Blue nevus presenting as an endocervical polyp

Introduction

Blue nevi of the uterine cervix are benign melanocytic neoplasms, which were once considered to be rare and were usually found incidentally in hysterectomy specimens [1, 2, 3, 4, 5, 6, 7, 8].
We report herein a case of blue nevus of the uterine cervix presenting as an endocervical polyp. Histological findings were completely the same as previously reported, but immunohistochemical findings were in partial disagreement with those described in some previous publications [8, 9, 10]. We discuss possible reasons for this discordance.

Case report

A 58-year-old Japanese female who complained of body weight loss (–4.7 kg/year) was referred to our hospital. The patient had no medical history of abnormal genital tract bleeding but a gynecological examination was performed as a part of a systemic examination. In addition to multiple uterine myomas (up to 4 cm in diameter) detected by transvaginal ultrasonography, a small endocervical polyp (5 mm in length) was found and excised promptly. Although the macroscopic observation by the gynecologist revealed no remarkable findings, examination of the histological specimen showed many pigmented spindle-shaped cells distributed in the stromal portion of the polyp (Fig. 1). Histochemical special stains verified that the intracellular pigments were melanin granules (Fig. 2). Immunohistochemical analyses using red chromogen (Bond Polymer Refine Red Detection, Leica Biosystems, Nussloch, Germany) further revealed that the cells were positive for S100 protein, SOX10, HMB45, and MART-1 (Fig. 3). Based on the characteristic cellular morphology and immunohistochemical findings, the lesion was diagnosed as being a blue nevus, and malignant melanoma was denied. Despite detailed medical examinations, the cause of the body weight loss was not identified.

Discussion

Although reports of endocervical blue nevi have been few, recent comprehensive pathologic studies revealed that this type of melanocytic disease was not so rare, especially in Japan [11, 12]. Their biological nature is completely benign corresponding to cutaneous tumors [10, 13]. The origin of melanin-loaded tumor cells has been suggested to differ from that of cutaneous tumors [8, 11, 12]. However, the present immunohistochemical results, S100 protein (+), SOX10 (+), HMB45 (+), and MART-1 (+), indicated that tumor cells of our case possessed representative melanocytic characters [14].
Their distinctive morphology, spindle-shape or dendritic contours and dark brown cytoplasmic pigments serve as reliable diagnostic hallmarks [10, 13]. A careful differential diagnosis is necessary to distinguish blue nevi from their malignant counterpart, desmoplastic melanoma, which can develop as a primary uterine cervical tumor [15]. Immunohistochemically, whereas blue nevi are positive for most of the representative melanocytic markers including S100 protein, HMB45 and MART-1, desmoplastic melanomas are negative for the latter two markers [13].
We could diagnose the present lesion as a benign blue nevus through prudent interpretation of the histological, histochemical and immunohistochemical findings, which were in agreement with descriptions in a dermatopathology textbook and most previous pathologic case reports. Concerning immunohistochemical features, the tumor cells were described as being positive for S100 protein, HMB45 and MART-1 [2, 3, 4, 5, 6, 7, 13]. Surprisingly, however, the immunohistochemical features described in latest edition of a gynecopathology textbook were different from our findings and previous reports; that is, this textbook stated that endocervical blue nevi are usually negative for HMB45 and MART-1 [10]. Certainly, two reports described that endocervical blue nevi were negative for HMB45 [8, 9], but no report has stated MART-1 negative. We could not find the reason why the textbook explained that MART-1 was usually negative.
As for the discordance in the HMB45-immunostaining results, we considered two possibilities. One is the existence of tumor subtypes. HMB45 is a melanosome-related antigen. While premature melanosomes are intensely stained with the antibody, late-stage melanosomes are hardly stained [16]. As above, the cellular origin of endocervical blue nevi has been suggested to be different from cutaneous tumors [8, 11, 12], and there may be tumor subtypes depending on cellular maturation.
The other possibility is derived from differences in the immunohistochemical techniques used. Standard brown chromogen potentially induces misinterpretation of findings on melanin-loaded cells. A pre-stain bleach technique seems to provide a reasonable resolution, but may weaken immune reactivity [7]. An alternative red chromogen has a great advantage when the immunohistochemical staining targets melanin-loaded cells [17].
In conclusion, we experienced a case of blue nevus of the uterine cervix presenting as an endocervical polyp. Detailed histological and immunohistochemical examinations led to the correct pathologic diagnosis. Endocervical blue nevi, as well as cutaneous tumors, are usually positive for S100 protein, SOX10, HMB45 and MART-1 immunohistochemically.

Acknowledgments

The authors thank Mr. Takeshi Nakatani for his excellent technical support.

The authors declare no conflict of interest.

References

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Address for correspondence

Yoshihiro Ikura
Department of Pathology
Takatsuki General Hospital
1-3-13, Kosobecho
Takatsuki 569-1192, Japan
tel. & fax: +81 72 684 0295
e-mail: ikura@ajk.takatsuki-hp.or.jp