Andreozzi, A.

Di Maio, M.

Gorzegno, G.

Muratori, L.

Scagliotti, G. V.

Sperone, P.

English

Institutional Research Information System University of Turin

Contents lists available at ScienceDirectGynecologic Oncology Reportsjournal homepage: www.elsevier.com/locate/gynorCase reportLong term control of luteinized thecoma with sclerosing peritonitis withleuprorelin and tamoxifen treatmentMuratori L.a,⁎, Gorzegno G.a, Sperone P.a, Andreozzi A.c, Di Maio M.b, Scagliotti G.V.aaMedical Oncology, Department of Oncology, University of Turin, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Regione Gonzole 10, 10043 Orbassano, Turin,ItalybMedical Oncology, Department of Oncology, University of Turin, Azienda Ospedaliera Ordine Mauriziano, Corso Re Umberto 109, 10128 Turin, Italyc Anatomopathology, Department of Pathology, University of Turin, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Regione Gonzole 10, 10043 Orbassano, Turin,ItalyA R T I C L E I N F OKeywords:ThecomaSclerosingPeritonitisHormonalTherapyOvaryA B S T R A C TBackground: Luteinized thecoma with sclerosing peritonitis (LTSP) is a very rare condition, and its clinicalmanagement is not evidence-based. Here we describe a case of long-term disease control achieved with leu-prorelin and tamoxifen therapy.Case presentation: A 18-year-old woman with acute abdomen underwent surgical removal of an ovarian massand received diagnosis of LTSP. Treatment plan consisted of leuprorelin and tamoxifen, followed by a goodinstrumental response. After 5 years, leuprorelin was stopped, and the patient continued tamoxifen alone. Tenyears after diagnosis, she is still disease free.Conclusion: Even in the absence of solid evidence, the combination of leuprorelin and tamoxifen could beconsidered as a possible medical treatment of LTSP. Considering the limitations related to the rarity of disease,further studies are needed to improve its management.1. IntroductionThecoma is a very uncommon cancer, originated by ovarian thecacells, that represents less of 5% of all ovarian cancers (Chechia et al.,2008). It arises normally in young and midlife women, presenting as asingle round mass in the abdomen. An even rarer variant of thecoma isluteinized thecoma with sclerosing peritonitis (LTSP). This entity wasoriginally described in 1994 and represents less than 0.01% of allovarian cancers (Clement et al., 1994). Sclerosing peritonitis, that is acomplication of this kind of cancer, consists of an abnormal prolifera-tion of fibroblasts below the mesothelium, resulting in the growth of amass of fibrous tissue that incorporates abdominal organs (Iwasa et al.,1996). The consequence is the progressive incarceration of intestinalloops, followed by clinically relevant gut obstruction. Nowadays, thepathogenesis of LTSP is still unknown; an association between thiscondition and antiepileptic drugs administration was proposed basedon clinical observations (Levavi et al., 2009). Currently, there are noclear guidelines about the management of LTSP, and the few availableevidences are mostly based on the description of single cases. Surgery isburdened by a high mortality rate; therefore, it is normally reserved tothe emergency treatment of intestinal obstruction. Regarding thepharmacological therapy, a single case of objective response to hor-monal therapy has been reported in literature: after surgical resection ofthecoma, a 39-year-old patient was treated with toremifene and leu-prorelin, achieving the complete regression of peritoneal lesions after3months of therapy (Bianco et al., 2005). Another case report showed asimilar therapeutic result with the combination of corticosteroid andleuprorelin in a 25-year-old patient with LTSP (Schonman et al., 2008).Here we report the very long follow-up (10 years) of an 18-year-oldwoman affected by LTSP, treated with leuprorelin and tamoxifen.2. Case presentationAn 18-year-old woman was admitted to the emergency room inFebruary 2008 because of the progressive onset of severe abdominalpain. An exploratory laparotomy was performed, showing appendicitis,and a right ovarian mass. The patient underwent appendicectomy andleft salpingo-oophorectomy, and a biopsy of the ovarian mass wasperformed, without removing the mass. The histological exam showedonly cells of ovarian fibroma with hemorrhagic infarction. One monthhttps://doi.org/10.1016/j.gore.2019.02.004Received 12 December 2018; Received in revised form 12 February 2019; Accepted 14 February 2019⁎ Corresponding author.E-mail addresses: leonardo.muratori@unito.it (L. Muratori), g.gorzegno@sanluigi.piemonte.it (G. Gorzegno), a.andreozzi@sanluigi.piemonte.it (A. Andreozzi),massimo.dimaio@unito.it (M. Di Maio), giorgio.scagliotti@unito.it (G.V. Scagliotti).Gynecologic Oncology Reports 28 (2019) 44–46Available online 16 February 20192352-5789/ © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).Tlater, due to the occurrence of a partial bowel obstruction, the patientwas again referred to the surgeons. Another laparotomy was performedand the ovarian mass in the right ovary was completely removed, aswell as a portion of peritoneum. The histological examination showedcells of luteinized thecoma (Fig. 1), associated with follicular cysts andgranulosa-cells hyperplasia, and sclerosing peritonitis with foreign-body giant cells (Fig. 2). Expression of estrogen-receptors (Fig. 3) andprogesterone-receptors (Fig. 4) was detected by immunohistochemistryon thecoma cells. No assumption of antiepileptic drugs was reported bythe patient. The case was initially assessed by gynecologist and hor-monal therapy with the aromatase inhibitor letrozole, 2.5mg/day wassuggested. Because of the extreme rarity of the disease, the patient wascollectively evaluated by a multidisciplinary team of gynecologists andoncologists, in June 2008. A treatment with leuprorelin 3.75mg/monthand tamoxifen 20mg/day was started and the hormonal therapy withletrozole was suspended. In the next two months, the patient experi-enced a relevant clinical improvement, moving to a regular function ofbowel and she regularly restarted oral intake of food. A single episodeof severe vomiting occurred in May 2008, and the patient underwent aCT scan that showed a thickening of intestinal loops, compatible withsclerosing peritonitis, and a mild amount of peritoneal effusion. How-ever, this episode resolved spontaneously, and the patient continuedthe hormonal treatment with leuprorelin and tamoxifen. In December2009, after 18 months of disease stabilization and progressive resorp-tion of peritoneal effusion, as showed in two follow-up CT scans, thepatient had a new episode of partial bowel obstruction. At that time, anMRI of abdomen was conducted, showing that the sclerosing peritonitiswas substantially unchanged. During next four years, the patient didnot develop any other episode of complete or partial bowel obstruction,but a bone densitometry showed a condition of osteoporosis (T-score offemoral neck: −2.1), and a therapy with zoledronic acid (a single in-travenous infusion of 5mg, administered once a year) was initiated.Because of the complete absence of symptoms, no radiological re-as-sessments were conducted until October 2013, when a new CT scanshowed the complete regression of peritoneal lesions. Based on thisfavorable CT findings, and considering the time elapsed from diagnosis,after multidisciplinary re-assessment, therapy with leuprorelin wasstopped, while continuing tamoxifen. In February 2014, after five years,also the treatment with zoledronic acid was suspended. In April 2014,the patient underwent a further CT scan, that confirmed the absence ofthe relapse of the disease. Nowadays, the patient is continuing herfollow-up, and since the last CT scan, she did not show any sign orsymptom related to the relapse of the disease. In April 2018, withinmultidisciplinary re-assessment, considering the time of ten yearselapsed from starting of hormonal treatment with leuprorelin and ta-moxifen, the decision to stop tamoxifen was taken.Fig. 1. Cells of thecoma, immunohistochemistry positive for inhibin (40×).Fig. 2. Sclerosing peritonitis with granulomas and foreign-body giant cells(20×).Fig. 3. Immunohistochemical expression of estrogen-receptors (40×).Fig. 4. Immunohistochemical expression of progesterone-receptors (40×).L. Muratori, et al. Gynecologic Oncology Reports 28 (2019) 44–46453. DiscussionTo our knowledge, this case represents the first experience of a long-term disease control in a patient with LTSP treated with leuprorelin for5 years and tamoxifen for 10 years. LTSP is a very uncommon disease,with a few cases reported in literature and scanty evidence about ef-fective treatments. The first attempts of a systemic treatment for thisdisease were based on the hypothesis that hormonal stimulation coulddrive the growth of this neoplasm, even triggering the formation offibrous tissue in the peritoneum. At the same time, tamoxifen had al-ready shown activity in the treatment of fibrosis associated with peri-toneal dialysis, a clinical-radiological condition similar to thecoma-re-lated sclerosing peritonitis (Bajo et al., 2003). In the present case, ahormonal therapeutic approach with an aromatase inhibitor, not jus-tified by the existing evidence, was initially attempted, but shortly in-terrupted thereafter in favor of a treatment with leuprorelin plus ta-moxifen, based on the already mentioned case report that, at the time ofdiagnosis, represented the only treatment experience that had demon-strated activity (Bianco et al., 2005). However, the management of thedisease was not without complications. First of all, the clinical historywas characterized, mainly in the first years, by repeated episodes ofpartial bowel obstruction caused by the develop of abdominal adhe-sions, which was followed by a progressive impairment of food oralintake and weight loss, as well as therapy discontinuation. Secondly,the effect of bone depletion induced by leuprorelin prevailed over thebone protective effect of tamoxifen, causing osteoporosis that requiredbisphosphonate therapy. However, hormonal therapy has been suc-cessful and the patient now, disease-free ten years after diagnosis, couldbe considered potentially healed. Nowadays, despite the time elapsed,the evidence about the treatment of this disease is substantially un-changed. In 2008, a review of 27 cases of LTSP was published, in whichthe immunohistochemical profile of the primary ovarian lesion wasevaluated, reporting that a subgroup of patients had tumor cells ex-pressing estrogen (ER) and progesterone (PgR) receptors (Staats et al.,2008). This receptor status would justify the successes obtained withhormonal therapy, but at the same time it suggests that patients ben-efiting from this approach could represent only a subgroup of theoverall group of patients with a diagnosis of thecoma. In the future,patients with thecoma should be investigated for theimmunohistochemical positivity of ER and PgR receptors, which couldhelp to select the patients who would most likely benefit from hormonaltreatment. However, the rarity of the disease makes hard to adequatelydescribe the interaction between the efficacy of treatments and poten-tial predictive factors. Generally, the rarity of the disease makes un-realistic any attempt to perform randomized clinical trials and producesolid evidence-based treatment guidelines. Therefore, reporting theclinical experience of individual cases or collecting retrospective seriesrepresent a potentially useful way to accumulate novel data, that overtime could potentially improve the management of this rare disease.Author contributionAll authors contributed equally to the paper.Conflict of interest statementAll authors declare to have no conflict of interest.ReferencesBajo, M.A., et al., 2003. Clinical experience with tamoxifen in peritoneal fibrosing syn-dromes. In: Advances in Peritoneal Dialysis. Conference on Peritoneal Dialysis.vol. 19.Bianco, R., et al., 2005. Ovarian luteinized thecoma with sclerosing peritonitis in an adultwoman treated with leuprolide and toremifene in complete remission at 5 years.Gynecol. Oncol. 96 (3), 846–849.Chechia, A., et al., 2008. Incidence, clinical analysis, and management of ovarian fi-bromas and fibrothecomas. Am. J. Obstet. Gynecol. 199 (5), 473–e1.Clement, P.B., et al., 1994. Sclerosing peritonitis associated with luteinized Thecomas ofthe ovary: a clinicopathological analysis of six cases. Am. J. Surg. Pathol. 18 (1),1–13.Iwasa, Y., et al., 1996. Sclerosing peritonitis associated with luteinized thecoma of theovary. Pathol. Int. 46 (7), 510–514.Levavi, H., et al., 2009. Sclerosing peritonitis associated with bilateral luteinized the-coma, linked to anticonvulsant therapy. Eur. J. Gynaecol. Oncol. 30 (6), 695–700.Schonman, R., et al., 2008. Luteinized thecoma associated with sclerosing peritoni-tis—conservative surgical approach followed by corticosteroid and GnRH agonisttreatment—a case report. Gynecol. Oncol. 111 (3), 540–543.Staats, P.N., et al., 2008. Luteinized thecomas (thecomatosis) of the type typically asso-ciated with sclerosing peritonitis: a clinical, histopathologic, and im-munohistochemical analysis of 27 cases. Am. J. Surg. Pathol. 32 (9), 1273–1290.L. Muratori, et al. Gynecologic Oncology Reports 28 (2019) 44–4646

Long term control of luteinized thecoma with sclerosing peritonitis with leuprorelin and tamoxifen treatment

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Long term control of luteinized thecoma with sclerosing peritonitis with leuprorelin and tamoxifen treatment

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