Cancer Research and Treatment 2003;35(2):165-167 Müllerian-Type Gland Inclusions in Pelvic Lymph Nodes Mimicking Metastasis: A Case Report and Review of the Literature

Jinyoung Yoo, M.D., Ph.D., Hyun Joo Choi, M.D. and Seok Jin Kang, M.D., Ph.D.

Department of Pathology, St. Vincent’s Hospital, The Catholic University, Suwon, Korea

Benign inclusions are rare, and can be ment. Furthermore, pelvic and aortic lymphadenectomies mistaken for metastasis. We report, herein, a case of a may be warranted, as neoplastic transformation of preex- 50-year-old woman who underwent a hysterectomy, with isting metaplastic tubal-type epithelium is strongly sug- a lymphadenectomy, for an endometrial carcinoma. There gested. This paper presents a case of intranodal endosal- was no lymph node metastasis; however, the left external pingiosis mimicking metastasis. ( Research and and demonstrated a few Treatment 2003;35:165-167) glands, consistent with Müllerian-type inclusions (endos- ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ alpingiosis). Awareness of these lesions is important to Key Words: Endosalpingiosis, Lymph nodes avoid either unnecessary therapy or any delay in treat-

was diagnosed as having an endometrial adenocarcinoma on an INTRODUCTION endometrial curettage at another institution. There was no other significant past medical or surgical histories. The general examination was unremarkable. Following a preoperative MRI The presence of exogenous cells in lymph nodes are gen- of the pelvis, which demonstrated an ill-defined hypointense erally diagnostic of metastasis. An exception to this rule are mass at the endocervical canal, possibly representing cervical the benign inclusions, either glandular or nonglandular, with the involvement of an endometrial malignancy, the patient under- glandular being more common, of a Müllerian origin (endosal- pingiosis) (1∼5). Endosalpingiosis-type inclusions are observed within pelvic and , exclusively in wom- en, with or without concomitant disease of the female genital tract (1). Rare cases have been described in men (6). Although intranodal endosalpingiosis is a well-recognized entity, it may be confused with a metastatic carcinoma, especially in patients with known primary malignancies. It is thus important to be aware that benign intranodal inclusions may occur, and mimic metastasis. However, to our knowledge no such lesions have previously appeared in the Korean literature. This paper presents a case of endosalpingiosis in the pelvic lymph nodes of a 50-year-old woman, with a review of the relevant literature.

CASE REPORT

A 50-year-old woman was admitted, with a known endome- trial carcinoma, to the department of Gynecologic Oncology Service at our hospital. One month prior to her admission, she

Correspondence: Seok Jin Kang, Department of Pathology, St. Vin- cent’s Hospital, The Catholic University, Chi-dong 93, Paldal-gu, Suwon 442-723, Korea. (Tel) 031-249-7591, (Fax) 031-244- 6786, (E-mail) [email protected] Fig. 1. A few glands located in the fibrous capsule of the lymph Received January 24, 2003, Accepted March 13, 2003 node (Hematoxylin-eosin stain, ×40).

165 166 Cancer Research and Treatment 2003;35(2)

look exploration. The included structures may be either glan- dular or nonglandular. Several types of epithelial differentiation have been des- cribed: squamous, renal tubular, colonic and Müllerian. The Müllerian-type of inclusions are much more common, ranging from 5 to 41%, based on lymph nodes sampled in women (1). The glands are lined by an admixture of ciliated, secretory and intercalated cells, with (endometriosis) or without (endosal- pingiosis) associated stroma (7). These inclusions may cause a diagnostic problem, with regard to whether they are benign and incidental, or if they are related to the tumor metastasis in patients with gynecological malignancies (8). The increased frequency of these lymph node inclusions, sampled for primary ovarian malignancies, suggested they were more likely the bland- appearing forms of metastatic tumor (9). However, much of the recent literature considers these inclusions as benign, incidental lesions. Features favoring benignity include: a cap- sular or interfollicular location of the glands, different types of lining cells, including ciliated forms, a lack of significant cellu- lar atypia and mitoses, periglandular basement membranes and the absence of stromal desmoplasia (1,7). The histogenesis of Müllerian inclusions is unclear. Al- though, metaplasia of the embryonic rests of the coelomic epithelium is the most widely accepted mechanism (1,3,4). Other theories have been postulated, including peritoneal im- plantation of sloughed tubal epithelium, lymphatic dissem- Fig. 2. Higher magnification showing a gland lined by a single- ination of tubal mucosa and surgical implantation (10∼12). layer of ciliated, cuboidal-to-columnar epithelium, resembl- However, it is our belief that surgical implantation is the least ing tubal epithelium. Neither atypia nor mitosis are present likely, because intranodal inclusions are often seen in patients (Hematoxylin-eosin stain, ×200). with no previous surgical history. Malignancies found within the intranodal glandular inclusions have been reported (13∼15). There was a well-documented went a hysterectomy and selective bilateral pelvic and periaortic case of an ovarian, serous borderline tumor, with pelvic lymph lymphadenectomies. nodes, showing an admixture of benign endosalpingeal gland Histologically, multiple sections of the revealed inclusions and neoplastic tissue, which were identical to the extensive adenomyosis, with no residual tumor. Both ovarian tumor (13). Whether the neoplastic epithelium found in showed no malignancy, but exhibited endosalpingiosis. Most of the lymph nodes represented true metastasis, or a synchronous the regional lymph nodes showed reactive changes, but with no malignant transformation of the metaplastic Müllerian epithe- metastatic tumor, with the exception of the left external, and lium, is uncertain. If it was a true metastasis, occult micro- common, iliac lymph nodes, where glandular structures were invasion should be considered as a possible source of the found. These glands were distributed at the periphery of the metastasis. In their case, however, there was a lack of stromal lymph nodes, and were lined by a single layer of cuboidal to microinvasion, or destructive invasion, in the multiple sections columnar endosalpingiotic epithelium (Fig. 1). Ciliated cells from the ovaries. This, along with the juxtaposition of the were occasionally present. The nuclei were regular, basally benign endosalpingeal epithelium to the neoplastic serous epi- oriented or pseudostratified, and large, round to oval, with thelium, strongly suggested the possibility of the synchronous occasional small nucleoli (Fig. 2). Mitoses were absent. There development of a primary serous borderline tumor from a was no evidence of inflammatory, or fibrous, reactions or preexisting endosalpingiosis of the lymph nodes. This was sup- endometrial-type stroma, around the inclusions. ported by other investigators, who described, not only trans- The patient tolerated the procedure well, made an uncom- itional forms from endosalpingiosis to evolution of papillary plicated postoperative recovery, and was discharged on the serous borderline tumor in lymph nodes (14), but also a pa- seventh postoperative day. pillary serous cystadenocarcinoma, arising in inclusion cysts in pelvic and , with no other synchronous tumor identified (15). Due to the small number of such cases DISCUSSION in the literature, and a lack of follow-up data, the mode of nodal spread, the role of Müllerian inclusions, as an indepen- Intranodal inclusions of exogenous cells generally give rise dent source for tumor development, and their prognosis, remain to a strong possibility of metastasis. However, benign in- to be determined. clusions may occur, and should not be mistaken for metastasis The much less common nonglandular (nonepithelial) inclu- at the time of primary staging and diagnosis, or at a second- sions that have been described were nevus cells, mesothelial Jinyoung Yoo, et al：Intranodal Endosalpingiosis 167 cells, decidua and leiomyomatosis (1). Nevus cells are observed surgical material in males and females. Am J Clin Pathol in cervicoaxillary lymph nodes, but rarely in inguinal lymph 1969;52:212-218. nodes, whereas mesothelial inclusions most commonly involve 4. Kempson RL. Consultation case: glandular inclusions in lymph the mediastinal lymph nodes, followed by abdominal lymph nodes. Am J Surg Pathol 1978;2:321-325. nodes. In most intranodal mesothelial inclusion cases, there is 5. Farhi DC, Silverberg SF. Pseudometastases in female genital cancer. Pathol Annu 1982;17:47-76. hyperplasia, with inflammation of the associated serosal mem- 6. Huntrakoon M. Benign glandular inclusions in the abdominal branes, thus, its distinction from mesothelioma may be difficult. lymph nodes of a man. Human Pathol 1985;16:644-646. Benign inclusions, however, consists of cytologically bland- 7. Kurmam RJ. Blaustein's pathology of the female genital tract. looking cells, not impinging on the nodal structure. The meso- 3rd ed. Springer-Verlag, New York, 1987;542-544. thelial cells found in the lymph nodes are thought to be trans- 8. Lee EJ, Lee CH, Joo HJ. Sonographic appearance of endos- ported to the draining lymph nodes through the lymphatic alpingiosis. J Korean Soc Med Ultrasound 1998;17:147-153. system, which may be facilitated by the inflammatory process. 9. Moore WF, Bentley RC, Berchuck A, Robboy SJ. Some This is the first case reported in the Korean literature of Müllerian inclusion cysts in lymph nodes may sometimes be benign, Müllerian-type, glandular inclusions in the pelvic lym- metastases from serous borderline tumors of the . Am J ph nodes of a patient with an endometrial adenocarcinoma. Surg Pathol 2000;24:710-718. 10. Tsuchiya A, Kikuchi Y, Matsuoka T, Yashima R, Abe R, Awareness of these inclusions is essential, in that they simulate Suzuki T. Endosalpingiosis of nonmetastatic lymph nodes metastatic adenocarcinomas, potentially resulting in unneces- along the stomach in a patient with early gastric cancer: report sary therapy, or in the decision to withhold therapy. Fur- of a case. Surg Today 1999;29:264-265. thermore, pelvic and aortic lymphadenectomies may be war- 11. Gritsman AY, Schwartz AM. 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