Case Of Large Cell Neuroendocrine Carcinoma Research Articles

Secretagogin, a marker for neuroendocrine cells, is more sensitive and specific in large cell neuroendocrine carcinoma compared with the markers CD56, CgA, Syn and Napsin A.

A common method to distinguish large cell neuroendocrine carcinoma (LCNEC) from non-neuroendocrine large cell carcinoma (non-NE LCC) is from using specific immunohistochemistry markers, such as CgA, Syn, CD56 and Napsin A, however, the results remain controversial using these markers. Secretagogin (SCGN) is a newly discovered biomarker of neuroendocrine cells. In the present study, the expression of SCGN in 33 cases of human lung large cell carcinoma (LCC), including 17 cases of LCNEC and 16 cases of non-neuroendocrine (NE) LCC and lung cancer cell lines (A549, H1650, H358, H292 and H661). The association between SCGN expression and the clinicopathological characteristics of patients, including sex, age, clinical stage and metastasis, was analyzed. The results revealed that the different lung cancer cell lines had different expression levels of SCGN, and the SCGN protein was localized in the nucleus and cytoplasm of A549 cells detected using immunofluorescence. A total of 54.5% (18/33) of specimens positively expressed the SCGN protein. Of the 17 patients with LCNEC, only 23.5% (4/17) of cases were CgA positive, 35.29% (6/17) were Syn positive, 41.2% (7/17) were CD56 positive, and 41.2% (7/17) were Napsin A positive. However, SCGN was positively detected in 94.1% (16/17) of patients with LCNEC, which was more frequent compared with that in CgA, Syn, CD56 and Napsin A. Analysis of the clinical characteristics indicated that SCGN expression was only significantly associated with pathological type in patients with lung cancer (P<0.001). Furthermore, a positive correlation was observed between SCGN expression and CgA, Syn, and CD56 expression in patients with LCNEC. SCGN was co-localized with the NE markers (CgA, Syn, and CD56) in A549 lung cancer cells and in LCNEC tissues. Thus, SCGN displayed more sensitivity and specificity in lung cancer cells with NE differentiation. A combined analysis of SCGN and other common NE markers may be a potential tool for diagnosing these tumors.

Large Cell Neuroendocrine Tumor of the Lung: A Diagnostic Challenge

Lung neuroendocrine carcinoma (NEC) is a rare heterogeneous carcinoma with NE cells in the pulmonary and bronchial epithelium as the site of origin. We describe a case of large cell NEC (LCNEC) in a 55-year-old male, smoker with 25 pack-years, who presented with cough, dyspnea, hemoptysis, and loss of appetite for 6 months. There was no diabetes, hypertension, asthma, chronic obstructive pulmonary disease, tuberculosis, or contact with tuberculosis or malignancy. The presence of a large homogenous mass lesion in the right chest on chest X-ray, further clearly defined on chest computed tomography scan (130/94/123 mm) was suggestive of huge mass. There was no mediastinal or pleural involvement. Possibility of LCNEC was suspected as the ultrasound-guided biopsy was indicating the presence of poorly differentiated carcinoma. Immunohistochemistry was negative for thyroid transcription factor, cytokeratin 7 but was positive for synaptophysin and P40, suggestive of high-grade LCNECs. It was in T4N0M0, stage 3A and treatment with combination chemotherapy was initiated.

Gynecologic large cell neuroendocrine carcinoma: A review.

Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neoplasms within the neuroendocrine cell lineage spectrum. This manuscript provides a detailed review of published literature on LCNEC of gynecological origin. We performed a PubMed search for material available on gynecologic LCNEC. We analyzed 104 unique cases of gynecologic LCNECs, of which 45 were cervical primary, 45 were ovarian, 13 were uterine, and 1 was vaginal. A total of 45 cases of cervical LCNEC were identified with a median age of 36 years. Median overall survival was 16 months. We identified 45 ovarian LCNEC cases in the published literature with a median age of 54 years. Median overall survival was 8 months. 13 LCNEC cases of uterine origin were identified; 12 out of 13 were of endometrial origin and the median age was 71 years. The majority of patients presented with Stage III/IV disease (stages I–IV were 31%, 8%, 38%, and 23%, respectively). Gynecologic LCNEC is an aggressive malignancy. Our current understanding of the disease biology is very limited. Efforts are required to better understand the genomic and molecular characterizations of gynecological LCNEC. These efforts will elucidate the underlying oncogenic pathways and driver mutations as potential targets.

Clinical and histological features of primary pure large-cell neuroendocrine carcinoma of the ovary

Primary pure large-cell neuroendocrine carcinoma (LCNEC) of the ovary is a rare entity which has been reported only through few cases. It is described as an aggressive tumor with the tendency to present at advanced stages and to cause death after a short postoperative time. Until nowadays, there is no standard therapeutic protocol that helps to guide the treatment of this malignancy. In this article, we report two cases of pure LCNEC of the ovary to make physicians aware of this entity and to show its clinical and pathological features in order to put emphasis on its aggressiveness. The first case was a 38-year-old patient diagnosed in 2015. The ovarian LCNEC was classified according to the International Federation of Gynecology and Obstetrics (FIGO) staging classification as FIGO Stage IV and was treated by surgery and chemotherapy. The second case was a 67-year-old patient diagnosed in 2017. The ovarian LCNEC was classified as Stage IIIB and not resectable and was treated by paclitaxel–carboplatin chemotherapy.

Large cell neuroendocrine carcinoma of the lung: A population-based study.

e13122 Background: In 2015, the World Health Organization dissolved the category of non-small cell lung cancer (NSCLC) that was previously known as “large cell carcinoma” into adeno- or squamous cell carcinomas, with the exception of large cell neuroendocrine carcinoma (LCNEC), which is now grouped with other neuroendocrine carcinomas of the lung. There is limited data on the epidemiology and best treatment practices for this malignancy, and studies comparing prognosis with SCLC and NSCLC have been conflicting. Methods: We reviewed the epidemiology of LCNEC using data from the Surveillance, Epidemiology and End Results Program from 2010 – 2015. Demographical features and overall survival were compared with SCLC and NSCLC. Trends in incidence and mortality rates were observed from 2004 – 2015. Results: We analyzed 195,148 cases of lung cancer, including 1,681 (0.9%) cases of LCNEC. Age-adjusted incidence of LCNEC was 0.31 per 100,000 people and had increased by 50% over the period studied. This increased incidence was primarily the result of increased incidence of stage IV disease. LCNEC was more likely to present with brain metastasis at diagnosis (19.2%) than either SCLC (16.7%, p = .01) or NSCLC (13.0%, p &lt; .001). Survival patterns for LCNEC mirrored NSCLC in stage I – III disease and SCLC in stage IV disease. After adjusting for other clinical and demographic variables, survival for LCNEC was not different than SCLC but worse than NSCLC (HR = 0.88 for NSCLC vs. LCNEC, p &lt; .001). Survival rates for LCNEC and SCLC did not significantly change over the time period studied, whereas survival rates for NSCLC significantly improved. Consistent with our findings of increased incidence of LCNEC with no change in survival patterns, age-adjusted incidence-based mortality increased by two-fold over the time period studied. Conclusions: LCNEC generally has a worse prognosis than NSCLC and better than SCLC. LCNEC presents with brain metastases more frequently than SCLC. Incidence of LCNEC is consistently increasing in the U.S. Despite this, it remains poorly studied and prognosis for LCNEC has not improved with time. LCNEC has, therefore, become an increasing cause of lung cancer mortality in the American population.

Clinicopathological characteristics and prognostic factors of pulmonary large cell neuroendocrine carcinoma: A large population-based analysis.

BackgroundThe study was conducted to compare the clinicopathological characteristics, survival outcomes, and metastatic patterns between pulmonary large cell neuroendocrine carcinoma (LCNEC) and other non‐small cell lung cancer (ONSCLC), and to identify the prognostic factors of LCNEC.MethodsData of patients diagnosed with LCNEC and ONSCLC from 2004 to 2014 were obtained from the Surveillance, Epidemiology, and End Results dataset. Pearson’s chi‐square tests were used to compare differences in clinicopathological characteristics. The Kaplan–Meier method was used for survival analysis. A propensity score was used for matching and a Cox proportional hazards model was used for multivariate and subgroup analyses.ResultsA total of 2368 LCNEC cases and 231 672 ONSCLC cases were identified. LCNEC incidence increased slightly over time. Except for marital status, LCNEC patients had obviously different biological features to ONSCLC patients. Survival analysis showed that LCNEC had poorer outcomes than ONSCLC. Multivariate analysis revealed that female gender, black race, surgery, radiation, and chemotherapy were protective factors for LCNEC. Matched subgroup analysis further demonstrated that most subgroup factors favored ONSCLC, especially in early stage. Early‐stage LCNEC patients had a higher risk of lung cancer‐specific death than early‐stage ONSCLC patients. Moreover, metastatic patterns were different between LCNEC and ONSCLC. LCNEC patients with isolated liver metastasis or combined invasion to other organs had poorer survival rates.ConclusionsLCNEC has totally different clinicopathological characteristics and metastatic patterns to ONSCLC. LCNEC also has poorer survival outcomes, primarily because of isolated liver metastasis or combined invasion to other organs. Most subgroup factors are adverse factors for LCNEC.

Orthopedia homeobox protein (OTP) is a sensitive and specific marker for primary pulmonary carcinoid tumors in cytologic and surgical specimens

Orthopedia homeobox protein (OTP) was recently demonstrated to be a pulmonary neuroendocrine marker showing specificity for pulmonary carcinoid tumors in histologic sections. Little is known of OTP performance and specificity for pulmonary neuroendocrine tumors in lung fine-needle aspiration (FNA) cell blocks (CBs), however. We evaluated OTP expression in lung non-neuroendocrine and neuroendocrine tumor CBs to determine its diagnostic utility in these specimens. Pulmonary typical carcinoid (TC) and atypical carcinoid (AC), small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), and squamous cell carcinoma (SQ) and adenocarcinoma (ADC) CBs were retrieved along with matched surgical cases and assessed for nuclear OTP expression with immunohistochemistry. Nuclear OTP was seen in 82% TCs (9 of 11) and 83% ACs (10 of 12), but not in SCLC (0 of 9), LCNEC (0 of 9), SQ (0 of 10) or ADC (0 of 6) cytology cases. Similar to the cytologic specimens, nuclear OTP was seen in 82% TCs (9 of 11) and 80% ACs (8 of 10) but in none of the SCLC (0 of 8), LCNEC (0 of 7), SQ (0 of 8) or ADC (0 of 6) resections. Both AC and TC CBs showed a similar percentage of cells expressing nuclear OTP. By contrast, in resection specimens, 30% ACs (3 of 10) compared with 73% TC (8 of 11) cases showed >40% of cells nuclear OTP staining. Nuclear OTP demonstrated 80-83% sensitivity and 100% specificity for pulmonary carcinoid tumors in cytology and surgical specimens. In the context of pulmonary malignancies, nuclear OTP immunohistochemistry is highly sensitive and specific in distinguishing carcinoid tumors from other pulmonary neuroendocrine and non-neuroendocrine malignancies in cytologic and surgical specimens.

Challenges in the management of neuroendocrine cervical cancer during pregnancy: A case report.

Large-cell neuroendocrine carcinoma (LCNEC) is an uncommon histological subtype of cervical cancer that is associated with poor survival and its occurrence during pregnancy is particularly rare. We herein present the case of a female patient who was diagnosed with cervical LCNEC during pregnancy. The patient declined pregnancy termination and was treated with neoadjuvant chemotherapy with cisplatin and etoposide, without associated toxicity and with good fetal development. At 31.4 weeks of gestation, the fetus was delivered by caesarean section, and the patient underwent radical nerve-sparing hysterectomy with bilateral adnexectomy, along with pelvic and inframesenteric para-aortic lymphadenectomy. The patient received adjuvant chemoradiotherapy and there was no evidence of recurrence or metastasis at 38 months postoperatively. The baby has also been followed up, without any signs of neurodevelopmental disorders. To the best of our knowledge, the present report describes the first case of LCNEC with pregnancy-preserving management in the literature to date.

PS02.193: A CASE OF LARGE CELL NEUROENDOCRINE CARCINOMA OF THE ESOPHAGOGASTRIC JUNCTION

Abstract Background The frequency of occurrence of neuroendocrine carcinoma (NEC) in the upper gastrointestinal tract is low, and especially large cell neuroendocrine carcinoma (LCNEC) is extremely rare disease. We report a case of LCNEC of the esophagogastric junction with relapse-free survival in 1 year and 3 months after surgical treatment. Methods An 81 - year—old Japanese man was referred to our hospital because of a semicircular ulcerative lesion in the esophagogastric junction (EGJ) by esophagogastroduodenoscopy of routine medical checkup. Biopsy from the lesion showed proliferation of tumor cells with clear nuclear bodies and irregular nuclei. Immunohistochemistry (IHC) demonstrated weakly positive staining of AE1/AE3, and CD3, CD20, S-100 and HMB 45 were negative. Computed tomography (CT) revealed a thickened wall of the EGJ and a lymphadenopathy of the cardiac node without any metastases to other organs. The patient was diagnosed with carcinoma in EJG, Stage III T3N1M0. We performed thoracoscopic esophagectomy with two-filed lymphadenectomy. Results Macroscopically, the ulcerative tumor measured 55 × 50mm invaded to the adventitia and was approximately centered in the EGJ. Histologically, the tumor cells showed large nuclei with highly frequent mitoses. IHC revealed that tumor was LCNEC positive for synaptophysin. One lymph node metastasis was found among 39 dissected lymph nodes. Finally, the pathological stage was T3N1M0, IIIA. On postoperative day 7, we performed the drainage for intra-abdominal abscess. He was discharged on postoperative day 44. Adjuvant chemotherapy was not performed, because the patient refused it. He was well and had no evidence of recurrence 15 months after surgery. Conclusion LCNECs of the esophagus or stomach are very rare but highly malignant tumors. It is expected that the number of reports of LCNEC in the upper gastrointestinal tract will increase. It is necessary to collect information on more cases to improve prognosis and to establish appropriate treatment guidelines. Disclosure All authors have declared no conflicts of interest.

ALK-rearrangement neuroendocrine carcinoma of the lung: a comprehensive study of a rare case series and review of literature.

Driver mutations involving tyrosine kinase receptors play crucial roles in the oncogenesis of lung adenocarcinoma. However, receptor tyrosine kinase mutations are extremely rare events in primary pulmonary neuroendocrine carcinoma (NEC), which is a molecular heterogeneous entity. In this study, we examined 4 cases of NEC with anaplastic lymphoma kinase (ALK) rearrangement between 2008 and 2018 at our hospital. We comprehensively analyzed the carcinomas’ clinicopathological features, genetic alterations, and response to ALK inhibitor. One case of atypical carcinoid tumor and 1 case of large cell NEC (LCNEC) achieved response to ALK inhibitor (crizotinib) treatment. One case of combined LCNEC with adenocarcinoma harboring KLC1-ALK (K9:A20) fusion genes was confirmed by NGS of both components, while only the LCNEC component presented RB1 mutation. Notably, tumor cells of different components exhibited different ALK-positive signal patterns by fluorescence in situ hybridization, which revealed isolated 3′ signals in the adenocarcinoma component but split signals in the LCNEC. As the largest case series study, our findings suggested that preliminary screening for ALK rearrangement should also be considered in atypical carcinoid and high-grade NEC. Patients with ALK rearrangement-positive NEC would benefit from ALK inhibitor intervention.

Large Cell Neuroendocrine Carcinoma of the Larynx: A Case Report and Review of Literature

Laryngeal neuroendocrine carcinomas (LNEC) constitute <1% of all tumours originating from the larynx and are believed to originate from pluripotential stem cells located in the submucosa of the larynx. It is hard to estimate the true incidence of large-cell neuroendocrine carcinoma (LCNEC) because the WHO classification does not make a distinction between atypical carcinoid tumors and large-cell neuroendocrine carcinoma. In the current classification, laryngeal LCNEC is considered synonymous with atypical carcinoid/moderately-differentiated (Grade II) neuroendocrine carcinoma. This distinction is clinically important as the clinical behavior and response to treatment differs greatly between subtypes. We report a rare case of metastatic LCNEC of subglottic region of larynx who is treated with chemotherapy and radiotherapy and a review of literature on the diagnosis and treatment of these tumors is presented.

Distinct clinicopathologic features, genomic characteristics and survival of central and peripheral pulmonary large cell neuroendocrine carcinoma: From different origin cells?

BackgroundPulmonary large cell neuroendocrine carcinoma (LCNEC) represents a rare entity in lung cancer with dismal prognosis. In the present study, we investigated whether there are significant differences between central and peripheral tumors of LCNEC, in terms of clinicopathologic features, genomic profiles, and survival. Methods and materialsA total of 126 cases of LCNEC were included. The tumors with invasion of the segmental and/or lobar bronchus were classified as central LCNEC and those without as peripheral LCNEC. EGFR/BRAF/Kras mutations and ALK/ROS1 translocations were detected. Overall survival (OS) was evaluated by the Kaplan-Meier plots. ResultsThe majority of LCNEC proved to be of the peripheral type (64.3%, 81/126). Central tumors were associated with smoking habit (p = 0.047), higher TNM-stage (p = 0.014) and larger tumor size (p < 0.001). Expression of neuroendocrine markers (CD56, CGA, and SYN) was not significantly different by tumor location but central tumors had higher serum levels of NSE (p = 0.004). Peripheral tumors had a higher incidence of EGFR mutations (18.8% vs. 0%, p = 0.023). ROS1 translocation was detected in 1 patient with peripheral LCNEC. RB1 protein was more frequently expressed in peripheral tumor than central tumor. The median OS was 3.71 years in the entire cohort. Peripheral tumors had better survival compared with central tumors (median OS: 4.04 vs. 1.51 years, p < 0.001). Multivariate analyses demonstrated tumor location (hazard ratio [HR], 6.07, 95% confidence interval [CI], 1.57-23.44, p = 0.009), resection status (HR, 6.58, 95% CI, 1.92-22.51, p = 0.003) and EGFR mutational status (HR, 0.18, 95% CI, 0.04-0.75, p = 0.018) were independent prognostic factors for OS. ConclusionPrimary tumor location of LCNEC, divided into central and peripheral type, has distinct clinicopathologic features, genomic characteristics and survival. These differences are likely due to differences in the origin cells and pathogenesis of these tumors.

Therapeutic strategies and genetic profile comparisons in small cell carcinoma and large cell neuroendocrine carcinoma of the lung using next-generation sequencing.

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung are classified as variants of endocrine carcinoma and subdivided into pure or combined type. Clinical benefit of target therapy has not been established in these tumors. This study aimed to compare genetic and clinicopathological features between SCLC and LCNEC or pure and combined types, and explore the possibility of target therapy using next-generation sequencing. In 13 SCLC and 22 LCNEC cases, 72 point mutations, 19 deletions, and 3 insertions were detected. As therapeutically targetable variants, mutations in EGFR (L858R), KRAS (G12D, G12A, G12V), and PIK3CA (E545K) were detected in 5 cases. The case harboring EGFR mutation showed response to EGFR-tyrosine kinase inhibitor. However, there are no clinicopathological features associated with therapeutically targetable cases. And there was no significant genetic feature between SCLC and LCNEC or pure and combined types. In conclusion, although patients with SCLC and LCNEC may benefit from target therapy, they were not identifiable by clinicopathologic background. And there was not significant genetic difference between SCLC and LCNEC, including between pure and combined types. Classifying SCLC and LCNEC in same category is reasonable. However, distinguishing the pure type from combined type was not validated. Comprehensive genetic analysis should be performed to detect targetable variants in any type of SCLC and LCNEC.

Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder.

Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

Update on large cell neuroendocrine carcinoma.

High-grade neuroendocrine carcinomas of the lung are classified into two categories: large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). While typical cases of LCNEC are morphologically distinct from SCLC, the differentiation between LCNEC and SCLC can be challenging in some cases. In fact, there are borderline high-grade neuroendocrine carcinomas that morphologically fall between LCNEC and SCLC. Growing evidence suggests that LCNEC is a histologically and biologically heterogeneous group of tumors. Molecular profiling with next-generation sequencing (NGS) has revealed a few biologically distinct subsets of LCNEC. Of those, the SCLC-like subset is characterized by concurrent inactivating mutations in TP53 and loss of RB1 that are typically seen in SCLC, whereas the non-small cell lung cancer (NSCLC)-like subset frequently harbors molecular alterations that are usually seen in NSCLC. Furthermore, the SCLC-like subset exhibits morphologic features of SCLC, and NSCLC-like morphology predominates in the NSCLC-like subset, although there was a substantial overlap in morphologic features between these subsets. As for the treatment of LCNEC, surgery is advocated for early stage tumors, but surgery alone does not appear to be sufficient and adjuvant chemotherapy, consisting of platinum/etoposide, likely prevents recurrence in patients with completely resected LCNEC. For advanced disease, there have been conflicting reports as to whether LCNEC responds to chemotherapeutic regimens in the similar manner to SCLC rather than NSCLC, and the heterogeneous biology of LCNEC may contribute in part to the discrepant results. A further understanding of the biology of LCNEC will lead to novel approaches to clinical managements of patients with LCNEC.

Relationship of tumor PD-L1 (CD274) expression with lower mortality in lung high-grade neuroendocrine tumor.

Programmed death‐ligand 1 (PD‐L1) promotes immunosuppression by binding to PD‐1 on T lymphocytes. Although tumor PD‐L1 expression is a potential predictive marker of clinical response to anti‐PD‐1/PD‐L1 therapy, little is known about its association with clinicopathological features, including prognosis, in high‐grade neuroendocrine tumors (HGNETs), including small‐cell lung carcinoma (SCLC) and large‐cell neuroendocrine carcinoma (LCNEC), of the lung. We immunohistochemically examined the membranous of expression of PD‐L1 in 115 consecutive surgical cases of lung HGNET (74 SCLC cases and 41 LCNEC cases). We examined the prognostic association of tumor PD‐L1 positivity using the log‐rank test as well as Cox proportional hazards regression models to calculate the hazard ratio (HR) for mortality. Programmed death‐ligand 1 immunostaining (at least 5% tumor cells) was observed in 25 (21%) of the 115 HGNET cases. In a univariable analysis, PD‐L1 positivity was associated with lower lung cancer‐specific (univariable HR = 0.23; 95% confidence interval [CI] = 0.056–0.64; P = 0.0028) and overall (univariable HR = 0.28; 95% CI = 0.11–0.60; P = 0.0005) mortality. Additionally, in a multivariable analysis, PD‐L1 positivity was independently associated with lower lung cancer‐specific (multivariable HR = 0.24; 95% CI = 0.058–0.67; P = 0.0039) and overall (multivariable HR = 0.29; 95% CI = 0.11–0.61; P = 0.0006) mortality. Our study demonstrated the prevalence of PD‐L1 positivity in lung HGNET cases, and the independent association of tumor PD‐L1 positivity with lower mortality in lung HGNET cases. Further studies are needed to confirm our findings.

Aggressive large-cell neuroendocrine carcinoma of the sigmoid colon in a patient with ulcerative colitis

Colonic inflammation seen in inflammatory bowel disease (IBD) predisposes to the development of colorectal adenocarcinoma. In contrast, colorectal neuroendocrine carcinomas (NECs) have rarely been reported in the setting of IBD,...

A Semi-Quantitative Approach to Biopsy Diagnosis of Large Cell Neuroendocrine Carcinoma of the Lung

The current WHO diagnostic criteria strongly discourages diagnosis of pulmonary large cell neuroendocrine carcinoma (LCNEC) on anything less than resection material. Possibly as a result, this is a rare diagnosis and a therapeutic approach is not well defined. One group has proposed biopsy criteria but those have not been evaluated quantitatively in a large cohort with resection confirmation and compared to more common types of lung cancer. A tissue microarray (TMAs) was generated from cases of resected LCNEC as biopsy surrogates. The TMA was stained for neuroendocrine markers, KI-67, NapsinA and p40. A scoring system was devised, which assigned points for classical morphologic features of LCNEC, neuroendocrine marker positivity, and high Ki-67 proliferative index (>40%), with a maximum possible total score of 9. In comparison to a control TMA of generic NSCLC, a cutoff score of 5 showed high sensitivity and specificity for diagnosis of LCNEC (91% and 99%, respectively) with an excellent 93% agreement among four pathologists. On the basis of these results we propose a semi-quantitative approach to the diagnosis of LCNEC on biopsy based on a combination of specific morphologic and immunohistochemical features.

Rapidly progressing large-cell neuroendocrine carcinoma arising from the uterine corpus: A case report and review of the literature.

Large-cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor. LCNECs arising from the genital organs are highly malignant and rare, with <20 cases of LCNEC developing from the uterine endometrium reported to date. We herein present the case of a patient with LCNEC of the endometrium. The patient was a 52-year-old woman, who exhibited lower abdominal pain and rapid uterine enlargement during outpatient treatment for uterine myoma. The endometrial biopsy suggested a diagnosis of poorly differentiated carcinoma or carcinosarcoma. Based on magnetic resonance imaging and positron emission tomography/computed tomography, endometrial stromal sarcoma was suspected. The serum lactate dehydrogenase level was abnormally high. Due to the suspicion of stage IIIC malignant tumor of the uterine corpus, surgery was performed. The pathological diagnosis was stage IIIC2 LCNEC of the endometrium. Recurrence occurred in the vaginal stump, and concurrent chemoradiotherapy (CCRT) was initiated 1 month after the surgery. The residual lesions markedly shrank, but metastasis to the upper abdominal region and cervix subsequently developed. CCRT was attempted, but the associated adverse effects were severe and was switched to palliative treatment. The patient eventually succumbed to the disease 309 days after surgery.

胸腺発生大細胞神経内分泌癌術後長期生存の1例

症例は47歳女性．胸痛を主訴に近医を受診し，縦隔腫瘤を指摘され，当科紹介となった．胸部CT検査では，前縦隔に52×48 mm大の内部不均一な腫瘤を認め，心囊・右肺に接し，少量の胸水を伴っていた．FDG-PET検査では同腫瘤にSUVmax 5.34の集積を認め，胸腺癌の疑いで拡大胸腺摘出術を施行した．病理組織検査では胸腺原発の大細胞神経内分泌癌，正岡病期分類I期と診断した．術後70ヵ月現在無再発生存中である．