—  SPECIALTY CONFERENCE  —

Cytopathology

Case 5 - Fibroadenoma with Extensive Involvement by LCIS

Dr. Andrea E. Dawson
Cleveland Clinic Foundation
Cleveland, Ohio


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Clinical History:
A 29 year old woman presents with a smoothly outlined spherical mass on a screening mammogram. An FNA is performed. (Images 5A, 5B)

Cytologic Findings:
The FNA diagnosis is positive for malignant cells; adenocarcinoma, favor lobular type. Due to the discrepancy between the FNA result and the clinical impression (rule out fibroadenoma) a core biopsy is performed.


Figure 5A - This aspirate is a high cellularity with numerous single epithelial cells. A stromal fragment is apparent in this photomicrograph which might raise the possibility of a fibroadenoma, however, the marked cellularity and discohesion is worrisome. (Papanicolaou stain, low power)

Figure 5B - A higher power shows a monomorphic population of small bland nuclei in clusters and singly. The cells have feature of lobular neoplasia. This aspirate was from a fibroadenoma that was extensively involved by LCIS. (Papanicolaou stain, high power)

The false- negative rate is often the focus of discussion of breast FNA. Although overall sensitivity and specificity rates in the literature for breast FNA are generally excellent, criticisms of breast FNA generally revolve around false negative rate(FNR). Most series that have analyzed the FNR in breast FNA have shown that the rate varies from 5 to 20% and is due predominantly to sampling errors by the aspirator not to interpretative errors. The Triple Test or correlation of the mammographic, clinical and cytologic findings is usually very helpful in these cases since a negative cytology and suspicious mammographic lesion will be referred for core or open biopsy. Less attention is paid to the false positive rate in breast FNA. The false positive rate is generally quite low, most series report a less than 1% false positive rate. When we include false suspicious diagnosis, the rate is higher however in this category an uncertainty regarding the diagnosis has been conveyed to the clinicians, therefore, most patients will have further biopsy or frozen section confirmation prior to proceeding to definitive surgical treatment. In the false suspicious/false positive category, many of the lesions are fibroadenomas or fibrocystic changes with varying degrees of hyperplasia. Inflammatory lesions can also be difficult to differentiate from malignancy and may elicit a false suspicious or positive diagnosis.

In this case presentation, I have presented the unusual circumstance of LCIS extensively involving a fibroadenoma to make several points regarding breast FNA.

In the ideal world we would all practice cytology with all of the available clinical information. For breast FNA it has clearly been demonstrated that incorporating the clinical and mammographic findings improves accuracy and leads to improved patient management. At the time this FNA was interpreted the information given was "rule out cancer", with no description of the mammographic or ultrasound characteristics of the lesion. If the cytopathologist had known that this lesion was smoothly outlined in a relatively young woman, a differential diagnosis could have been generated based on these findings. The following chart gives a brief overview of breast neoplasms that present as smoothly outlined lesions and their corresponding cytologic findings.

Smoothly Outlined Lesions of the Breast and their Cytologic Findings:
Diagnosis Cytologic Findings
Fibroadenoma Staghorn epithelial clusters, stroma, naked (bipolar) nuclei
Papillary Neoplasm Papillary architecture, single cuboidal to columnar cells, little atypia
Medullary Carcinoma High grade malignant cells in sheets and single, background inflammatory cells
Mucinous (Colloid) Carcinoma Mucinous material in background with low grade cells in clusters and single, eccentric nuclei

Histology and Clinical Follow-Up:

Discussion:
The core biopsy diagnosis is: Favor fibroadenoma involved by lobular carcinoma in situ. The lesion is excised and the diagnosis is: Fibroadenoma with extensive involvement by LCIS.

Fibroadenomas, generally occur more commonly in young women, but can occur in any age group. The other smoothly outlined lesion that occurs more frequently in younger women is medullary carcinoma. FNA can be extremely useful in preventing delay in diagnosis in this circumstance as medullary carcinoma is a straightforward cancer diagnosis on FNA. Mucinous carcinoma occurs more commonly in older woman and can usually be diagnosed as malignant in FNA. Overlap does occur at times between papillary neoplasms and fibroadenoma and mucinous cancers and fibroadenoma.

Typical Diagnoses In FNA Of Fibroadenoma
Simsir, et al reviewed 25 cases with a preoperative FNA diagnosis of FA with excision recommended due to atypical features. In this series, 88% of FA with an atypical diagnosis were benign on excision. There were two cases (8%) with a cancer diagnosis on biopsy. The false negative diagnoses were attributed to sampling error and interpretative error. These authors recommended a conservative approach to FNA which demonstrate a fibroadenomatous pattern but that have atypical features such as discohesion and mild nuclear atypia.

Cancer Involving A Fibroadenoma
Rarely, carcinoma may involve a fibroadenoma. The most common type is lobular carcinoma in situ (more than 50%) and 20% of the time ductal carcinoma in situ may be present in the FA. It has been shown that if DCIS is confined to the FA it has less likelihood of recurring. LCIS is rarely diagnosed in breast FNA as it is often an incidental finding in a biopsy for another reason. It is also difficult to distinguish lobular from ductal cancer both invasive and in situ types in FNA. In general, classic lobular carcinoma has monomorphic small uniform nuclei, bland chromatin and high nucelar/cytoplasmic vacuoles. There may be intracytoplasmic vacuoles. These were the features seen in this case in addition to marked cellularity so it is easy to see why a diagnosis of malignancy was made. The use of the triple test saved this patient from unnecessary surgery. A core biopsy was done when the cytologic and mammographic findings did not fit. The lesion was excised to rule out any invasive component.

References

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