A case of leiomyoadenomatoid tumour of uterine serosa: speculations about differential diagnosis

Abstract

Adenomatoid tumour is a benign rare lesion of the female genital tract, localised in the wall of fallopian tubes or beneath the uterine serosa. It is often accompanied by smooth muscle proliferation, obscuring the presence of adenomatoid tumour, resulting in misdiagnosis of cellular leiomyoma.

Here, a case of uterine serosal adenomatoid tumour associated with multiple leiomyomas and pelvic endometriosis in a 44-year-old woman who underwent surgical removal for uterine bleeding and abdominal pain is presented.

BACKGROUND

Adenomatoid tumours are benign histopathological entities occurring in male (epididymis and testis) and female (fallopian tubes and uterus) genital tracts. Rare cases have been described in extragenital sites.¹ The histological appearance of these tumours consists of gland-like spaces lined by flat or cuboidal cells with monomorphic nuclei and cytoplasmic vacuoles. These epithelioid structures are separated by fibromuscolar stroma, sometimes with abundant smooth muscle hypertrophical elements, mimicking leiomyoma, particularly in female uterine masses.²

Uncommonly, adenomatoid tumours can present necrotic or infarcted areas, associated with reactive changes instead of malignant aspects, in absence of appreciable mitotic activity and atypical mitotic figures.³

In the present report we discuss a case of leiomyoadenomatoid tumour in a 44-year-old woman localised in uterine serosa, associated to multiple leiomyomas and pelvic endometriosis.

CASE PRESENTATION

In December 2008, a 44-year-old woman with negative obstetric history presented to our hospital with uterine bleeding and dysmenorrhoea. Pelvic ultrasonography revealed numerous uterine masses with intramural, submucosal and serosal localisations. The patient underwent laparotomic removal. Four irregular, elastic and greyish masses were removed. The largest measured 11 cm in maximum length and it was examined in frozen section during the operation. An ematoxilin–eosin (EE) section slide revealed a monomorphic myometrial proliferation, in absence of necrosis. A pelvic peritoneal biopsy was also taken.

On pathological examination, the masses were extensively sampled and numerous EE routine slides were prepared and microscopically examined. On histology, all the masses constituted prominent fascicle of smooth muscle without significant mitosis or necrotic areas. Peritoneal biopsy revealed the presence of heterotopic endometrial tissue, as in endometriosis. During observation, attention was particularly focused on a 2.5 cm large lesion corresponding to a nodule in the serosa of the anterior uterine wall.

On routine stain, this lesion presented hypercellularity, with epithelioid structures entrapped in smooth muscle fibres (fig 1). Immnunohistochemical investigation revealed cords, tubular and glandular formations intermixed to muscular fibres (fig 2). These monomorphic epithelioid elements expressed pancytokeratin (fig 3), low molecular weight cytokeratins (CK7, CK5/6) (fig 4), mesothelial antigens (calretinin and Hector Battifora mesothelial antigen-1 (HBME-1)) (figs 5 and 6) and vimentin. Carcinoembryonic antigen (CEA), gross cystic disease fluid protein 15 (GCDFP15), cadherin E, vascular antigens (CD31, CD34) and actin were negative in these cells.

Figure 1.

Microscopic examination. Adenomatoid tumour (ematoxilin–eosin (EE) stain, ×4).

Figure 2.

Immunohistochemistry (×10). Actin is positive only on the muscular fibres, but it is negative in the adenomatoid tumour.

Figure 3.

Immunohistochemistry (×4). Pancytokeratin positivity.

Figure 4.

Immunohistochemistry (×20). Low molecular weight cytokeratin 5 and 6 positivity.

Figure 5.

Immunohistochemistry (×10). Calretinin positivity.

Figure 6.

Immunohistochemistry (×20). Hector Battifora mesothelial antigen-1 (HBME-1) positivity.

A diagnosis of leiomyoadenomatoid tumour with multiple uterine leiomyoma was made.

DISCUSSION

Adenomatoid tumour is a benign incidental finding reported in 1% of hysterectomy specimens. Due to the histological appearance and anatomical localisation, it is difficult to distinguish this peculiar lesion from a common tumour of the smooth muscle, especially in its solid, firm and elastic macroscopic variant. The cystic large form of adenomatoid tumour is more common and the identification is easier; it is present in male genital tract and in extragenital sides.

This tumour was first reported in 1925, when Strong described a singular lymphangioma of the fallopian tube.⁴ A mesothelial origin of adenomatoid tumour was suspected for the first time in 1942 by Masson et al.⁵ They observed the presence of microvilli on the surface of the epithelioid elements, similarly to mesothelial reactive cells. Many other hypotheses were made about the embryogenetic origin of this lesion. In 1953 Sundarasivarao suggested a possible mullerian origin because of the epithelial appearance of the single elements, their arrangement in cords and pseudoglandular structures and their anatomical distribution, corresponding to the one typical of mullerian remnants.⁶ The localisation of these lesions induced many authors to suspect a hamartomatous origin by mesonephros and its collecting system.⁷

Although the development of immunohistochemistry and electron microscopy have supported the original hypothesis from Masson et al about a mesothelial derivation for adenomatoid tumour,⁸ other authors found that some lesions expressed endothelial features. Cases characterised by immunohistochemical positivity for factor VIII-related antigen in lining epithelioid cells were detected. These particular lesions were examined on electron microscopy, which confirmed the presence of Weibel–Palade bodies, suggesting an endothelial origin in some rare cases.⁹

Goddard and Grant in an article published in 1992 summarised the principal arguments about the source of the debate on the histogenesis of adenomatoid tumour.² As they suggested, from an immunohistochemical and mucin histochemical study of 16 reviewed cases of adenomatoid tumours, most of the evidence confirms the mesothelial origin of this neoplastic entity even if some tumours show endothelial markers.

The morphological aspects and the immunohistochemical pattern of adenomatoid tumours probably reflect the line of differentiation of the neoplasia rather than its histogenesis, but our opinion is that the two issues are linked. Only molecular biology studies can help to resolve this debate, when one or more mutated genes can be revealed in all the cases named “adenomatoid tumour” by pathologists on the basis of morphological and immunohistochemical aspects.

In conclusion, this case represents the difficult identification of this kind of lesion in the context of a leiomyoadenomatous pattern on routine histological slides, and the challenge in differential diagnosis with a localisation of malignant carcinoma in smooth muscle proliferation of uterus.

LEARNING POINTS

• Adenomatoid tumour is a benign rare lesion of the female genital tract, localised in the wall of the fallopian tubes or beneath the uterine serosa.

• Due to the histological appearance and anatomical localisation, it is difficult to distinguish this peculiar lesion from a common tumour of the smooth muscle, especially in its solid, firm and elastic macroscopic variant.

• This case represents the difficult identification of this kind of lesion in the context of a leiomyoadenomatous pattern on routine histological slides, and the challenge in differential diagnosis with a localisation of malignant carcinoma in smooth muscle proliferation of uterus.