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CASE REPORT
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Inflammatory myofibroblastic tumor of colon and duodenum: Metachronous, metastatic or local recurrence? An unusual presentation


1 Department of Pathology, Lady Hardinge Medical College, New Delhi, India
2 Department of Histopathology, Sir Gangaram Hospital, New Delhi, India
3 Department of Laproscopic and Bariatric Surgery, Sir Gangaram Hospital, New Delhi, India
4 Department of Radiology, Sir Gangaram Hospital, New Delhi, India

Date of Submission30-Jan-2022
Date of Acceptance15-Jun-2022

Correspondence Address:
Shashi Dhawan,
Senior Consultant, Department of Histopathology, Sir Gangaram Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_258_22

 > Abstract 


Inflammatory myofibroblastic tumor (IMT) is a tumefactive proliferation of spindled myofibroblastic cells admixed with inflammatory infiltrate. This tumor has a predilection for the involvement of visceral soft tissues and has a tendency for local recurrence. Occurrence of metastatic or metachronous IMTs is a rare presentation. We report a rare case of a 50-year-old man with metastatic IMTs in the colon and duodenum.

Keywords: Anaplastic lymphoma kinase-1 (ALK-1), inflammatory myofibroblastic tumor, metachronous, metastatic, recurrence



How to cite this URL:
Osama MA, Dhawan S, Khetan M, Rawat KS. Inflammatory myofibroblastic tumor of colon and duodenum: Metachronous, metastatic or local recurrence? An unusual presentation. J Can Res Ther [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=357869




 > Introduction Top


Inflammatory myofibroblastic tumor (IMT) is an infrequent neoplasm of myofibroblastic origin composed of predominant spindle cell proliferation along with a variable inflammatory component of lymphocytes and plasma cells. These tumors have an intermediate malignant potential. Although, individuals of any age may be affected, it has a preponderance for children and young adults.[1] The most common location is the lungs, but there are rare reports of occurrence in extrapulmonary sites like mesentery of the small intestine, omentum, central nervous system, salivary glands, larynx, breasts, pancreas, spleen, liver and skin.[1],[2] In around 15%–30% of cases, IMTs may be associated with systemic symptoms like fever, weight loss and malaise. Preoperative diagnosis is challenging as the clinical and radiological features mimic malignancy. Here, we present a case of IMTs in duodenum in a patient who was earlier operated for the same in colon.


 > Case History Top


A 50-year-old, non-diabetic, non-hypertensive male patient presented with right upper abdominal pain and bleeding per rectum for four months. Contrast-enhanced computerized tomography (CECT) abdomen showed a polypoidal tumor mass measuring 8.6 × 7.8 × 7.4 cm in the ascending colon with extramural extension in the paracolic fat [Figure 1]a and [Figure 1]b. The possibility of lymphoma or gastrointestinal stromal tumor was suggested on CECT. On colonoscopy, a large mass was seen in the hepatic flexure with an ulcerated mucosal surface. The patient underwent an extended right hemicolectomy. On gross examination, the tumor mass in colon measured 10 × 7.5 cm. Mucosa overlying the mass was completely flattened out and focally ulcerated. Cut surface of the tumor was grey–white with focal areas of hemorrhage. Microscopically, the tumor was largely in the submucosa infiltrating the mucosa [Figure 2]a as well as muscularis propria, reaching up to the serosa and beyond. Thick and thin fibrous bands traversed the tumor, giving it a lobulated configuration. Tumor was composed of mixed inflammatory cell infiltrate comprising of neutrophils, foamy histiocytes, lymphocytes, eosinophils, plasma cells, along with a few scattered fibroblastic or myofibroblastic spindle cells showing mild-to-moderate nuclear pleomorphism [Figure 2]b. There was marked pleomorphism in a few foci. Prominent neutrophilic phagocytosis and occasional giant cells were noted. No increase in mitosis (0-2/10HPF) or necrosis was seen. The tumor was seen superficially infiltrating into the liver tissue at one focus [Figure 2]c. The neoplastic cells showed patchy positivity for SMA and were negative for Desmin, confirming myofibroblastic phenotype. They were immunologically negative for DOG-1, CD117, CD34, S-100, Cyclin D1 and ALK-1. Ki67 proliferative index was low (0%–2%) [Figure 2]d. Interspersed histiocytes showed CD68 positivity. A diagnosis of IMT was rendered.
Figure 1: (a) Axial view of intravenous contrast-enhanced CT image shows homogeneously enhancing submucosal tumor in colon (blue arrow); (b) Coronal view of intravenous contrast-enhanced CT image shows the mass in hepatic flexture of colon (blue arrow), extending into subhepatic region and infiltrating the hepatic parenchyma with no involvement of duodenum (yellow arrow)

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Figure 2: (a) Tumor present in the colonic submucosa and infiltrating into the mucosa (H&E 100×); (b) Tumor composed of mixed inflammatory cell infiltrate comprising of neutrophils, lymphocytes, eosinophils, plasma cells, foamy histiocytes along with few scattered fibroblastic/myofibroblastic spindle cells with moderate-to-marked atypia (H&E 200×); (c) Colonic tumor superficially infiltrating the liver tissue (H&E 200×); (d) Low Ki67 proliferative index in colonic tumor (0%–1%) (200×)

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Two years later, the patient presented again with complaints of abdominal pain, vomiting and fever for two days. Physical examination revealed a palpable lump in the right flank region. CECT scan revealed a large mass lesion, measuring 7 × 7 × 5.5 cm at the junction of second and third parts of the duodenum [Figure 3]a and [Figure 3]b. On endoscopy, the mass showed an irregular surface and appeared to be arising from the submucosal plane. The patient underwent Whipple's pancreaticoduodenectomy. A well-circumscribed tumor measuring 6 × 5 cm with a grey yellow homogeneous cut surface was noted in the wall of the duodenum [Figure 3]c. Histopathological examination exhibited a tumor with histological features similar to that in the colon, seen two years ago [Figure 4]a. However, higher number of inflammatory cells and phagocytic cells with very sparse fibroblastic cells were observed at this site [Figure 4]b compared to the previous tumor. The fibroblastic cells showed only mild nuclear atypia compared to colonic mass [Figure 4]c. Immunopositivity for CD68 and alpha-1-antitrypsin with focal positivity for SMA was noted. Staining for ALK-1 was negative. Ki67 proliferative index was low (0%–2%) [Figure 4]d. Other immunomarkers like DOG-1, CD117, CD34, S-100, Cyclin D1 were negative. On the basis of earlier and present histological appearance along with immunohistochemistry (IHC) and clinical findings, a diagnosis of inflammatory myofibroblastic tumor of the duodenum was rendered. The patient at his most recent follow-up (of two-and-half years) showed no signs of recurrence.
Figure 3: (a) Axial view intravenous contrast-enhanced CT image shows homogeneously enhancing submucosal mass in the second part of duodenum (blue arrow); (b) Coronal view intravenous contrast-enhanced CT image shows homogenously enhancing submucosal mass in the second part of duodenum (blue arrow); (c) Gross examination of Whipple's pancreaticoduodenectomy specimen showing a well circumscribed tumor in the wall of duodenum

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Figure 4: (a) Tumor present in the duodenal submucosa (H&E 100×); (b) Duodenal tumor showing predominantly inflammatory cells, few spindle-shaped cells and prominent neutrophilic phagocytosis (H&E 100×); (c) Duodenal tumor showing increased inflammatory cells and phagocytic activity with very sparse fibroblastic cells (H&E 200×); (d) Low Ki67 proliferative index in duodenal mass (0%–1%) (200×)

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 > Discussion Top


IMT is also known as inflammatory pseudotumor, myofibroblastoma, plasma cell granuloma and inflammatory myofibroblastic sarcoma. The most common location of its occurrence is the lungs.[2] According to the World Health Organization (WHO) classification, IMTs are intermediate grade neoplasms.[3] There is lack of consensus among experts about whether they are reactive or neoplastic. Extensive studies on this tumor over the years have proven it to be neoplastic as 50%–60% of them showed genetic alteration in ALK gene, suggesting its role in the pathogenesis of IMT.[3] Coffin et al.[4] in their study of 59 cases, described three histological patterns including myxoid/vascular, compact spindle cell and fibromatosis-like patterns. The myxoid/vascular pattern has an appearance similar to fasciitis and is composed of loosely arranged plump spindle cells in an edematous/myxoid stroma with prominent blood vessels. The inflammatory infiltrate is richer in neutrophils and eosinophils with relatively sparse plasma cells than the other two patterns. Second pattern showed compact spindle cells with storiform architecture in a collagenous stromal background. These are typically rich in plasma cells and lymphocytes admixed with the spindle cells. The fibromatosis-like pattern is hypocellular, with elongated spindle cells admixed with scattered lymphocytes, plasma cells and eosinophils in a dense collagenous stroma. Coffin et al.[4] also stated that majority (72.9%) of IMTs have atypical histological appearance as they display features of increased cellularity, cellular atypia and presence of multinucleated/anaplastic giant cells, atypical mitosis and necrosis. The remaining tumors were bland on histology, and hence, were called classical IMT. Both our cases had histological features similar to first type and both the tumors had loose edematous stroma, rich inflammatory infiltrate and sparse fibroblasts.

In view of this rich inflammatory component and ALK negativity, inflammatory fibroid polyp was considered as one of the differential diagnoses. However, due to absence of perivascular fibroblastic cuffing, negative CD34, the large tumor size and its widespread infiltration in the pericolic fat and liver, the diagnosis of IMT was favored. In contrast to inflammatory fibroid polyp where eosinophils are more prominent, the inflammatory exudate in this case had more neutrophils as is seen in IMT. Inflammatory myofibroblastic tumor was diagnosed in the duodenum too, in view of prior colonic mass with a similar histology. Other tumors like gastrointestinal stromal tumor (GIST), inflammatory leiomyosarcoma, liposarcoma, malignant fibrous histiocytoma, and malignant peripheral nerve sheath tumor (MPNST) were ruled out on histology and/or IHC results.

The possibility of both the tumors being either metachronous or metastatic is debatable. Although, there are a few case reports of colonic carcinoma metastasizing to duodenum, the occurrence of metastatic IMTs from the colon to the duodenum has never been reported.[5] The probability of the duodenal mass being a metastatic tumor was argued as IMTs characteristically metastasize to the lungs, brain, liver and bone, and metastasis to gastrointestinal tract is extremely rare. No report of intra-gastrointestinal metastasis of IMTs have been seen yet.[4],[6] Metastatic tumors are usually poorly differentiated compared to primary tumors, but there was significantly lower degree of nuclear atypia seen in the duodenal mass than in the colonic mass in our patient. However, many authors have negated the correlation of morphological features and metastatic propensity of the tumor.[6] Although earlier case reports have termed them as metachronous tumors, they are reported as metastatic in later publications. Hence, the metastatic tumor in the duodenum from a colon primary is very well a possibility.

This case was further analyzed to rule out the possibility of tumor recurrence, as incomplete tumor resection may lead to local recurrence in high percentage of cases.[7] The histology, radiological picture and the intraoperative findings of both tumors were critically analyzed. CECT abdomen images of both the tumors were reviewed and extramural extension of the colonic mass, to the paracolic fat was thoroughly evaluated. There was an extension up to the subhepatic plain and periduodenal soft tissue, sparing the duodenual wall in the CECT of colonic mass. While performing right hemicolectomy, the surgeon further added that the colonic tumor was densely adhered to the subhepatic surface and serosal aspect of duodenum was spared. On gross examination, the hemicolectomy specimen showed a thin frill of liver tissue, which on microscopy was superficially infiltrated by the tumor in one focus. No adhered duodenal tissue was seen on gross inspection as well as on microscopy. Secondly, CECT of duodenal mass showed relatively spared subseroal fat. Whipple's pancreaticduodenenctomy specimen didn't show serosal involvement by the tumor. Because of these reasons, the possibility of local recurrence is ruled out and most plausible theory of metastatic IMT is entertained.

At present, there are no definite histopathological, molecular, or cytogenetic features to predict the risk of malignant transformation, recurrence, or metastasis.[4] In the previously published case reports, no definite correlation of ALK immunoreactivity and tumor recurrence or metastasis has been identified. Coffin et al.[4] deduced that ALK positive IMTs tend to recur while the ALK-negative ones showed metastases.

The mainstay of management of IMT is surgical excision. Incomplete tumor removal frequently results in local recurrence. These tumors also show regression in response to corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). Our patient did not receive any other treatment post surgery, and he is doing well without any evidence of recurrence or metastasis after two-and-half years of follow-up. Da et al.[8] in their case series showed a local recurrence rate of 21%. A novel ALK-targeted inhibitor, crizotinib has been found to be effective in treatment of unresectable and metastatic ALK-expressing IMT.[9]


 > Conclusion Top


Despite the presence of novel imaging modalities and laboratory techniques, IMT masses are often confused with other neoplasms, because of their nonspecific clinical and morphological findings, hence making the diagnosis difficult. It is not possible to categorize the tumor as metastatic or metachronous due to their bland morphology. Chances of recurrence or metastasis is high in locally advanced tumors, even though they appear bland morphologically.

Declaration of patient consent

The authors certify that they have obtained the appropriate consent from the patient. The patient has given his consent for the images and other clinical information to be reported in the journal. The patient understands that the name and initials will not be published, and due efforts have been made to conceal the same.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Saxena S, Dhal I, Mohanpuria A, Garg J, Karnik S, Khedkar B. Extrapulmonary inflammatory myofibroblastic tumor at different sites with histopathology and immunohistochemical analysis: A case series. Oncol J India 2018;2:80-5  Back to cited text no. 1
    
2.
Camela F, Gallucci M, di Palmo E, Cazzato S, Lima M, Ricci G, et al. Pulmonary inflammatory myofibroblastic tumor in children: A case report and brief review of literature. Front Pediatr 2018;6:35. doi: 10.3389/fped. 2018.00035.  Back to cited text no. 2
    
3.
Fletcher CD, Bridge JA, Hogendoorn P, Mertens F. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon: IARC Press, 2013. p. 83-4.  Back to cited text no. 3
    
4.
Coffin CM, Hornick JL, Fletcher CD. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 2007;31:509-20.  Back to cited text no. 4
    
5.
Matsuo M, Hatano Y, Imaizumi Y, Kuroda T, Arai T, Tomita H, et al. Metastatic colon cancer of the small intestine diagnosed using genetic analysis: A case report. Diagn Pathol 2020;15:106. doi: 10.1186/s13000-020-01019-6.  Back to cited text no. 5
    
6.
Libby EK, Ellis LT, Weinstein S, Hammer RD, Murray KS. Metastatic inflammatory myofibroblastic tumor of the bladder. Urol Case Rep 2018;23:10-2.  Back to cited text no. 6
    
7.
Lorenzi L, Cigognetti M, Medicina D, Pellegrini V, Balzarini P, Cestari R, et al. ALK-positive inflammatory myofibroblastic tumor of the abdomen with widespread microscopic multifocality. Int J Surg Pathol 2014;22:640-4.  Back to cited text no. 7
    
8.
Da M, Qian B, Mo X, Xu C, Wu H, Jiang B, et al. Inflammatory myofibroblastic tumors in children: A clinical retrospective study on 19 cases. Front Pediatr 2021;9:543078. doi: 10.3389/fped. 2021.543078.  Back to cited text no. 8
    
9.
Schöffski P, Kubickova M, Wozniak A, Blay JY, Strauss SJ, Stacchiotti S, et al. Long-term efficacy update of crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumor from EORTC trial 90101 CREATE. Eur J Cancer 2021;156:12-23.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

 
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