Ectopic hyperprolactinaemia due to a malignant uterine tumor resembling ovarian sex cord tumors (UTROCST)

Abstract

Purpose Moderate hyperprolactinaemia (2–5 times upper limit of normal) occurring in a patient with a normal pituitary MRI is generally considered to be due to a lesion below the level of detection of the MRI scanner assuming macroprolactin and stress have been excluded. Most patients with mild-to-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We present the rare case of a patient who had prolactin elevation typical of a prolactin-secreting pituitary macroadenoma,with a normal cranial MRI, and in whom the prolactin rose further with dopamine agonist treatment. Subsequent investigations revealed ectopic hyperprolactinaemia to a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which resolved following tumor resection. Although mostly considered to be benign, the UTROSCT recurred with recurrent hyperprolactinaemia and intraabdominal metastases. Methods We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. Results Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. Conclusions Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10× ULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs.

Prolactinoma or leiomyoma-associated hyperprolactinemia—this is the question, a case report and review of the literature

“…Only a few case reports in the literature presented patients with leiomyoma-associated hyperprolactinemia (Table 1, Ref. [5,6,9,10,[16][17][18][19][20][21]). Common characteristics of all cases were the presence of normal pituitary gland, large uterine fibroids (at least 5.5 cm), mild to moderate prolactin increase with classic clinical symptoms, complete resistance to dopamine agonist treatment, a rapid decrease of the hormonal concentrations after tumour removal, and negative immunostaining for prolactin by an immunohistochemical study of the leiomyomas [9,[16][17][18][19].…”

“…However, in all described patients with leiomyoma-associated hyperprolactinemia the dopamine agonist treatment was ineffective (Table 1, Ref. [5,6,9,10,[16][17][18][19][20][21]). Thus, the development of systemic hyperprolactinemia in women with leiomyomas might be a sign of complete autonomization of prolactin secretion potentiating the tumour growth and resistant to medical treatment.…”

“…However, the pituitary incidentaloma might co-exist with secondary hyperprolactinemia leading to huge obstacles in the differential diagnosis. Moreover, ectopic intracranial prolactinomas originating from pharyngeal pituitary remnants as well as ectopic prolactin production by mesenchymal and other tumours have been described in the literature since 1970ies [3][4][5][6][7][8]. Leiomyoma-associated hyperprolactinemia has also been reported, though contradictory results have been obtained by immunostaining for prolactin in fibroid tissues [9,10].…”

Prolactin-Secreting Leiomyoma Causing Hyperprolactinaemia Unresponsive to Dopamine Agonist Therapy and Resolution following Myomectomy

“…Six of the eight cases revealed leiomyomas on histopathology [ 3 , 5 – 9 ]. Of the two other cases, histopathology revealed a low-grade mesenchymal tumour [ 4 ] and a uterine tumour resembling ovarian sex cord tumour [ 10 ]. Of the six leiomyomas reported, all women were premenopausal (25–47 years).…”

“…ere are 8 cases in literature reporting resolution of hyperprolactinaemia after removal of a uterine mass [3][4][5][6][7][8][9][10]. Six of the eight cases revealed leiomyomas on histopathology [3,[5][6][7][8][9].…”