 My name is Rachel Epstein. I am a visiting a fourth year med student from Chicago. I have the pleasure of working in Dr. Manless's lab. And I'm going to present a case of a rapidly progressive unilateral ptosis in a child. So the chief complaint is this is progressive swelling of the left eye and blurry vision for two to three weeks. This is a previously healthy 10 year old girl presenting as an emergent referral from an outside eye to the eye center. For progressive swelling around the left eye and blurry vision for two weeks. The patient had sustained minor trauma to the left side of the face. She had been hit with a snowball. Had some edema, erythema in the weeks that followed and failed to resolve. Was seen by an outside physician and at that point he decided to get some scans as the presentation was suggested for some kind of mass. So when she was sent here on exam she denied any pain or any headache but did report the onset of blurry vision. With the past medical history is full term delivery, C-section, normal growth and development, no other past medical history. Family history of cancer in the maternal grandmother as well as the maternal aunt and glaucoma in a paternal grandfather. No meds and no allergies. No known drug allergies just seasonal. On examination the initial visual acuity uncorrected right eye is 2040 pinholing to 2025 and then in the left eye was 2400 pinholing to 2025. The functional exam there was an APD with 0.3 to 0.6 long units. Extracellular movement was restricted on left bladder of the gaze to about a 9 to 2. The confrontational visual fields were grossly full and then there was just a difference of 2 millimeters between the two eyes with the hurdle. I'll talk about the examiner examinations with the normal limits bilaterally and then there was a slight 1 plus discadema on the left eye with a little blurring at the nasal margin. So this is just a picture of her external exam you can kind of see. So you can just see kind of this violations appearing of subcutaneous mass with sort of mass effect on the globe. And then in the next picture we can see that it's actually also quite prevalent along the zygomatic bone and the cheekbone as well. As far as imaging she did come in with some imaging so we're going to take a quick look at that. This is a CT orbit without contrast and axial view. You can see kind of where the arrow is that there is a large, homogenous mass, relatively isodense to the f-jocular muscles along the left lateral orbital wall. And then also kind of coursing around the zygomatic bone here. You can see this better on the next scan. This is again a CT without contrast to coronal view. You can actually see here that there is actually kind of a cortical interruption and non-displaced fracture of the zygomatic bone. And then the mass is seen at this aspect as well without extension into the maxillary sinus. This is a post-genolinium axial T1-readed MRI. And we can see this homogeneously enhancing contralesion that is also coursing around extra-orbitally. And again just another view of the coronal shot. You can see this kind of homogeneously enhancing mass lesion. So at this point differential diagnosis, and this is not in any particular order of likelihood, it's just good for your... Just in terms of neoplasm, we can think both benign and malignant. Rhabdomyrocylcoma is obviously a big consideration here. You know, unilateral proptosis, painless. She's a good age for it. And then there's that homogenous lesion that we see on the imaging. Dermaitis, you know, obviously it would be more of an... Usually it would be more of an insidious presentation, but she did have a little trauma, could represent a rupture. Dermaitis, we would probably see more of a heterotonous pattern on the imaging with that. Metastatic neuroblastoma, you know, generally in a younger child, but still a consideration here. And then not necessarily for kids lymphoma, as that would be more endemic to Africa, but more of we could also consider lymphoma in our differential here. As far as vascular, looking at capillary hemangioma, again probably a younger patient also would appear probably differently on the imaging. And then the lymphangioma might appear more heterogenous or hemorrhagic in nature on imaging. In terms of inflammatory, we want to consider pseudo-tumor as there could be a similar presentation. It might be more painful, might not, but again with a biopsy that might be a better determination of distinguishing that from other. Just infectious, you know, common things happen commonly. So we want to obviously consider a cellulitis, might be more of a fever, leukocytosis associated with this, but still consideration. So we're going to take a quick look at the histopath that was obtained from a biopsy. This is a light micrograph H&E stain at about four times magnification. So it's just kind of taking a bigger look at the tumor itself. The tumor is quite cellular with these islands of tumor cells kind of growing between these large fibrobascular sub-day. Again in this area over here we can see that the tumor cells have actually started to infiltrate around this reactive bone. A higher mag H&E stain again, this is a better look at the cells of the tumor. We can see these kind of large tumor cells that are dark staining nuclei. They have a scant amount of cytoplasm and some of it is eosinophilic in nature. And then like we see right here we get these occasional very large pleomorphic cells. And then this cellular picture is kind of surrounded by this dense irregular connective tissue which is suggested of a fibroblastic reaction. Immunohistochemistry, we can see a positive stain for myogenin as well as Desmond. I'll get more into the specifics of that in a bit. Additional immunohistochemistry was negative for both CD45 and CD99, ruling out lymphoma as well as Ewing sarcoma. And then this is a positive stain for INI1 which is suggested that this is actually a malignancy. So in taking the imaging, the clinical history as well as the biopsy and the immunohistochemistry, this case is rabdomyro sarcoma. Rabdomyro sarcomas are malignant tumors that are derived from undifferentiated mesenchymal tissue. So they're primitive myoblasts. And they are the precursors to skeletal muscle and connective tissue. So the interesting thing about these tumors is that they actually, a large percent of them arise in areas that are normally lacking skeletal muscle, the bladder, prostate, vagina, bile ducts. So it just speaks to the kind of pluripotent nature of the cells that form it. As far as epidemiology, it's the most common pediatric soft tissue malignancy, or sarcoma, and it makes up about 5% of all childhood and adolescent malignancies. The annual incidence is about 4.3 cases per million children, and then the orbit is the primary site in 10% of the cases. So basically if there is about 350 new cases a year in the United States, there are about 35 that are orbital. It's usually seen as a tumor of the orbit, but less frequently has been found to involve the conch, the eyelid, or the globe itself. And it's regarded as the most common malignant orbital tumor of childhood in the United States. Clinical features of specifically orbital, rabbi myosarcoma, usually presenting in the first decade of life. There is just a slight male-to-female predilection, no racial predilection. And it usually presents, like our patient, with this rapidly progressive unilateral proptosis that can present following a minor trauma. You can also possibly have a palpable subconch or lid nodule with lidodemocomosis. So this is just looking at the histo, the morphology of it. The two most common types that are found are the embryonal version at the top. And this is the most common and generally the most favorable prognosis. It's generally found more in a superior nasal location of the orbit. And then it's characterized by these kind of mixture of cells. They can be either round or elongated spindle cells that have an eosin acetylplasm, and then they're contained within this myxoid stroma. Occasionally, with a higher mag or with a trichromestane, you can identify cross-driations that would be suggestive of the skeleton muscle type origin. The lower example is the alveolar type, which is actually more malignant and less common than the embryonal. It's usually more common in the inferior orbit, and then you can see these, it's characterized by these small round tumor cells that are loosely adherent to a very thin network of these fibrovascular septae. So they kind of resemble what you would see in the alveoli of the lung. So the difference between what we're seeing with the tumor in this patient is quite variant from this kind of like thin, delicate interstitial septae that are characteristic of an alveolar. This is just a close-up view of the cross-driation. It's kind of blurry, sorry. The cross-driations that you could see potentially at higher mag, and this would usually be more in the embryonal variant, but this was not the case in our tumor. Radiologic feature is kind of what we already talked about. Usually it's a kind of homogenous mass that's iso-dense to the extraocular muscles on CT. It does enhance with contrast generally, and then earlier tumors are usually found without bony invasion, but the tumor that does actually have some bony invasion here. And then on MRI, with a T1 weighted, it's usually the mass would be either iso-intense or hyper-intense to the extraocular muscles, and then there's generally moderator-marked post-contrast enhancement. In terms of diagnosis, just in the initial phase, any child with progressive proptosis within the first two decades of life should have a detailed history clinical examine and imaging studies. If it's suggested for a rhabdo or a mass, you would want to get a prompt biopsy for a few things. The histopathologic diagnosis, which is generally how these tumors are diagnosed is then in terms of management and prognosis. The histo is key. Immunohistochemistry can be obtained. The Desmond is more, it can be positive in various types of muscles, so it's not necessarily specific to rhabdomyro sarcoma. The more specific markers are sensitive and specific or myogen and myod1, which have been found to be about 97% sensitive, and then 90% and 91% respectively with specificity for detecting rhabdomyro sarcoma. Then we can use some additional markers just to rule out other types of spinal cell tumors. Additionally, if there is a questionable histologic picture, like what we're seeing with our patient, we can obtain various cytogenic analysis via a fish, a fluorescent in situ hybridization, or reverse transcriptase PCR for detection of this gene or gene fusion that has been found to be present in about 80% of the alveolar variants of rhabdomyro sarcoma. This can be very crucial in terms of prognosis as well as different staging schemes. We'll take a look at that real quick. For staging, there are various components that go into staging, the first of which is a loosely TMM-based schematic that takes into account, just for example, the stage one, the site of the primary tumor, and then the favorable sites generally regarded as the orbit, non-perimonangial, had a neck genital urinary tract, not kidney, the bladder, the prostate, and the biliary tract. Unfavorable sites would be other than those that are listed as favorable. Then taking into account the actual invasiveness of the tumor, if it's confined to the original, the primary site, the size less than five centimeters, larger than that, and then if there's any regional lymph node involvement and additionally any metastasis. So we take that into consideration along with the surgical pathological group, which is based on the initial surgical management. A lot of the tumors that will be related to group three as most of the forms of management are not necessarily to actually resect or excise the entire tumor. In the primary surgery, it's more to get the biopsy and then if debulking is possible. So there will be a growth residual disease after most of the biopsies, most of the tumors would be in group three. And then that's taken into consideration with the actual histology of the tumor. And then these patients are stratified into various risk groups and then managed in that regard. In terms of management, until the late 1960s actually, exenteration was the treatment of choice. But there was an extremely high mortality rate that remained with this treatment. So after the 1970s, there was a movement towards a different type of management for these patients, which involves surgical biopsy and excision if possible, chemotherapy as well as radiation. The chemotherapy regimens are mostly comprised now of the vincristine, ectinomyosind, and cyclophosphamide, although the last agent can vary in certain forms of management. And then in terms of if there's like a lower risk, sometimes cyclophosphamide isn't always brought on board. And then exenteration is generally reserved for recurrent or locally persistent disease at this point. In terms of prognosis, the IRS is the intergroup RABDO myosarcoma study. It was a conglomerate of various research groups that were investigating RABDO myosarcoma separately and kind of came together to take a look at all of the RABDO myosarcomas in the United States together. We've done various studies. I believe there's a fifth one that was more recently completed. But the fourth study showed actually a three-year failure-free survival rate of 91%, 94%, and 80% for groups 1, 2, and 3, respectively. And then in terms of what I was talking about with the histological morphology, that actually plays into the prognosis for patients as the five-year survival rate varies between 94% for the embryonal type versus 74% for the alveolar. And then complications of the disease are generally related to the management in terms of side effects of radiation as well as the chemotherapeutic drugs. And those are just briefly discussed there. So back to our patient real briefly. As I discussed before, the patient had been taken to the OR. The tumor was biopsied and debulked at that time. It was about, I believe they said, 2.4 centimeter mass. Obviously from what we looked at with the histo, it's unclear morphology at this point with evidence of bony invasion. The immunohistochemistry suggestive of a myogenic origin. And then the cytogenic analysis is still pending at this point. At this point, she has been diagnosed with a preliminarily stage one group three. And then in terms of the low intermediate risk, that will be determined following the determination of the histologic, her composition of the tumor. She's currently undergoing a hemorrhagic workup and the bone marrow and PET CTs are still pending. When she was seen in the clinic on post-op day five, she was doing well. Visual acuity, uncorrected. Left had improved from the 2400 on initial exam to 2050 at this point. And there was no APD. So the take home points in children or patients with a sudden onset of proptosis want to consider an urgent workup, a biopsy, and histopathologic exam to confirm a diagnosis. Two major histological types, embryonic and alveolar. Radiation therapy and chemo are treatment schemes and it's generally a pretty good survival rate if caught early. These are my references and just wanted to say a quick thanks to the Phenomenal Intermountain Ocular Research Team and Freelace Leaders, Dr. Warner and Dr. Mamelis for being so tremendous and welcoming me and also to Drs. Adesina and Patel for helping me out with the case and letting me present their patient. Thank you. Thank you.