Hepatic Cysts: Reappraisal of the Classification, Terminology, Differential Diagnosis, and Clinicopathologic Characteristics in 258 Cases.

The literature on liver cysts is highly conflicting, mostly owing to definitional variations. Two hundred and fifty-eight ≥1 cm cysts evaluated pathologically using updated criteria were classifiable as: I. Ductal plate malformation related (63%); that is, cystic bile duct hamartoma or not otherwise specified-type benign biliary cyst (35 with polycystic liver disease). These were female predominant (F/M=2.4), large (10 cm), often multifocal with degenerative/inflammatory changes and frequently misclassified as "hepatobiliary cystadenoma." II. Neoplastic (13%); 27 (10.5%) had ovarian-type stroma (OTS) and qualified as mucinous cystic neoplasm (MCN) per World Health Organization (WHO). These were female, solitary, mean age 52, mean size 11 cm, and 2 were associated with carcinoma (1 in situ and 1 microinvasive). There were 3 intraductal papillary neoplasms, 1 intraductal oncocytic papillary neoplasm, 1 cystic cholangiocarcinoma, and 2 cystic metastasis. III. Infectious/inflammatory (12%). These included 23 hydatid cysts (including 2 Echinococcus alveolaris both misdiagnosed preoperatively as cancer), nonspecific inflammatory cysts (abscesses, inflammatory cysts: 3.4%). IV. Congenital (7%). Mostly small (<3 cm); choledochal cyst (5%), foregut cyst (2%). V. Miscellaneous (4%). In conclusion, hepatic cysts occur predominantly in women (3/1), are mostly (90%) non-neoplastic, and seldom (<2%) malignant. Cystic bile duct hamartomas and their relative not otherwise specified-type benign biliary cysts are frequently multifocal and often misdiagnosed as "cystadenoma/carcinoma." Defined by OTS, MCNs (the true "hepatobiliary cystadenoma/carcinoma") are solitary, constitute only 10.5% of hepatic cysts, and have a significantly different profile than the impression in the literature in that essentially all are perimenopausal females, and rarely associated with carcinoma (7%). Since MCNs can only be diagnosed by demonstration of OTS through complete microscopic examination, it is advisable to avoid the term "cystadenoma/cystadenocarcinoma" solely based on radiologic examination, and the following simplified terminology would be preferable in preoperative evaluation to avoid conflicts with the final pathologic diagnosis: (1) noncomplex (favor benign), (2) complex (in 3 subsets, as favor benign, cannot rule out malignancy, or favor malignancy), (3) malignant features.

Sequential thermal ablation in combination with sclerotherapy using lauromacrogol as a successful translative therapy for an unresectable huge biliary cystadenocarcinoma: The first experience assisted by contrast-enhanced ultrasound.

Biliary cystadenocarcinoma (BCAC) is an extremely rare intrahepatic cystic tumor. Patients usually present with nonspecific symptoms such as abdominal pain, abdominal distention, and abdominal mass. This tumor occurs most commonly in the left hemiliver and is thought to mainly develop from a benign biliary cystadenoma (BCA). At present, the disease is mainly diagnosed by ultrasound, CT, MR, and other imaging methods, and the main treatment is radical surgical resection. We reported a 75-year-old female with an unresectable huge BCAC (i.e., 161×145×122 mm in three orthogonal directions) and poor general condition (40 in Karnofsky Performance Status, KPS) who received sequential thermal ablation (i.e., cryoablation and microwave ablation) in combination with sclerotherapy using lauromacrogol. The diagnosis of intrahepatic BCAC was confirmed pathologically. Preablation grayscale US showed the BCAC with a clear boundary, regular shape, and cystic-solid mixed echogenicity, which appeared as a huge multilocular cystic lesions with thick internal sepatations. Preablation contrast-enhanced ultrasound (CEUS) showed honeycomb-like hyper-enhancement of the thick internal sepatations and cystic wall in the arterial and portal phase, and sustained enhancement of the thick internal sepatations and cystic wall in the late phase. 6-month postablation CEUS showed non-enhancement in most parts of the lesion in the arterial phase and 6-month postablation MRI showed the volume reduction ratio (VRR) was about 70%. The abdominal pain and abdominal distension were relieved remarkably, and her quality of life was greatly improved (70 in KPS). In conclusion, sequential thermal ablation in combination with sclerotherapy provides a successful translative therapy for this unresectable huge BCAC with a poor general condition, which makes subsequent curative surgery or ablation possible.

Nevus Sebaceous of the Scalp With Stepwise Progression Into Invasive Syringocystadenocarcinoma Papilliferum.

Syringocystadenocarcinoma papilliferum (SCACP), the malignant counterpart of syringocystadenoma papilliferum (SCAP), is an extremely rare malignant adnexal neoplasm. It is described by the World Health Organization as a malignant transformation of SCAP occurring in middle-aged to elderly individuals with a predilection for the head and neck. SCACP seems to arise from a long-standing syringocystadenoma probably on a background of nevus sebaceous (NS) through a multistep progression. A 75-year-old man was referred to our department with a long-standing NS with a recent newly developing nodule on his scalp. The tumor was excised. On histology, the overall architecture of the tumor still resembled an unusual SCAP within NS but simultaneously showed transition to syringocystadenocarcinoma papilliferum in situ and invasive SCACP as recognizable by the presence of areas of nuclear atypia, increased proliferative activity, and infiltrative growth. In summary, we report an extremely rare case of an invasive SCACP of the scalp that demonstrates histological evidence for all transitive steps in the hypothetical multistep progression from NS to invasive SCACP in one single lesion. The implications of these findings are discussed in the light of the relevant literature.

Non-Neoplastic and Neoplastic Cysts of the Pancreas.

Inflammatory, developmental, and neoplastic lesions may all present as cystic masses on imaging. Pseudocyst is the most common of these and presents in association with a history of pancreatitis. Pancreatic cystic neoplasms are uncommon compared to solid neoplasms. They often present incidentally; therefore, an incidentally discovered cyst in the pancreas should be assessed with a high index of suspicion for neoplasm. The most common and frequently encountered cystic neoplasms include serous cystadenoma, mucinous cystic neoplasm, and intraductal papillary mucinous neoplasm. Less common epithelial cystic neoplasms include acinar cell cystadenoma and cystadenocarcinoma. Any solid neoplasm occurring in the pancreas or vicinity of the pancreas that has undergone cystic degeneration may present as a cystic mass. Non-epithelial lesions, such as lymphangioma, are also included in the differential diagnosis. The work-up needs to begin with a review of the clinical and imaging findings to establish a differential diagnosis. The primary focus of the pathologist will be first on differentiating mucinous from non-mucinous entities, since this will determine if the mass is an intraductal papillary mucinous neoplasm or a mucinous cystic neoplasm. If it is mucinous, the next step is to determine if the cystic neoplasm contains cells with high-grade cytological features. If it is non-mucinous, the pathologist needs to assess for neoplastic cells that would indicate a different neoplastic process. The cytological features need to be integrated with cyst fluid carcinoembryonic antigen and amylase measurements. Currently, molecular pathology is being integrated into the analysis of pancreatic cyst fluids. Here we will cover the cytological features and ancillary findings in cystic masses of the pancreas.

Clinicopathological study of intraductal carcinoma of the salivary gland, with emphasis on the apocrine type.

Intraductal carcinoma (IC) is a rare salivary gland tumor with low- to intermediate-grade cytological features. It is further classified into intercalated duct type and apocrine type based on its distinct histologic and immunohistochemical expression. Conventional salivary duct carcinoma (SDC) is an aggressive carcinoma with high-grade features and is usually associated with poor prognosis. In this study, immunohistochemistry and mutation analyses (including HRAS/PIK3CA mutations, RET rearrangement, and human epidermal growth factor receptor 2 [HER2] amplification) of 9 ICs (including 3 pure ICs, 6 ICs with invasive carcinoma) and 24 conventional SDCs were performed and the results were compared. Four intercalated duct-type cases were positive for SOX10 and S100 and negative for AR; five apocrine-type cases showed opposite results. All five apocrine-type cases had cysts with relatively circumscribed tumor borders and morphologically mimicking breast low-grade ductal carcinoma in situ or papillary carcinoma. RET fusion is detected in half of the 4 intercalated duct-type IC but not in the apocrine-type or conventional SDC. HER2 amplification was only observed in conventional SDC. The monoclonal antibody (clone RBT-NRAS) against NRAS Q61R is a sensitive and specific marker used for detecting HRAS Q61R mutation in the salivary gland tumors. The apocrine-type IC had different cytological grades, distinct tumor growth patterns, and no evidence of low- to high-grade transition, suggesting that apocrine-type IC should be distinguished from apocrine SDC with an in situ component.

Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm.

AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.

VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer.

Blockading programmed death ligand 1 (PD-L1) shows promising results in patients with some cancers, but not in those with ovarian cancer. V-domain Ig suppressor of T cell activation (VISTA) is a recently discovered immune checkpoint protein that suppresses T cell activation. This study aimed to investigate the expression and clinical significance of VISTA in ovarian cancer as well as its relationship with PD-L1. VISTA and PD-L1 levels in 146 ovarian cancer samples were assessed using immunohistochemistry. We investigated the association between VISTA and other clinicopathological variables, including survival. The associations between the VISTA-encoding C10orf54 gene, other immune checkpoints, and survival were analyzed. VISTA was detected in 51.4% of all samples and 46.6% of PD-L1-negative samples; it was expressed in 28.8%, 35.6%, and 4.1% of tumor cells (TCs), immune cells (ICs), and endothelial cells, respectively. Furthermore, VISTA expression was associated with pathologic type and PD-L1 expression. Moreover, VISTA expression in TCs, but not in ICs, was associated with prolonged progression-free and overall survival in patients with high-grade serous ovarian cancer. The expression of C10orf54 mRNA was associated with prolonged overall survival and immune escape-modulating genes. These results showed that VISTA expression in ovarian tumor cells was associated with a favorable prognosis in patients with high-grade serous ovarian cancer; however, additional studies are required to better understand the expression and role of VISTA in ovarian cancer.

A Prospective Study on Contrast-Enhanced Endoscopic Ultrasound for Differential Diagnosis of Pancreatic Cystic Neoplasms.

BACKGROUND AND AIMS: To determine the value of contrast-enhanced endoscopic ultrasound (CE-EUS) for differentiation of pancreatic cystic neoplasms (PCNs). METHODS: From April 2015 to December 2017, 82 patients were enrolled in this study. All patients were confirmed to have PCNs by surgical pathology. Prior to surgery, all patients underwent fundamental B-mode EUS (FB-EUS) and CE-EUS, 65 of whom underwent computed tomography (CT) and 71 of whom underwent magnetic resonance imaging (MRI). The enhanced mode data of PCNs were recorded. The diagnostic accuracy of CE-EUS in classifying PCNs was compared with that of CT, MRI and FB-EUS. The ability of CE-EUS to identify PCNs was evaluated by comparing the enhanced mode of PCNs. RESULTS: There was a significant difference between benign and malignant lesions in enhanced mode (P = 0.017). The enhanced modes of benign lesions were mostly type II and type III, while those of malignant lesions were type 0, type I, and type IV. The sensitivity, specificity, and accuracy of type 0, type I, and type IV enhanced mode as the diagnostic criterion for malignant lesions were 80%, 65.3%, and 67.1%, respectively. CE-EUS demonstrated greater accuracy in identifying PCNs than did CT, MRI, and FB-EUS (CE-EUS vs. CT: 92.3% vs. 76.9%; CE-EUS vs. MRI: 93.0% vs. 78.9%; CE-EUS vs. FB-EUS: 92.7% vs. 84.2%). CONCLUSION: Compared with CT, MRI, and FB-EUS, CE-EUS is better at differentiating PCNs. CE-EUS is expected to be another important imaging technique for the diagnosis of PCNs.

miR-340-FHL2 axis inhibits cell growth and metastasis in ovarian cancer.

Although increasing evidence indicated that deregulation of microRNAs (miRNAs) contributed to tumor initiation and progression, but little is known about the biological role of miR-340 in ovarian cancer (OC). In this study, we found that miR-340 expression was downregulated in OC tissues compared with its expression in normal ovarian epithelium and endometrium, and treatment with 5-aza-2'-deoxycytidine (5-Aza-dC) or trichostatin A (TSA) increased miR-340 expression in OC cells. In addition, ectopic miR-340 expression inhibited OC cell growth and metastasis in vitro and in vivo. Four and a half LIM domains protein 2 (FHL2) was confirmed as a direct target of miR-340 and silencing FHL2 mimicked the effects of miR-340 in OC cells. Further mechanistic study showed that miR-340 inhibited the Wnt/ß-catenin pathway by targeting FHL2, as well as downstream cell cycle and epithelial-to-mesenchymal transition (EMT) signals in OC cells. Moreover, the greatest association between miR-340 and FHL2 was found in 481 ovarian serous cystadenocarcinoma tissues via pan-cancer analysis. Finally, we revealed that lower miR-340 or higher FHL2 was associated with poor OC patient outcomes. Our findings indicate that the miR-340-FHL2 axis regulates Wnt/ß-catenin signaling and is involved in tumorigenesis in OC. Therefore, manipulating the expression of miR-340 or its target genes is a potential strategy in OC therapy.

Laparoscopic Left Lateral Sectionectomy Using the Extrahepatic Glissonean Approach: A Secure Option for Achieving a Negative Margin for Lesions with Ductal Extension.

INTRODUCTION: In patients with liver lesions with ductal extension, the corresponding Glissonean pedicle should be divided at its origin to achieve a negative ductal margin; however, during laparoscopic hepatectomy, it is difficult to precisely transect the liver and divide the Glissonean pedicle as planned. METHODS: We present a video of a laparoscopic left lateral sectionectomy using the extrahepatic Glissonean approach for a lesion with ductal extension. RESULTS: A 76-year-old woman presented with a cystic neoplasm in the liver segment 3 bile duct (B3). The preoperative workup suggested biliary extension of the lesion towards the origin of B3. A decision was made to perform laparoscopic left lateral sectionectomy with division of the segment 3 Glissonean pedicle (G3) at its origin, and, additionally, left hepatectomy if the B3 ductal margin turned out to be positive. During the procedure, prior to parenchymal transection, the Arantius' ligament was dissected, and G2 and G3 were extrahepatically taped. The ischemic border was visualized by clamping the isolated pedicle, and was also clearly demonstrated by indocyanine green fluorescence. After transecting the liver towards the tape, G3 was divided at its origin, and the frozen section of the ductal margin was negative for tumors. CONCLUSION: The extrahepatic Glissonean approach can help to obtain a maximal ductal margin for liver lesions with possible biliary extension, although the technique potentially poses the risk of bleeding and/or biliary injury, and requires expertise in hepatobiliary surgery. Further studies with larger sample sizes are warranted to validate the feasibility and efficacy of this strategy.

Survival outcomes of adjuvant radiotherapy and chemotherapy in women with stage I serous papillary and clear cell carcinoma of the endometrium: a Korean multicenter study.

OBJECTIVE: To compare the survival outcomes of adjuvant radiotherapy and chemotherapy in women with uterine-confined endometrial cancer with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CCC). METHODS: Medical records of 80 women who underwent surgical staging for endometrial cancer were retrospectively reviewed. Stage I UPSC and CCC were pathologically confirmed after surgery. Survival outcomes were compared between the adjuvant radiotherapy and chemotherapy groups. RESULTS: Fifty-four (67.5%) and 26 (32.5%) women had UPSC and CCC, respectively. Adjuvant therapy was administered to 59/80 (73.8%) women (25 radiotherapy and 34 chemotherapy). High preoperative serum cancer antigen-125 level (25.1±20.2 vs. 11.5±6.5 IU/mL, p<0.001), open surgery (71.2% vs. 28.6%, p=0.001), myometrial invasion (MI) ≥1/2 (33.9% vs. 0, p=0.002), and lymphovascular space invasion (LVSI; 28.8% vs. 4.8%, p=0.023) were frequent in women who received adjuvant therapy compared to those who did not. However, the histologic type, MI ≥1/2, and LVSI did not differ between women who received adjuvant radiotherapy and those who received chemotherapy. The 5-year progression-free survival (78.9% vs. 80.1%, p>0.999) and overall survival (77.5% vs. 87.8%, p=0.373) rates were similar between the groups. Neither radiotherapy (hazard ratio [HR]=1.810; 95% confidence interval [CI]=0.297-11.027; p=0.520) nor chemotherapy (HR=1.638; 95% CI=0.288-9.321; p=0.578) after surgery was independently associated with disease recurrence. CONCLUSION: Our findings showed similar survival outcomes for adjuvant radiotherapy and chemotherapy in stage I UPSC and CCC of the endometrium. Further large study with analysis stratified by MI or LVSI is required.

Clinicopathological analysis of borderline ovarian tumours and risk factors related to recurrence: experience of single institution.

This study was conducted to determine the demographic and clinicopathologic characteristics and evaluate the prognostic value of various factors, such as the extensiveness of surgery, related to the tumour itself and the clinical features in the recurrence of borderline ovarian tumours (BOT). We retrospectively evaluated the data of 103 patients with a borderline ovarian tumours treated at our institution between the years 2000 and 2012. The median age was 37 (16-79) years and the majority of the patients were premenopausal (76.7%). During the follow-up, 16 recurrences were observed (15.5%). The multivariate analysis showed that the micropapillary architecture and fertility sparing surgery were the only significant independent predictors for the development of a recurrence amongst all of the demographic and clinicopathological features. In our study group, we identified that the micropapillary architecture itself and the fertility sparing surgery had a significant impact on the development of a BOT recurrence. The patients who possess these features should be followed up more closely for a long time period. Impact statement What is already known on this subject? A borderline ovarian tumour is known as a recurrent disease. The recurrence rate varies between 5 and 20%. It is well known in the literature that patients treated by an oophorectomy have a relatively lower risk of development of a recurrence compared to the patients treated by cystectomy. What do the results of this study add? Although some of the clinicopathological features are shown to be risk factors for the development of a recurrence in many studies, some of the pathological-clinical and the demographic features have not been described as yet, or have been considered to be equivocal regarding the development of a recurrence. In this study, we investigate all possible demographic, pathological, and clinical factors associated with a recurrence. Not only the well-known pathological characteristics but also the new pathological parameters and clinical approaches have been investigated. For instance, microinvasion architecture and lymphadenectomy speculated in the literature as the risk factors for the development of a recurrence, have not been identified as risk factors in our study. On the other hand, our statistical analyses have revealed that micropapillary architecture should be described as a risk factor for the development of a recurrence. What are the implications of these findings for clinical practice and/or further research? We hope our study becomes influential in the literature on the field of a micropapillary architecture and the development of a recurrence. The patients carrying this feature have to be followed up very closely and carefully. Furthermore, our findings have indicated no significant relation between the performing of a lymphadenectomy and the rate of a recurrence. This result might be encouraging for the gynaecological surgeons to refrain from a lymphadenectomy for the borderline ovarian tumours.

Sudden, Unexpected Death Due to Pseudo-Meigs Syndrome: A Case Report and Review of the Literature.

Meigs syndrome is the triad of ascites, hydrothorax, and benign ovarian tumor (mostly fibroids). It is a diagnosis of exclusion, and the characteristic symptoms disappear after resection of the tumor. Instead, in Pseudo-Meigs syndrome, the triad includes a nonfibroma ovarian tumor. The latter may consist of benign tumors (ie, of fallopian tube or uterus, struma ovarii, and ovarian leiomyomas) but can also comprise ovarian or metastatic gastrointestinal malignancies.The authors describe a case of sudden death in a 43-year-old woman, with no noteworthy reported history of present illness or medical history and in apparently good health before death.The autopsy showed a picture of bilateral hydrothorax with lung collapse, ascites, and a large left-sided ovarian mass, approximately 15 cm in diameter. Histopathological examinations revealed an ovarian epithelial malignancy (cystadenocarcinoma). There was also lung atelectasis with accompanying thrombosis of small and medium blood vessels. The combination of autopsy and histological findings allowed us to establish the diagnosis of Pseudo-Meigs syndrome, undiagnosed antemortem, resulting in death due to pulmonary and thrombotic complications. Our subsequent review of the literature found no case reports of undiagnosed Pseudo-Meigs syndrome presenting as sudden death, highlighting the uniqueness of the case presented herein.

Intramural florid cystic endosalpingiosis of the uterus after menopause.

Endosalpingiosis is a benign condition characterized by the presence of tubal epithelium outside the fallopian tube and the absence of endometrial stroma. Florid cystic endosalpingiosis is a very rare form of endosalpingiosis that presents as a tumor-like lesion. We report the case of a 67-year-old woman who presented with a cystic lesion of the uterus. Macroscopically, a cut section revealed a multicystic, whitish mass in the myometrium of the fundus. Histologically, the lesion consisted of numerous variably sized glands that were lined with a single or stratified layer of ciliated columnar cells similar to tubal epithelium.