Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. @*Materials and Methods@#Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. @*Results@#Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. @*Conclusion@#Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

Rapid progression of sarcomatoid carcinoma of the common bile duct

Since sarcomatoid carcinoma in the common bile duct (CBD) is rarely reported, the clinical course and prognosis after surgery are unclear. We report a case of a patient who died within 1 month after surgery due to rapid tumor progression. A 65-year-old woman had abdominal pain with jaundice. She was diagnosed with CBD cancer and underwent pancreatoduodenectomy. Pathologic examination revealed sarcomatoid carcinoma. There was no postoperative complication, but multiple liver metastasis was diagnosed on computed tomography at 7 days after surgery. Also, the patient complained of abdominal pain and had jaundice with elevated liver enzyme on the 14th postoperative day. Her general condition was getting worse and she died of hepatic failure 23 days after surgery. We report a case of sarcomatoid carcinoma of the CBD that progressed very rapidly. Further research and case reports are needed to establish proper diagnostic and treatment tools.

Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients. METHODS: To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival. RESULTS: PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses. CONCLUSIONS: Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

Development of Cholangiocarcinoma Arising from Remnant Intrapancreatic Cyst 15 Years after Choledochal Cyst Excision / 대한췌담도학회지

Among complications of choledochal cysts, malignant transformation is most concerning and management of choledochal cyst now includes complete cyst excision, whenever possible. In cases of choledochal cyst associated with pancreaticobiliary maljunction like our case, cholecystectomy along with the resection of dilatated bile duct and the biliary diversion are generally performed. However, incomplete cyst excision can result in malignant transformation within the remnant cyst. We present the case of cholangiocarcinoma arising from remnant intrapancreatic cyst 15 years after choledochal cyst excision in a patient with Todani type 1 choledochal cyst associated with pancreaticobiliary maljunction. We learn from the case that a careful long-term follow-up is needed in patients with choledochal cysts if residual cyst is remained after excision.

Symptomatic Choledochal Cyst in Association with Pregnancy Managed with EUS-guided Choledochoduodenostomy without Fluoroscopic Guidance / 대한췌담도학회지

Choledochal cyst has only rarely been encountered in association with pregnancy. The clinical manifestations are nonspecific and variable that makes it difficult to differentiate from physiologic changes in pregnancy. Consequently, diagnosis is often delayed until patients present with life-threatening complications. During pregnancy, symptoms of choledochal cyst may be developed by hormonal changes and the enlarged uterus. Because of the risk of fetal mortality and maternal morbidity, definitive surgical treatment should be delayed and step-by-step management should be carefully implemented to avoid complication until delivery. Herein, we report a case of enlarged, symptomatic choledochal cyst that developed in a 26-year-old pregnant woman. The temporal relationship between pregnancy and symptom development, as well as the biliary sludge formation in the enlarged cyst, suggest that the choledochal cyst was influenced by pregnancy. In order to buy time for fetal maturation, endoscopic ultrasonography-guided choledochoduodenostomy was performed for biliary decompression as a bridge to surgical excision.

Mammary-Type Myofibroblastoma: A Report of Two Cases

Mammary-type myofibroblastoma (MFB) is a rare, benign spindle cell neoplasm occurring along the milkline, with extension from the mid-axilla to the medial groin. It is histologically and immunohistochemically identical to MFB of the breast and is part of a spectrum of lesions that includes spindle cell lipoma and cellular angiofibroma. Recently, we experienced two cases of mammary-type MFB involving male patients aged 30 and 58 years, respectively. The tumors were located in the right scrotal sac and in the right axilla. Wide excisions were performed. Microscopically, the masses were composed of haphazardly arranged, variably sized fascicles of bland spindle cells and were admixed with mature fat tissue. The spindle cells in both cases showed immunopositivity for desmin and CD34 and negativity for smooth muscle actin. Loss of retinoblastoma (RB)/13q14 loci is a characteristic genetic alteration of mammary-type MFB, and we identified loss of RB protein expression by immunohistochemical staining. We emphasize the importance of awareness of this rare neoplasm when a spindle cell neoplasm is accompanied by desmin immunopositivity. The second patient was alive without recurrence for 20 months, and the first patient had not been followed.

Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. METHODS: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. RESULTS: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. CONCLUSIONS: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.

Primary Bronchial Granular Cell Tumor in an Adult Male

We report a rare case of granular cell tumor arising in the left lower lobe (LLL) bronchus with secondary obstructive change in a 60-year-old male. The patient was found to have a nodule in the LLL on a computed tomography scan, three months prior to his presentation to the Asan Medical Center. Bronchoscopic biopsies revealed a granular cell tumor. After undergoing LLL lobectomy with bronchoplasty, the patient has not experienced any tumor recurrence.

Extrauterine Epithelioid Trophoblastic Tumor of Lung in a 35-year-old Woman

Extrauterine epithelioid trophoblastic tumors constitute an extremely rare gestational trophoblastic disease. We report the case of an extrauterine trophoblastic tumor that was incidentally detected in the left lung. Squamous cell carcinoma was suspected after microscopically examining the specimen obtained upon preoperative needle biopsy. After surgery, the tumor was confirmed by microscopic findings and immunohistochemical features.

Beef-Induced Anaphylaxis Confirmed by the Basophil Activation Test

Beef allergies are relatively rare, especially in adults. However, clinical manifestations can vary from urticaria, angioedema, anaphylaxis to gastrointestinal symptoms. Currently available tests, such as skin testing or in vitro determination of beef-specific immunoglobulin E (IgE), do not provide an accurate diagnosis of beef allergy. The recent development of the basophil activation test (BAT) presents a new opportunity for the diagnosis of food allergies. Here, we report a 37-year-old woman with a history of recurrent generalised urticaria, nausea, vomiting and hypotension after ingestion of beef, suggesting a beef allergy. Although the skin prick test and serum specific IgE to beef, pork and milk allergens showed negative results using commercial kits, the BAT showed significant upregulation of CD203c in a dose-dependent manner compared to both non-atopic and atopic controls. To our knowledge, this is the first case study of beef allergy consisting of a non-IgE-mediated reaction. The detection of food allergies using direct basophil activation is suggested to complement conventional diagnostic tests.

A Case of Occupational Rhinitis Caused by Rice Powder in the Grain Industry

Rice is the major staple food in a large part of the world, especially in Asia. Hypersensitivity reactions to rice are rare. Moreover, cases of occupational allergies induced by inhalation of rice powder are uncommon. We report a 31-year-old male with work-related rhinitis and conjunctivitis symptoms caused by occupational exposure to rice powder in the grain industry. He showed positive responses to rice extracts on a skin prick test, and a high level of serum specific IgE to rice was detected by ELISA. Occupational rhinitis was confirmed by a nasal provocation test with rice extracts. An IgE ELISA inhibition test showed cross-creativity between rice and various grass pollen extracts. These findings suggest that the inhalation of rice powder can induce IgE-mediated occupational rhino-conjunctivitis, which may be derived from cross-reactivity to major grass pollens.

A Case of Occupational Rhinitis Caused by Rice Powder in the Grain Industry

Rice is the major staple food in a large part of the world, especially in Asia. Hypersensitivity reactions to rice are rare. Moreover, cases of occupational allergies induced by inhalation of rice powder are uncommon. We report a 31-year-old male with work-related rhinitis and conjunctivitis symptoms caused by occupational exposure to rice powder in the grain industry. He showed positive responses to rice extracts on a skin prick test, and a high level of serum specific IgE to rice was detected by ELISA. Occupational rhinitis was confirmed by a nasal provocation test with rice extracts. An IgE ELISA inhibition test showed cross-creativity between rice and various grass pollen extracts. These findings suggest that the inhalation of rice powder can induce IgE-mediated occupational rhino-conjunctivitis, which may be derived from cross-reactivity to major grass pollens.