A 59‐Year‐Old Woman with a Retroauricular Tumor

Clinical History

A 59‐year‐old woman presented with an 8‐year history of generalized malaise, neck and arm pain and hearing impairment. Six months prior to admission she developed night sweats and a 4 kg weight loss. These symptoms progressed to include headaches, gait instability and the appearance of a painful retroauricular mass. Laboratory analysis showed the following results: haemoglobin, 12.7 g/dl; mean corpuscular volume (MCV), 78.7 fl; thrombocytes count, 483 × 10³/μl; white blood cell count, 15.84 × 10³/μl; neutrophiles count 13.46 × 10³/μl; lymphocytes count, 1.34 × 10³/μl; 4.8% microcytic erythroblasts; sodium, 131 nmol/L. Cranial computed tomography (CT) revealed an osteolytic mass lesion measuring 5 cm in diameter that, extended from the right mastoid to the medial and posterior cerebral fossae. On cranial magnetic resonance imaging (MRI, Figure 1a) the 6.8 × 5.3 × 4.8 cm, poorly circumscribed, extra‐axial mass with progressive perifocal edema was noted to extend into the cerebellum, with compression of the IV ventricle and the brainstem. On T1‐weighted images, the lesion appeared iso‐ to hypointense, with solitary intratumoral vessels and haemorrhagic components. T2‐weighted images of the mass showed low‐signal intensity with inhomogeneous contrast‐enhancement. The preoperative differential diagnosis included osteosarcoma, hemangiopericytoma, and metastatic disease. Preoperative fine needle aspiration biopsy (FNA) of the extracranial retroauricular mass was performed. Thorax/abdomen CT performed as part of a metastatic workup did not reveal evidence of other mass lesions. The patient underwent complete surgical resection of the lesion following embolisation.

Figure 1.

 

Gross and Microscopic Pathology

Grossly, the mass was firm and hemorrhagic, measuring 5.0 × 4.5 × 1.5 cm. Microscopic examination revealed several patterns (Figure 1b) including areas dominated by widely‐scattered, plump, ganglion‐like cells with prominent nucleoli embedded in a dense, hyalinized matrix (Figures 1c and 2a). In other regions, the matrix was loose and contained slender spindle cells. Multifocal collections of chronic inflammatory cells, especially plasma cells, were present (Figures 1c and 2b). Additionally, there was evidence of recent and old hemorrhage. Occasional mitotic figures, including atypical forms, and necrosis were identified. The ganglion‐like cells stained strongly and diffusely for smooth muscle actin (Figure 2c) with occasional cells labeling with desmin (Figure 2d). Immunostaining was negative for anaplastic lymphoma kinase‐1 (ALK‐1), myo‐D1, myogenin, cytokeratin, EMA, S‐100, and panMela. Fluorescence in situ hybridization (FISH) performed on the direct smears of the FNA did not reveal rearrangement of the ALK‐1 gene. Latent membrane protein‐1 (LMP‐1) and ISH for Epstein‐Barr encoded RNAs (EBER) showed no association with an EBV‐infection. What is the diagnosis?

Figure 2.

 

Diagnosis

Inflammatory myofibroblastic tumor.

Discussion

Inflammatory myofibroblastic tumor (IMT) is a histologically distinctive lesion that occurs primarily in the viscera and soft tissue of children and young adults, and usually pursues a benign clinical course 2. Although original descriptions of this entity were mostly in the lung, IMT has been described in virtually every anatomic location. In the past, IMT has been classified under many designations, including plasma cell granuloma, plasma cell pseudotumor, inflammatory myofibrohistiocytic proliferation, omental‐mesenteric myxoid hamartoma and, most commonly, inflammatory pseudotumor. In the 2002 World Health Organization classification of soft tissue tumors, this heterogeneous group of lesions were renamed “IMTs” 3. The etiology of IMT remains unknown 2.

Presenting symptoms depend on the site of primary tumor involvement. Some patients have prominent systemic manifestations, including fever, night sweats, weight loss and malaise 7.

Histopathologically, IMT is essentially a diagnosis of exclusion. The differential diagnosis includes mainly low‐grade myofibroblastic sarcoma (LGMS) and other benign or malignant spindle‐cell tumors such as leiomyoma, solitary fibrous tumor, spindle‐cell carcinoma, nodular fasciitis, desmoids, infantile myofibromatosis, and peripheral nerve‐sheath tumor 4.

A variety of histologic patterns are recognized, sometimes even in the same tumor. Some tumors are composed predominantly of cytologically bland spindle‐ or stellate‐shaped cells loosely arranged in a myxoid or hyaline stroma with scattered inflammatory cells, somewhat resembling nodular fasciitis. Other tumors are composed of a compact proliferation of spindle‐shaped cells arranged in a storiform or fascicular growth pattern. Mitotic figures are variable. These foci are usually associated with prominent lymphoplasmacytic infiltrates, occasionally with the formation of germinal centers. Other foci may be sparsely cellular, with cytologically bland cells deposited in a sclerotic stroma resembling a scar. In some lesions, there is pronounced cytological atypia, with cells containing large nuclei and distinct nucleoli, which resemble ganglion cells 7.

Tumor cells stain strongly for calponin (100%), fibronectin (100%), and variably with myoid markers, including smooth muscle actin (95.8%), muscle‐specific actin (100%), desmin (33.3%) and laminin (81.8%) 6. Focal cytokeratin (13.6%) can be seen; however, CD34 and S‐100 protein are negative in all cases. As noted, some IMTs stain for ALK‐1 (40.9%). Remarkably, 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.

Rearrangement of the ALK‐1 locus on chromosome 2p23, which codes for a tyrosine kinase receptor member of the insulin growth factor receptor superfamily, has been documented in approximately 50% of cases and implicated in the pathogenesis of IMT 1. Of note, the majority of ALK‐1 negative cases are associated with EBV, whereas in our case, the tumor lacked both ALK‐1 rearrangement and was EBV negative.

The therapeutic approach for IMT encompasses surgery, steroid therapy, radio‐ and chemotherapy 4. In a recent retrospective study, the presence of positive surgical margins was the most significant independent predictor for local relapse. The progression‐free‐survival for 2 and 5 years was 72% and 65%, respectively 5. For a more complete discussion please go to http://path.upmc.edu/divisions/neuropath/bpath/cases/case258.html