Clinicopathological features and prognosis of SMARCA4-deficient non-small cell lung carcinoma: an analysis of 127 cases / 中华病理学杂志

Objective: To investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer. Methods: The clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital, Shanghai, China from January 2020 to March 2022. The variation and expression of biomarkers related to treatment were retrospectively reviewed. Results: One hundred and twenty-seven patients were eligible for enrollment. Among them 120 patients (94.5%) were male and 7 cases (5.5%) were female, while the average age was 63 years (range 42-80 years). There were 41 cases (32.3%) of stage Ⅰ cancer, 23 cases (18.1%) of stage Ⅱ, 31 cases (24.4%) of stage Ⅲ and 32 cases (25.2%) of stage Ⅳ. SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases (92.1%) and partially absent in 10 cases (7.9%). PD-L1 immunohistochemical analyses were performed on 107 cases. PD-L1 was negative, weakly positive and strongly positive in 49.5% (53/107), 26.2% (28/107) and 24.3% (26/107) of the cases, respectively. Twenty-one cases showed gene alterations (21/104, 20.2%). The KRAS gene alternation (n=10) was most common. Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females, and was associated with positive lymph nodes and advanced clinical stage (P<0.01). Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor, and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection. Conclusions: SMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis, and often occurs in elderly male patients. However, SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients. Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor. Early detection and access to treatment are important for improving patient survivals.

Primary lung salivary gland-type duct carcinoma: a clinicopathological analysis of two cases and review of literature / 中华病理学杂志

Objective: To investigate the clinicopathological features, diagnostic criteria and differential diagnosis of primary salivary gland-type duct carcinoma of lung(LSDC). Methods: Two patients with LSDC after surgical resection in Shanghai Pulmonary Hospital from 2020 to 2021 were included; their clinical parameters as well as pathological, immunohistochemical and molecular characteristics of the tumors were analyzed. The relevant literature was also reviewed. Results: Both patients were male, aged 49(case 1) and 64(case 2) years, respectively, and with a history of smoking. The chest computed tomography scan showed both lesions to be centrally located. Gross examination showed the maximum diameters were 16 mm and 35 mm, respectively. The histomorphology of LSDC resembled ductal carcinoma of breast, with intraductal islands of neoplastic cells, which also formed solid nests, papillary, micropapillary and cribriform structures. There was frequent accompanying comedo-like necrosis. The neoplasm cells were markedly heteromorphic, possessing large irregular nuclei with prominent nucleoli, abundant eosinophilic or clear cytoplasm, and mitotic figures were common. Both cases of LSDC were immunoreactive for CKpan, CK7, AR, HER2 staining was (2+) and were negative for TTF1, Napsin A, p40, GATA3, mammaglobin, GCDFP15, SOX10, PSA, P504S, ER, PR, vimentin, S-100, SMA, CK5/6 and p63. The tumor showed double-layer cell structure of the duct, and some basal cells/myoepithelial cells expressed p40 and CK5/6. Case 1 had no gene mutation while case 2 harbored TP53 and KMT2A gene mutation detected by next generation sequencing. Conclusions: LSDC is a very rare and highly aggressive salivary-type malignant tumor. The postoperative diagnosis mainly depends on histopathology and immunohistochemistry, attention should be paid to differential diagnosis to prevent missed diagnosis.

Analysis of Clinicopathological Characteristics and Prognosis of 112 Patients with Primary Waldeyer's Ring Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and pathological characteristics of patients with primary Waldeyer's ring lymphomas (PWRL), and to analyze its therapeutic efficacy and prognostic factors.</p><p><b>METHODS</b>A total of 112 patients with PWRL confirmed by pathological and immunohistochemical methods between January 2009 and January 2014 were studied. Clinical data were collected and analyzed retrospectively.</p><p><b>RESULTS</b>PWRL accounted for 3.9% of lymphoma over the same period. Median age of patients with PWRL was 51.5 years old. The affected areas were tonsil, nasopharynx, tongue base and oropharynx, which accounted for 63.4% (71/112), 22.3% (25/112), 5.3% (6/112) and 4.5% (5/112) respectively. The most common pathological types of these four areas were diffused large B-cell lymphoma (DLBCL) and extranodal NK/T cell lymphoma (NKTCL) which accounted for 58% and 15.2%. The overall response rate (CR/CRu = 51.4%; PR = 30.8%) in all patients was 82.2%, the estimated 5-year overall survival (OS) rate were 71.6%. The 5-year OS rate were 94.7% in the group used Rituximab. Meanwhile, chemotherapy combined with radiotherapy could improve the outcome of T-cell PWRL patients and the 5-year OS rate were 88.9%. Age, disease stages, pathological types, IPI scores, LDH level, β2-MG level and the efficacy of initial therapy were prognostic factors with statistical significance. Cox multivariate analysis showed that age of more than 60 years, LDH level, pathological types and the efficacy of the initial therapy were independently associated with OS.</p><p><b>CONCLUSION</b>PWRL has a relatively good prognosis. The pathological types affect the prognosis directly and guide treatment. Combined modality therapy should be chosen for patients with PWRL. Patients with T-cell PWRL should accept chemotherapy combined with radiotherapy, while rituximab may be better for B-cell PWRL. The efficacy of initial therapy is crucial for the outcome of patients. Age and LDH level are also important prognostic factors.</p>

Cloning and characterization of down-regulated genes in neural tube defects of golden hamster induced by hyperthermia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To clone down-regulated genes in neural tube defects of golden hamster induced by hyperthermia and to explore the molecular mechanism.</p><p><b>METHODS</b>A reversed subtractive cDNA library was constructed using suppression subtractive hybridization. Clones with inserts were selected by combination of alpha complementary phenomenon and colony PCR. Then sequence and homology analysis of the inserts were made. And mRNA expression conditions were confirmed by Northern blot.</p><p><b>RESULTS</b>The reversed subtractive cDNA library was successfully constructed. Fifteen recombinant clones were sequenced and recognized homologous to known genes. The results of Northern blot showed that all these genes were down-regulated in defected neural tubes induced by hyperthermia compared to normal developed neural tubes.</p><p><b>CONCLUSION</b>Some important genes are identified which might be involved in neural tube defects induced by hyperthermia.</p>