Medulloblastoma and other neoplasms in patients with heterozygous germline SUFU variants: A scoping review.

In 2002, heterozygous suppressor of fused variants (SUFU+/-) in the germline were described to have a tumor suppressor role in the development of pediatric medulloblastoma (MB). Other neoplasms associated with pathologic germline SUFU+/- variants have also been described among patients with basal cell nevus syndrome (BCNS; BCNS is also known as Gorlin syndrome, nevoid basal cell carcinoma [BCC] syndrome or Gorlin-Goltz syndrome; OMIM 109400), an autosomal-dominant cancer predisposition syndrome. The phenotype of patients with germline SUFU+/- variants is very poorly characterized due to a paucity of large studies with long-term follow-up. As such, there is a clinical need to better characterize the spectrum of neoplasms among patients with germline SUFU+/- variants so that clinicians can provide accurate counseling and optimize tumor surveillance strategies. The objective of this study is to perform a scoping review to map the evidence on the rate of medulloblastoma and to describe the spectrum of other neoplasms among patients with germline SUFU+/- variants. A review of all published literature in PubMed (MEDLINE), EMBASE, Cochrane, and Web of Science were searched from the beginning of each respective database until October 9, 2021. Studies of pediatric and adult patients with a confirmed germline SUFU+/- variant who were evaluated for the presence of any neoplasm (benign or malignant) were included. There were 176 patients (N = 30 studies) identified with a confirmed germline SUFU+/- variant who met inclusion criteria. Data were extracted from two cohort studies, two case-control studies, 18 case series, and eight case reports. The median age at diagnosis of a germline SUFU+/- variant was 4.5 years where 44.4% identified as female and 13.4% of variants were de novo. There were 34 different neoplasms (benign and malignant) documented among patients with confirmed germline SUFU+/- variants, and the most common were medulloblastoma (N = 59 patients), BCC (N = 21 patients), and meningioma (N = 19 patients). The median age at medulloblastoma diagnosis was 1.42 years (range 0.083-3; interquartile range 1.2). When data were available for these three most frequent neoplasms (N = 95 patients), 31 patients (32.6%) had neither MB, BCC nor meningioma; 51 patients (53.7%) had one of medulloblastoma or BCC or meningioma; eight patients (8.4%) had two of medulloblastoma or BCC or meningioma, and five patients (5.3%) had medulloblastoma and BCC and meningioma. This is the first study to synthesize the data on the frequency and spectrum of neoplasms specifically among patients with a confirmed germline SUFU+/- variant. This scoping review is a necessary step forward in optimizing evidence-based tumor surveillance strategies for medulloblastoma and estimating the risk of other neoplasms that could impact patient outcomes.

A challenging case of pseudo Meigs syndrome: A case report.

Meigs Syndrome is a rare condition characterised by Ovarian fibroma, ascites and pleural effusion. Pseudo Meigs is called so because it mimics Meigs but occurs with tumours other than fibromas. The objective of this case report is to shed light on the diverse presentations of Ovarian carcinomas. We herein report a rare case of Pseudo Meigs syndrome in a 32-year-old female patient parity one and no miscarriage and who had right-sided ovarian mass, gross ascites and right-sided pleural effusion with cancer antigen 125 value of 518.5 IU/L. Clinical Diagnosis was that of Meigs Syndrome. The patient underwent laparotomy for surgical staging and large right-sided ovarian mass with draining of nine litres of ascitic fluid and total abdominal hysterectomy and bilateral salpingo-oophorectomy. The histopathology report showed that it was Endometroid Adenocarcinoma FIGO Grade 3. Definitive diagnosis was that of Pseudo Meigs Syndrome. The case was a diagnostic challenge and difficult to manage. The diverse presentation of ovarian carcinomas makes them difficult to diagnose and clinicians should have a high index of suspicion while managing such cases.

A case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion.

BACKGROUND: Meigs' syndrome is defined as the presence of a benign ovarian tumor with pleural effusion and ascites that resolve after removal of the tumor. The pathogenesis of the production of ascites and pleural effusion in this syndrome remains unknown. Aside from pleural effusion and ascites, pericardial effusion is rarely observed in Meigs' syndrome. Here, we report the first case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion. CASE PRESENTATION: An 84-year-old Japanese non-smoking woman with a history of lung cancer, treated by surgery, was admitted due to gradual worsening of dyspnea that had occurred over the previous month. She had asymptomatic and unchanging pericardial effusion and a pelvic mass, which had been detected 3 and 11 years previously, respectively. The patient was radiologically followed-up without the need for treatment. Two months before admission, the patient underwent a right upper lobectomy for localized lung adenocarcinoma and intraoperative pericardial fenestration confirmed that the pericardial effusion was not malignant. However, she began to experience dyspnea on exertion leading to admission. A chest, abdomen, and pelvis computed tomography scan confirmed the presence of right-sided pleural and pericardial effusion and ascites with a left ovarian mass. Repeated thoracentesis produced cultures that were negative for any microorganism and no malignant cells were detected in the pleural effusions. Pleural fluid accumulation persisted despite a tube thoracostomy for pleural effusion drainage. With a suspicion of Meigs' syndrome, the patient underwent surgical resection of the ovarian mass and histopathological examination of the resected mass showed ovarian fibroma. Pleural and pericardial effusion as well as ascites resolved after tumor resection, confirming a diagnosis of Meigs' syndrome. This clinical course suggests a strong association between pericardial effusion and ovarian fibroma, as well as pleural and peritoneal fluid. CONCLUSIONS: In female patients with unexplained pericardial effusion and an ovarian tumor, clinicians should consider the possibility of Meigs' syndrome. Although a malignant disease should be suspected in all patients with undiagnosed pleural and/or pericardial effusion, Meigs' syndrome is curable by tumor resection and should be differentiated from malignancy.

Meigs syndrome presenting with recurrent unilateral pleural effusion.

Pelvic tumours are a rare cause of pleural effusion. We describe an approach to a case of Meigs syndrome with recurrent unilateral pleural effusion. A woman in her 60s' presented with recurrent right-sided pleural effusion, leading to cough and shortness of breath. Thoracentesis yielded exudative pleural fluid with cytology negative for malignancy. Pleuroscopy revealed inflamed pleura, and pleural biopsy was consistent with inflammatory changes. The patient's cancer antigen 125 level was elevated at 256 U/mL. Given the high suspicion of malignancy, a computed tomography scan of the chest, abdomen, and pelvis was performed and revealed ascites and a large left ovarian and uterine mass. The patient underwent a total abdominal hysterectomy and bilateral salphingo oophorectomy after experiencing three additional episodes of pleural effusion. Histological examination revealed the left ovarian mass to be a cellular fibroma and the uterine masses to be leiomyomata. Following the operation, there was no recurrence of pleural effusion.

Laparoscopic ovarian-sparing surgery for a young woman with an exophytic ovarian fibroma.

Ovarian fibroma can occur in young women of reproductive age. Despite its benign feature, most surgical removals are done in open surgery with oophorectomy. However, an ovarian-sparing tumor resection can be an option, especially for an exophytic type of fibroma, which accounts for more than half of ovarian fibromas. Here we report a case of exophytic ovarian fibroma in a young woman treated by laparoscopic ovarian-sparing surgery. A 27-year-old woman presented with a pelvic mass. Magnetic resonance imaging revealed an 11 cm × 8 cm solid mass connected to the normal-appearing left ovary by a pedicle-like structure. A clinical diagnosis of an exophytic ovarian fibroma was made, and laparoscopic ovarian-sparing surgery with an intraoperative pathological examination was planned. The tumor was resected by cutting the pedicle, morcellated in a pouch and removed. All procedures were performed laparoscopically and the affected ovary was completely preserved. Having confirmation of its benign characteristics by the intraoperative examination, no further excision was performed. The patient conceived 3 months after the surgery and no recurrence was reported. We propose that gynecologists should consider laparoscopic ovarian-sparing surgery for exophytic ovarian fibroma in women of reproductive age.

Bilateral ovarian fibromas as the sole manifestation of Gorlin syndrome in a 22-year-old woman: a case report and literature review.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is a rare autosomal dominantly inherited disorder that is characterized by multisystem disorder such as basal cell carcinomas, keratocystic odontogenic tumors and skeletal abnormalities. Bilateral and/or unilateral ovarian fibromas have been reported in individuals diagnosed with NBCCS. CASE PRESENTATION: A 22-year-old female, presented with low back pain, and was found to have bilateral giant adnexal masses on pelvic ultrasonography, which had been suspected to be malignant ovarian tumors. Positron emission tomography/computed tomography showed multiple intracranial calcification and skeletal abnormalities. The left adnexa and right ovarian tumor were resected with laparotomy, and pathology revealed bilateral ovarian fibromas with marked calcification. We recommended the patient to receive genetic testing and dermatological examination. No skin lesion was detected. Germline testing identified pathogenic heterozygous mutation in PTCH1 (Patched1). CONCLUSIONS: The possibility of NBCCS needs to be considered in patients with ovarian fibromas diagnosed in an early age. Skin lesions are not necessary for the diagnosis of NBCCS. Ovarian fibromas are managed with surgical excision with an attempt at preserving ovarian function. Follow-up regime and counseling on options for future fertility should be offered to patients.

Surgical Treatment of a Rare Case of Ovarian Fibroma Associated With Elevated CA125 Levels in a Patient of Reproductive Age: A Case Report.

Small ovarian fibromas (< 10cm) associated with elevated serum CA125 levels are rarely encountered, particularly in women of reproductive age. We report a rare case diagnosed in a 35-year-old patient after adnexectomy for a solid ovarian mass of approximately 5cm in maximum diameter, accompanied by elevated serum CA125 levels. In preoperative evaluation, no signs of inflammation from the genital tract were found, and no medical history of endometriosis, uterine leiomyomas, or non-gynecological cancer was reported. Intraoperative frozen section biopsy of surgical specimen obtained from the ovarian tumor had negative evaluation for malignancy. Histological examination of the surgical specimen confirmed the diagnosis of ovarian fibroma. The postoperative course was uneventful. Two months after surgery, the blood serum CA125 levels were within normal ranges. The patient is assessed at regular intervals in the gynecology outpatient clinic. In this paper, based on the data of the modern literature, a brief review of this rare nosological entity is made.

A rare case of Demons-Meigs' syndrome with a 7.5 kg giant ovarian fibroma associated with severe dyspnea: case report.

Introduction and importance: Demons-Meigs syndrome is a rare condition characterized by the presence of a benign fibroma of the ovary, ascites, and pleural effusion. It is very uncommon, and the diagnosis is made with difficulty based on symptoms that usually mimic disseminated malignancy or tuberculosis, but imaging may confirm the diagnosis. The definitive treatment is laparotomy, after which the symptoms resolve. Case presentation: We present a 36-year-old female with Demons-Meigs' syndrome with severe dyspnea who underwent an abdominal surgical exploration, which revealed ascites of 1500 ml and an ovarian fibroma weighing 7.5 kg and measuring 12 cm in length. There were no postoperative complications. CA-125 was undetectable at 3 months post-procedure. Clinical discussion: The most common symptoms are dyspnea, fever, fatigue, and weight loss. In low- and middle-income countries, patients usually present with late-stage disease. The treatment of choice for Demons-Meigs' syndrome is exploratory laparotomy. Conclusion: This tumor is often misdiagnosed as a uterine myoma on sonography. The symptoms resolved, and the patient became asymptomatic after laparotomy and thoracocentesis. For this reason, when patients present with effusion and an abdominal mass, a thorough assessment should be done to confirm if it is Demons-Meigs' syndrome, which can be completely cured by the removal of the tumor.

Ovarian Fibroma Presents As Uterine Leiomyoma in a 61-Year-Old Female: A Case Study.

Uterine leiomyoma should be considered when a female patient reports symptoms of abdominal pressure and abnormal vaginal bleeding. However, the symptoms of a uterine leiomyoma are vast and overlap with other possible diseases that are difficult to distinguish even with imaging studies. This is why it is important for physicians and healthcare providers to keep an open mind and have a broad differential diagnosis.  In this case study, we present a 61-year-old postmenopausal female patient who presented to the emergency department with complaints of pelvic and abdominal pain, as well as vomiting and diarrhea. She was admitted for observation. A complete blood count (CBC), comprehensive metabolic panel (CMP), and urinalysis revealed no abnormalities; a pelvic ultrasound and CT scan reported possible adnexal torsion. The patient remained stable and the pain had subsided when she was seen the next morning by her gynecologist (GYN) who discharged her to follow-up in the office. Subsequent examinations that aided in the diagnosis included, but were not limited to pelvic and transvaginal ultrasounds, an abdominal and pelvic CT, and a pelvic MRI. In this case, the MRI revealed an 11-cm mass that could represent a torsioned pedunculated necrotic fibroid originating from the uterus. Radiology recommended surgical removal. Upon removal and review of the pathology of the mass, it was revealed to be a torsioned, partially necrotic fibroma that had originated from the ovary and not from the uterus, as imaging had originally suggested.

A case of death of patient with ovarian fibroma combined with Meigs Syndrome and literature review.

Ovarian fibroma is the most common benign pure stromal tumor. It has no specific clinical manifestation, most of which are pelvic or adnexal masses. 10-15% of cases with hydrothorax or ascites, after tumor resection, hydrothorax and ascites disappear, known as Meigs Syndrome. The elevated level of CA125 in a few patients was easily misdiagnosed as ovarian malignant tumor. A case of bilateral Ovarian fibroma associated with Meigs Syndrome is reported and the literature is reviewed in order to improve the understanding of the changes and avoid misdiagnosis.

Inhibin B Secreting Ovarian Fibroma.

Background: Nearly 90% of all the hormone-producing ovarian tumours are sex cord-stromal tumours (SCSTs). The Ovarian fibroma is a hormonally inactive variant of SCST. It is composed of spindle, oval, round cells producing collagen and accounts for approximately 4% of all ovarian neoplasms. Amongst the other SCSTs, Inhibin B is an important tumour marker. It is a heterodimeric glycoprotein hormone that is secreted primarily by the granulosa cells of the developing follicles. High levels of Inhibin-B can hamper follicular recruitment, leading to amenorrhea in a reproductive age woman. Finding: In this case report, we describe a rare case of a reproductive age female presenting with secondary amenorrhea, having an Ovarian Fibroma, producing massive amounts of Inhibin B. Significance: Although some pathological variants of ovarian fibromas like cyst-adeno-fibroma and ovarian fibro-thecoma are known to secrete inhibin B, benign /pure ovarian fibromas rarely do so.

Calcified Ovarian Fibromas Complicated with Basal Cell Nevus Syndrome.

Basal cell nevus syndrome (BCNS) is a rare neurocutaneous syndrome characterized by tumorigeneses such as basal cell carcinomas, jaw cysts, ovarian fibromas, and cardiac fibromas. We present a 24-year-old female with calcified ovarian fibromas associated with BCNS. She had a surgical history of the maxillary cyst and was diagnosed with BCNS due to the cutaneous pits. Magnetic resonance imaging indicated an 8-cm mass and a 4-cm mass, which had been suspected to be a subserosal myoma and a fibroma, respectively. GnRH agonist was preoperatively administered; however, the size of the masses did not change. In laparoscopy, a tumor consisting of 8- and 5-cm masses in the right ovary was identified, and tumorectomy was performed. Because both tumors were extraordinarily rigid and could not be morcellated with scalpels or scissors, we removed them by the Luer Bone Rongeurs with minilaparotomy. The histopathological diagnosis was the ovarian fibromas with marked calcification.

Two Patients With Meigs' Syndrome and Elevated Serum CA-125: A Case Report.

Patients with Meigs' syndrome and elevated serum CA-125 are not frequently reported. A 59-year-old woman and a 48-year-old woman sought help because of progressive shortness of breath caused by pleural effusion. The presence of a pelvic mass was noted in both the patients and was thought to be the cause of the effusion. Both patients had elevated serum CA-125, which raised the possibility of malignancy. After complete resection of the tumors, the pathologic reports confirmed a benign and a low-grade malignant ovarian neoplasia, respectively. We comment on the outcome and follow-up of these two cases and briefly review Meigs' syndrome.

Molecular comparison of pure ovarian fibroma with serous benign ovarian tumours.

OBJECTIVE: Ovarian fibromas and adenofibromas are rare ovarian tumours. They are benign tumours composed of spindle-like stromal cells (pure fibroma) or a mixture of fibroblast and epithelial components (adenofibroma). We have previously shown that 40% of benign serous ovarian tumours are likely primary fibromas due to the neoplastic alterations being restricted to the stromal compartment of these tumours. We further explore this finding by comparing benign serous tumours to pure fibromas. RESULTS: Performing copy number aberration (CNA) analysis on the stromal component of 45 benign serous tumours and 8 pure fibromas, we have again shown that trisomy of chromosome 12 is the most common aberration in ovarian fibromas. CNAs were more frequent in the pure fibromas than the benign serous tumours (88% vs 33%), however pure fibromas more frequently harboured more than one CNA event compared with benign serous tumours. As these extra CNA events observed in the pure fibromas were unique to this subset our data indicates a unique tumour evolution. Gene expression analysis on the two cohorts was unable to show gene expression changes that differed based on tumour subtype. Exome analysis did not reveal any recurrently mutated genes.

Bilateral ovarian fibroma associated with Gorlin syndrome.

Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare inherited multisystem disorder. This paper presents a 22-years-old Iranian woman with this syndrome whose past history was multiple keratocysts of maxillary bone. She was referred to gynecology clinic with the chief complaint of irregular menses and vaginal spotting. On examination, frontal bossing and hypertelorism were detected. Physical examination of genitalia disclosed bilateral adnexal masses. Pelvic ultrasound showed two solid, echogenous and calcified masses measuring 100*50*10 & 60*50*45 mm in the left and right ovaries, respectively. The patient underwent right oophorectomy and ovarian mass resection with preservation of intact ovarian tissue on the left side. On frozen and permanent histological sections, bilateral and calcified ovarian fibromas were diagnosed. Surprisingly, during the last follow-up one year after the surgery, we found that our patient was expecting a baby. It can be concluded that in the presence of bilateral and calcified ovarian fibromas, the possibility of GS should be considered. Accurate diagnosis is only possible with close attention to the familial and past medical history and physical examination. In these patients, careful follow up for detecting malignancies and other complications is highly recommended.

Fibroma bilateral de ovario en mujer posmenopáusica. Reporte de un caso y revisión de la literatura / Bilateral ovarian fibroma in postmenopausal woman. Case report and literature review

Los fibromas ováricos son tumores benignos poco frecuentes, generalmente unilaterales, que se presentan principalmente en mujeres perimenopáusicas y posmenopáusicas. Los síntomas pueden variar y en algunos casos están asociados a ascitis y derrame pleural, conocido como síndrome de Meigs. Se presenta un caso de una paciente de 55 años de edad con antecedentes de hipertensión arterial y asma bronquial, quién acude a ginecólogo por dolor en fosa ilíaca derecha de tres meses de evolución. Se realizan diferentes estudios incluyendo ecografía y tomografía abdomino-pélvica, los cuales revelan una tumoración sólida bilateral de ovarios. Se realiza histerectomía abdominal total más salpingo-oforectomía bilateral y a pesar de sus características, el estudio histopatológico hace el diagnóstico de fibroma bilateral. La presentación clínica de los fibromas de ovario es inespecífica, por lo que suelen confundirse con patología maligna del ovario u otras patologías benignas de útero u ovario, constituyendo un reto para el diagnóstico preoperatorio(AU)

Ovarian fibromas are rare tumors that mainly occur in perimenopausal and postmenopausal women. Symptoms can vary, and in some cases, they may be associated with ascites and pleural effusion, known as Meigs Syndrome. The article presents the case of a 55-year-old patient with a history of hypertension and bronchial asthma, who visit a gynecologist due to pain in the right iliac fossa of three months duration. Various studies were performed, including ultrasound and abdominal and pelvic CT, which reveal the presence of solid bilateral ovarian tumors. The patient undergoes a total hysterectomy and bilateral salpingo-oophorectomy and despite it's characteristics, the histopathological study makes the diagnosis of bilateral ovarian fibroma with no signs of malignancy. The clinical presentation of ovarian fibromas is nonspecific, often leading to confusion with malignant ovarian pathology or other benign uterine or ovarian conditions, representing a challenge for preoperative diagnosis(AU)

Conservative Management of Ovarian Fibroma in A Case of Gorlin-Goltz Syndrome Comorbid with Endometriosis.

Ovarian fibromas are the most common benign solid ovarian tumors, which are often difficult to diagnose preoperatively. Ovarian fibromas, especially in bilateral cases, may be cases of Gorlin-Goltz syndrome (GGS), a rare autosomal dominant disorder with predisposition to basal cell carcinomas (BCCs) and other various benign and malignant tumors. This case report describes a 25 year-old female with GGS, bilateral ovarian fibroma, endometriosis and septated uterus, which was referred to the Gynecology Clinic of Rasoul-e-Akram Hospital in October 2016. This patient had facial asymmetry due to recurrent odontogenic keratocysts. In young cases of ovarian fibromas as reported here, conservative surgical management can preserve ovarian function and fertility. These patients must be followed up by a multidisciplinary team and submitted to periodic tests.

Ovarian fibroma with luteinized thecal cells and minor sex cord element: A rare case report.

Ovarian fibroma with minor sex cord element (MSCE) is a rare tumor. The increased estrogen production due to the presence of MSCE and/or luteinized thecal cells within fibroma can be a risk factor for endometrial hyperplasia or carcinoma.

Ovarian Fibroma: A Clinico-pathological Study of 23 Cases with Review of Literature.

PURPOSE: The purpose of this study was to correlate the clinical findings, RMI-4 index and frozen section, in cases of ovarian fibroma with the final histopathology. METHODS: This is a retrospective study of clinical and pathological features of 23 patients of ovarian fibroma. The patient's age ranged from 34 to 66 years (mean-49 years). The most common presenting symptom was abdominal pain. On clinical examination, the mean size of ovarian tumor was 9.5 cm, CA-125 levels were found to be raised in 14 patients, and it was associated with ascites in 10 patients. USG showed a well-circumscribed mass (with a mean size of 14 cm), on the left side in 14 cases and on the right side in 9 patients. RMI-4 was calculated in all the patients, and it revealed the possibility of a benign histology in 17 patients. All patients underwent exploratory laparotomy with the removal of ovarian tumor followed by frozen section examination. All but one (22/23) patient had positive correlation among frozen section and final histopathological findings. RESULT: Ovarian fibroma generally tends to occur in post-menopausal women. All the patients in our study of ovarian fibroma were symptomatic, with the presence of palpable mass in majority of patients. RMI-4 Index correlated very well with benign nature of disease. Frozen section has an invaluable role at surgery; fertility-conserving surgery is the choice in young women. CONCLUSION: Clinical findings, RMI-4 Index and frozen section, play vital roles before and during surgery in cases of benign ovarian tumors.