Inflammatory myofibroblastic tumours of the duodenopancreaticobiliary tract

Abstract

Inflammatory myofibroblastic tumours (IMTs) are rare benign neoplasms of intermediate malignant potential that are found in the lungs and rarely at extrapulmonary sites common in children and young adults. IMTs tend to be locally invasive and have some amount of metastatic potential as well. We present two cases of IMTs involving the duodenum, pancreas and distal bile duct. The first case presented with extensive involvement of the first three parts of the duodenum and head of the pancreas, while the second presented with a pancreatic and biliary tree involvement. Upon examinations and investigations, these tumours mimicked malignant neoplasms. A Whipple procedure for surgical resection was undertaken in both cases. The histological findings showed fascicles of spindle cells with infiltration of lymphocytes and plasma cells. The inflammatory myofibroblastic tumour was diagnosed based on pathological grounds with immunohistochemistry. Preoperative diagnosis of IMTs is difficult and complete surgical resection is the primary treatment.

Introduction

Inflammatory myofibroblastic tumour (IMT) is a rare, uncommon lesion whose cause is not yet known. It is inclusive of a spectrum of myofibroblast cell proliferative mass admixed with varying amount of inflammatory infiltrate such as plasma cells, lymphocytes and eosinophils. The current WHO classification for this rare tumour entity is a fibroblastic sarcoma or myofibroblastomas.¹ This is a distinctive neoplasm of intermediate biological potential that may be malignant or aggressive based on the underlying genetic variants. The worldwide incidence of IMT is about 0.04%–0.7% and clinical data acquired so far have shown that IMTs have a 25%–33% rate of local recurrence and up to a 5% rate of distant metastasis.¹

IMTs were first observed and described by Bunn in 1939 and were later named by Umiker and Iverson.² IMTs can affect different anatomical locations of the body, and they make up 0.7% of tumours in the lung parenchyma and bronchus (most common site is of pulmonary origin). The extrapulmonary locations of IMTs are in the orbit (eye socket), peritoneum (lining of the abdominal cavity and internal organs) and mesentery. However, they are also extremely rarely found in the head region.^{3 4}

The IMTs in the gastrointestinal tract (GIT) are extremely rare and their locations are highly variable. Their symptoms are according to the anatomical location and associated involvement of the tumour. In this review, we present a two case series explaining our rare findings of IMTs in the duodenum, biliary tract and pancreas (case 1 and case 2).

Case report 1

Case presentation

A 56-year-old man was admitted on 30 December 2019 with a 2-month history of pain abdomen with vomiting. There were symptoms of gastric outlet obstruction with significant weight loss for approximately more than a month. No history of jaundice was present. Loss of weight of about 10 kg in 2 months was reported by the patient. The patient has a known history of diabetes and hypertension. Physical examination was essentially normal. The levels of CEA (carcinoembryonic antigen) and CA19.9 (carbohydrate antigen 19-9) were within normal limits.

Investigations and treatment

Enhanced abdominal CT and PET scan (positron emission tomography scan; Siemens Biograph mCT 128 slice PET CT scanner) investigation revealed a dilated stomach with a large mass arising from the wall of the duodenum involving pylorus with first and second segments of duodenum (D1 and D2) (figure 1A, B). Evidence of enlarged lymph nodes along the porta hepatic which lie anterior and posterior to the portal vein and extend down along the hepatoduodenal ligament and retro duodenal region was observed. Endoscopy revealed a mass obstructing the pylorus beyond which the scope could not be passed. Biopsy was taken which showed eosinophilic infiltration of mucosa. An endoscopic ultrasound (EUS) revealed a solid obstructing mass at the pylorus (figure 2A) and a fine needle aspiration (FNA) sample was taken. The FNA revealed a scattered spindle-shaped cell which was indicative of spindle cell neoplasm. The endoscopic biopsy of the mass was inconclusive since it demonstrated an eosinophilic infiltration of mucosa with spindle-shaped cells without any other clear evidence of malignancy. Since the tumour was invading the duodenum involving the D1 and extending to D2+D3 which was resectable, it was discussed by the tumour board for a surgical treatment.

Figure 1.

(A, B) CT and positron emission tomography scan of abdominal findings in case 1.

Figure 2.

(A) Endoscopic image showing a solid obstructing mass at the pyloric junction. (B) Resected tumour (4.5×2×1.2 cm) along with associated structures from the Whipple procedure (intraoperative resected image).

A hard mass of 4.5×2×1.2 cm (figure 2B) was noted arising from the first part of the duodenum intraoperatively and infiltrating the second and third parts of the duodenum and head of the pancreas. A few soft insignificant nodes were noted around. Whipple’s pancreaticoduodenectomy procedure for resection of the mass was performed.

The resected specimen was sent for histopathological examination. The polypoid mass was grey white–grey brown, infiltrating into the duodenal wall. The tissue sections were stained with H&E and were examined microscopically. Histopathological sections revealed duodenal mucosal ulceration, the floor of which was formed of acute inflammatory exudate and proliferating capillaries along with the presence of Brunner gland hyperplasia. Lamina propria showed a lesion composed of spindle-shaped cells with elongated nucleus and tapered ends. Amidst the spindle cells, dense mixed inflammatory cell infiltrates composed of eosinophils in addition to mononuclear cells were observed (figure 3A, B).

Figure 3.

(A, B) H&E staining of tumour sections showing mucosal ulceration of the floor containing acute inflammatory exudate and proliferating capillaries along with the presence of Brunner gland hyperplasia. Spindle cells, mixed inflammatory cell infiltrate composed of eosinophils in addition to mononuclear cells were seen.

Immunohistochemical staining panel showed the spindle cells positive for anti-human smooth muscle actin (focal positivity), calponin and desmin (focal positivity) and negative for ALK-1 (anaplastic lymphoma kinase-1).

Outcomes and follow-up

During the postoperative course, the patient had an episode of bleeding from a portal vein branch on postoperative day 1 (POD1) followed by a re-exploratory surgery to control the bleeding. The patient was then started orally with a soft diet on POD3 of re-exploration followed by the drain removal on POD5 and discharge on POD8. Six months later, a follow-up CT was done which showed no evidence of recurrent mass.

Case report 2

Case presentation

A 54-year-old man presented with 1-month history of pain abdomen and a history of jaundice since the past 15 days with one episode of fever 15 days ago. There was no history of pruritus or subsequent episodes of fever after the first one. There was no history of any significant GI symptoms except for loss of appetite. The patient reported loss of weight of about 5 kg in the past 1 month. The patient was a known tobacco chewer and frequent alcoholic. Physical examination was essentially normal except for icterus.

Investigations and treatment

Laboratory tests showed abnormal liver function tests with markedly elevated alkaline phosphatase 235 IU/L (normal range 44–147 IU/L) and total bilirubin level 3.5 mg/dL (normal range 0.1–1.2 md/dL). Other results were within normal range. The levels of CEA and CA19.9 were within normal limits as well.

Enhanced abdominal CT and PET scan (positron emission tomography scan; Siemens Biograph mCT 128 slice PET CT scanner) revealed mild intrahepatic biliary radicular dilatation with no focal lesions. The gallbladder was over distended with mild wall thickening and pericholecystic oedema. The mid common bile duct showed periductal enhancing metabolically active mass lesion, measuring approximately 2×1.3 cm (figure 4). There was a significant stranding in the surrounding area with infiltration of adjacent head of the pancreas and mild narrowing of the extrahepatic main portal vein. Stranding around the first part of the duodenum with small calcific foci in the head of the pancreas with minimal peripancreatic stranding was also observed.

Figure 4.

Enhanced abdominal CT and positron emission tomography scan of findings in case 2.

Magnetic resonance cholangiopancreatography revealed mid and distal bile duct lesion with shouldering present along with dilatation of intrahepatic biliary radicals. In view of typical features of cholangiocarcinoma and portal vein involvement of less than 180 degrees, a surgical resection was opted as the surgical treatment of choice. A Whipple’s pancreaticoduodenectomy was performed and intraoperative findings of a hard mass involving the distal bile duct and head of pancreas was observed. The entire pancreas was firm to hard in consistency with changes of chronic pancreatitis. The portal vein was dissected without the need for portal vein resection. No distant metastasis was observed. The mass after resection, along with the samples, was sent for histopathological examination. The grey white, diffusely infiltrating solid mass on H&E stained sections revealed an ill-defined lesion composed of fascicles of spindle-shaped cells along with lymphocytes, plasma cells and occasional eosinophils (figure 5A–C). The lesion locally infiltrated the surrounding adipose tissue and lymph nodes. No evidence of carcinoma was seen while the surrounding pancreatic parenchyma showed areas of mild fibrosis and periductular lymphoplasmacytic infiltrate.

Figure 5.

H&E staining of tumour sections showing spindle cells in ulcer floor(A), fascicles of spindle-shaped cells with inflammatory cells (B), fascicles of spindle-shaped cells with plasma cells, lymphocytes and eosinophils (C).

Immunohistochemical staining panel showed the spindle cells to be positive for anti-human smooth muscle actin, calponin and desmin (focal positivity) while negative for ALK-1. Histopathological features suggested a diagnosis of IMT of the pancreas invading the common bile duct with aortocaval, portal and common hepatic artery lymph node involvement.

Outcomes and follow-up

During the postoperative period, the patient was shifted to the ward on POD1 and was started on with oral clear fluids. A soft diet was initiated on POD2 followed by drain removal on POD3 and discharge on POD6. An FJ (feeding jejunostomy) was started on POD1 but was stopped on discharge as it was not considered necessary.

Discussion

IMT is a rare, uncommon lesion whose cause is not yet known. It is inclusive of a spectrum of myofibroblast cell proliferative mass admixed with varying amount of inflammatory infiltrate such as plasma cells, lymphocytes and eosinophils. The current WHO classification for this rare tumour entity is a fibroblastic sarcoma or myofibroblastomas.¹ It was named as IMT by Umiker and Iverson because it mimics a malignant neoplasm clinically, radiologically and histopathologically.² Various pathogenetic backgrounds have been proposed as initiating factors such as reactive, infections, autoimmune and neoplastic processes, but the aetiology of most remains unknown. Recently, the concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and cytogenetic evidence of acquired clonal chromosomal abnormalities.⁵

Rearrangement of the ALK-1 locus on chromosome 2p23, which codes for a tyrosine kinase receptor member of the insulin growth factor receptor superfamily is the key genetic alteration associated with IMT. The average patient age for ALK-1-positive cases was 14.8 years, whereas the average age for ALK-negative cases was 37.9 years.⁶ This indicates that there might be a variation in the genetic basis for different age groups. ALK-1 rearrangements result in constitutive expression and activation of this gene with abnormal phosphorylation of cellular substrates. The majority of ALK-1 negative cases are associated with EBV(Ebstein Barr Virus), whereas in both of our reported cases, the tumour lacked both ALK-1 rearrangement and was EBV negative.

The clinical presentation of IMT varies depending on its anatomic location and whether it involves vital organs. For patients with IMT with GI involvement, it is often inconclusive, since patients may generally present with non-specific symptoms such as abdominal pain, weight loss and jaundice. In rare cases, IMT may present with anaemia, fatigue, sudden diabetes or a palpable mass.

The most common site is pulmonary in origin. The extrapulmonary locations of IMTs are in the orbit (eye socket), peritoneum (lining of the abdominal cavity and internal organs) and mesentery. However, they are also extremely rarely found in the head region. Among IMTs occurring in the GIT, duodenal and pancreatic IMTs are rare. The duodenum is among the rarest sites of IMTs to occur.⁴

As listed in table 1, among the 13 reported cases of IMTs involving the duodenum, the most common site involved was the second part of the duodenum (n=4) and only two rare cases of multiple site involvement. In our case 1, we report the involvement of the duodenum segments 1 through 3 along with the head of the pancreas which has not been reported before. The preferred procedure performed among the reported cases was a Whipple procedure (n=7), while only a few cases performed an en bloc wide local excision, indicating the most preferred procedure to opt in such further situations would be a Whipple’s pancreaticoduodenectomy.

Table 1.

Comparison of IMTs affecting various duodenal segments and its interventional associations

Authors (published year)	Sex	Symptoms	Involvement (Site)	Treatment	Recurrence
Stringer et al (1992)12	5/F	Vomiting	Second	Whipple operation	None
Mattei et al (2008)13	13/M	Asymptomatic	First, second	NSAIDS (ketorolac) Laparotomy (tumour mass regression)—Roux-en-Y gastrojejunostomy	None
Wynn et al (2008)14	16/M	Epigastric pain	First	En bloc excision with primary closure of the duodenum	Recurrence
Kim et al (2009)15	10/M	Abdominal pain	Multiple	Open biopsy	–
Kwak et al (2010)16	65/F	Epigastric pain	Ampulla of Vater	Endoscopic papillectomy	None
Mirshemirani et al (2011)17	13/M	Weight loss	First	Resection	–
Fong et al (2012)18	57/F	Obstruction	Second, third	Whipple operation	None
Xiang et al (2012)19	20/M	Epigastric pain	Multiple	Whipple operation	None
Petrovic et al (2016)20	58/M	Epigastric pain	Fourth	Resection of duodenojejunal flexure with termino-terminal anastomosis	None
Sinha et al (2017)21	36/F	Abdominal bloating	Multiple	Whipple operation	–
Sang Park et al (2018)22	49/M	Asymptomatic	Second	Whipple operation	None
Current study (2019–2020)—Report 1	54/M	Obstruction and weight loss	First, second and third+head of pancreas	Whipple operation	None

IMTs, inflammatory myofibroblastic tumours; NSAIDS, Non Steroidal Anti Inflammatory Drugs.

While IMTs present along the biliary tract are rare, only six cases have been reported solely involving the distal biliary segments as per acquired knowledge. As cited in table 2, among the six reported cases, only one of them had an involvement of the head of the pancreas as well. We report the other such case as per our knowledge. The preferred surgery of choice in all of them is resection with the Whipple’s procedure, while one case reported a debulking procedure was done for tumour removal.⁷

Table 2.

Comparison of IMTs of the distal biliary tract and its interventional associations

Authors	Age at presentation and symptoms	Location	Therapy	Follow-up
Haith et al (1964)23	6/M, vomiting, diarrhoea, fever and obstructive jaundice	Distal common bile duct	Surgical resection	5 months, no recurrence
Fukushima et al (1997)24	58/F, obstructive jaundice	Mid and distal common bile duct	Surgical resection with Whipple’s procedure	–
Sobesky et al (2003)25	51/F	Distal common bile duct	Surgical resection with Whipple’s procedure	No recurrence
Lopez-Tomassetti Fernandez et al (2006)26	55/F	Distal common bile duct and pancreas	Surgical resection with Whipple’s procedure	Recurrence after 4 years
Abu-Wasel et al (2012)27	55/M	Distal common bile duct	Surgical excision	No recurrence
D’Cunha et al (2016)7	12/F	Distal common bile duct	Debulking procedure	No recurrence
Current study—Report 2 (2020)	54/M, pain abdomen and jaundice	Distal common bile duct and pancreas head	Surgical resection with Whipple’s procedure	No recurrence

IMTs, inflammatory myofibroblastic tumours.

Workup

The primary modes of investigation are CT, MRI and PET scan imaging studies, the results of which are mainly non-specific usually masquerading the findings of malignancies. Due to its non-specific symptoms and imaging findings, definitive diagnosis of IMT relies on histological evaluations of biopsies which can be obtained by endoscopic or USG-guided endoscopic means. The findings initially are highly variable and non-specific. Biopsy studies using IHC(Immunohistochemistry) markers are usually used to establish a probable histological diagnosis. A good biopsy specimen would help to establish a preoperative diagnosis. In the present cases, gastroscopic biopsies of the lesion were inconclusive, and surgical resection of the tissues aided to obtain the final diagnosis of IMT.

Treatment and prognosis

Currently, due to the difficulty of obtaining a definitive diagnosis based on biopsies and radiological examinations, surgery with complete excision remains the primary therapeutic option for IMT, although no guidelines regarding the treatment of IMT exists. The current risk of malignant transformation or metastasis that has been described in previous cases of IMT indicate it to be <5%, but if the excision is incomplete, the risk increases up to 25%.⁸ Since there is a possibility of malignancy and relapse, a number of authors have reported that a simple tumour excision to be uncertain and wide excision may be appropriate if the patient’s physical condition is satisfactory. For non-excisable lesions even though several medical treatments, including chemotherapy, radiation therapy, corticosteroids and antitumour necrosis factor-binding antibodies, non-steroidal anti-inflammatory drugs, have been previously administered to shrink or palliate these IMTs to a resectable size and configuration, the medical treatment modality is not clearly defined due to a lack of strong clinical trial-based evidence.⁹ Due to this, palliative treatment programmes cannot be recommended as a standard regimen. Based on the recent advances in ALK inhibitors and ALK target gene discoveries, these therapies might prove to be the most effective way and thus could be offered to patients with IMT in the forthcoming future. Whether surgical resection or medical-drug therapy is the selected treatment, the prognosis of the disease has been considered as favourable, with distant metastases occurring rarely. The current 5-year survival rate of IMTs is 91% according to the study conducted by Gleason and Hornick.¹⁰ Along with the above mentioned, a close and long-term follow-up is necessary due to the probability of malignancy, distant metastasis and recurrence potential exhibited by IMTs.¹¹

Learning points.

• This is a case of a rare tumour where the preoperative diagnosis is difficult and hence must be considered for radical surgical procedures such as the Whipple procedure similar to any other malignant mass.

• It is valuable to know the rarity of this tumour as it is sporadically seen over the years and it is vital to add to the differentials of various other tumours commonly arising in these locations.

• A close and long-term follow-up is necessary due to the probability of malignancy, distant metastasis and recurrence potential exhibited by IMTs.