MyoD1 expression in fibroepithelial stromal polyps.

Fibroepithelial stromal polyps (FESPs) are benign polypoid mesenchymal lesions thought to arise from desmin-positive specialized stromal cells of the female genital tract. Although most cases are easily diagnosed by morphology alone, the morphology of FESPs is variable and in some instances can contain hypercellular stroma with numerous atypical desmin-positive cells, simulating botryoid embryonal rhabdomyosarcoma (ERMS). Recently, we encountered a cellular FESP showing desmin expression as well as nuclear immunoreactivity for the skeletal muscle-associated transcription factor MyoD1. Although these lesions are widely known to express desmin, there are very few studies examining expression of the more specific markers of skeletal muscle differentiation, myogenin and MyoD1. The aim of our study was to examine desmin, MyoD1, and myogenin expression in a series of 25 FESPs. Of the 25 cases, desmin expression was present in 23 (92%), at least focal MyoD1 expression was present in 10 (40%), and all cases were negative for myogenin. Follow-up data were available for all 25 cases, and none recurred or behaved in a malignant fashion. Awareness of this potential immunohistochemical pitfall and careful morphologic evaluation should allow for the confident distinction of MyoD1-positive FESP from botyroid ERMS in almost all instances.

Fibroepithelial lesions; The WHO spectrum.

Fibroepithelial lesions of the breast comprise a morphologically and biologically heterogeneous group of biphasic tumors with epithelial and stromal components that demonstrate widely variable clinical behavior. Fibroadenomas are common benign tumors with a number of histologic variants, most of which pose no diagnostic challenge. Cellular and juvenile fibroadenomas can have overlapping features with phyllodes tumors and should be recognized. Phyllodes tumors constitute a spectrum of lesions with varying clinical behavior and are graded as benign, borderline or malignant based on a set of histologic features according to recommendations by the World Health Organization (WHO). Recent developments have significantly expanded our understanding of the pathogenesis of fibroepithelial lesions, highlighting fibroadenomas as true neoplasms and underscoring a commonality with phyllodes tumors in the form of recurrent MED12 exon 2 mutations. In addition, sequencing studies have elucidated pathways associated with phyllodes tumor progression. Accurate diagnosis and grading of phyllodes tumors are important for patient management and prognosis, as grade broadly correlates with increasing local recurrence risk, and essentially only malignant tumors metastasize. However, classification of fibroepithelial lesions in many cases remains challenging on both core biopsy and excision specimens. A commonly encountered problem at the benign end of the spectrum is the distinction of benign phyllodes tumor from cellular fibroadenoma, which is largely due to the subjective nature of histologic features used in diagnosis and histologic overlap between lesions. Grading is further complicated by the requirement to integrate multiple subjective and ill-defined parameters. On the opposite end of the histologic spectrum, malignant phyllodes tumors must be distinguished from more common metaplastic carcinomas and from primary or metastatic sarcomas, which can be especially difficult in core biopsies. Immunohistochemistry can be useful in the differential diagnosis but should be interpreted with attention to caveats. This review provides an overview and update on the spectrum of fibroepithelial lesions, with special emphasis on common problems and practical issues in diagnosis.

Phosphohistone H3 expression correlates with manual mitotic counts and aids in identification of "hot spots" in fibroepithelial tumors of the breast.

Classification of mammary fibroepithelial tumors (FETs) relies on assessment of mitotic activity, among other histopathologic parameters. Routine hematoxylin and eosin (H&E) mitotic counts can be subjective and time consuming. Difficulty may arise in identifying "true" mitoses for a variety of reasons. Phosphorylation of histone H3 protein (PHH3) is correlated with mitotic chromatin condensation. The utility of PHH3 immunohistochemical staining to identify mitoses has been demonstrated in multiple organ systems. In this study, we examined the utility of PHH3 in assessing mitotic activity in FETs and compared PHH3- with H&E-determined mitotic counts. PHH3-stained mitoses were readily identifiable at ×10 magnification and allowed for rapid identification of mitotic "hot spots." Median mitotic counts/10 high-power fields for fibroadenoma, benign phyllodes tumor, borderline phyllodes tumor (BlnPT), and malignant phyllodes tumor (MPT) were 0, 0.5, 4.25, and 9, respectively on H&E, and 0, 0.75, 4.5, and 8, respectively for PHH3. Among all FETs, there was a strong positive correlation between H&E- and PHH3-determined mitotic counts (r=0.91, P<.001). Using PHH3, 2 cases would be reclassified, both from BlnPT to MPT. PHH3-determined counts correlated with H&E-determined counts in FETs. Using PHH3, a small number of cases were reclassified from BlnPT to MPT, for which treatment is similar. Although H&E-determined counts remain the criterion standard for assessing mitotic activity in FETs, PHH3 may be a useful adjunctive tool in some cases and is helpful in identifying mitotic hot spots.