A 54-year-old, non-smoking woman was diagnosed as stage ⅣB adenocarcinoma with widespread bone metastasis (cT4N2M1c) in the First Affiliated Hospital, Zhejiang University School of Medicine. Immunohistochemistry result showed the presence of anaplastic lymphoma kinase (ALK) gene rearrangement; next-generation sequencing (NGS) indicated EML4-ALK fusion (E6:A20) with concurrent CCDC148-ALK (C1:A20), PKDCC-ALK (Pintergenic:A20)and VIT-ALK (V15:A20) fusions. After 32 weeks of alectinib treatment, the patient complained cough and exertional chest distress but had no sign of infection. Computed tomography (CT) showed bilateral diffuse ground glass opacities, suggesting a diagnosis of alectinib-related interstitial lung disease (ILD). Following corticosteroid treatment and discontinuation of alectinib, clinical presentations and CT scan gradually improved, but the primary lung lesions enlarged during the regular follow-up. The administration of crizotinib was then initiated and the disease was stable for 25 months without recurrence of primary lung lesions and ILD.
Female ; Humans ; Middle Aged ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Crizotinib/therapeutic use* ; Lung Neoplasms/drug therapy* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Lung Diseases, Interstitial/diagnosis*

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.
Humans ; Carcinoma/diagnosis* ; Oropharyngeal Neoplasms/diagnosis* ; Retrospective Studies ; Neoplasms, Second Primary/diagnosis*

Oropharyngeal carcinoma is one of the most common malignant tumors of head and neck. In recent years, the incidence of Human papilloma virus-associated oropharyngeal squamous cell carcinoma（HPV-OPSCC） has been increasing year by year. With the advancement of minimally invasive surgical techniques, the wide application of intensity modulated radiation therapy, and the demand of patients for organ function protection and higher quality of life, the unique biological behavior and better prognosis of HPV-OPSCC have led to the exploration of a series of attenuated treatment modes. This article reviews the diagnosis and treatment status of oropharyngeal cancer and related research progress based on relevant reports.
Humans ; Papillomavirus Infections/diagnosis* ; Quality of Life ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Head ; Human Papillomavirus Viruses ; Oropharyngeal Neoplasms/therapy* ; Head and Neck Neoplasms

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 compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM). METHODS: We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient. RESULTS: In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05). CONCLUSION ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.
Female ; Male ; Humans ; Adult ; Middle Aged ; Aged ; Carcinoma, Renal Cell/diagnosis* ; Retrospective Studies ; Kidney ; Carcinoma ; Kidney Neoplasms/diagnosis*

Objective: To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma (SOC). Methods: Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2015 to July 2021, including ascites from 32 SOC, 10 gastrointestinal adenocarcinomas, 5 pancreatic ductal adenocarcinomas, 6 lung adenocarcinomas, 4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients, pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma. Serous cavity effusion samples of all patients were collected, conventional smears were made through centrifugation, and cell paraffin blocks were made through centrifugation of remaining effusion samples. Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics. The levels of serum tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected. Results: Of the 32 SOC patients, 5 had low-grade serous ovarian carcinoma (LGSOC) and 27 had high-grade serous ovarian carcinoma (HGSOC). 29 (90.6%) SOC patients had elevated serum CA125, but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study (P>0.05); The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.001); The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.05). The serum CA125, CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia. LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern, and psammoma bodies could be observed in some LGSOC cases. The background cells were fewer and lymphocytes were predominant; the papillary structure was more obvious after making cell wax blocks. HGSOC tumor cells were highly heterogeneous, with significantly enlarged nuclei and varying sizes, which could be more than 3-fold different, and nucleoli and nuclear schizophrenia could be observed in some cases; tumor cells were mostly clustered into nested clusters, papillae and prune shapes; there were more background cells, mainly histiocytes. Immunocytochemical staining showed that AE1/AE3, CK7, PAX-8, CA125, and WT1 were diffusely positively expressed in 32 SOC cases. P53 was focally positive in all 5 LGSOCs, diffusely positive in 23 HGSOCs, and negative in the other 4 HGSOCs. Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery, and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests. Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic "open window" phenomenon. Conclusion: Combining the clinical manifestations of the patient, the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC, and the immunocytochemical tests can further improve the accuracy of the diagnosis.
Female ; Humans ; Carcinoembryonic Antigen ; Ascites ; CA-19-9 Antigen ; Mesothelioma, Malignant/diagnosis* ; Hyperplasia ; Adenocarcinoma/pathology* ; Cystadenocarcinoma, Serous/diagnosis* ; Biomarkers, Tumor ; Carcinoma, Ovarian Epithelial ; Diagnosis, Differential ; Ovarian Neoplasms/pathology* ; Carbohydrates

Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ²=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ²=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ² =4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ²=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/diagnosis* ; alpha-Fetoproteins/analysis* ; Biomarkers, Tumor ; Glypicans ; Ascites ; Venous Thromboembolism ; Peritoneal Neoplasms ; Liver Cirrhosis

Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ²=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ²=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.
Pregnancy ; Humans ; Female ; Adult ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervical Dysplasia/pathology* ; Biopsy ; Colposcopy/methods* ; Squamous Intraepithelial Lesions/pathology* ; Carcinoma in Situ/pathology* ; Papillomaviridae/genetics* ; Papillomavirus Infections/diagnosis* ; Squamous Intraepithelial Lesions of the Cervix/pathology*