Cytomorphological features of complex fibroadenoma breast

Dear Editor, Fibroadenomas are the most common solid benign breast lesions in women having epithelial and stromal components. It may occur at any age, with the peak incidence being in adolescent girls around their 20s and 30s, except for complex fibroadenoma occurring in older women.[1,2] Hormonal stimulations have an etiological role, particularly an increase in estrogen and progesterone activity, pregnancy, and lactation. Being hormone-dependent, tumor dimensions increase during these hormonally active periods and decrease during the perimenopausal period.[2,3] The size of the lump in complex fibroadenoma is relatively smaller (average 1.3 cm in diameter) compared to simple fibroadenoma (average diameter: 3 cm). Fibroadenoma is termed complex fibroadenoma when it possesses either of the histological features, cyst >3 mm in diameter, sclerosing adenosis, epithelial calcification, and papillary apocrine metaplasia.[1,3,4] We report a case of a 48-year-old postmenopausal woman who presented with a history of a painless, mobile lump in the right breast for 1 month. The lump was single, nonprogressive in size, and was not associated with pain or nipple discharge. The patient did not give any history of hormonal therapy or surgery. On examination, a solitary, round to oval hard, nontender mass was felt in the right breast’s upper outer and central quadrant measuring 6 × 5 cm. No significant ipsilateral axillary lymph node was palpable. She had no family history of any breast lumps. At our center, mammography of the right breast revealed an irregular-shaped high-density lesion with a microlobulated margin in the upper outer quadrant extending into the upper-central and lower-outer quadrant measuring 64 × 58 × 40 mm and a focus of macrocalcification within it (Breast Imaging Reporting and Data System: BIRADS 4b). The possibility of benign phyllodes tumor was rendered [Figure 1a]. Similarly, ultrasonography of the right breast exhibited an irregular-shaped heterogeneously hypoechoic lesion with a few cystic areas measuring 63 × 54 mm (BIRADS 4b), the possibility of phyllodes tumor. Subsequently, ultrasound-guided fine-needle aspiration cytology was performed from the lesion. The smear from the representative site was cellular, comprising sheets of benign ductal epithelial cells and a few mildly cellular stromal fragments [Figure 1b]. Few epithelial cell clusters show discohesiveness at the periphery with nuclear pleomorphism in the form of enlarged nuclei, prominent nucleoli, and occasional mitosis. The background showed bare bipolar nuclei and blood [Figure 1c-e]. Based on these findings, the fine-needle aspiration cytology was reported as an atypical breast lesion according to The International Academy of Cytology Yokohama system, and the patient was advised to excision biopsy for a definitive diagnosis.Figure 1: (a) Mammography of the right breast shows an irregularly shaped (microlobulated margin) high density, heterogeneously hypoechoic lesion with internal cystic areas, and macrocalcification is seen in the upper outer quadrant extending into the upper central and lower outer quadrant. (b) May Grunwald-Giemsa (MGG x100)–stained smear shows irregular and variable sheets of ductal epithelial cells. (c) and (d) Atypical epithelial cells with larger nuclei and forming loosely organized cell clusters at the periphery with discohesiveness (red arrow) (Papanicolaou [PAP] x100; MGG x200). (e) Epithelial cells display enlarged nuclei, prominent nucleoli, and atypical mitosis (green arrow). (f) Haematoxylin and eosin (H and E x40)–stained sections show irregularly distributed ducts with dilations and areas of dense sclerosis. (g) In the fibrotic background, there is a proliferation of disordered tiny ducts, which is suggestive of sclerosing adenosis (H and E x100). (h) Apocrine metaplasia of the ducts with areas of sclerosis (H and E x400)The patient underwent a lumpectomy and the gross cut surface showed a solid-cystic tumor, measuring 6.2 × 5.8 × 4 cm. On serial slicing, multiple cystic areas of varying diameter, ranging from 4 to 8 mm in diameter with mucoid material interspersed in between. A microscopic examination of those white areas displayed a well-defined tumor with multiple cystic spaces lined by cuboidal to columnar cells having round to oval nuclei and inconspicuous nucleoli [Figure 1f]. The lumen showed eosinophilic material. The adjacent area showed bland ductal adenosis and a thin, delicate papillary pattern. Also noted were areas of typical fibroadenoma having both intracanalicular and pericanalicular patterns of the proliferation of ductal and stromal elements [Figure 1g and 1h]. Thus, a histomorphological diagnosis of complex fibroadenoma was made [Table 1].Table 1: Cytology quizComplex fibroadenoma cytomorphological differs from noncomplex type fibroadenoma in having sheets of ductal and myoepithelial cells. In addition, it displays irregularly bordered, variable-sized sheets of ductal epithelial cells with significant discohesiveness. Also, a few atypical ductal cells show nuclear enlargement and prominent nucleoli. Few myoepithelial cells can be identified.[3–5] Complex fibroadenomas were primarily reported in older women (median age of 47 years) as compared to simple fibroadenomas (median age is 28.5 years).[5,6] It is necessary to identify the different variants of fibroadenomas because every variant has differences in prognosis and treatment as complex fibroadenoma has a risk of developing malignancy in 2.17% and also 3.1-fold risk of developing invasive breast carcinoma in the same or contralateral breast.[2,3] As per the literature, patients with complex fibroadenomas have a relative risk of developing carcinoma 3.1 times that of women in the general population, while a noncomplex type of fibroadenoma carries a relative risk of 1.89 times.[3–6] Therefore, a precise understanding of complex fibroadenomas features is required in the daily practice of cytopathology diagnosis. Overall, the cytology of complex fibroadenomas can be variable, but they are generally considered benign tumors. On cytology, cells appear uniform in size and shape and they have a low nuclear-to-cytoplasmic ratio. The cells may be arranged in a variety of patterns, including sheets, trabeculae, and clusters. Cytologically, complex fibroadenomas may show the presence of epithelial and stromal components, which can make them more complex than simple fibroadenomas. The epithelial cells may show mild atypia, which means that they have slightly irregular nuclei, but the atypia is not severe enough to suggest malignancy. The stromal cells may show areas of hyalinization, which means that the tissue has become hardened due to the deposition of collagen. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.