Severe Chronic Rectocolitis Associated With a Characteristic Sunflower Magnetic Resonance Imaging Pattern.

Question: A 51-year-old Caucasian woman suffering from long-term severe ulcerative colitis was referred to our department for discussion of rectosigmoid resection with colon-anal anastomosis. She presented severe pelvic pain resistant to opioid medication, major daily rectorragia, anal incontinence, and loss of stool/gas discrimination, leading to major impacts on her daily life. In the past 10 years, she had consulted many different specialists to seek both diagnostic and therapeutic opinions and to adapt painkiller treatments. Indeed, she received many drugs, including analgesics, antidepressants, and antiepileptic drugs, all of them being ineffective on her complaints. Her last colonoscopy revealed bluish appearance of the rectosigmoid mucosa and nodular vascular ectasias responsible for hemorrhagic signs (Figure A) without any histologic abnormalities suggestive of Crohn’s disease or ulcerative rectocolitis on biopsy. These lesions were stable over time. Abdominal computed tomography (CT) revealed a thick rectal and sigmoid wall associated with perirectal fatty infiltration containing few ovoid hyperdense foci in favors of calcifications (Figure B). Magnetic resonance imaging (MRI) demonstrated an increased wall thickness of both sigmoid and rectum (Figure C), in major T2-weighted hypersignal (Figure D), which confirmed the diagnosis of severe rectocolitis. Interestingly, these features were associated with major perirectal hypersignal on T1-weighted MRI, suggestive of circumferential overgrowth of the perirectal fat (Figure C) associated with hyperintense radial strips on fat-suppressed T2-weighted images (Figure D) spreading around the rectum, displaying a sunflower pattern. This pattern, as well as previously cited findings, were compatible with low-flow vascular malformations, and more precisely of a venous component, based on both purplish mucosa on colonoscopy and multiple focal calcifications on CT, suggestive of phleboliths. What could the diagnosis be, considering this association of sunflower pattern and perirectal fat hypertrophy? How should it be demonstrated and treated? Look on page 531 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Based only on clinical complaints of the patient, both Crohn’s disease and ulcerative rectocolitis would have to be excluded, but those diagnoses were ruled out by several biopsies performed during the previous 20 years. Moreover, no endoscopy, CT, or MRI findings were suggestive of those conditions. Based on imaging data, the patient was diagnosed with rectal cystic lymphatic malformation, which led to performing endorectal sclerotherapies without any improvement of her clinical status. One should note that the circumferential overgrowth of the perirectal fat was very unusual for an isolated lymphatic cystic malformation, and this feature led to considering PIK3CA-related overgrowth spectrum (PROS). Indeed, such lipomatosis associated with infiltrative low-flow malformations represents a key feature of segmental overgrowth syndrome related to PROS.1Keppler-Noreuil K.M. Rios J.J. Parker V.E.R. et al.PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation.Am J Med Genet. 2015; 167: 287-295Crossref Scopus (319) Google Scholar Therefore, because such a condition can involve all parts of the body, a perirectal biopsy was performed to look for PIK3CA post-somatic activating mutations. Rectal ultrasound endoscopy demonstrated an inflammatory purplish mucosa with a thickening of the 3 layers affecting almost the last 30 cm of the colorectal wall (Figure E), allowing uncomplicated 22-G needle biopsy. After DNA extraction from a formalin-fixed paraffin-embedded tissue sample, a next-generation DNA sequencing panel was performed, confirming PIK3CA somatic gain of function mutation (variant c.3140A>G). This diagnosis led to opting for medical treatment using an oral alpha-specific PI3K inhibitor, alpelisib (BYL719), as recently published for PROS.2Delestre F. Venot Q. Bayard C. et al.Alpelisib administration reduced lymphatic malformations in a mouse model and in patients.Sci Transl Med. 2021; 13eabg0809Crossref PubMed Scopus (17) Google Scholar,3Morin G. Degrugillier-Chopinet C. Vincent M. et al.Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib.J Exp Med. 2022; 219e20212148Crossref PubMed Scopus (10) Google Scholar After 1 month of this targeted therapy (125 mg alpelisib twice a day) both rectorragia and disabling pelvic pain completely disappeared. Because PI3K inhibitors may affect glucose homeostasis, glycemic variations were closely monitored and no hyperglycemia was observed. MRI examination performed 4 months after institution of alpelisib demonstrated significant reductions of both low-flow vascular malformations and colorectal wall thickness (Figure F). At 6-month follow-up, all of the symptoms had disappeared. Considering the few side-effects of alpelisib in this patient (transient dysgeusia) and its major impact on her quality of life, this treatment should be considered as a long-term treatment, because discontinuation of the treatment would risk relapse. In conclusion, this case demonstrates that PIK3CA gain-of-function mosaicism should be looked for when facing focal fatty tissue hypertrophy associated with infiltrative low-flow vascular malformations, wherever the anatomic location on the body, even if other frequent features of PROS are not present, especially limb overgrowth or superficial vascular malformations. From a gastroenterology point of view, this case illustrates that a focal PIK3CA mutation involving colorectal tract can induce severe rectocolitis. Therefore, when facing chronic colitis without any features suggestive of Crohn’s disease or ulcerative rectocolitis, identification of both perirectal fat hypertrophy associated with a characteristic sunflower MRI pattern and phleboliths should prompt endorectal biopsy to look for a PIK3CA-activating variant. Indeed, in such a case, targeted inhibitor of PIK3CA represents a rapid and life-changing therapy to both solve patient complaints and avoid the risks of a complex surgical procedure.