Role of cytology in fibroadenoma with clinging carcinoma.

Fibroadenoma is the most common benign breast tumor in adolescent girls and young women with a peak incidence in the second and third decades of life. Carcinoma arising within a fibroadenoma is rare and is usually discovered incidentally. We describe a case of clinging type of ductal carcinoma in situ (DCIS) arising within a fibroadenoma. Clinging carcinoma, a variant of DCIS is an under recognized entity. Diagnosis of DCIS is made based on architecture and cytology. This case report highlights the role of fine needle aspiration cytology in the diagnosis of this entity coexisting in a fibroadenoma.

Introduction

Clinging carcinoma, a variant of ductal carcinoma in situ (DCIS), is an under recognised entity.[1] It is identified by the presence of cytologic atypia of luminal epithelial cells without simultaneous alterations of basally located myoepithelial cells. Generally, intraluminal proliferation of the involved ducts or ductules is not seen. Fibroadenoma is the most common benign breast tumor in adolescent girls and young women with a peak incidence in the second and third decades of life. It is a biphasic tumor composed of stromal component and epithelial component.[2] The epithelial elements of a fibroadenoma can undergo a variety of proliferative changes similar to that seen elsewhere in the breast. Co-existing carcinoma is rare and is usually discovered incidentally. This case report highlights the role of fine needle aspiration cytology (FNAC) in the diagnosis of this entity coexisting in a fibroadenoma.

Case Report

A 48 years old lady, a known diabetic and hypertensive, presented with bilateral breast lumps of one week duration. There was no family history of breast or ovarian tumors. Patient had regular menstrual cycles in the past. On examination, there was a 4 × 4 cm hard lump in lower inner quadrant of left breast which was fixed to the chest wall and there was a lump in right breast, firm mobile measuring 1 × 1 cm in the lower outer quadrant. Impression of left breast lump on magnetic resonance imaging (MRI) was suspicious of malignancy [Figure 1]. Right breast lump was a 2.3 × 1.5 cm well defined mass lesion with type 1 contrast enhancement pattern (less than 6% malignant probability) with bilateral axillary lymphadenopathy. Ultrasound and bone scan were negative for detectable metastasis.

Figure 1

MRI of bilateral breast lumps- 3.8 × 3.5 × 3 cm irregular speculated mass in left breast (Suspicious of malignancy), 2.3 × 1.5 cm well defined mass lesion in right breast (less than 6% malignant probability)

FNAC was done from both the breast lumps and left axillary lymph node. Right axillary lymph node was clinically not palpable. Smears from the left breast showed poorly cohesive clusters of ductal cells with pleomorphism, hyperchromasia and prominent nucleoli. Myoepithelial cells and bare nuclei were not seen. FNAC from left axillary lymph node also showed similar cells.

The smears from the right breast mass showed three dimensional clusters of cells with hyperchromatic nuclei, prominent nucleoli. There were singly scattered pleomorphic cells with mitotic figures. Admixed with these clusters were benign ductal cells with no nuclear pleomorphism along with myoepithelial cells. A few bare nuclei were also seen. Cytologic diagnosis of duct cell carcinoma of bilateral breast lumps with left axillary lymph node metastasis was made [Figure 2].

Figure 2

(a) Benign ductal epithelial cell cluster (Pap, ×100); (b) Lesion with bare bipolar nuclei in the background (MGG, ×400); (c) and (d) Clusters of cells with hyperchromatic nuclei and prominent nucleoli (MGG, ×400)

Trucut biopsy of left breast lump showed features of infiltrative duct cell carcinoma. Immunohistochemistry was positive for estrogen and progesterone receptors. On the basis of the physical examination results, right breast lump was suspected as a fibroadenoma. Hence, lumpectomy was performed. The specimen grossly was a 1 × 1 cm, circumscribed tumor. Histopathology of multiple and serial sections revealed ductal structures surrounded by hyalinized stroma with focal myxoid areas. The lining of the ductal structures was bilayered. A significant number of ducts showed stratification of the lining epithelium, nuclear hyperchromasia and irregular nuclear contours, but myoepithelial lining was intact. There were no solid or cribriform areas, no stromal infiltration. The latter was confirmed by immunohistochemical staining with smooth muscle actin (SMA) and pancytokeratin (Pan CK). A diagnosis of fibroadenoma with DCIS, clinging type, was made (DCIS) [Figure 3].

Figure 3

(a) Benign glands in fibroadenoma area (H and E, ×100); (b) Dilated duct with necrotic material (H and E, ×400); (c and d) Nuclear hyperchromasia with irregular nuclear contours (H and E, ×400)

Discussion

The term “clinging carcinoma in situ” was coined by Azzopardi when a carcinoma was missed and the patient developed infiltrating ductal carcinoma 8 years later.[3] It is characterized by atypical cells replacing the single layer of luminal epithelial cells in a flat fashion without any proliferation or micropapillary structure formation. Though it was ignored for a long time, there is a renewed interest as Moinfar and Schnitt[1] equated it with high grade flat epithelial atypia.

In the present case, the cytologic features of the lesion were unequivocally malignant. Lower magnification of histologic sections resembled a fibroadenoma. A detailed evaluation of tubules and the lining epithelium showed foci with intraluminal necrotic debris and occasional rigid tubule. The involved structures showed hyperchromatic nuclei of epithelial cells.

Epithelial hyperplasia developing within a fibroadenoma is a common finding. There are a few case reports with in situ/invasive ductal and lobular carcinoma in a fibroadenoma which are either cribriform/solid variants.[4-6] There are no reported cases of clinging carcinoma with fibroadenoma. An important differential diagnosis for clinging carcinoma is low grade flat epithelial atypia. Since both are architecturally similar, significant cytologic atypia is the differentiating feature. The incidence of carcinoma within fibroadenoma is reported to be between 0.1% and 0.3%, with a peak age between 42 and 44 years.[5-7] The biological behavior of carcinoma occurring within fibroadenoma does not differ from that of breast carcinoma which is unrelated to fibroadenoma.[5] Preoperative clinical and radiological diagnosis of malignancy in a fibroadenoma, especially of in situ carcinoma, is usually not possible.

FNAC is a useful test that guides the clinician to decide further step of patient management. However, FNAC diagnosis may not always represent the actual lesion. This occurs due to sampling error which is a known drawback of cytology. Surprisingly, in the present case, though the clinical examination was suggestive of fibroadenoma and MRI was suspicious of malignancy, FNAC revealed features of duct cell carcinoma which was confirmed as clinging carcinoma on histopathology.

Conclusion

Cytology is advantageous in the diagnosis of clinging carcinoma. We stress upon the need for compulsory excision of clinically diagnosed fibroadenomas and also the importance of histopathological evaluation of all breast masses irrespective of their clinical diagnosis as benign lesions. Special attention is warranted in women older than 35 years and with risk factors for carcinoma breast presenting with a fibroadenoma.