Mesenchymal Components Research Articles

Cutaneous pilomatrical carcinosarcoma: a case report with molecular analysis and literature review

BackgroundCutaneous pilomatrical carcinosarcoma (CS) is a very rare biphasic tumor composed of admixed epithelial and mesenchymal malignant cells, with limited information on its pathogenesis. We report a case of pilomatrical CS of the scalp with comparative immunohistochemical and molecular analysis together with a review of the literature.Case presentationA 74-year-old woman presented with a rapidly growing long-standing tumor of the scalp. The tumor was surgically resected. Histologically, the tumor was 25 mm in diameter, and was composed of carcinoma showing a clear pilomatrical differentiation and sarcoma with pleomorphic spindle cells and giant cells. Both epithelial and mesenchymal components shared focal cytoplasmic and/or nuclear accumulation of β-catenin based on immunohistochemical analysis, although a mutation of exon 3 of the CTNNB1 gene was not detected. Fluorescence in situ hybridization analysis revealed gains of chromosomes 9p21, 3, and 7 in both the epithelial and sarcomatous components.ConclusionsThe current case demonstrated characteristic findings of pilomatricoma and further evidence of partial clonality between the carcinomatous and sarcomatous component, suggesting the possibility of malignant transformation of pilomatricoma. Rapid growth of a pilomatrical tumor should warrant the development of a malignant tumor, including CS.

BCOR Expression in Mullerian Adenosarcoma: A Potential Diagnostic Pitfall.

Adenosarcoma can mimic high-grade endometrial stromal sarcoma with ZC3H7B-BCOR fusion that may show entrapped glands and often exhibits diffuse BCOR expression. We encountered diffuse BCOR expression in rare adenosarcomas and sought to define its frequency among a larger cohort of these tumors. BCOR immunohistochemistry was performed on archival formalin-fixed paraffin-embedded tumor tissue in 13 of 14 adenosarcomas with and without stromal overgrowth arising in the uterus or ovary. The staining intensity and percentage of positive tumor nuclei in the mesenchymal component were evaluated. Eleven cases with sufficient tumoral tissue were subjected to fluorescence in situ hybridization for the detection of BCOR, BCORL1, NUTM1, ZC3H7B, and JAZF1 rearrangement. Three cases were subjected to targeted RNA sequencing. BCOR was expressed in 9 of 13 (70%) tumors, including 6 with and 3 without stromal overgrowth. Moderate to strong staining in >70% of cells was seen throughout in 1 low-grade and 6 high-grade tumors, 5 of which had stromal overgrowth. No staining was seen in 3 low-grade and 1 high-grade tumors with stromal overgrowth. One tumor demonstrating extensive sex cord-like differentiation and diffuse BCOR expression harbored JAZF1 and BCORL1 rearrangements. No BCOR or BCORL1 rearrangement was identified in the remaining tumors. BCOR expression is seen in most adenosarcomas with and without stromal overgrowth. BCORL1 rearrangement is seen in rare tumors with diffuse BCOR expression. Assessment of BCOR or BCORL1 rearrangement status is required in adenosarcomas demonstrating BCOR expression.

Trichoblastoma in a Dog: A Clinical, Diagnostic and Therapeutic Analysis

Background: Trichoblastoma is a rare skin neoplasm derived from the primitive hair follicle, having epithelial and mesenchymal components. Despite being commonly described as a benign tumor, there are reports in the literature of tumors with characteristics of malignant neoplasia. It affects adult dogs and cats, with no predilection for sex. Although rare, in studies in Brazil the pathology shows variable rates of occurrence. This work describes a case of tricoblastoma in a 4-year-old mixed breed dog, submitted to care at the Veterinary Hospital of the Federal University of Western Bahia (HVU-UFOB).Case: A 4-year-old male mixed breed dog with 7 kg of body weight, was referred to the HVU-UFOB. The main complaint reported by the canine’s tutor was an increase in volume in the region of the animal's face, which evolved slowly, associated with itching, bleeding and sensitivity to touch. During the physical examination, a round, elevated mass was observed in the subcutaneous tissue of the left face, in the mandible region, with local alopecia. On palpation, the neoformation showed a firm consistency, well-defined and fluctuating, with no solutions for continuity or discomfort to touch. The animal's physiological parameters were within the normal for the species. CBC, chest X-rays, abdominal ultrasound and aspiration cytology of the mass were requested. The blood count and image tests did not reveal any changes. On cytological examination, small, grouped basal epithelial cells were observed, characterized by a high nucleus-cytoplasm ratio, monomorphic nuclei and intensely basophilic and pigmented cytoplasm, a suggestive diagnosis of basal cell tumor. Due to the findings, an excisional biopsy of the mass was performed, with margins of 2 cm. The mass with its margins was sent for histopathological examination at the Animal Pathology Laboratory of the HVU. Macroscopically, an expansive mass was observed, covered by skin, was well defined, not encapsulated, distending the dermis, with a dome shape, measuring 8.0 x 5.0 x 4.0 cm in length, white and firm to the cut, with discrete lobulation. Microscopically, there was a proliferation of small cuboidal to elongated cells with a round to oval nucleus of loose chromatin and little evident nucleolus, and of a pale, scarce eosinophilic cytoplasm. Neoplastic cells were sometimes arranged in strings, palisades (ribbon type) or islands and were sometimes seen centrally aggregated emitting strands of cells (medusoid type) separated by moderate fibrovascular stroma, compatible with trichoblastoma. Tissue healing occurred satisfactorily, and the stitches were removed 10 days after the surgical procedure.Discussion: The clinical analysis of the case associated with the cytological and histopathological examination of the lesion allowed the visualization of physical and cellular changes, confirming the diagnosis of trichoblastoma. The animal involved was 4-years-old, within the chronological variability most affected by the tumor. The macroscopic lesions and the location of the neoplasia were also similar to those described in the literature. However, their race (mixed breed) was different from the most evident. Treatment based on total surgical excision of the neoplasia proved to be effective. This work is the first reported in the Western of Bahia describing a case of trichoblastoma in a dog.

Ameloblastic fibro-odontoma in an unusual area of the maxilla: Two Case Reports.

Ameloblastic fibro-odontoma (AFO) is a mixed odontogenic tumor, which has an epithelial and mesenchymal component. It can be observed in imaging tests as a radiomixed lesion, with some authors claiming it represents only the predecessor of an odontoma. Epidemiologically, it appears between the second and third decade of life, predominantly in males and with a predilection for the posterior area of the mandible. This lesion presents a good prognosis and it responds well to enucleation by curettage with a low rate of recurrence. In the present article, two cases of ameloblastic fibro-odontoma in an unusual region of the maxilla are presented.

Malignant phyllodes tumors of the breast associating malignancy of both mesenchymal and epithelial components (invasive or in situ ductal carcinoma).

Phyllodes tumors of the breast are biphasic tumors consisting from an epithelial component and a mesenchymal component. Usually, the mesenchymal component of the tumor is the one who dictates the malignancy of the biphasic proliferation. Presence of the malignancy of the both, epithelial [under the form of invasive carcinoma or ductal carcinoma in situ (DCIS)] and mesenchymal components is very rare. Most of the data available from the literature refers to single case presentations. This paper presents the experience of Prof. Dr. Ion Chiricuţă Oncological Institute (IOCN), Cluj-Napoca, Romania, with the malignant phyllodes tumors with both epithelial and mesenchymal components showing malignancy. Over two decades (1999–2018), four cases of malignant phyllodes tumors with concomitant epithelial and mesenchymal malignancy were found and presented as a case series. Two out of four cases were malignant phyllodes tumors harboring invasive breast carcinomas (one case with associated DCIS and one case of pure invasive carcinoma) and two cases were malignant phyllodes tumors with the epithelial component showing DCIS. Average follow-up period was 67 months (from 39 to 132 months) with a disease-free survival of 58 months.

The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components.

ABSTRACTIn the anterior foregut (AFG) of mouse embryos, the transcription factor SOX2 is expressed in the epithelia of the esophagus and proximal branches of respiratory organs comprising the trachea and bronchi, whereas NKX2.1 is expressed only in the epithelia of respiratory organs. Previous studies using hypomorphic Sox2 alleles have indicated that reduced SOX2 expression causes the esophageal epithelium to display some respiratory organ characteristics. In the present study, we produced mouse embryos with AFG-specific SOX2 deficiency. In the absence of SOX2 expression, a single NKX2.1-expressing epithelial tube connected the pharynx and the stomach, and a pair of bronchi developed in the middle of the tube. Expression patterns of NKX2.1 and SOX9 revealed that the anterior and posterior halves of SOX2-deficient AFG epithelial tubes assumed the characteristics of the trachea and bronchus, respectively. In addition, we found that mesenchymal tissues surrounding the SOX2-deficient NKX2.1-expressing epithelial tube changed to those surrounding the trachea and bronchi in the anterior and posterior halves, as indicated by the arrangement of smooth muscle cells and SOX9-expressing cells and by the expression of Wnt4 (esophagus specific), Tbx4 (respiratory organ specific), and Hoxb6 (distal bronchus specific). The impact of mesenchyme-derived signaling on the early stage of AFG epithelial specification has been indicated. Our study demonstrated an opposite trend where epithelial tissue specification causes concordant changes in mesenchymal tissues, indicating a reciprocity of epithelial-mesenchymal interactions.

MORPHOLOGICAL CHARACTERISTICS OF PLEOMORPHIC ADENOMAS OF SALIVARY GLANDS (ANALYSIS OF THE SURGICAL MATERIAL)

The aim of the study is to reveal the morphological features of pleomorphic adenomas of the salivary glands during a comprehensive examination of the surgical material. Materials and methods: Surgical material from 30 patients with pleomorphic adenomas of the salivary glands was studied. Microspecimens stained with hematoxylin and eosin were studied, using an Olympus BX-41 microscope (Japan) with subsequent processing with the Olympus DP-soft version 3.1 software, which was used to conduct a morphometric study. By morphometry in the tumor tissue, the specific volumes of the parenchyma and stroma, the thickness of the capsule located between the tumor tissue and the tissue of the salivary gland were determined; the absolute number of vessels in the field of view of the microscope was counted at × 100 magnification. Results: Comprehensive morphological analysis of the surgical material of removed neoplasms of the salivary glands has showed that mesenchymal (15 cases, 50.0%) and mixed (10 cases, 33.3%) variants of pleomorphic adenomas are more common, and less often epithelial variants (5 cases, 16.7%). Pleomorphic adenoma is characterized by a different ratio of the epithelial (parenchymal) and mesenchymal (stromal) components forming this tumor, structural diversity and heterogeneity of the structure of these components, which do not have clear boundaries and are mixed with each other. A characteristic feature of pleomorphic adenoma is also the combination in each case of different types of epithelial cells and the structures that they form, as well as areas of various differentiation of the mesenchymal component. Mesenchymal and mixed variants of pleomorphic adenomas, in comparison with the epithelial variant, are more prone to progression and recurrence, as evidenced by our identified active processes of angiogenesis in tumor tissue, frequent tumor invasion of the capsule, thinning of the capsule or the absence of the capsule, less pronounced infiltration of the capsule by immune cells. Conclusions: The morphological features of mesenchymal, mixed and epithelial variants of pleomorphic adenomas of the salivary glands revealed by the authors should be takeninto account by clinicians during choosing the tactics for treating the patient, which will undoubtedly help to reduce the incidence of tumor malignization and its recurrence.

Sarcomatoid carcinoma of adrenal gland: a rare case report

Adrenal sarcomatoid carcinoma (ASC) are very rare and aggressive malignant tumors of adrenal glands containing both epithelial (carcinomatous) and mesenchymal (sarcomatous) components. ASC presents a diagnostic challenge due to its atypical symptoms and histological patterns which influence treatment.At the time of diagnosis, a large percentage of patients are already at the metastatic stage and succumb within a few months. Here, we report a case of functional sarcomatoid carcinoma in right adrenal gland in a 37-year-old female, who presented with new onset hypertension. The patient underwent right sided adrenalectomy and she was alive at the time of writing the current report.To the best of our knowledge, ASC reported in literature to date showed only few patient presented with endocrine hypersecretion and only one patient presented with both hypertension and endocrine dysfunction. So, our case is the rarest among the rare.
 Birdem Med J 2020; 10(1): 73-75

IMMUNOHISTOCHEMICAL EXPRESSION OF FASN AND COX-2 IN AMELOBLASTOMA, AMELOBLASTIC FIBROMA, AND MALIGNANT COUNTERPARTS

Objective Analyze for the first time the immunohistochemical expression in tooth germ (TG) ameloblastoma (AM), ameloblastic carcinoma (AC), ameloblastic fibroma (AF) and ameloblastic fibrosarcoma (AFS) of fatty acid synthase (fasn) and cyclooxygenase (cox-2), which are highly associated to tumorigenic events and poor prognosis in several types of cancer and also are promising chemotherapy targets. Study Design Immunohistochemistry for fasn and cox-2 was performed in 10 TG, 44 solid or conventional AM, 10 AC, 9 AF, and 5 AFS. Results were analyzed using the Immunoreactive Score (IRS). Results Most TG were strongly positive for fasn and negative or weakly positive for cox-2. All AM and AC expressed fasn and cox-2. AC showed higher expression of both markers. In AF, fasn and cox-2 were variably expressed in epithelium and negative in the mesenchyme, while in AFS, the mesenchymal malignant component was strongly positive for fasn, whereas cox-2 was negative in both components. Conclusions The coexpression of fasn and cox-2 may be involved in the pathogenesis and behavior of AM and AC, while in AFS only fasn seems to play a role in the sarcomatous component. These markers could be a potential therapeutic target in the future; however, further studies are necessary.

Pulmonary blastoma in an adult male

Pulmonary blastoma is one of the rare lung tumors and is considered to be dissnct from other lung tumors by its pathological features, clinical course and prognosis.1 Classic pulmonary blastoma is composed of both malignant mesenchymal stroma and epithelial components resembling embryonic lung tissue. Surgery is the standard treatment and the efficacy of adjuvant chemotherapy and radiotherapy has not yet been established

Trichoblastic carcinosarcoma: A case report and literature review

Trichoblastic carcinosarcoma is a rare biphasic adnexal neoplasm. This case report chronicals the eighth occurrence of this tumor published in the English literature and provides a review of the prior publications. Clinically, this tumor presents as an isolated, rapidly growing lesion in elderly patients and is usually cured by complete surgical excision, with no evidence of recurrence or metastasis at follow-up (7/8 cases). Histopathologically, trichoblastic carcinosarcoma is dermal-based, with an epithelial component of basal cells and a mesenchymal component of spindle cells, both of which display malignant features. In addition to a morphologic description of trichoblastic carcinosarcoma, a discussion of the differential diagnoses, including other biphasic neoplasms, is also included. The small number of cases of trichoblastic carcinosarcoma is most likely secondary to under-recognition and underreporting and a larger case volume is needed to more accurately assess the clinical course and treatment strategies.

Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition

Uterine carcinosarcoma is an aggressive variant of endometrial carcinoma characterized by unusual histologic features including discrete malignant epithelial and mesenchymal components (carcinoma and sarcoma). Recent studies have confirmed a monoclonal origin, and comprehensive genomic characterizations have identified mutations such as Tp53 and Pten However, the biological origins and specific combination of driver events underpinning uterine carcinosarcoma have remained mysterious. Here, we explored the role of the tumor suppressor Fbxw7 in endometrial cancer through defined genetic model systems. Inactivation of Fbxw7 and Pten resulted in the formation of precancerous lesions (endometrioid intraepithelial neoplasia) and well-differentiated endometrioid adenocarcinomas. Surprisingly, all adenocarcinomas eventually developed into definitive uterine carcinosarcomas with carcinomatous and sarcomatous elements including heterologous differentiation, yielding a faithful genetically engineered model of this cancer type. Genomic analysis showed that most tumors spontaneously acquired Trp53 mutations, pointing to a triad of pathways (p53, PI3K, and Fbxw7) as the critical combination underpinning uterine carcinosarcoma, and to Fbxw7 as a key driver of this enigmatic endometrial cancer type. Lineage tracing provided formal genetic proof that the uterine carcinosarcoma cell of origin is an endometrial epithelial cell that subsequently undergoes a prominent epithelial-mesenchymal transition underlying the attainment of a highly invasive phenotype specifically driven by Fbxw7.

COMP-15. MOLECULAR AND CLONAL EVOLUTION IN RECURRENT METASTATIC GLIOSARCOMA

Abstract Gliosarcoma, a World Health Organization grade IV glioma, is a rare variant of glioblastoma (GBM) that contains distinct glial and mesenchymal components. Histologically, the glial component matches criteria for glioblastoma, and both components share genetic alterations common to GBM. Though GBM are known to strongly infiltrate surrounding tissue, extracranial metastases are rare, and the underlying mechanisms are still poorly understood. We present a rare case of a 37-year-old woman who was initially diagnosed with IDH wild-type gliosarcoma in the frontal lobe and later developed two local recurrences and extracranial metastases to the vertebral and pelvic bones. In order to understand the clonal relationships between four tumor instances and the origin of metastasis, we performed whole genome sequencing of the intracranial tumors and the tumor located in the right iliac bone. We compared mutational and copy number profiles and inferred tumor clonal phylogeny. The tumors harbored shared GBM alterations including TP53, NF1, and RB1 mutations and CDKN2A deletion. Comparisons of the metastatic to intracranial tumors highlighted a high similarity in molecular profiles, but contrasting evidence regarding the origin of the metastasis. The metastasis was most similar to the second recurrence with respect to mutational signatures, reflected in the activity of signatures associated with defective DNA mismatch repair not observed in the primary or first recurrent tumor. The metastasis was most similar to the first recurrence with respect to copy number profile; both samples displayed widespread amplifications indicative of whole genome doubling. Results of subclonal reconstruction suggested that the second recurrent and metastatic tumors originated from more than one clone and developed subclone-specific driver mutations. The branching phylogeny and copy number profiles suggest the metastasis was largely derived from the first recurrence. This is the first analysis of clonal evolution of extracranial metastasis in gliosarcoma and highlights alterations driving aggressive GBM progression.

A case of hepatic leiomyosarcoma with osteosarcomatous differentiation (malignant mesenchymoma) in a dog

A rare spontaneous hepatic leiomyosarcoma with osteosarcomatous differentiation was observed in a female beagle dog and its morphological and immunohistochemical characteristics were examined. Upon necropsy, an endoceliac mass originating from the liver was detected, which was composed of hematoid fluid-filled cysts and white to grayish solid tissue. There were no macroscopic findings in other organ systems. Histopathologically, the hepatic mass consisted of two different mesenchymal components. One form was spindle cells arranged in interlacing fascicles immunohistochemically positive for smooth muscle actin (SMA) and smoothelin, indicating leiomyosarcomatous differentiation. The other form was composed of short spindle cells positive for S-100 and was producing various amounts of eosinophilic osteoid and trabecula-like matrices positive for osteocalcin, indicating osteosarcomatous differentiation. In addition, invasive growth in the hepatic parenchyma and cell atypia were observed. Based on these findings, the mass was diagnosed as hepatic leiomyosarcoma with osteosarcomatous differentiation (malignant mesenchymoma), which might be derived from undifferentiated mesenchymal cells.

A unique uterine cervical \u201cteratocarcinosarcoma\u201d: a case report

BackgroundTeratocarcinosarcoma (TCS) is a rare aggressive tumor of the nasal cavity and paranasal sinuses and has both epithelial and two or more mesenchymal components. In other organs, 5 cases of ovarian tumors closely resembling TCS have been reported; however, there has been no published case of cervical TCS. Herein, we describe a unique case of cervical tumor that had carcinosarcomatous and teratomatous features, resembling a sinonasal TCS.Case presentationA 45-year-old woman presented to our hospital for evaluation of a cervical lesion. The gynecologist found a large polypoid mass, whose biopsy showed glandular components of probable germ cell origin based on the immunohistochemical features. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy. The cervical polypoid mass was found to consist of both epithelial and mesenchymal tissues, including immature glandular structure resembling fetal enteric tubules, neuroepithelial cells, hyaline cartilage, and rhabdomyosarcoma cells. This tumor was diagnosed as TCS of the uterine cervix. Following the surgery, the patient received radiotherapy and has been free of disease for 13 months.ConclusionThis is the first case report of cervical TCS. The tumor is thought to be histogenetically less associated with HPV infection, and its teratomatous components with an absence of cytogenetic abnormalities (including isochromosome 12p (i(12p)) suggest a analogous histogenesis compared to pure mature or immature teratoma.

Mutational and Immunophenotypic Profiling of a Series of 8 Tubo-ovarian Carcinosarcomas Revealed a Monoclonal Origin of the Disease.

Carcinosarcomas are rare, highly aggressive neoplasms composed of a combination of carcinomatous and sarcomatous elements. These tumors represent a paradigmatic field for the study of intratumor heterogeneity. A series of 8 tubo-ovarian carcinosarcomas was characterized for the following: (i) immunohistochemical expression of MNF116, epithelial membrane antigen, vimentin, S100, chromogranin, synaptophysin, desmin, myogenin (MYF4), and p53; (ii) mutational profiling of KRAS, BRAF, PIK3CA, NRAS, TP53, and DICER1 genes. Heterologous differentiation was present in 6 of 8 tumors. Cytokeratin MNF116 and epithelial membrane antigen were positive in all the carcinomatous components and in 87.5% and 50.0% of the sarcomatous components, respectively. The sarcomatous components showed positive staining for vimentin in all cases. Two cases demonstrated positivity for neuroendocrine markers in their carcinomatous components. All rhabdomyosarcomas were positive for desmin and MYF-4. Chondrosarcomas were positive for S100. All but one tumor showed similar p53 immunoreactivity in both the carcinomatous and sarcomatous components, and one case showed cytoplasmic p53 expression. Three of 8 cases (37.5%) showed TP53 mutations, and, in 2 cases, the TP53 mutation was shared by both epithelial and mesenchymal components. DICER1 mutation was found in all components of one case. Mutations in KRAS, NRAS, BRAF, and PIK3CA genes were not found in the study cohort. Our results highlight the heterogeneity of ovarian carcinosarcomas at the phenotypic level. A common mutational signature was observed in both components in 3 of 4 informative tumors. More studies are required to dissect different levels of ovarian carcinosarcomas' heterogeneity in order to define the best therapeutic approaches to these aggressive neoplasms.

Endobronchial Hamartoma: A Rare Cause of Chronic Cough

A 57-year-old man with a 37-pack year history of smoking was referred to the pulmonary clinic for evaluation of chronic cough, shortness of breath, and intermittent episodes of right-sided chest pain of 6 months' duration. He reported a history of cocaine and heroin abuse, which he had quit 11 years before, and denied any other medical problems. Physical examination did not reveal any abnormalities. Computed tomography of chest revealed an endobronchial nodule in the right upper lobe (Panel A). Bronchoscopy revealed a smooth mass occluding the entrance of the right upper lobe bronchus (Panel B). Biopsies followed by argon plasma coagulation for tumor destruction was performed. Histopathology revealed epithelial and mesenchymal components consistent with hamartoma (Supplemental Image, Panel C, available online at http://www.mayoclinicproceedings.org). On follow-up 2 months later; the patient is doing well without respiratory limitations, with repeat bronchoscopy showing almost complete resolution (Supplemental Image, Panel D). Hamartomas are the most common benign tumors of the lung; however, the majority of these tumors are found peripherally, with an endobronchial location reported in 1.4% to 10% of cases.1Ahmed S. Arshad A. Mador M.J. Endobronchial hamartoma; a rare structural cause of chronic cough.Respir Med Case Rep. 2017; 22: 224-227Crossref PubMed Scopus (11) Google Scholar Download .pdf (3.67 MB) Help with pdf files Supplemental Image, Panel CHistopathology sections showing cartilage and adipose tissue, with respiratory epithelium consistent with hamartoma. Download .pdf (1.24 MB) Help with pdf files Supplemental Image, Panel DFollow up bronchoscopy showing almost complete clearance of tumor. Supplemental material can be found online at http://www.mayoclinicproceedings.org. Supplemental material attached to journal articles has not been edited, and the authors take responsibility for the accuracy of all data.

Molecular: Genetic analysis of uterine carcinosarcomas

Abstract Background Tissue precursors of uterine carcinosarcomas remain unknown, therefore targeted therapy has not been determined. Methods This research is based on the investigation of formalin‐fixed, paraffin‐embedded tissue blocks from 17 women undergoing primary surgical treatment between 1961–2010, that were retrieved from the pathoanatomical department of the Institute of Oncology named after N.N.Petrov. In the present study, molecular investigations were applied to determine the pathogenesis of uterine carcinosarcomas. We have analyzed microsatellite instability, mutations of TP53 (exons 5-9), PTEN (exons 5, 8), K-RAS (exon 1) and loss of heterozygosity of variable loci of the chromosome 17 in epithelial and mesenchymal components of uterine carcinosarcomas. DNAs were extracted by proteinase K digestion («Fisher» US) by Herrington, C.S. & McGee, J.O. Mutations of TP53, PTEN and K-RAS were defined by SSCP with the next sequence. Highly sensitive markers BAT 26 and BAT 40 were used for analysis of microsatellite instability. Results The loss of heterozygosity of variable markers of the short arm of the 17th chromosome was detected (in 9 of 17 tumours- 52,9%). All 17 tumours were microsatellite stable. K-ras mutations were detected in 2 of 17 tumours - 11,7%. One tumour contained identical mutations in both components, other one contained mutations only in the epithelial component. Mutations in the TP53 were identified in 13 of 17 tumours - 76,5%. Five (29,4%) tumours contained identical mutations in both components, 8 (47,1%) - only in the epithelial component and 4 showed wild-type TP53. PTEN mutations were detected in 11 of 17 tumours - 64,7%. Six tumours (35,3%) contained wild-type PTEN. Tumours with PTEN mutations showed worse prospects than ones with wild-type PTEN: 1-yr overall survival - 12,5% vs 60 %, р Conclusions Uterine carcinosarcomas are the microsatellite stable tumours. This type of tumours is associated with chromosomal instability of the genome. PTEN mutations are matched with poor prognosis and low overall survival. The present study of PTEN damages may be important for targeted therapy by the PARP inhibitors. Legal entity responsible for the study Russian Medical Academy for Continuous Professional Education. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Multicystic dysplastic kidney: Ten-year evaluation

Introduction: Multicystic dysplastic kidney (MCDK) is the most common form of developmental abnormality seen in infants and children. It is almost always unilateral and slightly more frequent in boys and on the left side. The other associated extra-renal abnormalities include esophageal atresia, tracheoesophageal atresia, ventricular septal defect and patent ductus arteriosus. The routine widespread use of antenatal ultrasonography has led to early detection of this abnormality. Materials and Methods: We retrospectively assessed fourteen cases of Multicystic dysplastic kidney between January 2004 and December 2014. All the cases underwent total nephrectomy and the specimens were sent to the department of Pathology with their respective clinical details and pathological findings were analyzed. Results: A total of fourteen (14) patients were diagnosed with unilateral MCDK over a period of 10 years with no sex predilection. Majority were on left side and antenatally diagnosed. Some patients had associated hypertension, vesicoureteral reflux and ureteropelvic junction obstruction. Microscopy revealed renal parenchyma replaced by cysts of variable sizes lined by flattened cuboidal epithelium. Intervening fibrotic stroma with mesenchymal components, primitive glomeruli, nerve bundles and dysplastic ducts. Conclusion: MCDK is mostly a unilateral sporadic anomaly usually found on the left side, however can be familial. It may be associated with hypertension, vesicoureteral reflux and ureteropelvic junction obstruction. Most of the patients can be diagnosed antenatally and confirmed on histopathology. Keywords: Multicystic dysplastic kidney, Dysplastic kidney, Cystic kidney.

Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma: Impact on Prognosis and Insights Into Tumorigenesis.

Endometrial carcinosarcoma (ECS) is a rare and aggressive mixed-type epithelial and mesenchymal tumor. This study focused on the histologic appearance, loss of DNA mismatch repair (MMR) protein expression, and aberrant p53 expression in the epithelial component, and overall prognosis of 57 cases with ECS. Histologically, 21 and 36 cases exhibited low-grade (endometrioid grade 1 and 2) and high-grade (others) epithelial components, respectively. In a Kaplan-Meier analysis, patients with a high-grade epithelial component exhibited worse progression-free survival (PFS), compared with those with a low-grade component. Although the former group also exhibited worse overall survival, the difference was not significant. Thirty-six cases exhibited aberrant p53 expression. Of these, 5 cases exhibited focally aberrant p53 expression in carcinomatous components with diffuse aberrant p53 expression in mesenchymal components. Aberrant expression of p53 did not show significant association with prognosis. Six patients with MMR deficiency exhibited relatively better PFS. In conclusion, a low-grade epithelial component is a superior predictor of the PFS of ECS, compared with MMR protein and p53 expression status. In some cases of ECS, TP53 mutation may be a late event associated with histogenesis of the sarcomatous component.