BACKGROUND: Lung adenocarcinoma (LUAD) is the predominant subtype of non-small cell lung cancer (NSCLC). Damage-specific DNA binding protein 1 (DDB1), as a core protein of the CUL4-DDB1 ubiquitin ligase complex, is involved in the regulation of DNA damage repair, epigenetic modification, and cell cycle checkpoint activation. While the involvement of DDB1 in tumour progression through DNA repair and RNA transcriptional regulation has been reported, its expression and role in LUAD remain to be elucidated. This study aims to investigate the expression and role of DDB1 in LUAD. METHODS: The expression, clinicopathological features and prognosis of DDB1 in LUAD were analysed using databases such as UALCAN, Kaplan-Meier Plotter and GEPIA; The interaction network and enriched functional pathways were constructed by GeneMANIA and Metascape; the correlation between DDB1 and immune cells by combining with TISIDB infiltration was evaluated, and the clustering results of cell subtypes and the expression of DDB1 in different immune cell subpopulations were analysed by single-cell sequencing; finally, tissue microarrays were used to further verify the expression and prognostic value of DDB1 in LUAD. RESULTS: The mRNA and protein expression of DDB1 in LUAD tissues were significantly higher than those in normal tissues (P<0.01), and the high expression correlated with later clinical stage (P<0.001), lymph node metastasis (P<0.001) and poor prognosis (P<0.001). Functional enrichment showed that DDB1 was involved in DNA repair and RNA transcriptional regulation, and TISIDB evaluation revealed that DDB1 was negatively correlated with the expression level of immune cells, suggesting the potential regulation of the immune microenvironment. Single cell analysis showed that DDB1 was mainly expressed in T cells, alveolar macrophages and dendritic cells. Tissue microarrays confirmed that overall survival was shorter in the DDB1 high expression group (P<0.001), and Cox multifactorial analysis showed that DDB1 was an independent predictor of LUAD prognosis. CONCLUSIONS DDB1 is highly expressed in LUAD, which is associated with poor prognosis, and is closely related to tumor immune cell infiltration, and is involved in tumourigenesis and development through DNA repair and RNA transcriptional regulation. DDB1 can be used as a potential prognostic marker and therapeutic target for LUAD.
Humans ; Adenocarcinoma of Lung/immunology* ; DNA-Binding Proteins/metabolism* ; Lung Neoplasms/diagnosis* ; Gene Expression Regulation, Neoplastic ; Prognosis ; Male ; Female ; Middle Aged

Immune checkpoint inhibitors (ICIs) have been approved for the treatment of a variety of solid tumors and hematological malignancies. Adverse reactions caused by ICIs have been gradually focused on. Cytomegalovirus (CMV) gastritis after ICIs treatment is relatively rare. Here we reported a case of advanced lung adenocarcinoma who experienced recurrent upper abdominal pain and vomiting after Pembrolizumab treatment. CMV gastritis was diagnosed through gastroscopy. The patient's symptoms improved after antiviral treatment. During the treatment of ICIs, attention should be paid to the differential diagnosis of upper abdominal pain symptoms, and vigilance should be maintained against CMV gastritis. It is difficult to differentiate CMV gastritis and immune-related gastritis judging from symptoms, and gastroscopy is important for differential diagnosis.
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Humans ; Adenocarcinoma of Lung/drug therapy* ; Cytomegalovirus/physiology* ; Cytomegalovirus Infections ; Gastritis/diagnosis* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/drug therapy*

Occult breast cancer (OBC) refers to a type of breast cancer where no primary lesion is detected through physical examination, imaging, and pathology. This report presents a clinical case of OBC with intestinal obstruction as the initial symptom. A 67-year-old female with no underlying conditions presented to Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University with intestinal obstruction. Contrast-enhanced CT of the abdomen showed thickening of the lower rectum and ascending colon, suggestive of a neoplastic lesion. Chest CT showed multiple enlarged lymph nodes in the left axilla. Colonoscopy revealed only mucosal congestion, roughness, and thickening. Suspecting an intestinal tumor, laparoscopic radical resection of the rectal stenosis was performed. Postoperative pathology indicated poorly differentiated adenocarcinoma of the rectum. Immunohistochemistry showed positive expression of estrogen receptor (ER), progesterone receptor (PR), GATA-binding protein 3 (GATA3), and cytokeratin 7 (CK7), suggesting breast cancer metastasis. Breast MRI revealed multiple proliferative nodules in both breasts (breast imaging reporting and data system, BI-RADS 2). Biopsies of the right lower-inner breast, bilateral axillary, and supraclavicular lymph nodes were performed. No carcinoma was found in the right breast tissues; however, small foci of carcinoma was detected in the right axillary lymph nodes, and poorly differentiated carcinoma of suspected breast origin was found in the bilateral supraclavicular and left axillary lymph nodes. The final diagnosis was OBC with lymph node and rectal metastasis. The patient died 16 months postoperatively. OBC often lacks identifiable primary breast lesions, and gastrointestinal metastases are particularly rare. Clinical manifestations are frequently masked by symptoms of metastatic lesions, making diagnosis challenging. Clinicians should maintain a high index of suspicion. Due to rapid disease progression and multiorgan involvement, prognosis is extremely poor. Early identification of the primary lesion in OBC is crucial for improving outcomes.
Humans ; Female ; Aged ; Intestinal Obstruction/etiology* ; Breast Neoplasms/pathology* ; Adenocarcinoma/diagnosis* ; Neoplasms, Unknown Primary/complications* ; Rectal Neoplasms/complications*

Lung cancer is the most common in incidence and mortality worldwide. With the development of next generation sequencing (NGS) detection technology, more and more patients with rare anaplastic lymphoma kinase (ALK) fusion mutations were detected. A case of advanced lung adenocarcinoma with rare COX7A2L-ALK (C2:A20) fusion detected by NGS was reported in Peking Union Medical College Hospital, and all cases with rare ALK fusion mutations were searched from medical datebase from January 1, 2014 to March 31, 2021, to investigate the treatment of rare ALK fusion mutations with ALK inhibitors. The best response of the patient was assessed as partial response (PR) with Ceritinib treatment. By literature review, 22 cases of rare ALK fusion were reported in 19 articles. Combined with this case, 23 cases were analyzed. The objective response rate (ORR) was 82.6% (19/23) and disease control rate (DCR) was 95.7% (22/23) for rare ALK fusions patients treated with ALK inhibitors. Lung adenocarcinoma patients with rare ALK fusion could benefit from ALK inhibitors.
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Humans ; Anaplastic Lymphoma Kinase/genetics* ; Lung Neoplasms/diagnosis* ; Crizotinib ; Adenocarcinoma of Lung/genetics* ; Protein Kinase Inhibitors/pharmacology* ; Oncogene Proteins, Fusion/genetics*

Objective: To analyze the clinicopathological characteristics and prognosis of patients with small bowel tumors. Methods: This was a retrospective, observational study. We collected clinicopathological data of patients with primary jejunal or ileal tumors who had undergone small bowel resection in the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between January 2012 and September 2017. The inclusion criteria included: (1) older than 18 years; (2) had undergone small bowel resection; (3) primary location at jejunum or ileum; (4) postoperative pathological examination confirmed malignancy or malignant potential; and (5) complete clinicopathological and follow-up data. Patients with a history of previous or other concomitant malignancies and those who had undergone exploratory laparotomy with biopsy but no resection were excluded. The clinicopathological characteristics and prognoses of included patients were analyzed. Results: The study cohort comprised 220 patients with small bowel tumors, 136 of which were classified as gastrointestinal stromal tumors (GISTs), 47 as adenocarcinomas, and 35 as lymphomas. The median follow-up for all patient was 81.0 months (75.9-86.1). GISTs frequently manifested as gastrointestinal bleeding (61.0%, 83/136) and abdominal pain (38.2%, 52/136). In the patients with GISTs, the rates of lymph node and distant metastasis were 0.7% (1/136) and 11.8% (16/136), respectively. The median follow-up time was 81.0 (75.9-86.1) months. The 3-year overall survival (OS) rate was 96.3%. Multivariate Cox regression-analysis results showed that distant metastasis was the only factor associated with OS of patients with GISTs (HR=23.639, 95% CI: 4.564-122.430, P<0.001). The main clinical manifestations of small bowel adenocarcinoma were abdominal pain (85.1%, 40/47), constipation/diarrhea (61.7%, 29/47), and weight loss (61.7%, 29/47). Rates of lymph node and distant metastasis in patients with small bowel adenocarcinoma were 53.2% (25/47) and 23.4% (11/47), respectively. The 3-year OS rate of patients with small bowel adenocarcinoma was 44.7%. Multivariate Cox regression-analysis results showed that distant metastasis (HR=4.018, 95%CI: 2.108-10.331, P<0.001) and adjuvant chemotherapy (HR=0.291, 95% CI: 0.140-0.609, P=0.001) were independently associated with OS of patients with small bowel adenocarcinoma. Small bowel lymphoma frequently manifested as abdominal pain (68.6%, 24/35) and constipation/diarrhea (31.4%, 11/35); 77.1% (27/35) of small bowel lymphomas were of B-cell origin. The 3-year OS rate of patients with small bowel lymphomas was 60.0%. T/NK cell lymphomas (HR= 6.598, 95% CI: 2.172-20.041, P<0.001) and adjuvant chemotherapy (HR=0.119, 95% CI: 0.015-0.925, P=0.042) were independently associated with OS of patients with small bowel lymphoma. Small bowel GISTs have a better prognosis than small intestinal adenocarcinomas (P<0.001) or lymphomas (P<0.001), and small bowel lymphomas have a better prognosis than small bowel adenocarcinomas (P=0.035). Conclusions: The clinical manifestations of small intestinal tumor are non-specific. Small bowel GISTs are relatively indolent and have a good prognosis, whereas adenocarcinomas and lymphomas (especially T/NK-cell lymphomas) are highly malignant and have a poor prognosis. Adjuvant chemotherapy would likely improve the prognosis of patients with small bowel adenocarcinomas or lymphomas.
Humans ; Prognosis ; Intestinal Neoplasms/diagnosis* ; Duodenal Neoplasms ; Gastrointestinal Stromal Tumors ; Lymphoma ; Adenocarcinoma/surgery* ; Constipation ; Abdominal Pain ; Retrospective Studies

OBJECTIVE: To investigate and summarize the clinicopathological features, immunophenotype, differential diagnosis and prognosis analysis of mucinous tubular and spindle cell carcinoma (MTSCC). METHODS: The data of thirteen cases of MTSCC were retrospectively analyzed, the clinical and pathological characteristics and immunohistochemical expression were summarized, and fluorescence in situ hybridization was detected. RESULTS: Among the thirteen patients, four were males and nine females, with a male-to-female ratio of 1 ∶2.25. The average age was 57.1 years, ranging from 39 to 78 years. The maximum diameter of the tumor was 2-12 cm. All cases had no symptoms, and were accidentally discovered, 3 cases underwent partial renal resection, 10 cases underwent radical renal resection, 9 cases were located in the left kidney, and 4 cases were located in the right kidney. Most of the cases showed the classical morphological changes, with 11 cases of nuclear grading [World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading system] being G2 and 2 cases being G3. There were 6 cases of stage PT1a, 3 cases of PT1b, 2 cases of PT2a, and 1 case of PT2b and 1 case of PT3a. The positive rates of immunohistochemical staining were: vimentin, AE1/AE3, α-methylacyl-CoA racemase (αMACR) and cytokeratin (CK) 8/18, 100% (13/13); CK7, 92.3% (12/13); epithelial membrane antigen (EMA), 92.3% (12/13); CK20, 46.2% (6/13); CD10, 30.8% (4/13); synaptophysin (Syn), 7.7% (1/13); chromogranin A (CgA), CD57, WT1 and Ki-67, 0 (0/13), and fluorescence in situ hybridization showed that no trisomy of chromosomes 7 and 17 were observed in any of the cases. The follow-up period was 6 months to 7 years and 6 months, 2 cases died after lung metastasis (one with ISUP/WHO grade G3, one with necrosis), and the remaining 11 cases had no recurrence and metastasis. CONCLUSION MTSCC is a unique type of low-grade malignancy kidney tumor, occurs predominantly in females, widely distributed in age, the current treatment method is surgical resection, and cases with necrosis and high-grade morphology are prone to recurrence and metastasis, although most cases have a good prognosis, but they still need close follow-up after surgery.
Humans ; Male ; Female ; Middle Aged ; Kidney Neoplasms/surgery* ; Carcinoma, Renal Cell/diagnosis* ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Adenocarcinoma, Mucinous/pathology* ; Kidney/pathology* ; Prognosis ; Necrosis

OBJECTIVE: To investigate the clinicopathological features of Helicobacter pylori (Hp)-negative early gastric cancer. METHODS: The clinicopathological data of 30 cases of Hp-negative early gastric cancer were collected retrospectively at Pingdingshan Medical District, 989 Hospital of PLA Joint Logistics Support Force, and Beijing Chaoyang Hospital, Capital Medical University, from 2009 to 2021, and the histomorphological characteristics and immunophenotype were observed, and combined with the literature to explore. RESULTS: The median age of 30 patients was 58.5 years (range: 21-80 years), including 13 males and 17 females. The upper part of the stomach was 13 cases, the middle part of the sto-mach was 9 cases, and the lower part of the stomach was 8 cases. The median diameter of the tumor was 11 mm (range: 1-30 mm). According to the Paris classification, 9 cases were 0-Ⅱa, 7 cases were 0-Ⅱb, and 14 cases were 0-Ⅱc. Endoscopic examination showed that 18 cases of lesions were red, 12 cases of lesions were faded or white, and microvascular structures and microsurface structures were abnormal. In all the cases, collecting venules were regularly arranged in the gastric body and corner mucosa. There were 18 cases of well differentiated adenocarcinoma in the mucosa. The tumor presented glandular tubular-like and papillary structure, with dense glands and disordered arrangement; the cells were cuboidal or columnar, with increased nuclear chromatin and loss of nuclear polarity, and most of them expressed gastric mucin. Signet-ring cell carcinoma was found in 7 cases, all the cancer tissues were composed of signet-ring cells, and the cancer cells were mainly distributed in the middle layer to the surface layer of mucosa. Gastric oxyntic gland adenoma (gastric adenocarcinoma of the fundic gland type confined to mucosa) in 2 cases, gastric adenocarcinoma of the fundic gland type in 2 cases, and gastric adenocarcinoma of fundic gland mucosa type in 1 case. The tumor tissue was composed of branching tubular glands, except 1 case of mucosal surface epithelium was partially neoplastic, the other 4 cases of mucosal surface epi-thelium were all non-neoplastic; the cells were arranged in a single layer, and the nucleus was close to the basal side, and the nucleus was only slightly atypical. Pepsinogen I and H⁺/K⁺ ATPase were positive in 5 cases of gastric fundus gland type tumors, and 1 case of foveolar-type tumor cells at the surface and depth of mucosa showed MUC5AC positive. The gastric mucosa adjacent to cancer was generally normal in all cases, without atrophy, intestinal metaplasia and Hp. CONCLUSION Hp-negative early gastric cancer is a heterogeneous disease group with various histological types, and tubular adenocarcinoma and signet-ring cell carcinoma are common. Tubular adenocarcinoma mostly occurs in the elderly and the upper to middle part of the stomach, while signet-ring cell carcinoma mostly occurs in young and middle-aged people and the lower part of the stomach. Gastric neoplasm of the fundic gland type is relatively rare.
Male ; Aged ; Middle Aged ; Female ; Humans ; Young Adult ; Adult ; Aged, 80 and over ; Stomach Neoplasms/pathology* ; Helicobacter pylori ; Retrospective Studies ; Helicobacter Infections/diagnosis* ; Adenocarcinoma/pathology* ; Carcinoma, Signet Ring Cell/pathology*

Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.
Humans ; Female ; Middle Aged ; Carcinoma, Endometrioid/pathology* ; Uterine Cervical Neoplasms/pathology* ; Human Papillomavirus Viruses ; Papillomavirus Infections/pathology* ; Uterus/pathology* ; Adenocarcinoma/diagnosis*

Objective: To explore the feasibility and application value of intraoperative direct immunohistochemical (IHC) staining in improving the diagnosis accuracy in difficult cases of bronchiolar adenoma (BA). Methods: Nineteen cases with single or multiple pulmonary ground-glass nodules or solid nodules indicated by imaging in Cancer Hospital of Chinese Academy of Medical Sciences from January to July 2021 and with difficulty in differential diagnosis at frozen HE sections were selected. In the experimental group, direct IHC staining of cytokeratin 5/6 (CK5/6) and p63 was performed on frozen sections to assist the differentiation of BA from in situ/micro-invasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the control group, two pathologists performed routine frozen HE section diagnosis on these 19 cases. The diagnostic results of paraffin sections were used as the gold standard. The sensitivity and specificity of BA diagnosis, consistency with paraffin diagnosis and time used for frozen diagnosis were compared between the experimental group and the control group. Results: The basal cells of BA were highlighted by CK5/6 and p63 staining. There were no basal cells in the in situ/microinvasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the experimental group, the sensitivity and specificity with aid of direct IHC staining for BA were 100% and 86.7%, respectively, and the Kappa value of frozen and paraffin diagnosis was 0.732, and these were significantly higher than those in the control group (P<0.05). The average time consumption in the experimental group (32.4 min) was only 7 min longer than that in the control group (25.4 min). Conclusions: Direct IHC staining can improve the accuracy of BA diagnosis intraoperatively and reduce the risk of misdiagnosis, but require significantly longer time. Thus frozen direct IHC staining should be restricted to cases with difficulty in differentiating benign from malignant diseases, especially when the surgical modalities differ based on the frozen diagnosis.
Humans ; Paraffin ; Sensitivity and Specificity ; Adenocarcinoma in Situ ; Adenoma/diagnosis* ; Adenocarcinoma, Mucinous/surgery* ; Frozen Sections/methods*

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Adenocarcinoma ; Biomarkers, Tumor/genetics* ; Colorectal Neoplasms/pathology* ; DNA Mismatch Repair ; DNA-Binding Proteins/genetics* ; Epstein-Barr Virus Infections/diagnosis* ; Herpesvirus 4, Human/metabolism* ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Tibet ; Young Adult ; Aged, 80 and over