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Cytology of minimal deviation endocervical adenocarcinoma (adenoma malignum) on a ThinPrep Pap test

Dear Editor: Minimal deviation adenocarcinoma (MDA) of the endocervix, also known as adenoma malignum, is a rare and diagnostically challenging tumor, both in cytology and surgical pathology, due to minimal cytological atypia. Herein, we present a case of MDA on a Papanicolaou (Pap)-stained ThinPrep Pap test (TPPT). The patient was a 64-year-old postmenopausal woman with a history of breast carcinoma, diagnosed in 2004 and treated with tamoxifen. Prior to that, she had been on estrogen replacement therapy for five years (until 2002). There was a family history of colon and endometrial carcinoma. In 2007, the patient presented with scant brown vaginal spotting. An EM biopsy (EMBx) was benign. Four subsequent and consecutive TPPT were negative. In February 2009, the fifth TPPT was signed out as atypical endocervical cells (AEC). It showed a cellular specimen with numerous endocervical (EC) cells in a background of thick clumps of mucin. The EC cells showed architectural variability and were dispersed as small and large twodimensional groups and sheets with a honeycomb configuration, complex branching structures, and small strips of cells with peripheral nuclear palisading (“feathering”) (Fig. 1). Individual tumor cells were round to columnar with mucinous and vacuolated cytoplasm. Nuclei were round to oval, mildly hyperchromatic with subtle nuclear membrane irregularity and prominent nucleoli. Nucleus to cytoplasmic (N/C) ratio ranged from low to moderately high. A human papillomavirus (HPV) test was negative. A pelvic sonogram, performed within one month of that Pap test, revealed a thickened heterogeneous endometrium with cystic foci, measuring up to 1.8 cm. A repeat EMBx, three weeks later, showed benign endocervical mucosa only. The patient underwent a D&C hysteroscopy, which grossly identified two EM polyps that were confirmed on subsequent histology. An EC curettage, performed at this time, dissolved on processing. A follow-up TPPT, within 6 months of this biopsy, was again diagnosed as AEC. Cytological findings were similar to the prior Pap. A cold knife cone and repeat D&C hysteroscopy revealed no gross abnormality. Histologically, a cone biopsy revealed MDA of the cervix, invading to a depth of at least 2.5 mm. The tumor was comprised of mucinous glands with abnormal architectural configurations and associated desmoplastic stromal response. The tumor cells had abnormal cytological features including a vesicular appearance with prominent nucleoli and scattered, easily identifiable mitotic figures. The tumor, which exhibited lobular endocervical glandular hyperplasia (LEGH), extended to the deep and ectocervical margins (Fig. 2). Immunohistochemical stains for ER and PR were positive within the stromal cells but negative within the glandular epithelium. The neoplastic glandular cells were also negative for p16. The Ki67 index was up to 30% within the tumor (Fig. 3). The patient underwent a robotic radical hysterectomy, bilateral salpingo-oopherectomy, and pelvic lymph node dissection. Focal residual MDA of the cervix, invading 1 mm into a 9 mm thick stromal wall (Fig. 2) was noted. The patient has remained asymptomatic and disease free to the present date. MDA is a well-differentiated mucinous EC adenocarcinoma (ECA), which accounts for 1–3% of all ECA. It *Correspondence to: Erika Hissong, MD, Department of Pathology, Weill Cornell Medical College, New York Presbyterian Hospital, Starr 10, East 68th Street, New York, NY 10065, USA. E-mail: emh9016@nyp.org Received 29 December 2015; Revised 25 February 2016; Accepted 26 February 2016 DOI: 10.1002/dc.23470 Published online 18 March 2016 in Wiley Online Library (wileyonlinelibrary.com).