|Year : 2007 | Volume
| Issue : 2 | Page : 76-79
Inflammatory myofibroblastic tumour of maxilla
SA Deshingkar, JV Tupkari, SR Barpande
Department of Oral Pathology and Microbiology, Government Dental College and Hospital, Aurangabad - 431 001, Maharashtra, India
S R Barpande
Department of Oral Pathology and Microbiology, Government Dental College and Hospital, Aurangabad - 431 001, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Inflammatory myofibroblastic tumour (IMT) is a biologically controversial entity that was originally described as non-neoplastic lesion in the lungs and designated initially as inflammatory pseudotumour. The lesion has recently been recognized to occur at various sites but rarely affects head and neck region. Controversies still exist regarding its reactive versus neoplastic nature. The lesion has a potential for recurrence, persistent local growth, progression to frank sarcoma and metastasis. Hence IMT can best be regarded as a low-grade sarcoma. A case of a 30-year-old female with swelling in the right maxilla and associated ophthalmic manifestations is discussed here. Contribution of immunohistochemistry for diagnosis of IMT is emphasized. Additional cytogenetic studies of this highly enigmatic and minimally studied tumour are warranted.
Keywords: Inflammatory myofibroblastic tumour, inflammatory pseudotumour, maxilla
|How to cite this article:|
Deshingkar S A, Tupkari J V, Barpande S R. Inflammatory myofibroblastic tumour of maxilla. J Oral Maxillofac Pathol 2007;11:76-9
|How to cite this URL:|
Deshingkar S A, Tupkari J V, Barpande S R. Inflammatory myofibroblastic tumour of maxilla. J Oral Maxillofac Pathol [serial online] 2007 [cited 2022 May 25];11:76-9. Available from: https://www.jomfp.in/text.asp?2007/11/2/76/37388
| Introduction|| |
Myofibroblastic sarcomas are soft-tissue neoplasms arising in myofibroblasts - ubiquitous cells sharing ultrastructural features of both muscle cells and fibroblasts.  In 1978, Vasundev and Harris described for the first time a sarcoma with ultrastructural features of myofibroblast.  These tumours fall into four main groups: (1) the family of reactive fascitis-like lesions, (2) a group of benign lesions (e.g., mammary myofibroblastoma, intranodal myofibroblastoma, dermatomyofibroblastoma), (3) the locally aggressive fibromatosis (either superficial or deep) which shares features of fibroblasts in varying degree and (4) the sarcomas showing myofibroblastic differentiation (low-grade lesions - infantile myofibroblastic sarcoma, inflammatory myofibroblastic tumour (IMT), low-grade myofibroblastic sarcoma, inflammatory fibrosarcoma; and high-grade lesions - malignant fibrous histiocytoma). 
Inflammatory myofibroblastic tumour (IMT) was originally described as a non-neoplastic lesion in the lungs and designated initially as inflammatory pseudotumour.  It represents a spectrum of myofibroblastic proliferation that includes reactive to benign to malignant lesions.  Some lesions are difficult to distinguish from reactive process whereas others appear sarcomatous.  The lesion may show neoplastic features like persistent local growth, recurrence and metastasis. Hence recently, IMT is best considered as a low-grade neoplastic lesion. 
| Case Report|| |
A 30-year-old female presented with an eight-month-lasting history of painless swelling in right maxillary region. Initially small, the swelling gradually grew large and reached a size of approximately 7 × 5 cm. History revealed that the swelling was initiated during the second month of pregnancy and was associated with ipsilateral epiphora and rhinorrhea since six months. There was proptosis and diplopia associated with the right eye since four months.
Extraorally the lesion extended superoinferiorly from supraorbital ridge to 1 cm below the line joining corner of mouth to tragus of right ear, and anteroposteriorly it extended from right side of nose to 2 cm anterior to the right ear. The swelling was roughly oval, smooth surfaced with indistinct borders, firm in consistency and nontender on palpation. Right submandibular lymph nodes were enlarged, mobile and nontender. Chest radiograph was within normal limits, and no obvious lesion was noticed elsewhere in the body. On intraoral examination a well-defined swelling, measuring about 3 × 4 cm, extended anteroposteriorly from 14 to 18 with obliteration of the buccal sulcus; and mediolaterally from midline of hard palate to right maxillary buccal vestibule [Figure - 1]. The swelling was smooth surfaced, of the same color as that of the adjacent mucosa, firm in consistency and nontender. Displacement of 15-18 was seen with associated tenderness and mobility.
Hematological and biochemical tests were within normal limits except for hemoglobin, which was considerably low (5.8 gm%). Intraoral periapical radiograph showed diffuse radiolucency with irregular borders associated with 15 to 18 and extensive root resorption of 16 to 18. Complete haziness of right maxillary sinus was noticed on PA Waters' view. Contrast Enhancing Computed Tomography (CECT) showed a large, ill-defined and heterogeneously enhancing lesion arising from right maxillary sinus with destruction of its walls [Figure - 2].
Macroscopically, the excised specimen with six teeth measured approximately 6 × 5 × 3.5 cm. It had an irregular shape, grayish-white color and firm consistency. The cut surface was whitish in color. Microscopically, the tumour comprised of large pleomorphic, spindle-to-oblong-shaped cells arranged in fascicles (compact spindle-cell pattern) [Figure - 3]. Storiform pattern was also seen at few places. The nuclei were large, spindle shaped and hyperchromatic. Some nuclei showed abnormal mitoses [Figure - 4]. Distinct infiltrate of lymphocytes and plasma cells was seen. Immunohistochemically, the tumour cells showed pancytoplasmic positivity for smooth muscle actin (SMA) [Figure - 5]; and S-100 protein [Figure - 6] and negativity for desmin, pancytokeratin and HMB-45. Based on these findings, the diagnosis of 'inflammatory myofibroblastic tumour of maxilla' was rendered.
| Discussion|| |
IMT is a rare spindle-cell neoplasm arising from myofibroblasts. The numerous terms used to describe this lesion - like pseudosarcomatous myofibroblastic proliferation, inflammatory sarcoma, plasma-cell granuloma, inflammatory pseudotumour and inflammatory histiocytic proliferation - reflect the initial controversies regarding its etiopathogenesis, histopathology and nomenclature.  Eventually, electron microscopic and immunohistochemical examinations clarified that the proliferating spindle cells in these tumours were myofibroblasts, and therefore these distinctive tumours are today preferentially called IMTs. 
Coffin et al. suggested that IMTs were benign proliferations, while Meis et al. proposed that some of the intra-abdominal tumours which were previously diagnosed as IMTs were actually sarcomas.  IMT has a potential for recurrence, persistent local growth; may progress to frank sarcoma; and metastasis has been recorded. Hence IMT is best regarded as a low-grade sarcoma.  It was first recognized as a distinctive lesion in the lungs; and later described in retroperitoneum, abdomen and extremities but seldom affects head and neck region. According to the available literature approximately 29 cases of IMT have been reported in head and neck region, out of which 20 cases have been described in the naso-maxillary region and nine cases in the oral cavity (with mandible as the site of predilection). 
Coffin et al. observed 84 cases of extrapulmonary IMT and found that it affects infants and adults younger than 20 years, mainly females.  Here in the present case, the lesion was seen in a 30-year-old female. This unusual finding suggested that the lesion was not restricted to younger age group but can also be seen in later adult life. Gale et al. had reported a case of IMT in naso-maxillary region occurring in a 22-year-old pregnant woman.  In the present case also, the lesion was initiated during pregnancy. This association between pregnancy and IMT might be explained by the fact that in response to the pregnancy-related hormones many tissues of body undergo pronounced proliferative changes even as a result of minor trauma or irritation (as seen in pregnancy tumour/granuloma gravidarum). It has been shown that myofibroblasts participate in many reactive processes like wound healing, and aberrant or exaggerated response to tissue injury without an established cause has generally been considered in the etiology of IMT.  On this basis, it may be hypothesized that pregnancy has some role in the pathogenesis of IMT. This aspect has not been yet studied and needs further confirmation.
The most common clinical presentation of the lesion is an incidentally discovered mass, followed by specific symptoms related to the site of origin. Computed tomography and/or magnetic resonance imaging of IMT in the head and neck region often suggest infiltrative growth and aggressive malignant potential.  Sciott et al. had reported two cases of IMT in bone of young adults presenting as slightly painful, osteolytic and well-delineated lesions of the distal femur.  While a case reported by Watanabe et al. in the left iliac bone showed an aggressive expanding growth in the surrounding tissue.  Histologically, IMT is composed of interwoven fascicles of myofibroblastic spindle cells admixed with prominent infiltrates of lymphocytes and plasma cells. Three basic histological patterns, none of which appears to have discernible association with the clinical behavior, have been described - namely, (1) myxoid/vascular pattern resembling inflammatory granulation tissue; (2) compact spindle-cell pattern with fascicular and/or storiform areas and variation in cellular density; and (3) hypocellular pattern, densely collagenized and reminiscent of fibrous scar. Three patterns may well be equally represented within the tumour, often blending into one another with one or two patterns predominating.  In all forms, the inflammatory background is a distinctive microscopic feature.  The tumour cells show mild-to-moderate nuclear atypia with enlarged, hyperchromatic nuclei.  In some cases lack of atypia, hyperchromasia and abnormal mitotic figures point towards possibility of benign nature of the lesion. However, Yamamota et al. proposed that IMT shows wide spectrum of cellular atypia and biological behavior with p 53 and MDM2 expression. 
Immunohistochemistry confirms the myofibroblastic phenotype of spindle cells, which are typically reactive to vimentin, alpha-smooth muscle actin and muscle-specific actin. In addition the spindle cells may be focally positive for desmin and cytokeratin.  These cells are typically negative for caldesmon. Caldesmon is a high molecular weight protein that binds to actin and tropomycin and regulates cellular contraction. It is highly specific for mature smooth muscle cells and hence is not expressed by reactive myofibroblasts. 
Regarding treatment, radical excision is curative in more than 90% of the extrapulmonary IMTs, including head and neck IMTs.  Most reports and series of extrapulmonary IMTs indicate that these tumours pursue an innocuous clinical course with frequency of local recurrence approximately 25%. Recurrence may occur many years later, and strict follow-up after surgery is required.  Reliable histological criteria for predicting the clinical outcome of IMT have not been firmly established so far. The combination of cellular atypia, p 53 expression and DNA aneuploidy might help to identify IMTs that have potential for aggressive clinical behavior and recurrence. 
The etiology and pathogenesis of IMT still remain unknown. An aberrant or exaggerated response to tissue injury without an established cause has generally been favored as the pathogenesis of IMT. An immunological pathogenesis remains a possibility. However, some subsets of pulmonary and abdominal IMTs are most probably associated infection - like Epstein-Barr virus, actinomyces, nocardia and mycoplasma .  Controversies still exist as to the reactive versus neoplastic nature of IMT. Cytogenetic and molecular studies point to the possibility that at least some subsets are in fact true neoplasms. Griffins et al. reported three cases in which consistent clonal chromosomal abnormality was found and suggested that the specific chromosomal region 2 p 23 and specifically alteration near or within the ALK-gene are consistently involved in this tumour. There is fusion of ALK-gene with TPM (tropomycin)-4 and TPM-3 gene.  Additional studies of this highly enigmatic and minimally studied tumour are warranted to confirm the breakpoint on chromosome 2 p and the role of the ALK-gene.
Inflammatory fibrosarcoma (IFS) was the designation proposed by Meis and Enzinger for the tumours that are locally aggressive or that can cause distant metastasis. Although there has been a controversy as to whether IMT and IFS are different tumours, it is currently recognized that they are interrelated neoplastic lesions. These lesions exhibit a range of morphologic atypia; and the behavior is characterized by local recurrence, aggressiveness and rare metastasis. 
IMT should be histologically differentiated from malignant fibrous histiocytoma (MFH) and leiomyosarcoma. MFH shows more pleomorphism and abnormal mitoses as compared to IMT.  When IMT contains large histiocyte-like cells, inflammatory MFH should be taken into consideration, characteristically containing a 'sea' of neutrophils.  Differentiation between IMT and leiomyosarcoma is difficult because both lesions show interlacing fascicles of eosinophilic spindle cells and intense immunoreactivity for smooth muscle actin. However, use of caldesmon antibody is found to be extremely useful in the differential diagnosis as IMT shows negative reactivity.  Conventional fibrosarcoma is ruled out by its histologic characteristics, which include interlacing fascicles with herringbone arrangement and lack of myofibroblastic differentiation. Finally, distinction from low-grade myofibroblastic sarcoma is difficult as this tumour also shows myofibroblastic proliferation with low grade of pleomorphism; however, it lacks distinct inflammatory component as in IMT.  Diagnosis of IMT in oral cavity and paranasal sinuses is challenged by nodular fascitis, fibromatosis and follicular dendritic cell tumour as they also are composed of myofibroblasts and fibroblasts. Compact cellularity, fascicular pattern and nuclear atypia should also raise suspicion of other neoplasms with spindle-cell appearance, such as sarcomatoid carcinoma, high-grade angiosarcoma with spindle-cell areas. 
| Conclusion|| |
In conclusion, a case of IMT in the maxilla in an unusual age group and associated with pregnancy is discussed. On histological examination, tumour was composed of compact spindle-cell pattern with varying degrees of inflammatory cell infiltration, which is the distinctive feature. Radical surgery is the best treatment option for IMT. Local recurrence may occur many years later; thus a strict vigilant follow-up after surgery is mandatory.
| References|| |
|1.||Fernandez-Acenero MJ, Sanz-Laguna A, Carrascoso-Arran J, Lopez-Criado P. Low-grade myofibroblastic sarcoma of the bone. Int J Pathol 2005;4:1. |
|2.||Behranwala KA, Straker P, Wan A, Fisher C, Thompson JN. Inflammatory myofibroblastic tumour of the gallbladder. World J Surg Oncol 2005;3:24. [PUBMED] [FULLTEXT]|
|3.||Gale N, Zidar N, Podboj J, Volavsek M, Luzar B. Inflammatory myofibroblastic tumour of paranasal sinuses with fatal outcome: Reactive lesion or tumour? J Clin Pathol 2003;56:715-7. [PUBMED] [FULLTEXT]|
|4.||Roy S. Myofibroblastic tumours. Available from: http://www.histopathology-india.net/myofibroblastictumours.htm. [Last updated on 2006 Jul]. |
|5.||Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ. Recurrent involvement of 2p23 in inflammatory myofibroblastic tumours. Cancer Res 1999;59:2776-80. |
|6.||Watanabe K, Tajino T, Sekiguchi M, Suzuki T. Inflammatory myofibroblastic tumour (Inflammatory fibrosarcoma) of the bone. Arch Pathol Lab Med 2000;124:1514-7. [PUBMED] [FULLTEXT]|
|7.||Sciott R, Dal CP, Christopher F, Jesus H, Juan G, Ignace S, et al. Inflammatory myofibroblastic tumour of bone: Report of two cases with evidence of clonal chromosomal changes. Am J Surg Pathol 1997;21:1166-72. |
|8.||Yamamota H, Oda Y, Saito T, Sakamoto A, Miyajima K, Tamiya S, et al. p 53 mutation and MDM2 amplification in inflammatory myofibroblastic tumors. Histopathology 2003;42:431-9. |
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]