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This case report presents the rare occurrence of a large dedifferentiated liposarcoma originating from the abdominal wall in a 57-year-old male. The patient's initial complaint was the gradual development of an abdominal mass over six months without associated urinary or digestive symptoms. Clinical examination revealed a firm, non-mobile mass in the left lumbar region, prompting further investigation. Imaging studies confirmed the presence of a sizable soft tissue mass with calcifications, suggestive of a sarcoma. Preoperative biopsy indicated a malignant mesenchymal tumor, leading to surgical intervention. Intraoperative findings revealed characteristics consistent with a low-grade malignancy, prompting complete tumor resection with flap reconstruction. Subsequent histopathological analysis confirmed the diagnosis of dedifferentiated liposarcoma with negative surgical margins. The patient was referred for palliative chemotherapy due to the aggressive nature of the tumor. This case underscores the diagnostic challenges and therapeutic considerations associated with rare abdominal wall liposarcomas, emphasizing the importance of a multidisciplinary approach in their management.

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Recent studies have challenged the traditional belief that mature fat cells are irreversibly differentiated and revealed they can dedifferentiate into fibroblast-like cells known as dedifferentiated fat (DFAT) cells. Resembling pluripotent stem cells, DFAT cells hold great potential as a cell source for stem cell therapy. However, there is limited understanding of the specific changes that occur following adipocyte dedifferentiation and the detailed regulation of this process. This review explores the epigenetic, genetic, and phenotypic alterations associated with DFAT cell dedifferentiation, identifies potential targets for clinical regulation and discusses the current applications and challenges in the field of DFAT cell research.

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BACKGROUND: While liposarcomas tend to mainly occur in the soft tissues of the extremities and retroperitoneum, esophageal liposarcoma is rare. Herein, we report a case of a patient who underwent complete resection of an esophageal dedifferentiated liposarcoma via the cervical approach, leading to the preservation of the esophagus. CASE PRESENTATION: A 69-year-old man underwent an upper gastrointestinal endoscopy, as a result of which a submucosal-like tumor was observed. Upper gastrointestinal imaging showed a 12-cm tumor with a stalk arising from the esophageal entrance, extending to the middle intrathoracic esophagus, with a normal surface mucosa. Endoscopic ultrasound-fine needle aspiration biopsy showed that the nuclei of tumors cells were positive for murine double minute (MDM) and weakly positive for cyclin-dependent kinase 4 (CDK4). We diagnosed the tumor as the esophageal dedifferentiated liposarcoma, and planed tumor resection via the cervical approach. The tumor was successfully resected and the postoperative course was uneventful. CONCLUSION: This case report highlights the use of tumor resection via the cervical approach as a good option for esophageal liposarcoma.

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Primary liposarcoma of the lung is an exceedingly rare phenomenon, with fewer than ten cases reported in prior literature as of 2024. Rarer still, dedifferentiated liposarcoma of pulmonary origin is even less frequently reported, with only two cases having been described. Here, we detail the case of a 66-year-old female who presented with a large left-sided obstructing lung mass and underwent bronchoscopy with tumor cryoprobe debulking. Histological examination revealed a spindle cell sarcoma corresponding to a dedifferentiated liposarcoma with leiomyosarcomatous features as murine double minute 2 translocation was identified by fluorescence in situ hybridization and desmin by immunohistochemistry. The patient completed multiple radiotherapy sessions followed by pneumonectomy and a relatively uncomplicated postoperative course. As pulmonary liposarcoma tends to be poorly responsive to typical chemotherapy, standard management of pulmonary liposarcoma in the absence of metastases is surgical intervention to improve patient survival. Thus, we maintain that pulmonologists, oncologists, and radiologists should have a heightened awareness of this unique pathology in patients presenting with solitary lung mass.

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Melanoma is a malignant neoplasm that arises in melanocytes, pigment-producing cells present primarily in the skin. However, not all malignant melanomas originate from the skin, and the other sites of origin include the uveal (eye) or mucosa (rectal or oral); it can have different patterns of mutations. While targeted therapies and immunotherapies have transformed the treatment of this disease in the metastatic setting, resistance mechanisms can still pose challenges for patients and their healthcare providers. We present a case of a male patient with metastatic melanoma and discuss its clinical presentation, diagnostic workup, treatment options, and outcomes. By exploring the complexities of this multifaceted disease process, clinicians and researchers can gain valuable insights into potential areas for improved management strategies. Ultimately, we should aim to deepen our understanding of melanoma and work towards better patient outcomes.

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Hypercalcemia is a significant complication in cancer patients, primarily caused by parathyroid hormone-related peptide (PTHrP) and, rarely, by parathyroid hormone (PTH) production from tumors. We report a case of severe hypercalcemia in a woman with uterine cancer who exhibited elevated PTH and PTHrP levels. Surgical intervention revealed dedifferentiated endometrial carcinoma. Postoperatively, PTH and PTHrP levels normalized but subsequently increased due to metastases. A molecular analysis confirmed the expression of the PTH gene and protein within the tumor, indicating ectopic PTH production. In diagnosing and treating cancers, it is necessary to consider not only PTHrP production but also ectopic PTH production.

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BACKGROUND: mTORC1 activity is dependent on the presence of micronutrients, including Asparagine (Asn), to promote anabolic cell signaling in many cancers. We hypothesized that targeting Asn metabolism would inhibit tumor growth by reducing mTORC1 activity in well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS). METHODS: Human tumor metabolomic analysis was utilized to compare abundance of Asn in WD vs. DD LPS. Gene set enrichment analysis (GSEA) compared relative expression among metabolic pathways upregulated in DD vs. WD LPS. Proliferation assays were performed for LPS cell lines and organoid models by using the combination treatment of electron transport chain (ETC) inhibitors with Asn-free media. 13C-Glucose-labeling metabolomics evaluated the effects of combination treatment on nucleotide synthesis. Murine xenograft models were used to assess the effects of ETC inhibition combined with PEGylated L-Asparaginase (PEG-Asnase) on tumor growth and mTORC1 signaling. RESULTS: Asn was enriched in DD LPS compared to WD LPS. GSEA indicated that mTORC1 signaling was upregulated in DD LPS. Within available LPS cell lines and organoid models, the combination of ETC inhibition with Asn-free media resulted in reduced cell proliferation. Combination treatment inhibited nucleotide synthesis and promoted cell cycle arrest. In vivo, the combination of ETC inhibition with PEG-Asnase restricted tumor growth. CONCLUSIONS: Asn enrichment and mTORC1 upregulation are important factors contributing to WD/DD LPS tumor progression. Effective targeting strategies require limiting access to extracellular Asn and inhibition of de novo synthesis mechanisms. The combination of PEG-Asnase with ETC inhibition is an effective therapy to restrict tumor growth in WD/DD LPS.

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Undifferentiated pleomorphic bone sarcoma (UPS-B) is a rare high-grade sarcoma of bone that is usually seen in advanced age. There is no specific line or pattern of differentiation, and the diagnosis is often made by exclusion. It is especially important to differentiate it from osteosarcoma and dedifferentiated chondrosarcoma. It tends to be located most frequently in the lower extremity, particularly the femur. It is treated with the osteosarcoma protocol. In this study, a case of undifferentiated high-grade pleomorphic bone sarcoma located in the distal femur was reported. It aimed to discuss the patient's clinical presentation, diagnostic approach, treatment, and follow-up process in light of the literature. In this case, the tumor was resected with wide margins after neoadjuvant chemotherapy. He died of diffuse lung metastases during the adjuvant chemotherapy process. Unlike the literature, the patient was only 29 years old. The patient died 8 months after the first diagnosis.

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AIMS: Melanomas are recognised for their remarkable morphological plasticity. Some tumours may lose conventional features and/or acquire non-melanocytic characteristics, referred to as undifferentiated, dedifferentiated and transdifferentiated melanoma. Despite this phenotypical variability, melanomas typically maintain their cancer driver aberrations, affecting genes such as BRAF, NRAS and NF1. Currently, little is known about whether the DNA methylation profile follows the loss or change of differentiation or is retained despite extensive morphological transformation. METHODS AND RESULTS: In this study we analysed 11 melanoma cases, comprising six males and five females, with a median age of 67 years, including five undifferentiated, four trans-differentiated and two de-differentiated melanomas. Undifferentiated and trans-differentiated tumours either arose in a patient with known melanoma and/or presented in the groin/axilla with molecular alterations consistent with melanoma. Cases with heterologous differentiation resembled chondrosarcoma, osteosarcoma, angiosarcoma and rhabdomyosarcoma both morphologically and immunohistochemically, while undifferentiated tumours resembled undifferentiated pleomorphic sarcoma. Methylome profiling was performed, and unsupervised clustering analysis revealed nine cases (five undifferentiated, three trans-differentiated and one de-differentiated) to cluster closely together with conventional melanomas from a reference set. Two cases clustered separately with a distinct group of conventional melanomas exhibiting H3K27me3 loss. CONCLUSIONS: Despite loss of differentiation and phenotypical plasticity, methylation patterns seem to be retained in undifferentiated, de-differentiated and trans-differentiated melanomas and represent useful diagnostic tools to enhance diagnostic precision in these diagnostically challenging cases.

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Liposarcoma is a malignant soft tissue tumor that rarely involves the gastrointestinal tract. The dedifferentiated type typically carries the worst prognosis. Here, we describe a rare case of dedifferentiated liposarcoma of the rectum in a young male patient who was treated with surgical excision. Treatment is often difficult and there is no clear consensus on the benefits of radiotherapy or chemotherapy.

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PURPOSE: We investigated the effects of mouse-derived DFAT on the myogenic differentiation of a mouse-derived myoblast cell line (C2C12) and examined the therapeutic effects of rat-derived DFAT on anal sphincter injury using a rat model. METHODS: C2C12 cells were cultured using DMEM and DFAT-conditioned medium (DFAT-CM), evaluating MyoD and Myogenin gene expression via RT-PCR. DFAT was locally administered to model rats with anorectal sphincter dysfunction 3 days post-CTX injection. Therapeutic effects were assessed through functional assessment, including anal pressure measurement using solid-state manometry pre/post-CTX, and on days 1, 3, 7, 10, 14, 17, and 21 post-DFAT administration. Histological evaluation involved anal canal excision on days 1, 3, 7, 14, and 21 after CTX administration, followed by hematoxylin-eosin staining. RESULTS: C2C12 cells cultured with DFAT-CM exhibited increased MyoD and Myogenin gene expression compared to control. Anal pressure measurements revealed early recovery of resting pressure in the DFAT-treated group. Histologically, DFAT-treated rats demonstrated an increase in mature muscle cells within newly formed muscle fibers on days 14 and 21 after CTX administration, indicating enhanced muscle tissue repair. CONCLUSION: DFAT demonstrated the potential to enhance histological and functional muscle tissue repair. These findings propose DFAT as a novel therapeutic approach for anorectal sphincter dysfunction treatment.

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Dedifferentiated liposarcoma (DDLPS) is a non-lipogenic sarcoma, generally arising from well-differentiated liposarcoma (WDLPS), although it can develop de novo. DDLPS tumors rarely trans-differentiate into non-adipose mesenchymal tissues; however, the latter lack notable variety and mostly show striated muscle or osteogenic/chondrogenic differentiation. Here, we report a case of DDLPS that contained numerous atypical vessels. A man in his sixties presented with a large tumor in his right thigh, and the tumor was surgically resected. Microscopically, most of the tumor was WDLPS, but a minor portion showed DDLPS, consisting of high-grade spindle cells. Remarkably, the DDLPS contained vessels of various sizes with atypical cytoarchitecture, including vessels with seemingly muscular layers. Immunohistochemically, the atypical cells within the vascular wall expressed aSMA, consistent with smooth muscle cells or pericytes, whereas surrounding high-grade spindle cells only focally expressed it, and these aSMA-positive cells within the vessels exhibited MDM2 amplification by immuno-fluorescence in situ hybridization. Our results demonstrate that DDLPS can trans-differentiate into smooth muscle cells of various-sized accompanying vessels, which may support their survival and proliferation.

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Distinct lesions are derived from notochordal cells (NCDL), ranging from benign to malignant ones. This study presents fifty NCDL cases diagnosed in a tertiary hospital of reference from the past 55 years: forty-two conventional chordomas, including one chondroid chordoma subtype, four benign notochordal cell tumors (BNCT), two conventional chordomas with BNCT foci, and two dedifferentiated chordomas. All patients were adults. Three BNCT were incidentally diagnosed, and one case presented local pain. Chordomas began with local pain and/or neurological symptoms. BNCT were well-defined intraosseous lesions, hypointense on T1-weighted images (WI) and hyperintense on T2-WI, without enhancement in the contrast. Conventional chordomas, including its chondroid subtype, were lobulated masses with cortical disruption and soft tissue extension, hypointense on T1-WI and hyperintense on T2-WI, with variable contrast enhancement. BNCT were histologically composed of solid sheets of vacuolated cells with clear cytoplasm and round and central nuclei. No atypia, lobular growth pattern, myxoid matrix, or bone infiltration were seen. Conventional chordomas were histologically composed of physaliphorous cells in a myxoid stroma with lobulated and infiltrating growth patterns. Observational follow-up using radiological controls was decided on for the BNCT cases. None of these cases presented local recurrence or metastasis. En-bloc resection and adjuvant radiotherapy were selected for sacral and vertebral chordoma cases. Sixteen patients died due to tumor-related factors; twenty-eight presented local recurrence, and four developed distant metastases. New therapeutic options are being studied for chordoma cases. Clinical, radiological, and histopathological data are necessary to properly diagnose and follow up of NCDL.

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OBJECTIVE: Dedifferentiated endometrial carcinoma (DDEC) characterized by SWItch/Sucrose Non-Fermentable (SWI/SNF) complex inactivation is a highly aggressive type of endometrial cancer without effective systemic therapy options. Its uncommon nature and aggressive disease trajectory pose significant challenges for therapeutic progress. To address this obstacle, we focused on developing preclinical models tailored to this tumor type and established patient tumor-derived three-dimensional (3D) spheroid models of DDEC. METHODS: High-throughput drug repurposing screens were performed on in vitro 3D spheroid models of DDEC cell lines (SMARCA4-inactivated DDEC-1 and ARID1A/ARID1B co-inactivated DDEC-2). The dose-response relationships of the identified candidate drugs were evaluated in vitro, followed by in vivo evaluation using xenograft models of DDEC-1 and DDEC-2. RESULTS: Drug screen in 3D models identified multiple cardiac glycosides including digoxin and digitoxin as candidate drugs in both DDEC-1 and DDEC-2. Subsequent in vitro dose-response analyses confirmed the inhibitory activity of digoxin and digitoxin with both drugs showing lower IC50 in DDEC cells compared to non-DDEC endometrial cancer cells. In in vivo xenograft models, digoxin significantly suppressed the growth of DDEC tumors at clinically relevant serum concentrations. CONCLUSION: Using biologically precise preclinical models of DDEC derived from patient tumor samples, our study identified digoxin as an effective drug in suppressing DDEC tumor growth. These findings provide compelling preclinical evidence for the use of digoxin as systemic therapy for SWI/SNF-inactivated DDEC, which may also be applicable to other SWI/SNF-inactivated tumor types.

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Dedifferentiated liposarcoma is a rare cancer with a poor prognosis. A 52-year-old man presented with a chief complaint of a mass in his left scrotum. He came with suspected testicular tumor, but all the measured tumor markers were negative. Imaging test showed approximately 2 cm diameter mass accompanied by calcification with some substantial components between the testis and epididymis. Left high testicular resection was performed. The tumor had no continuity between the testis and epididymis, and the spermatic cord transection was negative. Pathological findings showed well differentiated fatty component and a dedifferentiated component around the trabecular bone-like tissue. We observed dedifferentiated dysmorphic cells mixed with fatty droplets of unequal size. Immunostaining led to the diagnosis of dedifferentiated liposarcoma. No additional postoperative therapy was performed. The possibility of dedifferentiated liposarcoma should be kept in mind even if mass is confined to the scrotum and consisted of calcification. In the case of an intrascrotal calcified mass with malignant perspective, radical surgery is highly recommended.

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Liposarcoma is the most common soft tissue sarcoma type in adults, originating mainly from the retroperitoneum and lower extremities. Mediastinal liposarcomas constitute an extremely rare clinical entity of mesenchymal origin. Among subtypes, dedifferentiated liposarcoma is characterized by poor survival, but little is known about its biological behavior. We present the case of a 78-year-old male patient who presented with vague symptoms, predominantly dyspnea and chest pain. Imaging revealed a large mediastinal mass and surgical resection was performed in a piecemeal manner due to the inability to achieve a microscopically negative surgical margin (R0 resection) for the residual tumor. Histological examination confirmed the diagnosis of dedifferentiated liposarcoma. The patient's postoperative course was uneventful, with discharge from the hospital on the 10th postoperative day. However, local recurrence was detected after two months and the patient died four months after the operation. The present case report highlights the importance of radical excision for the prevention of local recurrence and the presentation of histological characteristics of this tumor. Radical surgical resection remains the fundamental treatment, while chemo and radiotherapy may have an adjuvant role. In cases of inability to obtain negative margins, surgical debulking can offer symptomatic relief.

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INTRODUCTION: Acinic cell carcinoma (AciCC) is a rare clinical entity and a salivary gland malignancy. It is associated with wide histological variations in the cytomorphological patterns. METHODS: Sixty cases diagnosed as AciCC from 2002 to 2023 were assessed for diverse cytomorphological patterns. RESULTS: The mean age of patients at the time of diagnosis was 44.35±16.8 years ranging from 15 to 81 years. Females comprised 58.3% for a F: M ratio of 1.4:1. Fifty three cases (88.3%) occurred in the parotid gland, two cases in the nasal region (3.3%), and one case each in the soft plate and upper lip (1.7%). The location of the remaining three cases was not specified. The most common presenting complaint was a well-defined facial swelling associated with pain. The average tumor size was 3.8±1.9 cm. The most predominant architectural pattern was solid (83.3%) followed by microcystic (60%), then follicular (41.7%), papillary cystic (14.3%), and tubulocystic (28.6%), and AciCC with de-differentiation/high-grade transformation was reported in three cases (5%). In 83.3% of the cases (50 out of 60), we noticed a mixture of two or more growth patterns. Other degenerative changes included prominent lymphoid stroma, hemorrhage, and cystic change. CONCLUSION: Awareness and recognition of diverse cytomorphological patterns of AciCC, especially in institutions of a developing country where there is limited availability of highly specific and sensitive immunohistochemical stains or molecular diagnostics, are crucial and essential.

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A primary malignant bone tumor, or more commonly, metastasis, can occur in the proximal femur. Surgical treatment can have palliative or curative purposes. In the case of the latter, it involves two stages: resection of the tumor, which aims to address the cancer, and reconstruction of the bone and soft tissue, which aims to restore function. It is important for the excision to be wide with adequate resection margins in the soft tissue, particularly when the goal is curative treatment. Typically, surgery involves excision and reconstruction to ensure good mechanical stability. Reconstruction can be done using different methods, such as a composite prosthesis or a massive prosthesis, which may be modular or custom-made. Joint reconstruction options include hemiarthroplasty, intermediate prosthesis, or, in some cases, total hip replacement.

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The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a principal regulator of calcium homeostasis through activation of the vitamin D receptor (VDR). Previous studies have shown that 2α-(3-hydroxypropyl)-1,25D3 (O1C3) and 2α-(3-hydroxypropoxy)-1,25D3 (O2C3), vitamin D derivatives resistant to inactivation enzymes, can activate VDR, induce leukemic cell differentiation, and increase blood calcium levels in rats more effectively than 1,25(OH)2D3. In this study, to further investigate the usefulness of 2α-substituted vitamin D derivatives, we examined the effects of O2C3, O1C3, and their derivatives on VDR activity in cells and mouse tissues and on osteoblast differentiation of dedifferentiated fat (DFAT) cells, a cell type with potential therapeutic application in regenerative medicine. In cell culture experiments using kidney-derived HEK293 cells, intestinal mucosa-derived CaCO2 cells, and osteoblast-derived MG63 cells, and in mouse experiments, O2C2, O2C3, O1C3, and O1C4 had a weaker effect than or equivalent effect to 1,25(OH)2D3 in VDR transactivation and induction of the VDR target gene CYP24A1, but they enhanced osteoblast differentiation in DFAT cells equally to or more effectively than 1,25(OH)2D3. In long-term treatment with the compound without the medium change (7 days), the derivatives enhanced osteoblast differentiation more effectively than 1,25(OH)2D3. O2C3 and O1C3 were more stable than 1,25(OH)2D3 in DFAT cell culture. These results indicate that 2α-substituted vitamin D derivatives, such as inactivation-resistant O2C3 and O1C3, are more effective than 1,25(OH)2D3 in osteoblast differentiation of DFAT cells, suggesting potential roles in regenerative medicine with DFAT cells and other multipotent cells.

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Purpose: To investigate prognostic factors affecting cancer-specific survival (CSS) and to analyze the survival outcomes of patients with undifferentiated and dedifferentiated endometrial carcinoma (UDEC) who underwent various postoperative adjuvant therapies. Methods: The independent risk factors affecting CSS were studied using univariate and multivariate Cox regression analysis, and CSS in the presence of various postoperative treatments was evaluated using Kaplan-Meier method based on the cohort with pathologically confirmed UDEC from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, the study included 18 cases with UDEC in our center and explored their molecular characteristics and prognosis. Results: Between 2000 and 2019, a total of 443 patients were included from the SEER database. The median CSS duration was 14 months, with corresponding 3- and 5-year CSS rates of 45.9% and 44.0%, respectively. Factors such as pTNM stage, surgical resection of primary lesion, and chemoradiation independently influenced CSS. Postoperative chemotherapy alone improved CSS in patients with initial tumor spread beyond the uterus (pT3 and pT4), or lymph node (LN) invasion, or distant metastases. Additionally, postoperative radiotherapy enhanced CSS in patients who had undergone postoperative chemotherapy, those with primary tumors progressing to stage pT3, and those with LN involvement but without distant metastases. Of the 18 patients diagnosed at our center, with a median follow-up of 15.5 months, one experienced relapse and two succumbed to UDEC, who exhibited aberrant p53 expression in immunohistochemical staining. Conclusion: Postoperative chemotherapy and radiotherapy are beneficial for UDEC patients with tumors extending beyond the uterus or involving lymph nodes.