Gastric-Type Expression Signature in Hepatocellular Carcinoma.

It is known that V-set and immunoglobulin domain containing 1 (VSIG1) is a cell-cell adhesion molecule that can serve as an indicator of better survival in patients with gastric cancer. Its interaction with cytoplasmic thyroid transcription factor 1 (TTF-1) has been hypothesized to characterize gastric-type HCC, but its clinical importance is far from understood. As VSIG1 has also been supposed to be involved in the epithelial-mesenchymal transition (EMT) phenomenon, we checked for the first time in the literature the supposed interaction between VSIG1, TTF-1, and Vimentin (VIM) in HCCs. Immunohistochemical (IHC) stains were performed on 217 paraffin-embedded tissue samples that included tumor cells and normal hepatocytes, which served as positive internal controls. VSIG1 positivity was seen in 113 cases (52.07%). In 71 out of 217 HCCs (32.71%), simultaneous positivity for VSIG1 and TTF-1 was seen, being more specific for G1/G2 carcinomas with a trabecular architecture and a longer OS (p = 0.004). A negative association with VIM was revealed (p < 0.0001). Scirrhous-type HCC proved negative for all three examined markers. The present paper validates the hypothesis of the existence of a gastric-type HCC, which shows a glandular-like architecture and is characterized by double positivity for VSIG1 and TTF-1, vimentin negativity, and a significant OS.

Bioinformatic Identification of TP53 Gene Mutation Hotspots in Colorectal Cancer.

Mutations and inactivation of the TP53 gene are frequently observed in various types of malignancies. Precise knowledge of the genetic structure and detection of mutation hotspots are crucial, as these indicate a high probability of developing cancer. The aim of our study was to perform the bioinformatic detection of mutation hotspots in the TP53 gene in patients diagnosed with malignant colon neoplasms using self-developed software (version 1). We compared TP53 gene sequences from 50 healthy individuals with those from 50 patients diagnosed with colorectal carcinoma. Of the 50 samples from cancer patients, the most frequent mutations were observed in exons 5 and 8 (12 mutations per exon) and gene sequences of 12 samples, which differed from those of the 50 samples from healthy individuals. Based on our results, the distribution of mutations in the TP53 gene structure was not even across different exons. By comparing the gene sequences of healthy individuals with those of colon cancer samples, we conclude that structural changes occurring in similar gene regions are not associated with increases in susceptibility to malignancies in every case, namely, that the pathological mechanism is multifactorial.

Molecular Diagnostics, Pathology and Biomarkers of Gastrointestinal Neoplasms.

This Special Issue aims to highlight the advances made regarding the molecular profile of digestive system tumors in experimental and clinical studies [...].

Mucin-Phenotype and Expression of the Protein V-Set and Immunoglobulin Domain Containing 1 (VSIG1): New Insights into Gastric Carcinogenesis.

In gastric cancer (GC), intestinal metaplasia (IM) is a common precursor lesion, but its relationship to the MUC2/MUC5AC/CDX2 axis is not completely understood. Although V-set and immunoglobulin domain containing 1 (VSIG1) is supposed to be a specific marker for gastric mucosa and GC, respectively, no data about its relationship with IM or mucin phenotype have been published. The aim of our study was to explore the possible linkage between IM and these four molecules. The clinicopathological features of 60 randomly selected GCs were examined in association with VSIG1, MUC2, MUC5AC and CDX2. Two online database platforms were also used to establish the transcription factors (TFs) network involved in MUC2/MUC5AC/CDX2 cascade. IM was more frequently encountered in females (11/16 cases) and in patients below 60 years old (10/16 cases). Poorly differentiated (G3) carcinomas tended to show a loss of CDX2 (27/33 cases) but not of MUC2 and MUC5AC. MUC5AC and CDX2 were lost in parallel with the depth of invasion of the pT4 stage (28/35 and 29/35 cases), while an advanced Dukes-MAC-like stage was only correlated with CDX2 and VSIG1 loss (20/37 and 30/37 cases). VSIG1 was directly correlated with MUC5AC (p = 0.04) as an indicator of gastric phenotype. MUC2-negative cases showed a propensity towards lymphatic invasion (37/40 cases) and distant metastases, while CDX2-negative cases tended to associate with hematogenous dissemination (30/40 cases). Regarding the molecular network, only 3 of the 19 TFs involved in this carcinogenic cascade (SP1, RELA, NFKB1) interacted with all targeted genes. In GC, VSIG1 can be considered an indicator of gastric phenotype carcinomas, where carcinogenesis is mainly driven by MUC5AC. Although infrequently encountered in GC, CDX2 positivity might indicate a locally advanced stage and risk for vascular invasion, especially in tumors developed against the background of IM. The loss of VSIG1 indicates a risk for lymph node metastases.

Signet-Ring Cell Squamous Cell Carcinoma: A Biphenotypic Neoplasm of the Gastro-Esophageal Junction with Uncertain Biological Potential: Case Report and Literature Review.

The signet-ring cell variant of squamous cell carcinoma (SCC) is an extremely rare histological subtype, with only 24 cases (including the present case) reported in the Medline database: 15 affecting the external surface of the body, 3 in the lung, 2 affecting the uterine cervix, 1 involving the gingiva, another one affecting the esophagus and the present case that is the first reported at the gastro-esophageal junction (GEJ). In one case, the location of the lesion was not mentioned. A 59-year-old male patient underwent segmental eso-gastrectomy for carcinoma of the GEJ. The microscopic examination showed a pT3N1-staged SCC composed of solid nests admixed in over 30% of the tumor, with cells having eccentrically located nuclei and clear vacuolated cytoplasm. The signet-ring cells did not show mucinous secretion and were positive for keratin 5/6 and vimentin, with nuclear expression of ß-catenin and Sox2 and focal membrane positivity for E-cadherin. Based on these features, the case was considered a signet-ring SCC with epithelial-mesenchymal transition. Thirty-one months after surgery, the patient was disease-free, with no local recurrence and no known distant metastases. In SCC, a signet-ring cell component might be an indicator of the dedifferentiation of tumor cells towards a mesenchymal molecular subtype.

The Importance of Aortic Valve Bicuspid Phenotype in Valvular Evolution in Pediatric Patients: A Case Report and Literature Mini-Review.

Bicuspid aortic valve (BAV) is the most commonly encountered congenital malformation in the pediatric population, associated with aortic leaflet degeneration and aortopathy. However, studies on BAV and its complications in children are limited. We present the case of a 16-year-old with type 1B BAV with a raphe with fusion between the right and non-coronary cusps who exhibited severe aortic stenosis, regurgitation, and progressive dilatation of the ascending aorta. Surgical intervention, including aortic valve and aortic root replacement, was performed due to the patient's deteriorating condition. Histopathological examination revealed degenerative changes and calcifications in the aortic valve and mucoid fibrosis in the ascending aorta. The results are consistent with BAV patients being predisposed to aortic stenosis and regurgitation due to increased mechanical stress and hemodynamic abnormalities. Although more common in adults and a rare complication in pediatric patients, calcification was previously observed concurrently with rapid valve degeneration in our daily practice. Further studies are needed to improve our understanding of the mechanisms underlying BAV-related complications and refine treatment strategies for pediatric patients.

Histopathological Gap in Aortic Diseases: A Prospective Analysis.

Aortic dissection (AD) is a critical cardiovascular condition with the potential for devastating consequences. This study evaluated the histological changes in the aorta wall in patients with AD and aortic aneurysm (AA) who received surgical aortic replacement. Histopathological data showed that modifications of the media layer (p = 0.0197), myxomatous aspect (p = 0.0001), and subendothelial layer degeneration (p = 0.0107) were more frequently seen in AA versus AD samples. Patients with AA were approximately twice as likely to develop histological changes than those with AD (p = 0.0037). Patients with moderate or severe medial degeneration had a higher chance of developing AD (p = 0.0001). Because the histopathological score proved to be a predictor of both in-hospital and overall mortality, its evaluation should become the standard of care in any patients who undergo aortic replacement. Individualized postoperative management might be influenced by the histopathological aspect of the aortic layer.

From Dukes-MAC Staging System to Molecular Classification: Evolving Concepts in Colorectal Cancer.

This historical review aimed to summarize the main changes that colorectal carcinoma (CRC) staging systems suffered over time, starting from the creation of the classical Duke's classification, modified Astler-Coller staging, internationally used TNM (T-primary tumor, N-regional lymph nodes' status, M-distant metastases) staging system, and ending with molecular classifications and epithelial-mesenchymal transition (EMT) concept. Besides currently used staging parameters, this paper briefly presents the author's contribution in creating an immunohistochemical (IHC)-based molecular classification of CRC. It refers to the identification of three molecular groups of CRCs (epithelial, mesenchymal and hybrid) based on the IHC markers E-cadherin, ß-catenin, maspin, and vimentin. Maspin is a novel IHC antibody helpful for tumor budding assessment, which role depends on its subcellular localization (cytoplasm vs. nuclei). The long road of updating the staging criteria for CRC has not come to an end. The newest prognostic biomarkers, aimed to be included in the molecular classifications, exert predictive roles, and become more and more important for targeted therapy decisions.

Staphylococcus-induced proliferative glomerulonephritis and cerebral hemorrhage - fatal complications in a young female with postpartum cardiomyopathy and an implanted left ventricular assist device: a case report and review of the literature.

Background: The continuous-flow left ventricular assist device (CF-LVAD) is used to save the lives of patients in the final stage of congestive heart failure, replacing the pump function of the left ventricle. Although quality of life increases significantly, CF-LVAD-related complications might prove fatal, as in the case presented in this paper.Methods: A 20-year-old female, during her second pregnancy, presented with signs of heart failure. Emergency caesarean section was necessary to save the baby, but peripartum cardiomyopathy developed in the mother. The use of an implantable cardioverter-defibrillator (ICD) was necessary 5 years later. As the clinical progression was unfavorable under medical treatment, with the patient reaching INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) Profile 1 (refractory cardiogenic shock), the treatment of choice was the implantation of a CF-LVAD.Results: After 3 years of follow-up (at the age of 28), the patient presented with a positive hemoculture for Staphylococcus aureus. Prolonged antibiotic therapy and attentive follow-up was prescribed. Although an effective antiplatelet and anticoagulant treatment was applied, and despite therapeutic values of prothrombin time and international normalized ratio (INR), the patient died as result of a fatal cerebral hemorrhage. The autopsy also revealed septic emboli, disseminated intravascular coagulation, and focal proliferative glomerulonephritis.Conclusions: Although the benefits of CF-LVAD are significant, bleeding episodes can be severe and LVAD-associated infection can trigger glomerular injury and increase mortality.

Interaction between cadherins, vimentin, and V-set and immunoglobulin domain containing 1 in gastric-type hepatocellular carcinoma.

In hepatocellular carcinomas (HCCs), the role of the cell surface protein V-set and immunoglobulin domain containing 1 (VSIG1), which is known as a specific marker of the gastric mucosa and testis, has not yet been determined. We examined VSIG1 immunohistochemical (IHC) expression in 105 consecutive samples provided by HCC patients, along with the IHC expression of three of the biomarkers known to be involved in the epithelial-mesenchymal transition (EMT): vimentin (VIM), and E- and N-cadherin (encoded by CDH1 and CDH2 genes). IHC subcellular localization of thyroid transcription factor 1 (TTF1), in which nuclear-to-cytoplasmic translocation is known to cause a lineage shift from lung to gastric-type adenocarcinoma, was also checked. The obtained data were validated using the miRNET program. In the examined HCC samples, VSIG1 expression was observed in the cytoplasm of normal hepatocytes and downregulated in 47 of the 105 HCCs (44.76%). In 29 cases (27.62%), VSIG1 was co-expressed with cytoplasmic TTF1. VSIG1 expression was positively correlated with both E-cadherin and N-cadherin and negatively correlated with VIM (p < 0.0001). The VSIG1+/E-cadherin+/N-cadherin-/VIM phenotype was seen in 13 cases (12.4%) and was characteristic of well-differentiated (G1/2) carcinomas diagnosed in pT1/2 stages. Like pulmonary carcinomas, simultaneous cytoplasmic positivity of HCC cells for VSIG1 and TTF1 may be a potential indicator of a lineage shift from conventional to gastric-type HCC. The E-cadherin/VSIG1 complex can help suppress tumor growth by limiting HCC dedifferentiation. The miRNET-based interaction between VSIG1/VIM/CDH1/CDH2 genes might be interconnected by miR-200b-3p, a central regulator of EMT which also targets VIM and VSIG1.

Relevance of BRAF Subcellular Localization and Its Interaction with KRAS and KIT Mutations in Skin Melanoma.

Although skin melanoma (SKM) represents only one-quarter of newly diagnosed skin malignant tumors, it presents a high mortality rate. Hence, new prognostic and therapeutic tools need to be developed. This study focused on investigating the prognostic value of the subcellular expression of BRAF, KRAS, and KIT in SKM in correlation with their gene-encoding interactions. In silico analysis of the abovementioned gene interactions, along with their mRNA expression, was conducted, and the results were validated at the protein level using immunohistochemical (IHC) stains. For IHC expression, the encoded protein expressions were checked on 96 consecutive SKMs and 30 nevi. The UALCAN database showed no prognostic value for the mRNA expression level of KRAS and BRAF and demonstrated a longer survival for patients with low mRNA expression of KIT in SKMs. IHC examinations of SKMs confirmed the UALCAN data and showed that KIT expression was inversely correlated with ulceration, Breslow index, mitotic rate, and pT stage. KRAS expression was also found to be inversely correlated with ulceration and perineural invasion. When the subcellular expression of BRAF protein was recorded (nuclear vs. cytoplasmatic vs. mixed nucleus + cytoplasm), a direct correlation was emphasized between nuclear positivity and lymphovascular or perineural invasion. The independent prognostic value was demonstrated for mixed expression of the BRAF protein in SKM. BRAF cytoplasmic predominance, in association with KIT's IHC positivity, was more frequently observed in early-stage nonulcerated SKMs, which displayed a low mitotic rate and a late death event. The present study firstly verified the possible prognostic value of BRAF subcellular localization in SKMs. A low mRNA expression or IHC cytoplasmic positivity for KIT and BRAF might be used as a positive prognostic parameter of SKM. SKM's BRAF nuclear positivity needs to be evaluated in further studies as a possible indicator of perineural and lymphovascular invasion.

Parietex ProGrip™ Self-Fixating Mesh in Surgical Treatment of Pelvic Organ Prolapse.

Introduction: Advanced pelvic organ prolapse is a public health problem, and its treatment can be difficult, requiring a multidisciplinary approach. Aim: The main objective of this article is to describe particular aspects of the use of Parietex ProGrip trade; Self-Fixating Mesh for abdominal sacrocolpopexy or sacrocervicopexy. The secondary objective is to present the initial results of the use of these self-fixating meshes. Results: Ten successive patients with a POP of grade 2 or higher have benefited from this procedure. No complications or recurrences of prolapse were detected at 1, 3 and 6 months postoperatively. The mean operative time was 102Â+-25.84 minutes. The mean length of hospital stay was 6.7Â+-0.67 days. Conclusions: The results of this surgical procedure demonstrate that Parietex ProGrip trade; Self- Fixating Mesh can be used without complications and with good postoperative results. The main advantage of using this mesh is that it does not require other fastening means. The lack of rejection reaction or foreign body pathology encourages the implementation of this surgical procedure. Further study is needed to consolidate these results.

Long Term Results of Modified Intersphincteric Resections for Low Rectal Cancer: A Single Center Experience.

BACKGROUND AND OBJECTIVES: The objective of this article is to evaluate the long-term oncological and functional outcomes following modified intersphincteric resections (ISR) for low rectal cancer. The modified technique consisted of the abandonment of colonic J-pouches, transverse coloplasty, or defunctioning temporary stoma in favor of a direct handsewn coloanal anastomosis (CAA). MATERIAL AND METHODS: Sixty consecutive patients with type II and III (juxta-anal or intra-anal) low rectal tumors underwent modified ISR by the same surgical team and were followed for a period of five years. Functional outcomes using the Wexner Score, postoperative complications, recurrence rates, morbidity, and mortality rates were assessed. RESULTS: The five-year survival rate was 93.3% with a disease-free interval at three years of 98%. Morbidity was 15% (n = 9) consisting of intestinal wall necrosis (n = 6), stenosis (n = 2), and sacral metastasis (n = 1). The Wexner score values were, at 1 year, 8.5 (range, 4-13); at three years 7.2 (range, 2-11); and at 5 years 6.7 (range, 2-12). A second surgery was needed in only one case that showed postoperative transmural necrosis of the colonic wall. CONCLUSIONS: In highly selected patients with type II or III low rectal tumors and proper preoperative imaging staging, ISR might be a viable alternative to other techniques such as abdominoperineal resection and low anterior resection, both from a functional and an oncological perspective.

Angiomyofibroblastoma mimicking an inguinal hernia: a challenging diagnosis in a male patient.

INTRODUCTION: Angiomyofibroblastoma is a rare benign myofibroblastic neoplasm which mainly occurs in the soft tissues of the pelvi-perineal region of females. AIM: To present an unusual case of angiomyofibroblastoma mimicking an inguinal hernia in a 62-year-old male. MATERIAL AND METHODS: The patient was hospitalized with an irreducible, painless inguinal mass and surgical intervention for inguinal hernia was decided. The well-defined nodular mass was sent for histological examination. RESULTS: Under microscope, proliferation of spindle and oval cells around thin-walled vessels was observed, being intermingled with mature adipocytes. We did not identify necrosis, haemorrhage, cytologic atypia or mitotic figures. The tumour cells displayed positivity for desmin, vimentin, CD34, oestrogen and progesterone receptors, a low Ki67 index and unusual nuclear positivity for c-theta (PKCθ). They were negative for smooth muscle actin (SMA), S100, CD44, maspin, synaptophysin, DOG1 and CD117. The case was diagnosed as angiomyofibroblastoma, the main challenge being the differential diagnosis with aggressive angiomyxoma, which can present a similar histologic aspect and immunophenotype and recurs more frequently. No recurrences were observed 8 months after the surgery. CONCLUSIONS: Angiomyofibroblastoma should be included in the differential diagnosis of inguinal hernia. This is the fourteenth case of angiomyofibroblastoma diagnosed in males.

Different synovial vasculogenic profiles of primary, rapidly destructive and osteonecrosis-induced hip osteoarthritis. An immunohistochemistry study.

PURPOSE: To present a hypothesis regarding the pathways of angiogenesis in primary versus secondary hip osteoarthritis (OA). METHODS: In synovial tissue samples provided by 57 consecutive patients who underwent hip arthroplasty, immunohistochemical examinations were performed using the following angiogenesis-related antibodies: VEGF-A, COX-2, maspin and the endothelial cells markers CD31 and CD105. The cases were divided into three categories: classic primary hip OA (group A; n = 16), rapidly destructive hip OA (group B; n = 24) and hip OA secondary to avascular osteonecrosis of the femoral head (group C; n = 17). The endothelial area (EA) was digitally quantified for both CD31 and CD105. RESULTS: The large mature vessels with CD105-positive activated endothelium predominated in group C, which also showed the highest CD105 median EA value (7.31 ± 4.01, compared to 4.76 ± 3.73 for group A and 6.69 ± 3.53 for group B). In groups A and B, synovial cell hyperplasia and the predominance of small immature vessels were characteristic. CD105, VEGF-A and COX-2 were focally seen in the synovial membrane, without maspin positivity. CONCLUSIONS: The severity of hip OA can be related to angiogenesis pathways that are not maspin-mediated. In primary hip OA, angiogenesis may be induced by a combined mechanism: hypoxia-related VEGF-dependent vasculogenesis and endothelial differentiation of the activated pluripotent cells, which are released from the hyperplastic synovial cells layer. An endothelial mesenchymal transition is assumed to be involved in the fibrotic process.

Unusual Location of Hydatid Cysts: Report of Two Cases in the Heart and Hip Joint of Romanian Patients.

Hydatid cyst is usually located in the liver and lungs, rare cases showing localization in other organs or tissues. In the unusual location, echinococcosis is an excluding diagnosis that is established only after microscopic evaluation. Our first case occurred in a 67-year-old female previously diagnosed with pulmonary tuberculosis and hospitalized with persistent pain in the hip joint. The clinical diagnosis was tuberculosis of the joint, but the presence of the specific acellular membrane indicated a hydatid cyst of the synovial membrane, without bone involvement. Fewer than 25 cases of joint hydatidosis have been reported in literature to date. In the second case, the intramural hydatid cyst was incidentally discovered at autopsy, in the left heart ventricle of a 52-year-old male hospitalized for a fatal brain hemorrhage, as a result of rupture of an anterior communicating artery aneurysm. The conclusion of our paper is that echinococcosis should be taken into account for the differential diagnosis of cystic lesions, independently from their location.

Surgical reconstruction of the genitalia in a 3-year-old infant with a 46XX karyotype: case report.

UNLABELLED: A 3-year-old patient was hospitalized with ambiguous genitalia (clitoromegaly, labioscrotal fusion, absence of vaginal introitus), classified as stage III/IV according to Prader's virilization scale. Our patient, with a 46XX karyotype, was previously diagnosed with congenital adrenal hyperplasia caused by a deficiency of the adrenal enzyme 21-hydroxylase; corticosteroids and salt replacement therapy have been used. At the present admission, the surgical treatment consisted on clitoroplasty (with the removal of erectile tissue), reconstruction of the labia minor, creation of a neovulva and vaginoplasty. It was a single-step operation to restore the anatomical female structures. She had an uneventful postoperative period and the wound healed well with good cosmetic results. We present the details about the surgical procedure and a short review of data from literature. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Pathogenetic and molecular classifications of soft tissue and bone tumors: A 2024 update.

Soft tissue and bone tumors comprise a wide category of neoplasms. Their diversity frequently raises diagnostic challenges, and therapeutic options are continuously developing. The therapeutic success rate and long-term prognosis of patients have improved substantially due to new advances in immunohistochemical and molecular biology techniques. A fundamental contribution to these achievements has been the study of the tumor microenvironment and the reclassification of new entities with the updating of the molecular pathogenesis in the revised 5th edition of the Classification of Soft Tissue Tumors, edited by the World Health Organization. The proposed molecular diagnostic techniques include the well-known in situ hybridization and polymerase chain reaction methods, but new techniques such as copy-number arrays, multiplex probes, single-nucleotide polymorphism, and sequencing are also proposed. This review aims to synthesize the most recent pathogenetic and molecular classifications of soft tissue and bone tumors, considering the major impact of these diagnostic tools, which are becoming indispensable in clinicopathological practice.

Combined hepatocellular-cholangiocarcinoma: from genesis to molecular pathways and therapeutic strategies.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. Little is known about the combined hepatocellular-cholangiocarcinoma (cHCC-ICC) variant and the proper therapeutic strategies. Out of over 1200 available studies about cHCC-ICC, we selected the most representative ones that reflected updated information with application to individualized therapy. Based on literature data and own experience, we hypothesize that two molecular groups of cHCC-ICC can be identified. The proposed division might have a significant therapeutic role. Most cases develop, like HCC, on a background of cirrhosis and hepatitis and share characteristics with HCC; thus, they are named HCC-type cHCC-ICC and therapeutic strategies might be like those for HCC. This review also highlights a new carcinogenic perspective and identifies, based on literature data and the own experience, a second variant of cHCC-ICC called ICC-type cHCC-ICC. Contrary to HCC, these cases show a tendency for lymph node metastases and ICC components in the metastatic tissues. No guidelines have been established yet for such cases. Individualized therapy should be, however, oriented toward the immunoprofile of the primary tumor and metastatic cells, and different therapeutic strategies should be used in patients with HCC- versus ICC-type cHCC-ICC.

Metaplastic bone formation in the abdominal wall--an incidental finding in a patient with gastric cancer. Case report and hypothesis about its histogenesis.

A 64-year-old man was hospitalized showing symptoms suggesting gastric cancer. The gastroscopy showed a 70 × 30-mm tumor. The intraoperatory findings indicated an inoperable gastric tumor located in the antrum and gastric body, which invaded the spleen and pancreas. The abdominal incision was closed without performing gastrectomy. Considering his general condition, after 1 month, he was transferred to our hospital. We decided to perform a total gastrectomy of necessity, spleno-pancreatectomy, and dissection of regional lymph nodes. The surgical incision was performed along to the previous one. At palpation, a well-defined nodule with hard consistency was observed in the surgical scar, which microscopically was composed by osteoblasts-lining mature lamellar bone intermingled with osteoid and cartilage in the intermediary layer and fibroblasts in the central area, without atypia. The final diagnosis was localized metaplastic bone formation. This is a rare condition which can be related to trauma or surgery and should be differentiated by foreign-body granuloma and osteosarcoma.