We describe a phyllodes tumor of borderline malignancy in the labium majus of a 49-year-old woman. The histogenetic origin of phyllodes tumors in the vulva is controversial. Strong immunoreactivity for NY-BR-1, a novel breast differentiation antigen, was demonstrated within the epithelial components of the phyllodes tumor. A similar expression pattern was observed in mammary-like glands of the vulva. These findings provide further evidence that phyllodes tumors of the vulva might derive from mammary-like glands in the labium majus or from ectopic breast tissu

Giger, Olivier

Honegger, Christoph

Lacoste, Elena

Moch, Holger

Padberg, Barbara

Varga, Zsuzsanna

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CASE REPORTExpression of the breast differentiation antigen NY-BR-1in a phyllodes tumor of the vulvaOlivier T. Giger & Elena Lacoste & Christoph Honegger &Barbara Padberg & Holger Moch & Zsuzsanna VargaReceived: 5 December 2006 /Accepted: 25 January 2007 / Published online: 21 February 2007# Springer-Verlag 2007Abstract We describe a phyllodes tumor of borderlinemalignancy in the labium majus of a 49-year-old woman.The histogenetic origin of phyllodes tumors in the vulva iscontroversial. Strong immunoreactivity for NY-BR-1, anovel breast differentiation antigen, was demonstratedwithin the epithelial components of the phyllodes tumor.A similar expression pattern was observed in mammary-like glands of the vulva. These findings provide furtherevidence that phyllodes tumors of the vulva might derivefrom mammary-like glands in the labium majus or fromectopic breast tissue.Keywords Vulva . Phyllodes tumor . NY-BR-1 .Mammary-like glandsIntroductionMammary glands are modified apocrine glands arisingalong the mammary ridges, which appear on either side ofthe body in the fourth week of embryonal development,persisting only for a week. Remnants of these ridges canresult in an arborising mesh of canals, giving rise toaberrant lactiferous ducts at anatomical sites other than thebreast in the form of ectopic breast tissue. A fully formedmammary gland arising in the vulvar region was firstdescribed in 1872 by Hartung in a 30-year-old woman atthe left labium majus. Since then, various benign andmalignant variants of epithelial mammary tumors have beendescribed, and ectopic mammary glands have beenregarded as the tissue of origin of these neoplasms.It has been reported that histologic changes in theectopic breast tissue are, in general, similar to hormon-induced lesions in the breast occurring during puberty andearly pregnancy [9]. Benign or malignant tumors of thevulva other then squamous neoplasms occur very rarely[20]. Whether proliferative processes mimicking breastlesions in the anogenital region evolve from remnants ofthe mammary ridges or originate from local adnexalstructures, e.g. eccrine, sebaceous and apocrine glands ofthe skin, from mammary-like glands (MLGs) of the vulva,or whether they arise in neoplastically transformed ectopicbreast tissue are still a question of debate.In this report, we present a rare case of a phyllodes tumorin the vulva. We show that the recently described breastdifferentiation antigen NY-BR-1 is expressed in this tumorat an extramammary site as well as in MLGs of the vulva.Clinical historyA 49-year-old hysterectomized, smoking (60 packageyears) but otherwise healthy perimenopausal patient pre-sented with a rapidly growing mass at the labium majusnear the clitoris on the right side. The patient was treatedwith 17-β-estradiole for menopausal symptoms. Thesymptoms were spotting and discharge. The lesion, whichdeveloped within 5 weeks, measured 3.7 cm in diameterand appeared sharply circumscribed. The tumor wasexcised surgically. A second resection was performed2 months after the first tumor excision.Virchows Arch (2007) 450:471–474DOI 10.1007/s00428-007-0377-8O. T. Giger (*) :B. Padberg :H. Moch : Z. VargaInstitute of Surgical Pathology, University Hospital of Zurich,Schmelzbergstrasse 12,CH 8091 Zurich, Switzerlande-mail: Olivier.giger@hispeed.chE. Lacoste : C. HoneggerDepartment of Gynecology, Hospital Uster,Uster, SwitzerlandMaterials and methodsThe surgical specimen was fixed in 4% buffered formalinand submitted entirely for histology. Two-micrometersections from the paraffin-embedded tissue were taken forimmunohistochemistry and haematoxylin and eosin (H&E)staining (Superfrost Plus, Menzel, Braunschweig, Ger-many). Immunostaining for mAb NY-BR-1 [21]; LudwigInstitute, New York) was performed on Ventana Benchmark(Ventana Medical Systems, Tucson, AZ) at a dilution of1:400 (concentration, 2 μg/ml), MIB-1 (DAKO Diagnos-tics, dilution 1:20), CD34 (Serotec, dilution 1:50), estrogenreceptor (6F11, Ventana dispenser), and progesteronereceptor (1A6, Ventana dispenser).ResultsOn gross examination, the specimen appeared as a polypoidfirm lesion, with an uneven surface. The polypwas covered bynormal epidermis. The cut surface was light gray, showing afirm sharply demarked tumor of 3.7 cm in diameter (Fig. 1).The histological examination of the tumor revealed asubcutaneous mass consisting of a predominant stromalcomponent, interrupted by leaf-like spaces lined by anepithelial component with bilayered epithelia consisting ofmyoepithelial and secretory cells, which directly harboredto the surface and covered the same one superficially. Thesurface of the tumor was focally ulcerated, without directinfiltration through neoplastic cells (Fig. 2).The lining was predominantly composed of secretory(apocrine)-type epithelia and resembled mammary glandu-lar epithelia. The secretory epithelial cells demonstrated astrong nuclear and cytoplasmatic immunoreactivity to NY-BR-1 and a 100% nuclear immunoreactivity for estrogenand progesterone receptors. No atypia or significant mitoticactivity was present in the epithelial tumor component. Thestroma was hypercellular with spindle-shaped, moderatelypleomorphic cells with pale elongated nuclei and scantycytoplasm. Focally, the mitotic activity of the stroma wasincreased (three to four mitoses per ten high-power fields,HPF). The proliferation index was 5% (MIB-1, Ki67). Theneoplastic stroma demonstrated a stronger immunoreactiv-ity for CD34 than the surrounding subcutaneous connectivetissue. There was a small intraductal papilloma within thepolypoid lesion. Overtly polymorphic stromal cells, necro-sis or brisk mitotic activity exceeding ten mitoses per tenHPF were absent. Therefore, the tumor was diagnosed as aphyllodes tumor with “borderline” malignancy.Eccrine glands and MLGs were observed adjacent to thetumor. The latter also showed nuclear and cytoplasmicreactivity for NY-BR-1.Because of the incomplete resection and the unpredict-able behavior of “borderline” phyllodes tumors, a secondresection was performed 2 months after the primaryexcision. The resection specimen contained MLGs, regen-erative tissue with foreign body reaction but no remnants ofthe phyllodes tumor.DiscussionIn this report, we describe a phyllodes tumor of the vulvaand discuss its histogenesis in the light of its expression ofthe novel breast differentiation antigen NY-BR1.Various benign and malignant tumors resembling breastneoplasms have been described in the vulvar region [1–3, 5,6, 8, 9, 15, 16, 20]. It has been suggested that these tumorsderive from ectopic breast tissue or from MLG.Cystosarcoma phyllodes of the breast, today preferen-tially named phyllodes tumor, was first described byJohannes Müller in 1838 [7]. According to our knowledge,five phyllodes tumors [4, 14, 17, 18] of the vulva and onephyllodes tumor of the perineum [13] have been reported.More than two dozen fibroadenomas of the vulva have beendescribed, and it has been discussed whether these neo-plasms arise from skin adherence glands or from ectopicmammary tissue.The epithelial cells of the present tumor demonstratestrong cytoplasmic and nuclear NY-BR-1 immunoreactivi-ty. NY-BR-1 is a novel mammary differentiation antigen. Itwas recently identified by SEREX analysis of a metastaticbreast carcinoma patient [10–12]. The NY-BR-1 gene hasbeen mapped to chromosome 10p11–12 and is composed of37 exons. It encodes a peptide of Mr 150,000 to 160,000,which is regarded as a putative transcription factor. NY-BR-Fig. 1 Phyllodes tumor of the vulva. Overview (H&E). Typical leaf-like pattern (scale bar=1 cm)472 Virchows Arch (2007) 450:471–4741 mRNA expression was found in a high percentage ofbreast cancers (84%) and normal breast tissue and at amuch lower level in normal adult testis but not in othernormal tissues [10]. We have recently demonstrated strongprotein expression in mammary glands and in carcinomasof the breast using immunohistochemistry [21]. Ourfindings suggest that the novel monoclonal NY-BR-1antibody can be used as a surrogate marker for tumors ofbreast origin.The NY-BR-1 expression is a strong argument for aderivation of the phyllodes tumor of the vulva from MLGsor from ectopic breast tissue. Further evidence for aderivation of the phyllodes tumor from MLGs is itslocation at the inner side of the labium majus and theFig. 2 Phyllodes tumor of the vulva. Histology and immunohisto-chemistry. A–B Mammary-like glands in the vicinity of the phyllodestumor (arrowhead) HE (a) and NY-BR-1 immunohistochemistry (b;A–B scale bar=1 mm). C–E Detail of stroma with increased mitoticactivity. Arrows indicate two mitoses in one HPF (c); Bilayeredepithelium consisting of myoepithelial- and secretory-cell layers (d );NY-BR-1 immunoreactivity in cytoplasm and nuclei of secretoryductal cells (e; C–D scale bar=20 μm). Legend to figures: F–G MLGin the surroundings of the phyllodes tumor. HE ( f ) and NY-BR-1(g; F–G scale bar=0.15 mm)Virchows Arch (2007) 450:471–474 473prominent MLGs in the immediate surroundings. Van derPutte [19, 20] suggests that vulvar neoplasms resemblingbreast tumors most probably arise in MLGs. He observedthat many of these lesions (a) greatly resemble but are notidentical to corresponding lesions of the breast, (b) occuralso in the perineum and around the anus but rarelyelsewhere on the skin and (c) are elements of discussionconcerning their derivation that focus on eccrine or apocrineglands or their precursor cells rather than on mammary tissue.He further argues that these features reflect basic elements ofthe MLGs that are directly related to eccrine glands and showapocrine metaplasia. Some MLGs reveal a mammary-typehistology as the predominant feature.The behavior of phyllodes tumors is difficult to predictby histology alone. In the breast, phyllodes tumors areclassified into benign, borderline and malignant accordingto mitotic rate, nuclear pleomorphism and presence of necrosis.Because of the increased mitotic activity, the tumor ofour patient was classified as “borderline.” After incompleteexcision of the lesion, an additional resection wasperformed to prevent local recurrence.In summary, we present a phyllodes tumor of the vulvawith strong expression of the breast differentiation antigenNY-BR-1. MLGs of the vulva also express this antigen andwere abundantly present in close vicinity to the tumor.Therefore, we speculate that at least some phyllodes tumorsof the vulva are derived from such glands, although wecannot exclude that ectopic mammary glands are also theorigin of such vulvar tumors.References1. Baisre A, Heller DS, Lee J, Zheng P (2002) Fibroadenoma of thevulva. A report of two cases. J Reprod Med 47(11):949–9512. 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Expression of the breast differentiation antigen NY-BR-1 in a phyllodes tumor of the vulva

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Expression of the breast differentiation antigen NY-BR-1 in a phyllodes tumor of the vulva

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