Peritoneal melanosis associated with serous carcinoma of the ovary: A case report and literature review.

A 67-year-old female patient, gravida 6, para 5, with a medical history of type 2 diabetes on insulin, hypertension on amlodipin 5mg 1 tablet/day, WHO status (World health organization performance score) of 1, BMI at 21.2 Kg/m2, presented with abdominal distension and altered general health evolving for 16 months. The patient was used a combined oral contraceptive for menstrual regulation. Surgical history was unremarkable. There are no proven genetic abnormalities in her family. The clinical examination found a distended abdomen with diffuse dullness. The patient reported a chronic pain in the hypogastrium with severity of 3 in 10 of 3 months duration. The findings of laboratory tests were unremarkable. The tumor marker CA-125 was very high at 4337 IU/ml (normal value < 35 IU/ml). The thoracic and abdomino-pelvic computed tomography scan showed a locally advanced right pelvic ovarian mass measuring 110 × 84 × 82mm. These radiological explorations objected a probable invasion of the uterus and the anterior rectal wall, with presence of several peritoneal carcinosis and abundant pleural effusion ( Fig. 1 ). There was no secondary metastatic lesion of the liver or lungs. Recto-sigmoidoscopy was normal. Fig. 1 Enhanced abdomino-pelvic computed tomography scan showed a right pelvic ovarian mass measuring 110 × 84 × 82mm (arrow). Fig. 1 Enhanced abdomino-pelvic computed tomography scan showed a right pelvic ovarian mass measuring 110 × 84 × 82mm (arrow). The case was analyzed by a multidisciplinary committee, and the decision was to perform an exploratory laparotomy. During exploration, we found an abundant ascitic fluid with generalized peritoneal carcinosis, and a locally advanced bilateral ovarian mass invading the uterus and small bowel. A surgical biopsy of the carcinosis nodule was performed. The pathological study showed enlarged fibrofatty tissue infiltrated by a carcinomatous process arranged in nests and solid, cribriform masses. The tumor cells are enlarged, with hyperchromatic nuclei, marked anisokaryosis and abundant eosinophilic cytoplasm. The immunohistochemical staining objected a poorly differentiated carcinomatous cell expressing WT1, CK7 and CK20 in favor of an ovarian origin ( Fig. 2 ). Fig. 2 Immunohistochemical analysis showed diffuse strong WT1 positivity. Fig. 2 Immunohistochemical analysis showed diffuse strong WT1 positivity. The patient was referred to the oncology department and received 7 courses of chemotherapy consisting of a combination of carboplatin (AUC 5), Paclitaxel (175mg/m3), and bevacizumab 7,5mg/kg (used as a maintenance therapy alongside another drug) with good clinical response and radiological stability. Abdomino-pelvic CT scan of control showed a heterogeneously enhancing, solid-cystic, pelvic mass with lobulated contours, encompassing the uterus, bounded anteriorly by the gastrointestinal tract and laterally by the bladder, of reduced size measuring 46 × 32mm compared to the previous CT scan ( Fig. 3 ). Subsequently, a second exploratory laparotomy (second look) was indicated. Intra-operative exploration found a persistence of the right ovarian mass that remained attached to the sigmoid, rectum and bladder with the appearance of several parietal and pelvic nodules of dark-brown color. We performed a hysterectomy associated with appendectomy and omentectomy with biopsy of the burned nodules ( Fig. 4 ). Fig. 3 CT scan of control showed a solid-cystic, pelvic mass with lobulated contours, encompassing the uterus. Fig. 3 Fig. 4 Intraoperative view of burned nodules. Fig. 4 CT scan of control showed a solid-cystic, pelvic mass with lobulated contours, encompassing the uterus. Intraoperative view of burned nodules. Pathological study and immunohistochemical staining revealed tumor residues of a high-grade serous carcinoma on both ovaries, and a well-limited histiocytic proliferation containing numerous large brownish pigments in their cytoplasm, stained by Perls and Fontana on the brown nodules ( Fig. 5 ). Based on these data, a diagnosis of benign peritoneal melanosis associated with serous carcinoma of the ovary was made. The postoperative course was simple and the patient was discharged 7 days after surgery. The multidisciplinary committee decided clinical and radiological surveillance. No adjuvant chemotherapy was used. The patient is doing well after a follow up of 1 year without recurrence. Fig. 5 Photomicrograph showing a well-limited histiocytic proliferation stained by Perls and Fontana on the brown nodules. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.) Fig. 5 Photomicrograph showing a well-limited histiocytic proliferation stained by Perls and Fontana on the brown nodules. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Our paper is a case report; no registration was done for it.

Dr Mhand Mohammed: [email protected] Have written the article, have consulted the patient, prescribed all of the tests and prepared the patient for surgery and participated in the surgery. Dr Obed Rockson [email protected] : have helped writing the article, data collection. Dr Harouachi Abdelhakim [email protected] : Data collection. Dr Haloui Anass: Interpretation of histological data. Pr Bouhout Tariq [email protected] (oncology surgery professor): supervised the writing of manuscript. Pr Bennani Amal [email protected] (anatomopathology professor): confirm the histological diagnosis. Pr Serji Badr [email protected] (oncology surgery professor): supervised the writing of manuscript. Pr El Harroudi Tijani [email protected] : (oncology surgery professor): have supervised the writing of the paper.

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

No ethical approval necessary.

This research has not been supported by any private or corporate financial institutions nor has any grant been received for this study.

The author(s) received no financial support for the research, authorship and/or publication of this article.

Mhand Mohammed.

To our best knowledge, this is the first case associated with serous carcinoma of the ovary. The major differential diagnosis with poor prognosis is metastatic melanoma.

The first case of peritoneal melanosis was reported by Afonso in 1962 secondary to the rupture of a bilateral ovarian cystic teratoma 4 . Up-to-date, only 18 cases have been reported in the English literature [ 5 ]. It is an extremely rare condition affecting women between the ages of 18 and 28 year with only 1 of the cases reported in male [ 6 ]. It may be incidentally encountered during the course of an exploratory laparotomy [ 3 ]. The condition is associated with ovarian lesions in 57% of the cases [ 7 ]. organs frequently affected are the ovaries, peritoneum, omentum, appendix, enteric cyst, intestine, liver and gallbladder [ 3 ]. The present case is a documented report of peritoneal melanosis discovered after two exploratory laparotomies. In previous cases, there have been conflicting reports regarding the exact source and nature of the pigment. Among the recognized theories, spillage of pigment from ruptured ovarian teratomas is the most accepted. It was proposed that the melanin was produced in the cystic teratoma and with its rupture, the spillaged pigment was phagocytosed by histiocytes and deposited within the peritoneum [ 4 , 5 ]. In addition, some authors have hypothesized that the pigmentation originated from hemorrhage in the teratoma containing the gastric mucosa and gastric ulceration [ 1 ] but those theories are only validated for cases associated with a ruptured ovarian teratoma. Another theory proposes that excessive migration of neural crest cells before the 10th week of development leads to the formation of pigmented mesothelial cells and dendritic melanocytes in the peritoneum. An additional hypothesis is that pigmentation originates from neural crest cells through a defect in the regression of the neuroenteric duct [ 8 , 9 ]. A different hypothesis proposed for the case associated with enteric duplication is that the source of melanin was the basal cells of the esophageal mucosa within the ruptured enteric cyst, this hypothesis was confirmed by the observation that megaloblasts can be derived not only from neural crest epithelium, but also from stem cells of the esophageal mucosa [ 10 ]. In peritoneal melanosis associated with metastatic melanoma, it has been proposed that the melanin present in macrophages is derived from the pigment of tumor cells [ 7 , 11 ]. The main differential diagnosis, which can associate or no, to the peritoneal melanosis is metastatic melanoma [ 7 , 8 , 11 ]. It has a poor prognosis in comparison with benign peritoneal melanosis. Metastatic melanoma may share the same macroscopical aspect, although it forms large masses rather than small nodules [ 12 ]. It has to be differentiated by identifying the primary lesion, the reason that impose a clear examination of the skin, the anorectal canal and the ocular epithelium [ 7 ]. Microscopically, metastatic melanoma cells can be identified using hematoxylin and eosin-stained sections, and by using immunohistochemical staining with S-100 and HMB-45 [ 7 , 11 ]. Another condition that can mime peritoneal melanosis is peritoneal endometriosis. It is dark brown in color and can be distinguished histologically by identifying endometrial glands surrounded by stroma and the presence of macrophages carrying hemosiderin. This can be confirmed using immunohistochemical staining with CD10. A rare condition reported that can that be distinguished from peritoneal melanosis by histochemical methods using Fontana Masson staining is Peritoneal lipofuscinosis [ 2 , 13 ]. Different condition reported is the diffusion of Indian ink from a preoperative endoscopic tattoo, but without pathological significance.

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Peritoneal melanosis (PM) is a rare unusual benign entity, characterized by the deposit of diffuse or focal, black to gray or brown pigmentation in the abdominal cavity. The nature of the pigmentation is still unclear as the features are consistent with melanin or non-melanin pigments [ 1 , 2 ]. Although generally considered as a benign condition, it is mostly associated with other disorders such as desmoid ovarian cyst, enteric duplication cyst, gastric triplication, and ovarian cystadenomas [ 3 ] (see Table 1 ). Table 1 Summary of published reports on comparison with our case. Table 1 Author/year Patient gender and age Mode of revelation Association with other tumors Association with melanoma Immunohistochemical analysis Treatment follow up, and outcomes Our case 67 F abdominal distension -Serous carcinoma of the ovary. No – -Chemotherapy -Hysterectomy + bilateral adnexectomy + appendectomy + Omentectomy + biopsy of epiploic nodules - 6 months after the operation, the patient is going well. Barghash et al., 2021 [ 5 ] 86 M -Large right inguinal hernia -ADK of the sigmoid Colon No CD 68: + -Hernia repair + endoscopic resection of a sigmoidal polyp. - No surgical resection. - Regular surveillance. Kwang Kiat Sim et al, l 2021 [ 14 ] – – -Metastatic melanoma evolving the spleen. Yes – – – Ea-sle Chang et al. 2015 [ 6 ] 23 F -Fresh blood in the stools. Adenocarcinoma of the rectum No -CD68: + -HMB-45: -laparoscopic anterior resection of the rectum - No signs of cancer recurrence Jamkhandi et al., 2014 [ 3 ] 20 F pre-term labor pains and fetal distress at the 35th week of gestation In pregnancy No Data unavailable -right salpingo-oopherectomy −08 months postpartum, both newborn and mother are doing well Lim et al. 2012 [ 7 ] 79F abdominal pain with history of a desmoplastic melanoma on her right anterior leg had been excised. metastatic melanoma involving the omentum Yes S 100: + HMB 45: + Melan A: + -Resection of the epiploic mass, the mesocolic nodule and part of the peritoneum. −02 years after the operation, the patient passed away. Hirasawa et al, l 2012 [ 15 ] 42 F polycystic mass of the uterine cervix on Gynecological physical examination -Lobular endocervical glandular hyperplasia + Peutz–Jeghers syndrome No HIK1083 + -modified radical hysterectomy and bilateral salpingo-oophorectomy – Dragoslav Miljković et al., 2011 [ 16 ] 76 M bloody stools with altered general condition MELANOMA OF THE ANAL CANAL Yes S-100: + -Chemotherapy with remission. -One year after the initial diagnosis, patient died of intra-abdominal metastases. Kim et al., 2010 [ 2 ] 68 F lower abdominal pain and distension that -Mucinous Cystadenoma of the Ovary - Adenocarcino-ma of the Colon None CD68: + S-100: HMB-45: - Modified radical hysterectomy with bilateral salpingo-oophorectomy, a bilateral pelvic lymph node dissection, and a low anterior resection. – Kim et al., 2002 [ 13 ] 23 F Palpable pelvic mass. -Serous cystadenoma of the ovary. None S100: HMB-45: CD68: + Lysosome: + α-1-antitrypsin:+ α-1-antichymotrypsin:+ E-cadherin: + N-cadherin: + -Right salpingo-oophorectomy, appendectomy and omental biopsy were undertaken. -Free of tumor after 5 year and half of follow up. Richard et al., 2001 [ 1 ] 27 F Severe left iliac fossa pain -Ovarian Dermoid Cyst None None A left salpingo-oophorectomy and biopsies of the peritoneal and omental pigmented lesions . – Nada et al, l 2000 [ 17 ] 1 and a half F – -Enteric duplication cyst None – – – Luis et al., 1997 [ 9 ] 6 months asymptomatic abdominal mass in the upper abdomen that -Gastric triplication None -LN-5: + -PS-100: + -HMB-45: + -Resection of 2 gastric masses, Appendectomy, and biopsies of the peritoneum and omentum - Asymptomatic after 3 years of follow up. Jung et all 1996 [ 10 ] 2 F – -Enteric duplication None – – – Drachenberg C et all 1990 [ 8 ] – – -Melanotic peritoneal cyst – – – – Sahin et al, l 1990 [ 18 ] 28 F – ovarian mature cystic teratoma – – – – M.Fukushima et al., 1984 [ 19 ] 28 F Large pelvic mass Dermoid cyst of the ovary None None -Left salpingo-oophorectomy, appendectomy,and peritoneal and omental biopsies. -Disease free tumor. - 03 years and 3 months. Lee et al., 1975 [ 20 ] 27 F distended lower abdomen and dysuria -Ovarien dermoid cyst -Mucinous cystadenoma None None -bilateral oophorectomy and an omental biopsy. – Afonso et al, l 1962 [ 21 ] 18 F Abdominal swelling -Ovarien cyst None None Total hysterectomy + Bilateral salpingo-oophorectomy + appendicectomy + Biopsies of peritoneum remained asymptomatic and entirely well since the last operation Summary of published reports on comparison with our case. Herein, we report an unusual case of PM in a 67-year-old patient which was revealed as a surprise during exploratory laparotomy and the diagnosis was confirmed after histopathological study. We decided to report this case due to its rarity highlighting the unusual mode of revelation and discussing the diagnostic and therapeutic modalities. This case has been reported following the SCARE criteria 2020 [ 22 ].

The authors declared no potential conflicts of interests with respect to research, authorship and/or publication of the article.