Comparative Outcomes in Patients With Small- and Large-Cell Neuroendocrine Carcinoma (NEC) and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the Stomach

2020 ◽  
pp. 000313482095000
Author(s):  
Nam Young Choi ◽  
Byung-Sik Kim ◽  
Sung Tae Oh ◽  
Jeong Hwan Yook ◽  
Beom Su Kim
Keyword(s):  
Clinical Outcomes ◽  
Disease Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
High Grade ◽  
Intermediate Grade ◽  
Free Survival ◽  
Neuroendocrine Carcinomas

Background Gastric neuroendocrine carcinomas (NECs), consisting of both large- and small-cell NECs, and mixed adenoneuroendocrine carcinomas (MANECs), including mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), are a group of high-grade malignancies. Few studies to date have reported clinical outcomes, including prognosis, in patients with these tumors. This study therefore evaluated the clinicopathologic outcomes and prognosis in patients with NECs and MANECs. Methods This study included 36 patients diagnosed with gastric NECs, including 23 with large-cell and 13 with small-cell NECs, and 85 with MiNENs, including 70 with high-grade and 15 with intermediate-grade MiNENs. Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed. Results DFS was significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN ( P < .05), whereas both OS and DFS were similar in patients with NEC and high-grade MiNEN ( P > .05). Patients with large-cell NEC were more likely to undergo aggressive surgery than patients with high-grade MiNEN ( P < .05). Lymphovascular invasion was more frequent and DFS poorer in patients with large-cell than small-cell NECs ( P < .05 each). Conclusion DFS is significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN and significantly lower in patients with large-cell than small-cell NECs.

scholarly journals Mixed Neuroendocrine/Non-neuroendocrine Neoplasm (MiNEN) of the Ovary Arising from Endometriosis: Molecular Pathology Analysis in Support of a Pathogenetic Paradigm

2021 ◽  
Author(s):  
Roberta Maragliano ◽  
Laura Libera ◽  
Ileana Carnevali ◽  
Valeria Pensotti ◽  
Giovanna De Vecchi ◽  
...  
Keyword(s):  
Large Cell ◽  
Neuroendocrine Neoplasm ◽  
Molecular Profile ◽  
Neuroendocrine Neoplasms ◽  
Fish Analysis ◽  
Sequencing Analysis ◽  
Endometrioid Carcinoma ◽  
Preneoplastic Lesions ◽  
Ovarian Endometriosis ◽  
Neuroendocrine Carcinomas

AbstractPrimary ovarian neuroendocrine neoplasms (Ov-NENs) are infrequent and mainly represented by well-differentiated forms (neuroendocrine tumors — NETs — or carcinoids). Poorly differentiated neuroendocrine carcinomas (Ov-NECs) are exceedingly rare and only few cases have been reported in the literature. A subset of Ov-NECs are admixed with non-neuroendocrine carcinomas, as it occurs in other female genital organs, as well (mostly endometrium and uterine cervix), and may be assimilated to mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs) described in digestive and extra-digestive sites. Here, we present a case of large cell Ov-NEC admixed with an endometrioid carcinoma of the ovary, arising in the context of ovarian endometriosis, associated with a uterine endometrial atypical hyperplasia (EAH). We performed targeted next-generation sequencing analysis, along with a comprehensive immunohistochemical study and FISH analysis for TP53 locus, separately on the four morphologically distinct lesions (Ov-NEC, endometrioid carcinoma, endometriosis, and EAH). The results of our study identified molecular alterations of cancer-related genes (PIK3CA, CTNNB1, TP53, RB1, ARID1A, and p16), which were present with an increasing gradient from preneoplastic lesions to malignant proliferations, both neuroendocrine and non-neuroendocrine components. In conclusion, our findings underscored that the two neoplastic components of this Ov-MiNEN share a substantially identical molecular profile and they progress from a preexisting ovarian endometriotic lesion, in a patient with a coexisting preneoplastic proliferation of the endometrium, genotypically and phenotypically related to the ovarian neoplasm. Moreover, this study supports the inclusion of MiNEN in the spectrum ovarian and, possibly, of all gynecological NENs, among which they are currently not classified.

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study.

1993 ◽  
Vol 11 (2) ◽  
pp. 248-254 ◽  
Author(s):  
B A Parker ◽  
M Santarelli ◽  
M R Green ◽  
J R Anderson ◽  
M R Cooper ◽  
...  
Keyword(s):  
Large Cell ◽  
High Grade ◽  
Intermediate Grade ◽  
Free Survival ◽  
Major Toxicity ◽  
Central Pathology ◽  
Group B ◽  
Hodgkin's Lymphomas ◽  
Leukemia Group

PURPOSE In an attempt to improve the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphomas, a phase II evaluation of a regimen consisting of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, Oncovin (vincristine; Eli Lilly Co, Indianapolis, IN), prednisone, leucovorin, cytarabine (ara-c), cyclophosphamide, and etoposide (AMOPLACE) was conducted. This regimen includes three additional agents not found in CHOP, uses weekly doses of alternating myelosuppressive and nonmyelosuppressive drugs, and incorporates most single agents active against diffuse lymphomas. PATIENTS AND METHODS Ninety-one previously untreated patients were enrolled and 60 patients were confirmed eligible after central pathology review. Fifty-eight percent of patients had diffuse large-cell lymphoma (DLCL), 83% had stage III or IV disease, and 45% had B symptoms. RESULTS Patients were treated with six to eight cycles of AMOPLACE and analyzed for response and survival. With a median follow-up of 48 months, complete responses (CRs) were seen in 68% of all patients with failure-free survival (FFS) and overall survival (OS) estimates at 4 years of 45% and 54%. In the DLCL subset, the CR rate was 69% and FFS and OS estimates at 4 years were 49% and 60%, respectively. The major toxicity was myelosuppression, with 73% of patients having WBC nadirs less than 1,000/microL; two treatment-related deaths occurred. CONCLUSION We conclude that AMOPLACE is associated with CR and OS rates comparable with those of other third-generation regimens.

scholarly journals Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1211
Author(s):  
Frediano Inzani ◽  
Angela Santoro ◽  
Giuseppe Angelico ◽  
Angela Feraco ◽  
Saveria Spadola ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Target Therapy ◽  
Somatostatin Receptors ◽  
Neuroendocrine Differentiation ◽  
Large Cell ◽  
Cell Types ◽  
Somatostatin Analogues ◽  
Small Cell ◽  
Neuroendocrine Neoplasms ◽  
Neuroendocrine Carcinomas

Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2–2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retrieved and tested by immunohistochemistry (IHC) for 12 markers including markers of neuroendocrine differentiation (chromogranin A, synaptophysin, CD56), transcription factors (CDX2 and TTF1), proteins p40, p63, p16INK4a, and p53, somatostatin receptors subtypes (SST2-SST5) and the proliferation marker Ki67 (MIB1). Results. All cases were poorly differentiated neuroendocrine carcinomas (NECs), 10 small cell types (small cell–neuroendocrine carcinomas, SCNECs) and 6 large cell types (large cell–neuroendocrine carcinomas, LCNECs); in 3 cases a predominant associated adenocarcinoma component was observed. Neuroendocrine cancer cells expressed at least 2 of the 3 tested neuroendocrine markers; p16 was intensely expressed in 14 (87.5%) cases; SST5 in 11 (56.25%, score 2–3, in 9 cases); SST2 in 8 (50%, score 2–3 in 8), CDX2 in 8 (50%), TTF1 in 5 (31.25%), and p53 in 1 case (0.06%). P63 and p40 expressions were negative, with the exception of one case that showed moderate expression for p63. Conclusions. P40 is a more useful marker for the differential diagnosis compared to squamous cell carcinoma. Neither CDX2 nor TTF1 expression may help the differential diagnosis versus potential cervical metastasis. P16 expression may suggest a cervical origin of NEC; however, it must be always integrated by clinical and instrumental data. The expression of SST2 and SST5 could support a role for SSAs (Somatostatin Analogues) in the diagnosis and therapy of patients with cervical NECs.

Neuroendocrine Tumors of Larynx

1992 ◽  
Vol 101 (8) ◽  
pp. 710-714 ◽  
Author(s):  
Adel K. El-Naggar ◽  
John G. Batsakis ◽  
Mario A. Luna
Keyword(s):  
Survival Rate ◽  
Neuroendocrine Tumors ◽  
Small Cell ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
Neural Basis ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Typical Carcinoid ◽  
Clinical Behavior ◽  
Neuroendocrine Carcinomas

Neuroendocrine neoplasms of the larynx have either an epithelial or a neural basis. The former are more numerous and are classified as typical or atypical carcinoids and small cell neuroendocrine carcinomas. Paraganglioma is the sole type of neural neuroendocrine neoplasm. There is a significant worsening of prognosis from typical carcinoid to small cell neuroendocrine carcinoma, with the latter having a dismal 5-year survival rate regardless of therapy. Paragangliomas are the most benign of laryngeal neuroendocrine neoplasms, but their clinical behavior may not be predictable on the basis of their histologic appearance.

Autotransplants in Advanced Non-Hodgkin Lymphoma: Are They Effective?

1992 ◽  
Vol 1 (5) ◽  
pp. 343-347
Author(s):  
Antonella Surbone ◽  
James O. Armitage ◽  
Robert Peter Gale
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Intensive Therapy ◽  
Disease Free Survival ◽  
Large Cell ◽  
High Grade ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Large Cell Lymphoma ◽  
Disease Free

Recent data suggest that intensive therapy followed by a bone marrow antotransplant is effective in advanced intermediate and high-grade non-Hodgkin lymphoma (predominantly large-cell lymphoma). Twelve studies of autotransplants were analyzed to determine outcome. Results compared to data from 29 chemotherapy studies. Complete remission was reported in 53% of autotransplant recipients versus 17% of persons receiving chemotherapy. Two-year disease-free survival was 16 and 2%, respectively. It is uncertain whether these differences indicate superiority of autotransplants or reflect selection biases. Also unknown is whether similar results might not be obtained with similarly intensive treatment without an autotransplant.

scholarly journals SOX11 is a sensitive and specific marker for pulmonary high-grade neuroendocrine tumors

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Lu Yu ◽  
Yuting Dong ◽  
Jin Xue ◽  
Sanpeng Xu ◽  
Guoping Wang ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Large Cell ◽  
Small Cell ◽  
Specific Marker ◽  
Tumor Type ◽  
High Grade ◽  
Immunohistochemical Expression ◽  
Small Cell Lung ◽  
Sox11 Expression ◽  
Neuroendocrine Carcinomas

Abstract Background Synaptophysin (SYN), chromogranin A (CGA), CD56 and insulinoma-associated protein 1 (INSM1) are proposed neuroendocrine (NE) markers used for diagnosis of pulmonary NE tumors. These NE markers have been identified in subsets of non-NE tumors requiring differential diagnosis, thus we sought to explore new NE markers. Methods We evaluated the immunohistochemical expression of SOX11, a transcription factor involved in neurogenesis, in pulmonary NE tumors and large cell carcinomas (LCCs). Results We found that SOX11 showed a sensitivity similar to INSM1 and CGA, and less than SYN and CD56 in small cell lung carcinomas (SCLCs) and large cell neuroendocrine carcinomas (LCNECs). While SOX11 is more specific than the other four markers for diagnosis of high-grade neuroendocrine carcinomas (HG-NECs) because 1) None of LCCs (0/63), the most challenging non-NE tumor type for differential diagnosis due to overlapped morphology with LCNECs displayed SOX11 positivity. While expression of at least one of SYN, CGA, CD56 or INSM1 was identified in approximately 60% (18/30) of LCCs. 2) SOX11 was only expressed in 1 of 37 carcinoid tumors in contrast to diffuse expression of SYN, CGA, CD56 and INSM1. In HG-NECs, we noticed that SOX11 was a good complementary marker for SCLC diagnosis as it was positive in 7 of 18 SYN−/CGA−/CD56− SCLCs and 3 of 8 SYN−/CGA−/CD56−/INSM1− SCLCs, and SOX11 positivity in 4 of 6 SYN−/CGA−/CD56− cases previously diagnosed as LCCs with NE morphology provides additional evidence of NE differentiation for reclassification into LCNECs, which was further confirmed by electromicroscopical identification of neurosecretory granules. We also found SOX11 expression cannot predict the prognosis in patients with HG-NECs. Conclusions Therefore, SOX11 is a useful complementary transcriptional NE marker for diagnosis and differential diagnosis of SCLC and LCNEC.

scholarly journals Primary neuroendocrine neoplasm of the esophagus – Report of 14 cases from a single institute and review of the literature

2017 ◽  
Vol 54 (1) ◽  
pp. 4-10 ◽  
Author(s):  
Francisco TUSTUMI ◽  
Flavio Roberto TAKEDA ◽  
Rodrigo Hideki UEMA ◽  
Guilherme Luiz Stelko PEREIRA ◽  
Rubens Antonio Aissar SALLUM ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neuroendocrine Tumors ◽  
Squamous Cell ◽  
Large Cell ◽  
Small Cell ◽  
Esophageal Neoplasm ◽  
Neuroendocrine Neoplasm ◽  
High Grade ◽  
Esophageal Tumors

ABSTRACT BACKGROUND Most prevalent esophageal neoplasm is squamous cell carcinoma and adenocarcinoma. Other tumors are uncommon and poorly studied. Primary neuroendocrine esophageal neoplasm is a rare carcinoma and most of its therapy management is based on lung neuroendocrine studies. Neuroendocrine tumors can be clustered in the following subtypes: high grade (small cell carcinoma or large cell carcinoma) and low grade (carcinoids). OBJECTIVE The present study aims to assess clinical and pathological neuroendocrine esophageal tumors in a single oncologic center. METHODS A retrospective analysis of patients and review of the literatures was performed. RESULTS Fourteen patients were identified as neuroendocrine tumors, 11 male and 3 female patients. Mean age was 67.3 years old. Ten patients were classified as small cell, 3 as large cell and 1 as carcinoid. Four patients presented squamous cell carcinoma simultaneously and 1 also presented adenocarcinoma. Main sites of metastasis were liver, peritoneum, lung and bones. Most patients died before 2 years of follow-up. Patient with longer survival died at 35 months after diagnosis. CONCLUSION Neuroendocrine esophageal tumors are rare; affect mainly men in their sixties or seventies. High grade tumors can be mixed to other subtypes neoplasms, such as adenocarcinoma and squamous cell carcinoma. Most of these patients have poor overall survival rates.

scholarly journals Lung neuroendocrine neoplasms: recent progress and persistent challenges

2021 ◽  
Author(s):  
Natasha Rekhtman
Keyword(s):  
Recent Progress ◽  
Small Cell Lung Carcinoma ◽  
Predictive Biomarkers ◽  
Large Cell ◽  
Small Cell ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
Tumor Type ◽  
Cell Lung Carcinoma ◽  
Immunohistochemical Markers

AbstractThis review summarizes key recent developments relevant to the pathologic diagnosis of lung neuroendocrine neoplasms, including carcinoids, small cell lung carcinoma (SCLC), and large cell neuroendocrine carcinoma (LCNEC). Covered are recent insights into the biological subtypes within each main tumor type, progress in pathological diagnosis and immunohistochemical markers, and persistent challenging areas. Highlighted topics include highly proliferative carcinoids and their distinction from small cell and large cell neuroendocrine carcinomas (NECs), the evolving role of Ki67, the update on the differential diagnosis of NEC to include thoracic SMARCA4-deficient undifferentiated tumors, the recent data on SCLC transcriptional subtypes with the emergence of POU2F3 as a novel marker for the diagnosis of SCLC with low/negative expression of standard neuroendocrine markers, and the update on the diagnosis of LCNEC, particularly in biopsies. There has been remarkable recent progress in the understanding of the genetic and expression-based profiles within each type of lung neuroendocrine neoplasm, and it is hoped that these insights will enable the development of novel diagnostic, prognostic, and predictive biomarkers to aid in the pathologic assessment of these tumors in the future.

scholarly journals Evaluation of PARP and PDL-1 as potential therapeutic targets for women with high-grade neuroendocrine carcinomas of the cervix

2020 ◽  
Vol 30 (9) ◽  
pp. 1303-1307 ◽  
Author(s):  
Matthew Ryan Carroll ◽  
Preetha Ramalingam ◽  
Gloria Salvo ◽  
Junya Fujimoto ◽  
Luisa Maren Solis Soto ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Treatment Options ◽  
Therapeutic Targets ◽  
Large Cell ◽  
Small Cell ◽  
Cancer Center ◽  
High Grade ◽  
Mismatch Repair Proteins ◽  
Parp 1 ◽  
Neuroendocrine Carcinomas

ObjectivesWomen with recurrent high-grade neuroendocrine cervical cancer have few effective treatment options. The aim of this study was to identify potential therapeutic targets for women with this disease.MethodsSpecimens from patients with high-grade neuroendocrine carcinomas of the cervix were identified from pathology files at MD Anderson Cancer Center. Immunohistochemical stains for PD-L1 (DAKO, clone 22-C3), mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), somatostatin, and Poly (ADP-ribose) polymerase (PARP) were performed on sections from formalin-fixed paraffin-embedded tissue blocks. Nuclear PARP-1 staining was quantified using the H-score with a score of <40 considered low, 40–100 moderate, and ≥100 high.ResultsForty pathologic specimens from patients with high-grade neuroendocrine carcinomas of the cervix were examined (23 small cell, 5 large cell, 3 high-grade neuroendocrine, not otherwise specified, and 9 mixed). The mean age of the cohort was 43 years and the majority of patients (70%) were identified as white non-Hispanic. All 28 (100%) samples tested stained for mismatch repair proteins demonstrated intact expression, suggesting they were microsatellite stable tumors. Of the 31 samples tested for PD-L1 expression, only two (8%) of the 25 pure high-grade neuroendocrine carcinomas were positive whereas three (50%) of the six mixed carcinoma tumors tested positive. Of the 11 small cell specimens tested for PARP-1, 10 (91%) showed PARP expression with six (55%) demonstrating high expression and four (36%) showing moderate expression. Somatostatin staining was negative in 18 of 19 small cell cases (95%).ConclusionsPure high-grade neuroendocrine cervical carcinomas were microsatellite stable and overwhelmingly negative for PD-L1 expression. As the majority of tumors tested expressed PARP-1, inclusion of PARP inhibitors in future clinical trials may be considered.

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