/or a multimodality approach may yield better outcomes. This paper provides a summary of the aetiopathogenesis of carcinosarcomas (MMMT) limited to the uterus with special emphasis on the controversies in the management of these patients