Clinicopathological analysis of 23 cases of primary pulmonary mucoepidermoid carcinoma

Primary pulmonary high-grade mucoepidermoid carcinoma (MEC) with a cystic airspace is uncommon, and early metastasis is extremely rare. In such cases, however, it is clinically important for clinicians to consider whether the tumor has spread to the lymph nodes through the cystic airspace. A 77-year-old man presented to our hospital with cough and hemoptysis. Chest computed tomography showed a 25-mm-diameter mass with a cystic airspace located in the upper lobe of the left lung. The possibility of malignancy was considered. Without a definitive preoperative diagnosis, left upper lobectomy and mediastinal lymphadenectomy were performed. Histopathological examination revealed the typical histological characteristics of high-grade MEC (stage IA) and no lymph node metastasis. However, lymph node metastasis was found 6 months after surgical resection, and radiochemotherapy was performed. The patient developed widespread metastatic disease 4 months following completion of radiochemotherapy and died 2 months later. Primary pulmonary MEC with a cystic airspace is a rare malignant disease with uncommon imaging findings. Complete surgical resection is the main treatment method for high-grade MEC. In this case, we hypothesize that early metastasis was caused by seeding of tumor cells through the cystic airspace.

IntroductionPulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm of the lung and the main salivary gland-type lung carcinoma. The aims of this study were to review the clinicopathological and immunohistochemical features of PMEC and characterize the genetic events in PMEC.MethodsWe reviewed the pathology cases in our hospital and found 34 initially diagnosed PMEC cases, 26 of which were confirmed as PMEC after excluding 8 cases of MEC-like pulmonary carcinoma. The clinicopathological characteristics of the 26 PMEC cases and the 8 cases of MEC-like pulmonary carcinoma were retrospectively reviewed. MAML2 rearrangement was detected by fluorescence In Situ Hybridization (FISH). Immunostains of ALK, calponin, collagen IV, CK7, EGFR, HER2, Ki-67, Muc5Ac, p63, p40, and TTF-1 were performed. DNA was extracted from 23 cases of PMEC. Mutation profiling of the EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 genes were carried out using next-generation sequencing (NGS), Sanger sequencing, and quantitative polymerase chain reaction (QPCR) in 9 successfully amplified cases.ResultsTwenty-six cases of PMEC (18 low-grade, 8 high-grade) included 13 men and 13 women aged 12–79 years. Twenty-two cases had a central/endobronchial growth pattern, and 4 cases had a peribronchial growth pattern. Immunohistochemically, CK7, Muc5Ac, p40, and p63 were positive in all cases (26/26);EGFR was positive in 11 cases (11/26); TTF-1, Calponin, HER2 and ALK were negative in all cases (0/26). MAML2 rearrangement was identified in 12 of 18 PMEC cases. No mutations were detected in any of the 7 genes in the 9 cases that qualified for mutation analysis. Twenty-three PMEC patients had follow-up information with a median interval of 32.6 months. Both the 5- and 10-year overall survival rates (OS) were 72.1%, and a high-grade tumor was an adverse prognostic factor in PMEC. There were 8 cases of MEC-like pulmonary carcinoma aged 36–78 years: 2 cases were located in the bronchus, and 6 cases were located in the lung. p63 and TTF-1 were positive in all cases (8/8), p40 was positive in 5 cases (5/8), and ALK was positive in 5 cases (5/8). No cases of MAML2 rearrangement were detected, but there were 5 cases of ALK rearrangement.ConclusionsPMEC is a primary malignant pulmonary tumor with a relatively good prognosis that is historically characterized by the presence of mucous cells and a lack of keratinization. There are distinct differences between PMEC and MEC-like pulmonary carcinoma in tumor location preference, immunophenotype, and molecular genetics, and the differential diagnosis is critical due to the therapeutic and prognostic considerations.

Objective: To investigate MAML2 gene rearrangement, gene fusion patterns, and the clinicopathological characteristics of primary pulmonary mucoepidermoid carcinoma (PMEC). Methods: Forty-six cases of primary PMEC from Fudan University Zhongshan Hospital and Fudan University Shanghai Cancer Center between 2017 and 2020 were collected. MAML2 gene rearrangement in all cases was detected by fluorescence in situ hybridization (FISH). In 20 cases, MAML2 fusion patterns were detected by targeted RNA sequencing (RNAseq). The relationship between MAML2 gene rearrangement, fusion patterns, clinicopathological characteristics, and prognosis was analyzed. Results: The average age of PMEC patients was 41 years (range 15-71 years); the ratio of male to female was about 1.1 ∶ 1.0. Most PMECs were low grade in histopathology with an early clinical stage (stageⅠ-Ⅱ).The overall positive rate of MAML2 gene rearrangement detected by FISH was about 80.4% (37/46), and the rate was higher in low-grade PMEC (91.7%, 33/36). Of the 20 cases detected by RNAseq, all the 19 FISH positive cases showed gene fusion, mainly CRTC1-MAML2 fusion (16/19), the other three cases showed CRTC3-MAML2 fusion (3/19), the break point of all the fusion patterns was CRTC1/3 (exon 1)-MAML2 (exon 2); No gene fusion was detected in the single FISH negative case; Compared with the MAML2 FISH negative patients, the PMECs carrying CRTC1-MAML2 fusion were more commonly found in patients age ≤ 40 years, maximum tumor diameter ≤ 2 cm, low histopathological grade and early clinical stage (all P<0.05); The three PMECs carrying CRTC3-MAML2 fusion gene were all female with early clinical stage; Univariate analysis showed that MAML2 gene rearrangement/fusion, onset age ≤ 40 years old, smaller tumor size, low histopathological grade, early clinical stage, no metastasis at diagnosis and surgical treatment were significantly correlated with overall survival (P<0.05), but Cox regression analysis suggested that none of the above indicators were the independent prognostic factors for the survival of PMEC. Conclusions: The high incidence of MAML2 gene rearrangement in PMEC suggests that it is an important molecular diagnostic marker of PMEC. RNAseq confirms that CRTC1/3-MAML2 is the main fusion pattern in PMEC, suggesting that MAML2 fusion transcription may be an important driving factor of PMEC. MAML2 rearrangement/fusion and related clinicopathological characteristics are associated with good prognosis.

BackgroundMucoepidermoid carcinoma is dominant in salivary glands and rarely occurs in the lung. Primary pulmonary mucoepidermoid carcinoma is a type of non-small-cell lung cancer, but the prognostic factors in Chinese patients remain controversial. This investigation aimed to review cases of pulmonary mucoepidermoid carcinoma, analyse the prognosis of this disease.MethodsPatients with pathologically proven pulmonary mucoepidermoid carcinoma were screened at the Department of Respiratory and Critical Care Medicine at the Peking University Third Hospital, Beijing Friendship Hospital Affiliated to Capital Medical University, and Peking University Cancer Hospital for inclusion in this retrospective study. Demographic data, including age, sex, clinical symptoms, smoking, alcohol consumption, allergies, family history, imaging findings, fibrobronchoscopy findings, surgical procedures, tumour location and pathologic stage, were collected. Telephone follow-up was conducted for all patients not lost to follow-up. The associations of sex, age, smoking, tumour differentiation, tumour size, lymph node metastasis, pathologic stage, and patient survival were retrospectively analysed. Kaplan–Meier, univariate and multivariate analysis curves were used to analyse patient prognosis and prognostic factors.ResultsThirty-one patients, comprising 23 males and 8 females, were enrolled in the analysis. The mean age was 60.77 ± 11.44 years. The first symptom was nonspecific, with cough being the most common (21/31, 67.77%); smokers accounted for 16 of the 31 patients, and ten patients had a history of alcohol consumption. Overall, the tumours could occur in either lobe of the lungs; tumours occurred in the right lung in 19/31 patients, and tumours occurred in the left lung in 12/31 patients. Regarding TNM stage, 10 patients had stage I (5 with stage 1a, 5 with stage 1b), 5 had stage II (1 with stage 2a, 4 with stage 2b), 3 had stage III (1 with stage 3a, 2 with stage 3b), and 13 had stage IV (10 with stage 4a, 3 with stage 4b). In our Cox univariate survival analysis of patients with pulmonary mucoepidermoid carcinoma, we found that TNM stage IV, degree of differentiation and lymph node metastasis were risk factors for pulmonary mucoepidermoid carcinoma and that degree of differentiation was an independent risk factor.ConclusionThe clinical, radiographical and pathological features of pulmonary mucoepidermoid carcinoma were systemically analysed and summarized, and the degree of differentiation and lymph node metastasis, as well as prognostic factors in addition to clinical stage, were confirmed.

Objective: To investigate MAML2 gene-translocation in primary pulmonary mucoepidermoid carcinoma (PMEC) and pulmanary adenosquamous carcinoma, and the optimal diagnostic immunohistiochemical (IHC) panel in distinguishing PMEC from adenosqumous carcinoma. Methods: Twenty-four cases of PMEC and 44 adenosqumous carcinoma diagnosed in the Guangdong General Hospital were tested for MAML2 translocation by fluorescent in-situ hybridization (FISH) using tissue array. An IHC panel including TTF1, Napsin A, CK5/6, p63, p40 and Ki-67 was performed on the cohort. The clinical data for all cases were collected and all PMEC patients had follow-up information. Results: The patients' age ranged form 6 to 73 years, with a median age of 32 years. The male to female ratio was 1.4∶1.0. MAML2 translocation was found in 16/24 (66.7%) cases of PMEC whereas all 44 cases adenosqumous carcinoma were negative for translocation. All the cases of the PMEC were negative for TTF1 and Napsin A but positive for CK5/6, p63 and p40 in the intermediate cells and epidermal-like cells. In most PMEC cases, the Ki-67 expression index was lower than 10%. In contrast, most cases of adenosqumous carcinomas expressed TTF1 and Napsin A in the adenomatous component and CK5/6, p63 and p40 in the squamous component, which expression pattern was different from that of PMEC. Based on IHC staining, 2 cases of highly invasive ALK-positive adenocarcinoma mimicing PMEC were also found in the study. Conclusions: MAML2 gene translocation can be detected in about two-third of PMEC. Translocation of MAML2 gene and lower morphology grading are associated with good prognosis. The combined use of IHC antibodies panel is helpful to distinguish PMEC from the adenosqumous carcinoma and adenocarcinoma mimicing PMEC.

Primary pulmonary mucoepidermoid carcinoma: Cyto-histologic correlation and review of the literature

The differential diagnosis of primary pulmonary mucoepidermoid carcinoma (PMEC) and pulmonary adenoid cystic carcinoma (PACC) is difficult, because both tumors could be similar in terms of certain characteristics on CT. The CT findings from 24 cases of PMEC and 30 cases of PACC were retrospectively analyzed. According to the position of the lesion in airway, we divided these cases into three types: central, hilar, and peripheral. In PMEC, there were 7 cases of central type, 14 cases of hilar type, and 3 cases of peripheral type. And, 57.1% PMEC cases of the hilar type were accompanied by distal bronchial dilatation with mucoid impaction. Patchy areas of low density were observed in 79.2% cases of PMEC. The solid part of most lesions showed moderate (37.5%) or severe enhancement (45.8%). However, in PACC, there were 24 cases of central type, 3 cases of hilar type, and 3 cases of peripheral type. PACC had more cases of central type than PMEC. Moreover, longitudinal extent greater than 3 cm was observed in 62.5% PACC cases of the central type, while infiltration of the luminal perimeter more than 1/2 perimeter was observed in 95.8% PACC cases of the central type. Patchy areas of low density were observed in 26.7% cases of PMEC. In PACC cases, the solid part of 76.7% lesions showed slight enhancement. Cavities could be observed in PMEC, but not in PACC. PMEC and PACC have different CT features in various airway locations. PMEC is usually the hilar type, accompanied by distal bronchial dilatation with mucoid impaction. However, PACC is usually the central type, with longitudinal extent greater than 3 cm and infiltration of the luminal wall more than 1/2 perimeter. Patchy areas of low density and moderate or severe enhancement are more prominent in PMEC. However, slight enhancement is more common in PACC.

8586 Background: Primary pulmonary NUT carcinoma is an exceedingly rare and aggressive malignancy characterized by chromosomal rearrangements involving the NUT gene. With limited therapeutic options and an extremely poor prognosis, treatment strategies have focused on identifying effective targeted and immunotherapeutic approaches. Pembrolizumab, an anti-PD-1 immune checkpoint inhibitor, has shown promise in various malignancies, particularly those with high tumor mutational burden or PD-L1 expression. However, despite its use, its efficacy in NUT carcinoma remains poorly understood due to the rarity of this disease and a paucity of robust clinical data. This systematic review and meta-analysis aim to explore the available evidence on the clinical data of pembrolizumab in treating primary pulmonary NUT carcinoma, focusing on progression-free survival (PFS), and overall survival (OS) by consolidating outcomes from case reports and case series. Methods: A systematic review and meta-analysis were conducted to evaluate the effectiveness of pembrolizumab in the treatment of primary pulmonary NUT carcinoma. A comprehensive search of PubMed, Embase, and Cochrane was performed for articles published between January 2014 and December 2024, using the keywords “pembrolizumab,” “Pulmonary NUT carcinoma,” and “NUT midline carcinoma.” Inclusion criteria included reports of patients treated with either pembrolizumab monotherapy or pembrolizumab in conjunction with other therapies for Primary Pulmonary NUT Carcinoma for any duration. Reports that did not mention PFS or OS were excluded. Results: A total of 39 reports involving 56 patients with primary pulmonary NUT carcinoma treated with pembrolizumab, either in conjunction with other therapies or monotherapy, were analyzed. The median overall survival (OS) was 7.3 months (95% CI: 5.2–8.8), and the median progression-free survival (PFS) was 4.6 months (95% CI: 3.1–5.7). Among three patients receiving pembrolizumab monotherapy as a second-line or later treatment, the median PFS was 2.9 months. Conclusions: Pembrolizumab has been explored as second-line or later therapy for primary pulmonary NUT carcinoma based on its success in treating NSCLC. Our analysis revealed a median progression-free survival of 4.6 months and a median overall survival of 7.3 months for patients with primary pulmonary NUT carcinoma receiving pembrolizumab, illustrating the continuing challenge of treating this rare malignancy. Importantly, there are no randomized controlled trials investigating pembrolizumab in this rare malignancy, highlighting a critical gap in evidence. Prospective clinical trials and further research into biomarkers predictive of treatment response are urgently needed to optimize therapeutic strategies and improve outcomes for patients with this aggressive disease.

IntroductionPrimary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19) resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied.MethodsWe detected MAML2 rearrangement using fluorescence in situ hybridization (FISH) in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC), and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC). The findings were then examined regarding the clinicopathological parameters and patient outcomes.ResultsFISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001) and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively). Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023) or disease-free survival (p = 0.027) as well as correlation between FLT1 and overall survival (p = 0.009).ConclusionsMAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC.

Clinicopathological and multisection CT features of primary pulmonary mucoepidermoid carcinoma

To investigate the clinicopathological features and epidermal growth factor receptor (EGFR) gene mutation of primary pulmonary mucoepidermoid carcinoma (PMC). Fifth-five cases of PMC were included in the study; their clinicopathological, immunohistochemical features were evaluated, and in 31 cases, paraffin embedded specimens were subjected to mutation analysis of exons 18, 19, 20 and 21 of the EGFR gene by ARMS method. There were 32 females and 23 males. The patients' age ranged from 11 to 68 years(mean 36 years). The tumor size ranged from 0.7 to 5.5 cm(mean 2.4 cm). The tumors were located in the segmental bronchus and upper segmental bronchus. The tumors were well-demarcated, had no obvious capsules, and protruded into the bronchial lumen. Microscopically, there were three types of tumor cells including squamous cells, mucin-producing cells and intermediate cells. Fifty-three cases were low grade, two were high grade and both showed lymph node metastases. Immunohistochemically the tumor cells were uniformly negative for TTF1, Napsin A and ALK (Ventana D5F3) in all 55 cases. The tumor cells were positive for CK7, and some squamous and intermediate cells were positive for p63 and CK5/6 in all 55 cases; whereas they were positive for p40 in 53 cases. The mucin-producing cells were negative for CK5/6, p63 and p40, but were positive for PAS in all 55 cases. The Ki-67 positive rate was <10% in the low grade PMC, and was about 80%-90% in the high grade cases. Follow-up information was available in 37 patients, with no recurrence or death. There were no EGFR gene mutations in all 31 patients of PMC. PMC is a rare malignant salivary gland-type tumor occurring mainly in the central trachea of young patients.Most PMCs are low grade with good prognosis. The rate of lymph node metastasis of high grade PMC is high. Diagnosing PMC in small biopsies could be problematic. The lack of TTF1 expression is helpful to differentiate from other primary lung cancers. There is no EGFR gene mutation in PMC.

EP1.18-15 Surgical Results of Primary Mucoepidermoid Carcinoma of Lungs: A 9 Years' Experience

MUCOEPIDERMOID CARCINOMA: A RARE MALIGNANCY TREATED ENDOBRONCHIALLY

Objective: To investigate the clinicopathological characteristics of primary pulmonary NUT carcinoma. Methods: A total of 7 cases of primary pulmonary NUT carcinoma were collected from Fujian Provincial Hospital (n=5), Fuzhou Taijiang Hospital (n=1) and Binzhou City People's Hospital of Shandong Province (n=1) from January 2021 to April 2023. The clinical, histopathological, and immunohistochemical features were analyzed, and NUT rearrangement were detected by fluorescence in situ hybridization (FISH) with break-apart probes. Results: Seven cases were all male with age ranging from 32 to 73 years. The main clinical manifestations were cough, expectoration and chest tightness. Microscopically, NUT carcinoma was composed of monotonous proliferation of primitive-appearing small-to-medium round cells, with few eosinophilic cytoplasm, arranged in solid sheets, nests or clusters. Abrupt keratinization was typically observed in 4 cases (4/7), with high mitotic activities and necrosis. Immunohistochemistry (IHC) showed that the tumors were positive for NUT (7/7), CK7 (4/4), CK5/6 (5/6), p40 (6/7). Ki-67 index were 30%-80%. NUT gene segregation (7/7) was detected by FISH break probes. Conclusions: Primary pulmonary NUT carcinoma is rare and highly malignant. Diagnosis depends on histopathology and IHC, with molecular detection as an adjunct for diagnosis. Pathologists should be aware of the clinicopathological characteristics to avoid misdiagnosis.

Objective: To investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma. Methods: Fifty-nine cases of primary pulmonary adenoid cystic carcinoma were collected from August 2011 to December 2017 at the First Affiliated Hospital of Zhengzhou University. All cases were retrospectively studied by hematoxylin-eosin staining and immunohistochemistry. The clinicopathological features were reviewed and patient survival analysis was performed using Kaplan-Meier method and Cox regression model. Status of epidermal growth factor receptor (EGFR), KRAS, BRAF genes was analyzed in 15 of the 59 study cases. Results: Among 59 cases, there were 25 males and 34 females with male to female ratio of 1.0 to 1.4. The patient age ranged from 29 to 81 years with a mean age of 55 years. The tumor max diameters ranged from 1.0 to 9.6 cm with an average diameter of 2.8 cm. Fifteen (25.4%) patients were smokers while 44 patients (74.6%) were non-smokers. Tumors predominantly occurred in the trachea (28/59,47.5%), the left main bronchus (7/59,11.9%) and the right bronchus (5/59,8.5%). Grossly, the tumors were well circumscribed, greyish-white nodules. Microscopically the tumor cells were small and uniform, and arranged in tubular, cribriform, and solid patterns. Immunohistochemistry showed that the tumor cells were positive for CK7, S-100 protein, Sox-10, CD117 and p63. TTF1 was only positive in 2 cases and Ki-67 index ranged from 3% to 40%. Eighteen cases (30.5%) were gradeⅠ, 26 cases (40.1%) grade Ⅱ, and 15 cases (25.4%) grade Ⅲ. Overall, 39 cases (66.1%), 7 cases (11.9%), 10 cases (16.9%), and 3 cases (5.1%) were at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. Twenty-three patients (39.0%) received surgical therapy, 3 patients (5.1%) surgery combined with radiotherapy, 9 patients (15.2%) surgery combined with chemotherapy, and 24 cases (40.7%) chemotherapy only. No mutation of EGFR, KRAS and BRAF was detected in all 15 tested cases. The overall survival rate at the first, third and fifth years was 94.9%, 86.4% and 84.7%, respectively. Prognostic analysis showed that patient's age and tumor size were statistically associated with the survival (P<0.05). Conclusions: Majority of the patients with primary pulmonary adenoid cystic carcinoma are at an early clinical stage with a favorable prognosis. The size of the tumor and the age of the patients are independent prognostic indicators.