eP174 - Anal Phyllodes Tumor as a Manifestation of Cowden Syndrome

Purpose/Background: We present the case of an anal phyllodes tumor in association with a germline mutation of the phosphatase and tensin homolog (PTEN) tumor suppressor gene in a patient later diagnosed with Cowden Syndrome (CS). A 46-year-old female presented with several weeks of increasingly painful bowel movements and an enlarging anal mass. Past medical history was notable for cerebellar dysplastic ganglioglioma and multinodular goiter; past surgical history for suboccipital craniotomy and hemithyroidectomy. Physical exam revealed a 6 centimeter (cm) pedunculated and multilobulated right perianal mass, a 1cm polypoid mass at the left anal verge (Figure 1), and innumerable 1-2 millimeter sessile polyps on anoscopy.Methods/Interventions: The patient underwent excision of the anal masses, colonoscopy, genetic testing, and mammogram. On histopathology, the anal masses demonstrated fibroepithelial proliferation with prominent leaf-like architecture and focal, mildly increased stromal cellularity (Figure 2A-B). Immunohistochemistry (IHC) was positive for CKAE1/AE3, GATA3, GCDFP15, CK5/6, estrogen receptor, and progesterone receptor. The morphologic and IHC pattern was consistent with benign phyllodes tumor, likely arising from anogenital mammary-like glands (AGMLG). Colonoscopy demonstrated hundreds of polyps throughout the colon, confirmed to be hyperplastic polyps on multiple biopsies. Genetic testing revealed a germline PTEN mutation (C.367A>G, p.His123Arg), confirming a diagnosis of CS. Screening mammogram demonstrated bilateral Breast Imaging Reporting and Data System (BI-RADS) 3 lesions. Mammogram 15 months later demonstrated a new BI-RADS 5, 6cm right breast mass, found to be a triple negative, poorly differentiated carcinoma (Figure 3).Results/Outcomes: One year following excision of the anal lesions, the patient developed recurrence of several anal lesions which were excised and found to be hidradenoma papilliferum, supportive of AGMLG on histopathology. For the breast lesions, the patient was initiated on neoadjuvant carboplatin/paclitaxel, but the tumor rapidly grew to 15cm, thus she was switched to doxorubicin/cyclophosphamide. The patient underwent modified radical mastectomy with removal of a 17cm poorly differentiated neoplasm and negative lymph nodes and received radiation therapy and adjuvant capecitabine. She declined prophylactic left-sided mastectomy, but remains under consideration for prophylactic hysterectomy and is followed for endoscopic, thyroid, and breast surveillance.Conclusion/

Discussion: Phyllodes tumors typically arise in the breast, but can also develop via transformation of mammary-like glands in the anogenital region and exist on a spectrum of benign to malignant. Phyllodes tumors are rare in association with CS, a hereditary cancer predisposition syndrome characterized by germline pathologic mutations in the PTEN gene, and have only previously been reported as phyllodes tumor of the vulva arising from AGMLG. More common gastrointestinal manifestations of CS include colonic polyps, typically hamartomas, and less often, gangliomas. Given that CS is associated with increased risk of numerous malignancies, including that of the breast and colon, the development of an anal mass demonstrating pathological changes consistent with transformation of AGMLG in the appropriate patient should prompt consideration of hereditary cancer predisposition syndromes, initiation of genetic counseling, and multidisciplinary care." Figure 1

Gross appearance of anal mass on physical examination
Figure 2A

Hematoxylin and eosin (H&E) staining (10x) shows prominent leaf-like fibroepithelial proliferation. 
 Figure 2B

H&E (40x) shows mild stromal hypercellularity.
 Figure 3

Computed Tomography shows a 15-cm right breast mass, ultimately found to be a 17-cm, poorly differentiated malignant neoplasm"