Reassessment of EUS features in preoperative diagnosis of pancreatic serous cystic neoplasm: Lessons to avoid misdiagnosis.

OBJECTIVES: Pancreatic serous cystic neoplasm (SCN) is a benign cystic neoplasm that is likely to be surgically resected due to preoperative misdiagnosis or tentative diagnosis even using endoscopic ultrasonography (EUS). We aimed to analyze EUS findings of SCN associated with misdiagnosis. METHODS: Between January 2012 and September 2023, histologically confirmed pancreatic SCN were included and EUS features were reviewed. RESULTS: Overall, 294 patients with 300 surgically resected SCNs were included. The median age of the patients was 51 years and 75.9% were females. The lesions were predominantly located in the body/neck/tail of the pancreas (63.0%). The overall preoperative diagnostic rate of SCN was 36.3%, with the most common misdiagnosis being intraductal papillary mucinous neoplasm (IPMN) (31.3%), while 16.3% remained undefined. The preoperative diagnostic rate of SCN varied across different endosonographic morphologies, with oligocystic, macrocystic, microcystic, and solid patterns yielding rates of 12.8%, 37.9%, 76.5%, and 19.2%, respectively. Notably, the presence of central scar and vascularity improved the diagnostic accuracy and correctly identified 41.4% and 52.3% of the lesions. While mucus or pancreatic duct (PD) communication significantly increased the likelihood of misdiagnosis, particularly as IPMN. Multivariate analysis revealed a morphological pattern, mucin-producing signs, wall thickening, vascularity, and PD communication were independent factors related to preoperative misdiagnosis, with an overall accuracy of 82.3%. CONCLUSIONS: Preoperative diagnosis of SCN remains challenging. The microcystic pattern emerged as a reliable feature, while mucin-producing signs, including mural nodules, mucus, and PD communication, pose diagnostic pitfalls despite the presence of typical central scar or vascularity commonly in SCN.

Imaging of pancreatic serous cystadenoma and common imitators.

Pancreatic cystic neoplasms are lesions comprised of cystic components that show different biological behaviors, epidemiology, clinical manifestations, imaging features, and malignant potential and management. Benign cystic neoplasms include serous cystic neoplasms (SCAs). Other pancreatic cystic lesions have malignant potential, such as intraductal papillary mucinous neoplasms and mucinous cystic neoplasms. SCAs can be divided into microcystic (classic appearance), honeycomb, oligocystic/macrocystic, and solid patterns based on imaging appearance. They are usually solitary but may be multiple in von Hippel-Lindau disease, which may depict disseminated involvement. The variable appearances of SCAs can mimic other types of pancreatic cystic lesions, and cross-sectional imaging plays an important role in their differential diagnosis. Endoscopic ultrasonography has helped in improving diagnostic accuracy of pancreatic cystic lesions by guiding tissue sampling (biopsy) or cyst fluid analysis. Immunohistochemistry and newer techniques such as radiomics have shown improved performance for preoperatively discriminating SCAs and their mimickers.

INSM1 is a useful neuroendocrine marker to differentiate pancreatic serous cystadenoma from pancreatic well-differentiated neuroendocrine tumors in cytology and surgical specimens.

INTRODUCTION: Differentiating pancreatic serous cystadenoma (SCA) from well-differentiated neuroendocrine tumors (WDNETs) based on histomorphology is critical yet challenging, particularly in small biopsy samples. Our study aimed to examine the expression profile of INSM1 in cytologic and surgical resection specimens from pancreatic SCA to evaluate its potential as a discriminative marker against pancreatic WDNET. METHODS: We characterized INSM1 immunohistochemistry in 34 patients with pancreatic SCA, comprising 23 surgical resections and 11 cytology specimens. As a control, we used 28 cytology specimens from pancreatic WDNET. Clinical information was retrieved through a review of electronic medical records. RESULTS: All 11 pancreatic SCA cytology specimens and 15 of 23 pancreatic SCA surgical resections exhibited absent INSM1 immunostaining. Each of the remaining eight surgical resection specimens demonstrated 1 % immunoreactivity. In contrast, 27 out of 28 (96 %) pancreatic WDNET cytology specimens were positive for INSM1 immunostaining, with a median immunoreactivity of 90 % and a range of 30-90 %. Overall, INSM1 immunostains perform similarly to chromogranin and synaptophysin in pancreatic SCA. CONCLUSIONS: The results indicate that INSM1 immunohistochemistry staining may serve as a useful neuroendocrine marker to differentiate pancreatic SCA from pancreatic WDNET in clinical practice. To our knowledge, this represents the first large-scale study to evaluate INSM1 immunostaining in surgical and cytology specimens from pancreatic SCA.

Improving diagnostic yield of pancreatic serous cystadenoma with cyst fluid ancillary testing, adjunct immunohistochemistry, and additional fine-needle biopsy sampling.

BACKGROUND: Fine-needle aspiration (FNA) diagnosis of pancreatic serous cystadenoma (SCA) remains challenging. This retrospective study aimed to evaluate the roles of cyst fluid ancillary testing and combined fine-needle biopsy (FNB) in improving the diagnostic yield. METHODS: The authors retrospectively reviewed cytology cases that were histologically confirmed SCAs. Clinical features and FNA cyst fluid biochemical and molecular analysis results along FNB findings were reviewed. RESULTS: The study cohort included 31 cases from 13 male and 18 female patients with a mean age of 65. The original cytologic diagnoses were nondiagnostic (n = 6, 19%), negative for malignant cells/cyst contents (n = 7, 23%), atypical cells (n = 3, 10%), nonmucinous cyst (n = 11, 35%), and serous cystadenoma (n = 4, 13%). Cyst fluid carcinoembryonic antigen (CEA) analysis was performed in 17 cases, all of which showed a low CEA level (<192 ng/mL). All 14 cases with molecular testing showed a wild-type KRAS. Inhibin immunohistochemistry was retrospectively performed on the FNA cell blocks, inhibin was positive in six of seven cases tested. In 15 cases with concurrent FNA and FNB biopsies, the diagnosis of SCA was seen in only one FNA case (7%) but 13 FNB cases (87%). CONCLUSIONS: This study suggests that FNA diagnosis of SCA remains challenging even with ancillary testing including cyst fluid CEA level and KRAS mutation analysis. Adjunct inhibin immunostaining may help improve the cytologic diagnosis of selective SCA cases. FNB appears superior to FNA for a definite diagnosis of SCA.

Natural history and growth prediction model of pancreatic serous cystic neoplasms.

OBJECTIVE: Serous cystic neoplasms (SCN) are benign pancreatic cystic neoplasms that may require resection based on local complications and rate of growth. We aimed to develop a predictive model for the growth curve of SCNs to aid in the clinical decision making of determining need for surgical resection. METHODS: Utilizing a prospectively maintained pancreatic cyst database from a single institution, patients with SCNs were identified. Diagnosis confirmation included imaging, cyst aspiration, pathology, or expert opinion. Cyst size diameter was measured by radiology or surgery. Patients with interval imaging ≥3 months from diagnosis were included. Flexible restricted cubic splines were utilized for modeling of non-linearities in time and previous measurements. Model fitting and analysis were performed using R (V3.50, Vienna, Austria) with the rms package. RESULTS: Among 203 eligible patients from 1998 to 2021, the mean initial cyst size was 31 mm (range 5-160 mm), with a mean follow-up of 72 months (range 3-266 months). The model effectively captured the non-linear relationship between cyst size and time, with both time and previous cyst size (not initial cyst size) significantly predicting current cyst growth (p < 0.01). The root mean square error for overall prediction was 10.74. Validation through bootstrapping demonstrated consistent performance, particularly for shorter follow-up intervals. CONCLUSION: SCNs typically have a similar growth rate regardless of initial size. An accurate predictive model can be used to identify rapidly growing outliers that may warrant surgical intervention, and this free model (https://riskcalc.org/SerousCystadenomaSize/) can be incorporated in the electronic medical record.

Paraovarian tumor of borderline malignancy: A case report.

Paraovarian tumors of borderline malignancy (PTBM) are exceedingly rare, with only slightly over 60 cases reported worldwide. This report presents the case of a 22-year-old nulliparous patient who incidentally discovered a left paraovarian mass during a routine abdominal ultrasound. Subsequent MRI revealed a 2.5×2.1 cm cystic lesion located in close proximity to, but outside of, the left ovary, with no other pathological findings. A laparoscopic cystectomy was performed with meticulous care to prevent tumor spillage, and the patient experienced an uneventful recovery. Histopathological examination unveiled irregularly shaped tissue measuring 2.2×1.2×1 cm, characterized by fibrous tissue/wall with spindle cell stroma and an epithelium displaying features consistent with a serous borderline tumor. Our multidisciplinary team recommended diligent follow-up. This case contributes to the existing literature on PTBM and highlights the imperative for additional cases to enhance our comprehension of the optimal management of these exceedingly rare tumors.

Utilization of texture features of volumetric ADC maps in differentiating between serous cystadenoma and intraductal papillary neoplasms.

INTRODUCTION: The rising incidence of incidental detection of pancreatic cystic neoplasms has compelled radiologists to determine new diagnostic methods for the differentiation of various kinds of lesions. We aim to demonstrate the utility of texture features extracted from ADC maps in differentiating intraductal papillary mucinous neoplasms (IPMN) from serous cystadenomas (SCA). METHODS: This retrospective study was performed on 136 patients (IPMN = 87, SCA = 49) split into testing and training datasets. A total of 851 radiomics features were extracted from volumetric contours drawn by an expert radiologist on ADC maps of the lesions. LASSO regression analysis was used to determine the most predictive set of features and a radiomics score was developed based on their respective coefficients. A hyper-optimized support vector machine was then utilized to classify the lesions based on their radiomics score. RESULTS: A total of four Wavelet features (LHL/GLCM/LCM2, HLL/GLCM/LCM2, /LLL/First Order/90percent, /LLL/GLCM/MCC) were selected from all of the features to be included in our classifier. The classifier was optimized by altering hyperparameters and the trained model was applied to the validation dataset. The model achieved a sensitivity of 92.8, specificity of 90%, and an AUC of 0.97 in the training data set, and a sensitivity of 83.3%, specificity of 66.7%, and AUC of 0.90 in the testing dataset. CONCLUSION: A support vector machine model trained and validated on volumetric texture features extracted from ADC maps showed the possible beneficence of these features in differentiating IPMNs from SCAs. These results are in line with previous regarding the role of ADC maps in classifying cystic lesions and offers new evidence regarding the role of texture features in differentiation of potentially neoplastic and benign lesions.

Belzutifan for von Hippel-Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study.

PURPOSE: Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas]. PATIENTS AND METHODS: Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor >3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily. End points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and linear growth rate (LGR) in all pancreatic lesions and pNETs per RECIST version 1.1 by independent review committee, and safety. RESULTS: All 61 enrolled patients (100%) had ≥1 pancreatic lesion and 22 (36%) had ≥1 pNET measurable at baseline. Median follow-up was 37.8 months (range, 36.1-46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs. Median DOR and median PFS were not reached in pancreatic lesions or pNETs. After starting treatment, median LGR for pNETs was -4.2 mm per year (range, -7.9 to -0.8). Eleven patients (18%) had ≥1 grade 3 treatment-related adverse event (AE). No grade 4 or 5 treatment-related AEs occurred. CONCLUSIONS: Belzutifan continued to show robust activity and manageable safety in VHL disease-associated pNETs.

Mullerian Serous Cystadenoma Occurring in the Scrotum Post-Orchidopexy: A Rarely Reported Yet Distinctive Entity.

Serous cystadenoma is a rare lesion in the para-testicular tissue, with even rarer reports of this entity occurring in the scrotum post-orchidopexy. We present such an occurrence, adding support for its existence as a distinct entity.

Moderately-differentiated Ovarian Sertoli-Leydig Cell Tumor With a Concurrent Serous Borderline Tumor in a 16-year-old Girl.

Sertoli-Leydig cell tumors (SLCT) are rare tumors of the ovary with a peak incidence in the second to third decade of life. Serous borderline tumors (SBT) are epithelial ovarian neoplasms which occur at a median age of 50 years. A co-occurrence of SLCT and SBT has not yet been reported. Here, we describe a case of a 16-year-old girl who presented with irregular menses, virilization, and an abdominopelvic mass. The mass was surgically removed and an intraoperative consultation revealed an 18.5 cm solid and cystic ovarian mass with the presence of co-existing SLCT and SBT. The diagnosis was confirmed on permanent sections after extensive sampling and immunohistochemical stains. The SLCT showed positive staining for calretinin, inhibin, CD99, and androgen receptor. MART-1 immunostain highlighted the Leydig cells. The SBT showed classic features including hierarchically branching papillae lined by stratified serous epithelium. This pediatric case is the first reported case of a Sertoli-Leydig cell tumor arising in association with a serous borderline tumor.

Microcystic Serous Cystadenoma Masquerading as Pancreatic Neuroendocrine Tumor on 99m Tc-HYNIC-TOC SPECT/CT.

ABSTRACT: We present 99m Tc-HYNIC-TOC SPECT/CT findings in a case of microcystic serous cystadenoma of the pancreatic head. The pancreatic tumor showed intense 99m Tc-HYNIC-TOC uptake mimicking neuroendocrine tumor on SPECT/CT. This case indicates that microcystic serous cystadenoma should be included in the differential diagnosis of 99m Tc-HYNIC-TOC-avid pancreatic masses.

Massive serous cyst adenoma with ovarian abscess causing fatal septicaemia.

Isolated unilateral ovarian tumour without obvious concomitant tubal pathology is unlikely to cause intrabdominal abscess or septicaemia. Benign serous cystadenoma is a fairly common ovarian tumour but rarely causes fatality. We present a patient in mid-30s with massive ovarian serous cystadenoma presenting with abscess and septicaemia, leading to mortality. To our knowledge, no previous serous cystadenoma causing abscess formation has been reported before.

Coexisting ovarian serous cystadenoma with fibroma: A very unusual combination.

Surface epithelial neoplasms are the most common ovarian tumors, constituting around 60% of all ovarian malignancies. They are classified as benign, borderline, and malignant. Ovarian cystadenomas are common benign epithelial neoplasms which carry an excellent prognosis. Ovarian thecoma-fibroma groups are uncommon sex cord-stromal neoplasms, constituting 1.0%-4.0% of all ovarian tumors. Most of them are benign and often found in postmenopausal patients. Combination tumors in the ovary are known. The most common combination is mucinous cystadenoma which occurs in association with Brenner tumor, mature cystic teratoma, Sertoli-Leydig cell tumor, or even a serous cystadenoma. A combination of surface epithelial and thecoma-fibroma group is very rarely encountered. A case of one such combination of serous cystadenoma and fibroma of the ovary is being presented here in a postmenopausal woman.

Increased Uptake in Microcystic Serous Cystadenoma Mimicking Pancreatic Neuroendocrine Tumor on 68 Ga-DOTATATE PET/MRI.

ABSTRACT: A 2.6-cm solid cystic lesion in the pancreatic head was found in a 51-year-old woman on CT. A pancreatic neuroendocrine tumor was suspected, and a 68 Ga-DOTATATE PET/MRI was performed, which showed increased tracer uptake in the lesion. However, postsurgical pathologic examination indicated a pancreatic serous cystadenoma. Here, we reported a case of microcystic pancreatic serous cystadenoma that could be misdiagnosed as a pancreatic neuroendocrine tumor on a 68 Ga-DOTATATE PET/MRI.

Radiomics Based on Contrast-Enhanced Ultrasound Images for Diagnosis of Pancreatic Serous Cystadenoma.

OBJECTIVE: The purpose of the study was to develop and validate a radiomics model by using contrast-enhanced ultrasound (CEUS) data for pre-operative differential diagnosis of pancreatic cystic neoplasms (PCNs), especially pancreatic serous cystadenoma (SCA). METHODS: Patients with pathologically confirmed PCNs who underwent CEUS examination at Chinese PLA hospital from May 2015 to August 2022 were retrospectively collected. Radiomic features were extracted from the regions of interest, which were obtained based on CEUS images. A support vector machine algorithm was used to construct a radiomics model. Moreover, based on the CEUS image features, the CEUS and the combined models were constructed using logistic regression. The performance and clinical utility of the optimal model were evaluated by area under the receiver operating characteristic curve (AUC), sensitivity, specificity and decision curve analysis. RESULTS: A total of 113 patients were randomly split into the training (n = 79) and test cohorts (n = 34). These patients were pathologically diagnosed with SCA, mucinous cystadenoma, intraductal papillary mucinous neoplasm and solid-pseudopapillary tumor. The radiomics model achieved an AUC of 0.875 and 0.862 in the training and test cohorts, respectively. The sensitivity and specificity of the radiomics model were 81.5% and 86.5% in the training cohort and 81.8% and 91.3% in the test cohort, respectively, which were higher than or comparable with that of the CEUS model and the combined model. CONCLUSION: The radiomics model based on CEUS images had a favorable differential diagnostic performance in distinguishing SCA from other PCNs, which may be beneficial for the exploration of personalized management strategies.

Fertility-sparing management of stage IIIC serous borderline ovarian tumor: A case report of a 20-year follow-up.

Multimodal treatment, including assisted reproductive technology, is necessary in young patients with advanced borderline ovarian tumors. However, the details of long-term follow-up cases have not been reported. In this report, a 19-year-old patient presented with a stage IIIC serous borderline tumor. The patient underwent five fertility-sparing surgeries. The tumor did not respond to any of the three lines of chemotherapy administered. Serological and radiological responses were observed following hormonal treatment with leuprorelin, followed by a fourth surgery. Before the planned fifth surgery for complete resection of both adnexa, cryopreservation of the fertilized eggs was performed. At age 36, when the disease-free interval exceeded the previous one, we proposed embryo transfer; however, she declined fertility treatment. The patient had developed rheumatoid arthritis and childbirth not a priority. The patient had lived without any evidence of disease for 7 years following the last surgery and 20 years after the initial visit.