Follow-up in patients with disseminated peritoneal leiomyomatosis: a report of an unusual, high-risk case.

Leiomyomatosis peritonei disseminata is a condition seen uncommonly in states of oestrogen hypersecretion in women of childbearing age. There are no clear guidelines for the primary management and follow-up of these patients. Here, a rare case in a postmenopausal woman with a normal hormonal state who may be considered higher risk is presented, with a review suggesting a management pathway in these patients.

Leiomyomatosis peritonei disseminata is a rare condition in general, but particularly in patients who are postmenopausal with normal hormonal states. It presents a diagnostic conundrum and can therefore mislead clinicians when planning surgical treatment. There is also little evidence regarding management of this condition with regard to time frames. We felt it was important to highlight this condition as a differential diagnosis and also to provide a review of the literature with a management pathway that could provide a reliable guide to clinicians. CASE PRESENTATION A 69-year-old African woman presented to a 2-week wait at the colorectal cancer clinic for increasing left iliac fossa pain, worsening longstanding constipation and abdominal distension. She had no gynaecological or urinary symptoms and was postmenopausal with her only surgical history being a caesarean section and myomectomy 20 years previously. She had never been on any hormonal preparations and exhibited no signs or symptoms of hormonal stimulation. Examination of her abdomen was unremarkable. INVESTIGATIONS As part of her diagnostic pathway, she had a CT scan of the neumocolon, which demonstrated three solid abdominal and pelvic masses. One of these appeared to be a 5×5×6 cm slightly heterogeneous midabdominal mass at the level of the umbilicus either arising from the small bowel mesentery or from the serosal surface of the small bowel. It was some distance from the uterus but in close relation to the superior mesenteric vein. There were two other masses of similar size, one near the dome of the bladder which was reported as a pedunculated fibroid and another similar mass to the left of the uterus with several other fibroid-like structures on the posterior uterus (fig 1). There was no colonic pathology identified. She went on to have a normal flexible sigmoidoscopy, tumour markers (CA125, carcinoembryonic antigen (CEA), CA19-9, chromagranin and gut hormone profile) and positron emission tomography (PET) scan, which were all normal. DIFFERENTIAL DIAGNOSIS It was difficult to ascertain from these appearances whether these were gastrointestinal stromal tumours (GISTs), desmoids or lymphomatous tumours or a completely different pathology. TREATMENT The patient was discussed at a multidisciplinary team (MDT) meeting, and a diagnostic laparoscopic resection was planned. At laparoscopy she was found to have three egg-shaped, solid, cream coloured masses measuring up to 10×10×8 cm in diameter; two in the pelvis, one of which was abutting the uterus (fig 2). Both the ovaries were normal. The third mass was found in the small bowel mesentery. There was also a deposit on the anterior abdominal wall, which was excised. These were removed with the assistance of a midline hand port. OUTCOME AND FOLLOW-UP On histology all of the mass lesions were grossly similar in appearance. They ranged in size from 10–65 mm in maximum dimension and were solid masses with smooth external aspects and pale, whorled cut surfaces. Pinpoint haemorrhages were found but there was no macroscopic evidence of necrosis. The lesions also all had a similar appearance on microscopic examination, showing the features of benign smooth muscle tumours (leiomyomas) with extensive hyaline degeneration and foci of calcification. There was no cytological atypia and no mitotic activity or necrosis was evident (fig 3). Immunostaining revealed positivity for smooth muscle actin (SMA), desmin, oestrogen receptors and progesterone receptors. Staining for CD117 was negative. The appearance was therefore considered to be that of disseminated peritoneal leiomyomatosis. On follow-up 6 weeks postoperatively she was symptom free and well. Continued follow-up over 1 year with a repeat CT and carcinoembryonic antigen (CEA) test continued to show disease-free survival.

Leiomyomatosis peritonei dessimanata (LPD) is a rare condition first described by Willson and Peale1 in 1952; there have been 103 cases reported to date,2 and only 4 cases have been previously reported in postmenopausal women.2,3 The definitive pathogenesis of this disease remains to be unconfirmed but it is strongly associated with high oestrogen states. The hormonal background of LPD has been proven in animal studies where 4 months of oestrogen with and without progesterone led to submesothelial nodule formation in guinea pigs; however, the nodules were made of fibroblasts, whereas in women with LPD they consist of myofibroblasts and myocytes.4 Patients are usually asymptomatic and it is commonly diagnosed in women of child-bearing age, incidentally during pregnancy or at caesarean section, prolonged oral contraceptive (OC) use, alongside subserosal uterine leiomyomata, functional granulosa cell tumours and endometriosis.3,5,6 Suggested aetiological mechanisms include smooth muscle metaplasia of the subcoelomic mesenchymal stem cells the so-called pluripotent Mullerian stem cells or a fibrosing reaction to ectopic omental deciduosis induced by hormonal imbalance or excess.3,5–7 LPD often presents a diagnostic conundrum as it often mimics disseminated intra-abdominal malignancy.3,6,8 Macroscopically it appears as numerous hard nodules measuring up to 7 cm diameter on the surface of the peritoneum, especially the pelvic, uterine fundus, colon mesentery, the omentum, ovaries, spleen and pancreas.2,9 Microscopically LPD differs from leiomyosarcoma as the latter has a higher mitotic index and shows nuclear atypia, tumour necrosis and infiltrative growth into adjacent structures/organs. A benign metastasising leiomyoma is characterised by fewer nodules and often presents with metastases in the lungs.6 A gastrointestinal stroma cell tumour can resemble LPD but does not commonly have smooth muscle cells in the nodules, and have immunohistochemical expression of CD117.10 There have been 10 cases of malignant transformation to sarcoma reported in LPD.5,8,11–16 The interval between the initial detection of LPD and development of sarcoma varies from synchronous, 7 months, to up to 8 years.2,5,8,11 Malignancy is thought to be more common in LPD without exogenous or increased endogenous exposure and in tumours without expression of oestrogen receptor or progesterone receptors3,5 and also in postmenopausal women with comparatively larger benign nodules, reported in two of the three cases in this age group.2,3,12,16 Although incidentally-diagnosed LPD carries an excellent prognosis with most cases regressing after cessation of hormonal stimulation and only some cases requiring gonadotrophin releasing hormone agonists or surgical castration, malignant change carries a very poor prognosis despite multi modality combination therapy,3 hence suggesting that the pathogenesis of these patients is different to the benign disease seen in younger patients. More recently the use of aromatase inhibitor (anastrozole) has been found to have some success in the treatment of LPD in postmenopausal women, particularly in non-resectable cases.17 This effect is thought to be due to the inhibition of intrinsic oestrogen production of the tumour and therefore limitation of progression. Due to the rarity of the condition there are no clear guidelines on the management of this condition. It is believed that an aggressive approach in LPD should be avoided through minimally invasive techniques.18,19 Given the advent of increasingly advanced laparoscopic surgery it is very feasible to carry out complete resection through minimally invasive approaches. However we believe that more aggressive approaches should be taken in higher risk groups that include patients who develop LPD in the absence of hormonal stimulation, including postmenopausal women as reported in our case. Curative resection should be attempted in these patients and surveillance undertaken postoperatively through CT imaging and tumour marker testing (CA125, which is reported to increase in these patients).8 We suggest that the reported recurrence interval from 7 months to 8 years may indicate that surveillance should take place for at least 3 years post initial resection. In non-resectable cases, the use of aromatase inhibitors may be attempted. LEARNING POINTS Leiomyomatosis peritonei dessimanata (LPD) should be remembered as a differential diagnosis in patients with the appearance of disseminated intra-abdominal malignancy. Curative excision should be undertaken in high-risk groups of patients who develop LPD in the absence of hormonal stimulation, including postmenopausal women. Surveillance postoperatively through CT imaging and tumour marker testing should be carried out on an annual basis for 3 years. Footnotes Competing interests: None. Patient consent: Patient/guardian consent was obtained for publication.

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