| BackgroundInflammatory myofibroblastic tumor (IMT) is a borderline tumor with origination from mesenchymal tissue. Pathologically, it can be observed with a variety of morphological proliferative spindle myofibroblasts, accompanied by infiltration of inflammatory cells, such as plasma cells and lymphocytes. According to the histologic morphology, IMTs can be divided into three basic patterns:compact spindle cells pattern, myxoid/vascular pattern, hypocellular fibrous pattern.In the majority of cases in the past, it behaves as a reactive hyperplasia, which was also referred to as inflammatory pseudotumor. But aggressive growth, local recurrence, distant metastases and even malignant biological potential have also been reported in this field recently. Depending on the site of origin, IMTs may present as incidentally discovered space-occupying lesions, or local inflammatory reaction, such as swelling and pain. In the absence of pathognomonic features at imaging, diagnosis is usually obtained only by histopathological examination of a tissue sample combined with a series of immune histochemical detection of antibodies. Currently it is believed that ALK gene rearrangements of genetic variation and IgG4mediated inflammatory response are the possible pathogenesis of this tumor. To date, there is no prospective study or any recommended treatment protocol for IMTs in the literature, and therapeutic efficacy is difficult to determine from nonrandomized retrospective study. Whether IMTs are prolific reactive processes or true neoplasms is under debate. Unknown pathophysiological mechanisms ang limity of reliable clinical diagnosis and prognosis evaluation can not develop effective treatment programs, resulting in patients with inadequate treatment or overtreatment.By summarization of the clinical data and immunohistochemistry detection of ALK, IgG4and Ki-67antibody, this study was intended to explore the correlation between various clinicopathological factors and biogical behaviors such as invasion, recurrence malignant transformation in head and neck IMTs. Finally, it was hoping to determine the prognosis of head and neck IMT, and provide an objective reference for clinical practice to develop an appropriate treatment plan.ObjectiveThis study was to summarise the clinical features and outcomes of head and neck the IMTs, combined with immunohistochemistry test of tumorous or inflammatory antibody, building the database, to analyze the relationgship between clinicopathologic features of IMT and immunohistochemistry expression of ALK, IgG4, Ki-67. The purposes of this study are to further investigate the biogical behavior features and establishing the clinical diagnosis, treatment protocol and evaluating prognosis of IMTs. Materials and Methods1. Summarizing the clinical features and follow-up data in head and neck IMTs: We conducted a retrospective review of31head and neck IMTs patients treated at Nanfang Hospital of southern Medical University from2005to2012. The clinical, diagnostic, pathologic, imaging, treatment and follow-up data of all cases were investigated from the electronic medical record system, to analyze the clinical features of head and neck IMTs.2. Histopathological study of head and neck IMTs:Using the31head and neck IMTs H.E. stained slice in the part one of the experiment, which were collected from the Department of Pathology, we classified the IMTs histological features of IMT according to the depth of tumor invasion in the head and neck tissue as well as the microscopic type of histologic morphology, under the optics microscope, and analyze the relationship between different types of IMT with the clinicopathological features.3. Immunohistochemical expression studies of ALK, IgG4and Ki-67in head and neck IMT:With the collected specimens of31patients with head and neck the IMT tumor tissue wax block from the Department of Pathology and made slices in the first part of the experiment, we conducted ALK, IgG4and Ki-67immunohistochemistry in Envision two-step method, to analyze the relationship between the expression of ALK, IgG4and Ki-67IMT clinicopathological parameters.Result1.31patients with head and neck IMT patients, the male to female ratio of about1.1:1, age range of2years to73years, mean age37.4years,20to39years old accounted for38.71%, different gender comparison of age of onset, male age distribution was significantly larger than females (P<0.05);22.58%(7/31) of patients had surgery or trauma history of the lesion area; craniofacial bone (22.58%) the orofacial (19.35%) and neck deep (12.9%) were the most common sites of IMT; clinical manifestations local mass (19/31), and (or) pain (13/31) is the most common; Imaging can be expressed as inflammation, benign or malignant with local invasion levy; treatment with surgery (28/31), in some cases supplemented by postoperative radiotherapy (n=2) and glucocorticoid treatment (n=1), chemotherapy is used only for cases of distant metastasis (1/31); the average follow-up time of38.3months,1patient was lost,10cases of recurrence (recurrence rate of33.3%, the average time to recurrence was10.5months after treatment, the fastest after15days, after a maximum of42months),4deaths (mortality rate of13.3%are malignant or metastatic disease), one case of self-limiting, in addition to the original four cases of malignant transformation and distant metastasis, no new malignant transformation or metastasis; in malignant group, the age distribution of the death group was significantly greater than in non-malignant group, non-death group (P<0.05), malignant transformation and tumor-related death was significantly correlated (P<0.05), but found no significant correlation with malignant tumor recurrence (P>0.05).2.31patients with head and neck IMT,19cases of violations of the adjacent hard and soft tissues, six cases of visible mitotic figures,6patients with varying degrees of atypia (mild cases, moderate in3cases,2cases of severe); be classified according to the depth of invasion of the tumor in the head and neck tissue,5cases were superficial IMT cases, coming with14intermediate IMTs and12deep IMTs; classified according to the type of histologic morphology of the microscopic tumor,15cases was compact spindle cells pattern, myxoid/vascular pattern and hypocellular fibrous pattern got7cases respectively,2remaining cases were mixed pattern; tumor adjacent tissue invasive and age were significantly associated (P<0.05), tumor recurrence, malignant transformation and death was no significant correlation (P>0.05); mitotic figures, atypia appear IMT malignant and death were significantly associated (P<0.05); tumor tissue invasion found no recurrence and malignant transformation was significantly associated (P<0.05), but deep IMT proportion of deaths far higher than the the shallow central IMT (4:0); distribution of different types of organizational structure between the patient’s age, sex ratio, recurrence, malignant transformation and the proportion of deaths compared with no significant difference (P>0.05), adjacent tissue invasive compact spindle cells pattern was significantly higher than the other two types (P<0.05), while the comparison between the myxoid/vascular pattern and hypocellular fibrous pattern found no significant difference.3. Among31patients with head and neck IMT tumor tissues, the positive expression rate of ALK was32.3%(10/31), average immunohistochemical score (IHS) was3.0, which belongs to a weak immune expression level;45.2%(14/31) IMTs visibly expressed IgG4-positive plasma cells, and the average number of positive plasma cells was29.93. Ki-67was expressed in all IMT tumor tissue, with the average9.68%Ki-67proliferation index. ALK-positive expression appeared to have significantly relation (P<0.05) with IMT adjacent tissue invasion, mitotic activity, atypia and malignant transformation; high expression of IgG4had significantly related (P<0.05) with tumor recurrence; increasing of Ki-67proliferation index showed significantly related (P<0.05) with tumor adjacent tissue invasion, mitotic activity, malignant recurrence and death. Positive expression of ALK and increasing Ki-67proliferation index were positively correlated (P<0.05), but there were no significant correlations (P>0.05) between the expression of IgG4and either ALK or Ki-67. Conclusion1. Head and neck IMT high incidence in young adults aged20to39, no significant gender differences, but the age distribution of male patients was significantly larger than females.22.58%of patients had a lesion area of trauma surgery. Craniofacial bone predilection sites, followed by facial and deep neck. Local tumor growth and (or) pain for IMT were the main symptoms, and systemic symptoms are generally mild. Imaging could perform as inflammation-like, benign or even malignant invasive lesions. Tumors were vulnerable to relapse with the recurrence rate of approximately33.3%. IMTs appeared to be benign and the prognosis is well; but the malignant or distant metastasis IMTs were rare, and mostly occurs in middle-aged patients with a poor prognosis.2. Head and neck IMT has rich and varied histological features, which were mostly composted of spindle-shaped myofibroblasts and inflammatory cell infiltration. Tumors usually invaded into the adjacent soft or hard tissues, especially in elderly cases. But the gender difference was not significant and did not find a significant effect on the prognosis. IMT of the head and neck are mostly benign lesions, with an average Ki-67proliferation index was9.68%. Histological observation of significant atypia or increased mitotic cells should be highly suspected tumor may be malignant. According to the different components of the tumor cells and matrix form, IMTs were divided into three different type of histologic morphology, which compact spindle cells pattern is the most common type, and the adjacent tissue invasive stronger than the myxoid/vascular pattern and hypocellular fibrous pattern, but this classification had little of prognosis significance. ALK positive expression rate of positive strength in the head and neck IMT is not high, and its expression often prompted strong locally aggressive atypia and malignant head and neck IMT, but did not find a significant effect on tumor prognosis; increased number of IgG4-positive plasma cells prompted IMTs with strong recurrence; increased Ki-67proliferation index indicated IMTs with overall poor prognosis.3. Surgy was the main treatment of head and neck IMTs. Benign IMTs should be ensured that the cutting edge were within the range of normal tissues. And malignant IMT should be treated by extended radical resection. Complete resection failed due to anatomical restrictions of ALK positive or malignant IMTs, postoperative radiotherapy should be performed; IgG4-positive plasma cells elevated IMT, regardless of whether the tumor complete resection, postoperative should be secondary to glucocorticoid treatment. Patients should be is strictly close follow-up, especially for the middle-aged, deep lesions, atypia, increased mitotic activity, relapse, malignant transformation, the increased number of IgG4-positive plasma cells and Ki-67expression in high IMT. |
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