Cancer-Associated Mutations in Endometriosis without Cancer.

BACKGROUND: Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. METHODS: We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients). Mutations were validated with the use of digital genomic methods in microdissected epithelium and stroma. Epithelial and stromal components of lesions from an additional 12 patients were analyzed by means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent activating KRAS mutations. RESULTS: Exome sequencing revealed somatic mutations in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing System or immunohistochemical analysis. The likelihood of driver genes being affected at this rate in the absence of selection was estimated at P=0.001 (binomial test). Targeted sequencing and a droplet digital PCR assay identified KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with mutations in the epithelium but not the stroma. One patient harbored two different KRAS mutations, c.35G→T and c.35G→C, and another carried identical KRAS c.35G→A mutations in three distinct lesions. CONCLUSIONS: We found that lesions in deep infiltrating endometriosis, which are associated with virtually no risk of malignant transformation, harbor somatic cancer driver mutations. Ten of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions.

Management options for a patient with squamous cell carcinoma arising in a mature cystic teratoma of the ovary.

OBJECTIVE: Mature cystic teratomas, also referred to as dermoid cysts, are one of the commonly occurring ovarian germ cell tumors. Malignant transformation of a germ cell tumor occurs approximately 1-2% of the time. Treatment options vary by stage and are not well outlined in the literature. Here we report a case of a perimenopausal female who presented with increasing abdominal girth and an elevated CA-125. Final pathology revealed an invasive squamous cell carcinoma, moderately to poorly differentiated, multifocal, arising in a cyst on the left ovary, possibly a teratoma. At the time of diagnosis, the patient was FIGO stage IA. The decision was made against adjuvant treatment. Squamous cell carcinoma arising in a mature cystic teratoma of the ovary is rare. Treatment options are not well outlined in the literature, especially for disease less than stage II. Further research is needed to better inform the clinician on management recommendations.

Synchronous papillary-medullary thyroid microcarcinoma: a case report.

Background: Papillary thyroid carcinoma is the most common type of thyroid carcinoma, making up 85-90% of all thyroid carcinomas. Medullary thyroid carcinoma is the third most common type of thyroid carcinoma, making up less than 5% of all thyroid carcinomas. However, synchronous papillary-medullary thyroid carcinoma is exceedingly rare and has not been well described historically. There have been fewer than 40 cases reported in the current literature. Case Description: In this case report we present a 65-year-old man with synchronous papillary-medullary thyroid carcinoma. A 65-year-old man presented with a symptomatic multinodular thyroid goiter. Ultrasound (US) confirmed bilateral thyroid nodules, and he was initially managed nonoperatively. Fine needle aspiration (FNA) biopsy of the left dominant nodule revealed atypia of undetermined significance (AUS) (Bethesda class III). Further assessment of the FNA specimen with ThyGeNEXT® (mutation panel) revealed no mutations and the ThyraMIR® (microRNA risk classifier) was negative, which classified the results as very highly likely to be benign. Due to worsening local compressive symptoms, a total thyroidectomy was performed. Final surgical pathology revealed incidental multicentric, multifocal micropapillary carcinoma foci from (0.1 to 0.5 cm), and a 0.3 cm medullary carcinoma in the left thyroid lobe on the background of nodular hyperplasia. Conclusions: Synchronous papillary-medullary thyroid carcinoma is a rare finding that should be considered in patients with symptomatic multinodular thyroid goiters. It is important to report this case to increase awareness and improve our understanding and management of these unusual carcinomas in the future.