OBJECTIVE: The existing prediction models for metastasis in pheochromocytomas/paragangliomas (PPGLs) showed high heterogeneity in different centers. Therefore, this study aimed to establish new prediction models integrating multiple variables based on different algorithms.
METHODS: Data of patients with PPGLs undergoing surgical resection at the Peking Union Medical College Hospital from 2007 to 2022 were collected retrospectively. Patients were randomly divided into the training and testing sets in a ratio of 7:3. Subsequently, decision trees, random forest, and logistic models were constructed for metastasis prediction with the training set and Cox models for metastasis-free survival (MFS) prediction with the total population. Additionally, Ki-67 index and tumor size were transformed into categorical variables for adjusting models. The testing set was used to assess the discrimination and calibration of models and the optimal models were visualized as nomograms. Clinical characteristics and MFS were compared between patients with and without risk factors.
RESULTS: A total of 198 patients with 59 cases of metastasis were included and classified into the training set (n = 138) and testing set (n = 60). Among all models, the logistic regression model showed the best discrimination for metastasis prediction with an AUC of 0.891 (95% CI, 0.793-0.990), integrating SDHB germline mutations [OR: 96.72 (95% CI, 16.61-940.79)], S-100 (-) [OR: 11.22 (95% CI, 3.04-58.51)], ATRX (-) [OR: 8.42 (95% CI, 2.73-29.24)] and Ki-67 ≥ 3% [OR: 7.98 (95% CI, 2.27-32.24)] evaluated through immunohistochemistry (IHC), and tumor size ≥ 5 cm [OR: 4.59 (95% CI, 1.34-19.13)]. The multivariate Cox model including the above risk factors also showed a high C-index of 0.860 (95% CI, 0.810-0.911) in predicting MFS after surgery. Furthermore, patients with the above risk factors showed a significantly poorer MFS (P ≤ 0.001).
CONCLUSIONS: Models established in this study provided alternative and reliable tools for clinicians to predict PPGLs patients\' metastasis and MFS. More importantly, this study revealed for the first time that IHC of ATRX could act as an independent predictor of metastasis in PPGLs.

OBJECTIVE: To evaluate the prognostic value of S-100 protein and Ki-67 labeling index in olfactory neuroblastomas.
METHODS: A retrospective study was conducted on a cohort of 85 patients with olfactory neuroblastomas. The immunohistochemical expression of S-100 and Ki-67 was assessed, and the predictive value of S-100 and Ki-67 was further evaluated. The optimal cutoff value of Ki-67 labeling index was determined using time-dependent receiver operating characteristic curve analysis. Overall survival and progression-free survival were assessed using the Kaplan-Meier method.
RESULTS: A cut-off Ki-67 labeling index value of 67.5% was determined for prognosis in patients with olfactory neuroblastomas. There was a significant correlation between Ki-67 expression and cervical lymph node metastasis (P = 0.049). Compared with S-100 (+), S-100 (-) was associated with a higher rate of lymph node metastasis and a higher level of Ki-67 (P = 0.007, < 0.001, respectively), as well as an advanced Kadish stage (P = 0.037). Survival analyses showed that patients with S-100 (+) had better 5-year overall survival than those with S-100 (-) (P = 0.028), and patients with both S-100 (+) and Ki-67 (<67.5%) had superior 5-year overall survival compared with all the other patients (P = 0.0225).
CONCLUSIONS: Our findings suggest that S-100 combined with Ki-67 labeling index are reliable prognostic factors in patients with olfactory neuroblastomas.

This study aimed to evaluate immunohistochemical markers of pheochromocytoma/paraganglioma (PPGL) and the relationships between the grading system for adrenal pheochromocytoma and paraganglioma (GAPP) and the prognosis of PPGL in a Chinese population. A retrospective analysis was conducted on a cohort of 102 PPGL cases, from January 2012 to December 2019, with complete clinicopathological and follow-up data. Surgical pathology slides were re-reviewed. All histological parameters involved in GAPP were summarized. The relationship between clinical characteristics, expression of SDHB (succinate dehydrogenase), S-100 and Ki-67 as well as GAPP classifications and prognosis of PPGL was statistically analyzed. The 102 cases included 51 males (50%) and 51 females (50%) with a median age of 48.7 years. The median tumor size was 6.8 cm. Metastases or relapse developed in 23 (22.5%) cases. Larger tumor size, extra-adrenal location, and poorly differentiated PPGL according to GAPP were associated with metastases or relapse (P < 0.05). Histological parameters, including the appearance of large or fused cell nests, necrosis, vascular invasion, and capsular invasion, were more common in the cases with metastases or relapse (P < 0.01). Loss of SDHB or S-100 expression was more common in poorly differentiated PPGL and associated with metastases or relapse (P < 0.01). However, no significant difference in the Ki-67 index between the clinically malignant and benign group was observed. GAPP is thus helpful for evaluations of the biological behavior of PPGL.

BACKGROUND: Primary malignant melanoma of the esophagus (PMME) is rare with high malignancy and poor prognosis. The aim of this study was to investigate the relationship between prognosis and clinicopathological characteristics of this disease.
METHODS: A total of 9 patients with PMME were treated in Zhejiang Cancer Hospital between 2009 and 2019 retrospectively. According to 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction, none of the patients were in stage I. However, 5 patients were in stage II, 2 patients were in stage III, and 2 patients were in stage IV at diagnosis. Five patients received surgery, while one of them received palliative resection. Three patients received postoperative chemotherapy; two of them (2/5) were diagnosed with recurrence. One patient in stage II received targeted therapy. One patient in stage III received first line chemotherapy and efficacy evaluation was stable disease (SD). Another one in stage III received biotherapy. One patient in stage IV received Chinese Medicine treatment and another received chemotherapy and palliative surgery.
RESULTS: The 1-year disease-free survival (DFS) and overall survival (OS) rates of stage II who received surgery were 50% (2/4) and 100% (4/4) respectively. The 2-year DFS and OS rates were 50% (2/4) and 75% (3/4), respectively. However, patients with stage III-IV have a very poor prognosis. The 1-year OS is 0%.
CONCLUSIONS: Due to the small sample size, the statistic efficacy is low, but it can provide a certain theoretical basis for future research.

Gastrointestinal schwannoma is a rare, slow-growing and benign tumor that mostly originates in the Auerbach myenteric nerve plexus in the gastrointestinal tract. The clinical manifestations may be associated with the location, size, differentiation type, and degree of malignancy of the tumor. Endoscopy, ultrasound and imaging examinations serve an important auxiliary role in the clinical identification, diagnosis and differential diagnosis of lesions; assessment of risk; and preparation for surgery. S-100 positivity is a hallmark of schwannoma. CD34, CD117, discovered on GIST-1, P53, ALK, β-catenin, smooth muscle actin and Desmin negativity are helpful for the identification of other gastrointestinal stromal tumors. Surgical removal of the tumor is the main treatment for schwannoma. Benign gastrointestinal schwannoma has a good prognosis without recurrence and metastasis; malignant transformation is extremely rare and has a poor prognosis.

OBJECTIVE: Esophageal schwannoma (ES) are rare and mostly benign neurogenic tumors. The clinical misdiagnosis rate of it is high. In this study, the clinicopathologic features of ES in mainland China were studied to better understand the disease and improve the diagnosis and treatment rate.
METHODS: A systematic review was conducted in accordance with PRISMA guidelines. The keywords \"esophageal schwannoma\", \"esophageal neurinoma\" and \"esophageal neurilemoma\" were searched for databases such as Pubmed, EMbase, Wanfang Database and Chinese National Knowledge Infrastructure. The search time frame for database was until July 2019. Combined with our patient, the clinicopathological data and the diagnosis and treatment of ES were summarized.
RESULTS: ES occurs in the upper part of the mediastinum and in the thoracic esophagus in most patients in the neck, upper and middle segments. CT and PET/CT examinations can be used for diagnosis, but the differentiation value of both benign and malignant ES is similar. The histopathological findings of forceps biopsy specimens are often difficult to diagnose, and deep tissue biopsies may increase pathological accuracy. EUS-FNA is also recommended for ES diagnosis, but it may also be misdiagnosed. Pathological features include a fusiform arrangement in a palisade-like structure or a tumor cell arranged in a network to form a loose structure. ES characteristic immunohistochemistry results showed that S-100 protein has strong immunological activity.
CONCLUSIONS: The definitive diagnosis requires immunohistochemistry, especially immunological reaction with S-100 protein. The appropriate treatment plan should be selected according to the diameter of the lesion. The overall prognosis of ES is good, but attention should be paid to follow-up.

OBJECTIVE: In view of the existence of multifarious pathologic subtypes of spindle cell lipoma (SCL), which is easily misdiagnosed as other benign and malignant soft tissue tumors, we performed this study and aimed to better define the category of SCL.
METHODS: We collected and analyzed 40 cases of SCL with complete clinical and pathologic information from January 2010 to December 2018. Clinical and histopathologic analyses of SCL were performed, as well as immunohistochemical staining and fluorescence in situ hybridization (FISH) using probes for RB1 and MDM2, and the related literature was reviewed.
RESULTS: In 40 cases, the male to female ratio was 3.4:1, and the mean age was 54 years old. SCL of our study included six pathologic subtypes: classic (25/40), fibrous (4/40), myxoid (4/40), low-fat (3/40), pseudoangiomatous (2/40), and fat-rich (2/40) changes. Microscopically, SCL showed distinctive morphology, with uniform spindle cells and a variably adipocytic component. The spindle cells were bland in morphology, without prominent atypia or pleomorphism, set in a myxoid or fibrous matrix. Immunohistochemically, CD34 and vimentin were positive in spindle cells, and spindle cells of 6 cases also expressed S-100 protein. FISH analysis of 10 cases revealed that heterozygous deletion of RB1 was in six samples with chromosome 13 aberrations and MDM2 gene amplification was not detected in any cases. Surgical resection is considered as the primary treatment for SCL, as there was no any recurrence or metastasis in our cases after 2-105 months of follow-up.
CONCLUSIONS: SCL is a rare benign lipoma, and the proportion of spindle cells and adipocytic component varies, which may form various pathologic changes. The diagnosis needs to be combined with clinicopathologic features, immunophenotypes, and genetics. It has to be differentiated from mammary-type myofibroblastoma, cellular angiolipoma, solitary fibrous tumor, and myxoid liposarcoma.

BACKGROUND: Congenital Self-Healing Langerhans Cell Histiocytosis (CSHLCH) is rare, characterized by cutaneous lesions at birth or in the neonatal period, and absence of systemic lesions.
METHODS: Skin biopsy was performed and the histologic examination of the skin section, routinely stained with hematoxylin-eosin. Paraffin sections were stained by immunohistochemical study which were carried out according to the manufacturer\'s protocols.
RESULTS: Seven cases of CSHLCH were recruited. 28.6% (2/7) of the cutaneous lesions were multiple, 71.4% (5/7) were solitary. Skin biopsy was performed and the histologic examination of the skin section, routinely stained with hematoxylin-eosin. Microscopically, in the dermis, a dense infiltrate of histiocytic cells mixed with numerous eosinophils. These histiocytes were immunohistochemically positive for CD1a and S-100. All of the cutaneous lesions regress spontaneously, and lack of systemic involvement, the final diagnosis of Congenital Self-Healing Langerhans Cell Histiocytosis were made. No recurrence had been observed.
CONCLUSIONS: The cutaneous lesions of CSHLCH may regress spontaneously. Spontaneous resolution of cutaneous lesions and lack of systemic involvement are essential for the diagnosis of CSHLCH. It needs long-term follow-up.

BACKGROUND: Hemangiopericytoma (HPC) is an uncommon soft tissue tumor arising from pericytes. The urogenital system is rarely affected.
METHODS: The review of the literature used the PubMed database which was searched up to March 2015.
RESULTS: Herein, we report the first case of lipomatous HPC of the corpus spongiosum in a 37-year-old man in China. The lesion presented as a quickly growing mass. Contrast enhanced CT showed a heterogeneous fatty mass with a multifocal enhancing soft-tissue component. Microscopically, the neoplasm was composed of spindle cells, a mature fat component and collagenous stroma. The mitotic index was low at 1 to 3 mitoses per 10 high-power fields. Immunohistochemically, STAT6, Bcl-2, CD99 and CDK4 were positive; CD34 and SMA were negative. The mature adipocytes were positive for S-100. Ki-67 expression was found in approximately 5% of the tumor cells. Surprisingly, there was a diffuse and strong nuclear expression of MDM2, but, no amplification of MDM2 was demonstrated by FISH. An adequate excision of the tumor was performed.
CONCLUSIONS: No local recurrence or distant metastases occurred during the 18-month follow-up. In view of the unpredictable biological behavior of this tumor, a long follow-up period is mandatory.

BACKGROUND: This study aimed at establishing the autoimmune hepatitis (AIH) model of C57BL/6 mice, and examining the expression and significance of T follicular helper (Tfh) cells, T follicular regulatory (Tfr) cells, effector B cells and other indicators in this experimental autoimmune hepatitis (EAH) model.
METHODS: C57BL/6 mice in experimental group were administered by intraperitoneal injection after fully emulsified on 1st day and 7th day with 0.5 mL of 0.5-2.0 g/L S-100 and an equal volume of Buddha Complete Adjuvant (CFA). The levels of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and interleukin-21 (IL-21) were tested by the corresponding kit. Tfr, Tfh and B cell subsets were quantified by flow cytometry. Histological pathology was completed by pathological section experiments.
RESULTS: In comparison with that in the healthy controls (HC), significantly increased numbers of serum ALT and AST, Tfr, IL-21 was observed. The hepatic lobules and hepatocyte cords were severely disorganized.
CONCLUSIONS: The results of liver pathological changes and serum index changes were similar to the chronic and progressive pathogenesis and pathology of AIH patients, providing a detailed pathological basis for the basic research and clinical experiments of AIH.