Acta Oto-Laryngologica, 2005; 125: 433 /437

CASE REPORT

Inflammatory myofibroblastic tumor of the parotid gland: Case report and review of the literature

STIJN VAN WEERT1, JOHANNES J. MANNI1 & ANN DRIESSEN2

Departments of 1Otorhinolaryngology, Head and Neck Surgery and 2Pathology, University Hospital Maastricht, Maastricht, The Netherlands
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Abstract An inflammatory myofibroblastic tumor, previously known as an inflammatory pseudotumor, is an uncommon neoplasm. This tumor, which has characteristic morphological and immunohistochemical features, is mostly seen in the lung. Herein we present a rare case of an inflammatory myofibroblastic pseudotumor of the parotid gland as well as a review of the literature. The patient was a 66-year-old man with recurrent painful swelling of the parotid gland. A total parotidectomy with preservation of the facial nerve branches was performed. The patient showed no signs of recurrence /3 years after surgery. The presence of clonal cytogenic abnormalities supported the neoplastic origin of this process. The treatment consisted of complete resection. Clinicians should however be aware that an inflammatory myofibroblastic tumor may mimic a reactive process.

Keywords: Inammatory myobroblastic tumor, inammatory pseudotumor, parotid gland, treatment

Introduction A diffuse swelling of the parotid gland is usually caused by a parenchymal disorder such as sialadenosis or myoepithelial sialadenitis. When a patient presents with diffuse swelling, hyperemia of the skin and pain on palpation, the favored clinical diagnosis is an inflammatory condition such as epidemic parotitis or acute sialadenitis. A localized swelling of a parotid gland is more characteristic of a neoplasm. The commonest tumor of the parotid gland is a benign tumor, namely pleiomorphic adenoma [1]. In contrast, an inflammatory myofibroblastic tumor of the parotid gland is an extremely rare tumor, as described in case reports in the literature. An inflammatory myofibroblastic tumor is composed of a proliferation of myofibroblasts in a background of chronic inflammatory cells, such as plasma cells, lymphocytes and eosinophils. The heterogeneous composition of the tumor is reflected in the variety of names applied to this pathology, such as inflammatory pseudotumor, plasma cell granuloma, pseudosarcomatous myofibroblastic proliferation, xanthomatous pseudotumor and atypical

fibromyxoid nodule [2,3]. Although this neoplasm may be found throughout the whole body, it is generally located in the lung. Other frequently involved organs are the mesentery, liver, spleen and intestine [4]. The patients, who are mostly children and young adults, may present with constitutional symptoms such as fever and malaise and laboratory findings indicating an inflammatory response [4]. Because of these features inflammatory myofibroblastic tumor was originally thought to be a reactive process, secondary to infectious agents such as Epstein /Barr virus, Actinomyces and human herpesvirus 8 [5 /7]. However, the discovery of clonal cytogenetic abnormalities in a series of inflammatory myofibroblastic tumors supports the neoplastic origin of this process. Approximately 50% of inflammatory myofibroblastic tumors show clonal gene rearrangements of the short arm of chromosome 2, some of which result in an anaplastic lymphoma kinase (ALK) gene rearrangement [2,8]. The ALK gene encodes for ALK, a tyrosine kinase receptor, which was originally described in anaplastic lymphoma [9]. The ALK gene rearrangement results in expression of ALK-1 in 35 /60% of inflammatory

Correspondence: Stijn van Weert, MD, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Maastricht, P. Debyelaan 25, NL-6202 AZ Maastricht, The Netherlands. E-mail: Svwe@skno.azm.nl

(Received 18 May 2004; accepted 19 August 2004)

ISSN 0001-6489 print/ISSN 1651-2551 online # 2005 Taylor & Francis DOI: 10.1080/00016480410025225

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S. van Weert et al. left lateral mandibular region. The swelling was a 4-cm solid mass that was painful on palpation. Inspection of the orifice of the parotid duct and external massage of the parotid gland revealed no purulent discharge. There was no local hyperemia of the skin. Facial nerve function was normal. Fineneedle aspiration cytology revealed an inflammation. There was no evidence of malignancy. Based on these features a diagnosis of left-sided chronic parotitis was made. The patient was treated with antibiotics and anti-inflammatory drugs. Despite this treatment no change in the size or consistency of the swelling was observed. In consultation with the patient, surgical treatment was proposed. The patient underwent a total parotidectomy due to possible macroscopic involvement of the deep lobe peroperatively. The procedure was devoid of complications. Facial nerve function was still intact after surgery. The patient is currently doing well and there is no evidence of recurrent disease after 3 years of follow-up. Histopathology The surgical specimen was fixed in 10% formaldehyde and embedded in paraffin for hematoxylin/ eosin (H&E) staining and immunohistochemical analysis. Immunohistochemistry was performed on semi-serial sections (4 mm) using an indirect

myofibroblastic tumors [8,10]. ALK-1 expression is observed in inflammatory myofibroblastic tumors occurring in young males and is associated with a higher prevalence of recurrence of the disease [8]. In this article we present a case of inflammatory myofibroblastic tumor of the parotid gland. In the literature only a few reports of inflammatory myofibroblastic tumors, situated in the major salivary glands, have been published [11 /18]. To date only 12 cases, including our patient, with a tumor situated in the parotid gland have been described (Table I) [11 /14]. The clinical presentation of our patient was first misdiagnosed as an inflammatory process. Clinicians should however be aware of this rare neoplastic tumor, as it may mimic a reactive process.
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Case report In 1999 a 66-year-old male presented with a 2-year history of a recurrent painful swelling in the left lateral mandibular region unrelated to food intake. There was no history of pyrexia, night sweating or malaise. The patients medical history revealed a coronary bypass operation and hypertension. Medical therapy consisted of aspirin, anti-hypertriglycemic and anti-hypertensive drugs. A routine ENT examination revealed a parotid gland swelling in the

Table I. Reported cases of inammatory myobroblastic tumors in the major salivary glands. Age (years) 68 35 74 N.R. 46 87 83 61 69 76 63 66 53 58 70

Reference 11,12

Localization Parotid glanda Parotid gland Parotid glanda

Sex M F M M M F F M F M M F F M M

Treatment Surgery ()/3) with radiation therapy after recurrence Surgery (parotidectomy) Surgery (parotidectomy and partial mandibulectomy) Surgery Surgery Surgery Surgery Surgery Surgery Surgery Antibiotics (on suspicion of sialadenitis); surgery Surgery Surgery and corticosteroids; one recurrence Surgery Surgery and CHOP (on suspicion of mucosa-associated lymphoid tissue lymphoma) Antibiotics (on suspicion of sialadenitis); surgery (total parotidectomy)

Follow-up 21 months N.E.D. 14 months N.E.D. 36 months N.E.D. N.R. Lost to follow-up 8 years N.E.D. 1 year N.E.D., then lost to follow-up 7 months N.E.D. 4 months N.E.D. 3 months N.E.D. 2.5 years N.E.D. N.R. Follow-up N.R. Lost to follow-up 3 years N.E.D.

12 13

Parotid Parotid Parotid Parotid

gland gland gland gland

15 14 16 17 18

Parotid gland Parotid gland Parotid gland Submandibular gland Near lower pole parotid gland Submandibular gland Submandibular gland Submandibular gland

Present work
a

Parotid gland

66

3 years N.E.D.

In combination with other inflammatory myofibroblastic tumor sites. N.R. 0/not reported; N.E.D. 0/no evidence of disease; CHOP0/cyclophosphamide, doxorubicin, vincristine, prednisone.

Inflammatory myofibroblastic tumor of the parotid gland immunoperoxidase technique. Primary antibodies were directed against CD68 (monoclonal, dilution 1/100; Dako, Glostrup, Denmark), desmin (monoclonal, dilution 1/100; ICN, Biomedicals BV, Zoetermeer, The Netherlands) and a-smooth muscle actin (mono-clonal, dilution 1/8000; Sigma-Aldrich, Bornem, Belgium). The slide was pretreated with pepsin for immunohistochemical staining with CD68. Gross examination of the surgical specimen, which measured 9)/5 )/2 cm3, showed an unilocular cyst (diameter 1 cm) containing yellow /green fluid. Microscopic examination revealed that this cyst corresponded to an extensive dilated duct. In the neighborhood of this dilated duct a less well-circumscribed tumor (diameter 1.5 cm) was found. This tumor was not encapsulated, and only partially surrounded by fibrous connective tissue (Figure 1). The tumor, which was characterized by high cellularity, was composed of bundles of spindle cells arranged in a storiform pattern (Figure 2a). These spindle cells had elongated nuclei, surrounded by a moderate amount of cytoplasm. Some mild atypia was occasionally seen. Mitotic figures were only rarely seen. Plasma cells, lymphocytes and foamy macrophages were intermingled with these spindle cells (Figure 2b). The parotid gland tissue in the neighborhood of the tumor showed no abnormalities. Immunohistochemical analysis, performed on the tumor, revealed expression of a-smooth muscle actin at the level of the spindle cells. The foamy macrophages

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Figure 1. The inammatory myobroblastic tumor (arrows ) was situated in the neighborhood of a salivary duct, causing obstruction and secondary dilatation of this duct. H&E staining; original magnication)/25.

and some spindle cells expressed CD68 (Figure 2c). These cells did not express desmin. Microorganisms were not detected in the specimen. Based on the morphological and immunohistochemical features, the mass, situated in the parotid gland, was diagnosed as an inflammatory myofibroblastic tumor. Discussion Inflammatory myofibroblastic tumors are an unusual group of neoplasms, which were originally desig-

Figure 2. (a) The inammatory myobroblastic tumor was composed of spindle cells, arranged in a storiform pattern. These tumor cells expressed (b) a-smooth muscle actin and (c) CD68. H&E staining; original magnications )/400.

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S. van Weert et al. signs of inflammation, clinically mimicking a malignant tumor [33]. Keen et al. [25] reported a patient with an inflammatory myofibroblastic tumor of the pterygomaxillary space with anesthesia of the lower lip due to involvement of the mandibular nerve. All patients underwent surgery and follow-up was reported in 6/12 patients, resulting in cure in all 6. Whereas an inflammatory myofibroblastic tumor was originally thought to be a reactive process, the etiopathogenesis of which involved infections, trauma or auto-immune processes, the discovery of specific cytogenetic abnormalities supports the common knowledge that this tumor is a neoplastic process. This tumor has three different growth patterns: these may either be equally distributed or one or two may predominate. Our case is an example of a storiform pattern, in which the tumor cells have a spindle-cell appearance. In a myxoid vascular pattern the myofibroblastic cells are arranged in an edematous, myxoid background, infiltrated by different types of inflammatory cells. The third type is characterized by a low cellularity, in which inflammatory and myofibroblastic cells are dispersed in an abundant plate-like collagen matrix, resembling a scar [4]. In the differential diagnosis of inflammatory myofibroblastic tumor different neoplasms should be considered, such as sarcomas (e.g. rhabdomyosarcoma, leiomyosarcoma), lymphomas or anaplastic carcinoma [34]. Inflammatory myofibroblastic tumor normally has a low mitotic rate. Sometimes this tumor may show a prominent cytologic pleiomorphy, which however is not a good predictor of the risk of malignant transformation. Other features, such as the presence of ganglion-like cells, p53 expression and aneuploidy, may identify those patients at higher risk. Although this tumor normally has a benign behavior, local recurrence occurred in 15% of a series of extrapulmonary inflammatory myofibroblastic tumors [4]. Cases have been reported in the literature in which the tumor underwent a malignant transformation into a sarcoma or progressed to metastatic disease [35,36]. Nevertheless, the clinical behavior of this tumor is difficult to predict and hence complete excision of the tumor is the preferred treatment. The benefit of chemotherapy and radiotherapy remains to be proven. Corticosteroid treatment, although effective for orbital lesions [37], revealed contradictory results when applied for head and neck lesions [26,27]. Weisman and Osguthorpe [38] suggested that the response to corticosteroids was reduced when the lesions were more fibrotic. Inflammatory myofibroblastic tumors of the parotid gland are treated with (partial) parotidectomy with preservation of the facial nerve branches.

nated as reactive lesions. This neoplasm was described for the first time in the lymph nodes by Symmers in 1921 [19]. Besides the lung, which is the commonest location, the tumor has since been diagnosed in various extrapulmonary localizations, such as the gastrointestinal tract, spleen, liver and urinary bladder [20 /24]. This neoplastic process has also been described in different locations in the head and neck, namely the pterygomaxillary space [25], larynx [26 /28], paranasal sinuses [29], nasal cavity [30] and oral cavity [31]. A review of the literature shows that this tumor may also occur, albeit rarely, in major salivary glands such as the submandibular gland [15 /18] and parotid gland [11 /14]. In a study by Seifert et al. [32], 10 944 tumors of the salivary glands, the majority of which (90%) were situated in the parotid gland, were re-evaluated. Only one tumor, for which the salivary gland involved was not specified, showed histopathologic resemblance to an inflammatory myofibroblastic tumor. This neoplasm, diagnosed as a xanthogranuloma, was composed of foam cells, histiocytes and fibrocytes. In the study of van der Wal et al. [1], morphological examination of nearly 500 parotid gland tumors revealed no inflammatory myofibroblastic tumors. To date only four reports of inflammatory myofibroblastic tumors of the parotid gland have been published [11 /14]. The first inflammatory myofibroblastic tumors of the parotid gland were reported by Wold and Weiland [11], who described the pathological features of the lesions in three patients. The clinical data of these patients, together with that for one additional patient, were reported by Olsen et al. [12]. Two of their patients had a multifocal tumor; in addition to the parotid gland other organs were also involved, namely the neck, orbit and liver in one patient and the mandible and neck in the other. Williams et al. [13] published the largest series of inflammatory myofibroblastic tumors of the parotid gland, comprising six patients. Based on the literature, inflammatory myofibroblastic tumors of the parotid gland show no gender predilection and occur at a mean age of 66 years (range 35 /76 years). The age distribution in this population with tumors of the parotid gland is higher than that at other locations, as inflammatory myofibroblastic tumors at locations outside the parotid gland are predominantly found in children and young adults. Patients usually have an asymptomatic swelling of the parotid gland region [11 /14]. Our patient had a painful swelling of the parotid gland, which had persisted for 2 years. However, the pain may have been related to compression of the salivary duct, which was near the tumor. A rare presentation of an inflammatory myofibroblastic tumor is facial nerve paralysis and

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