This article reports the diagnosis and treatment process of a 65-year-old male patient diagnosed with xanthoma dissseminatum. The patient sought medical attention due to reddish brown patchy rashes on the skin of the arms, knees and abdomen. The results of positron emission tomography and computed tomography (PET/CT) suggested that non-Langerhans cell histiocytosis might involve multiple blood vessels, the skin of the posterior neck and right forearm, multiple soft tissues, the descending duodenum and possibly the spine. Biopsy on skin of right arm showed non-Langerhans cell proliferative changes, with a pathological diagnosis of xanthoma dissseminatum. The rash improved after 6 cycles of monotherapy with cladribine. Follow-up PET/CT results indicated that multiple foci of abnormally increased glucose metabolism in the skin, joints, and soft tissues had decreased compared to previous examinations, suggesting disease remission. After stopping medication for 9 months, the patient underwent PET/CT reexamination, which showed new bone lesions. Bone marrow puncture was performed which suggested xanthoma dissseminatum involvement. Subsequently, the patient received chidamide combined with cladribine. By January 2025, the third cycle of chemotherapy had been completed. The patient is still under follow-up.

Purpose To explore the clinical and pathological features,differential diagnosis,treatment methods and prognosis of urachal adenocarcinoma.Methods Nineteen cases of urachal adenocarcinoma were collected and an-alyzed by combining clinical symptoms,auxiliary examinations,histology,immunohistochemical,and genetic testing and 11 cases of bladder adenocarcinomas.Results Among the 19 patients(15 males,4 females;age range:33-75 years,mean:55 years),tumors were located at the dome or anterior wall of the bladder.Histological subtypes includ-ed mucinous adenocarcinoma(6 cases),adenocarcinoma not otherwise specified(4 cases),enteric-type adenocarci-noma(6 cases),adenocarcinoma with focal mucinous differentiation(1 case),adenocarcinoma with signet-ring cell carcinoma(1 case),and metastatic urachal adenocarcinoma(1 case).Immunophenotypic analysis revealed membra-nous positivity for β-catenin,diffuse positivity for CK34βE 12,MUC-2,and CK20,focal CK7 positivity in some cases,and rare GATA-3 positivity.Mutations in p53 were observed,while KRAS,NRAS,BRAF,and PIK3CA mutations were absent.In colorectal adenocarcinomas,CK34βE12 positivity was 40％,nuclear β-catenin positivity was 48％,and MUC-2 expression was approximately 50％.In bladder adenocarcinomas,GATA-3 and MUC-2 positivity rates were 45％and 63.6％,respectively.Conclusion Distinguishing urachal adenocarcinoma from colorectal and primary bladder adenocarcinomas remains challenging.Urachal adenocarcinoma should be suspected in patients with anterior bladder wall or dome lesions,gross hematuria,or mucinuria.No definitive diagnostic markers currently exist for ura-chal adenocarcinoma.Immunophenotypic features such as membranous β-catenin,MUC-2,and CK7 positivity may fa-vor urachal adenocarcinoma over colorectal adenocarcinoma.Additional markers(e.g.,GATA-3,CK20,CK34βE12)aid in differential diagnosis,though individual markers lack specificity.Comprehensive evaluation integrating clinical presentation,imaging,and clinicopathological features is essential for accurate diagnosis.

Objective:To investigate the clinicopathological features, gene mutations, and distribution of bronchial adenoma (BA).Methods:Eighty-eight cases of BA diagnosed via routine section diagnosis between May 2015 and February 2024 were collected at the Pathology Departments of Zhongshan Hospital Affiliated to Fudan University (71 cases), Shanghai, China and Jining No.1 People′s Hospital (17 cases), Jining, China. Clinical data, image features, histopathological sections, immunohistochemical stains, and genetic testing results were reviewed.Results:Among the 88 patients with BA, there were 36 males and 52 females. The incidence of proximal-type BA was the same in both genders (50%, 28/56), while distal-type BA was more commonly found in females (75%, 24/32, P=0.022). BA predominantly affected middle-aged and elderly adults, with an age range of 30-78 years (median, 61 years). Clinically, BA generally presented without obvious symptoms. Radiologically it mainly manifested as peripheral lung ground-glass nodules, mixed ground-glass nodules, or solid nodules, primarily located in the lower lobes of the lungs (72.7%, 64/88). Proximal-type BA was characterized by solid nodules (53.6%, 30/56), while distal-type BA by ground-glass nodules (56.3%, 18/32), with a statistically significant difference between the two types ( P<0.01). The tumor was non-encapsulated, with a gray-white cut surface, and some areas were gray-brown. In 18.2% (16/88) of cases, the cut surface was slippery, with soft to medium-firm consistency and poorly defined margins. The smooth texture was predominantly found in proximal-type BA (14/16), whose tumor diameters ranged from 0.2 to 4.6 cm. Microscopically, the lesions exhibited glandular, papillary, or relatively flat patterns, with the main cellular components consisting of basal cells, ciliated columnar cells, mucinous cells, and alveolar epithelial cells in various proportions. Proximal-type BA resembled the morphology of proximal bronchioles and commonly contained mucinous and ciliated cells, while distal-type BA typically lacked mucinous and ciliated cells. The frequency of ciliated cell micropapillae in proximal-type BA (64.3%, 36/56) was significantly higher than that in distal-type BA (31.3%, 10/32, P=0.003). The morphological manifestation of glandular duct dilation was more commonly noted in proximal-type BA (98.2%, 55/56) than that in distal-type BA (81.25%, 26/32, P=0.009). Overall, the disagreement rate between frozen-section and routine diagnoses was 19.5% (17/87). Immunohistochemistry for cytokeratin 5/6 (CK5/6) and p40 showed that basal cell continuity in proximal-type BA (82.1%, 46/56) was significantly higher than that in distal-type BA (56.2%, 18/32, P=0.009). Molecular testing showed an accumulative gene mutation rate of 60.5% (23/38) in BA, including mutations in BRAF V600E (34.2%, 13/38), KRAS (18.4%, 7/38), ALK (5.3%, 2/38), and EGFR (2.6%, 1/38). Proximal-type BA was associated with BRAF V600E mutations, while distal-type BA with KRAS mutations ( P=0.025). Conclusions:BA is a rare benign bronchial tumor and has a high diagnostic error-rate on intraoperative frozen section. Proximal-type BA often presents with ciliated cell micropapillae, which supports the diagnosis, while distal-type BA frequently shows a partial reduction or absence of basal cells, increasing the diagnostic difficulty. The different subtypes of BA exhibit distinct genetic (mutation) profiles that may assist in its diagnosis and histological classification

Purpose To investigate the clinicopathological features and prognostic factors of follicular dendritic cell carcinoma(FDCS).Methods Hospital records of 23 patients diagnosed with FDCS were retrospectively re-viewed.The morphological,immunohistochemical features,including the detection of CD21,CD23,and CD35 using the EnVision method,and in-situ hybridization for Epstein-Barr virus encoded nuclear RNA(EBER)were evaluated.Clinicopathological characteristics were analyzed for the evaluation of prognosis.Results The median age of all 23 pa-tients was 50 years(range:27 to 72)and the female to male ratio was 1.3.The median maximum diameter of tumor was 7.0 cm(range:0.5 to 20.0 cm).One case was located in cervical lymph node,while another 22 were discovered in extranodal sites.20 cases were single organ and 3 cases were multiple organs involvement.Microscopically,tumor cells exhibited spindle,oval,or markedly pleomorphic morphology,accompanied by variable lymphoplasmacytic infil-tration in the stroma.CD21,CD35 and CD23 were positive in 22 of 23(95.6％),23 of 23(100.0％)and 4 of 15(26.7％)patients,respectively.EBER in-situ hybridization was positive in 9 of 23 patients(39.1％).The median follow-up time was 84.0(95％CI:50.7-117.3)months,and the 5-year survival rate was 80.2％(95％CI:62.8-97.6).Twelve(52.2％)patients were alive,5(21.7％)were dead,and 6(26.1％)were lost of follow-up.We es-tablished a pathological scoring system containing 5 indexes,i.e.,tumor maximum diameter,mitotic figures,tumor necrosis,cellular pleomorphism and histologic types.Patients with greater than 4 points had a significant poor progno-sis.Conclusion FDCS features a broad spectrum of histologic appearances and behavior.Combined morphological observations(HE staining),applications of a panel of follicular dendritic cell markers and EBER in-situ hybridization are helpful for accurate diagnosis.FDCS poses risks for recurrence,metastasis and death,and those with greater than 4 points in the scoring system have a significant poor prognosis.Long-term follow up is needed.

Objective:To investigate the clinicopathological features, gene mutations, and distribution of bronchial adenoma (BA).Methods:Eighty-eight cases of BA diagnosed via routine section diagnosis between May 2015 and February 2024 were collected at the Pathology Departments of Zhongshan Hospital Affiliated to Fudan University (71 cases), Shanghai, China and Jining No.1 People′s Hospital (17 cases), Jining, China. Clinical data, image features, histopathological sections, immunohistochemical stains, and genetic testing results were reviewed.Results:Among the 88 patients with BA, there were 36 males and 52 females. The incidence of proximal-type BA was the same in both genders (50%, 28/56), while distal-type BA was more commonly found in females (75%, 24/32, P=0.022). BA predominantly affected middle-aged and elderly adults, with an age range of 30-78 years (median, 61 years). Clinically, BA generally presented without obvious symptoms. Radiologically it mainly manifested as peripheral lung ground-glass nodules, mixed ground-glass nodules, or solid nodules, primarily located in the lower lobes of the lungs (72.7%, 64/88). Proximal-type BA was characterized by solid nodules (53.6%, 30/56), while distal-type BA by ground-glass nodules (56.3%, 18/32), with a statistically significant difference between the two types ( P<0.01). The tumor was non-encapsulated, with a gray-white cut surface, and some areas were gray-brown. In 18.2% (16/88) of cases, the cut surface was slippery, with soft to medium-firm consistency and poorly defined margins. The smooth texture was predominantly found in proximal-type BA (14/16), whose tumor diameters ranged from 0.2 to 4.6 cm. Microscopically, the lesions exhibited glandular, papillary, or relatively flat patterns, with the main cellular components consisting of basal cells, ciliated columnar cells, mucinous cells, and alveolar epithelial cells in various proportions. Proximal-type BA resembled the morphology of proximal bronchioles and commonly contained mucinous and ciliated cells, while distal-type BA typically lacked mucinous and ciliated cells. The frequency of ciliated cell micropapillae in proximal-type BA (64.3%, 36/56) was significantly higher than that in distal-type BA (31.3%, 10/32, P=0.003). The morphological manifestation of glandular duct dilation was more commonly noted in proximal-type BA (98.2%, 55/56) than that in distal-type BA (81.25%, 26/32, P=0.009). Overall, the disagreement rate between frozen-section and routine diagnoses was 19.5% (17/87). Immunohistochemistry for cytokeratin 5/6 (CK5/6) and p40 showed that basal cell continuity in proximal-type BA (82.1%, 46/56) was significantly higher than that in distal-type BA (56.2%, 18/32, P=0.009). Molecular testing showed an accumulative gene mutation rate of 60.5% (23/38) in BA, including mutations in BRAF V600E (34.2%, 13/38), KRAS (18.4%, 7/38), ALK (5.3%, 2/38), and EGFR (2.6%, 1/38). Proximal-type BA was associated with BRAF V600E mutations, while distal-type BA with KRAS mutations ( P=0.025). Conclusions:BA is a rare benign bronchial tumor and has a high diagnostic error-rate on intraoperative frozen section. Proximal-type BA often presents with ciliated cell micropapillae, which supports the diagnosis, while distal-type BA frequently shows a partial reduction or absence of basal cells, increasing the diagnostic difficulty. The different subtypes of BA exhibit distinct genetic (mutation) profiles that may assist in its diagnosis and histological classification

Purpose To investigate the clinicopathological features and prognostic factors of follicular dendritic cell carcinoma(FDCS).Methods Hospital records of 23 patients diagnosed with FDCS were retrospectively re-viewed.The morphological,immunohistochemical features,including the detection of CD21,CD23,and CD35 using the EnVision method,and in-situ hybridization for Epstein-Barr virus encoded nuclear RNA(EBER)were evaluated.Clinicopathological characteristics were analyzed for the evaluation of prognosis.Results The median age of all 23 pa-tients was 50 years(range:27 to 72)and the female to male ratio was 1.3.The median maximum diameter of tumor was 7.0 cm(range:0.5 to 20.0 cm).One case was located in cervical lymph node,while another 22 were discovered in extranodal sites.20 cases were single organ and 3 cases were multiple organs involvement.Microscopically,tumor cells exhibited spindle,oval,or markedly pleomorphic morphology,accompanied by variable lymphoplasmacytic infil-tration in the stroma.CD21,CD35 and CD23 were positive in 22 of 23(95.6％),23 of 23(100.0％)and 4 of 15(26.7％)patients,respectively.EBER in-situ hybridization was positive in 9 of 23 patients(39.1％).The median follow-up time was 84.0(95％CI:50.7-117.3)months,and the 5-year survival rate was 80.2％(95％CI:62.8-97.6).Twelve(52.2％)patients were alive,5(21.7％)were dead,and 6(26.1％)were lost of follow-up.We es-tablished a pathological scoring system containing 5 indexes,i.e.,tumor maximum diameter,mitotic figures,tumor necrosis,cellular pleomorphism and histologic types.Patients with greater than 4 points had a significant poor progno-sis.Conclusion FDCS features a broad spectrum of histologic appearances and behavior.Combined morphological observations(HE staining),applications of a panel of follicular dendritic cell markers and EBER in-situ hybridization are helpful for accurate diagnosis.FDCS poses risks for recurrence,metastasis and death,and those with greater than 4 points in the scoring system have a significant poor prognosis.Long-term follow up is needed.

Purpose To explore the clinical and pathological features,differential diagnosis,treatment methods and prognosis of urachal adenocarcinoma.Methods Nineteen cases of urachal adenocarcinoma were collected and an-alyzed by combining clinical symptoms,auxiliary examinations,histology,immunohistochemical,and genetic testing and 11 cases of bladder adenocarcinomas.Results Among the 19 patients(15 males,4 females;age range:33-75 years,mean:55 years),tumors were located at the dome or anterior wall of the bladder.Histological subtypes includ-ed mucinous adenocarcinoma(6 cases),adenocarcinoma not otherwise specified(4 cases),enteric-type adenocarci-noma(6 cases),adenocarcinoma with focal mucinous differentiation(1 case),adenocarcinoma with signet-ring cell carcinoma(1 case),and metastatic urachal adenocarcinoma(1 case).Immunophenotypic analysis revealed membra-nous positivity for β-catenin,diffuse positivity for CK34βE 12,MUC-2,and CK20,focal CK7 positivity in some cases,and rare GATA-3 positivity.Mutations in p53 were observed,while KRAS,NRAS,BRAF,and PIK3CA mutations were absent.In colorectal adenocarcinomas,CK34βE12 positivity was 40％,nuclear β-catenin positivity was 48％,and MUC-2 expression was approximately 50％.In bladder adenocarcinomas,GATA-3 and MUC-2 positivity rates were 45％and 63.6％,respectively.Conclusion Distinguishing urachal adenocarcinoma from colorectal and primary bladder adenocarcinomas remains challenging.Urachal adenocarcinoma should be suspected in patients with anterior bladder wall or dome lesions,gross hematuria,or mucinuria.No definitive diagnostic markers currently exist for ura-chal adenocarcinoma.Immunophenotypic features such as membranous β-catenin,MUC-2,and CK7 positivity may fa-vor urachal adenocarcinoma over colorectal adenocarcinoma.Additional markers(e.g.,GATA-3,CK20,CK34βE12)aid in differential diagnosis,though individual markers lack specificity.Comprehensive evaluation integrating clinical presentation,imaging,and clinicopathological features is essential for accurate diagnosis.

Purpose To investigate the expression of fork-head box protein A1(FOXA1)in esophageal squamous cell car-cinoma(ESCC)and its association with clinicopathologic char-acteristics and prognosis.Methods Immunohistochemistry was used to detect FOXA1 protein expression in 532 cases of esopha-geal squamous cell carcinoma.The correlation between FOXA1 protein expression and clinicopathologic features and prognosis of patients was analyzed.Results In 532 cases of esophageal squamous cell carcinoma,183 cases overexpressed FOXA1 pro-tein(34.4％).FOXA1 overexpression was associated with ES-CC vascular infiltration(P=0.032),poorly differentiation(P=0.032),and tumor size(P＜0.001).The overall survival(OS)and disease free survival(DFS)of patients with stage Ⅰ+Ⅱ esophageal squamous cell carcinoma with high FOXA1 ex-pression tended to be poor(OS:P=0.094;DFS:P=0.107).In ESCC patients with survival longer than 24 months,the high FOXA1 expression group had significantly shorter OS and DFS(OS:P=0.048;DFS:P=0.047).Multivariate survival anal-ysis showed that the depth of tumor invasion was an independent prognostic factor affecting the prognosis of esophageal squamous cell carcinoma.Conclusion FOXA1 is overexpressed in e-sophageal squamous cell carcinoma,and its high expression is related to tumor size,vascular infiltration and poorly differentia-tion.Patients with high FOXA1 expression tended to have poor prognosis in OS and DFS.When OS and DFS≥24 months,high FOXA1 expression may be used as a reference indicator for poor prognosis in ESCC patients.

Objective:To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification.Methods:A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically.Results:There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant ( P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference ( P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant ( P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant ( P<0.001). Conclusions:GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

Objective:To investigate the clinicopathological features and treatment of gastric alpha-fetoprotein (AFP)-producing adenocarcinoma with SWI/SNF complex deletion.Methods:Four cases of gastric AFP-producing adenocarcinoma with SWI/SNF complex deletion diagnosed in Zhongshan Hospital of Fudan University from January 2021 to December 2022 were collected, and their histomorphological characteristics, immunohistochemical (IHC), in situ hybridization of Epstein-Barr virus-encoded RNA (EBER), next-generation sequencing results, clinicopathological features and treatment were summarized, and literature review was conducted.Results:Among the 4 patients, there were three males and one female. They presented with abdominal pain, belching and melena. Serum AFP was significantly elevated in three patients, and endoscopy showed ulcerative lesions. Microscopically, the tumor cells showed mainly diffuse flaky or nest-like growth and typical characteristics of hepatoid adenocarcinoma. In two cases there were adenoid growth, and the tumor cells in these areas possessed clear cytoplasm, suggesting enteroblastic differentiation. The tumor cell nuclei were pleomorphic with large nucleoli and brisk mitoses. The IHC results showed that the tumor cells expressed AFP, GPC3 and SALL4, and there was retained expression of broad-spectrum keratin (CKpan) and E-cadherin. IHC detection of SWI/SNF complex subunits, namely INI1 (SMARCB1), BRG1 (SMARCA4), BRM (SMARCA2), ARID1A protein was performed. In all four cases the hepatoid adenocarcinoma region and enteroblastic differentiation region showed SMARCA2 deletion, and one case with enteroblastic differentiation also showed ARID1A deletion. SMARCB1 and SMARCA4 deletions were not seen. All the four cases were diffusely positive for p53 protein, and the Ki-67 proliferation index was 80%-90%. There were no mismatch repair deletion detected; one cases showed HER2 was strongly positive (3+), and EBER was negative. None of the four cases had mutations in the SWI/SNF complex-related subunits detected by next-generation sequencing. Among the four patients, two underwent palliative surgery due to distant metastasis at the time of surgery, two underwent radical resection. Postoperative adjuvant chemotherapy was given to three patients.Conclusions:AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.