A Rare Inflammatory Myofibroblastic Tumor of the Spleen: A Case Report.

BACKGROUND/AIM: Inflammatory myofibroblastic tumors (IMTs) are rare, solid, potentially malignant lesions of uncertain etiology. Histologically, IMTs exhibit a combination of lymphocytes and inflammatory cells within a fibroblastic myxoid layer. The diagnosis of IMTs poses a challenge for various medical specialties, including surgeons, pathologists, and oncologists, due to their non-specific clinical presentation. Furthermore, radiologists face difficulties in interpreting computed tomography (CT) or magnetic resonance imaging (MRI) results, which often yield polymorphic and inconclusive findings. Ultimately, histopathologists play a crucial role in reaching a definitive diagnosis based on the tumor's histological characteristics. They are detected in every system of the human body, most commonly in the lungs. Here, we report an uncommon occurrence of IMT in the spleen of a patient with nonspecific abdominal pain. CASE REPORT: A 56-year-old Caucasian female presented to Konstantopouleio General Hospital of Nea Ionia, Athens, Greece, with abdominal pain and discomfort. The patient had no significant medical history and normal laboratory tests. An abdominal CT revealed a large mass in the spleen. A splenectomy was performed. Histopathological analysis of the tumor revealed IMTS. CONCLUSION: Splenic IMT is a rare benign tumor with moderate malignant potential. It lacks a distinct clinical presentation and is typically identified either incidentally or during the examination of abdominal pain.

Multiple non-syndromic basal cell carcinoma with the chest as primary site and lung metastases: A rare case.

Basal cell carcinoma (BCC) is the most commonly diagnosed cancer in humans, usually affecting elderly Caucasian men and skin regions mostly exposed to the sun, that rarely metastasizes. We report an unusual and aggressive case of multiple, non-syndromic metastatic BCC with an uncommon primary site in the chest and pulmonary metastases, treated successfully with surgery and vismodegib. A 51-year-old woman presented with a large pigmentary lesion of the chest, close to the sternum. She had the lesion for > 25 years and lately noticed multiple facial lesions. The diagnosis of multiple BCC was suspected and a punch biopsy of the primary lesion was performed. Diagnosis was confirmed by immunohistochemistry (BerEp4+, EMA- phenotype). After excision, staging with a thorax computed tomography scan revealed metastatic micro-nodules in the left lung, confirmed histologically after video-assisted thoracic surgical biopsy. Adjuvant chemotherapy with vismodegib was proposed and administered. At 30 days follow-up, thorax computed tomography scan was unaltered and her facial lesions showed significant regression. Although prognosis remains poor, early diagnosis and prompt management complimented by novel biological agents, like vismodegib, targeting disease pathogenesis, seems to bring promising results.

Association of Notch and Hedgehog Pathway Activation With Prognosis in Early-stage Colorectal Cancer.

BACKGROUND/AIM: Early-stage colorectal cancer (CRC) carries a wide range of survival probabilities. Novel biomarkers in this setting are eagerly awaited. Cancer stem cells (CSCs) are considered one of the reasons for treatment failure. This study sought to determine whether activation of pathways governing the function of CSC's could correlate with treatment outcomes. MATERIALS AND METHODS: Tumor specimens from 325 patients were analyzed with immunohistochemistry (IHC) for Hedgehog and Notch pathway activation and results were correlated with prognosis. RESULTS: Positive Notch3 protein expression was an unfavorable prognostic factor for disease-free survival (DFS) and overall survival (OS) (HR=2.43, p=0.024 and HR=2.56, p=0.028, respectively). Activation of the Shh pathway showed univariately longer DFS (HR=0.49, p=0.032). Possible crosstalk between the two pathways was indicated. No further associations between pathway activation and outcome were evident. CONCLUSION: Apart from Notch 3, activation of the pathways, as indicated by IHC expression of their components, did not result in differences in terms of DFS or OS.

Prognostic significance of tumor genotypes and CD8+ infiltrates in stage I-III colorectal cancer.

BACKGROUND: We explored the clinical significance of tumor genotypes and immunophenotypes in non-metastatic colorectal cancer (CRC). METHODS: In primary tumors (paraffin blocks) from 412 CRC patients treated with adjuvant chemotherapy, we examined pathogenic mutations (panel NGS; 347 informative); mismatch repair (MMR) immunophenotype (360 informative); and CD8+ lymphocyte density (high - low; 412 informative). The primary outcome measure was disease-free survival (DFS). RESULTS: We evaluated 1713 pathogenic mutations (median: 3 per tumor; range 0-49); 118/412 (28.6%) tumors exhibited high CD8+ density; and, 40/360 (11.1%) were MMR-deficient. Compared to MMR-proficient, MMR-deficient tumors exhibited higher CD8+ density (chi-square, p<0.001) and higher pathogenic mutation numbers (p=0.003). High CD8+ density was an independent favorable prognosticator (HR=0.49, 95%CI 0.29-0.84, Wald's p=0.010). Pathogenic BRCA1 and ARID1A mutations were inversely associated with each other (p<0.001), were not associated with MMR-deficiency or CD8+ density, but both independently predicted for unfavorable DFS (HR=1.98, 95%CI 1.12-3.48, p=0.018 and HR=1.99, 95%CI 1.11-3.54, p=0.020, respectively). CONCLUSION: In non-metastatic CRC, high CD8+ lymphocyte density confers a favorable prognosis and may be developed as a single marker in routine diagnostics. The unfavorable prognostic effect of pathogenic BRCA1 and ARID1A mutations is a novel observation that, if further validated, may improve treatment selection.

Expression Patterns of Growth and Survival Genes with Prognostic Implications in Advanced Pancreatic Cancer.

AIM: The aim of this study was to evaluate the mRNA expression pattern of growth- and survival-related genes and assess their prognostic significance in patients with advanced pancreatic cancer. PATIENTS AND METHODS: In total, 98 patients were included in this retrospective translational research study and were evaluated for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status, and v-akt murine thymoma viral oncogene homolog 1 (AKT1), AKT serine/threonine kinase 2 (AKT2), AKT serine/threonine kinase 3 (AKT3), cyclin D1 (CCND1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), hepatocellular growth factor receptor (MET), avian myelomatosis viral oncogene homolog (MYC), nuclear factor kappa B subunit 1 (NFKb1), phosphatase and tensin homolog (PTEN) and mechanistic target of rapamycin (FRAP1) genes mRNA expression. Among these patients, 73 received first-line gemcitabine combined with erlotinib (N=57) or gefitinib (N=16). RESULTS: KRAS mutation did not correlate with mRNA gene expression. Unsupervised hierarchical clustering according to mRNA gene expression successfully distinguished four prognostically distinct groups of tumors. Overexpression of all genes was associated with best prognosis, while suppression or heterogeneous expression patterns of the examined genes were associated with expression patterns of growth- and survival-related genes, classifying pancreatic tumors into distinct groups with possibly different outcomes.

Positive para-aortic lymph nodes following pancreatectomy for pancreatic cancer. Systematic review and meta-analysis of impact on short term survival and association with clinicopathologic features.

BACKGROUND: The relation between para-aortic lymph nodes (PALN) involvement and pancreatic ductal adenocarcinoma (PDAC) survival, along with the optimal handling of this particular lymph node station remain unclear. A systematic review and meta-analysis was performed to assess this. METHODS: A search of Medline, Embase, Ovid and Cochrane databases was performed until July 2015 to identify studies reporting on the relation of PALN involvement and PDAC outcomes and a meta-analysis was performed following data extraction. RESULTS: Ten retrospective studies and two prospective non randomized studies (2467 patients) were included. Patients with positive PALN had worse one (p < 0.00001) and two year (p < 0.00001) survival when compared with patients with negative PALN. Even when comparing only patients with positive lymph nodes (N1), patients with PALN involvement presented with a significant lower one (p = 0.03) and two (p = 0.002) year survival. PALN involvement was associated with an increased possibility of positive margin (R1) resection (p < 0.00001), stations' 12, 14 and 17 malignant infiltration (p < 0.00001), but not with tumour stage (p = 0.78). DISCUSSION: Involvement of PALN is associated with decreased survival in pancreatic cancer patients. However, existence of long term survivors among this subgroup of patients should be further evaluated, in order to identify factors associated with their favourable prognosis.

Innovations in macroscopic evaluation of pancreatic specimens and radiologic correlation.

The purpose of this study was to evaluate the feasibility of a novel dissection technique of surgical specimens in different cases of pancreatic tumors and provide a radiologic pathologic correlation. In our hospital, that is a referral center for pancreatic diseases, the macroscopic evaluation of the pancreatectomy specimens is performed by the pathologists using the axial slicing technique (instead of the traditional procedure with longitudinal opening of the main pancreatic and/or common bile duct and slicing along the plane defined by both ducts). The specimen is sliced in an axial plane that is perpendicular to the longitudinal axis of the descending duodenum. The procedure results in a large number of thin slices (3-4 mm). This plane is identical to that of CT or MRI and correlation between pathology and imaging is straightforward. We studied 70 cases of suspected different solid and cystic pancreatic tumors and we correlated the tumor size and location, the structure-consistency (areas of necrosis-hemorrhage-fibrosis-inflammation), the degree of vessels' infiltration, the size of pancreatic and common bile duct and the distance from resection margins. Missed findings by imaging or pitfalls were recorded and we tried to explain all discrepancies between radiology evaluation and the histopathological findings. Radiologic-pathologic correlation is extremely important, adding crucial information on imaging limitations and enabling quality assessment of surgical specimens. The deep knowledge of different pancreatic tumors' consistency and way of extension helps to improve radiologists' diagnostic accuracy and minimize the radiological-surgical mismatching, preventing patients from unnecessary surgery.

HER Family Protein Expression in a Greek Population with Gastric Cancer. A Retrospective Hellenic Cooperative Oncology Group Study.

BACKGROUND: Gastric cancer is a relatively common malignancy. Recently, the presence of the human epidermal growth factor receptor 2 (HER2) was identified as a molecular target in a proportion of patients who benefited from the addition of appropriate anti-HER2 treatments. Our study explored the clinical and prognostic role of known HER family members, human epidermal growth factor receptor 1 (EGFR or HER1), HER2, HER3 and HER4. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 249 gastric cancer patients were studied by immunohistochemistry for protein expression of EGFR, HER2, HER3 and HER4. RESULTS: Of the 249 evaluable patients, 32 did not have complete data of treatment details and/or follow-up and were excluded from the survival analyses. Of the 217 patients with complete treatment and follow-up data, 178 were operated and treated for early disease (group 1), while 39 for advanced disease (group 2). The frequency of positive EGFR, HER2, HER3 and HER4 protein expression in all patients was 17.5%, 11.8%, 14.8% and 32.9%, respectively. There were no differences in protein expression of any of the markers between the two groups. There were, however, statistically significant associations between HER4 and all other HER family members, as well as between HER2 and HER3 expression. Of note, EGFR-positive membranous protein expression was significantly associated with the presence of lymphovascular invasion (p=0.027) and HER3 and HER4 negative cytoplasmic protein expression with well/moderately-differentiated tumors (p=0.030 and p=0.014, respectively). None of the HER family members were of prognostic value for OS in univariate analysis. CONCLUSION: The present study confirmed the known protein expression frequencies of HER family members in gastric cancer in a Greek population. Several associations were observed among the HER family members and between clinicopathological characteristics and HER family members. Further research is needed on their exact prognostic role, as well as their therapeutic targeting.

Hemiepiphysiodeses for guided growth in children.

Lower-extremity angular deformities are among the most common non-traumatic conditions in children being referred to pediatric orthopedists. Understanding of this abnormality and knowledge of current treatment is essential for pediatricians and primary caregivers. A development in the surgical management of these problems has improved the quality of care of affected children and adolescents. Traditionally, angular deformities are treated by means of osteotomy. In patients who are skeletally immature, this major intervention can be avoided by influencing or guiding the growth of the affected physis using hemiepiphysiodesis techniques. Recently, alternative surgical techniques and implants have been described for improved control of the guided growth.

Donor's site evaluation after restoration with autografts or synthetic plugs in rabbits.

AIM: To investigate donor site's area histological and immunohistochemical knee cartilage appearances after resurfacing iatrogenic defects with biosynthetic plugs orautografts. METHODS: Thirty New Zealand White rabbits were used in this study. A full-thickness cylindrical defect of 4.5 mm (diameter) × 7 mm (depth) was created with a hand drill in the femoral groove of every animal. In Group A (n = 10) the defect of the donor site was repaired with a biosynthetic osteochondral plug, in Group B (n = 10) with an osteochondral autograft, while in Group C (control group of 10) rabbits were left untreated. RESULTS: Twenty-four weeks postoperatively, smooth articular cartilage was found macroscopically in some trocleas' surfaces; in all others, an articular surface with discontinuities was observed. Twenty-eight out of 30 animals were found with predominantly viable chondrocytes leaving the remaining two -which were found only in the control group- with partially viable chondrocytes. However, histology revealed many statistical differences between the groups as far as the International Cartilage Repair Society (ICRS) categories are concerned. Immunofluoresence also revealed the presence of collagen II in all specimens of Group B, whereas in Group A collagen II was found in less specimens. In Group C collagen IIwas not found. CONCLUSION: The matrix, cell distribution, subchondral bone and cartilage mineralization ICRS categories showed statistically differences between the three groups. Group A was second, while group B received the best scores; the control group got the worst ICRS scores in these categories. So, the donor site area, when repairing osteochondral lesions with autografting systems, is better amended with osteochondral autograft rather than bone graft substitute implant.

Pancreatic neuroendocrine tumors: current opinions on a rare, but potentially curable neoplasm.

Pancreatic neuroendocrine tumors (PNETs) share a unique genetic identity, functional behavior, and clinical course. Compared with tumors of the exocrine pancreas, they are rare and show a different biologic behavior and prognosis. On the basis of data from recent studies, all PNETs, outside of small insulinomas, should be considered potentially malignant and treated accordingly. Untreated tumors have a high possibility to grow locally into adjacent structures or spread to distant organs. Although surgical excision irrespective of tumor functioning or nonfunctioning state remains the cornerstone of therapy, providing the best disease-free and survival rates to date, the understanding of the genetic nature of the disease yields new 'targets' to consider in drug development. The aim of this review is to summarize all recent advances of genetic research and new drug development in terms of PNETs, especially their genetic identity and subsequent alterations leading to the development of near or total malignant activity, and the new medical treatment strategies of this potentially curable disease on the basis of therapeutical agents acting, where possible, at the genetic level.

Extra-gastrointestinal stromal tumor of the omentum: a rare case report and review of the literature.

Gastrointestinal stromal tumors (GIST) are uncommon mesenchymal spindle-cell or epithelioid neoplasms, located mainly with higher frequency in the stomach and small bowel. GISTs represent the majority of primary non-epithelial neoplasms of the digestive tract, most frequently expressing the KIT protein a transmembrane tyrosine kinase receptor for stem cell factor. Extra-gastrointestinal stromal tumors tend to present In fewer than 5% of cases; they originate primarily from the mesentery, omentum or peritoneum. Furthermore, these extra-gastrointestinal tumors (EGIST) tend to be more common in patients over the age of 50 years. EGISTs are neoplasms with overlapping immunohistological features, occurring in the abdomen outside the gastrointestinal tract with no connection to the gastric or intestinal wall. We describe here a rare case of EGIST of the lesser omentum and report the clinical, macroscopic, immunohistological and radiological features of an EGIST arising in the lesser omentum of a 63-year old man. Clinical course and the prognostic factors of such lesions will also be discussed. EGISTs in the lesser omentum can grow slowly and remain silent despite a large tumor size. In most cases, a pre-operative diagnosis is not possible, and the patient undergoes a surgical operation for the generic diagnosis of abdominal mass. During the intervention it is important to achieve a complete removal of the mass and to examine every possible adhesion to the gastrointestinal wall.

Pigmented villonodular synovitis of the distal tibiofibular joint: a case report.

Pigmented villonodular synovitis (PVNS) is a proliferative disorder of the synovium. Monoarticular involvement is the more common process. This article presents a case of PVNS with rare location at the distal tibiofibular joint and discusses the current concepts of diagnosis and treatment of this disease.

The effect of local use of nandrolone decanoate on rotator cuff repair in rabbits.

OBJECTIVE: There is still controversy about the effect of anabolic steroid on connective tissue. This study examines the hypothesis that the local use of nandrolone decanoate, an anabolic steroid on rotator cuff, facilitates the healing process when used in combination with surgical repair. METHODS: Forty-eight male rabbits were divided in four groups with anabolic steroids (Nandrolone Decanoate 10 mg/kg) and immobilization as variables. The groups were the following: first group, nonsteroid use-immobilization (NSI); second group, nonsteroid use-nonimmobilization (NSNI); third group, steroid use-immobilization (SI); fourth group steroid use-nonimmobilization (SNI). Every rabbit underwent a rotator cuff incision and reconstruction. Fifteen days later the tendons were sent for biomechanical and histological evaluation. RESULTS: Groups that did not receive anabolic steroids showed better healing and more tendon strength in comparison to groups that received anabolic steroids. Microscopic examination of specimens from the groups without the use of anabolic steroid showed extensive fibroblastic activity whereas the specimens from those groups with anabolic steroid use showed focal fibroblastic reaction and inflammation. Immobilization provided better results in the groups with anabolic steroid use but it did not influence healing in groups without steroids. CONCLUSIONS: The effect of local nandrolone decanoate use on a rotator cuff tear is detrimental, acting as a healing inhibitor.

Microsurgical muscle-splitting approach for extracanalicular lumbar disc herniation: an analysis of 28 consecutive cases.

Extracanalicular lumbar disc herniation (ELDH) is a specific clinical entity with compression of the nerve root in its extraforaminal course. The classical midline interlaminar approach is often difficult because the facet joint obviates a direct view of the nerve, and a partial facetectomy is required. Consequently, the risk of instability or continued postoperative back pain is increased. The authors performed a microsurgical muscle-splitting approach in an attempt to obtain a direct view of the disc rupture without sacrificing the facet joint. Twenty-eight consecutive patients were operated upon with this surgical procedure. A retrospective study showed that 10 patients (35.7%) had an excellent, 13 (46.4%) a good, 4 (14.3%) a fair and one (3.6%) a poor result, according to the Macnab criteria. No serious postoperative complications were noted. This procedure is safe, effective and less invasive.

Extraskeletal myxoid chondrosarcoma of the perineum.

Extraskeletal myxoid chondrosarcoma is an aggressive tumor with significant metastatic potential. A 40-year-old man presented with an asymptomatic mass at the left ischial fossa. Magnetic resonance imaging showed a 9x6-cm mass with variable signal intensity and cystic formations. A computed tomography scan of the chest showed multiple pulmonary nodules. A computed tomography-guided core needle biopsy was consistent with low-grade extraskeletal myxoid chondrosarcoma. Despite the presence of lung metastases, wide resection of the primary tumor was performed. Wide resection included the perineal mass and the adjacent ischiopubic ramus. Postoperative recovery was uneventful. One month postoperatively, thoracotomy was performed, and approximately 20 pulmonary nodules were excised. Histological analysis of the excised specimens was consistent with extraskeletal myxoid chondrosarcoma metastases. Two years postoperatively, the patient is alive without evidence of local recurrence or distant disease. Extraskeletal myxoid chondrosarcoma is an unusual soft tissue sarcoma with ultrastructural and molecular features distinct from that of skeletal myxoid chondrosarcoma. The EWS-CHN gene fusion is highly specific to extraskeletal myxoid chondrosarcoma; the gene fusion is positive in >or=75% of cases. Treatment should include wide excision for local tumor control. Resection of the lung metastases is feasible. Because of the prolonged survival of patients with extraskeletal myxoid chondrosarcoma, long-term follow-up is recommended for early detection of local recurrence or distant metastases.

Ewing's sarcoma of the hip presenting as a benign cystic lesion.

A 14-year-old girl with a Ewing's sarcoma of the left femoral head and neck is presented. The imaging features mimicked a benign cystic lesion. Biopsy and molecular analysis confirmed the diagnosis. The patient was treated with chemotherapy, wide tumor resection, and proximal femoral reconstruction using an allograft-prosthesis composite. Differential diagnosis, imaging, and pathologic features of Ewing's sarcoma are discussed.

Extraskeletal chondroma of the foot.

Benign extraskeletal chondromas are uncommon lesions with a predilection for the hands and the feet and can exhibit worrisome radiographic and histologic features mimicking chondrosarcomas. The authors present herein the case of a 74-year-old man with a painful mass at the dorsomedial aspect of the left foot. At 34 months after surgery the patient is disease-free with no evidence of recurrence.

Current trends in the management of extra-abdominal desmoid tumours.

Extra-abdominal desmoid tumours are slow-growing, histologically benign tumours of fibroblastic origin with variable biologic behaviour. They are locally aggressive and invasive to surrounding anatomic structures. Magnetic resonance imaging is the modality of choice for the diagnosis and the evaluation of the tumours. Current management of desmoids involves a multidisciplinary approach. Wide margin surgical resection remains the main treatment modality for local control of the tumour. Amputation should not be the initial treatment, and function-preserving procedures should be the primary treatment goal. Adjuvant radiation therapy is recommended both for primary and recurrent lesions. Chemotherapy may be used for recurrent or unresectable disease. Overall local recurrence rates vary and depend on patient's age, tumour location and margins at resection.