Summary of Langerhans cell histiocytosis
LCH includes three syndromes: eosinophilic granuloma in bone, Hand - Schüller - Christian disease and Letterer - Siwe disease. According to the degree of clinical damage, LCH can be divided into a localized type and an extensive type. Among the three syndrome types, bone eosinophilic granuloma is a localized type, Hand-Schüller-Christian disease progresses slowly and is likely an extensive type, and Letterer-Siwe disease progresses quickly and urgently, which likely makes it an extensive type with a poor prognosis . LCH can involve multi-organ and multisystem. Lung and bone were the more frequent involved regions. For the single bone destruction, can be simple surgical curettage. In case of the recurrence patient may require systemic chemotherapy. According to patient’s concrete condition, arrange periodic reviews from 6 weeks to one year. In our group, all 23 cases underwent surgical resection, and postoperative chemotherapy was given subsequently, most of the cases have a good prognosis up to now.
The clinical manifestations of LCH with orbital involvement
LCH is a rare disease with an incidence of 0.2-2.0 cases per 100,000 children under 15 years of age in the worldwide , and it has a high incidence 23%-37.5% of orbital involvement [15,16]. In our study, the average age was 6.3 years, including 20 patients (86.9%) under the age of five, and 2 cases occurred in adults who were 21 years old and one patient was 14 years old. There were 18 male patients (78.3%). The results demonstrated that LCH are more common in pre-adolescent males, that is the same with the previous literature . From patients recognizing the symptoms to the diagnosis, the course of disease were shorter, there were 15 cases that lasted less than one month and 5 cases that lasted approximately two months. The most common clinical manifestations included eyelid swelling and exophthalmos. Majority patients had swollen eyelids (fig.6), including 14 cases accompanied with pain and fever and 6 cases with poor treatment effects after a mistaken diagnosis of an inflammatory pseudotumor, this led us to the conclusion that the clinical manifestations of orbital LCH were almost similar to the inflammatory pseudotumor, and it is apt to be misdiagnosed. In our research group, patients also had some relatively rare symptom: ptosis, fluctuations in the affected part, tearing, decreased vision, dizziness, and nausea clinical symptoms which have not been mentioned in previous studies [3,18, 19]. There was one child appeared lump after trauma, a previous literature reported that trauma might be a factor that can trigger an immune response, and predisposed children may subsequently develop LCH . Three patients were diagnosed with eosinophilic granuloma of the bone, and one case presented "bone destruction-exophthalmos-diabetes insipidus" syndrome, which is the trigeminy sickness of the Hand-Schüller-Christian disease. Regrettably, due to a lack of body multi-system check data, we could not determine the exact type of the remaining cases.
Magnetic resonance imaging findings of orbital LCH
MRI has a high resolution of soft tissue, and can clearly show the skull bone destruction, soft tissue mass, dural thickening and other morphological changes of LCH lesion in orbit, but the MRI signal of LCH lesions changes in a large range, the MRI features reported in the literature are not consistent [21, 22, 24]. In fact, according to the results of our study, we found that the MRI manifestation of orbital LCH possess certain characteristics actually. In our group, 17 lesions located in the superior or superlateral orbital roof that accounted for 74% of the total cases. So we know that orbital LCH mainly occurs in the superior or superlateral wall of orbit. It should be noted that the lesions locations were superficial. We found that mostly lesions of orbital LCH presented as a mass or triangular, the triangular lesions were similar in shape to the bone section of the site, and 3 cases showed bone thickening. From this representation, we speculate that the shape of the first-stage lesion is the same as the original bone form, and then it further progressed to a lump shape. In our group, most lesion boundaries were not clear except for 3 cases, and those 3 cases were diagnosed as bone eosinophilic granuloma by pathology, the characteristics was consistent with the findings of previous study . The boundaries of other types of LCH lesions are often unclear.
Based on our MRI observations, most lesions appeared isointensity and iso-hypointensity on T1WI. On T2WI, the lesions mostly exhibited hyper-hypointense mixed signals. Most lesions presented heterogeneous signal, some studies considered that heterogeneous signals are related to different pathological stages or the lipid content of lesions [26,27]. Histological observations of pathological material revealed, we found that lesions containing many red blood cells, where presented patchy hyperintense signals on T1WI and conformed to a focal hemorrhage. Another feature is that the area near the edge of lesions usually had capsule hyperintense signals on T2WI and which were not enhanced, these areas correlated with the necrosis area of lesions shown by a microscope (Fig.4, 5). Post enhancements revealed that lesions mostly showed significantly heterogeneous enhancement signals, and we found a key characteristic that the edges of the lesion and surrounding tissue presented significant enhancement, which was more obvious than the central of the lesion. We suggest that this characteristics performance may help in the diagnosis of orbital LCH. Besides, A few lesions were surrounded by a low signal ring on the pre-enhanced and post-enhanced imaging, which did not been reported before, and determining its diagnostic value requires further observation.
Believed through ours research on the MRI feature of the orbital LCH, lesions of LCH were pone to occur at the superior and superlateral wall of orbit, and the locations were superficial that near the surface (fig.7). The shape of lesion like lump or triangular with fuzzy boundaries. It presented isointensity and iso-hypointensity on T1WI and hyper-hypointense mixed signals on T2WI, pone to hemorrhage and necrosis in lesions. It need to be emphasized that the edges of the lesion and surrounding tissue presented more significant enhancement, it concluded that LCH lesions affected the surrounding soft tissue. Base on above MRI characteristics performance, it can improve the diagnostic accuracy of the orbital LCH for radiologists. These specific MRI manifestations have not been previously reported.
The differential diagnosis of orbital LCH
The diagnosis and differential diagnosis of LCH is mainly based on clinical manifestation, imaging and pathological examinations, and imaging examination especially plays an important role in the diagnosis of the disease, but the final diagnosis is still requires histopathology for confirmation. The histopathological features of LCH include the proliferation of large number of Langerhans cells with eosinophils and neutrophils, lymphocytes and a small amount of plasma cell infiltration. The IHC staining shows positive signals for S – 100， CD 68 and CD1a (fig.4,5). "Birbeck granules" can be found under the electron microscope, which is the gold standard for diagnosing LCH. But electron microscope may not be widely available for clinical purposes, the MRI and bioptate IHC findings are most available methods for LCH diagnostics. This signifies the importance of the MRI manifestations as MRI is widely available in clinical practice and that is a non-invasive method of diagnostic.
The main differential diagnoses for orbital LCH include leiomyosarcoma, metastases, chloroma, orbital inflammatory pseudotumor, epidermoid or dermoid cysts, multiple myeloma, et al. (1) Leiomyosarcoma: this tumor is also a common orbital malignancy in teenagers, progresses very quickly, often occurs at the outer upper quadrant of the extraconal orbital compartment, the location of lesions often deeper than the LCH. On MRI, the lesion mostly show low signal on T1WI, high signal on T2WI, and have homogenous and heterogeneous enhancement. It should be pointed out that the lesion is rarely hemorrhage, the edges of the lesion and surrounding tissue are not enhanced, that can be used to differentiated from the orbital LCH. And the lesion often has a little bone destruction. (2) Metastatic tumors: metastases in teenagers often come from neuroblastoma, most neuroblastomas occur in the retroperitoneal and adrenal areas. Patients demonstrate symptoms outside the orbital region, consistent with primary tumor localization, along with typical malignancy associated general symptoms. The lesion progresses fast, most patients had invasive bone destruction ，that is different from the bone defect of LCH. Presence of the primary tumor is the main finding in the differential diagnostic of the condition . (3) Chloroma: Leukemia cells infiltrating the orbital bone and soft tissue. The lesion show low signal on T1WI, slight-high signal on T2WI, and have a significantly homogenous enhancement, the MRI features are different from the LCH. The general condition of leukemia patients is poor, and systemic examination can ultimately diagnose leukemia . (4) Epidermoid or dermoid cysts are more common in middle-aged individuals, have a slow onset, and present pressure changes in bone. MRI signals of lesions change and present capsule wall enhancement as well as internal structures without enhancement. (5) Myeloma is more common in middle-old aged individuals; lesion show low signal on T1WI, high signal on T2WI, and have a a significantly homogenous enhancement, and present oval bone destruction on X-ray approximately 50% to 70% of the patients are positive for Bence-Jones protein.
The limitation of the current study is that only some patients from the study group had data available for diffusion-weighted magnetic resonance imaging (DWI) and dynamic enhanced scanning; these results were not included in the current study. However, from the partial datasets available (data not shown), it appears DWI, and dynamic enhanced scanning doesn't have the characteristic that can be helpful for LCH diagnosis.