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Background: When achieved, complete surgical resection improves outcomes in anaplastic thyroid carcinoma (ATC). However, most ATC patients present with advanced inoperable disease, often with impending airway obstruction, increased hemorrhage risk, and significant dysphagia. Novel treatment strategies are critically needed to improve disease control and decrease locoregional morbidity. The objective of this study was to determine the feasibility and effectiveness of a neoadjuvant regimen by using dabrafenib with trametinib followed by surgical resection in patients with initially unresectable BRAFV600E-mutated ATC. Methods: Case series of six consecutive patients with BRAFV600E-mutated ATC diagnosed between January 2017 and February 2018. Pathologic confirmation of ATC was obtained before treatment. BRAFV600E status was ascertained via immunohistochemistry or sequencing of circulating tumor DNA. All patients received dabrafenib and trametinib (DT) followed by surgical resection and adjuvant chemoradiation. Three patients also received pembrolizumab. Results: Complete surgical resection was achieved in all patients. Histopathologic analyses of resected specimens showed high pathologic response rates with significantly decreased ATC viability and residual papillary thyroid carcinoma components. Overall survival at six months and one year was 100% and 83%, respectively. Locoregional control rate was 100%. Two patients died of distant metastases without evidence of locoregional disease at 8 and 14 months from diagnosis. The remaining four patients had no evidence of disease at the last follow-up. Conclusions: We report the first series in the literature of BRAFV600E-mutated ATC patients with locoregionally advanced disease treated with DT followed by surgical resection. We demonstrated feasibility of complete resection, decreased need for tracheostomy, high pathologic response rates, and durable locoregional control with symptom amelioration. [ABSTRACT FROM AUTHOR]

Several subtypes of high-grade endometrial carcinomas (ECs) contain an undifferentiated component of non-epithelial morphology, including undifferentiated and dedifferentiated carcinomas and carcinosarcomas (CSs). The mechanism by which an EC undergoes dedifferentiation has been the subject of much debate. The epithelial-mesenchymal transition (EMT) is one of the mechanisms implicated in the transdifferentiation of high-grade carcinomas. To improve our understanding of the role of EMT in these tumors, we studied a series of 89 carcinomas including 14 undifferentiated/dedifferentiated endometrial carcinomas (UECs/DECs), 49 CSs (21 endometrial, 29 tubo-ovarian and peritoneal), 17 endometrioid carcinomas (grade 1-3), and 9 high-grade serous carcinomas of the uterus, using a panel of antibodies targeting known epithelial markers (Pan-Keratin AE1/AE3 and E-cadherin), mesenchymal markers (N-cadherin), EMT transcription factors (TFs) (ZEB1, ZEB2, TWIST1), PAX8, estrogen receptors (ER), progesterone receptors (PR), and the p53 protein. At least one of the three EMT markers (more frequently ZEB1) was positive in the sarcomatous component of 98% (n = 48/49) of CSs and 98% (n = 13/14) of the undifferentiated component of UEC/DEC. In addition, 86% of sarcomatous areas of CSs and 79% of the undifferentiated component of UEC/DEC expressed all three EMT-TFs. The expression of these markers was associated with the loss of or reduction in epithelial markers (Pan-keratin, E-cadherin), PAX8, and hormone receptors. In contrast, none of the endometrioid and serous endometrial carcinomas expressed ZEB1, while 6% and 36% of endometrioid and 11% and 25% of serous carcinomas focally expressed ZEB2 and TWIST1, respectively. Although morphologically different, EMT appears to be implicated in the dedifferentiation in both CSs and UEC/DEC. Indeed, we speculate that the occurrence of EMT in a well differentiated endometrioid carcinoma may consecutively lead to a dedifferentiated and undifferentiated carcinoma, while in a type II carcinoma, it may result in a CS. [ABSTRACT FROM AUTHOR]

Ameloblastic carcinoma (AC) is a rare malignant odontogenic tumor. Approximately 138 cases were reported. The majority of these cases occurred in the mandible. Only 57 cases were located in the maxilla. Most of AC cases occur in a primary type. Little is known about AC secondary type (dedifferentiated) since only six cases have been reported. All of previous six cases occurred in the mandible. Here, we presented the first case of maxillary AC secondary type (dedifferentiated) in a 46-year-old female. The first excisional biopsy was diagnosed as basal cell ameloblastoma. Then, the patient underwent partial maxillectomy. A recurrence occurred 17 months later. At this time, tumor cells with cytological atypia were clearly detected. A diagnosis of AC was rendered. Two years later, the patient suffered from another recurrence and received a wide excision with a diagnosis of AC. We considered our case as AC secondary type (dedifferentiated). We discussed the histopathological findings that may be helpful in making a diagnosis of AC. In addition, we consider that the basaloid pattern may be related to malignant transformation in ameloblastoma. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid cancer is a rare and aggressive thyroid cancer with an overall survival measured in months. Because of this poor prognosis and often advanced age at presentation, these patients have traditionally been treated palliatively and referred for hospice. However, recent progress using novel therapies has energized the field, and several promising clinical trials are now available for these patients. This review will highlight this progress and the potential treatments that could pave the way to improved outcomes and quality of life for patients with this disease.

Renal cell carcinoma (RCC) is the most common malignancy of the kidney and has multiple subtypes. The sarcomatoid variety is considered a form of dedifferentiated carcinoma, and when present, it is associated with significant decrease in patient survival due to its rapid growth and intrusive behavior. Here, we present a case of mixed chromophobe and clear cell type of renal cell carcinoma with heterologous sarcomatoid differentiation with radiological pathological correlation. [ABSTRACT FROM AUTHOR]

Atypical lipomatous tumor/well-differentiated liposarcoma is the most common sarcoma of soft tissue in adults. We describe the clinical, radiologic, and pathologic features of an atypical lipomatous tumor arising within the soft tissue of the left hand of a 68-year-old female that underwent transformation to dedifferentiated liposarcoma and eventually metastasized. At initial presentation, imaging demonstrated an extensively calcified fatty soft tissue mass with displacement of the digits. Following biopsy and staged debulking, the patient subsequently developed local recurrence, dedifferentiation, and widespread metastases to the lungs, pancreas, bone, and soft tissues. To our knowledge, this is the first case of a cytogenetically proven atypical lipomatous tumor of the hand that has undergone dedifferentiation with widespread metastases. [ABSTRACT FROM AUTHOR]

Adipocytic tumours are the most common soft tissue neoplasms. Among them, liposarcoma is the most frequent malignant neoplasm. However, to the best of our knowledge, no previously published study has assessed the evolution and oncological prognosis of the different subtypes of liposarcoma at the retroperitoneal level compared with at other locations. The present study is a retrospective observational study in which all patients were operated on between October 2000 and January 2020 with a histological diagnosis of liposarcoma. Variables, such as age, sex, location, histological type, recurrence, type of treatment and mortality, among others, were analysed. The patients were divided into two groups: Group A (retroperitoneal location) and group B (non-retroperitoneal location). A total of 52 patients with a diagnosis of liposarcoma (17 women and 35 men) and a mean age of 57.2±15.9 years were assessed. A total of 16 patients were classified into group A and 36 into group B. The OR of recurrence was 1.5 (P=0.02) for R1 vs. R0 resection in group A. The OR of recurrence in group B for R1 vs. R0 resection was 1.8 (P=0.77), whereas for R2 vs. R0 resection, the OR was 69 (P=0.011). In conclusion, 52 cases of malignant adipocytic tumours collected during 2000–2020 were analysed with the new World Health Organization classification (updated 2020). Although its recurrence potential and capacity for distant metastasis depended on each histological type, surgical treatment with unaffected margins was the main prognostic factor for survival. The present study identified differences in relation to the survival of each histological subtype and its location, finding greater survival in dedifferentiated liposarcoma, myxoid liposarcoma and pleomorphic liposarcoma located at the extraperitoneal level than in the retroperitoneal location. Resectability was not influenced by liposarcoma location. [ABSTRACT FROM AUTHOR]

Dedifferentiated chondrosarcoma (DDCS) comprises approximately 10% of all chondrosarcomas. The tumor generally occurs after the age of 50 years, with equal distribution among males and females. It is most often located in the bones of the pelvis, the proximal femur or humerus, the distal femur, and the ribs. Regardless of treatment, the prognosis is ominous with 90% of patients dying with distant metastases within 2 years. We report a case of DDCS of right proximal femur in a 73-year-old woman. The most important factors affecting survival are early recognition of the radiographic features, adequate histological sampling, and wide-margin resection of the lesion. So for the correct histopathological diagnosis the biopsy sample should be adequate to visualize both cartilaginous and noncartilaginous sarcomatous component which helps to increase the survival of patients before the distant metastasis occurs.

Laryngeal chondrosarcoma is an uncommon malignancy with a predilection for the cricoid cartilage of adult male patients. Although rare, identification of aggressive chondrosarcoma variants, such as dedifferentiated chondrosarcoma (DDCS) may influence preoperative patient counseling, definitive surgical management, potential implementation of post-operative adjuvant therapy and prognosis. Herein we describe clinical and imaging features of laryngeal DDCS, the unique perspective of fresh and formalin fixed macroscopic examination, a spectrum of histopathologic findings, and detail the full course of the patient's disease. [ABSTRACT FROM AUTHOR]

Chordomas are rare and low-grade malignant solid tumours, despite their histologically benign appearance, that arise in the bone from embryonic notochordal vestiges of the axial skeleton, a mesoderm-derived structure that is involved in the process of neurulation and embryonic development. Chordomas occurring in the skull base tend to arise in the basiocciput along the clivus. Three major morphological variants have been described (classical, chondroid, and atypical/dedifferentiated). The pathogenesis and molecular mechanisms involved in chordoma development remain uncertain. From a pathological standpoint, the microenvironment of a chordoma is heterogeneous, showing a dual epithelial-mesenchymal differentiation. These tumours are characterised by slow modality of biologic growth, local recurrence, low incidence of metastasis rates, and cancer stem cell (CSC) phenotype. The main molecular findings are connected with brachyury immunoexpression and activation of the downstream Akt and mTOR signalling pathways. The differentiation between typical and atypical chordomas is relevant because the tumoural microenvironment and prognosis are partially different. This review provides an insight into the recent and relevant concepts and histochemical markers expressed in chordomas, with special emphasis on dedifferentiated chordomas and their prognostic implications. [ABSTRACT FROM AUTHOR]

Atypical fibroxanthoma (AFX) is an uncommon, primary dermal neoplasm of uncertain histogenesis, typically originating in the sun-damage skin of the head and neck of the elderly. Since first description in 1958, ∼3000 cases have been reported in the literature. However, the disease is underreported as the neoplasm is considered a standard diagnosis in the last decades. On the other hand, many earlier reports likely have included non-AFX mimics or aggressive pleomorphic dermal sarcomas. In contrast to its alarming high-grade histology, AFX behaves indolently with rare recurrences/ metastatic rate of <2%. The overall 10- and 20-year disease-specific survival rates are ∼ 100% and 98%, respectively. Histologically, AFX displays undifferentiated pleomorphic spindle cell morphology akin to undifferentiated pleomorphic sarcoma (UPS), a feature that was the basis of the abandoned historical terminology "MFH of skin". However, in contrast to other undifferentiated sarcomatoid neoplasms, AFX is notorious for its highly variable histology with a plethora of patterns, underlining a wide differential diagnosis. Notably, spindle cell, keloid-like, pleomorphic, epithelioid, rhabdoid, clear cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, osteoclast-rich, and many others have been recognized with varying frequencies. Immunohistochemically, AFX is characterized by nonspecific profile with block-type expression of CD10 and aberrant p53 pattern and lack of pankeratin and other lineage-specific epithelial, mesenchymal, melanocytic and hematolymphoid markers. Sarcomatoid melanoma, spindle cell carcinoma and cutaneous anaplastic large cell lymphoma are major considerations. Distinction of AFX from pleomorphic dermal sarcoma (PDS) is arbitrary and is based on presence of ≥ 1 of four unfavorable histological features: more than minimal subcutaneous involvement, coagulative necrosis, lymphovascular invasion and perineurial invasion., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023. Published by Elsevier Inc.)

Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Canine liposarcoma is an uncommon soft tissue sarcoma usually arising in the subcutis. While liposarcoma classification in dogs is based solely on histology, in humans it depends on the detection of genetic abnormalities that can lead to specific protein overexpression. This study is an immunohistochemical evaluation of MDM2 and CDK4 expression in canine liposarcoma designed to assess the correlation of these proteins with histologic type, grade, mitotic index and Ki67 labeling index and evaluate their utility in improving tumor classification. Fifty-three liposarcomas were retrospectively collected: 24 were well differentiated liposarcomas (WDL), 16 of which expressed MDM2 and 21 CDK4; 7 were myxoid liposarcomas (ML), 1 of which expressed MDM2 and 5 expressed CDK4; 18 were pleomorphic liposarcomas (PL), all were MDM2 negative and 12 expressed CDK4. Four tumors were morphologically consistent with dedifferentiated liposarcoma (DDL) a subtype described only in humans: 3 expressed MDM2 and 4 expressed CDK4. MDM2 expression correlated with histotype (highly expressed in WDL and DDL) and grade (highly expressed in grade 1 tumors). Histotype correlated with the Ki67 labeling index (lowest in WDL and highest in DDL). A revised classification, considering MDM2 expression, allowed 8 WDL to be reclassified as PL and correlated significantly with mitotic and Ki67 labeling index (both significantly lower in WDL and progressively higher in ML and DDL). These results partially parallel data reported for human liposarcomas, suggesting that WDL and DDL are distinct neoplastic entities characterized by MDM2 expression, which may represent a useful diagnostic and potentially prognostic marker for canine liposarcoma. [ABSTRACT FROM AUTHOR]

Acinic cell carcinoma (AiCC) with high-grade transformation is a rare variant of AiCC composed of both a conventional low-grade (LG) AiCC and a separate high-grade (HG) component. We describe here, the clinicopathologic and immunohistochemical features of 25 cases diagnosed between 1990 and 2015. Available tissue was analyzed and compared with a cohort of pure LG AiCC for the morphologic and immunophenotypic profile. Incidence was higher in females (1.8:1) than males with an overall mean age at presentation of 63.2 years. All tumors occurred in the parotid gland including 76 % with facial nerve trunk and branches involvement. Most patients were treated with extensive resection and adjuvant therapy. Local recurrence or distant metastasis occurred in most patients, with 72.7 % dead with disease (mean 2.9 years) and 3 patients alive with disease (mean 2.4 years). The majority of the tumors were composed of a LG microcystic AiCC and a HG component consisting of invasive lobules of undifferentiated cells with predominantly solid, cribriform, and glandular patterns. Acinic differentiation was still present in HG areas but aggressive features such as perineural invasion (76 %), lymphovascular invasion (62 %), positive margins (72 %), high mitotic rate, atypical mitoses and/or comedonecrosis (86 %) were easily identified. Compared to the pure LG AiCC, the cases with HG transformation showed significantly increased expression of cyclin-D1, p53 and Ki-67. Most HG areas of AiCC expressed membranous β-catenin (92 %) and were negative for p63 (three cases were focally positive), S100, SMA, androgen, and estrogen receptors. DOG1 expression was present in all LG AiCC tested with retained expression in 91 % of cases with HG transformation, supporting acinic differentiation in the HG foci. Recognition of AiCC with high-grade transformation is imperative as more aggressive clinical management is warranted. [ABSTRACT FROM AUTHOR]

Leiomyosarcoma is the most common sarcoma of the uterine corpus, however, uterine dedifferentiated leiomyosarcoma remains a poorly characterized entity. Dedifferentiation in leiomyosarcoma can be defined as the occurrence of a high-grade undifferentiated sarcoma in association with a lower-grade sarcoma that demonstrates morphologic and immunophenotypic evidence of myogenic differentiation. The occurrence of extensive heterologous elements in the high-grade area can be problematic confusing the tumor with other more specific types of high-grade sarcomas. Available reports of this entity indicate aggressive biological behavior and poor prognosis. Herein, we describe a case of a 35-year-old woman who presented with menorrhagia and underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The histopathological examination of the surgical specimen revealed features of a low-grade leiomyosarcoma juxtaposed to a high-grade sarcoma with osteosarcomatous differentiation. [ABSTRACT FROM AUTHOR]

Sarcomas are malignant soft tissue tumors that constitute <1% of malignancies and liposarcoma (LS) is the most common sarcoma with about 20%. Majority of LSs are well-differentiated (40%). About 5-10% of them will further progress and develop abrupt shift into dedifferentiated neoplastic tissue and contain nonlipogenic component that are labeled as dedifferentiated LSs. LSs commonly affect age group of 50-70 years and commonly occur over extremities and in retroperitoneum. Prognosis of LS depends on various parameters such as histological grade, type, size, location, and presence, or absence of metastasis. We hereby, report a case in 30 years adult male patient with clinical and radiological diagnoses as "intramuscular lipoma" over the thigh. Cytological examination revealed malignant nature of the soft tissue lesion. Histopathology revealed dedifferentiated LS containing highly bizarre tumor giant cells. This case report reemphasizes the cytology findings of this rare entity and reviews the literature on a dedifferentiated variant of LS. [ABSTRACT FROM AUTHOR]

Background: Centrosome amplification (CA) has been reported in nearly all types of human cancer and is associated with deleterious clinical factors such as higher grade and stage. However, previous reports have not shown how CA affects cellular differentiation and clinical outcomes in breast cancer.Methods: We analyzed centrosomes by immunofluorescence and compared to ploidy and chromosomal instability (CIN) as assessed by 6-chromosome FISH in a cohort of 362 breast cancers with median clinical follow-up of 8.4 years. Centrosomes were recognized by immunofluorescence using antibodies for pericentriolar material (PCM; pericentrin) and centrioles (polyglutamylated tubulin). CA was experimentally induced in cell culture by overexpression of polo-like kinase 4 (PLK4).Results: CA is associated with reduced all-cause and breast cancer-specific overall survival and recurrence-free survival. CA correlates strongly with high-risk subtypes (e.g. triple negative) and higher stage and grade, and the prognostic nature of CA can be explained largely by these factors. A strong correlation between CA and high tumor ploidy demonstrates that chromosome and centrosome doubling often occur in concert. CA is proposed to be a method of inducing CIN via aberrant mitotic cell divisions; consonant with this, we observed a strong correlation between CA and CIN in breast cancers. However, some CA tumors had low levels of CIN, indicating that protective mechanisms are at play, such as centrosome clustering during mitosis. Intriguingly, some high-risk tumors have more acentriolar centrosomes, suggesting PCM fragmentation as another mechanism of CA. In vitro induction of CA in two non-transformed human cell lines (MCF10A and RPE) demonstrated that CA induces a de-differentiated cellular state and features of high-grade malignancy, supporting the idea that CA intrinsically causes high-grade tumors.Conclusions: CA is associated with deleterious clinical factors and outcomes in breast cancer. Cell doubling events are the most prevalent causes of CA in cancer, although PCM fragmentation may be a secondary cause. CA promotes high-risk breast cancer in part by inducing high-grade features. These findings highlight the importance of centrosome aberrations in the biology of human breast cancer. [ABSTRACT FROM AUTHOR]

Malignant myoepithelioma (MM) is an epithelial malignant tumor in which predominant differentiation of the tumor cells are myoepithelial in nature. Dedifferentiated MM is an extremely rare entity. We report here a rare case of the parotid tumor of dedifferentiated MM with its many morphological and immunohistochemistry features.

Liposarcomas of the paratesticular tissue is a rare pathological entity. The symptoms are similar to inguinal hernias or hydroceles. We present the case of an 84-year-old man with a rare paratesticular liposarcoma that manifested as painless right hemiscrotal swelling. Testicular tumour markers were negative. Imaging revealed a heterogeneous mass with a fat component. He underwent a radical orchiectomy on the left side to remove the associated mass. This revealed dedifferentiated liposarcoma (DDLS) with rhabdomyoblastic differentiation and MDM2 amplification. The surgical margins were negative, and the patient had a metastatic workup that included magnetic resonance imaging (MRI) of the abdomen and pelvis. Because of the disease's rarity, there is no clear agreement on radiotherapy and chemotherapy roles.

The role of the switch/sucrose nonfermenting chromatin remodeling complex in the initiation and progression of cancer is emerging. In the female genital tract, only ovarian small cell carcinoma, hypercalcemic type harbors recurrent inactivating SMARCA4 mutations. Otherwise, only rare case reports documented SMARCB1 involvement in endometrial cancer. We analyzed 24 grade 3 uterine endometrioid adenocarcinomas and 2 undifferentiated carcinomas for immunohistochemical expression of SMARCB1 and SMARCA4. All tumors showed high-grade nuclear features with a predominance of solid growth pattern. All cases showed intact nuclear SMARCB1 expression in all tumor cells. However, 1 case of a 78-year-old woman showed complete loss of SMARCA4 in 90% of the tumor with retained expression in 10% of the tumor. The SMARCA4-intact component was a moderate-to-poorly differentiated endometrioid adenocarcinoma. The SMARCA4-deficient dominating component showed solid growth of highly anaplastic undifferentiated large cells with prominent rhabdoid features. None of the 25 SMARCA4-intact cases showed rhabdoid cell morphology. To our knowledge, this is the first systematic study of SMARCB1 and SMARCA4 expression in endometrioid adenocarcinoma of uterus and the first description of a novel SMARCA4-deficient variant of dedifferentiated/undifferentiated endometrial carcinoma. The presence of a differentiated SMARCA4-intact endometrioid component points to a novel pathway of dedifferentiation in endometrioid adenocarcinoma as a consequence of a “second hit.” This case further underlines the close link between the “rhabdoid phenotype” and the SWI/SNF pathway. [ABSTRACT FROM AUTHOR]

Chondrosarcomas (CS) are slow-growing, malignant mesenchymal tumors characterized by the formation of cartilage by the tumor cells. Benign cartilage-producing tumors within the jaws are extremely uncommon, but most ultimately prove to represent low-grade CS. In the maxillofacial region, the maxilla is more commonly affected than the mandible, it comprises less than 2% of all jaw tumors. Clinically, the tumor presents as a swelling that may be painful and cause loosening of the involved teeth, with widening of the periodontal ligament space. The treatment of such lesions is wide surgical excision with regular follow up. The present report discusses the case of a 55-year-old female patient with massive multiple recurring dedifferentiated CS of mandible. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of gap junction strengthening agent PGE2 on the osteoblast transdifferentiation by adipocytes and the gap junction intercellular communication (GJIC). Methods Groin adipose tissue was taken from 3-month-old New Zealand white rabbits and the mature adipocytes were collected. The mature adipocytes were dedifferentiated and the dedifferentiated adipocytes were obtained. The 3rd generation of the dedifferentiated adipocytes were induced and differentiated into osteoblasts. PGE2 was additioncd in the enhanced group. The control group was also established. The effect of PGE2 on osteoblast proliferation was detected using MTT assay. Osteoblast phenotype was examined using Alizarin red staining and collagen type I immunohistochemistry staining. The expression of Cx43 was measured using Western blotting and sorape-loading and dye transfet (SLDT) method. Results The results of MTT assay showed that PGE2 had no significant effect on cell proliferation. The results of Alizarin red staining showed that calcified nodules were purple stained in all groups. The results of collagen type I immunohistochemistry staining showed that the expression of collagen type I was stimulated in the enhanced group. The results of SLDT showed that the spread of fluorescent dye was more in the enhanced group than in the control group. The results of Western blotting showed that the expression of Cx43 was stimulated in the enhanced group. Conclusion PGE2 enhanced the capability of osteoblast transdifferentiation by enhancement of GJIC. [ABSTRACT FROM AUTHOR]

We present a case (female, 61 years of age) of dedifferentiated liposarcoma of the deep, cervical (paralaryngeal) soft tissue with a significant myxoid component and characteristic immunohistochemical (strong and diffuse expression of p16, mdm2 and cdk4 in both the well differentiated liposarcomatous and dedifferentiated components) and molecular genetic findings ( MDM2-gene amplification on fluorescence in situ hybridization). The myxoid component which was present in the well differentiated liposarcomatous component gave the tumor atypical radiological features. The case presented initial diagnostic difficulties, mainly because of the bland histomorphological appearance of the limited biopsy material from the sampled non-lipogenic, dedifferentiated component. The dedifferentiated part of the tumor turned out to harbor significant heterogeneity with regards to cellularity, cytomorphology and proliferative activity. [ABSTRACT FROM AUTHOR]

Abstract: The histologic subtypes of chondrosarcoma are uncommon. Despite their rarity, they present with characteristic clinical and histopathologic features distinguishing them from conventional type of chondrosarcoma. The histologic variants, clear cell and mesenchymal chondrosarcoma, are reviewed herein. Dedifferentiated chondrosarcoma, although typically arising from conventional chondrosarcoma, is also reviewed due to its distinct histomorphology. Finally, so-called extraskeletal myxoid chondrosarcoma, which may rarely arise primary in bone, is also discussed despite its uncertain histogenesis. [Copyright &y& Elsevier]

Objectives: The main objective is to establish the overall survival and disease-free survival profiles regarding the patients with retroperitoneal liposarcoma, making a comparison based on the well-differentiated and dedifferentiated histological subtypes. The secondary objectives are to descriptively analyze the clinical characteristics of said patients and to identify and analyze other independent variables that might modify these survival profiles significantly., Methods: An observational and analytical study was performed using a retrospective historical cohort that was followed prospectively. The inclusion criteria consisted of: the procedure of liposarcoma located in the retroperitoneum, the well-differentiated and dedifferentiated histological subtypes, between January of 2002 and May of 2019. As a result, 32 patients took part in this study's sample. Kaplan-Meier estimator was used to summarise the results and log-rank test was used in the comparative analysis., Results: The overall survival at 5 years was around 59%. No differences were found between the patients with a well-differentiated subtype compared to the dedifferentiated ones (p = 0.834). The disease-free survival at 2 years was 59% regarding the well-differentiated and 26% regarding the dedifferentiated, with these differences being statistically significant (p = 0.005). None of the other studied variables modified these survival profiles significantly., Conclusions: Dedifferentiated retroperitoneal liposarcomas show less disease-free survival than well-differentiated liposarcomas. However, regarding overall survival no differences can be claimed., (Copyright © 2021 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

Dedifferentiated epithelial–myoepithelial carcinoma (DEMC) is very rare salivary gland neoplasm with only anecdotal reports. We present an analysis of DEMC, based on a case and review of literature. Our patient, an 85-year-old woman, presented with a submandibular mass of 5 years duration that was increasing in size over a 5-week period. Histologically, there were areas of typical epithelial–myoepithelial carcinoma, with dedifferentiation of both components, manifesting morphologically as salivary duct carcinoma and areas of myoepithelial carcinoma. A review of literature revealed 21 previously reported cases of DEMC. DEMC occurs at an average age of 72 years, most often in the parotid gland (72%) followed by submandibular gland (17%). Dedifferentiation more often involves the epithelial component (13/15 cases) than the myoepithelial component (5/15 cases). Although typical epithelial–myoepithelial carcinomas are fairly indolent (average disease-free survival of 11.34 years), dedifferentiation confers a poor prognosis (survival reported from 1 to 72 months). [ABSTRACT FROM AUTHOR]

Chondrosarcoma of the head and neck is uncommon and reported to constitute between 1% to 12% of all chondrosarcoma cases.1, 2, 3 Extraskeletal chondrosarcoma of the tongue is an extremely rare type of neoplasm with only three previously reported cases. The underlying origin of chondrosarcoma arising in the tongue is controversial. We describe a case of a low-grade chondrosarcoma arising in the base of the tongue of a 54-year-old woman with a central area of dedifferentiation. The patient was treated with complete surgical resection with no evidence of recurrence at 1 year follow-up. [ABSTRACT FROM AUTHOR]

Liposarcomas are the most common soft-tissue sarcoma of adults, but rare in the head and neck. Recently, a subtype of dedifferentiated liposarcoma with meningiothelial-like whorls was reported and we present the first description of such a tumor in the head and neck. A 65 year old male underwent a resection of a calcified retroesophageal mass that was in close relation to the left hemithyroid and recurrent laryngeal nerve. It was resected en bloc with the left thyroid lobe. Initial pathologic evaluation suggested the mass was a schwanomma of the recurrent laryngeal nerve, but positive staining for MDM2 and CDK4 indicated the tumor was a dedifferentiated liposarcoma. Further evaluation elucidated the unique meningothelial-like whorls within the tumor. This case demonstrates dedifferentiated liposarcomas do appear in the head and neck. Furthermore, this is the first report in the head and neck of the mengiothelial-like whorling pattern type of dedifferentiated liposarcoma. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (ACC) of the head and neck region is an uncommon epithelial tumor of the major and minor salivary glands. In the oral region, although ACC arising from the minor salivary glands is the second most commonly found tumor in the tongue base, its occurrence in the anterior part of the tongue is rare. Histopathologically, ACC is categorized into three growth patterns (tubular, cribriform, and solid types) and three histologic grades (I-III) that are based on the proportions of these patterns. According to this classification, tubular- and cribriform-type ACCs are considered to be lower grade lesions, while solid-type ACCs are considered to be higher grade lesions. A fourth histopathological type has recently been reported by some authors, namely, dedifferentiation or high-grade transformation of ACC. However, very few studies have focused on the imaging features of these ACCs. We report here the case of a 63-year-old female patient with ACC of the tongue with dedifferentiated components, together with the radiological images and pathological features of this ACC. [ABSTRACT FROM AUTHOR]

Abstract: Renal cell carcinoma (RCC) with rhabdoid morphology (RCC-RM) is a recently described variant of RCC, which has an aggressive biologic behavior and poor prognosis, akin to sarcomatoid RCC. The current World Health Organization classification of RCC does not include the rhabdoid phenotype as a distinct histologic entity. The aim of this study is to investigate whether RCC-RM represents a dedifferentiation of a classifiable-type World Health Organization RCC or a carcinosarcoma with muscle differentiation. We reviewed 168 cases of RCC obtained between 2003 and 2008. From these cases, 10 (6%) were found to have areas of classic rhabdoid morphology. Immunohistochemistry for cytokeratin, epithelial membrane antigen, desmin, CD10, and CD117 was performed in each case using the labeled streptavidin-biotin method. Rhabdoid differentiation was identified in association with conventional-type RCC (9) and with unclassifiable-type RCC with spindle cell morphology (1). In all cases, both the rhabdoid and nonrhabdoid tumoral areas were positive for cytokeratin and epithelial membrane antigen and negative for desmin. Cytokeratin positivity in the rhabdoid areas was focal. In cases associated with conventional-type RCC, CD10 was positive in both the rhabdoid and nonrhabdoid foci. CD117 was negative in these tumors. The unclassifiable-type RCC with spindle cell morphology was negative for both CD10 and CD117. The similar immunophenotype between the rhabdoid and nonrhabdoid tumoral foci supports the origin of the rhabdoid cells from the classifiable-type RCC. Areas of rhabdoid morphology do not represent muscle metaplastic differentiation. Renal cell carcinoma with rhabdoid morphology may represent a dedifferentiation of a classifiable-type RCC, similar to that of sarcomatoid differentiation. The recognition of RCC-RM is important as it allows for the inclusion of these high-grade malignancies into a category associated with poor prognosis despite lacking the spindle cell component classically identified as sarcomatoid change. [Copyright &y& Elsevier]

Abstract: Background: Dedifferentiated liposarcoma is a high-grade nonlipogenic sarcoma that arises in the background of a preexisting well-differentiated liposarcoma. The purpose of this work is to evaluate the spectrum of radiologic appearance of retroperitoneal dedifferentiated liposarcoma with clinicopathologic features. Methods: Radiologic images and clinical histories of 15 patients with histologically verified retroperitoneal dedifferentiated liposarcoma were retrospectively studied. Patients included 11 men and 4 women, with mean age of 55.8 years (range, 36–74 years), and they underwent computed tomography (CT) (n=15) and magnetic resonance imaging (MRI) (n=5). Results: The mean size of the tumor was 22.6 cm with a range of 9.5–38 cm. Both CT and MRI showed well-circumscribed, large round, or lobulated retroperitoneal mass. The appearance of the tumor was classified as follows: Category I, nonfatty component within predominant fatty mass (n=5); Category II, focal fatty component within large nonfatty mass (n=6); Category III, well-defined fatty mass and well-defined nonfatty mass (n=1); Category IV, two masses with predominantly nonfatty component (n=3). Conclusion: Retroperitoneal dedifferentiated liposarcomas present various spectra of imaging findings. While Categories I and III may suggest dedifferentiated liposarcoma, Categories II and IV may appear as other types of liposarcoma or other malignant retroperitoneal tumor. [Copyright &y& Elsevier]

Summary: In this article, we supplement the few published articles by describing the clinical and pathologic features of pleomorphic and dedifferentiated leiomyosarcoma from 41 patients (27 women and 14 men) with an age range of 25 to 75 years (mean, 56.5 years), representing the largest cohort reported to date. The typical leiomyosarcoma component accounted for <5% to 60% (mean, 15%) of the tumor. The pleomorphic sarcoma component was composed of polygonal cells in 57% of cases, spindle cells in 21%, a combination of polygonal, epithelioid, rhabdoid, and/or spindle cells in 18%, and predominantly epithelioid cells in 3%. The classical leiomyosarcoma component was positive for at least one myogenic immunohistochemical marker in 29 tumors tested; smooth muscle actin in 100% (27/27), calponin in 90% (9/10), muscle-specific actin in 90% (10/11), desmin in 86% (23/27), smooth muscle myosin heavy chain (SMMS-1) in 67% (4/6), and caldesmon in 57% (4/7). The pleomorphic sarcoma component was reactive for at least one muscle marker in 77% (23/30) of cases; smooth muscle actin in 63% (17/27), calponin in 60% (6/10), SMMS-1 in 60% (3/5), desmin in 59% (16/27), muscle-specific actin in 40% (4/10), and caldesmon in 29% (2/7). The classical leiomyosarcoma component was often strongly positive for myogenic markers, and the pleomorphic sarcoma component usually showed focal and less intense immunoreactivity. Based on staining for muscle markers in the pleomorphic component, twenty-three cases were designated as pleomorphic leiomyosarcoma, and 7 cases were designated as dedifferentiated leiomyosarcoma (negative for all muscle markers used). Eleven cases, in which tissue was not available for immunhistochemical stains, the question of pleomorphic versus dedifferentiated leiomyosarcoma could not be answered. The incidence of metastasis was 89% (32/36) and the mortality rate was 50% (18/36) at last follow-up (3-104 months; mean, 27.5 months). [Copyright &y& Elsevier]