Mesenchymal Components Research Articles

An Infrequent Adenosarcoma Mimicking other Uterine Rhabdoid Tumours

Uterine sarcomas are relatively rare and account for only 1-3% of all malignancies in the Female Genital Tract (FGT). Adenosarcomas of the uterus are uncommon accounting for only 5% of uterine sarcomas. They are considered less recurrent and less metastatic. However, those with sarcomatous overgrowth and heterologous differentiation are very rare, considered aggressive and need to be differentiated histologically from other sarcomas that mimic the same clinically and histologically. In the index case, a 50-year-old female presented with symptoms of pain in the abdomen and bleeding per vagina. Magnetic Resonance Imaging (MRI) showed a large polypoid solid mass in the endometrium, suggestive of a sarcoma. Positron Emission Tomography (PET) scan showed an Fluorodeoxyglucose (FDG) avid lesion in the endometrial cavity (SUV max-13.33). Total abdominal hysterectomy and salpingooophorectomy was performed. Histology showed a biphasic tumour (benign glands and malignant mesenchymal component) with rhabdomyoblastic differentiation and sarcomatous overgrowth. Presence of rhabdoid cells raises the possibility of other sarcomas with these features making the diagnosis challenging. Immunohistochemistry (IHC) confirmed it to be a high grade adenosarcoma with sarcomatous overgrowth. Desmin positivity was noted in the rhabdoid cells. Majority cases of adenosarcoma are low grade, the index case was however high grade with presence of heterologous elements and sarcomatous overgrowth. Neither radiology nor clinical features can reliably differentiate adenosarcomas from other uterine sarcomas. A definitive diagnosis can be made by understanding the overlapping morphological features and correlate it with IHC to reliably differentiate it with other similar looking uterine sarcomas.

Metaplastic breast carcinoma:series of cases and literature review

Introduction: Metaplastic breast carcinoma is a heterogeneous group of infrequent invasive carcinomas with aggressive behavior. It presents differentiation from the neoplastic ductal epithelium to squamous and/or sarcomatous mesenchymal component, through the epithelial-mesenchymal transition process, and may present morphology of epithelioid and fusiform cells, with possible cartilage, bone, lipomatous, fibromatous, smooth muscle or skeletal muscle differentiation, among others. Most of the cases present the triple-negative immunohistochemical profile. Objective: To report three cases of metaplastic carcinomas, with an emphasis on clinical and pathological aspects, in addition to conducting a literature review on this topic. Methods: The three cases were registered in the internal search system for reference services in breast pathology in São Paulo, between 2012 and 2019. For literature review, the keywords metaplastic carcinoma, breast, cancer, review, breast cancer subtype and pathological and clinical outcomes were used in PubMed. We found 154 articles, of which 42 were selected for full reading, based on the abstract and established inclusion criteria. After this initial selection, these articles were read and reviewed; nine articles that did not meet the inclusion criteria were excluded. Discussion: Three cases of metaplastic carcinoma with similar immunohistochemical characteristics have been reported. The first case is that of a 40-year-old patient with the diagnosis of metaplastic carcinoma producing a chondroid matrix with liposarcomatous and osteosarcomatous differentiation. The second case is that of a 50-year-old patient who presented with the final diagnosis for a fusocellular metaplastic carcinoma with lymph node metastasis. Finally, the third case described is that of a 59-year-old patient, who presented metaplastic carcinoma with chondroid differentiation. Conclusion: Metaplastic carcinoma is a rare and aggressive type of breast cancer, in which most of the patients have shorter survival and worse prognosis in relation to the other subtypes. More studies are needed in order to determine a gold standard treatment for this disease.

IMMUNOHISTOCHEMICAL FEATURES OF THE EXPRESSION OF HUMAN PAPILLOMA VIRUS TYPE 16 IN PLEOMORPHIC ADENOMAS OF SALIVARY GLAND

The aim is to reveal the immunohistochemical features of human papilloma virus type 16 expression in various histological variants of pleomorphic adenomas of the salivary gland. Materials and methods: The material of the study was surgical and biopsy material from 30 patients with pleomorphic adenomas of the salivary glands, among which in 15 cases mesenchymal was detected, in 10 - mixed, in 5 cases - epithelial histological variant, respectively. Immunohistochemical study was performed, using mouse monoclonal antibody to human papilloma virus type 16. Visualization was performed, using an EnVisionTM FLEX detection system. Histological sections of grade III cervical intraepithelial neoplasia (CIN III) were used as a positive control; for a negative control, the procedure was performed without primary antibodies. The immunohistochemical reaction was assessed by a semi-quantitative method by counting the percentage of positively stained cells in the field of view of a microscope × 400. Microspecimens were studied, photoarchived on an Olympus BX-41 microscope. Results: Expression of human papilloma virus type 16 of varying severity was determined in 26 cases of pleomorphic adenomas of the salivary glands, which was 86.7%. The epithelial component of the pleomorphic adenoma of the salivary gland was characterized by a more pronounced expression of the monoclonal antibody to human papilloma virus type 16 compared to the mesenchymal component of the tumor. The severity of the immunohistochemical reaction with a monoclonal antibody to human papilloma virus type 16 depended on the histological variant of the pleomorphic adenoma of the salivary gland. Epithelial, mixed and mesenchymal variants of pleomorphic adenoma of the salivary gland were characterized, respectively, by the most pronounced, pronounced and moderately pronounced expression of a monoclonal antibody to human papilloma virus type 16. Conclusions: A comprehensive immunohistochemical study with a monoclonal antibody to human papilloma virus type 16 revealed the presence of a causal relationship between the infection of a patient with human papilloma virus type 16 and development of pleomorphic adenoma of the salivary gland in him.

Carcinosarcoma Stomach with Biphasic Nodal Metastasis: A Rare Entity

Gastric carcinosarcoma is an extremely rare, aggressive, biphasic tumour composed of a mixture of carcinomatous and sarcomatous elements. Clinical symptoms and imaging studies of carcinosarcoma are not different from that of carcinoma. Biopsy of the lesions may not include both components. Thus, a diagnosis of carcinosarcoma is often rendered in surgical specimens. Immunohistochemistry will help to identify the various components. The relative proportion of the carcinomatous and sarcomatous elements is variable. One of the components may dominate the histologic picture. The common carcinomatous component described is adenocarcinoma with rare cases, showing neuroendocrine and squamous elements. The sarcomatous elements include spindle cell sarcoma which was Not Otherwise Specified (NOS), leiomyosarcoma, fibrosarcoma, osteosarcoma, chondrosarcoma, liposarcoma, undifferentiated sarcoma, myxoid sarcomas, and rhabdomyosarcoma. Herein, the authors are reporting the case of a 62-year-old female patient who presented with abdominal pain and vomiting of three-month duration. Endoscopic examination revealed a large polypoidal mass lesion in the body of stomach. Subtotal gastrectomy was done which showed large polypoidal mass lesion measuring 12×9.5×6 cm. Histopathological examination revealed a biphasic neoplasm with close intermingling of malignant epithelial and mesenchymal elements. Carcinoma component showed glandular, squamous and neuroendocrine areas. The sarcomatous component was spindle cell sarcoma, NOS. On immunohistochemical examination, epithelial component showed cytokeratin positivity. The neuroendocrine component was positive for synaptophysin, chromogranin A and CD56. The p40 positivity noted in the squamous component. The mesenchymal component showed positivity for vimentin. The nodal metastasis showed admixture of carcinoma (glandular and squamous components) and sarcoma.

Multifocal sarcomatoid urothelial carcinoma of the renal pelvicalyceal system and ureter: A diagnostic dilemma

Sarcomatoid urothelial carcinomas (SUCs) are characterized by intimately mixed malignant epithelial and malignant mesenchymal components. We present a case of a multifocal SUC in the left pelvicalyceal system of the kidney and the left ureter. SUC although rare should be included in the differential diagnosis of multifocal tumors of the renal pelvis and ureter. Immunohistochemistry is essential to confirm the diagnosis and rule out other differentials including pure sarcoma, sarcomatoid variant of renal cell carcinoma, and pseudosarcomatous mesenchymal proliferation.

Metaplastic Carcinoma with Mesenchymal Differentiation in Augmented Breast using Liquid Silicone Injection: A Case Report

The relationship between the use of liquid silicone for breast augmentation and carcinogenesis remains undetermined due to limited data reported, especially regarding its risks for acquiring cancer. We documented a case of an 81-year-old woman who presented with bilateral enlarging breast masses with a known history of breast augmentation using liquid silicone. On microscopic examination, the malignancy showed both mesenchymal and epithelial components in a background of stromal changes related to liquid silicone. Based from morphology and immunohistochemistry studies (p63, CK, HMW-CK, and CK5/6, CD34, and BcL-2), this case was signed out as metaplastic carcinoma with mesenchymal differentiation. This rare case of metaplastic carcinoma with mesenchymal differentiation coexisting with liquid silicone, provides evidence supporting the link between cancer development and siliconomas.

Hamartoma fibroso de la infancia: una serie de 21 casos y revisión de la literatura

BackgroundFibrous hamartoma of infancy (FHI) is a rare soft-tissue tumor usually seen in infants and young children. Histologically, the tumor is characterized by a triphasic morphology, and the clinical course is benign. MethodsWe described the histopathologic and immunohistochemical features in a series of 21 cases of FHI and reviewed the main entities to consider in differential diagnosis. ResultsMost patients in the series were male. The mean age was 3.7 years (range, 5 months–24 years), and lesions were found in locations that have been previously reported. Histopathologically, the tumors were composed of variable proportions of fibroblastic, mesenchymal, and mature adipose tissue. Three of the 13 immunohistochemically stained biopsies (14%) contained hyalinized zones with cracking artifacts, mimicking giant cell fibroblastoma. Eight of the 13 stained with smooth-muscle actin (61%) were positive in the fibroblastic component, 6 of the 8 stained with CD34 (75%) were positive in the immature mesenchymal and fibroblastic components, and all 7 stained with S100 were positive (100%) in adipose tissue. ConclusionsOur histopathologic findings are consistent with those described in larger series. However, in order to reach a precise diagnosis and plan treatment, clinical heterogeneity obliges us to become familiar with variations in the characteristic triphasic histology of FHI.

Mixed Endometrioid Adenocarcinoma and Müllerian Adenosarcoma of the Uterus and Ovary: Clinicopathologic Characterization With Emphasis on its Distinction From Carcinosarcoma.

Mullerian adenosarcoma is a biphasic neoplasm composed of benign or atypical Müllerian epithelium and a malignant mesenchymal component that is usually, but not always, of low grade. Focal architectural or cytologic atypia of the epithelial component resembling atypical hyperplasia may uncommonly be present and foci of adenocarcinoma have been rarely reported. Whether the coexistence of these 2 tumor components is a result of independent primaries (collision tumor), adenocarcinoma arising from the epithelial component of the adenosarcoma, an unusual form of carcinosarcoma or some other mechanism is uncertain. To establish the diagnostic criteria and clinical significance of the coexistence of adenocarcinoma in close association with Müllerian adenosarcoma, we conducted a multi-institutional study of these rare tumors. Twenty-six patients were identified with "mixed" adenosarcoma and adenocarcinoma; they ranged in age from 43 to 87 years (median: 66 y). Tumors occurred in the uterine corpus (n=22), ovary (n=2), and the pelvis (n=2). All but 6 had International Federation of Gynecology and Obstetrics (FIGO) stage I disease. All extrauterine tumors were associated with endometriosis. The tumor size ranged from 2 to 25 cm (median: 7.9 cm). The sarcomatous component was of low grade in 18 and high grade in 8 (the majority demonstrating rhabdomyoblastic differentiation); 9 had stromal overgrowth. Twenty-five carcinomas were endometrioid in type (23 FIGO grade 1; 3 FIGO grade 2) and 1 carcinoma was dedifferentiated with FIGO grade 1 endometrioid adenocarcinoma component; 33% of the uterine neoplasms were associated with adjacent endometrial hyperplasia. Next-generation sequencing in 2 tumors identified similar molecular abnormalities in the sarcomatous and carcinomatous components supporting a clonal relationship. Of 10 patients with available follow-up (median: 18 mo), 8 had no evidence of disease and 2 died of recurrent sarcoma at 7 and 8 months. Endometrioid adenocarcinomas that arise in close spatial association with Müllerian adenosarcoma appear to be clonally related to the sarcoma. Unlike carcinosarcomas, these tumors are usually early stage at presentation. The prognosis appears to be driven by the sarcomatous component. These tumors should be distinguished from carcinosarcomas, dedifferentiated endometrial carcinomas, and corded and hyalinized endometrioid carcinomas.

A REVIEW ON WOUND HEALING ACTIVITY OF DIETARY FLAVONOID NARINGENIN

Wound is known as disruption in the integrity of a tissue. The mechanisms of regeneration and tissue repair consist of a series of molecular and cellular events that occur after the onset of a tissue lesion to rebuild the damaged tissue. The remodelling phases of the exudative, proliferative, and extracellular matrix are concurrent events that occur through the interaction of complex processes involving soluble mediators, blood cells and parenchymal cells. Exudative phenomena that occur after injury, lead to tissue edema growth. The proliferative stage aims to minimize the area of tissue damage by myofibroblasts and fibroplasia contracting. Angiogenesis and reepithelialisation processes can still be observed at this point. Endothelial cells are capable of differentiating into mesenchymal components and this distinction seems to be finely coordinated by a series of signalling proteins. Many of the medicines available today is derived from natural sources. Flavonoids are essential components of the human diet apart from their physiological functions in plants, even though they are not considered as nutrients. In this review, naturally occurring flavonoid is discussed which occur in citrus fruits, vegetables, nuts, and beverages like coffee, tea, and red wine, and also in medical herbs. They exhibit different pharmacological actions, like antioxidant, anti-allergic, anti-bacterial, anti-inflammatory, anti-mutagenic and anti-cancer activity. One of the flavanones is Naringenin which is the ordinary dietary poly-phenolic constituent of the citrus fruits (grapefruit and oranges) and vegetables. It is beneficial in various neurological, cardiovascular, gastrointestinal, rheumatological, metabolic, malignant disorders, and functionally, this ameliorative effect of naringenin is primarily attributed to its anti-inflammatory (via inhibiting staffing of cytokines and inflammatory transcription factors) and anti-oxidant (via scavenging of free radicals, bolstering of endogenous antioxidant defence system and metal ion chelation) effects

A clinical perspective on adipose-derived cell therapy for enhancing microvascular health and function: Implications and applications for reconstructive surgery.

Restoration of form and function requires apposition of tissues in the form of flaps to reconstitute local perfusion. Successful reconstruction relies on flap survival and its integration with the recipient bed. The flap's precariously perfused hypoxic areas undergo adaptive microvascular changes both internally and in connection with the recipient bed. A cell-mediated, coordinated response to hypoxia drives these adaptive processes, restoring a tissue's normoxic homeostasis via de novo vasculogenesis, sprouting angiogenesis, and stabilizing arterialization. As cells exert prolonged and coordinated effects on site, their use as biological agents merit translational consideration of sourcing angio-competent cells and delivering them to territories enduring microcirculatory acclimatization. Angio-competent cells abound in adipose tissue: a reliable, accessible, and expendable source of adipose-derived cells (ADC). When subject to enzymatic digestion and centrifugation, adipose tissue separates its various ADC: A subset of buoyant oil-dense adipocytes (the tissue's parenchymal component) accumulates on a supra-natant layer, whereas the mesenchymal component remains in the infra-natant sediment, containing the tissue's stromal vascular fraction (SVF), where angio-component cells abound. The SVF can be further manipulated, selected, or culture expanded into more specific stromal subsets (herein defined as adipose stromal cells, ASC). While promising clinical applications for ADC await clinical proof and regulatory authorization, basic science investigation is needed to elucidate the specific ADC mechanisms that influence microvascular growth, remodeling, and function following flap surgery. The objective of this article is to share the clinical perspectives of reconstructive plastic surgeons regarding the use of ADC-based therapies to help with flap tissue integration, revascularization, and wound healing. Specifically, the focus will be on considering the potential for ADC as therapeutic agents and how their clinical application motivates basic science opportunities.

Detection of MED12 mutations in mesenchymal components of uterine adenomyomas

Adenomyoma of the uterus is a biphasic nodular lesion composed of a mesenchymal component with smooth muscle differentiation and a glandular epithelium. The neoplastic nature of uterine adenomyomas has been controversial because some are considered to be nodular adenomyosis. MED12 mutations are involved in the pathogenesis of uterine smooth muscle tumors (leiomyomas and leiomyosarcomas) and biphasic tumors of the breast (fibroadenomas and phyllodes tumor). To investigate the histogenesis of uterine adenomyomas, we performed pathological and genetic analyses, including Sanger sequencing of MED12. In total, 15 cases of uterine adenomyomas were retrieved and assessed for clinicopathological factors. Immunohistochemistry for smooth muscle actin, desmin, and CD10 was performed. Exon 2 of MED12 was Sanger sequenced using DNA obtained by macrodissection of the adenomyomas. For cases that were positive for somatic MED12 mutations, we next performed microdissection of the mesenchymal and epithelial components. The DNA extracted from each component was further analyzed for MED12 mutations. MED12 mutations were detected in two adenomyomas (2/15, 13%), all in a known hot spot (codon 44). In both lesions, MED12 mutations were detected in multiple spots of the mesenchymal component. The epithelial component did not harbor MED12 mutations. The relatively low frequency of MED12 mutations suggests that not all adenomyomas are leiomyomas with entrapped glands. However, the results of our study suggest that a subset of uterine adenomyomas are true mesenchymal neoplasms.

Cutaneous metastasis in a case of Wilm's tumor diagnosed on cytology ‐ A rare case report

A 12-year-old male child presented with complaints of a slow growing swelling in the right parasternal region noticed since one month. On examination, the lump was 2 × 2 cm firm, mobile nontender located in the subcutaneous plane which was also confirmed radiologically. Fine needle aspiration cytology was attempted showed small to medium sized monotonous round cell morphology, nuclear molding and mitotic figures were frequent. Few cells exhibiting rosettoid arrangement. No definite epithelial or mesenchymal component was evident. No glio-fibrillary matrix or lymphoglandular bodies were evident in the smears. Based on morphology, a small round cell tumor was considered with possibilities of Wilm's tumor and Ewing's family of tumor. Based on morphological differentials ICC was requested, tumor cells were positive for strong nuclear WT1 staining while CK and FLI1 were negative. The cytomorphology along with the ICC confirmed the diagnosis of metastatic wilm's tumor. Seven years back, patient had a history of nephrectomy, which on histopathology was reported as triphasic Wilms tumor with favorable histology. Generally Wilm's tumor recurs within 2 years of diagnosis. Late recurrence in Wilm's tumor is rare with only a handful of case reports. Common sites for metastasis include lung, liver, contralateral kidney. Cutaneous metastasis is very uncommon, early detection of which with helps in therapeutic and prognostic decisions. The interesting aspect of this article is cytological detection of cutaneous metastasis of late recurrence Wilm's tumor, which is extremely rare to occur.

A case of ovarian carcinosarcoma composed of endometrioid carcinoma and endometrial stromal sarcoma

Ovarian carcinosarcoma (OCS) is a rare malignancy accounting for only 1‒4% of all ovarian cancers. A 44-year-old premenopausal woman presented at the Obstetrics and Gynecology Department of the University Hospital of Saga, with the chief complaint of sudden abdominal pain. Tumor markers present in her serum were cancer antigen (CA) 19-9 (103U/mL), and CA 125 (114U/mL). Transvaginal ultrasound examination showed a complex mass (74×71×67mm) with solid and cystic components in the left abdominal area. Abdominopelvic computed tomography images showed a polycystic mass with a long diameter of 94 mm in the left adnexal area. The patient underwent a laparotomy immediately after the appropriate evaluation of examinations, leading to total abdominal hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy. Due to the emergency surgery, intraoperative histological diagnosis for ovarian tumor was not performed. The preoperative evaluation of radiological imaging revealed no evidence of lymph node swelling, therefore lymph node resection was omitted. The left ovarian tumor already showed a partial rupture. Pathological examination following surgery revealed tubular and solid growth of the epithelial component and fascicular growth of spindle-shaped mesenchymal cells. Immunohistochemistry identified the epithelial component as endometrioid carcinoma (EC) and the mesenchymal component as endometrial stromal sarcoma (ESS). Endometriotic tissue was attached to the malignant tumor. The patient was successfully treated with adjuvant chemotherapy (paclitaxel plus carboplatin) after surgery. The patient is still alive without recurrence at 9 months after surgery. Considering the rarity of OCS with EC and ESS, we present an overview of the literature and discuss several histological and clinical issues. The etiology and pathogenesis of such tumors require further investigation (words; 228).

Expression of EMT-Related Genes in Hybrid E/M Colorectal Cancer Cells Determines Fibroblast Activation and Collagen Remodeling.

Collagen, the main non-cellular component of the extracellular matrix (ECM), is profoundly reorganized during tumorigenesis and has a strong impact on tumor behavior. The main source of collagen in tumors is cancer-associated fibroblasts. Cancer cells can also participate in the synthesis of ECM; however, the contribution of both types of cells to collagen rearrangements during the tumor progression is far from being clear. Here, we investigated the processes of collagen biosynthesis and remodeling in parallel with the transcriptome changes during cancer cells and fibroblasts interactions. Combining immunofluorescence, RNA sequencing, and second harmonic generation microscopy, we have explored the relationships between the ratio of epithelial (E) and mesenchymal (M) components of hybrid E/M cancer cells, their ability to activate fibroblasts, and the contributions of both cell types to collagen remodeling. To this end, we studied (i) co-cultures of colorectal cancer cells and normal fibroblasts in a collagen matrix, (ii) patient-derived cancer-associated fibroblasts, and (iii) mouse xenograft models. We found that the activation of normal fibroblasts that form dense collagen networks consisting of large, highly oriented fibers depends on the difference in E/M ratio in the cancer cells. The more-epithelial cells activate the fibroblasts more strongly, which correlates with a dense and highly ordered collagen structure in tumors in vivo. The more-mesenchymal cells activate the fibroblasts to a lesser degree; on the other hand, this cell line has a higher innate collagen remodeling capacity. Normal fibroblasts activated by cancer cells contribute to the organization of the extracellular matrix in a way that is favorable for migratory potency. At the same time, in co-culture with epithelial cancer cells, the contribution of fibroblasts to the reorganization of ECM is more pronounced. Therefore, one can expect that targeting the ability of epithelial cancer cells to activate normal fibroblasts may provide a new anticancer therapeutic strategy.

Carcinosarcomas of Ovary/Fallopian Tube: A Rare Entity

Abstract Introduction/Objective Adnexal carcinosarcomas (MMMTs) are rare tumors (1–4% ovarian carcinomas) with worse prognosis than high grade serous carcinomas (HGS) at similar stage. They typically present at age 64–66, often with peritoneal involvement. They are biphasic tumors with stem cells undergoing divergent epithelial and sarcomatous differentiation. The epithelial component is usually HGS and drives progression of the tumor. The mesenchymal component can be homologous with high-grade spindled cells or heterologous with malignant cartilage, bone, muscle or fat. Metastases are mostly epithelial; metastatic sarcomatous components are unusual. We reviewed our single- institutional experience of adnexal MMMTs. Methods We reviewed our pathology database (2001–2019) to find all cases of adnexal MMMTs. We reviewed their histological features, histology of metastases and clinical outcomes. Results Our series consisted of 12 cases. Patients aged 41–82 years. The primary tumor sites were ovary (6 cases, 50%), fallopian tube (4, 33%), 1 each (8%) in paratubal region and infundibular ligament. Fallopian tube was involved in 8/12 cases (4 cases as primary MMMT, 4 cases with STIC or HGS). Epithelial component was serous (75%), endometrioid (17%) and mucinous (8%). Sarcomatous component was homologous in 5 cases (41%), heterologous in 7 cases: cartilage (33%), cartilage/muscle (8%), muscle (8%), cartilage/muscle/fat (8%). 3 cases were FIGO stage I, 9 had peritoneal metastases (8 stage III, 1 stage IV). Six cases had metastatic HGS; 3 had metastatic HGS with sarcomatous component, 2 with heterologous elements. Aberrant p53 pattern was seen in 7/12 and TP53 mutation was noted in 6/12. Ten patients received cytoreductive surgery and chemotherapy. 7 patients are alive with progression free survival ranging 6–59 months, 2 survived for 25 and 29 months, 3 are lost to follow-up. Conclusion Metastatic sarcomatous heterologous elements are rare in uterine carcinosarcomas and may suggest adnexal origin. They may correlate with worse outcome; in our series, 1/2 died after 29 months, the other was lost to follow-up. Fallopian tube involvement (75% of our cases) is of significance as identical TP53 mutation has been identified in a case report of ovarian carcinosarcoma with fallopian tube STIC. Also, our 2 cases of infundibular ligament and paratubal region may indicate seeding from fallopian tube. Further studies are needed to confirm the correlation.

Keratin 19 and mesenchymal markers for evaluation of epithelial–mesenchymal transition and stem cell niche components in primary biliary cholangitis by sequential elution-stripping multiplex immunohistochemistry

ABSTRACT Multiplexed immunohistochemical techniques give insight into contextual cellular relationships by offering the ability to collect cell-specific data with spatial information from formalin-fixed, paraffin-embedded tissue sections. We established an automated sequential elution-stripping multiplex immunohistochemical assay to address two controversial scientific questions in the field of hepatopathology: 1) whether epithelial-to-mesenchymal transition or mesenchymal-to-epithelial transition occurs during liver injury and repair of a chronic liver disease and 2) if there is a stromal:epithelial relationship along the canals of Hering that would support the concept of this biliary structure being a stem/progenitor cell niche. Our 4-plex assay includes both epithelial and mesenchymal clinical immunohistochemical markers and was performed on clinical human liver specimens in patients with primary biliary cholangitis. The assay demonstrated that in each specimen, co-expression of epithelial and mesenchymal markers was observed in extraportal cholangiocytes. In regard to possible mesenchymal components in a stem cell niche, 82.3% ± 5.5% of extraportal cholangiocytes were intimately associated with a vimentin-positive cell. Co-expression of epithelial and mesenchymal markers by extraportal cholangiocytes is evidence for epithelial to mesenchymal transition in primary biliary cholangitis. Vimentin-positive stromal cells are frequently juxtaposed to extraportal cholangiocytes, supporting an epithelial:mesenchymal relationship within the hepatobiliary stem cell niche. Our automated sequential elution-stripping multiplex immunohistochemical assay is a cost-effective multiplexing technique that can be readily applied to a small series of clinical pathology samples in order to answer scientific questions involving cell:cell relationships and cellular antibody expression.

ENDOBRONCHIAL HAMARTOMA: A RARE CAUSE OF WORSENING ASTHMA

SESSION TITLE: Fellows Procedures Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary Hamartomas have an incidence of 0.025-0.32% in the general population (1) and almost all are benign. Approximately 10% of them are endobronchial, and may present as refractory asthma. CASE PRESENTATION: A 46-year-old male with previously well controlled asthma, developed worsening respiratory symptoms including shortness of breath and wheezing over the past year. Despite good compliance, inhaler technique and up-titration of his asthma medications, his exacerbations became unpredictable and refractory to further medical therapy. Furthermore, he reported exertional dyspnea and persistent cough and denied sputa, weight loss, hemoptysis, or recent pneumonia. His physical exam revealed a mono-phasic wheeze on auscultation. Dyspnea workup included CT chest (Fig 1), which showed a right main stem endobronchial mass causing near-complete obstruction of the airway. He was referred to our hospital for resection of the mass. A rigid bronchoscopy was done under general anesthesia and a proximal right main bronchus lesion was noted protruding into the distal trachea (Fig 2). The bronchoscope bevel was advanced through the tumor base, with successful core-out of the 1.5cm tumor en bloc. Hemostasis was achieved from tamponade of the tumor base by the rigid scope and further bleeding was controlled with Argon Plasma Coagulation (APC). Post resection, the right bronchus was widely patent without any residual obstruction. He made a complete recovery with immediate post-op improvement in his breathing. Histopathology confirmed it to be a cartilaginous hamartoma (Fig 3). DISCUSSION: Pulmonary hamartomas are rare, benign tumors, originating from the bronchial primitive mesenchymal tissue, which differentiates into various mature components, such as cartilage, bone, fat and muscle tissue. To be classified as a hamartoma, two distinct mesenchymal components native to the organ must be present in a disorganized pattern. Generally, the cartilaginous component is predominant and is classified as a cartilaginous hamartoma. Endobronchial Hamartomas are asymptomatic, until they enlarge to cause bronchial obstruction. Clinical presentation includes persistent cough, dyspnea, wheezing, fever, sputum, hemoptysis or recurrent pneumonia. CT chest may provide a clue to diagnosis by the presence of high fat content in the mass, lack of contrast uptake or extra-bronchial invasion. Needle biopsy of the lesion is frequently inadequate or often misguiding if squamous metaplasia is present in the overlying epithelium. Endoscopic resection is the gold standard treatment. Traditional tracheotomy, wedge resection or lobectomy is reserved for non-resectable lesions or with underlying lung parenchymal damage with recurrence being extremely low. CONCLUSIONS: Endobronchial hamartomas may present as refractory asthma, and prompt evaluation can prevent recurrent hospitalizations, offer a cure and improve quality of life. Reference #1: Endobronchial hamartoma: a rare structural cause of chronic cough by Saman Ahmed et al. Respiratory Medicine Case Reports 22 (2017) 224e227 Reference #2: Endobronchial Hamartoma: literature search and case report. J.F. PATERSON. CHEST, November 1956. Reference #3: A Case Report of Endobronchial Hamartoma: surgical options for resection. Wen Xi. CHEST, April 2016, Vol149, Issue 4. DISCLOSURES: no disclosure on file for Fawad Chaudry; No relevant relationships by Maham Khan, source=Web Response No relevant relationships by Adam Przebinda, source=Web Response No relevant relationships by Aejaz Ul Haq, source=Web Response

Immunohistochemical markers and the clinical course of adenosarcoma: a series of seven cases

BackgroundUterine adenosarcoma, a rare uterine tumor subtype, is a biphasic tumor consisting of epithelial and mesenchymal elements. To date, there is no research comparing the histopathological features and immunohistochemistry of primary and recurrent tumors; furthermore, the relationship between pathology and the clinical course remains unclear. We reviewed the pathology and immunohistochemical features of patients with adenosarcoma and investigated the relevance of the histomorphological features to the clinical course. We also compared the immunohistochemical features of the primary and recurrent tumors.MethodsThe data of seven patients with adenosarcoma who underwent surgery in our hospital were evaluated. We performed immunohistochemical staining for the progesterone receptor, estrogen receptor, p53, and two Switch/Sucrose Non-Fermentable chromatin remodeling proteins (SMARCA4, BCOR), which were recently developed for the undifferentiated sarcoma diagnosis in addition to conventional staining methods.ResultsAll patients had International Federation of Gynecology and Obstetrics stage IB–IC diseases. All tumors were polypoid and every patient presented with abnormal uterine bleeding. Six patients aged over 50 years and were menopausal; one patient aged under 50 years and was non-menopausal (average age: 59.1 years). Histologically, the sarcomatous components were homologous and heterogenous in six and one patient, respectively. Four and three cases were recurrent and non-recurrent, respectively. The recurrent patients showed high-grade morphology with sarcomatous overgrowth and were negative for ER and PR. Three recurrences could be evaluated by imaging, showing recurrence only in a distant area; biopsy specimens from these tissues revealed the identical mesenchymal component found in the primary tumor without a benign epithelial component. Immunohistochemical staining results were also similar to the corresponding of the original tumor, except for the p53 expression in one patient. At the primary site, p53 was overexpressed in two recurrent patients and had a wild-type level in one recurrent patient; however, all three recurrent tissues showed p53 overexpression. None of our patients showed SMARCA4 loss, and BCOR expression was positive in one case.ConclusionsInitial pathological adenosarcoma analysis with appropriate immunohistochemical staining is vital for prognostic assessment. p53 expression might increase at recurrence. SMARCA4 and BCOR might not be an index of malignancy.

Targeted Next-Generation Sequencing and Allele-Specific Quantitative PCR of Laser Capture Microdissected Samples Uncover Molecular Differences in Mixed Odontogenic Tumors

The molecular pathogenesis of mixed odontogenic tumors has not been established, and understanding their genetic basis could refine their classification and help define molecular markers for diagnostic purposes. Potentially pathogenic mutations in the component tissues of 28 cases of mixed odontogenic tumors were assessed. Laser capture microdissected tissue from 10 ameloblastic fibromas (AF), 4 ameloblastic fibrodentinomas (AFD), 6 ameloblastic fibro-odontomas (AFO), 3 ameloblastic fibrosarcomas (AFS), and 5 odontomas (OD) were screened by next-generation sequencing and results confirmed by TaqMan allele-specific quantitative PCR. BRAF p.V600E mutation in the mesenchymal component was shown in 4 of 10 AF (40%), 2 of 4 AFD (50%), 2 of 6 AFO (33%), and 2 of 3 AFS (67%), whereas all 5 OD were wild type for BRAF p.V600E. Mutation in the epithelial component was only observed in one AF and one AFO. One AFS contained an area of benign AF, and the mesenchymal component of both (AFS and AF) contained BRAF p.V600E, supporting the concept of malignant progression from a benign AF precursor. KDR, TP53, KIT, and PIK3CA single-nucleotide polymorphisms are reported. In conclusion, AF, AFD, AFO, and AFS show BRAF p.V600E in their mesenchymal component, unlike OD, which are BRAF wild type, suggesting that at least a subset of AF, AFD, and AFO are molecularly distinct from OD, and may represent distinct entities and be neoplastic.

Lesion-targeted cytology to improve cytological sampling for atypical polypoid adenomyomas of the uterus: A case series and review of the literature.

Atypical polypoid adenomyomas (APAs) are uncommon tumours consisting of atypical endometrioid glands and fibromyomatous stroma. Identifying the biphasic nature of atypical glandular components and spindle mesenchymal components without atypia is crucial for the cytological diagnosis of APA. We investigated the utility of lesion-targeted cytology (LTC) to directly collect firm spindle components. We recruited seven consecutive surgical patients who underwent cytological examinations before surgery and were diagnosed with APA on postoperative histological examinations. Cytological smears were obtained by routine sampling in five cases and by targeted sampling using transvaginal ultrasonography, that is, LTC, in two cases. We retrospectively analysed the cytological findings from our cases and compared them to those of APA cases previously reported in the English literature. Among 5/7 cases that involved routine cytological sampling, normal cytological findings were found in 2 and atypical glandular cells were found in 3, but spindle cells from mesenchymal components were not detected. In contrast, among 2/7 cases in which sampling involved LTC, spindle cells without atypia, in addition to atypical glandular cells were found. Lesion-targeted cytology is useful to assess mesenchymal components of APAs and may improve the cytological diagnosis of APA.