Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: a narrative review.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) is a rare pancreatic tumor that accounts for less than 1% of all pancreatic malignancies. The characteristic pathological manifestation of UCOGCP is the presence of osteoclast-like giant cells (OGCs) distributed among pleomorphic undifferentiated tumor cells. UCOGCP can occur either alone or in association with other types of pancreatic tumors. At present, there is no unified consensus or guideline for the diagnosis and treatment of UCOGCP, and most of the literature are individual case reports. With the accumulation in the number of clinical cases and the development of precision medicine technology, the understanding of UCOGCP is also deepening. Researchers have begun to recognize that UCOGCP is a pancreatic tumor with distinctive clinical and molecular characteristics. In this review, we focus on the latest research status and future exploration directions in the diagnosis, treatment, and prognosis of UCOGCP.

Genomic analysis of bladder urothelial carcinoma with osteoclast­like giant cells: A case report.

Urothelial carcinoma of the bladder with osteoclast-like giant cells (UCOGCs) is rare among the subtypes of poorly differentiated urothelial carcinoma. Its clinical significance and optimal treatment are unknown, and few reports on genomic analysis of UCOGCs have been reported. Detailed analysis including genetic analysis for rare type variants of cancer could be a foothold for further research. The present case describes the case of a 75-year-old man who presented with a non-papillary bladder tumor 56 mm in diameter showing gross hematuria and pain on voiding. Following transurethral resection of the bladder tumor, the pathological diagnosis was invasive UCOGCs. Neoadjuvant chemotherapy and radical cystectomy were performed with the resected tumor pathologically diagnosed as invasive UCOGCs, high grade, pT3b, pN1. The present study also analyzed the genomic features using a cancer panel test. The panel test noted six gene alterations (PIK3CA p.E542K, HRAS p.G13R, ARAF copy number amplification, CDKN2A copy number loss, TP53 p.E285V, ARID1A p.S90Pfs*11) and telomerase reverse transcriptase (TERT) promoter variant. Accumulation of knowledge from molecular-based testing is anticipated to determine precise treatment for rare cancer.

Osteolytic Lesions (Brown Tumors) of Primary Hyperparathyroidism: A Report of Two Cases.

Primary hyperparathyroidism is characterized by excessive production of parathyroid hormone. As the condition progresses, bone loss primarily occurs due to resorption. A complication of this condition is the formation of fibrotic and cystic changes in the bone, known as brown tumors. These lesions occur in areas of significant bone resorption, where fibrovascular tissue and giant cells replace bone tissue, often accompanied by hemorrhage and hemosiderin deposits. These brown lesions are rare, with an occurrence rate ranging from 1.5% to 4.5%. We present two cases of middle-aged women who had presentations consistent with hyperparathyroidism and presented with complications such as bone pain and numbness. Both underwent parathyroidectomy to manage the cause and recovered after the surgery. These cases emphasize the importance of recognizing primary hyperparathyroidism as a potential cause of abnormal lesions and highlight the diverse presentations associated with this condition.

Invasive Breast Cancer of No Special Type With Osteoclast-Like Giant Cells: A Cytological Clue Providing the Final Diagnosis for Histology.

Breast cancer associated with osteoclast-like giant cells (OGCs) refers to a morphological pattern of invasive breast carcinoma of non-special type. Their presence is sometimes subtle, but OGCs can be appreciated both histologically and immunohistochemically. The origin of OGCs as well as their implication for prognosis remain debated. We describe the case of a 65-year-old woman, wherein the presence of OGCs in the fine-needle aspiration cytology of a metastatic axillary lymph node suggested the final diagnosis on histology. The differential diagnosis is broad, and here we provide evidence for strict cytological-histological correlation when dealing with unusual breast lesions.

Formation of Multinucleated Giant Cells after Experimental Intracerebral Hemorrhage: Characteristics and Role of Complement C3.

Hematoma clearance is critical for mitigating intracerebral hemorrhage (ICH)-induced brain injury. Multinucleated giant cells (MGCs), a type of phagocyte, and the complement system may play a pivotal role in hematoma resolution, but whether the complement system regulates MGC formation after ICH remains unclear. The current study investigated the following: (1) the characteristics of MGC formation after ICH, (2) whether it was impacted by complement C3 deficiency in mice and (3) whether it also influenced hematoma degradation (hemosiderin formation). Young and aged male mice, young female mice and C3-deficient and -sufficient mice received a 30 µL injection of autologous whole blood into the right basal ganglia. Brain histology and immunohistochemistry were used to examine MGC formation on days 3 and 7. Hemosiderin deposition was examined by autofluorescence on day 28. Following ICH, MGCs were predominantly located in the peri-hematoma region exhibiting multiple nuclei and containing red blood cells or their metabolites. Aging was associated with a decrease in MGC formation after ICH, while sex showed no discernible effect. C3 deficiency reduced MGC formation and reduced hemosiderin formation. Peri-hematomal MGCs may play an important role in hematoma resolution. Understanding how aging and complement C3 impact MGCs may provide important insights into how to regulate hematoma resolution.

Fine-needle aspiration cytology of diffuse type tenosynovial giant cell tumor with malignant trasformation and review of literature.

Tenosynovial giant cell tumors (TGCTs) arise from the synovium of joint, bursa, and tendon sheath. Diffuse type often affects large joints, has higher recurrence rates, metastases, and malignant transformation potential compared to the localized type. The cytopathology of TGCT, a fibrohistiocytic neoplasm distinct from other giant cell-rich soft tissue tumors, is rarely reported. Here we describe cytomorphology of a case of TGCT that was initially diagnosed on fine-needle aspiration cytology (FNAC) consisting of a mixture of singly scattered polygonal or spindle mononuclear cells with hemosiderin laden macrophages, inflammatory cells, and a population of multinucleated osteoclast-like giant cells. Persistent symptoms and repeat excision were consistent with high-grade malignant transformation of the TGCT. Atypical cytologic features in a recurrent, infiltrative, or a metastatic lesion should raise suspicion for malignancy.

Cytoplasmic PPARγ Significantly Correlates With P53 Immunohistochemical Expression and Tumor Size in Localized Tenosynovial Giant Cell Tumor.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a monoarticular fibrohistiocytic benign or locally aggressive soft tissue tumor that originates from the synovium of joints, bursae, and tendon sheaths. It has an inflammatory neoplastic nature, with a clinical presentation ranging from pain, swelling, stiffness, and limited range of movement to joint instability and blockage. Its uncommon incidence leads to a poorly understood pathogenesis. Localized forms of TGCT (LTGCT) can cause significant morbidity, interfere with daily patient activities, and decrease the patient's quality of life in challenging cases. This study aimed to investigate the immunohistochemical expression of PPARγ (peroxisome proliferator-activated receptor gamma) and P53 in LTGCT to understand the disease better and offer potential therapeutic targets. METHODS: The study is cross-sectional, in which 27 LTGCT cases were collected from the Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Solitary and multiple LTGCT cases retrieved between January 2018 and December 2022 were included, and immunohistochemically stained with anti-PPARγ and P53 antibodies. The TGCT samples were excluded if they were insufficient for sectioning, processing, and interpretation, over-fixed, had process artifacts, or were of the diffuse TGCT type. Scoring of stain expression was performed by ImageJ (National Institutes of Health, Bethesda, MD) analysis using the threshold method and was expressed in percent area/high power field. Clinicopathological correlations were analyzed. RESULTS: All the 27 collected LTGCT cases were located in the small joints of patients' hands. Cases with solitary LGTCTs constituted 55.6% (n = 15), while 44.4% (n = 12) had multiple LTGCTs related to one affected site/case (e.g., multiple tumors in one finger). PPARγ was expressed in the cytoplasm of mononuclear and multinucleated tumor cells and foamy histiocytes, while P53 expression was mainly in mononuclear cells' nuclei. PPARγ significantly correlated with P53 expression (r = 0.9 and P = 0.000). PPARγ (r = 0.4 and P = 0.02) and P53 (r = 0.5 and P = 0.01) were positively correlated with tumor size. Only P53 expression was positively correlated with tumor multiplicity (r = 0.4 and P = 0.03). Using the receiver operating characteristic curve test, the P53 cutoff score detecting the multiplicity of TGCTs was ≥20.5%, with a 75% sensitivity and 80% specificity. CONCLUSION: PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.

Chronic Idiopathic Ulcers Mimicking Cecal Carcinoma: A Case Report.

Chronic idiopathic ulcers of the colon pose diagnostic challenges due to their elusive etiology and potential resemblance to other intestinal pathologies, such as cecal carcinoma. This case report outlines the clinical course of a 68-year-old female patient who presented to the emergency department (ED) with persistent right lower quadrant pain. Despite multiple hospital visits yielding varied diagnoses, a definitive diagnosis was only made following a laparoscopic partial colectomy, which revealed chronic idiopathic ulcers with transmural scarring and adhesions to adjacent small intestine loops. Histological examination demonstrated a substantial ulcer bed populated by inflammatory cells, including large stellate and spindled stromal cells within the granulation tissue, alongside lymphoid hyperplasia and scar tissue extending into the muscularis propria. The initial presentation of this case could easily be mistaken for appendicitis, diverticulitis, carcinoma, or irritable bowel syndrome, highlighting the significance of considering chronic idiopathic ulcers in the differential diagnosis of patients presenting with cecal masses.

Expression of Selected miRNAs in Undifferentiated Carcinoma with Osteoclast-like Giant Cells (UCOGC) of the Pancreas: Comparison with Poorly Differentiated Pancreatic Ductal Adenocarcinoma.

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas represents a rare subtype of pancreatic ductal adenocarcinoma (PDAC). Despite a distinct morphology and specific clinical behavior, UCOGCs exhibit unexpected similarities in regard to DNA mutational profiles with conventional PDAC. Treating pancreatic ductal adenocarcinoma is particularly challenging, with limited prospects for cure. As with many other malignant neoplasms, the exploration of microRNAs (miRNAs, miRs) in regulating the biological characteristics of pancreatic cancer is undergoing extensive investigation to enhance tumor diagnostics and unveil the therapeutic possibilities. Herein, we evaluated the expression of miR-21, -96, -148a, -155, -196a, -210, and -217 in UCOGCs and poorly differentiated (grade 3, G3) PDACs. The expression of miR-21, miR-155, and miR-210 in both UCOGCs and G3 PDACs was significantly upregulated compared to the levels in normal tissue, while the levels of miR-148a and miR-217 were downregulated. We did not find any significant differences between cancerous and normal tissues for the expression of miR-96 and miR-196a in G3 PDACs, whereas miR-196a was slightly, but significantly, downregulated in UCOGCs. On the other hand, we have not observed significant differences in the expression of the majority of miRNAs between UCOGC and G3 PDAC, with the exception of miR-155. UCOGC samples demonstrated lower mean levels of miR-155 in comparison with those in G3 PDACs.

Functional studies of plant transcription factors and their relevance in the plant root-knot nematode interaction.

Root-knot nematodes are polyphagous parasitic nematodes that cause severe losses in the agriculture worldwide. They enter the root in the elongation zone and subtly migrate to the root meristem where they reach the vascular cylinder and establish a feeding site called gall. Inside the galls they induce a group of transfer cells that serve to nurture them along their parasitic stage, the giant cells. Galls and giant cells develop through a process of post-embryogenic organogenesis that involves manipulating different genetic regulatory networks within the cells, some of them through hijacking some molecular transducers of established plant developmental processes, such as lateral root formation or root regeneration. Galls/giant cells formation involves different mechanisms orchestrated by the nematode´s effectors that generate diverse plant responses in different plant tissues, some of them include sophisticated mechanisms to overcome plant defenses. Yet, the plant-nematode interaction is normally accompanied to dramatic transcriptomic changes within the galls and giant cells. It is therefore expected a key regulatory role of plant-transcription factors, coordinating both, the new organogenesis process induced by the RKNs and the plant response against the nematode. Knowing the role of plant-transcription factors participating in this process becomes essential for a clear understanding of the plant-RKNs interaction and provides an opportunity for the future development and design of directed control strategies. In this review, we present the existing knowledge of the TFs with a functional role in the plant-RKN interaction through a comprehensive analysis of current scientific literature and available transcriptomic data.

Bovine placental extracellular vesicles carry the fusogenic syncytin BERV-K1.

Syncytins are endogenous retroviral envelope proteins which induce the fusion of membranes. A human representative of this group, endogenous retrovirus group W member 1 envelope (ERVW-1) or syncytin-1 is present in trophoblast-derived extracellular vesicles and supports the incorporation of these extracellular vesicles into recipient cells. During pregnancy, placenta-derived extracellular vesicles participate in feto-maternal communication. Bovine fetal binucleate trophoblast cells express the syncytin, bovine endogenous retroviral envelope protein K1 (BERV-K1). These cells release extracellular vesicles into the maternal stroma, but it is unclear whether BERV-K1 is included in these extracellular vesicles. Here, extracellular vesicles were isolated from bovine placental tissue using collagenase digestion, ultracentrifugation, and size exclusion chromatography. They were characterized with transmission electron microscopy, nanoparticle tracking analysis, immunoblotting and mass spectrometry. Immunohistochemistry and immunoelectron microscopy were used to localize BERV-K1 within the bovine placental tissue. The isolated extracellular vesicles range between 50 and 300 nm, carrying multiple extracellular vesicle biomarkers. Proteomic analysis and immunoelectron microscopy confirmed BERV-K1 presence on the isolated extracellular vesicles. Further, BERV-K1 was localized on intraluminal vesicles in secretory granules of binucleate trophoblast cells. The presence of BERV-K1 on bovine placental extracellular vesicles suggests their role in feto-maternal communication and potential involvement of BERV-K1 in uptake of extracellular vesicles by target cells.

Pleomorphic Lipoma of the Parotid Gland: A Potential Cytological Pitfall.

Pleomorphic lipoma is an uncommon benign adipocytic tumor that arises from the subcutis. It has no risk of recurrence, metastasis or malignant transformation. The cytological findings of pleomorphic lipoma are often overdiagnosed as suspicious of malignancy owing to the pleomorphic morphology of the floret giant cells. We present a rare case of pleomorphic lipoma of the parotid gland which was misdiagnosed as a malignant tumor on fine needle aspiration cytology. Histopathological examination and positive expression for CD34 helped to arrive at the final diagnosis. Awareness about this rare entity will prevent overdiagnosis as a malignant tumor and unnecessary radical resections for this benign tumor.

Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: Molecular Genetic Analysis of 13 Cases.

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare malignancy regarded as a subvariant of pancreatic ductal carcinoma (PDAC) characterized by variable prognosis. UCOGC shows a strikingly similar spectrum of oncogenic DNA mutations to PDAC. In the current work, we analyzed the landscape of somatic mutations in a set of 13 UCOGC cases via next-generation sequencing (NGS). We detected a spectrum of pathogenic or likely pathogenic mutations similar to those observed in PDAC following previously published results (10 KRAS, 9 TP53, 4 CDKN2A, and 1 SMAD4, CIC, GNAS, APC, ATM, NF1, FBXW7, ATR, and FGFR3). Our results support the theory that UCOGC is a variant of PDAC, despite its unique morphology; however, a UCOGC-specific genomic signature as well as predictive markers remain mainly unknown. Programmed death ligand 1 (PD-L1) status remains an important predictive marker based on previous studies.

Ovaries of estrogen receptor 1-deficient mice show iron overload and signs of aging.

Introduction: Estrogens are crucial regulators of ovarian function, mediating their signaling through binding to estrogen receptors. The disruption of the estrogen receptor 1 (Esr1) provokes infertility associated with a hemorrhagic, cystic phenotype similar to that seen in diseased or aged ovaries. Our previous study indicated the possibility of altered iron metabolism in Esr1-deficient ovaries showing massive expression of lipocalin 2, a regulator of iron homeostasis. Methods: Therefore, we examined the consequences of depleting Esr1 in mouse ovaries, focusing on iron metabolism. For that reason, we compared ovaries of adult Esr1-deficient animals and age-matched wild type littermates. Results and discussion: We found increased iron accumulation in Esr1-deficient animals by using laser ablation inductively coupled plasma mass spectrometry. Western blot analysis and RT-qPCR confirmed that iron overload alters iron transport, storage and regulation. In addition, trivalent iron deposits in form of hemosiderin were detected in Esr1-deficient ovarian stroma. The depletion of Esr1 was further associated with an aberrant immune cell landscape characterized by the appearance of macrophage-derived multinucleated giant cells (MNGCs) and increased quantities of macrophages, particularly M2-like macrophages. Similar to reproductively aged animals, MNGCs in Esr1-deficient ovaries were characterized by iron accumulation and strong autofluorescence. Finally, deletion of Esr1 led to a significant increase in ovarian mast cells, involved in iron-mediated foam cell formation. Given that these findings are characteristics of ovarian aging, our data suggest that Esr1 deficiency triggers mechanisms similar to those associated with aging.

Haploinsufficiency of Adenomatous Polyposis Coli Coupled with Kirsten Rat Sarcoma Viral Oncogene Homologue Activation and P53 Loss Provokes High-Grade Glioblastoma Formation in Mice.

Glioblastoma multiforme (GBM) is the most common and deadly type of brain tumor originating from glial cells. Despite decades of clinical trials and research, there has been limited success in improving survival rates. However, molecular pathology studies have provided a detailed understanding of the genetic alterations associated with the formation and progression of glioblastoma-such as Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling activation (5%), P53 mutations (25%), and adenomatous polyposis coli (APC) alterations (2%)-laying the groundwork for further investigation into the biological and biochemical basis of this malignancy. These analyses have been crucial in revealing the sequential appearance of specific genetic lesions at distinct histopathological stages during the development of GBM. To further explore the pathogenesis and progression of glioblastoma, here, we developed the glial-fibrillary-acidic-protein (GFAP)-Cre-driven mouse model and demonstrated that activated KRAS and p53 deficiencies play distinct and cooperative roles in initiating glioma tumorigenesis. Additionally, the combination of APC haploinsufficiency with mutant Kras activation and p53 deletion resulted in the rapid progression of GBM, characterized by perivascular inflammation, large necrotic areas, and multinucleated giant cells. Consequently, our GBM models have proven to be invaluable resources for identifying early disease biomarkers in glioblastoma, as they closely mimic the human disease. The insights gained from these models may pave the way for potential advancements in the diagnosis and treatment of this challenging brain tumor.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: An individual participant data meta-analysis.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGCs) of the pancreas is a rare neoplasm that accounts for less than 1% of all pancreatic malignancies. The aim of this study was to review the literature regarding UC-OGC, and to highlight its biological behavior, clinicopathologic characteristics, prognosis, and therapeutic options. A systematic review of the literature in PubMed/Medline and Scopus databases was performed (last search October 31st, 2023) for articles concerning pancreatic UC-OGC in the adult population. Fifty-seven studies met the inclusion criteria, involving 69 patients with a male-to-female ratio of 1.1:1 and a mean age of 62.96. Main symptoms included abdominal pain (33.3%), jaundice (14.5%), weight loss (8.7%), while fourteen patients (20.3%) were asymptomatic. Surgical resection was performed in 88.4% of cases. Survival rates at one, three, and five years were 58%, 44.7%, and 37.3% respectively. Sex, age, size (cut-off of 4 cm), location, and adjuvant treatment did not significantly affect patient survival. UC-OGC of the pancreas is a rare subtype of undifferentiated pancreatic carcinoma with a better prognosis than conventional pancreatic ductal adenocarcinoma or undifferentiated carcinoma without giant cells. The establishment of a dedicated patient registry is imperative to further delineate the optimal treatment for this uncommon clinical entity.

Beyond typical histology of BAP1-inactivated melanocytoma.

BAP1-inactivated melanocytoma (BIM) is a novel subgroup of melanocytic neoplasm listed in the 5th edition of WHO classification of skin tumor. BIM is characterized by two molecular alterations, including a mitogenic driver mutation (usually BRAF gene) and the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21, which encodes for BRCA1-associated protein (BAP1). The latter represents a nuclear-localized deubiquitinase involved in several cellular processes including cell cycle regulation, chromatin remodeling, DNA damage response, differentiation, senescence and cell death. BIMs are histologically characterized by a population of large epithelioid melanocytes with well-demarcated cytoplasmic borders and copious eosinophilic cytoplasm, demonstrating loss of BAP1 nuclear expression by immunohistochemistry. Recently, we have published a series of 50 cases, extending the morphological spectrum of the neoplasm and highlighting some new microscopic features. In the current article, we focus on some new histological features, attempting to explain and link them to certain mechanisms of tumor development, including senescence, endoreplication, endocycling, asymmetric cytokinesis, entosis and others. In light of the morphological and molecular findings observed in BIM, we postulated that this entity unmasks a fine mechanism of tumor in which both clonal/stochastic and hierarchical model can be unified.

An Extremely Rare and Aggressive Case of Undifferentiated Carcinoma With Osteoclast-Like Giant Cells of the Pancreas Presenting as a Paraneoplastic Syndrome: A Case Report and Literature Review.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is a rare tumor type of pancreatic cancer. Paraneoplastic syndromes, an idiopathic inflammatory myositis characterized by various skin manifestations (such as dermatomyositis (DM)), cannot be attributed to the primary tumor itself. Here, we report an unusual case of UC-OGC presenting as a paraneoplastic syndrome, the first reported from Saudi Arabia and the Arabian Gulf states. A 49-year-old Eritrean woman with known DM was referred to our hospital with a left-sided pleural effusion. Computed tomography of the abdomen revealed a large necrotic splenic mass (~17 × 12.9 × 18.2 cm). The patient underwent exploratory laparotomy with en bloc resection of the mass (splenectomy, distal pancreatectomy, and partial excision of the left hemidiaphragm). Following a histopathological examination of the mass, UG-OGC of the pancreas, presenting as a paraneoplastic syndrome, was diagnosed. To our knowledge, this case is the first to present a paraneoplastic syndrome associated with UC-OGC. The identification of an exceedingly rare tumor presenting atypically as a paraneoplastic syndrome shows the importance of conducting comprehensive examinations of patients with malignancies, emphasizing the need for more reports of similar cases.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, a two cases report.

INTRODUCTION AND IMPORTANCE: Fine needle aspiration is the standard method for the pathological evaluation of pancreatic masses. In the following context, rare variants of such masses might present a challenge. Our goal is to describe the clinical, cytological, and histological findings of two cases of undifferentiated carcinoma with osteoclast-like giant cells (UCOCGC) a rare variant of pancreatic ductal adenocarcinoma (PDAC). CASE PRESENTATION: Two cases were identified. Cytological findings exhibit similarities between the two cases. One patient received multiple chemotherapy regimens and a surgery and recurred within three years of diagnosis, while the other succumbed to cholangitis resulting from hepatic metastases a year after their initial surgery. DISCUSSION: UCOCGC is a rare variant of pancreatic cancer, characterized by a unique cytological aspect. Recognizing this variant is essential considering its distinct prognosis compared to usual pancreatic adenocarcinoma. CONCLUSION: We presented two cases of UCOCGC a rare pancreatic cancer variant, exposing diagnostic particularities and clinical evolution.