ROS1-positive Inflammatory Myofibroblastic Tumor of the Small Bowel Causing Obstruction: A Case Report
ROS1-positive Inflammatory Myofibroblastic Tumor of the Small Bowel Causing Obstruction
A generally healthy 23 years old woman, with family history of colon cancer, presented to our emergency room (ER) with complaints of right lower quadrant abdominal pain and diarrhea. She underwent physical examination and abdominal ultrasound (US) that did not reveal any evidence of acute appendicitis. The blood tests have shown increased CRP of 53 mgL (normal 0.03-5 mgL) without leukocystosis. She was discharged with a diagnosis of gastroenteritis and antibiotic treatment. After 5 days the abdominal pain became constant and worse, so she returned to the ER. Physical examination revealed a generally distended abdomen, no obvious palpable masses and no signs of peritonitis. The blood tests showed increased CRP of 42.8 mgL, again without leukocytosis or any other abnormality. A gynecological US was performed and revealed a well-defined solid mass measuring 44 * 39 mm to the left of the uterus. The solid mass was heterogeneous with avid flow on Doppler images (figure 1). An abdominal computed tomography (CT) scan with parenteral and intravenous contrast materials was performed and confirmed the presence of a mass in the ileum causing small bowel obstruction (figure 2). There were no other acute findings in the abdominal or pelvic organs. Based on the CT findings, the patient underwent an urgent small bowel resection. On laparotomy, a large tumor with prominent vascularity was found to arise from the distal ileum. There was no evidence of metastasis. The mass was resected, along with involved sections of the small bowel, and a primary small bowel anastomosis was performed. There were no postoperative complications.
Figure 1: Gynecological Ultrasound 23-year-old female with IMT and small intestine obstruction. TECHNIQUE: Real time trans-vaginal ultrasound of tumor using 20 mHz linear probe. FINDINGS: Well-defined solid mass measuring 44 * 39 mm to the left of the uterus (A). The solid mass was heterogeneous with avid flow on Doppler images (B). Figure 2: Computer Tomography 23-year-old female with IMT and small bowel obstruction. TECHNIQUE: Abdominopelvic CT with administration of IV contrast material (100 ml Omnipaque 350) and oral contrast material (1500 ml diluted Telebrix), acquired on the portal phase with a 64 slice CT scanner, at 3 mm slice thickness, 120 kVp and 205 mAs. The images were acquired on the axial plane and coronal and sagittal reconstructions were created. FINDINGS: Complete small bowel obstruction caused by tumor. (A)CT scan shows the small bowel with marked distention (orange arrow) and (B)filled with fluid and air (blue arrow). (A)Totally collapsed bowel loops are seen after the transition zone (red arrow). (C)On axial slices well defined intraluminal encased solid mass (green arrow). Figure 3: Gross morphology 23-year-old female with IMT and small bowel obstruction. FINDINGS: Polypoid intestinal tumor, covered by intact and flattened mucosa with shallow ulcerations. Figure 4: Histological findings 23-year-old female with IMT and small bowel obstruction. TECHNIQUE: Formalin-fixed-paraffin-embedded Hematoxilin and Eosin (H&E) stained sections. FINDINGS: A: (H&E, 40x) The tumor shows bland spindle-cells (blue arrows) with admixed lymphocytes (red arrow). B: (H&E, 20x) The tumor may show delicate vasculature (blue arrow) and myxoid stroma. C: (H&E, 1x) The tumor show irregular infiltration of the muscular layer (arrow heads). Note the intact mucosal layer (bottom left). D: (H&E, 20x) The tumor shows fascicular architecture. Notice the background chronic inflammatory infiltrate (blue arrow). Figure 5: ROS1 Immunohistochemistry assay 23-year-old female with IMT and small bowel obstruction. TECHNIQUE: ROS1 (D4D6) monoclonal antibody, 1:250. FINDINGS: The IMT cells show positive intense cytoplasmic staining (brown).
*Etiologydemographics The first description of IMT was in 1937 as a lung tumor predominantly appearing in pediatric patients and young adults. The World Health Organization (WHO) classified the IMT as a fibroblastic/myofibroblastic neoplasm of intermediate biologic potential because of its potential for invasion of surrounding structures and development of local recurrence and distant metastases. There are several different names for IMT including: inflammatory pseudotumor, plasma cell granuloma, fibrous histiocytoma, solitary mast cell tumor, and fibroxanthoma. The factors responsible for the development of IMT are still not clearly established. IMT may represent an immunologic response to an infectious or noninfectious agent, or it may be a true tumor. Campylobacter jejuni, Epstein-Barr virus, and Escherichia coli have been associated with IMT. Also, trauma, steroid use, abdominal surgery, and genetic factors have been reported, but the pathogenesis of IMT remains unclear. *Clinical & imaging findings Presenting symptoms depend on the involved primary site. As mentioned before, the lung is the most commonly affected site, but extra-pulmonary IMTs may include the mesentery-omentum, upper respiratory tract, genitourinary tract, retroperitoneum, neck, spleen, brain, pancreas, liver, and the intestines. Patients with intra-abdominal IMTs most commonly present with intermittent abdominal pain due to the solid mass and abdominal distention, weight loss, malaise, anorexia, and vomiting. Rarely, the presentation may be complicated by an intussusception, acute abdomen mimicking acute appendicitis or intestinal obstruction as was the case in our patient. Laboratory abnormalities are present in a minority of the patients and include anemia; increased CRP, as in our patient; and sometimes thrombocytosis. Leukocytosis is rare. *Pathological examination The tumor was non-encapsulated and infiltrative (figure 3), showing alternating hypocellular areas with myxoid background and hypercellular fascicular areas with a collagenous background. The tumor cells were uniformly spindle, showing scant to moderate pale eosinophilic cytoplasm with a round to elongated bland nuclei and conspicuous nucleoli. Prominent lymphoplasmacytic infiltrate with minor polymorphonuclear cells component was also identified. Mitotic rate was low (4/10 HPF) and no tumor necrosis identified (figure 4). On immunohistochemistry, the tumor cells were negative for ALK, Keratins, c-kit, DOG1, STAT6, beta-catenin, S100, and Desmin, and showed immunoreactivity solely for Smooth-Muscle Actin, Vimentin, and ROS1 (figure 5). Molecular pathology studies had been performed by a targeted next-generation sequencing (NGS) based assay, for the detection of gene fusions from formalin-fixed paraffin-embedded (FFPE) tissues. A FN1-ROS1 fusion (chr2:216256355,chr6:117650609) was identified using the FusionPlex Sarcoma NGS Panel (Archer Dx, Boulder, CO.), based on a modified amplicon appro
Teaching point IMT is a solid tumor that can rarely present in a young adult as acute abdominal pain with bowel obstruction. A precise diagnosis should be based on histological findings, and complete surgical resection is necessary. Clinical and laboratory follow-up is mandatory due to increased risk of local recurrence.