Case Report: Incidental discovery of primary peritoneal psammocarcinoma

Psammocarcinoma is an uncommon subtype of low-grade serous carcinoma. It is characterized by the presence of extensive psammoma bodies and can have either an ovarian or peritoneal origin. To our knowledge fewer than 30 cases of primary peritoneal psammocarcinoma (PPP) have been reported in the English literature. We report a rare case of PPP in a 74-year-old female, discovered fortuitously within a laparotomy for gallbladder lithiasis. At laparotomy, multiple nodular implants involving the omentum, the peritoneum and a magma of intestinal loops in the right iliac fossa were noted. A biopsy from nodules was performed. Gross examination showed multiple nodules of different sizes in the fat tissue. Pathologic examination showed massive psammoma bodies representing more than 75% of the tumor. The final diagnosis was psammocarcinoma. Our patient was referred to the gynecologic department for further investigation and to ascertain whether the tumor arose from the ovaries or peritoneum. Hysterectomy, bilateral adnexectomy and omentectomy were performed. Macroscopic examination showed that both ovaries were intact having a normal size. No invasion of ovarian stroma was shown in microscopic examination. The patient died of SARS-CoV-2 (COVID-19) six days after the surgery. PPP is a rare type of low-grade serous carcinoma. The behavior of this tumor is unclear, and the treatment is not standardized because of its rarity and lack of long-term follow-up. More cases need to be studied for better understanding and improvement of the management protocols.


Introduction
Psammocarcinoma, firstly reported by Kettle et al in 1916, is an extremely rare low-grade serous carcinoma. 1,2Its diagnostic criteria have been clearly established, 74 years later, by Gilks et al. 1 Psammocarcinoma can arise from either the ovary or peritoneum.4][5][6] In the majority of cases, PPP has a favorable prognosis, although some may show recurrences and metastases. 7We report a rare case of primary peritoneal psammocarcinoma (PPP) in a 74-years-old female, discovered incidentally during a surgery for gallbladder lithiasis.

Case presentation
A 74-year-old postmenopausal woman, presented to the emergency department with fever and right upper abdominal pain.The patient, a Caucasian housewife, had no significant personal or family medical history.Physical examination on admission revealed tenderness and guarding of the right hypochondrium and a fever with a temperature of 38.2 degree Celsius.Her body mass index was 32.Routine laboratory tests were normal except for a leucocytosis and an increased C-reactive protein (CRP) level.Abdominal ultrasonography showed a lithiasic gallbladder with thickened walls (see Figure 1).The patient was referred to the surgery department for cholecystectomy for acute lithiasic cholecystitis.
At coelioscopy, multiple nodular implants involving the omentum, the peritoneum and a magma of intestinal loops in the right iliac fossa were noted.The nodules were sampled.Gross examination showed multiple nodules of different sizes in the fat tissue.Pathologic examination showed massive psammoma bodies representing more than 75% of the tumor invading the peritoneal fibro-adipose tissue (see Figure 2).Some papillary structures and isolated tumoral cells were seen.The epithelial cells had low to moderate nuclear grade features including small nuclei, inconspicuous nucleoli and rare mitoses.We haven't identified any solid area of epithelial proliferation.Vascular emboli and perineural involvement were absent.The final diagnosis was psammocarcinoma.

REVISED Amendments from Version 1
In accordance with the reviewers' recommendations, minor modifications were made: • The title was changed from "Case Report: Fortuitous discovery of primary peritoneal psammocarcinoma" from to "Case Report: Incidental discovery of primary peritoneal psammocarcinoma".• Some parts of the abstract were reworded.
• A more detailed description of the histological lesions was provided.
• Prognosis, therapeutic strategies, and indications for adjuvant treatment, were discussed in detail in the revised version of the manuscript.
The patient was referred to gynecologic department for further investigation and to ascertain whether the tumor arose from ovaries or peritoneum.A computerized tomography scan was undergone and revealed: an uncomplicated sigmoid diverticulosis, an agglutination of the last ileal loops in contact with the anterior abdominal wall, an infiltration of the mesenteric fat and multiple mesenteric lymphadenopathies (see Figure 3).Hysterectomy, bilateral adnexectomy, omentectomy and lymph node dissection were performed.Macroscopic examination showed that both ovaries were intact, with a normal size (see Figure 4).No invasion of ovarian stroma was shown in microscopic examination.No lymph node invasion or distant metastasis had been identified.The final diagnosis was primary peritoneal psammocarcinoma (PPP).It was classified as stage III C carcinoma according to the International Federation of Gynecology and Obstetrics' (FIGO) classification.
After a multidisciplinary meeting, the decision was made to complete the treatment by adjuvant chemotherapy.

Discussion
Psammocarcinomas of the peritoneum and the ovary are rare serous carcinomas sharing the same histologic characteristics, histogenesis, and treatment modalities. 8PPP is an extremely rare peritoneal carcinoma.[5][6] The mean age for diagnosis in PPP is 52.1 years, ranging from 27 to 83 years. 9Clinically, patients usually present with nonspecific symptoms, such as abdominal discomfort, increase in abdominal girth, nausea, or vomiting. 10In 40% of cases, PPP is asymptomatic and is discovered incidentally, 11 similar to our case and the case described by Grinaldi et al. 3 The diagnosis of PPP is based on histopathological findings.First, Gilks et al defined psammocarcinoma by the association of four specific histologic criteria: (i) a destructive invasion of ovarian stroma, a vascular invasion, or, in the extraovarian cases, an invasion of intraperitoneal viscera; (ii) a mild to moderate nuclear atypia; (iii) an absence of area of solid epithelial proliferation, except for occasional nests with no more than 15 cells in diameter; (iv) at least 75% of papillae associated with or totally replaced by psammoma bodies. 1,3en, in 1994, Chen et al adapted the diagnostic criteria established by Gilks et al and had added the presence of an invasive pattern of the peritoneum, as a supplementary diagnosis criterion for the diagnosis of PPP. 12 Our case fulfilled all the criteria defined by Gilks and updated by Chen et al.
It is sometimes arduous to specify whether the psammocarcinoma is of peritoneal or ovarian origin.In such cases, only histologic examination can differentiate PPP from ovarian psammocarcinoma.The most important feature is ovarian stromal invasion seen in ovarian psammocarcinoma. 1,13,14In PPP, psammoma bodies and nests of tumor cells may be seen in the serosal surface of ovaries but without any invasion of ovarian stroma.
We have faced such difficulties in the case we present.For our patient, both ovaries were of normal size, small nests and psammoma bodies were present in serosal surface of ovaries but ovarian stroma was intact.The peritoneal involvement was greater than the involvement on the ovarian surface.Therefore, the diagnosis of PPP was confirmed.
The main differential diagnoses of PPP include the other epithelial serous neoplasms, such as cystadenofibromas and serous borderline tumors. 9These tumors may present abundant psammoma bodies, but the invasion of surrounding structures excludes these diagnoses.Low-grade serous carcinoma with numerous psammomatous bodies is another differential diagnosis.The presence of several nests of more than 15 cells precludes the diagnosis of psammocarcinoma.The presence of marked nuclear atypia and numerous figures of mitosis distinguishes high-grade serous carcinoma from PPP.
Mesothelioma with massive psammoma bodies may simulate PPP but negativity of D2-40, calretinin and CK5/6 excludes the diagnosis of mesothelioma. 15Calcified leiomyomatosis peritonealis disseminata (LPD), an infrequent subtype of leiomyomatosis occurring amongst young women with history of myomectomy, is another differential diagnosis of PPP. 16We could rule out this diagnosis since our patient was 74 years-old with no history of myomectomy.
Given the rarity of theses tumors, management protocols are not standardized due to the rarity of these tumors. 17Maximal cytoreductive surgery with hysterectomy, bilateral salpingo-oophorectomy and omentectomy, is the recommended treatment in the first instance. 1,16,17For young women, conservative surgery can be discussed to preserve fertility. 3hemotherapy is thought to have a poor efficiency in PPP. 16Chemotherapy is thought to have a poor efficiency in PPP. 16n fact, recurrences were recorded in some patients who had received adjuvant chemotherapy. 5However, follow-up adjuvant chemotherapy and hormonotherapy (tamoxifen), may be an option for residual diseases, PPP with aggressive behavior, and in case of recurrence, with positive results. 7,17,18The chemotherapy protocols consisted of cyclophosphamide with cisplatin or carboplatin. 7,17Complete response was obtained after adjuvant chemotherapy in an aggressive residual PPP in the case reported by Takahashi et al. 7 Complete response was also seen after the administration of Tamoxifen therapy in a recurrent PPP. 19ven their rarity, we do not dispose enough elements to judge the scalability of PPPs.However, PPP is likely to have a high potential towards peritoneal recurrence, even after suitable treatment. 20Some of the reported cases had developed several recurrences with a period of more than 5 or 10 years between those recurrences. 8though most of PPP seem to display an indolent clinical course, some may be very aggressive, with distant metastases. 7e of the strengths of our study is that we were able to demonstrate with certainty that the primary origin of the psammocarcinoma was peritoneal and not ovarian.However, its major limitation consists in the lack of follow-up.In fact, since our patient had died of COVID-19 six days after the second surgery, we were not able to assess the response to treatment, the risk of recurrence and metastases and the prognosis of this tumor.The patient's obesity might be a factor that favored the COVID-19 related early post operative death.

Conclusions
PPP is a rare type of low-grade serous carcinoma.The behavior of this tumor is unclear, and the treatment is not standardized because of its rarity and lack of long-term follow-up.The investigation of supplementary cases is imperative for a better comprehension of this entity and for the enhancement of management protocols.-Data regarding presentation and treatment is insufficient.Can be added more.

Is the background of the case's history and progression described in sufficient detail
Additionally also there are few sentences can be rephrased.
There is doubling of a sentence.I would suggest to make sure to correct all the typos and necessary edits.
-Sizes of nodules in centimeters should be provided.It might affect the recurrence rate.Authors' response: We discussed factors favoring the early post-operative death due to the COVID-19 infection.Indeed, the patient was obese with a BMI of 32.The title of this report is "Fortuitous discovery of PPP".However, the patient died six days after the surgical staging for PPP.As the word fortuitous implies 'advantage', the title might be changed.

Authors' response:
We replaced the title in the revised version by "Case Report: Incidental discovery of primary peritoneal psammocarcinoma" Case presentation: a temperature of 38.2 degrees "Celsius" 1.

Authors' response:
The term "Celsius" was added in the revised manuscript.
Authors' response: the arrow was added in Figure 2 Figure 3: the figure should carry out an arrow pointing the agglutination of the last ileal loops. 1.

Authors' response:
The arrow pointing the agglutination of the last ileal loops was added in Figure 3.
Competing Interests: No competing interests were disclosed.

Marouen Braham
Aziza Othmana University hospital, Tunis, Tunisia This case report shows the approach in front of a suspicion of peritoneal psammocarcinoma, diagonostic difficulty and etiological research, the subject is interesting because primary peritoneal psammocarcinoma is a very rare pathology and the diagnosis is not obvious.

Recommendations:
Could you add pictures from the 1st or 2nd surgery? 1.
Could you elaborate on the anatomopathological examination with more detailed description?

2.
Regarding the discussion, could you note the prognosis in the literature and chemotherapy used in theses cases?

3.
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Figure 1 .
Figure 1.Abdominal ultrasound.The walls of the gallbladder (GB) are thickened, hyperechoic with a mobile gallstone.

Figure 3 .
Figure 3. Abdominal computerized tomography scan.Agglutination of the last ileal loops in contact with the anterior abdominal wall (see arrow), infiltration of the mesenteric fat and multiple mesenteric lymphadenopathies.

Figure 4 .
Figure 4. Macroscopic examination showed both ovaries with the circles indicating the normal size.
? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?No Is the case presented with sufficient detail to be useful for other practitioners?Partly Competing Interests: No competing interests were disclosed.Reviewer Expertise: Surgical oncology, peritoneal tumors/metastasis/ cytoreductive surgery I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.Reviewer Report 06 September 2024 https://doi.org/10.5256/f1000research.157236.r271805© 2024 Sapna F. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Fnu Sapna Anatomic and Clinical Pathology, Montefiore Medical Center, Albert Einstein School of Medicine, Bronx, New york, USA -History of SARS-CoV-2 infection is unclear.was the patient had SARS CoV-2 diagnosed before surgery?-No any pelvic imaging (CT/MRI) has been described before attempting hysterectomy and bilateral oophorectomy.
the background of the case's history and progression described in sufficient detail?Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Partly Is the case presented with sufficient detail to be useful for other practitioners?Partly Competing Interests: No competing interests were disclosed.Reviewer Expertise: Gynecologic and Breast Pathology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.Reviewer Report 03 September 2024 https://doi.org/10.5256/f1000research.157236.r215712© 2024 Braham M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Marouen Braham Aziza Othmana University hospital, Tunis, Tunisia Most corrections have been made .the paper is ready for indexing in this new version.Is the background of the case's history and progression described in sufficient detail?Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Partly Is the case presented with sufficient detail to be useful for other practitioners?Partly Competing Interests: No competing interests were disclosed.Reviewer Expertise: Reproductive Medicine / Gynecology Surgery / Fertility preservation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.Is the background of the case's history and progression described in sufficient detail?Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Partly Is the case presented with sufficient detail to be useful for other practitioners?Partly Competing Interests: No competing interests were disclosed.

Figure 3 . 3 .
Figure 3.The figures should carry an arrow pointing to "agglutination of the last ileal loops." 3.

Reviewer Report 22
August 2022 https://doi.org/10.5256/f1000research.121959.r144608© 2022 Braham M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.