Over the past decade, the field of urological and male reproductive system pathology has experienced rapid development. Numerous accomplishments were achieved in clinical diagnosis and molecular research in this area in China, gradually gaining international recognition. As the most influential academic journal in the field of pathology in China, the Chinese Journal of Pathology has witnessed the vigorous growth and innovation in this domain. On the occasion of the journal′s 70th anniversary, a summary on the developments in this field have been provided, along with an outlook for the future.

With the development of thyroid pathology in the past decade, thyroid pathological diagnosis has entered the era of molecular pathology. As the most influential academic journal in the field of pathology in China, Chinese Journal of Pathology has published nearly one hundred articles related to thyroid diseases in the past decade. These results have made a great difference to the scientific research and clinicopathological diagnosis of thyroid diseases in China, and have also provided Chinese data for the pathological communication of thyroid diseases internationally. Pathologists should make full use of thyroid cytology and histopathology, combined with molecular testing and digital intelligence technology, to play a core guiding role in the multidisciplinary precise diagnosis and treatment of thyroid diseases.

Immune checkpoint inhibitors targeting PD-1/PD-L1 are gradually being applied in the treatment of advanced urinary system tumors. Immunohistochemical analysis of PD-L1 expression is the most popular method for screening suitable patients for immunotherapy and predicting therapeutic efficacy. The current application status of PD-L1 detection for urinary system tumors (mainly urothelial carcinoma), methods of the different antibody tests and the precautions, challenges and solutions in the interpretation of immunostaining were summarized in this review.

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 clinicopathological characteristics, immunophenotypes, diagnostic criteria and differential diagnosis of atrophic kidney-like lesion (AKLL).Methods:Three cases of AKLL were collected from April 2021 to October 2023 at the Xiangya Hospital of Central South University, Changsha, Zhejiang Provincial People′s Hospital, Hangzhou and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinical, morphological, and immunohistochemical characteristics were analyzed. Relevant literature was also reviewed. A targeted DNA-based next-generation sequencing (a panel of 150 genes) was performed on one of the three cases.Results:There were 1 female and 2 males, aged 30, 57, and 17 years (mean 34.6 years), respectively. The lesions were all incidentally identified during physical or imaging examination. Radiologically, they were all presented as a unilateral renal parenchymal mass. Grossly, the maximum diameters of the lesions were 1.8, 4.0, and 6.5 cm (mean 4.1 cm), respectively. The tumor cut-surfaces were sponge-like, multilocular cystic, and solid, respectively. At low magnification, the lesions were well-circumscribed, while a thick fibromuscular capsule was noted in cases 1 and 3. Cases 1 and 2 were composed of thin-walled cysts or follicular like structures of varying sizes, with the cyst wall lined by flattened and atrophic, or hobnail cells. The luminal spaces contained dense eosinophilic secretion and associated calcifications, while some cysts contained discohesive cells floating in the eosinophilic material. The tissue between the cysts showed predominantly small atrophic tubular structures. Case 3 was almost entirely composed of atrophic and collapsed tubular structures with focal cyst formation, imparting a solid sheets growth pattern under low magnification. Immunohistochemical staining revealed that the cyst lining cells and the intracystic floating cells were WT1 positive, PAX8 negative and CK7 negative, while the atrophic renal tubules were WT negative, PAX8 positive and CK7 positive. Targeted next-generation sequencing in case 1 showed no significant genetic abnormalities. All 3 patients underwent partial nephrectomy. No evidence of recurrence or metastasis was found with a follow-up of 17 to 36 months.Conclusions:AKLL is a rare and novel benign renal disease. It is easily misdiagnosed as a renal neoplasm grossly and histologically. Careful morphological observation combined with characteristic immunophenotypes can aid in its diagnosis and differential diagnosis.

Objective:To understand the clinicopathological and molecular genetic characteristics of aggressive renal mucinous tubular and spindle cell carcinoma (MTSCC).Methods:The clinical features, histology, immunophenotype, molecular characteristics and prognosis of 4 cases of metastatic/recurrent renal MTSCC that were submitted to the Peking University Third Hospital (2 cases), Institute of Urology, Peking University (one case) and Zhejiang Provincial People′s Hospital (one case) from 2015 to 2020 were retrospectively reviewed and analyzed.Results:Among the four patients, two were male and two were female. The average age was 58 years, ranging from 28 to 77 years. Three patients underwent radical nephrectomy, while one underwent partial nephrectomy. The tumor size was 2-8 cm (mean, 5.6 cm). There were two cases classified as pT3a, one case as pT1b and one case as pT1a. Histologically, the tumors were mainly composed of tubules and spindle cell cords. For nuclear grade, three cases were G3 and one case was G2. Extracellular mucus was present in all four cases. Sarcomatoid features and tumor necrosis were observed in one and three cases, respectively. Immunohistochemistry showed that PAX8 (4/4), AMACR (4/4), CK7 (4/4), CKpan (3/3), vimentin (3/3) and CK8/18 (2/2) were positive in the tumor cells, but CAⅨ (1/4) or CD10 (2/3) were focally positive or negative. Fluorescence in situ hybridization showed that no trisomy of chromosomes 7 and l7 (2/2). Targeted next generation sequencing were performed in all four cases and showed that 3 cases had mutations in Hippo pathway involving MET (2/4), NF2 (1/4) and NTRK1 (1/4) genes. The other potentially pathogenic mutations involved KDM6A, SETD2 and PALB2. The follow-up period was 13 to 99 months. The time between diagnosis and metastasis/recurrence ranged from 6 to 58 months. Two patients died after lung metastasis occurred, one had multi-organ and multi-site lymph node metastases, and one achieved disease-free survival after resection of metastatic/recurrent foci.Conclusions:Renal MTSCC is a rare and distinct entity. The presence of high nuclear grade and pathological stage, high-grade morphology, lymphovascular invasion, and tumor necrosis suggests potential aggressive behaviors. It is thus recommended to report these histological features and conduct active follow-up and surveillance after surgery. The frequent mutations in MET, NF2 and NTRK1 suggest that dysregulation of Hippo pathway may be related to the development and progression of renal MTSCC.

Objective:To investigate the characteristics of RET gene rearrangement revealed by fluorescence in situ hybridization (FISH) in lung cancer.Methods:A total of 616 formalin-fixed paraffin-embedded surgical samples from lung adenocarcinomas with wild-type EGFR gene and no ALK protein expression by immunohistochemistry obtained at Peking Union Medical College Hospital, Beijing, China between December 2019 and April 2022 were included. Thirty-three tumors with RET gene rearrangement determined by imbalanced-based reverse-transcription droplet digital PCR (RT-ddPCR) were analyzed using break-apart FISH. The results were confirmed, and RET gene fusion variants were identified through next generation sequencing (NGS).Results:RET gene rearrangements were found in all 33 RET RT-ddPCR positive cases via NGS, including 27 cases of KIF5B::RET, 3 CCDC6::RET, 2 ERC1::RET and 1 CCDC186::RET rearrangements. Moreover, 32 RET positive and 1 RET negative cases were defined using FISH. Among the RET FISH-positive cases, 25 (78.1%, 25/32) showed break-apart FISH signal pattern in 52%-100% of tumor cells with the rearrangement and 7 cases (21.9%, 7/32) presented isolated 3′ signal type in 38%-88% positive tumor cells. There was no RET-positive case with single 5′ pattern in the cohort. The most common partner gene was KIF5B (81.8%, 27/33). Most of the patients with RET gene rearrangement were female (72.7%, 24/33).Conclusion:RET FISH-positive lung cancer is commonly characterized by a high proportion of rearrangement cancer cells and break-apart FISH signal type.

Objective:To investigate the clinicopathological and molecular genetic characteristics of intracranial mesenchymal tumors with FET::CREB fusion transcript.Methods:The clinical and imaging data of 6 cases of intracranial mesenchymal tumors with FET::CREB fusion from December 2018 to December 2023 were collected at the First Affiliated Hospital of Zhengzhou University. Their histological features, immunophenotype and molecular characteristics were analyzed.Results:Among the 6 patients, 4 were males and 2 were females, and the median age was 20 years. The clinical symptoms were increased intracranial pressure in 5 cases and epilepsy in 1 case. The lesion sites were cerebellum (2 cases), frontal lobe (2 cases), parietal lobe (1 case), and cranioorbital communication (1 case). The radiological features mainly showed solid or cystic components, with obvious annular enhancement on MRI. The histopathological features showed a wide spectrum of morphology, clear boundaries and fibrous pseudocapsule. The tumor cells were arranged in a lamellar or nodular pattern, and some in cord or loose network. The tumor cells were spindle, oval, epithelioid or stellate. The stroma was collagenous or mucin-rich, and accompanied by abundant lymphocytes and plasma cells infiltration. By immunohistochemical staining, desmin, CD99 and EMA were expressed in 6 cases, CD68 in 1 case, MUC4 in 1 case, synaptophysin in 2 cases, and ALK in 1 case. The Ki-67 proliferation index was between 1%-15%. Molecular analysis showed EWSR1::ATF1 fusion in 3 cases, EWSR1::CREB1 fusion in 2 cases, and EWSR1::CREM fusion in 1 case.Conclusions:Intracranial mesenchymal tumors with FET::CREB fusion are relatively rare and typically occur in children and younger adults. These tumors have a broad morphological spectrum and often express desmin, CD99 and EMA. The molecular characteristics are the gene fusions of FET family (mainly EWSR1, FUS) with CREB family transcription factors (ATF1, CREB1 or CREM). It is necessary to distinguish these tumors from meningiomas and solitary fibrous tumors, and the combination of immunohistochemical staining and molecular genetic testing can effectively help identify these tumors.

During the past decate, Chinese pathologists have made remarkable achievements in the area of soft tissue tumors. They have not only done in-depth researches in selected entities like liposarcoma and round cell sarcomas, but have also issued expert consenses and guideline, as well as published professional books and translation books, with purpose to comprehensively improve the level of diagnosis nationwide.

In the past decade, governments, including the national, provincial, municipal, and others, have increased their investment in children′s health. Pathologists, especially pediatric pathologists, have greatly promoted the development and progress of pediatric pathology in China with the guidance of molecular pathological technology. This article reviews the cultivation of pediatric pathology talents, the application of new technologies, clinical pathological diagnosis and research, as well as many other aspects over the past decade, and looks forward to the future development of pediatric pathology.