Mucinous metaplasia in a mixed epithelial and stromal tumour of the seminal vesicle: a potential precursor to mucinous adenocarcinoma

To the Editor, The distinction between mixed epithelial stromal tumours (MEST) and cystadenomas of the seminal vesicles (SVs) has recently been challenged by experts.1, 2 We present a case that further contributes to this discussion, highlighting that these lesions may exist along a biological spectrum, with potential for progression toward malignancy. A 65-year-old man with a history of gout, hyperlipidaemia, hiatal hernia and laparoscopic cholecystectomy had been under urological follow-up since 2013 for a MEST of the left SV. The lesion was discovered after he presented with haemospermia. Core biopsy showed dilated glandular-acinar structures lined by cubo-columnar epithelium with mildly hypercellular stroma lacking atypia, mitoses or necrosis (Figure 1A). Focal degenerative atypia was consistent with SV-type mucosa. Immunohistochemistry demonstrated diffuse progesterone receptor (PR) expression in the stroma with variable positivity for desmin, α-smooth muscle actin and CD34. S-100 was negative. The Ki-67 index was <1%. The epithelium was positive for GATA3 (Figure 1A, inset) and negative for prostate-specific antigen and prostatic acid phosphatase. Given benign features, expectant management was adopted. Over the subsequent 11 years, the lesion enlarged from 3 to 12 cm. Pelvic MRI in 2024 showed a stable, multicystic SV lesion without restricted diffusion, abnormal enhancement, lymphadenopathy or fat plane obliteration. Despite radiological features suggesting a benign process, continued growth and recurrent haemospermia prompted robotic excision of the left SV. The gross excision specimen is shown in Figure 1B. Histopathology revealed a multiloculated cystic tumour with classic MEST features (Figure 1C). The epithelium showed a SV-type immunoprofile with diffuse PAX8 and GATA3 positivity. The stroma was moderately cellular, expressing oestrogen receptor (Figure 1D) and PR. Importantly, multifocal mucinous metaplasia was present in the lining of several cystic spaces, with foci of low-grade dysplasia resembling mucinous borderline ovarian tumours (Figure 1E). These areas showed intestinal-type differentiation, confirmed by CDX2 and SATB2 (Figure 1E, inset). The Ki-67 index was >3% in metaplastic regions (Figure 1F). No invasive carcinoma was identified. Molecular testing for KRAS mutations, including all common variants, was negative. Primary SV tumours are extremely rare.1 Among malignant SV neoplasms, adenocarcinoma is the most common. MESTs, so far reported in <50 cases, display mixed epithelial and stromal elements and range from benign to high-grade invasive forms. Presentations include urinary tract complaints, haemospermia, fever or abdominal pain although some are incidental findings.1 The WHO classifies SV tumours into epithelial, MEST, mesenchymal and miscellaneous. Cystadenomas are classified as benign epithelial tumours. Reikie et al. questioned the distinction between cystadenomas and low-grade MESTs, proposing a spectrum of low-, intermediate- and high-grade MESTs based on stromal atypia, mitotic activity and necrosis.1 Others suggested a simplified two-tier scheme of low- and high-grade MESTs.2 This spectrum may extend to invasive adenocarcinoma. Chumbalkar et al. described a SV cystadenoma with dysplasia and suggested adenocarcinoma may arise from pre-existing cystadenomas.3 They noted Ki-67 was higher in dysplastic cells than benign cells. Similarly, intestinal metaplasia has been reported in post-radiation mucinous adenocarcinoma of the SV.4 These observations support progression from intestinal metaplasia to dysplasia to carcinoma, producing primary mucinous adenocarcinomas in addition to mesonephric carcinomas. Different potential precursor lesions in the mucosa of the SV have been described, including lesions with basal cell hyperplasia, intestinal metaplasia and MEST.5 To date, mucinous metaplasia in the context of SV MEST has not been reported. Galea et al. recently reported a low-grade mucinous SV lesion resembling low-grade appendiceal mucinous neoplasms (LAMNs).6 Genomic profiling of this case and another mucinous SV cystic lesion revealed KRAS gain-of-function variants, consistent with the high frequency of KRAS mutations in LAMNs.6, 7 Here, intestinal-type mucinous metaplasia with focal dysplasia and elevated Ki-67 indicates early neoplastic change. Dysplastic features included nuclear polarity loss, mucin depletion and prominent nucleoli. Although no invasive carcinoma was present, these findings highlight the malignant potential of such lesions. The absence of KRAS mutations suggests alternative oncogenic drivers. This case supports the hypothesis that mucinous metaplasia within MEST may represent a precursor to mucinous adenocarcinoma of the SV. Given the risk of malignant transformation, surgical excision may be preferable to prolonged surveillance. E. Sheldon and P. Oliveira reviewed the case. N. T. Tuffa wrote the article and designed the figures. E Sheldon and P. Oliveira reviewed and edited the article. No funding was received for this study by any author. The authors have no conflicts of interest to declare. Data are available on request from the authors.