Inflammatory myofibroblastic tumor: difficult to manage
Viewpoint on Thoracic Surgery

Inflammatory myofibroblastic tumor: difficult to manage

Peter Sze-Yuen Yu

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China

Correspondence to: Dr. Peter Sze-Yuen Yu, MBBS, MRCS. Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China. Email: peteryu@surgery.cuhk.edu.hk.

Received: 02 August 2017; Accepted: 11 October 2018; Published: 25 October 2018.

doi: 10.21037/jovs.2018.10.08


Introduction

Inflammatory myofibroblastic tumor (IMT) is considered a neoplastic reaction to an inflammatory insult (1). As a rare condition but masquerading as a number of common presentations, this inflammatory tumor deserves particular attention. IMT also causes dilemmas in diagnosis and management. Based on mainly small case series and scattered case reports, establishing a guide to diagnosis and management is difficult. In view of variability of its nature and complexity of information from the literature, a general consideration and approach to IMTs is discussed in this article.


Difficulty: diagnosis

As a rare tumor with incidence not more than 0.1% (2), and more common in the young population especially the paediatric patients (3), the presence of a lung tumor in a young patient seldom raises a suspicion of either lung malignancy or this ‘pseudotumor’. Other differential diagnoses, e.g., hamartoma, haemangioma or chondroma may be considered well-above an IMT. Clinically the presentation may be similar to a respiratory tract infection (e.g., cough, fever, pleuritic chest pain, dyspnea etc.) or asthma (4-6), or appear like malignancy-associated constitutional symptoms (e.g., weight loss, fatigue) (7). Association with a number of conditions (such as bacterial or viral infections, Sjogren syndrome, lymphoma, IgG4 syndrome, post-stem cell or solid organ transplantation etc.) seldom help raise the suspicion of IMTs, and the causal links are far from established (8-10). Radiologically when it presents as a solitary pulmonary nodule, it shows a solitary, sharply circumscribed and lobulated mass. Pleural effusion may occasionally be an accompanying feature (3). When developed endobronchially, atelectasis or obstructive pneumonia ensue. These findings add no distinguishing values to it from other types of lung tumors. The appearance of IMTs on computer tomography (CT) scans are variable and non-specific, and the addition of positron-emission tomography makes the picture even more perplexing, as IMTs demonstrate variably intense 18-FDG uptake depending on its pathological properties (e.g., cellularity, proliferative index, and the amount of plasma cell infiltrates) (11). Therefore, based on radiological features, surgeons can neither propose nor oppose the possibility of malignancy. There is no evidence to suggest that bronchoscopic or percutaneous needle biopsy can confidently diagnose or exclude malignancy (12). The appearance of spindle cells in the tiny specimen usually does not point towards IMTs unless a representative sampling and analysis including CD68 and vimentin can be performed (13). Therefore, confirmation of diagnosis mostly required excision of the tumor en bloc with the lobe in which it is located.


Difficulty: treatment

IMT has the potential to undergo malignant transformation or metastasize (13-15). Surgical resection with a view to both diagnosis and treatment should be the mainstay of management. However, major lung resection (which may be to the extent of lobectomy or even pneumonectomy) for a potentially benign ‘spindle cell’ tumor in young patients must be justified in times of uncertain preoperative diagnosis. Firstly, CT scan of the thorax and abdomen must be performed to exclude synchronous inflammatory tumors in other organs (16). Secondly, complete resection should be achieved to maximize post-operative survival (17), which could be more than 91% (13). Recurrence may be up to 8% if resection is partial without adjuvant therapy (14). Pre-operative embolization of the feeding artery to the IMT may reduce hypervascularity and facilitate complete resection (18). Still, contralateral recurrence after complete resection by pneumonectomy had been reported (19). Endobronchial IMTs can be removed under rigid bronchoscopy (20). Close surveillance is necessary for any persistence of the lesion (21).

There is no medical therapy indicated as primary therapy for IMTs. Scattered reports on the effectiveness of Celecoxib, a non-steroidal anti-inflammatory drug (NSAID), were available (22,23). Celecoxib inhibits cyclooxygenase-2 enzyme and vascular endothelial growth factors which are essential for angiogenesis. Regression of an IMT after a ‘neoadjuvant’ NSAIDs therapy may spare a pneumonectomy (22). Combination of Celecoxib with chemotherapeutic agent was reported to induce durable remission (24). It is known that IMTs also show response to corticosteroid therapy (25,26). However, this response may be attributed to the response of IgG4-related diseases to steroids, while not all IMTs are related to IgG4 disease. On the other hand, steroids had also been reported to aggravate disease progression of IMTs (27). IMTs may exhibit anaplastic lymphoma kinase (ALK) mutation in 40–50% cases (28,29). The use of ALK receptor tyrosine kinase inhibitors (e.g., Crizotinib, Ceritinib, and Alectinib) can be effective (30-33), and could be considered for inoperable cases.


Conclusions

A general summary of the difficulties in management of inflammatory fibroblastic tumor is discussed. Limited evidence from the literatures signifies the need of gathering and reporting more experience to the pool. Adequate suspicion of this condition and thorough discussion with patients regarding subsequent treatment are necessary. Optimal survival requires careful work-up and planning, and complete resection for surgical candidates.


Acknowledgements

None.


Footnote

Conflicts of Interest: The author has no conflicts of interest to declare.


References

  1. Dehner LP. Inflammatory myofibroblastic tumor: the continued definition of one type of so-called inflammatory pseudotumor. Am J Surg Pathol 2004;28:1652-4. [Crossref] [PubMed]
  2. Umiker WO, Iverson L. Postinflammatory tumors of the lung; report of four cases simulating xanthoma, fibroma, or plasma cell tumor. J Thorac Surg 1954;28:55-63. [PubMed]
  3. Agrons GA, Rosado-de-Christenson ML, Kirejczyk WM, et al. Pulmonary inflammatory pseudotumor: radiologic features. Radiology 1998;206:511-8. [Crossref] [PubMed]
  4. Naime S, Bandarkar A, Nino G, et al. Pulmonary inflammatory myofibroblastic tumour misdiagnosed as a round pneumonia. BMJ Case Rep 2018;2018.
  5. Zuo T, Fu J, Ni Z, et al. Pulmonary inflammatory Myofibroblastic tumor indistinguishable from tuberculosis: a case report in a five-year-old child with hemoptysis. J Cardiothorac Surg 2017;12:112. [Crossref] [PubMed]
  6. Li X, Li J, Rao X, et al. A case report of tracheal inflammatory myofibroblastic tumor in a 34-week pregnant woman misdiagnosed with asthma. Medicine (Baltimore) 2017;96. [Crossref] [PubMed]
  7. Coffin CM, Humphrey PA, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological survey. Semin Diagn Pathol 1998;15:85-101. [PubMed]
  8. Khatri A, Agrawal A, Sikachi RR, et al. Inflammatory myofibroblastic tumor of the lung. Adv Respir Med 2018;86:27-35. [Crossref] [PubMed]
  9. Fujino H, Park YD, Uemura S, et al. An endobronchial inflammatory myofibroblastic tumor in a 10-yr-old child after allogeneic hematopoietic cell transplantation. Pediatr Transplant 2014;18:E165-8. [Crossref] [PubMed]
  10. Schweckendiek D, Inci I, Schneiter D, et al. Inflammatory Myofibroblastic Tumor of the Lung: Two Progressing Pulmonary Nodules in a 25-Year-Old Adult With a Moraxella catharalis Infection. Ann Thorac Surg 2015;100:e123-4. [Crossref] [PubMed]
  11. Dong A, Wang Y, Dong H, et al. Inflammatory myofibroblastic tumor: FDG PET/CT findings with pathologic correlation. Clin Nucl Med 2014;39:113-21. [PubMed]
  12. Copin MC, Gosselin BH, Ribet ME. Plasma cell granuloma of the lung: difficulties in diagnosis and prognosis. Ann Thorac Surg 1996;61:1477-82. [Crossref] [PubMed]
  13. Melloni G, Carretta A, Ciriaco P, et al. Inflammatory pseudotumor of the lung in adults. Ann Thorac Surg 2005;79:426-32. [Crossref] [PubMed]
  14. Kovach SJ, Fischer AC, Katzman PJ, et al. Inflammatory myofibroblastic tumors. J Surg Oncol 2006;94:385-91. [Crossref] [PubMed]
  15. Meis JM, Enzinger FM. Inflammatory fibrosarcoma of the mesentery and retroperitoneum. A tumor closely simulating inflammatory pseudotumor. Am J Surg Pathol 1991;15:1146-56. [Crossref] [PubMed]
  16. Sakurai H, Hasegawa T, Watanabe S, et al. Inflammatory myofibroblastic tumor of the lung. Eur J Cardiothorac Surg 2004;25:155-9. [Crossref] [PubMed]
  17. Cerfolio RJ, Allen MS, Nascimento AG, et al. Inflammatory pseudotumors of the lung. Ann Thorac Surg 1999;67:933-6. [Crossref] [PubMed]
  18. Kim KN, Kim DW. Complete resection of a huge hypervascular inflammatory myofibroblastic tumor in right hemithorax after embolization. World J Pediatr 2016;12:498-500. [Crossref] [PubMed]
  19. Vis DC, Kelly MM, Lee AG, et al. Contralateral recurrence of inflammatory myofibroblastic tumour of the lung 10 years after pneumonectomy. Thorax 2018. [Epub ahead of print]. [Crossref] [PubMed]
  20. Oztuna F, Pehlivanlar M, Abul Y, et al. Adult inflammatory myofibroblastic tumor of the trachea: case report and literature review. Respir Care 2013;58:e72-6. [Crossref] [PubMed]
  21. Cerfolio RJ, Matthews TC. Resection of the entire left mainstem bronchus for an inflammatory pseudotumor. Ann Thorac Surg 2005;79:2127-8. [Crossref] [PubMed]
  22. Ghani S, Desai A, Pokharel S, et al. Pneumonectomy-Sparing NSAID Therapy for Pulmonary Inflammatory Myofibroblastic Tumor. J Thorac Oncol 2015;10:e89-e90. [Crossref] [PubMed]
  23. Su W, Ko A, O'Connell T, et al. Treatment of pseudotumors with nonsteroidal anti-inflammatory drugs. J Pediatr Surg 2000;35:1635-7. [Crossref] [PubMed]
  24. Johnson K, Notrica DM, Carpentieri D, et al. Successful treatment of recurrent pediatric inflammatory myofibroblastic tumor in a single patient with a novel chemotherapeutic regimen containing celecoxib. J Pediatr Hematol Oncol 2013;35:414-6. [Crossref] [PubMed]
  25. Shirakusa T, Kusano T, Motonaga R, et al. Plasma cell granuloma of the lung--resection and steroid therapy. Thorac Cardiovasc Surg 1987;35:185-8. [Crossref] [PubMed]
  26. Doski JJ, Priebe CJ Jr, Driessnack M, et al. Corticosteroids in the management of unresected plasma cell granuloma (inflammatory pseudotumor) of the lung. J Pediatr Surg 1991;26:1064-6. [Crossref] [PubMed]
  27. Panigada S, Sacco O, Girosi D, et al. Corticosteroids may favor proliferation of thoracic inflammatory myofibroblastic tumors. Pediatr Pulmonol 2014;49:E109-11. [Crossref] [PubMed]
  28. Hallberg B, Palmer RH. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat Rev Cancer 2013;13:685-700. [Crossref] [PubMed]
  29. Cessna MH, Zhou H, Sanger WG, et al. Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases. Mod Pathol 2002;15:931-8. [Crossref] [PubMed]
  30. Ono A, Murakami H, Serizawa M, et al. Drastic initial response and subsequent response to two ALK inhibitors in a patient with a highly aggressive ALK-rearranged inflammatory myofibroblastic tumor arising in the pleural cavity. Lung Cancer 2016;99:151-4. [Crossref] [PubMed]
  31. Mansfield AS, Murphy SJ, Harris FR, et al. Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib. Ann Oncol 2016;27:2111-7. [Crossref] [PubMed]
  32. Rafee S, Elamin YY, Joyce E, et al. Neoadjuvant crizotinib in advanced inflammatory myofibroblastic tumour with ALK gene rearrangement. Tumori 2015;101:e35-9. [Crossref] [PubMed]
  33. Butrynski JE, D'Adamo DR, Hornick JL, et al. Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med 2010;363:1727-33. [Crossref] [PubMed]
doi: 10.21037/jovs.2018.10.08
Cite this article as: Yu PS. Inflammatory myofibroblastic tumor: difficult to manage. J Vis Surg 2018;4:219.