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Early View Article: Online published version of an accepted article before publication in the

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Journal Name: Journal of Case Reports and Images in Oncology

Type of Article: Case Report

Title: Recurrence of Sex Cord tumor with annular tubules in young patient with Peutz-

Jeghers syndrome

Authors: Meher Slimane, Selma Gadria, Manel Hadidane, Houyem Mansouri, Maha Driss,

Khaled Rahal

doi: To be assigned

Early view version published: November 1, 2016

How to cite the article: Slimane M, Gadria S, Hadidane M, Mansouri H, Driss M, Rahal

K. Recurrence of Sex Cord tumor with annular tubules in young patient with Peutz-

Jeghers syndrome. Journal of Case Reports and Images in Oncology. Forthcoming 2016.

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TYPE OF ARTICLE: Case Report 1

2

TITLE: Recurrence of Sex Cord tumor with annular tubules in young patient with 3

Peutz-Jeghers syndrome 4

5

AUTHORS: 6

Meher Slimane1, 7

Selma Gadria1, 8

Manel Hadidane1, 9

Houyem Mansouri1, 10

Maha Driss2, 11

Khaled Rahal1 12

13

AFFILIATIONS: 14

1Oncologic Surgery Departement, Salah Azaiz Institut, Tunis, Tunisia 15

2Pathology Departement, Salah Azaiz Institut, Tunis, Tunisia 16

17

CORRESPONDING AUTHOR DETAILS 18

Selma Gadria, 19

Surgical Oncology departement, Salah Azaiz Institute, Postal address: C3 residence 20

Cordoba, Rue Tachkand, 2037, Ennasr1, Ariana, Tunisia. 21

Email: [email protected] 22

23

Short Running Title: Sex cord tumor and Peutz-Jeghers syndrome 24

25

Guarantor of Submission : The corresponding author is the guarantor of 26

submission. 27

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35

ABSTRACT 36

37

Introduction 38

Peutz-Jeghers syndrome (PJS) is a hereditary autosomal dominant disease 39

characterized by polyposis in the gastro-intestinal tract and melanin pigmented 40

macules on the skin mucosa. 41

In gynecology, it can be complicated with sex cord tumor with annular tubules 42

(SCTAT). Multifocal, bilateral, small and benign lesions that develop into mucinous 43

and serous ovarian tumors commonly characterize it. SCTATs associated with PJS 44

are usually benign and do not have malignant potentials, thus, unilateral 45

oophorectomy is curative. Recurrence is a common event. Subsequently, radical 46

surgery is recommended in these cases. 47

48

Case report 49

We report the case of a 32 years PJS patient, who underwent conservative surgery 50

for SCTAT 5 years ago. She shows up with a recurrent contralateral 75mm adnexal 51

cyst. Because of her will of childbearing, a conservative surgery was planned and 52

the patient underwent a laparoscopic cystectomy. One month after surgery, 53

hormonal rates were measured after ovarian stimulation and didn’t show hormonal 54

activity. 55

56

Conclusion 57

SCTAT associated to PJS is a rare and unusual variant of ovarian tumors. 58

Conservative surgery is indicated but recurrence is still a common event. Because of 59

its rarity and high recurrence rates, further studies are needed to confirm the effect of 60

radical surgery and adjuvant therapies. 61

62

Keywords : Sex cord tumors, ovarian tumors, Peutz-Jeghers syndrome, hereditary 63

disease. 64


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67

INTRODUCTION 68

Peutz-Jeghers syndrome (PJS) is a hereditary autosomal dominant disease 69

characterized by polyposis of the gastro-intestinal tract and melanin pigmented 70

macules on the skin mucosa. 71

In gynecology, it can be complicated with sex cord tumor with annular tubules 72

(SCTAT). 30% of the SCTAT are associated to PJS. Multifocal, bilateral, small and 73

benign lesions that develop into mucinous and serous ovarian tumors commonly 74

characterize it. SCTATs associated with PJS are usually benign and do not have 75

malignant potentials, thus, unilateral oophorectomy is curative. However, recurrence 76

is a common event. Different from epithelial ovarian cancer, surgery is still the main 77

treatment of choice for recurrent disease. Because of its rarity, there is no standard 78

treatment protocol and the effects of chemotherapy and radiation therapy are still 79

unclear. 80

81

CASE REPORT 82

A 32 years old woman case, with a family history of PJS, is reported. The patient 83

presented in 2011 an adnexal mass. Physical exam revealed perioral-pigmented 84

macule (Figure 1). In laparotomy, we discovered a left adnexal mass and an 85

intestinal polyp. No ascites or lymph nodes were reported. The contralateral ovary 86

was normal. The patient underwent a conservative staging including a left 87

oophorectomy. No contralateral adnexal biopsy was performed. Histologic finding 88

confirmed SCTAT associated to PJS intestinal polyp. The ovarian tumor were 89

classified FIGO IA. Subsequently, the patient did not receive adjuvant therapy. 90

Five years later she presents abdominal pain. CT scan shows a 75 mm right adnexal 91

mass evoking a cystic recurrence (Figure 2). The serum rate of anti-müllerian 92

hormone (AMH) was elevated and measured 325-ng/ml. CA-125 rates were less 93

than 35 UI/ml. In order to investigate PJS, a colonoscopy was performed and 94

showed recto-colic polyposis. Mammogram showed benign cystic lesion of the 95

breast. Papa smear didn’t show any abnormal cells. Radical surgery was 96


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recommended but the patient refused because of her will of childbearing. 97

Laparoscopic exploration found a right adnexal cystic mass (figure 3), with no 98

evidence of ascites or peritoneal carcinosis. We underwent a cystectomy; leaving an 99

ovarian tissue. The histologic findings showed circumscribed columnar epithelial 100

nests composed of ring shaped tubules, which are encircled by hyalinized basement 101

membrane-like material and concluded for a recurrent SCTAT. No mitotic count was 102

reported (Figure 4 and 5). One month after surgery, hormonal rates were measured 103

after ovarian stimulation and didn’t show hormonal activity. Fertility preservation 104

attempt was a failure and the patient is proposed for a complementary surgery. 105

Recurrence of SCTAT in young patient with PJS is a common event. Conservative 106

surgery is always a challenge. We attend to find the best alternative to treat them. 107

108

DISCUSSION 109

SCTATs are rare tumors. They represent only 2.3% of sex cord tumors. 30% of 110

SCTATs are associated to PJS [1]. Only few series reported SCTAT associated to 111

PJS cases. In 1970, Scully reported 6 cases of SCTAT associated to PJS. Young 112

and al reported in 1982, 27 additional cases. Most of the publications are case 113

reports. The diagnosis of SCTAT is usually based on pathological examination of the 114

tumor and typical presentations are most of the time consistent with hormone 115

secreting tumor [2, 3]. Researchers have demonstrated that SCTAT secretes not 116

only estradiol, but also progesterone, resulting as for our patient in menstrual 117

disturbances. Young and al confirmed that SCTATs associated to PJS was 118

multifocal, bilateral and small [1]. In contrast, SCTAT non associated to PJS are 119

usually unilateral, large and have malignant behavior [4]. SCTAT includes ovarian 120

Sertoli cell tumors, ovarian mucous or serous epithelial tumors and ovarian mature 121

teratoma [5]. 122

A preoperative diagnosis is difficult. It was reported in Qian study for two pediatric 123

patients who underwent ovarian biopsy for suspected physiological ovarian cyst [6]. 124

Ovarian biopsy is still dangerous and risky of disrupting the capsule and changing 125

prognosis by tumoral spread. 126

Because of its rarity, there is no standard treatment protocol for SCTAT patient. 127

Surgery remains the initial management. Because of its occurance in young or 128


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adolescent patient, fertility sparing surgery is important. Unilateral salpingo 129

oophorectomy is curative for intact capsule tumors confined to one ovary with no 130

involvement to the uterus and the contralateral ovary [6]. Despite that, SCTAT 131

associated to PJS are bilateral tumors, and not commonly synchronous. Wedge 132

section or biopsy of the contralateral ovary is not a routine procedure, but it should 133

be considered, especially for PJS patients. There are no studies that compared 134

unilateral to bilateral oophorectomy [1, 6]. 135

Adjuvant treatment for SCTAT is still a controversial point. The effects of 136

chemotherapy and radiotherapy are still not clear. Further studies are still needed to 137

confirm the effect on prognosis and survival [6]. 138

Recurrent SCTAT should be suspected by clinical symptoms related to hormone 139

secreting. A rise of the AMH is a major sign. Recurrent tumors can be located in the 140

contralateral ovary or in the retro peritoneum. They can be detected by imaging such 141

as ultrasonography, CT-scan or PET-scan. It is a fundamental evaluation of tumor 142

size, number and location [6, 7]. 143

Surgery for recurrent disease in SCTAT is a total hysterectomy, associated to 144

salpingo-oophorectomy, and lymph node dissection. Our patient had a 75 mm 145

adnexal cyst. A fertility sparing surgery consisted on a cystectomy, leaving a normal 146

residual ovarian tissue. Just like epithelial ovarian cancer, recurrent disease can be 147

located in the pelvic or para-aortic lymph nodes. A pelvic and para-aortic 148

lymphadenectomy should be considered [8]. Qian et al reported four cases of lymph 149

node dissection achieving complete response in three of them [6]. There is 150

unfortunately a lack of long term follow up. More studies should be considering 151

lymph node dissection [4]. 152

Prognosis for SCTAT is relatively favorable although recurrence rate is very high. 153

Literature reports a 1-year and 5-year PFS of 92% and 67% respectively. The 154

median PFS time was 97.8 months. The 5-year OS was 100% [1, 6, 9]. 155

156

CONCLUSION 157

SCTAT associated to PJS is a rare disease. Oophorectomy is a curative surgery for 158

unilateral tumors. Contralateral ovarian biopsy is a good alternative especially for 159

PJS because of the frequency of bilateral tumors. Although prognosis of SCTAT is 160


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favorable, recurrence rate is high. Long-term follow up is essential. Serum rates of 161

estradiol and progesterone in addition to AMH could be used as tumor markers 162

during follow-up. Further studies are needed to confirm the best surgery and the 163

effect of adjuvant therapies. 164

165

LIST OF ABBREVIATIONS: 166

SCTAT: Sex cords tumors with annular tubules 167

PJS: Peutz-Jeghers syndrome 168

AMH: anti-müllerian hormone 169

170

CONFLICT OF INTEREST 171

No conflict of interest are reported 172

173

AUTHOR’S CONTRIBUTIONS 174

Meher Slimane, Selma Gadria, Manel Hdidane and Houyem Mansouri made 175

substantial contributions to conception and design of the manuscript. Maha Driss 176

have been involved in drafting the manuscript and revising it critically for important 177

intellectual content. Khaled Rahal have given final approval of the version to be 178

published. 179

180

ACKNOWLEDGEMENTS 181

We would like to thank the head of the department and all staff members of 182

department of Surgery and Pathology for their support and encouragement to 183

prepare this report. The authors declare that there is no conflict of interest. 184

185

REFERENCES 186

1. Robert H. Young Wrw, G. Richard Dickerson and Robert E. Scully. Ovarian 187

sex cord tumor with annular tubules. Cancer. 1982; 50(1384). 188

2. Arisa Ueki IK, Kouji Banno, Megumi Yanokura, Kenta Masuda, Yusuke 189

Kobayashi, Akira Hirasawa, Daisuke Aoki. Gynecological tumors in patients 190

with Peutz-Jeghers syndrome (PJS). Open Journal of Genetics. 2011; 1:65-9. 191

3. Roberet. Scully M. Sex cord tumor with annular tubules a distinctive ovarian 192


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tumor of the peutz-jeghers syndrome. Cancer. 1970; 25. 193

4. Seung-Hun Song J-KL, Ho-Suk Saw, Sang-Yong Choi, Bum-Hwan Koo, 194

Aeree Kim, Bum-Woo Yeom, Insun Kim. Peutz-Jeghers Syndrome with 195

multiple Genital tract tumors and breast cancer: A case report with review of 196

literatures. J Korean Med Sci. 2006; 21. 197

5. Anthony Turpin SpC, Julie Leclerc, Agnès Wacrenier, Sylvie Manouvrier-198

Hanu, Marie-Pierre Buisine, Sophie Lejeune-Dumoulin. Prédisposition 199

héréditaire aux cancers digestifs, mammaires, gynécologiques et gonadiques 200

:état des lieux du syndrome de Peutz-Jeghers. Bulletin du cancer. 2014; 201

101(9). 202

6. Qiuhong Qian1 YY, Jiaxin Yang, Dongyan Cao, Zhaohui Zhu, Ming Wu, Jie 203

Chen, Jinghe Lang and Keng Shen. Management and prognosis of patients 204

with ovarian sex cord tumor with annular tubules: a retrospective study. BMC 205

Cancer. 2015; 15. 206

7. Shen K WP, Lang JH, Huang RL, Tang MT, Lian LJ. Ovarian sex cord tumor 207

with annular tubules: a report of six cases. Gynecol Oncol 1. 1993; 48(2):180. 208

8. Lele SM SR, Zaharopoulos P, Adesokan A, Smith M, Linhart JM, et al. . 209

Malignant ovarian sex cord tumor with annular tubules in a patient with Peutz-210

Jeghers syndrome: a case report. . Mod Pathol. 2000; 13(4):466. 211

9. Subodh M. Lele MD, Ravindranauth N. Sawh, M.B.B.S., D.M., Paul 212

Zaharopoulos, M.D.,, Adekunle Adesokan MD, Michael Smith, M.D., Jessica 213

M. Linhart, M.D., Concepcion D. Arrastia, M.D., Hannah R. Krigman, M.D. 214

Malignant Ovarian Sex Cord Tumor with Annular Tubules in a Patient with 215

Peutz-Jeghers Syndrome: A Case Report. Mod Pathol. 2000; 13:466-70. 216

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FIGURE LEGENDS 218

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Figure 1: Perioral pigmented skin macula 220

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Figure 2: CT-scan showing 75mm right adnexal mass 222

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Figure 3: adnexal cystic mass 224


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Figure 4: Sex cord stromal tumor with annular tubules of the ovary (H&E x10) 225

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FIGURES 229

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Figure 1: Perioral pigmented skin macula 233

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Figure 2: CT-scan showing 75mm right adnexal mass 239

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Figure 3: adnexal cystic mass 245

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