IMTs are mesenchymal neoplasm of intermediate biological potential with a predilection for the lung, abdomen, and pelvis of children and young adults [3]. Metastasis is a rare event in IMTs. Currently IMT is regarded as an intermediate, locally recurrent, rarely metastasizing neoplasm[4, 5].
IMTs are extremely rare in eyes, and most reported to be seen in the orbit. Intraocular IMTs appear to arise from uveal tissues and are associated with uveitis[6]. Common presentations include proptosis, ptosis, and painless loss of vision[7]. Dermarkarian et al [8]considered that these tumors were prone to invasively grow and be recurrence, so they recommended the complete removal as the first choice of treatment for this kind of tumor if possible. Usually, the diagnosis of IMTs may be delayed owing to nonspecific presenting symptoms[9]. Definitive diagnosis of IMTs relies on histopathologic examination with immunohistochemical characterization. The histopathology of IMTs are the variated product of erratic proportions of acute and chronic inflammation and fibrosis[10]. The principal components were plasma cells and spindle-shaped cells. Plasma cells were scattered throughout the lesions, often in small clusters, and predominated at the periphery. They were mature and occasionally large and multinucleated[2]. IMTs demonstrated positivity for vimentin (99%) and desmin (69%)[1]. Myofibroblasts express intermediate filaments and contain the phenotype VD, represented by cells positive for vimentin and desmin[11]. ALK expression has been documented in IMT cases[12]. The tumor has no positive response to myoglobin,cytokeratin, KP-1, CD30, and estrogen receptor[13]. This tumor can be difficult to distinguish from spindle cell tumors. The main differential diagnosis in the eye are leiomyomas and anaplastic large cell lymphomas.
Leiomyomas are rare benign tumors and commonly found in the uterus and alimentary tract[14].Light microscopically, the tumors are typically composed of interlacing bundles of spindle cells with blunt-ended oval nuclei, moderate amounts of eosinophilic fibrillation cytoplasm, and intracellular myoglial fibrils[15]. Leiomyomas are most consistently reactive to SMA and uniformly negative for staining with ALK, S-100, and HMB-45 [16]. The tumor in our patient occurred in the ciliary body, and spindle-shaped cells were seen in H&E staining. But immunohistochemistry showed negative for staining with SMA and ALK. And this patient has chronic inflammatory cell infiltration, therefore, the diagnosis of leiomyoma is not considered.
ALK positive is not a specific manifestation of IMT. Some aspects of the ALK activation mechanism in IMT are also seen in some anaplastic large cell lymphomas(ALCLs)[1]. Light microscopically, the ALCLs are typically composed of interwoven fascicles of histiocytes and myofibroblasts mixed with chronic inflammatory cells, mostly T lymphocytes[17]. The tumor in our patient does not conform to ALCL because of the large proportion of collagenized fibrous tissue, and smooth muscle-like cells. This patient's immunohistochemical examination ki-67 (2%), cell proliferation is not active, so it is not considered as ALCL. And the primary intraocular lymphomas are mostly large B-cell lymphomas, a few are T-cell sources[18].
In our case, other possible tumors were excluded. Combined with the HE staining and immunohistochemistry results of the above patients, the diagnosis of primary intraocular inflammatory myofibroblastic tumor with ALK overexpression was considered.
However, there were several differences between this case and other typical cases of IMT reported in the past. In previous studies, IMTs demonstrated positivity for SMA (92%), because the most common phenotype of intermediate filaments expressed by myofibroblasts is phenotype VA: represented by cells positive for vimentin and [alpha]-smooth muscle actin, but there are also reports of phenotype VD[11]. This patient is in line with phenotype VD. ALK expression has been documented in 35%-60% of IMT cases[12]. ALK markers are mainly expressed as light to moderate cytoplasmic staining. In addition to the classic IMT, the literature also reported the existence of special epithelioid subtypes[19, 20]. There are few reports of intraocular IMT, so it is speculated that there may be other subtypes of IMT, and ALK stains in the nucleus.
In conclusion, we reported a rare case of intraocular IMT, which is confirmed by H&E staining, and IHC positive staining for Vimentin, Desmin and ALK, while negative staining for SMA, S-100, ki-67, CK, CD68, and calponin. As far as we know, this case of IMT is the first report of an intraocular IMT of ciliary body.