 Thank you for coming this morning. My name is Eric Gulenkamp. I'm a visiting medical student from the University of Chicago. And I'd like to present a case to you today on the management of recurrent orbital hemangioparecytoma. I don't have any financial disclosures, unfortunately, for my bank account. So the history of present illness jumping right in, we have a 25-year-old female with a history of recurrent hemangioparecytoma of the right frontal lobe and orbit, presenting with fullness of the right upper eyelid and proptosis of the right eye for one week. Of note, she wasn't experiencing any pain, double vision, headaches, blurry vision, or tearing. And she was doing pretty well after a subtotal resection of a hemangioparecytoma back in August of 2016 with a combined surgery, with the neurosurgery, and oculoplastic services. So to give a little background on this patient's history, her very initial presentation was to Northwestern. In July of 2014, when she had headaches and bilateral vision loss, at the time of presentation, visual acuity was NLP in the right eye and count fingers in the left. And on imaging, she had a large frontal lobe mass. And so she underwent a resection, procedure, and histology confirmed it as a high grade or grade three hemangioparecytoma. And at that time, temozolamide and external beam radiation therapy were recommended, but the patient refused for reasons unknown to us at the time. So her first presentation to our institution at the University of Chicago was with proptosis and right eye pain in August of 2016, roughly two years later. Visual acuity was unchanged from her post-operative course at Northwestern. So from that August episode, I have some imaging here. You can see what is a not very subtle right frontal lobe mass. And taking another cut, it shows extension into the superior orbit. So at that time, she underwent a combined neurosurgery and orbit service resection of the frontal lobe mass with superior orbital extension. And again, radiation and chemotherapy were recommended, but the patient refused, opting for a more holistic approach to her tumor. And so she went home and was doing fine in the interim until the presentation to us. So now returning to her presentation of the case that I'd like to talk about, the recurrent presentation. On physical exam, her acuity was, again, NLP in the right eye, count fingers at two feet in the left. Normal pressure, her right pupil was fixed and dilated, had restriction in all fields. Her external exam showed exotropia and proptosis, which was confirmed on exophthalmometry. And I have some photos of the patient's motility examination. Notable, you can see the superior firm upper eyelid swelling. And the proptosis is quite apparent. And the exotropia is as well. On slit lamp exam, there was inferior scleral show. The iris was fixed and dilated. And the fundoscopic exam showed four plus disc pallor on the right side, three plus on the left, and was otherwise normal appearing. This time imaging showed a roughly 2.6 centimeter mass on CT in the superior lateral aspect of the orbit. MRI showed it to be just slightly larger, around 3.1 centimeters in total. Again, it's a well circumscribed mass in the superior aspect of the orbit with possible cavernous sinus extension. So with that, I'd like to talk about the presumed diagnosis given this patient's history of hemangiopericitoma. Hemangiopericitoma is a vascular tumor involving soft tissues, which arises from parasites. It's most often intracranial, but up to 10% can involve the extracranial head and neck, which includes the orbit. And signs and symptoms when it does have the orbital presentation are proptosis, such as in our patient, the perception of an interorbital mass, pain, diplopia, reduction in vision, and swelling of the eyelids. So with regard to the tumor itself, it's relatively rare, although 1% to 3% of all orbital biopsies do show hemangiopericitoma. It doesn't have any gender predominance, and the mean age of presentation is around 42 years old. But it can present at many different ages, spanning from late teens all the way to the geriatric population, in case reports. Recurrence rates are roughly 33%, but depend heavily on whether or not a total resection or a partial subtotal resection is achieved. Rates for total resection are lower than 33% and much higher for subtotal resection. Distant metastasis is uncommon, but does occur up to 15% of patients out to five years. The most common sites of metastasis are like lungs, pleura, and bone. And here I have a histology slide, not from our patient, but the classic image of hemangiopericitoma, which shows pardon me, which shows these staghorn branching vessels that are very thin-walled and they're surrounded by these spindle-looking cells. They classically stain CD34 and vimentin positive. The treatment options include surgical resection. This is typically the main option, the first line therapy recommended for an initial presentation of hemangiopericitoma with no metastasis or extension. And often this is enough, but in cases of recurrence, usually surgical resection with radiation is recommended. Sometimes adjuvant chemotherapy can be recommended as well for cases of multiple recurrence or if there's distant metastasis involved. Another option is orbital exenteration. But there is, in general, due to the rarity of this tumor, a paucity of data. So I wanted to present on the management of hemangiopericitoma and one particular study showed surgical resection plus external beam radiation therapy to be quite beneficial. So here we have a graph to show you on the x-axis. You have the time in months to recurrence and then the y-axis is the rate of recurrence. And so you can see in patients that received radiation, independent of resection, recurred more often and earlier. Although the total rates extended out indefinitely are very similar, the disease-free period is much better with external beam radiation therapy. And this was a case series of 39 patients ranging from the late 90s to 2008. The p-value on the disease-free recurrence interval, which was extended roughly 126 months with external beam radiation therapy, was 0.03. So this was significant even in a small case series. Touching on chemotherapy and immunotherapy, this is, again, typically reserved for recurrence or distant metastasis. Chemotherapy originally involved traditional chemotherapy agents like Doxorubicin, Phosphamide, Cisplatin, but it's been shown not to be very effective in controlling metastatic disease. It induced no remission in a review of 21 patients and stable disease only in about half of the patients. Newer therapies have shown to be perhaps a little effective when traditional chemotherapy fails or is refractory to initial chemotherapy. One such study examined 14 patients that used Temizolamide plus Bevacizumab, and these patients achieved partial response or stable disease in 79% of the cases. Two of the 14 even had, so the partial response was 30% reduction in tumor volume with just this chemotherapy and in patients that had already failed with traditional chemotherapy agents. Another study examined the use of Pazopinib, which is a tyrosine kinase inhibitor on the VEGF pathway. In three patients with metastatic disease, which, again, was refractory to Phosphamide, etoposide, and Cisplatin. One developed a partial response and two developed stable disease. So in both of these cases, alternative therapies to the traditional chemotherapeutic agents seem to be more effective. Pazopinib works best when there's a C-kit mutation. We examined that in our patient and unfortunately our patient was C-kit negative, so we opted not to recommend that. Returning back to our patient, so this is a patient with, who's young with a history of multiple local recurrences. So it presented sort of a therapeutic dilemma. She had already refused treatment, so we were wondering what should we recommend, should we recommend surgical resection with adjuvant external beam radiation therapy, plus or minus chemotherapy, and also should we consider the option of neo-adjuvant external beam radiation therapy given that the patient was already NLP in that eye and external beam radiation therapy has been shown to prevent or prolong disease free recurrence intervals. So with that in mind, we thought this was particularly beneficial for a patient with poor compliance. Maybe she'd be open to the idea of this neo-adjuvant option with a follow-up surgery four to eight weeks later, but there was one such case report which showed complete remission and disease-free recurrence after neo-adjuvant external beam radiation therapy. And then the question of whether or not our patient would benefit from chemotherapy or immunotherapy. In the end, the clinical course went as follows. We recommended external beam radiation therapy with chemotherapy, possibly Temizolamide, given the case series with the 14 patients I had discussed with you earlier. The patient agreed to resection, but again was reluctant to have either radiation or chemotherapy due to her resistance to the idea of it. She preferred a holistic approach and wanted to seek treatment elsewhere. So in the end, we compromised on a resection procedure without the use of adjuvant chemotherapy or radiation. The patient's been doing well so far. She had underwent a successful resection performed by the Oculoplastic's institution or at our institution and hasn't had her next follow-up appointment yet, but comes back in August. So we'll be looking forward to seeing how she's doing and hopefully she'll be disease-free. Thank you very much for your time. And I'd like to turn it over to any questions at this point. So I find that the patient autonomy really fascinating here and clearly, I mean, you know, the patient does have autonomy, should have autonomy to make clinical decisions, but it kind of begs the question for me, what can we do as clinicians to better educate what resources are available? And I'm wondering if you all, as you had this discussion, what solution or ideas you came up with if there were other resources for head-to-head resection at your university? So I, the way we had approached it was trying to explain, you know, this has recurred multiple times when we've resected, even when we thought we got a complete resection and had taken care of the disease, but it still came back and it's come back in multiple locations, both the frontal lobe and the superior aspect of the orbit. And so it's very likely if we take the same approach to do the same thing again. And even so, she still preferred this holistic approach. I think the family had a very negative opinion of chemotherapy and radiation to begin with. I wasn't able to get specifically at why that was the case, whether there was something in their history or someone close to them who had gone through it and had a bad outcome. But our approach was mainly to try to give her various options, either chemotherapy or radiation alone, maybe both of them, or maybe radiation beforehand with the justification that we know it prevents recurrence or seems likely to prevent recurrence and may help us shrink the tumor to a smaller size to perform the operation. But in the end, she was resistant to all our approaches. Yes? What's difficult about these cases is that the major pairs at Thomas are often not encapsulated. So even when you think you've got them all out, there's gonna be some kind of a remnant tumor left behind it. What I find interesting looking at the pathology on these is that they run a gauntlet from looking very benign to looking borderline, even looking malignant. And yet we can't make a correlation between how they behave and how malignant they look on the pathology. So this is a very odd lesion in that we've seen many of them that look relatively benign and recur rapidly. We've seen others that look relatively malignant and don't recur at all. And so this is one of those cases where the pathology is actually unhealthful and that we can't help to decide how aggressive the tumor's gonna be and how you're gonna treat it. In terms of the patient refusing treatment, it's a patient prerogative. And sometimes no matter what you say, you're not gonna sway them. You would think that the argument that, well, you had holistic treatment twice and it came back both times. Maybe you should give something else a try, but if you can't dissuade them, you can't dissuade them and that's their choice. Right. Yes. Just to continue on this holistic treatment issue, I think what succeeded at times is not to look at this as an either or, but to look at holistic medicine as a complementary approach and to treat the practitioners of it with respect and to look at how everything can be accomplished and it could be considered a win-win situation. And I don't know anything about this specific patient, but perhaps she might have been more willing to accept the treatment that you and your group prescribed if there had been room to have holistic medicine in addition in a complementary fashion. Yeah, we certainly would have been open to that option and we sort of recommended this in addition. I think the patient, where the place she was coming from especially her mother who was with her at all the visits was that she was very resistant to chemotherapy and radiation specifically. It seemed like she had had a bad experience, but we weren't able to parse out what that was. And so we certainly would have been open to that and we do have some providers at our institution who take a more holistic approach and so we would have been happy to connect her with that and I think it's a great suggestion for patients that really want a more holistic approach. All right, thank you very much.