BackgroundHistological transformation of lung cancer to small cell lung cancer (SCLC) is uncommon. It is a small subset of the possible resistance mechanisms, even in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors. Reports on programmed cell death-1 (PD-1) inhibitors are rare. We report two cases of lung squamous carcinomas that transformed to SCLC during anti-PD-1 therapy, and present a detailed description of histological examination of the pre-and post-transformation tissues, hitherto absent from reports on the topic.Case PresentationCase 1: A 69-year-old man was diagnosed with stage IVa squamous cell carcinoma of the lung. He had a programmed cell death-ligand 1 tumor proportion score ≥50%. He achieved partial response after four cycles of sintilimab as first-line treatment. However, sintilimab was discontinued because of severe decrease in hemoglobin levels and platelet counts. Moreover, the occurrence of pleural effusion favored disease progression. Interestingly, bone marrow puncture and biopsy showed transformation to SCLC. Case 2: A 71-year-old man diagnosed with stage IIIa lung squamous cell carcinoma received neoadjuvant chemotherapy, underwent radical surgery, and finally received adjuvant chemotherapy. Five months later, he presented with tumor recurrence. He was treated with nivolumab, though disease progression was observed after four cycles. Notably, a subsequent computed tomography-guided biopsy showed SCLC.ConclusionPhenotypic transformation to SCLC is a potential mechanism of resistance to immunotherapy in squamous cell carcinomas of the lung. Disease progression should prompt re-biopsy to diagnose potential histological changes to assess the requirement for change in treatment.

Purpose Talaromyces marneffei (TM) is a pathogenic fungus endemic in Southeast Asia and human immunodeficiency virus (HIV)-positive populations, but studies related to non-endemic areas and HIV-negative populations are still limited. Therefore, this study aims to provide more additional evidence for clinical work of talaromycosis. Methods To collect clinical information of patients with talaromycosis admitted to hospitals in Zhejiang Province, China from January 1, 2010 to May 31, 2020, retrospectively analyzed clinical characteristics and prognosis, COX multivariate regression analysis was used for survival analysis. Results A total of 92 patients were enrolled, including 76 males, 73 HIV-positive patients, with an average age of 40.1 ± 13.0. Compared to HIV-positive group, the negative group had higher admission age (47.7 ± 14.6 vs 38.1 ± 11.9, p = 0.003) and lower proportion of male (89.0% vs 57.9%, p = 0.004), there was no significant difference in imaging of lungs. There were significantly more HIV-positive patients in those with pleural effusion (100% vs 69.4%, p = 0.001). COX multivariate regression analysis suggested pleural effusion (HR = 3.220; 95% CI 1.117-9.287; p = 0.030) and HIV infection (HR = 0.057; 95% CI 0.009-0.370; p = 0.003) which were independent predictors of prognosis in patients with talaromycosis. Conclusions In non-endemic areas, clinical symptoms, signs, and laboratory tests of patients with talaromycosis are similar to those in endemic areas. Patients with pleural effusion have lower survival rate, HIV-infected people are less likely to relapse, and there is no significant correlation between extent of lung involvement and survival of infected patients.

Talaromyces marneffei is a rare dimorphic pathogenic fungus that can induce severe infections in human immunodeficiency virus (HIV)-infected patients. However, such infections have also been reported in non-HIV hosts. This current case report describes a very rare case of a T. marneffei pulmonary infection in an HIV-negative patient with a mutation in the tuberous sclerosis complex subunit 2 ( TSC2) gene. A 24-year-old male patient presented with cough and expectoration for 6 months. Computed tomography showed multiple ground-glass opacities and cystic and cavitated lesions in both lungs. Next generation sequencing (NGS) of the bronchoalveolar lavage fluid was performed to confirm T. marneffei pulmonary infection. The results were further verified using bronchoscopy specimen cultures. This was an HIV-negative patient without a travel history to endemic zones and his blood exon sequencing results showed a mutation in the TSC2 gene. To date, he has recovered well with voriconazole therapy. In summary, patients with TSC2 mutations that induce bronchopulmonary dysplasia may be potential hosts for T. marneffei. Early and timely diagnosis is important for improving prognosis. NGS plays a critical role in the diagnosis of T. marneffei pulmonary infection.

BACKGROUND Primary pulmonary enteric adenocarcinoma (PEAC) is a very rare subtype of invasive adenocarcinoma, and there have been no large studies on PEAC to date. Therefore, it is necessary to obtain much more information about the clinical and pathological features, diagnosis, differential diagnosis, and treatment of PEAC. CASE SUMMARY All clinical data of six patients with confirmed PEAC from 2013 to 2018 were collected, and data on diagnosis, differential diagnosis, and treatment of PEAC are discussed combined with all the associated literature. The mean age of six patients was 64.0 ± 5.6 (59-73) years old. Their clinical manifestations were heterogeneous, and during their disease course, there were no gastrointestinal symptoms. There was no evidence from colonoscopy or imaging studies to suggest digestive tract tumors or new metastases. The most commonly mutated gene was KRAS (50.0%), and the pathological features of the six cases were similar to those of colorectal cancer. CDX2 (83.3%) and CK7 (66.7%) had the highest positive rates upon immunohistochemical examination. In the associated literature, 252 cases were identified, and the most commonly mutated gene was KRAS (42.9%). Additionally, CDX2 (68.3%) and CK7 (85.8%) had the highest positive rates. Patients mainly received surgery, chemotherapy, and radiotherapy, immunotherapy was not included. CONCLUSION Positive results for CDX2 and CK7 play an important role in the diagnosis and differential diagnosis of PEAC, and immunotherapy or targeted therapy focused on KRAS needs to be further studied for the treatment of PEAC.

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