Uterine cervical mesonephric hyperplasia with focal cystic change ...

Human Pathology: Case Reports 12 (2018) 48–51

Contents lists available at ScienceDirect

Human Pathology: Case Reports journal homepage: www.elsevier.com/locate/ehpc

Case Report

Uterine cervical mesonephric hyperplasia with focal cystic change masquerading clinicopathologically as lobular endocervical glandular hyperplasia to malignancy

T

⁎

Ken-ichi Mizutania, Sohsuke Yamadaa,b, , Satoko Nakadaa,b, Nozomu Kurosea,b, Akane Aikawaa,b, Chizuru Futatsuyaa, Motona Kumagaia, Akihiro Shioyaa, Hiroshi Minatoa,c, Takayuki Nojimaa,d a

Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan Department of Pathology, Kanazawa Medical University Hospital, Ishikawa, Japan Department of Diagnostic Pathology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan d Department of Diagnostic Pathology, Kanazawa University Hospital, Japan b c

A R T I C L E I N F O

A B S T R A C T

Keywords: Uterine cervix Mesonephric hyperplasia (MH) Lobular endocervical glandular hyperplasia (LEGH) Adenocarcinoma

Introduction: Although uterine cervical mesonephric hyperplasia (MH) arising from mesonephric remnants is a well-known but uncommon entity, it might pose a clinicopathological diagnostic challenge to distinguish from lobular endocervical glandular hyperplasia (LEGH) or adenocarcinoma, if MH rarely presents as a lobular and/or cystic mass with expansion of the cervical wall. However, few papers have described the detailed clinicopathological characteristics of MH compared to those benign to malignant lesions. Case presentation: An early forties Japanese female presented with a history of increased vaginal watery discharge. Multiple cystic lesions measuring less than 3 mm in diameter generated a high signal intensity on T2weighted MRI, in the bilateral aspects of the variably enlarged uterine cervix. A gross examination of a hysterectomy specimen revealed bilateral small multicystic lesions, filled partly with secreted fluids, measuring approximately 25 × 7 × 5 mm, respectively, located in the superficial to relatively deep cervical wall. A microscopic examination showed that these lesions predominantly consisted of a lobular proliferation of small to medium-sized tubules and cysts containing occasionally periodic acid-Schiff-positive eosinophilic/pink secreted materials, lined by bland-looking cuboidal to flattened epithelium. Immunohistochemically, these lining cells were specifically positive for CD10 in a characteristic luminal staining pattern, whereas negative for MUC6, and had a low MIB-1 labeling index. We ultimately made a diagnosis of cervical MH, lobular type, with focal cystic change. Conclusion: We should be aware that, since gynecologists/pathologists might misinterpret MH as LEGH to malignancy, including the malignant counterpart of MH, a wide panel of immunohistochemical antibodies can be helpful supplemental tools.

1. Introduction Particularly in women, the mesonephric (Wolffian) ducts embryologically regress during their development, however, if persistent, those remnants might be recognized incidentally even in the lateral walls of the uterine cervix [1–4]. Mesonephric remnants were first described by Meyer in 1907 [3,4], and subsequently, Ferry and Scully reviewed their experience, in which mesonephric remnants comprised up to 20% of all the cervical specimens largely depending on the methods of sampling [3,5]. Hyperplasia of these elements, i.e., uterine

cervical mesonephric hyperplasia (MH), is a well-known established entity but occurs uncommonly, and MH not only involves the deep layer of the cervical wall, but also extends close to the luminal surface intermingled with pre-existing endocervical glands [3,4]. Although generally asymptomatic, if MH rarely presents as a lobular and/or cystic mass with expansion of the cervical wall, it might pose a clinicopathological diagnostic challenge to distinguish widely ranging from lobular endocervical glandular hyperplasia (LEGH) to malignancy, such as mesonephric carcinoma or minimal deviation adenocarcinoma (MDA) [6,7]. However, few papers have described the detailed

Abbreviations:MH, mesonephric hyperplasia ⁎ Corresponding author at: Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Uchinada, Ishikawa 920-0293, Japan. E-mail address: [email protected] (S. Yamada). https://doi.org/10.1016/j.ehpc.2018.01.006 Received 2 November 2017; Received in revised form 16 January 2018; Accepted 30 January 2018 2214-3300/ © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).


K.-i. Mizutani et al.

benign, such as a LEGH, but could not completely rule out malignancy. Simple total hysterectomy was performed, and a gross examination of its cut surface revealed bilateral small multicystic lesions, filled partly with secreted clear fluids, measuring 25 × 7 × 5 mm (lt. side) or 23 × 7 × 4 mm (rt. side), respectively, located in the superficial to relatively deep cervical wall variably thickened (Fig. 1B). On scanning magnification, these cervical lesions showed a well-circumscribed and localized multicystic-like foci, measuring less than 3 mm in diameter of each cyst or tubule (Fig. 1C). Resection was diagnosed as complete by this histopathological examination. Microscopically, these lesions predominantly comprised a lobular proliferation of small to medium-sized, non-complex tubules with focal cystic change (Fig. 2A), containing occasionally PAS-positive eosinophilic/pink, amorphous and secreted materials, lined by non-ciliated, one-layered cuboidal to flattened epithelium having bland nuclei and no cytoplasmic mucicarmine-positive mucin without any evidence of mitotic figures (Fig. 2B). They extended to not only middle deep layer of the cervix, separated by variable amounts of stroma, but also close to the cervical mucosal surface with focal cystic change (Fig. 2A & B). There were neither desmoplastic reaction to invasive growth nor periglandular stromal edema. Furthermore, pre-existing endocervical glands and endometrium/myometrium have no remarkable change. In immunohistochemistry, the lining cells of tubules/cysts were specifically positive for CD10 in a characteristic luminal staining pattern (Fig. 2C), whereas completely negative for MUC6 and estrogen receptor (ER), and demonstrated a low Ki67 (MIB-1) labeling index (1 to 3%) (Fig. 2D). In a background, immunohistochemically p16-positive cells were absent. Based on these features, we finally made a conclusive diagnosis of MH, lobular type, with focal cystic change, arising from the bilateral aspects of uterine cervix. To date, after approximately 1 and half years of post-operative follow-up, the patient remains well without any evidence of recurrence/metastases.

clinicopathological features of MH compared to those benign to malignant lesions. Histopathologically, MH of the uterine cervix has been sometimes classified into several types, based on the architectural pattern of the glands, even though there would be no clinical significance [3,4]. The lobular MH is the most common type, characterized by a lobular arrangement of clustered, small to medium-sized and round, but occasionally dilated cystically, mesonephric tubules filled with periodic acid-Schiff (PAS)-positive eosinophilic to pink amorphous materials, often arising deeper in the cervical stroma and separated by variable amounts of stroma [3]. The less common type is called the diffuse MH, characterized predominantly by a non-clustered, extensive and diffuse proliferation of mesonephric tubules separated by varying amounts of cervical stroma, coexisted occasionally with minor foci of the lobular MH [3]. Finally, the least common type of MH is the duct MH, composed of one or more ducts lined by hyperplastic-appearing epithelium without atypia, usually lacking the intraluminal eosinophilic/pink secretions and often displaying clefted contours [3]. We herein report a rare case of lobular type MH with focal cystic change originating from the bilateral aspects of the variably enlarged uterine cervix, showing unique clinicopathological features and masquerading as wide range from LEGH to malignancy. The first clinicopathological examinations did not allow for a conclusive diagnosis, and the final diagnosis was ultimately made based on a wide panel of immunohistochemical analyses, including its hallmark antibodies, CD10, MUC6 and MIB-1. 2. Case report An early forties Japanese female presented with a history of increased vaginal watery discharge. She had an unremarkable medical history, except for ventricular septal defect in childhood. The laboratory data, including the blood cell count, chemistry, and tumor markers, were within normal limits. Localized multiple cystic lesions measuring less than 3 mm in diameter generated a high (white to whitegrayish) signal intensity on T2-weighted MRI images of both sagittal and horizontal sections, in the bilateral aspects of the mildly enlarged uterine cervix (Fig. 1A). A routine cervical smear detected no apparent atypical cell clusters. The gynecologists first interpreted these lesions as

3. Discussion More recently, very few case reports and review articles available on uterine cervical MH have suggested that a confident and accurate diagnosis might be impossible based on a clinical and morphological (H&

B

A

C

49

Fig. 1. The imaging, gross and loupe findings at surgery of the uterine cervical MH. (A) Localized multiple cystic lesions measuring less than 3 mm in diameter generated a high (white to white-grayish) signal intensity (arrowheads) on T2-weighted MRI images of horizontal sections, in the bilateral aspects of the mildly enlarged uterine cervix wall. (B) On the cut surface from the hysterectomy specimen, gross examination showed bilateral small multicystic lesions, filled partly with secreted clear fluids, measuring approximately 25 × 7 mm, respectively (dot areas), located in the superficial to relatively deep cervical wall variably thickened. (C) On scanning magnification (H&E stain), these cervical lesions demonstrated a well-circumscribed and localized multicystic-like foci (arrowheads), measuring less than 3 mm in diameter of each cyst or tubule. Bar = 2 mm.



A

B

C

D

Fig. 2. The microscopic and immunohistochemical findings of the resected specimen of MH with focal cystic change, arising from the bilateral aspects of uterine cervix. (A) Under a low-power view, the cervical lesions predominantly comprised a lobular proliferation of small to medium-sized, non-complex tubules with focal cystic change, extending to not only middle deep layer of the cervix, separated by variable amounts of stroma, but also close to the cervical mucosal surface (arrowheads). There were neither desmoplastic reaction to invasive growth nor peri-glandular stromal edema. Bar = 500 μm (H&E stain) (original magnification: ×12.5). (B) Under a high-power view, those tubules and small cysts contained occasionally PAS-positive eosinophilic/pink, amorphous and secreted materials (inset), lined by non-ciliated, one-layered cuboidal to flattened epithelium having bland nuclei and no cytoplasmic mucin without any evidence of mitotic figures. Bar = 200 μm (H&E stain) (original magnification: ×100). (C, D) In immunohistochemistry, those lining cells of tubules/cysts were specifically positive for CD10 in a characteristic luminal staining pattern (inset) (C), and revealed a low Ki67 (MIB-1) labeling index (inset) (1 to 3%) (D). Bar = 200 μm (original magnification: ×100). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

examination of a resected specimen. However, we were finally able to accurately diagnose the current lesion after thorough analyses including the immunohistochemistry. All gynecologists/pathologists should be aware that the characteristic features of this lesion might result in a diagnostic pitfall. An appropriate and wide panel of immunohistochemical antibodies, such as CD10, MUC6 and MIB-1, can therefore be powerful supplementary tools for identifying benign lesions and reaching the correct, conclusive diagnosis of uterine cervical MH.

E staining) examination alone, after distinguishing this established entity from other benign to malignant lesions, including LEGH, mesonephric carcinoma or MDA. Indeed, since MH can potentially show diverse clinicopathological features, a lack of experience and/or misinterpretation of findings by medical doctors would prove to be a stumbling block [3,4]. From the pathological viewpoint, we thus agree with the importance of applying a wide panel of immunohistochemical antibodies in the conclusive diagnosis of multicystic lesions of the cervix [5,6], as described below. Among benign lesions, the clinicopathological differential diagnosis of the current case is only LEGH. The chief complaint and symptom of LEGH include watery and/or mucoid discharge in the reproductive to postmenopausal women, as presented in our patient, whereas uterine cervical MH is known to be usually asymptomatic [3,4]. In that sense, it is very likely that this case report of cervical MH is clinically remarkable. One explanation is that the present unusual symptom of increased vaginal discharge might be due to the activated pre-existing endocervical glands via MH. Moreover, lobular architecture with multicystic change might lead to clinical misdiagnosis of LEGH in the present case. Not only characteristic PAS-positive eosinophilic/pink, amorphous and secreted materials in the lumens of the tubules/cysts, but also immunohistochemical analyses, generally resolve these distinctions between MH and LEGH easily. As to the latter, based on the immunopositivity of CD10 with a luminal staining pattern and the immunonegativity of MUC6, we were able to exclude the possibilities of the above malignant neoplasm of MDA as well as LEGH [5,6,8]. In addition, the malignant counterpart of MH, mesonephric carcinoma, arising in the lateral wall of the uterine cervix, is one of critical differential diagnoses as shown herein, even though extremely rare. Unlike MH, it has been reported that mesonephric carcinoma typically shows an invasive and exophytic growth fashion of atypical tubules lined by disordered mucin-free cuboidal epithelium with mitotic figures [3,4]. Correspondingly, further analyses of the low MIB-1 labeling indices on the resected specimen of MH would be very powerful supplementary tools for excluding the possibility of malignancy including mesonephric carcinoma. We herein reported a rare case of lobular MH with focal cystic change, arising from the bilateral wall of the uterine cervix that proved very difficult to tentatively diagnose based solely on a morphological

Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. Availability of data and materials The dataset supporting the findings and conclusions of this case report is included within the article. Competing interests The authors declare no conflicts of interest in association with this study. Funding This work was partly supported by a grant from the fund of Kanazawa Medical University (KMU-2018-01) for Medical Research, Kanazawa, Japan (to S.Y.). Authors' contributions SY and KM participated in the conception of the study and writing and designing of the manuscript with figures and tables. SY, KM, SN, 50



NK, AA, MK, CF, AS, HM and TN performed the clinical imaging and/or pathological/immunohistochemical interpretation of this lesion. All of the authors have read and approved the final manuscript.

[3] J.A. Ferry, R.E. Scully, Mesonephric remnants, hyperplasia, and neoplasia in the uterine cervix. A study of 49 cases, Am. J. Surg. Pathol. 14 (1990) 1100–1111. [4] J.D. Seidman, F.A. Tavassoli, Mesonephric hyperplasia of the uterine cervix: a clinicopathologic study of 51 cases, Int. J. Gynecol. Pathol. 14 (1995) 293–299. [5] T. Welsh, Y.S. Fu, J. Chan, H.A. Brundage, J.L. Rutgers, Mesonephric remnants or hyperplasia can cause abnormal pap smears: a study of three cases, Int. J. Gynecol. Pathol. 22 (2003) 121–126. [6] P.B. Clement, R.H. Young, P. Keh, A.G. Ostör, R.E. Scully, Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases, including four with a malignant spindle cell component, Am. J. Surg. Pathol. 19 (1995) 1158–1171. [7] S. Bagué, I.M. Rodríguez, J. Prat, Malignant mesonephric tumors of the female genital tract: a clinicopathologic study of 9 cases, Am. J. Surg. Pathol. 28 (2004) 601–607. [8] M.R. Nucci, P.B. Clement, R.H. Young, Lobular endocervical glandular hyperplasia, not otherwise specified: a clinicopathologic analysis of thirteen cases of a distinctive pseudoneoplastic lesion and comparison with fourteen cases of adenoma malignum, Am. J. Surg. Pathol. 23 (1999) 886–891.

Acknowledgments We would like to thank Yuka Hiramatsu for her expert technical assistance. References [1] J.W. Huffman, Mesonephric remnants in the cervix, Am. J. Obstet. Gynecol. 56 (1948) 23–40. [2] V.D. Sneeden, Mesonephric lesions of the cervix; a practical means of demonstration and a suggestion of incidence, Cancer 11 (1958) 334–336.

51