In recent years, with the rapid development of artificial intelligence technology, the application of deep learning in the field of pathology has been continuously expanding. Particularly, the rise of multimodal data fusion methods has opened up new technical paths for the precise diagnosis, prognosis assessment, and individualized treatment of tumors. By integrating multi-level and multi-source data such as clinical information, pathological omics, molecular omics, and imaging omics, deep learning models can identify potential associated features and key biological mechanisms that are difficult to reveal by a single modality, thereby significantly improving the accuracy of disease classification and the scientific nature of risk stratification. This article systematically reviews the research progress of multimodal data fusion methods based on deep learning in the field of pathology in recent years, focuses on sorting out different types of fusion strategies, evaluates their advantages and challenges in practical clinical applications, and looks forward to future development trends.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

Purpose To investigate the clinical pathological features and treatment strategies of adult pineoblasto-ma(PB).Methods The clinical data of 11 cases of adult PB were retrospectively analyzed.Their imaging,histologi-cal morphology,and immunohistochemical characteristics were evaluated,and the relevant literature was reviewed.Re-sults Among the 11 PB cases,5 cases were female and 6 were male,aged 18-63 years with a median age of 39 years.Microscopically,the tumors were composed of dense small to medium-sized cells,showing a diffuse and sheet-like distribution.Rosette-like structures could be seen in some cases.The tumor cell nuclei were round or irregular with a high nuclear-cytoplasmic ratio.The mitotic figures and apoptosis were extremely common to see,and necrosis was observed in some cases.The tumor cells were uniformly positive for CD56(11/11),Syn(11/11),and CgA(11/11),with retained expression of INI-1(11/11).Some cases were positive for CD99(3/11)and S-100(1/11),while negative for BCOR,CKpan,GFAP,PLAP,CD3,and CD20.The Ki67 proliferation index ranged from 20％to 80％.Five patients were followed up for 2 to 39 months:1 patient developed spinal metastasis 26 months after postop-erative chemotherapy;1 patient had spinal metastasis 4 months after postoperative radiotherapy and temozolomide treat-ment;and 3 patients died.Conclusion PB is a rare,highly malignant tumor in the pineal gland region,even rarer in adults.Its morphology is similar to that of childhood PB,and its prognosis is slightly better than that in children.

Purpose To investigate the clinical pathological features and treatment strategies of adult pineoblasto-ma(PB).Methods The clinical data of 11 cases of adult PB were retrospectively analyzed.Their imaging,histologi-cal morphology,and immunohistochemical characteristics were evaluated,and the relevant literature was reviewed.Re-sults Among the 11 PB cases,5 cases were female and 6 were male,aged 18-63 years with a median age of 39 years.Microscopically,the tumors were composed of dense small to medium-sized cells,showing a diffuse and sheet-like distribution.Rosette-like structures could be seen in some cases.The tumor cell nuclei were round or irregular with a high nuclear-cytoplasmic ratio.The mitotic figures and apoptosis were extremely common to see,and necrosis was observed in some cases.The tumor cells were uniformly positive for CD56(11/11),Syn(11/11),and CgA(11/11),with retained expression of INI-1(11/11).Some cases were positive for CD99(3/11)and S-100(1/11),while negative for BCOR,CKpan,GFAP,PLAP,CD3,and CD20.The Ki67 proliferation index ranged from 20％to 80％.Five patients were followed up for 2 to 39 months:1 patient developed spinal metastasis 26 months after postop-erative chemotherapy;1 patient had spinal metastasis 4 months after postoperative radiotherapy and temozolomide treat-ment;and 3 patients died.Conclusion PB is a rare,highly malignant tumor in the pineal gland region,even rarer in adults.Its morphology is similar to that of childhood PB,and its prognosis is slightly better than that in children.

In recent years, with the rapid development of artificial intelligence technology, the application of deep learning in the field of pathology has been continuously expanding. Particularly, the rise of multimodal data fusion methods has opened up new technical paths for the precise diagnosis, prognosis assessment, and individualized treatment of tumors. By integrating multi-level and multi-source data such as clinical information, pathological omics, molecular omics, and imaging omics, deep learning models can identify potential associated features and key biological mechanisms that are difficult to reveal by a single modality, thereby significantly improving the accuracy of disease classification and the scientific nature of risk stratification. This article systematically reviews the research progress of multimodal data fusion methods based on deep learning in the field of pathology in recent years, focuses on sorting out different types of fusion strategies, evaluates their advantages and challenges in practical clinical applications, and looks forward to future development trends.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

Objective: To investigate the expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone (GCTB), and its value in the diagnosis of GCTB. Methods: Immunohistochemical (IHC) EnVision method was used to detect the expression of H3.3 G34W mutant-specific antibody and p63 in 83 GCTBs, 18 aneurysmal bone cysts, 23 chondroblastomas and 28 osteosarcomas diagnosed at Nanjing Jinling Hospital from June 2001 to April 2019. Results: Among the 83 cases of GCTB, 69 cases (69/83, 83.1%) expressed H3.3 G34W. H3.3 G34W expression was found exclusively in the mononuclear cell population with strong and diffuse nuclear staining. H3.3 G34W was expressed in 55 of 57 (96.5%) cases of GCTB in long bones, but only 14 of 26 (53.8%) cases of non-long bone GCTB. All recurrent (9/9)/metastatic GCTB (2/2), post-denosumab GCTB (3/3), primary malignant GCTB (3/3) and secondary malignant GCTB (5/5) also expressed H3.3 G34W. H3.3 G34W was negative in all aneurysmal bone cysts and chondroblastomas. H3.3 G34W was positive in 3 of 28(10.7%) cases of osteosarcomas, and giant cell-rich osteosarcoma(GCRO) was the only histological subtype of osteosarcoma that expressed H3.3 G34W. p63 was expressed in 71.1%(59/83) of GCTB, while the positive rates of p63 in aneurysmal bone cysts,chondroblastomas and osteosarcomas were 3/18, 43.5% (10/23) and 21.4% (6/28) respectively. The sensitivity and specificity of H3.3 G34W mutant-specific antibody in the diagnosis of GCTB were 83.1% and 95.7%. Conclusions H3.3 G34W mutant-specific antibody is a highly sensitive and specific marker for GCTB and helpful for the diagnosis of GCTB and its variants. The limitation of this antibody is that as a mall number of GCTB harbor G34 mutation other than G34W, and thus that cannot be detected. The incidental expression of H3.3 G34W mutant protein in osteosarcoma could be a potential diagnostic dilemma, and the results of H3.3 G34W IHC staining needs careful interpretation.

Objective:To investigate the clinical manifestations, imaging features, histopathologic, immunohistochemical (IHC) and ultrastructure features of neuronal intranuclear inclusion disease (NIID).Methods:HE, IHC staining and EM were performed in cases of NIID diagnosed at the Department of Pathology, Jinling Hospital from 2018 to 2019.Results:Two cases were identified, including one male and one female; both patients were 76 years old. They were hospitalized because of nervous system dysfunction. MRI showed abnormal high signal intensity in corticomedullary junction of bilateral frontal lobes (male patient) and bilateral cerebral hemispheres (female patient). Light eosinophilic transparent inclusion bodies were seen in the nuclei of neurons in both rectal mucosa and cutaneous sweat glands, and these were positive for p62 by IHC. By scanning EM, the inclusion bodies in the sweat gland cells nuclei were round membranous structures consisting of 8-18 nm microfilaments.Conclusions:NIID is a rare, multi-system and slowly progressive neurodegenerative disease. Its clinical manifestations are highly diverse and easily misdiagnosed or missed. Neuroimaging can make a preliminary diagnosis. In the past, NIID can only be diagnosed through autopsy, and this study demonstrates that NIID can be confirmed through skin or rectal mucosal biopsy.

Objective:To study the clinicopathologic features, immunophenotype, molecular genetics and differential diagnosis of biphenotypic sinonasal sarcoma (BSNS), and to evaluate the role of PAX3 and PAX8 immunohistochemical (IHC) antibodies in the diagnosis of BSNS.Methods:Nasal sinus spindle cell tumors surgically treated at the Jinling Hospital from 2000 to 2019 were collected, including three cases of BSNS, 10 cases of acinar rhabdomyosarcoma, eight cases of schwannoma, five cases of hemangiopericytoma, three cases of fibrosarcoma, and one case of triton tumor. The cases were evaluated by histology, IHC by EnVision for PAX3 and PAX 8 (including PAX8 murine monoclonal antibody, clone number OTI6H8, hereinafter referred to as PAX8-OTI6H8 antibody; PAX8 rabbit monoclonal antibody, clone number EP298, hereinafter referred to as PAX8-EP298 antibody) molecular genetic tests.Results:All three BSNS patients were elderly women with clinical manifestations of nasal congestion and bleeding. Imaging showed a soft tissue density shadow of the nasal cavity and sinuses with bone destruction. The boundaries of tumors which were covered with ciliated columnar epithelium were unclear, and mucosal invasion and squamous metaplasia could be seen. Tumor cells were spindle-shaped, arranged in a bundle-like, braided arrangement, with little cellular atypia and occasional atypical mitotic figures. The tumoral interstitial vessels were mostly thin-walled, some showing staghorn-like changes. There was focal striated muscle differentiation in two cases, and bone invasion was seen in two cases. IHC staining showed that all three cases of BSNS expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. All eight cases of schwannoma, five cases of hemangiopericytoma, and one case of triton tumor did not express PAX3, PAX8-OTI6H8 or PAX8-EP298. Eight of the ten cases of alveolar rhabdomyosarcoma expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. Three cases of fibrosarcoma showed weak PAX3 and PAX8-OTI6H8 expression, but there was no PAX8-EP298 expression. FISH detection showed that PAX3 break apart in the tumor cells from all three patients (four specimens).Conclusions:BSNS is a distinct sinonasal low grade malignancy with dual differentiation which could be readily confused with a variety of spindle cell tumors encountered in the sinonasal cavity. The molecular genetics of PAX3 gene break is the gold standard for diagnosis of this tumor. IHC marker monoclonal PAX3 is 100% expressed in BSNS, while the specificity is limited. PAX8-OTI6H8 is also expressed in BSNS due to the cross reaction with PAX3 antibody, while PAX8-EP298 is all negative for these tumors.

Objective: To investigate the clinical, histologic and immunophenotypic features, genetic alterations and prognosis of the rare Xp11 neoplasm with melanocytic differentiation. Methods: Twenty-one cases were selected from the Department of Pathology, Jingling Hospital, Nanjing University School of Medicine from May 2008 to May 2018. The clinicopathologic, immunohistochemical, molecular analysis and follow-up details were collected. Results: There were 7 males and 14 females, with their ages ranging from 4 to 57 years (mean 32.8 years). The tumors were located in kidney (11 cases), pelvis (three cases), and in pancreas, retroperitoneum, adrenal gland, small intestine, prostate, cervix and appendix (one case each). Microscopically, most tumors shared similar morphology such as purely nested or sheet-like architectures separated by a delicate vascular network, purely epithelioid cells with clear to granular eosinophilic cytoplasm, lacks of papillary structures, spindle cell or fat components, uniform round to oval nuclei with small visible nucleoli, and in most of them (16/21) melanin pigment. Immunohistochemically, all cases showed moderately (2+) or strongly (3+) positive staining for TFE3 and Cathepsin K. HMB45 and Melan A were focally expressed in three of 21 cases, while the remaining cases showed typically moderate(2+) or strong (3+) expression. None of the cases were immunoreactive for SMA, desmin, CKpan, S-100 and PAX8. All cases showed TFE3 rearrangement using fluorescence in-situ hybridization (FISH). Fusion FISH assays detected SFPQ-TFE3 gene fusion in 16 cases, NONO-TFE3 gene fusion in two, ASPL-TFE3 and MED15-TFE3 gene fusions in one case each. Polymerase chain reaction and direct sequencing detected SFPQ-TFE3 gene fusion in nine cases, NONO-TFE3 and MED15-TFE3 gene fusions in one case each. Clinical follow-up was available for 15 patients for 12 to 74 months. Six patients died of the disease; and three had recurrences and/or metastases. Six patients were alive with no evidence of disease after initial resection. Conclusions Xp11 neoplasm with melanocytic differentiation has unique morphologic, immunophenotypic and genetic characteristics. The tumor is aggressive, and should be differentiated from Xp11 translocation RCC and perivascular epithelioid cell tumor.