Case 1C -

Fibroepithelial lesion with increased cellularity and mitotic activity

History: This ultrasound-guided core needle biopsy specimen is from a 38 year old woman with a well-circumscribed solid mass by imaging. How would you report the findings and what is your recommendation? Case #1C - Figure 1 Diagnosis: Fibroepithelial lesion with increased cellularity and mitotic activity. Recommendation: Open biopsy. Discussion: Fibroadenomas are generally easily diagnosed on core needle biopsy. It has been advised that a fibroadenoma diagnosed at core needle biopsy can safely be managed by observation alone if the histologic findings are concordant with the imaging characteristics. The problem arises when the fibroepithelial lesion shows increased stromal cellularity making the diagnosis difficult sometimes in distinguishing between a cellular fibroadenoma and a phyllodes tumor, especially with a limited sample. Phyllodes tumors are relatively uncommon accounting for less than 1% of primary breast neoplasms. Clinically, phyllodes tumors occur in an older age group than do fibroadenomata, generally occurring in women aged 35-55 years. However, phyllodes tumors have been described in patients as young as 10 and as old as 88. There appears to be no particular racial predilection. These tumors are almost always unilateral with rare cases of bilaterality. The most frequent presentation is that of a mass discovered on exam, but sometimes the history is that of a suddenly increasing mass that was previously stable in size. Histologically, phyllodes tumors have a broad range of appearances covering the spectrum from benign to outright malignant histology. The classic "leaf-like" architecture originally described is often not found, particularly in the more malignant varieties. On the "benign" end of the spectrum, phyllodes tumors can resemble a fibroadenoma with pronounced intracanalicular growth. However, several features can be helpful in distinguishing a benign phyllodes tumor from the typical fibroadenoma: (1) the stromal cellularity should be greater in a phyllodes tumor, particularly in the subepithelial zones; (2) the pronounced intracanalicular appearance will be exaggerated forming elongated epithelial clefts and occasionally "leaf-like" projections into slit-like cystic spaces; and (3) mitotic activity will be present, a finding very rare in typical fibroadenomata. Any phyllodes tumor can show epithelial hyperplasia and carcinoma can arise in phyllodes tumors as in fibroadenomata. There are only a handful of studies describing the surgical outcome of problematic fibroepithelial lesions diagnosed at core needle biopsy. Dershaw and colleagues reported on seven cases of fibroepithelial lesions where the differential was "fibroadneoma versus phyllodes tumor" and three (43%) of these lesions at open biopsy revealed a benign phyllodes tumor. In another study Meyer et al. reported on nine fibroepithelial lesions and two (22%) of these lesions at open biopsy proved to be a phyllodes tumor. In a study carried out by Ioffee and colleagues, there was a single case of "cellular fibroadenoma versus phyllodes tumor" identified which at open biopsy revealed a cellular fibroadenoma. Recently, Komeneka et al. reported their findings on the use of core needle biopsy as a diagnostic tool to differentiate between phyllodes tumor and fibroadenoma. Komeneka et al. Arch Surg 138:987-990, 2003 Core Biopsy No. Surgical Excisional Biopsy Fibroadenoma Phyllodes Tumor Favor Fibroadenoma 25 23 2 Favor Phyllodes Tumor 23 4 19 Equivocal 9 5 4 In conclusion, they stated that core needle biopsy can reduce the need for operative management of fibroepithelial lesions of the breast based on their findings. Two abstracts are presented at this year's meeting looking at pathologic features of fibroepithelial lesions on core needle biopsy that are predictive of surgical outcome. Jacobs et al. analyzed 27 core needle biopsy cases diagnosed as fibroepithelial lesions with cellular stroma. They performed immunohistochemistry on all cases using antibodies against p53 as well as proliferation markers, MIB-1 and Topoisomerase 2-alpha (Topo). At open biopsy, 14 cases were diagnosed as cellular fibroadenomas, 12 cases diagnosed as phyllodes tumor (5 benign, 6 borderline, 1 malignant). They reported that MIB-1 staining was greater for phyllodes tumor than fibroadenomas on excision, with similar findings with Topo. However, p53 did not discriminate between these two entities. Histologic features examined included stromal mitoses, the proportion of stroma to epithelium, and stromal cellularity and nuclear pleomorphism. In conclusion, the data suggested that certain pathologic features on core needle biopsy may be useful in determining outcome of these lesions at excision. These features include: (1) mitotic rate, (2) proliferation markers, MIB-1 and Topo, and (3) stromal histology. Similarly, Ridgway et al. believe that the use of MIB-1 index may aid in the differentiation of phyllodes tumor from borderline cases of fibroadenoma, which may be useful in facilitating sufficient operative planning and decreasing re-excision rates. In another study, Lawton and Agoff, found that mitotic activity, even a single mitotic figure/10 HPF's, on core needle biopsy strongly suggests the need for surgical excision, since 73% of their cases resulted in phyllodes tumor at open biopsy. Periductal stromal condensation and nuclear pleomorphism were other features used to suggest phyllodes tumor at excisional biopsy. The distinctions between cellular fibroadenoma and phyllodes tumor are often difficult enough on excisional biopsy; however, with the increased use of core needle biopsy, this distinction is even more difficult for the pathologist. While it is not possible to adequately subtype a phyllodes tumor on core biopsy, the finding of increased stromal cellularity, a leaf-like architecture, or readily-found mitoses in a core biopsy should raise concern and the pathologist should recommend an excisional biopsy whenever the differential includes phyllodes tumor. References: Dershaw DD, Morris EA, Liberman L, Abramson AF. Nondiagnostic stereotaxic core breast biopsy: Results of rebiopsy. Radiology 1996; 198:323-325. Ioffe OB, Berg, WA, Silverberg SA, Kumar D. Mammogaphic-histopathologic correlation of large-core needle biopsies of the breast. Mod Path 1998; 11:721-727. Jacobs TW, Connolly JL, Schnitt SJ. Nonmalignant lesions in breast core needle biopsies. To excise or not to excise? AJSP 2002; 26:1095-1110. Jacobs TW, Chen Y-Y, Guinee DG, Holden J, Cha I, Bauermeister DE, Hashimoto B, Hartzog G. Fibroepithelial lesions with cellular stroma on breast core needle biopsy: predictors of outcome on surgical excision. Modern Pathology 2004; 17:135(a). Komenaka IK, El-Tamer M, Pile-Spellman E, Hibshoosh H. Core needle biopsy as a diagnostic tool to differentiate phyllodes tumor from fibroadenoma. Arch Surg 2003; 138:987-990. Lawton TJ, Agoff SN. Histologic features of fibroepithelial lesions of the breast on core needle biopsy that require surgical excision. Modern Pathology 2004; 17:147(a). Liberman L. Clinical management issues in percutaneous core breast biopsy. Radiol Clin North Am 2000; 38:791-807. Meyer JE, Smith DN, Lester SC, DiPior PJ, Denison CM, Harvey SC, Christian RL, Richardson A, Ko WD. Large-needle core biopsy: Nonmalignant breast abnormalities evaluated with surgical excision or repeat core biopsy. Radiology 1998; 206:717-720. Reynolds HE. Core needle biopsy of challenging benign breast conditions: A comprehensive literature review. AJR 2000; 174:1245-1250. Ridgway PF, Jacklin RK, Ziprin P, Harbin L, Peck DH, Darzi AW and Rajan PB. Perioperative diagnosis of cystosarcoma phyllodes of the breast may be enhanced by MIB-1 index. Journal of Surgical Research 2004, 122:83-88.