Objective:To investigate the clinicopathological features, diagnosis, genetic alterations, and biological behaviors of hamartomatous inverted hyperplastic polyp (HIHP) in the gastrointestinal tract.Methods:The clinical, sonographic, endoscopic and pathologic data of 10 HIHP cases diagnosed at the First Affiliated Hospital of Air Force Medical University, Xi′an, China from January 2013 to March 2024 were collected. Their clinicopathological features and histological morphology were analyzed. The cases were further divided into 3 histologic subtypes. Follow-up information was collected to analyze the relationship between histological subtype and prognosis.Results:There were 5 males and 5 females in this cohort. The age of onset was 45-68 years, with a median age of 60.5 years. The polyp-involved sites included 2 cases in gastric fundus, 6 cases in gastric body, 1 case in gastric antrum, and 1 case in duodenum. Digestive endoscopy showed mucosal protrusion lesions in all cases, except 1 case (case 10) of shallow depression on the surface, with the maximum diameter ranging 0.5-2.5 cm. Endoscopic ultrasonography showed multilocular cystic low-density shadows, with septal enhancement (case 4). The preoperative clinical diagnosis was gastric polyp, ectopic pancreas or gastrointestinal stromal tumor. Two cases showed type 1 morphology (i.e., connected with the mucosa, with clear smooth muscle boundaries). One of them (case 10) had a clear opening to form a vase-like morphology, while the other (case 4) had no obvious opening with the surface mucosa. Three cases showed type 2 morphology (i.e., not connected with the mucosa, with clear smooth muscle boundaries). Five cases showed type 3 morphology (i.e., not connected with the mucosa, without clear smooth muscle boundaries or hyperplastic smooth muscle that separated hyperplastic glands showing lobular configuration). Among them, one case of duodenal lesions (case 9) showed gastric type gland hyperplasia and expansion, including gastric fossa, gastric fundic gland and pyloric gland, with various arrangement and combination, accompanied by smooth muscle hyperplasia. In case 10, there was leiomyomatous proliferation in the stroma. The cases 2 and 4 had atypical glandular structures and cell morphology, but immunohistochemistry showed wild-type expression pattern of p53 and a Ki-67 proliferation index of less than 1%, suggesting that it was reactive atypia secondary to inflammation. The results showed that 3 cases had different gene mutations, and no recurrent gene change was identified. All patients survived without disease during the follow-up period of 1-130 months.Conclusions:HIHP is a benign lesion and has no consistently detectable genetic alterations. The histological characteristics of gastrointestinal polyps are complex. Especially, the types 1 and 3 of HIHP have unique gross and microscopic features, which require combination of proper endoscopic sampling and histological examination to correctly classify them.

Objective:To investigate the clinicopathological characteristics of solid, endometrial-like and transitional (SET) cell growth subtype in high-grade serous ovarian carcinoma (HGSC).Methods:Clinical data of 25 cases of HGSC-SET were collected from January 2020 to March 2024 at the Affiliated Suzhou Hospital of Nanjing Medical University, and their histological features were analyzed. Immunohistochemical stains were used to analyze the expression of ER, PR, PAX8, WT-1, p16, p53 and Ki-67. Next generation sequencing method was used to detect breast cancer susceptibility (BRCA1/2) gene mutation, homologous recombination deficiency (HRD) status, and other homologous recombination repair (HRR) genes. The difference of HRD status between HGSC-SET and typical HGSC patients was further compared.Results:The age of HGSC-SET patients ranged from 41 to 81 years, with an average age of 59 years and a median age of 57 years. Four cases were premenopausal and 21 were postmenopausal. There were 12 cases of bilateral ovarian masses and 13 cases of unilateral ovarian masses. Serum CA125 was elevated in 21 patients and CA19-9 in 2 patients. Lymph node involvement was found in 9 cases, and distant dissemination or metastasis was found in 15 cases. Tumor cells were found in ascites of 10 cases. All the cases were of mixed type, with both typical components (papillae, micropapillae, and glands) and SET components. The total proportion of SET components was>25%. There were 15 cases with comedo/map-like necrosis. Most of the SET form showed pushing pattern of invasion, while the classic form showed infiltrative pattern of invasion. All 25 cases of HGSC-SET showed mutant type staining of p53, of which 20 cases indicated missense mutation and 5 cases indicated nonsense mutation. The positive rates of PAX8, WT-1 and p16 were 100% (25/25), 84% (21/25) and 92% (23/25), respectively. The positive rate of ER was 80% (20/25) in the SET morphological region and 68% (17/25) in the classic morphological region. The positive rate of PR was 16% (4/25) in the SET morphological region and 32% (8/25) in the classic morphological region. The proliferative index of Ki-67 was 60%-95% in the SET region and 20%-90% in the classic region. BRCA1/2 gene mutation was detected in 36% (9/25) of HGSC-SET patients. Among them, 2 cases had BRCA1 gene mutation, 6 cases had BRCA2 gene mutation, and 1 case had gene mutation both in BRCA1 and BRCA2. HRD was positive in 84% (21/25) of patients and negative in 16% (4/25) of patients. The positive rate of HRD in BRCA1/2 wild-type cases was 12/16. A total of 21 patients had HRR-related gene alterations other than BRCA1/2. The mutation rate of BRCA1/2 gene in HGSC-classic patients was 4/20, and the positive rate of HRD was 11/20.Conclusions:Histologically, HGSC-SET presents as a mixed pattern, with comedo/map-like necrosis in most cases. The mutation rate of BRCA1/2 and the positive rate of HRD are higher in HGSC-SET than in HGSC-classic type. BRCA1/2 wild-type HGSC-SET also has a higher HRD positive rate. Besides BRCA1/2, other HRR related gene mutations should not be ignored to avoid missing patients who may benefit from PARP inhibitor treatment.

Objective:To investigate the clinicopathological and genetic features of infantile rhabdomyofibrosarcoma (IRFS) with EGFR kinase domain duplication (EGFR-KDD).Methods:The clinical, morphological and immunohistochemical features of three IRFS with EGFR-KDD diagnosed from January 2022 to January 2024 at Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed using PCR or next generation sequencing technique; and related literature was reviewed.Results:There were 1 male and 2 females, aged at presentation ranging from 1 to 4 years. The tumor occurred in the left thigh, right maxillofacial region, and right popliteal space. The presenting symptom was a painless mass which was accidentally discovered. The maximum diameter of tumors ranged from 3 to 5 cm. Microscopically, the tumors were poorly defined and composed of relatively monomorphic spindle cells, arranged in diffuse, fascicular growth patterns, with moderate pale eosinophilic cytoplasm. Mitoses were abundant. A few round rhabdomyoblastic tumor cells with abundant eosinophilic cytoplasm were found. There was no evidence of hemorrhage or necrosis. The tumor cells expressed vimentin, SMA, MSA, desmin, MyoD1 and myogenin; and the Ki-67 proliferation index was 10%-60%. RT-PCR showed EGFR-KDD in all three cases. Gene fusion was detected in three cases based on next generation sequencing, but only one case had EGFR-KDD. Follow-up data for 12 to 36 months showed two patients died of the disease and one patient was alive without recurrences and metastasis.Conclusions:IRFS is a rare soft tissue tumor that resembles infantile fibrosarcoma but has immunohistochemical evidence of rhabdomyoblastic differentiation. It more commonly occurs in infants and tends to appear in limbs and torso with poor prognosis. Aggressive multimodality treatment is recommended for these patients. EGFR-KDD may be a genetic driver to IRFS. Clinical response to EGFR targeted therapy might be promising in the future.

Phyllodes tumors (PT) of the breast is a rare fibroepithelial tumor, which can be divided into benign, borderline and malignant pathological types according to its histological characteristics. Malignant phyllodes tumor (MPT) accounts for 10%-20% of PT and has the ability of local recurrence and distant metastasis. Therefore, accurate diagnosis and identification of MPT are particularly important for patients to obtain appropriate treatment at the initial diagnosis. At present, histological morphology is the only diagnostic basis for MPT. However, due to the fact that phyllode tumor itself is a continuous disease spectrum with overlapping histological features, and the diagnostic classification adopts many histological parameters and their evaluation is subjective, pathologists lack consistency in MPT grading, and the biological behavior of PT is not completely consistent. Therefore, the existing MPT classification standards are facing challenges, and the accurate and reproducible classification is worthy of further exploration.

Chinese head and neck pathology has been comprehensively improved in the past ten year. This paper focuses on the observation and research of sinonasal epithelial tumors, non-epithelial tumors, inflammatory diseases, NK/T cell lymphoma, nasopharyngeal carcinoma, oropharyngeal HPV-associated squamous cell carcinoma, laryngeal squamous cell carcinoma, ear neuroendocrine tumor, adenoid cystic carcinoma, endolymphatic sac tumor, and hyperplastic disease of Waldeyer′s ring lymphoid tissue, etc. The difficult cases were reviewed. Hope to represent the whole picture of the progress of the subject. In the future, we will further strengthen the construction of discipline echelons, deepen the comprehensive and in-depth discussion and research of diseases, and make breakthroughs in the original understanding of diseases.

Objective:To investigate the clinicopathological features, immunohistochemical characteristics, and differential diagnosis of low-grade adenosquamous carcinoma of the breast arising from benign sclerosing lesions.Methods:Twelve cases of low-grade adenosquamous carcinoma arising from benign sclerosing lesions of the breast were collected, which were diagnosed from January 2010 to December 2023 at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital. Their clinical manifestations, histopathological morphology, and immunohistochemical characteristics were analyzed and related literatures were reviewed.Results:All the 12 patients were females with a median age of 42 years (21-60 years). Five of the 12 cases had coexisting complex sclerosing lesions, 5 with sclerosing adenosis, 1 with sclerosing intraductal papilloma, and 1 with ductal adenoma. Microscopically, low-grade adenosquamous carcinoma grew infiltratively in multinodular and sclerosing lesions. The carcinomatous component was characterized by small irregular glandular structures, tubular formations, solid nests, clusters, or a single tumor cell. The epithelium showed varying degrees of squamous differentiation. The carcinoma was surrounded by fibroadenomatoid and desmoplastic lesions. The invasive neoplastic component typically infiltrated normal breast structures, and might infiltrate nerves and adipose tissue. There were lymphocytic aggregates commonly seen at the periphery. By immunohistochemistry, the tumor cells of all 12 cases showed diffuse and strong immunopositivity for CK5/6; negative expression of ER, PR and HER2; and variable expression of myoepithelial markers such as SMA, calponin, SMMHC and others. There was varied staining pattern of tumor cells for p63. CK8/18 (or CK7) was variably positive or negative. The proliferative index measured by Ki-67 was low.Conclusions:Low-grade adenosquamous carcinoma of the breast is a rare variant, which is found to coexist with other benign sclerosing lesions and can be easily missed and/or misdiagnosed. Their invasive growth pattern, presence of sweat duct-like structures and immunophenotypic profile are key features for appropriate diagnosis.

Objective:To investigate the morphological changes and immunophenotypic characteristics of eosinophilic coarse granules in the cytoplasm of epithelial cells of breast adenosis, and their clinicopathological significance.Methods:A total of 64 cases containing eosinophilic coarse granules in the cytoplasm of breast epithelial cells admitted to the Department of Pathology of the Seventh Medical Center of People′s Liberation Army General Hospital and the Department of Pathology of Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University for admission and consultation from December 2019 to August 2023 were collected. The distribution and morphological characteristics of eosinophilic coarse granules in the epithelial cytoplasm in 64 cases of breast adenosis were observed. Some cases underwent immunohistochemical staining of lysozyme, α-antitrypsin, α-antichymotrypsin, cathepsin D, EMA, panCK, ER, PR, AR, GCDFP-15, Syn, CgA, NSE, CD68, S-100, anti-mitochondrial antibody, p63, and SMA; and some cases were stained with mucicarmine, and AB-PAS histochemical staining before and after amylase digestion.Results:The eosinophilic coarse granules in the breast epithelial cytoplasm of 64 cases were seen accidentally, of which most (43 cases) were located in adenosis adjacent to the intraductal papilloma. By HE sections, eosinophilic coarse granules were found with diffuse distribution in the cytoplasm, which were round in varying sizes, pink-bright red, and with a certain degree of refractivity. The size of the coarse granules could be divided into three types: small, medium and large. The medium to large granules were more prominent in the lesions. The eosinophilic coarse granules were all positive for lysozyme, α-antitrypsin, α-antichymotrypsin, cathepsin D, EMA and S-100. ER and PR were all nonclonal positive in glandular epithelial cells. Histochemical stains for PAS were all positive before and after digestion of amylase. AR, GCDFP-15, Syn, CgA, NSE, CD68 and anti-mitochondrial antibodies were all negative; mucicarmine and AB staining were also negative.Conclusions:The morphological characteristics and immunophenotype of cytoplasmic eosinophilic coarse granules in the epithelial cells of breast adenosis are the same as those of zymogen granules, their existence may be a non-specific morphological change, representing a metaplasia of breast epithelial cells. Positive results for lysozyme, antichymotrypsin, etc. cannot be considered evidence of specific cell differentiation. For the diagnosis of acinar cell carcinoma, it should be combined with morphological characteristics, immunohistochemical characteristics, etc. to make a comprehensive analysis.

Objective:To investigate the mutation spectrum of the PIK3CA gene in breast cancer, providing a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.Methods:A retrospective analysis was conducted on 144 breast cancer patients who underwent biopsy before neoadjuvant therapy archived from 2015 to 2020 at the Fourth Hospital of Hebei Medical University. Next-generation sequencing (NGS) was utilized to detect the mutations of 520 genes closely related to the development of solid tumors and targeted therapies. The study compared the differences between reported mutation types and focused on analyzing the mutation status of the PIK3CA gene. The clinical and pathological characteristics, including age of onset, molecular subtypes, and Ki-67, were also analyzed. The correlation between PIK3CA mutations and clinicopathological characteristics was examined using Pearson×s chi-square test and Mann Whitney test. Logistic regression was employed to analyze factors influencing PIK3CA mutations. Kaplan-Meier survival analysis and Cox regression models were constructed using R programming.Results:Among the 144 breast cancer samples, 61 (42.3%, 61/144) exhibited PIK3CA gene mutations, of which 23 cases (53.5%, 23/43) were HER2-positive breast cancer, 28 cases (44.4%, 28/63) were luminal breast cancer, and 10 cases (27.8%, 10/36) were triple-negative breast cancer. Of the detected mutations, three hotspot mutations (H1047R, E545K, and E542K) accounted for 72.1% of the total PIK3CA mutations, with H1047R (52.4%), E545K (16.4%), and E542K (3.3%) most commonly detected. The remaining rare mutations accounted for 26.3%. Co-mutations involving PIK3CA and other genes were also observed in the cohort, occurring with TOP2A and FOXA1, while being mutually exclusive with GATA3 and BRCA2. PIK3CA mutations were significantly associated with HER2 status and were not significantly correlated with the patient′s age, menopausal status, HR status, Ki-67 index, molecular typing, TNM stage or pCR status. Likewise, no significant correlation was found between different PIK3CA mutation status and overall survival.Conclusions:This cohort study shows the overall mutation rate of PIK3CA in breast cancer and the mutation frequencies across different molecular subtypes. The findings reveal a significant correlation between PIK3CA mutations and HER2 status, which provides a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.

For over a decade, Chinese cytopathologist has participated in the compilation of international reporting systems and subsequently promoted them widely in China; The clinical diagnostic level has significantly increased and has been widely recognized by clinical doctors in the industry; Dozens of clinical research papers have been published in international SCIE journals, among which the unique arrangement of cancer cell escape patterns was first discovered by Chinese cytology experts; Molecular detection methods are widely used in cytological specimens, and the differentiation between transient and persistent cervical HPV infection has achieved ideal results in the laboratory; The urgent need for standardized standards in clinical diagnosis has been resolved through expert consensus; Artificial intelligence assisted cervical cytology diagnosis has been applied in the screening of cervical cancer in a few hospitals and local areas.

In the past decade, significant progress has been made in the field of haematolymphoid pathology in China. Domestic experts have published nearly 100 articles in the Chinese Journal of Pathology and international authoritative journals. These achievements have deepened the fundamental theoretical research of haematolymphoid pathology and significantly improved the clinical pathological diagnosis level, providing valuable Chinese data for the pathological diagnosis and research of haematolymphoid diseases internationally. In addition, the domestic haematolymphoid pathological diagnosis and training system has been comprehensively optimized, with closer interaction and integration with clinical medicine, cultivating a large number of specialized pathologists, and driving innovation and development of the entire pathology discipline.