Histologic evaluation of parovarian nodules in the cat

Abstract

Objectives

A notable, although relatively uncommon, finding during feline ovariohysterectomy is the presence of parovarian nodules, located proximal to the ovary, near or within the ovarian vascular bundle. They are usually 2–3 mm in diameter, white-to-tan in color and glandular in appearance. The objective of this study was to either decisively reinforce the existing findings reported in the literature, which suggest that these parovarian nodules are incidental adrenocortical nodules that are clinically and surgically insignificant, or capture any samples that were not ectopic adrenal tissue in order to characterize them histologically.

Methods

Ninety-one formalin-preserved tissue sections containing parovarian nodules were collected during routine feline elective ovariohysterectomy and evaluated histologically.

Results

Definitive histologic information was obtained from 73/91 (80.2%) submitted samples. Fifty-two of 73 (71.2%) samples were determined to contain accessory adrenal gland cortex. Twenty of 73 (27.4%) samples were determined to contain residual mesonephric structures. While accessory adrenocortical nodules were found bilaterally in cats of all ages, mesonephric structures were predominantly right-sided, and only found in one cat over the age of 1 year. Ectopic or accessory ovarian tissue was not found in any of the samples.

Conclusions and relevance

This study adds to the existing body of data which suggest these nodules are incidental structures that do not need to be removed during surgical sterilization. However, further in vivo studies with larger sample sizes and years of follow-up would be required to more definitively prove this theory.

Introduction

Parovarian nodules (located proximal to the ovary, near or within the ovarian vascular bundle) are relatively uncommon findings during feline ovariohysterectomy, but they are clinically relevant as they may be interpreted as ovarian tissue. These structures are usually 2–3 mm in diameter, white-to-tan in color and glandular in appearance. In two published feline studies, 18 total samples were evaluated, all of which were determined to be ectopic adrenocortical tissue.^1,2 There are several reports of ectopic adrenal tissue near the reproductive tract in humans and also a variety of domestic mammals.^2–6 It is believed that this occurs developmentally from abnormal migration of the urogenital ridge; that is, the coelomic epithelial cells that derive the gonads and adrenal cortex.^7,8 Ectopic and accessory ovaries have been reported to exist in the cow and in humans, but they are otherwise rare.^9–11

The objective of this study was to either decisively reinforce the existing findings reported in the literature, which suggest that these parovarian nodules are incidental adrenocortical nodules that are clinically and surgically insignificant, or capture any samples that were not ectopic adrenal tissue in order to characterize them histologically.

With this information, veterinarians can be better informed of the proper course of action when encountering these parovarian nodules. If some of the nodules are determined to be ectopic or accessory ovarian tissue, this could provide additional insight to veterinarians evaluating cats with ovarian remnant syndrome (ORS), as it is possible the traditional surgical techniques that do not rupture the suspensory ligament may prevent surgeons from visualizing these nodules. ¹²

Materials and methods

Samples were collected by one of the authors (MLHB) and two other spay/neuter veterinarians during routine feline ovariohysterectomy of client-owned and shelter-owned cats. Samples were trimmed down to the area of interest; that is, the affected ovary, parovarian nodule, ovarian vascular bundle and suspensory ligament. Neither the contralateral ovary nor the uterine horns were evaluated in this study. The tissue was fixed in 10% neutral buffered formalin for a minimum of 72 h prior to transport. Each sample was catalogued, including date of collection, the cat’s signalment and nodule location.

The tissue was processed and sectioned for routine hematoxylin and eosin staining by standard methods. The slides were examined by a pathologist/theriogenologist (CP), and the nature of the parovarian nodules was assessed (see Figure 1).

Figure 1

(a,b) Two examples of the observed accessory adrenal glands during ovariohysterectomy (arrows) (courtesy of Dr Graciela C Park). (c) Representative photomicrograph of an accessory adrenal gland (bar = 200 μm). (d) Representative photomicrograph of dilated mesonephric duct remnants (bar = 50 μm)

Results

Ninety-one samples were submitted for analysis. Fifty-eight samples were found near the right ovary and 33 near the left ovary. The mean age of all cats with parovarian nodules was 12.5 months, and the median age was 6.0 months. The youngest cat was 2.0 months old, and the oldest was 10 years old.

Usable histopathologic information was obtained from 73/91 (80.2%) submitted samples; 49/58 (84.5%) samples from the right side and 24/33 (72.7%) samples from the left side. In the 18 remaining samples submitted, no histologic abnormalities were observed.

Fifty-two of 73 (71.2%) samples were determined to contain accessory adrenal gland cortex. The mean age of the cats with accessory adrenal gland nodules was 16.2 months, and the median age was 8.0 months.

Twenty of 73 (27.4%) samples were determined to contain residual mesonephric structures. The mean age of the cats with nodules owing to mesonephric remnants was 6.0 months, and the median age was 2.0 months. Only one of the cats with mesonephric remnants was older than 12 months. The mesonephric remnants were found predominantly on the right side (75.0% of samples).

The remaining four samples were determined to be fimbrial cysts (two samples), and parovarian cysts of unknown origin (two samples). The mean age of these cats was 13.8 months.

Five samples were submitted from cats with bilateral nodules. Two of these cats had bilateral accessory adrenal gland nodules, two of them had bilateral mesonephric remnant nodules and one had one nodule of each type.

No ovarian tissue was found in any of the samples.

Discussion

The adrenocortical and gonadal cell lines both differentiate from the same condensation of coelomic epithelial tissue overlying the urogenital ridge. It is thought that during the development of these organs, remnants of the urogenital ridge may migrate abnormally and subsequently undergo differentiation into the parovarian nodules found during ovariohysterectomy.^7,8

Prior to evaluating the samples in this study, it was hypothesized that these parovarian nodules may have clinical significance in cats being evaluated for ORS. Most studies retrospectively evaluate tissue removed from ovariohysterectomized pets with clinical signs of ORS, but not the nature or the incidence of aberrant parovarian tissue itself.^13–15 Owing to their location, traditional feline ovariohysterectomy methods that do not sever the suspensory ligament do not usually allow for visualization of these nodules. ¹² As surgical re-evaluation of cats with ORS generally results in the location of remnant ovarian tissue at the site of previous pedicle ligation,^13,14 an additional hypothesis of this study was that these nodules are accessory or ectopic ovarian tissue unable to be visualized at the time of surgery but close enough to the original surgical site to be assessed later as incompletely removed ovary. This hypothesis is unlikely based on the results reported here, as none of the slides evaluated showed any histologic characteristics of ovarian tissue.

The incidence of ectopic adrenal tissue appeared to be uniform across the age distribution of cats in this study. The age distribution in this study is similar to the typical age ranges of animals that are presented to the high-volume spay/neuter environment. However, the age distribution of cats with nodules owing to mesonephric remnants was significantly younger, with mesonephric structures found in only one cat over 12 months of age. The mesonephric remnants were found predominantly on the right side, although one cat had them bilaterally.

Based on the results of this study, it is reasonable to assume that most aberrant parovarian structures are clinically incidental and do not result in ORS related to the presence of ovarian tissue inadvertently left behind during surgery. One consideration is that the ectopic adrenal tissue may be endocrinologically active based on the shared embryologic nature of this tissue and the ovary. This scenario is unlikely based on the typical clinical signs of ORS. However, one approach to test this hypothesis would be to purposely leave the nodules in place and monitor the cat for signs of ORS. This could prove difficult, as the time from ovariohysterectomy surgery to clinical signs of ORS can vary from several months to several years,^13–15 and ethical concerns may arise from the medical consequences of retained ovarian tissue if this tissue is indeed endocrinologically active. Another approach would be to utilize immunohistochemistry to detect the production of estrogens in the ectopic adrenal gland; however, it would be difficult to conclude whether any estrogen present would be enough to manifest in ORS.

On a related note, parovarian cysts are a known (and usually incidental) finding in women, and are often surgically removed when discovered. Benign, borderline malignant and malignant parovarian tumors arising from mesonephric and paramesonephric structures have been reported in both humans and mice, but these findings have not been observed in the cat.^16–19

It is not incorrect to remove this tissue from feline patients in the interest of being cautious; however, it should be noted that surgical techniques that sever the suspensory ligament are often required for optimal visualization as the nodules may be some distance deep to the ovary.

Conclusions

The information obtained by this study helps to support the small amount of existing published data regarding parovarian nodules in the cat. It suggests that these nodules are likely incidental developmental remnants that do not need to be surgically removed during routine sterilization procedures, and do not likely play a role in ORS in the cat. However, further in vivo studies with larger sample sizes and years of follow-up would be necessary to definitively prove this theory.

Supplemental Material

Supplemental Material

Institutional Animal Care and Use Committee and owner consent statement