ALK-negative lung inflammatory myofibroblastic tumor in a young adult: A case report and literature review of molecular alterations.

RATIONALE: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that is prevalent among children and adolescents. Surgery is the most important therapeutic approach for IMT and complete resection is recommended. Although 50% of IMTs show anaplastic lymphoma kinase (ALK) rearrangements, crizotinib has proven an effective therapeutic approach. However, the genetic landscape of this tumor is still not fully understood and treatment options are limited, especially in the majority of ALK-negative tumors. PATIENT CONCERNS: We describe the clinical case of a healthy 18-year-old female in whom a pulmonary nodule was incidentally detected. DIAGNOSES: Following a small increase in the size of the nodule, the patient underwent both 18FDG-PET/CT and 68Ga-PET/CT, resulting in a suspicion of bronchial hamartoma. INTERVENTIONS: The patient underwent surgery and a salivary gland-like lung tumor was diagnosed. OUTCOMES: After surgery, the patient was referred to our cancer center, where a review of the histology slides gave a final diagnosis of ALK-negative lung IMT. Given the histology, it was decided not to administer adjuvant therapy and the patient was placed in a 3-monthly follow-up program. The patient is still disease-free 2 years post-surgery. LESSONS: Although there is no standard of care for the treatment of IMT, identifying genomic alterations could help to redefine the management of patients with negative-ALK disease. Our review of the literature on IMT and other kinase fusions revealed, in addition to ALK rearrangements, the potential association of ROS1, NTRK, RET, or PDGFR beta alterations with the tumor.

Inflammatory myofibroblastic tumour causing intestinal obstruction in a patient with neurofibromatosis type 1.

Inflammatory myofibroblastic tumours (IMTs) are rare tumours with unpredictable biological behaviour ranging from benign to locally invasive and rarely, distant metastasis. While neurofibromatosis type 1 (NF1) may manifest with gastrointestinal soft tissue tumours, this is the first report in the literature that describes an IMT occurring in a NF1 patient who presented with intestinal obstruction. Our patient presented with intestinal obstruction secondary to an obstructing terminal ileum mesenteric tumour. En bloc bowel resection was performed, with histology revealing an IMT and an adjacent neurofibroma. The resection margins were clear and the patient was free of recurrence at six months.

Inflammatory myofibroblastic tumor of the bladder.

We illustrate a case of an inflammatory myofibroblastic tumor (IMT) involving the bladder in a woman with dysuria and review the literature and differential diagnosis. Inflammatory myofibroblastic tumor, also referred to as pseudosarcomatous myofibroblastic proliferation, is a rare lesion that can arise in the genitourinary system and is characterized by a fascicular arrangement of myofibroblasts with admixed inflammatory cells and slitlike vessels. Urinary bladder IMT can be a diagnostic pitfall because its histologic features (brisk mitoses, invasion into muscularis propria, and prominent nucleoli) can mimic malignancy. The differential diagnosis of urinary bladder IMT includes sarcomatoid carcinoma and leiomyosarcoma. Diagnostic features such as bland nuclear chromatin, ganglion-like cells, pale eosinophilic cytoplasm with long processes, overexpression of anaplastic lymphoma kinase (immunohistochemistry or gene rearrangement studies), and the absence of atypical mitoses help distinguish IMT from its malignant mimics. Current controversies regarding postoperative spindle cell nodule and IMT are discussed.

Massive pericardial effusion caused by "inflammatory myofibroblastic tumour" in a 3-month-old child.

Tumours originating from cardiac tissues are rarely encountered during childhood, and fortunately most of these tumours are benign in nature. Inflammatory myofibroblastic tumour, which has unique clinical, pathological, and molecular characteristics, is a relatively new entity compared with previously mentioned tumoural processes originating from the heart. Most of the cardiac intima-media thickness patients are in the age group of 4 months to 17 years. This rarely seen tumoural process has not been subject of any specific research and the prognosis is not well known. Here we present the case of a 3-month-old child who was admitted to our outpatient clinic with massive pericardial effusion and who has shown excellent progress after surgical resection of over 1 year.

Inflammatory myofibroblastic tumor of the maxillary sinus related with pulp necrosis of maxillary teeth: case report.

Inflammatory myofibroblastic tumor (IMT) is a benign lesion composed of myofibroblasts accompanied by varying numbers of inflammatory cells. Various pathogenetic factors have been proposed, but the etiology of most IMTs remains unknown. This article presents a case of IMT occurring in the left maxillary sinus. A 24-year-old man complained of throbbing pain in the maxillary left molars and swelling of the left cheek. His maxillary left second molar was diagnosed as pulp necrosis and root canal treatment performed. After that, his symptoms continued and he was referred to the Department of Otolaryngology. Computerized tomography disclosed compact soft tissue masses in the left maxillary sinus with obstruction of maxillary ostium. Under general anesthesia, the lesions were fully excised. Histopathologically, the lesions were composed of plump or spindled myofibroblasts. Cells were immunoreactive for smooth muscle actin and ß-catenin, and were negative for ALK1, CD34, and EMA. The diagnosis was IMT of left maxillary sinus. Although it is very rare, IMT should be included as a differential diagnosis in patients with compact masses in maxillary sinus.

Perianal mammary-type myofibroblastoma.

We report a unique case of an extramammary mammary-type myofibroblastoma of the perianal region. The patient was a 40-year old female with no significant past history, who presented with a right side painless perianal mass. Gross examination of the excised mass showed a well-circumscribed, apparently encapsulated, nodular mass weighing 30 g and measuring 5 cm. in the greatest dimension. The cut surface showed solid, yellow homogenous tissue. Microscopically, the neoplasm was composed of bland spindled cells generally arranged into short fascicles with abundant myxoid stroma. The cells stained strongly for desmin and CD34. To our knowledge, a review of the literature discloses only ten cases of extramammary, mammary-type myofibroblastoma.

Inflammatory myofibroblastic tumor presenting as an abdominal wall mass in an adult patient.

Inflammatory myofibroblastic tumor of the abdominal wall is a rare soft-tissue tumor presentation in adults. A 50-year-old woman was referred with abdominal pain and a palpable mass in the left lower quadrant. Computed tomography scan and magnetic resonance investigation revealed an 8-cm heterogeneous abdominal wall mass. Tumor markers were within normal limits. Fine-needle aspiration cytology and tru-cut biopsies yielded necrotic material. A preoperative diagnosis of a resectable rhabdomyosarcoma was suggested. On exploration a tumor measuring 8 x 8 x 6 cm was resected along with the involved structures. Histopathologic examination of specimen revealed an inflammatory myofibroblastic tumor of the abdominal wall. The patient has been followed up for the last 12 months without clinical or radiographic evidence of recurrence. Inflammatory myofibroblastic tumor arising from the anterior abdominal wall in adults is an unusual manifestation of soft-tissue tumors, which can be managed by a multidisciplinary team of surgeons, oncologists, radiologists and pathologists.

[Role of myofibroblast in inflammatory bowel disease and tumor genesis]. / A myofibroblastok szerepe a vastagbél gyulladásos és daganatos folyamataiban.

Stroma cells with the microenvironment around them have primary role in the regulation of inflammation processes, conformation of tumors and development of metastasis. Myofibroblasts have essential role in inflammation processes and in the regeneration of encompassed tissue. Molecules produced by them operate the cells of the immune system and effect the proliferation of epithelium. Tumors can activate myofibroblasts which can lead to uncontrolled epithelium proliferation across production of changed and increased regulation ligands (such as cytokines, chemokines, chemotactic and other growth factors) and activation of stem cell. This process could lead piling of uncontrolled epithelial cells and can impact later on conformation of tumors. In this study we present an overview about of myofibroblasts and their roles in inflammation and neoplastic processes.

Time lag between the increase of IL-6 with fever and NF-kappaB activation in the peripheral blood in inflammatory myofibroblastic tumor.

We describe a case of inflammatory myofibroblastic tumor (IMT) that occurred in the retroperitoneum. The patient manifested systemic symptoms, such as intermittent fever, anemia, thrombocytosis, and hypergammaglobulinemia. In order to elucidate the mechanism of intermittent fever in IMT, we analyzed nuclear factor-kappa B (NF-kappaB) activation in peripheral blood mononuclear cells (PBMCs) using flow cytometry, and serum cytokine levels. NF-kappaB activation was observed in the peripheral blood T cells and monocytes/macrophages. Among the measured cytokines, only interleukin (IL)-6 levels were elevated. IL-6 levels during pyrexia in the afternoon were higher than those during apyrexia in the morning. In contrast to IL-6, NF-kappaB activation in PBMCs was lower during pyrexia than during apyrexia; this is considered to be because the activation is subject to negative feedback. The time lag between the increase of IL-6 in the serum and NF-kappaB activation in the PBMCs at the onset of intermittent fever in IMT may provide further insight into the role of cytokines and NF-kappaB activation in febrile inflammatory diseases.

Inflammatory myofibroblastic tumor of mesentery: a case report.

INTRODUCTION: Inflammatory myofibroblastic tumor occurring at intra-abdominal sites in children has rarely been described. In the abdomen, mesentery is a rare location for an inflammatory myofibroblastic tumor. CASE REPORT: A case report of inflammatory myofibroblastic tumor of mesentery presenting as painless abdominal swelling is presented. Histopathological study of specimen documented the diagnosis. Complete resection of tumor was done with no recurrence seen in follow-up.

Proliferation, ploidy and prognosis in uterine smooth muscle tumours.

DNA ploidy, mitotic rate (per 10 high power fields), mitotic index (per 1000 tumour nuclei), Ki-67 labelling index and S phase fraction were measured in 23 uterine leiomyosarcomas and 10 tumours of uncertain malignant potential. Correlations were calculated by Spearmann rank correlation. Univariate survival analysis was performed by log rank analysis and multivariate analysis performed by the Cox linear regression method. Ki-67 index and S phase fraction were significantly higher in leiomyosarcomas than in tumours of uncertain malignant potential. There was significant correlation between mitotic rate, mitotic index, Ki-67 index and S phase fraction in cases of leiomyosarcoma. Fifteen of 22 leiomyosarcomas and one of 10 tumours of uncertain malignant potential were DNA aneuploid. On univariate analysis of all the smooth muscle tumours, DNA ploidy, presence of significant nuclear atypia and presence of coagulative tumour cell necrosis were associated with outcome. Only DNA ploidy was associated with outcome in the group of leiomyosarcomas. On multivariate analysis of all of the smooth muscle tumours, DNA ploidy, age and grade of atypia were independently associated with outcome. No single factor was independently predictive of outcome in the group of leiomyosarcomas. Alternative indices of cell proliferation correlate with mitotic rate in uterine leiomyosarcoma and do not provide additional useful prognostic information. DNA ploidy, age and grade of atypia are independently associated with outcome in uterine smooth muscle tumours and measurement of DNA ploidy may be useful in identification of cases with an adverse prognosis.

Gastrointestinal stromal tumours: correlation of immunophenotype with clinicopathological features.

Stromal tumours of the gastrointestinal tract remain a persistent source of controversy with regard to both their proposed lines of differentiation and the difficulty in predicting their biological behaviour. We have examined 60 cases with a panel of seven antibodies directed at the identification of smooth muscular or neural differentiation. In our hands, 36 per cent of cases showed neural differentiation (although only 6.6 per cent expressed S-100 protein); 31 per cent appeared smooth muscular; 20 per cent manifested bidirectional differentiation; and 13 per cent were negative for all the markers used. Histological appearances do not reliably reflect immunophenotype. We have attempted to correlate immunophenotype with the site of the lesions and with their clinical behaviour. Mean follow-up of 5 years was obtained in 42 cases. Tumours with a neural phenotype have the best prognosis. Gastric tumours expressing both desmin and smooth muscle actin (in the absence of other markers) with up to 4 mitoses per 30 HPF behave in a benign fashion. Larger studies are required to substantiate the value of immunophenotyping this complex group of tumours.

Granular cell tumor of the stomach coincident with two early gastric carcinomas.

In a 64-yr-old Japanese man, granular cell tumor of the stomach plus two early gastric carcinomas were detected. The granular cell tumor was a 1.5 x 1.5-cm submucosal nodule located in the posterior wall of the fundus. The mucosa adjacent to the granular cell tumor showed two well-differentiated adenocarcinomas restricted to the mucosa, but there was no continuity among these three conditions. This seems to be the first report of this type of association. Immunohistochemical study revealed S-100 protein in the component cells of the granular cell tumor, thereby supporting the proposal that this granular cell is derived from Schwann cells.

Expression of the common acute lymphoblastic leukemia antigen (CD10) in mesenchymal tumors.

The expression of the CD10 antigen, formerly designated as common acute lymphoblastic leukemia antigen and recently identified as neutral endopeptidase, was examined immunohistochemically in 26 benign and in 55 malignant mesenchymal tumors. CD10 expression was found in 4 of 4 leiomyomas, 7 of 10 leiomyosarcomas, 1 of 6 rhabdomyosarcomas, 2 of 2 Triton tumors, 1 of 2 aggressive fibromatoses, 1 of 3 fibrosarcomas, 1 of 4 synovial sarcomas, 1 of 1 giant cell tumors of tendon sheath, 4 of 4 malignant fibrous histiocytomas, 3 of 3 Ewing's sarcomas, and 2 of 3 osteosarcomas. Furthermore, CD10 was expressed consistently in the myoepithelial compartment of 12 fibroadenomas and, in 7 of these cases, in a minor stromal cell population, probably of (myo-) fibroblastic origin. Tumors of adipose tissue (4 lipomas, 5 liposarcomas), tumors of autonomic ganglia (2 ganglioneuromas, 1 ganglioneuroblastoma, 2 neuroblastomas), tumors of peripheral nerves with purely schwannian differentiation (7 malignant schwannomas), and tumors of disputed origin were consistently CD10-negative, however, as were single cases of fibroma and chondrosarcoma. These findings indicate that the expression of CD10 is a frequent but not obligatory feature in some mesenchymal tumors. Therefore CD10 is of value in the differential diagnosis of mesenchymal tumors.

Alveolar soft part sarcoma: immunological evidence of rhabdomyoblastic differentiation.

Two cases of alveolar soft part sarcoma have been studied immunocytochemically using antisera against epithelial membrane antigen, lysozyme, keratins, S-100 protein, desmin, vimentin, fetal myosin, slow myosin, alpha-skeletal muscle actin, alpha-smooth muscle actin and myoglobin. The neoplastic cells were negative with all antisera employed with the exception of the alpha-skeletal muscle actin antiserum which stained the cytoplasm of numerous neoplastic elements, including the crystalloid rods, typical cytoplasmic inclusions of these tumours. It is suggested that the presence of this protein indicates rhabdomyoblastic differentiation of these tumours.

Granular cell tumours revisited. An immunohistological and ultrastructural study.

Twenty-five granular cell tumours were stained with a panel of antibodies to histiocytic, muscle, neural, neural crest, epithelial and endothelial markers. Electron microscopy was also performed in six cases. Twenty-four of the cases were similar morphologically and immunocytochemically. One case with features of an endothelial origin is described. The present study strongly supports the viewpoint that granular cell tumours are a distinct entity rather than being the common appearance of a group of lesions of differing histogenesis. Origin from a neural crest-derived peripheral nerve-related cell is favoured.