Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version).

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC.

BACKGROUND AND AIMS: Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present. METHODS: 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG. RESULTS: The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS. CONCLUSIONS: SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.

Liver Stiffness and Serum Alpha-Fetoprotein in Discriminating Small Hepatocellular Carcinoma from Cirrhotic Nodule.

AIM: This study aimed to investigate the clinical significance of liver stiffness and serum alpha-fetoprotein (AFP) in differentiating small hepatocellular carcinoma (HCC) from cirrhotic nodule. METHODS: A total of 95 chronic hepatitis B patients who were diagnosed with small HCC (n = 53) or cirrhotic nodule (n = 42) underwent ultrasound elastography point quantification (ElastPQ) examinations on lesion and background liver. Three stiffness parameters, lesion stiffness value (SV), absolute stiffness difference (ASD) of lesion and background liver, stiffness ratio (lesion/background liver) (SR), and serum AFP were retrospectively analyzed. Then, the capabilities of lesion SV, ASD, SR, AFP, and the combination of each individual stiffness parameter with AFP were evaluated in differentiating small HCC from cirrhotic nodule. RESULTS: Significantly higher lesion SV, ASD, SR, and serum AFP were observed in small HCC compared with cirrhotic nodule patients (all P ≤ 0.0001). By comparing the stiffness parameters on the patients with AFP greater than 20 ng/mL and AFP of 20 ng/mL or smaller, a higher lesion SV and comparable ASD and SR were found in the small HCC patients. The diagnostic accuracy of lesion SV, ASD, SR, and AFP in the discrimination of small HCC and cirrhotic nodule was 0.731, 0.825, 0.820, and 0.789, respectively. Moreover, the improved sensitivity was observed in the combination of liver stiffness with AFP (83%, 100%, and 92% for lesion SV/AFP, ASD/AFP, and SR/AFP, respectively). CONCLUSIONS: This study illustrated that the combination of liver stiffness and serum AFP has considerable clinical value in detecting suspicious small HCC from cirrhotic nodule.

Contrast-enhanced ultrasonographic findings of hepatic paragonimiasis.

AIM: To investigate the features of hepatic paragonimiasis on contrast-enhanced ultrasound (CEUS) imaging. METHODS: Fifteen patients with hepatic paragonimiasis who were admitted to our hospital between March 2008 and August 2012 were enrolled to this study. The conventional ultrasound and CEUS examinations were performed with a Philips IU22 scanner with a 1-5-MHz convex transducer. After conventional ultrasound scanning was completed, the CEUS study was performed. Pulse inversion harmonic imaging was used for CEUS. A bolus injection of 2.4 mL of a sulfur hexafluoride-filled microbubble contrast agent (SonoVue) was administered. CEUS features were retrospectively reviewed and correlated with pathological findings. RESULTS: In total, 16 lesions were detected on CEUS. The mean size of the lesions was 4.4 ± 1.6 cm (range, 1.7-6.6 cm). Subcapsular location was found in 12 lesions (75%). All the lesions were hypoechoic. Six lesions (37.5%) were of mixed content, seven (43.8%) were solid with small cystic areas, and the other three (18.8%) were completely solid. Ten lesions (62.5%) were rim enhanced with irregular tract-like nonenhanced internal areas. Transient wedge-shaped hyperenhancement of the surrounding liver parenchyma was seen in seven lesions (43.8%). Areas with hyper- or iso-enhancement in the arterial phase showed contrast wash-out and appeared hypoenhanced in the late phase. The main pathological findings included: (1) coagulative or liquefactive necrosis within the lesion, infiltration of a large number of eosinophils with the formation of chronic eosinophilic abscesses and sporadic distribution of Charcot-Leyden crystals; and (2) hyperplasia of granulomatous and fibrous tissue around the lesion. CONCLUSION: Subcapsular location, hypoechogenicity, rim enhancement and tract-like nonenhanced areas could be seen as the main CEUS features of hepatic paragonimiasis.

Hepatosplenic T-cell lymphoma: clinicopathologic, immunophenotypic, and molecular characterization of 17 Chinese cases.

Hepatosplenic T-cell lymphoma is a highly aggressive tumor with a poor outcome. About 210 cases were identified through PubMed, of which fewer than 20 originated in Asia. We reviewed 17 Chinese cases of hepatosplenic T-cell lymphoma, including an unusual one with cutaneous pink papules, for clinicopathologic, immunophenotypic, and genotypic features; Epstein-Barr virus status; treatment; and outcome. The median age of the patients was 23 years. All patients had splenomegaly, and 88.2% of them had hepatomegaly as well. Bone marrow involvement was present in 53.3%. Eleven patients underwent splenectomy for diagnosis and treatment. Twelve specimens were collected by image-guided liver core biopsy or wedge resection. Histologically, the homogeneous small- to medium-size neoplastic lymphoid cells infiltrated the sinuses or sinusoids of the spleen, bone marrow, and liver. Diagnosis was based on image-guided core-needle biopsy of the liver alone in 41.2% of the cases. Immunohistochemically, 15 of the lesions were hepatosplenic γδ T-cell lymphoma, and the remaining 2 were hepatosplenic αß T-cell lymphoma. Epstein-Barr virus was detected in both cases of hepatosplenic αß T-cell lymphoma and one case of hepatosplenic γδ T-cell lymphoma. Most of the patients received cyclophosphamide, doxorubicin, vincristine, and prednisone therapy or regimens similar to it. Follow-up data were available in 70.6% of the patients; half of them died of the tumor, and the median survival time was 6 months. The frequency of bone marrow involvement was lower than that reported in the literature. Image-guided core-needle biopsy of the liver is recommended for diagnosis.

Tetrodotoxin alleviates acute heroin withdrawal syndrome: a multicentre, randomized, double-blind, placebo-controlled study.

1. Tetrodotoxin (TTX) is a powerful sodium channel blocker extracted from the puffer fish. The efficacy and safety of TTX as monotherapy for the treatment of acute heroin withdrawal syndrome were evaluated in the present study. This 7-day, multicentre, randomized, double-blind, placebo-controlled study was carried out between December 2008 and October 2009. In total, 216 patients who met the Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of heroin addiction were recruited. After providing written informed consent, subjects were randomly assigned to double-blind treatment in one of the following groups: 5 µg TTX group (group 1), 10 µg TTX group (group 2) or the placebo group (group 3). 2. Evidence suggests that both 5 and 10 µg TTX significantly reduced withdrawal symptoms by day 3 compared with placebo, and there was no significant difference in the incidence of adverse events in the three groups. 3. In conclusion, this clinical trial shows that TTX (5 and 10 µg given t.i.d.) is effective in alleviating opiate withdrawal symptoms with few side-effects.

[Detection of TCR-gamma chain gene rearrangement in malignant histiocytosis].

OBJECTIVE: To investigate the lineage of the malignant cells in malignant histiocytosis. METHODS: Polymerase chain reaction with two groups of common primers for TCR-gamma gene was used to analyze the malignant cells of 28 autopsied cases of malignant histiocytosis. RESULTS: Monoclonal TCR-gamma gene rearrangements were detected in 12 out of the 28 samples (43%). CONCLUSION: Most cases diagnosed as malignant histiocytosis in Southwest China seems to be peripheral T-cell lymphomas.

[Analysis of clinicopathologic features and morphogenesis of carcinoid tumorlets in the lung with bronchiectasis].

OBJECTIVE: To describe the clinicopathologic features and immunophenotypes of carcinoid tumorlets in the lung with bronchiectasis, and to study the morphogenesis of these tiny tumors. METHODS: The histopathologic characteristics of 3 bronchiectasis cases with carcinoid tumorlets, 11 bronchiectasis and 2 normal lungs were studied. Specific markers of the tiny tumors and the number of neuroendocrine cells (NECs) in the airway mucosa were immunohistochemically detected by EnVision method. RESULTS: The tumorlets in the lungs presented as multi-focal nodules and most were displayed only under microscopy. These cells were arranged in clusters and foci of fascicles which were situated in the surrounding bronchial wall and bronchioles adjacent to bronchiectatic lesion, or in the scar tissues. The tiny tumors were consisted of short fusiform cells and small ovoid cells. Their nuclei were circular, oval or long fusiform and the cells were strongly argyrophilic on Grimelius staining. Intensive positive immunostaining for calcitonin, chromogranin A, NSE and gastrin were detected. Weak positive for CK, EMA, S-100 and focal positive for HC, ACTH, 5-HT were also observed. Proliferative NECs in airway mucosa adjacent to the tiny tumors increased significantly in number, compared with those in the airway mucosa of bronchiectasis without tumorlets and normal lungs (P < 0.001, respectively). CONCLUSIONS: The clinicopathologic features and immunophenotypes of carcinoid tumorlets resemble carcinoid tumors. They are the early stage of carcinoid development. Their development may be related to the chronic pulmonary damage resulting in hypoxia and stimulating the proliferation of NECs. These pulmonary carcinoid tumorlets can be used as a model to study the tumorigenesis of carcinoid carcinoma of the lung.