Pseudoangiomatous stromal hyperplasia with giant cells in the female breast. No association with neurofibromatosis?

Overview

A simultaneous finding of pseudoangiomatous stromal hyperplasia (PASH) and stromal multinucleated giant cells (MGC) in mammary tissue was previously observed in patients with type-1 neurofibromatosis, indicating that it can represent a morphologic marker for this syndrome. Here, we present PASH with MGC occurring in the left breast of a 39-years-old woman who does not have neurofibromatosis. This case, along with two additional ones reported previously, indicates that PASH with MGC in the female breast may not be associated with neurofibromatosis.

Keywords:
breast – multinucleated giant cells – pseudoangiomatous stromal hyperplasia – neurofibromatosis type-1

Pseudoangiomatous stromal hyperplasia (PASH) and stromal multinucleated giant cells (MGC) represent relatively rare findings in mammary pathology (1–3). They are benign, and when either is seen in isolation, they lack further clinical significance. However, a simultaneous finding of PASH and MGC in a single lesion was observed in mammary tissue in some patients with type-1 neurofibromatosis (4–6), indicating that PASH with MGC could represent a morphologic marker for this syndrome. Here, we present PASH with MGC occurring in the female breast in a patient without neurofibromatosis (NF). This case, along with two additional similar ones (7,8), shows that the previously mentioned association with neurofibromatosis is probably infrequent when PASH with MGC is found in the female breast.

Materials and Methods

The excised tissue was fixed in 4% formalin and processed routinely. The sections were stained with hematoxylin and eosin. For immunohistochemistry, the following primary antibodies were used: alpha-smooth muscle actin (1A4), calponin (CALP), desmin (D33) (all from DAKO, Glostrup, Denmark), and CD34 (Qbend/10, NeoMarkers, Westinghouse, CA, USA).

Immunostaining was performed according to standard protocols using an avidin-biotin complex labeled with peroxidase or alkaline phosphatase. Microwave antigen pretreatment was used for immunoreactions with CD34, only. Appropriate positive and negative controls were applied.

Case report

A 39-years-old para 1 gravida 1 woman overcame mastitis in her lactation period 7 months ago. She continued to have mild pain, and therefore she underwent ultrasound examination. Ultrasound found a non-palpable hypoechoic lesion measuring 1 cm in the upper lateral quadrant of the left breast. The lesion was marked with Frank biopsy guide and excised completely. In addition, the patient was treated for mild chronic endometritis diagnosed five weeks ago.

Grossly, the excision measuring 3 x 3 x 2.5 cm had a fatty and fibrous cut surface without cystic changes. The fibrosis appeared to be accentuated in some foci, but no circumscribed or stellated lesion was found.

Histologically, the excision showed diffusely a pattern of PASH that involved both peri- and intralobular stroma (Fig. 1). Both a dense fibrous pattern with slit-like empty spaces and a more proliferative cellular pattern of PASH (2) were seen. Stromal MGC (1) were scattered predominantly in paucicellular and collagenized areas of PASH. Although they appeared atypical at low power, a higher magnification demonstrated bland round nuclei and an absence of mitotic figures. The epithelium of the breast showed only focal and mild ductal hyperplasia and rare, mild cystic dilatations of the ducts. Many lobules appeared partially destroyed and atrophic due to intralobular fibrosis of PASH.

Immunohistochemically, both mono- and multinucleated stromal cells of PASH expressed CD34 (Fig. 2A), calponin (Fig. 2B), and alpha-smooth muscle actin. A few of these cells were positive for desmin.

The diagnosis of PASH with MGC was rendered and an exclusion of type-1 NF was recommended. Clinical examinations (including dermatologic, neurologic and internistic) ruled out NF in the patient and in her family.

Discussion

In our case, PASH showed typical morphology and myoid phenotype (2,3), and stromal MGC were similar to those described in mammary stroma (1). The single unusual feature in this case is an association of PASH and MGC. As mentioned above, this finding was observed in mammary tissue in patients with NF (4–6). However, the NF-associated lesions were described either in male breast or in vulvar mammary-like glands of female patients, and not in the female breast. Damiani et al. (4) and Zamecnik et al. (6) described PASH with MGC in gynecomastia in patients with NF. Kazakov et al. (5) described one case of vulvar PASH with MGC in a patient with NF. In the female breast, only two cases of PASH with MGC were reported to our best knowledge (7,8), and both of these patients did not have NF. We think that these cases unassociated with NF can be explained as an accidental and rare coincidence of PASH and MGC. As only 3 lesions were described to date, it is obvious that study of additional cases is necessary to determine exactly whether PASH with MGC in the female breast does or does not have any association with NF. We recommend that, at least for the present, a brief clinical examination focused on exclusion of NF should be done in all these cases.

Correspondence address:
Dr. M. Zamecnik
Medicyt s. r. o.
Legionarska 28, 81171 Trencin
Slovak Republic
E-mail: zamecnikm@seznam.cz
Tel.: (mobil): +421-907-156629

References

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