Intra-abdominal infantile inflammatory myofibroblastic tumors: A report of three cases.

Inflammatory myofibroblastic tumor occurring at intra-abdominal sites in children can be confused with malignancy because of its large size and location. It is a tumor classified as 'intermediate' between benign and malignant, but usually benign, with a strong tendency for recurrence. Treatment is surgical excision. Here, we present a brief outline of three such cases presenting as abdominal mass in infants.

INTRODUCTION

Inflammatory myofibroblastic tumor (IMT) occurring at intra-abdominal sites in children is a rare entity, which, because of its large size and location, may often be confused with malignancy.[1] It is usually a benign tumor, with a strong tendency for recurrence. The treatment of IMT is primarily surgical excision and re-excision of recurrent lesions.

As these tumors are rare, correct diagnosis is important in order to avoid unnecessary wide surgical removal and aggressive chemotherapeutic regimens.

We present here a brief outline of three such cases of IMT presenting as abdominal mass in infants.

CASE REPORTS

Case 1

The patient, a 5-month-old girl, weighing 6.9 kg, presented with a slow-growing abdominal mass, noted for one and half months. Ultrasonography revealed a heterogenous echogenicity of the mass. Blood examination showed microcytic, hypochromic anemia with hemoglobin 9 g%. On exploration, a mass of size approximately 8 × 5 cm, attached to the mesenteric border of the ileum, 25 cm from the ileo-cecal junction was noted. About 6 cm of the length of ileum was straddling the mass. It was resected with end-to-end anastomosis [Figure 1].

Figure 1

Mass attached with the mesenteric border of the ileum

On gross examination, the mass was firm and grey-white in color.

On light microscopic examination, the tumor was made up of loosely arranged spindle-shaped cells separated by abundant myxoid stroma sprinkled with inflammatory cells comprising mainly lymphocytes and plasma cells. Several thin-walled blood vessels were noted [Figure 2a,b]. Any evidence of mitosis, necrosis, and pleomorphism was absent. On immunohistochemistry, the tumor expressed desmin, vimentin, and smooth muscle actin; moreover, it was negative for anaplastic lymphoma kinase (ALK) [Figure 3]. The overall features were similar to those of IMT.

Figure 2

[H and E, ×100] Micro section shows part of the ileum and a mass composed of spindle-shaped cells; Inset: [H and E, ×100] Micro section shows spindle-shaped cells in the edematous stroma sprinkled with inflammatory cells

Figure 3

(×100) Immunohistochemistry of the tumor showing positivity for smooth muscle actin, vimentin, and desmin and negativity for ALK-1

Case 2

A 7-month-old girl presented with fever, weight loss, and abdominal mass. Her medical history was not significant. Computed tomography (CT) of the abdomen revealed a lobulated mass in the jejunum. She had anemia (Hb 8.5/dl), leukocytosis (18,500/mm3), mild thrombocytosis (5 lakh/mm3), and raised ESR (85 mm in the first hour). The patient underwent laparotomy and the mass was excised. Grossly, the mass was multinodular. The cut-section was rubbery, firm, and tan-yellow in color. Histologically, spindle cells were arranged in sweeping fascicles. The stroma was edematous and replete with prominent delicate vasculature. Inflammatory cell infiltration, mainly lymphocytes and plasma cells, were conspicuous. However, mitosis was lacking. A diagnosis of IMT was made.

Case 3

A one-year-old boy presented with a failure to thrive and recurrent intestinal obstruction. He had anemia (Hb 6.5 g/dl) and multiple lumps in the abdomen. On opening, large masses in the mesentery were found, stretching across 20 cm of the length of ileum and compromising the lumen at many places. The masses were excised along with the adjoining gut, with the restoration of gut continuity where required. Sections through the tumors were similar. They all comprised bland-looking spindle cells and mononuclear inflammatory cells. Mitotic activity was negligible. Histology confirmed IMT.

DISCUSSION

Inflammatory myofibroblastic tumor is a rare entity found in various sites and across all age groups. It is known by many names such as pseudosarcoma, atypical myofibroblastic tumor, atypical fibromyxoid tumor, and plasma cell granuloma. The sex ratio is 3:4, which is in favor of males.[2]

Lung is the most common site for the tumor.[3] However, among the extrapulmonary sites, similar tumors have been reported in multiple locations including the skin, orbit, gingiva, breast, thyroid, thymus, spleen, lymph nodes, tonsil, liver, gall bladder, pancreas, kidney, renal pelvis, urinary bladder, adrenal gland, uterus, ovary, brain, spinal cord, mesentery, appendix, and gastro-intestinal tract.[4] Intra-abdominal site is the most common extrapulmonary location.

The long list of differential diagnosis of intra-abdominal spindle cell lesions closely mimicking IMT include gastro-intestinal stromal tumor, fibromatosis, retroperitoneal fibrosis, solitary fibrous tumor, leiomyosarcoma, and malignant peripheral nerve sheath tumor. In adult women, the endometrial stromal sarcoma needs to be considered.[5]

Most patients present with fever, anemia, thrombocytosis, and hyperglobulinemia and weight loss.[6] All three of our patients came with anemia and the signs and symptoms of recurrent intestinal obstruction with failure to thrive.

Microscopically, the tumors are composed of an admixture of proliferating spindle cells and chronic inflammatory cells in a variably vascular stroma that ranges from being loosely myxoid to densely collagenous. The spindle cells have elongated pale staining vesicular nuclei and inclusion like nucleoli. Mitosis is generally rare. These spindle cells were eventually recognized as myofibroblasts, and the tumor was renamed IMT.[27]

Immunohistochemical staining further supports the myofibroblastic nature of the spindle cells, with a positivity of smooth muscle actin and vimentin. Anaplastic lymphoma kinase is positive in 50% of the cases of IMT. ALK-positive cases have a better outcome than ALK-negative cases. ALK positivity is related to clonal abnormalities involving the ALK gene located on 2p23, which encodes a tyrosine kinase receptor.[8] Ultrastructural studies of the spindle cells show features that are common to both smooth muscle cells and fibroblasts.[26]

There is a gradual transition in the concept of IMT. Although many of the previously reported pseudotumors of various organs pursued a benign clinical course, some lesions, particularly in the mesentery, retroperitoneum, and peritoneal surface of the abdominal cavity, show a remarkable propensity for recurrence and metastasis. It seems wise to interpret these lesions as more closely related to inflammatory fibrosarcoma than merely accepting them as a post-inflammatory process. The recent WHO classification of soft tissue tumors places them in the category of fibroblastic/myofibro-blastic tumors-Intermediate (rarely metastasizing). The involvement of ALK gene and cytogenetic clonality also support the neoplastic nature of IMT. Further studies are essential to decide whether IMT and inflammatory fibrosarcoma are closely related entities or not.[247]

Designating these lesions as ‘sarcoma’ does not necessarily mandate radical treatment. Complete excision and close clinical follow-up are recommended. About 18-44% of these are known to recur.[8] Very rarely fibrosarcomatous change occurs.

All of our cases are doing well on follow-up. Accurate diagnosis of this rare tumor is important in the pediatric age group to avoid unnecessary aggressive treatment.