scholarly journals Are G3 ENETS neuroendocrine neoplasms heterogeneous?

2013 ◽  
Vol 20 (5) ◽  
pp. 649-657 ◽  
Author(s):  
Fritz-Line Vélayoudom-Céphise ◽  
Pierre Duvillard ◽  
Lydia Foucan ◽  
Julien Hadoux ◽  
Cecile N Chougnet ◽  
...  
Keyword(s):  
Mitotic Index ◽  
Somatostatin Receptor ◽  
Neuron Specific Enolase ◽  
Morphological Differentiation ◽  
Large Cell ◽  
Cell Types ◽  
Small Cell ◽  
Neuroendocrine Neoplasms ◽  
Cell Type ◽  
Poorly Differentiated

The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung NEC. To characterize the subgroup of non-small-cell-type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathological features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small-cell-type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Twenty-eight patients (17%) fulfill the inclusion criteria. Tumors were classified as well-differentiated NET (G3-WDNET) in 42.8% of cases and poorly differentiated, large-cell NEC (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or neuron-specific enolase were elevated in 42 and 25% respectively of G3-WDNET and 31 and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88 and 50% of G3-WDNET or G3-LCNEC respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified as G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P=0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (P=0.049). G3 ENETS GEP and thoracic neuroendocrine neoplasms (NEN) could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis, and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.

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.

scholarly journals Classification of 1,198 Cases of Bovine Lymphoma Using the National Cancer Institute Working Formulation for Human Non-Hodgkin's Lymphomas

1992 ◽  
Vol 29 (3) ◽  
pp. 183-195 ◽  
Author(s):  
W. Vernau ◽  
V. E. O. Valli ◽  
T. W. Dukes ◽  
R. M. Jacobs ◽  
M. Shoukri ◽  
...  
Keyword(s):  
Mitotic Index ◽  
National Cancer Institute ◽  
Large Cell ◽  
Cell Types ◽  
High Grade ◽  
Human Beings ◽  
Cell Type ◽  
Follicular Tumors ◽  
Hodgkin's Lymphomas ◽  
Working Formulation

A retrospective histologic study was made of 1,198 cases of bovine lymphoma using the National Cancer Institute Working Formulation for human non-Hodgkin's lymphoma. This classification scheme was found to be readily applicable to bovine lymphoma. Most of the cell types described in the National Cancer Institute Working Formulation occurred in this series of bovine lymphomas, but the distribution of cell types varied markedly compared to that of human beings. Eighty-nine percent (1,067/1,198) of bovine lymphomas were high-grade tumors. The diffuse large cell type and its cleaved variant comprised 65.9% of all bovine lymphomas. Similar to the dog, but in marked contrast to human beings where at least 34% of non-Hodgkin's lymphomas were follicular, follicular tumors were found to be extremely rare in cattle (0.3% or 4/1,198). The prevalence of cell types varied significantly between the enzootic and sporadic lymphomas. The cleaved variant of the diffuse large cell type constituted 38% (406/1,072) of enzootic lymphomas versus 14% (18/126) of sporadic lymphomas. The mitotic index (100 × oil immersion field, 175 μm in diameter) of enzootic lymphomas (3.72 ± 0.06, mean ± standard error) was significantly greater than the mitotic index of sporadic lymphomas (2.82 ± 0.17). We concluded that the cleaved variant of the diffuse large cell type with high mitotic index is characteristic of enzootic lymphoma. This characteristic high-grade cell type may be a consequence of the viral etiology of the enzootic form of bovine lymphoma.

scholarly journals Poorly Differentiated Small-Cell-Type Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review

2018 ◽  
Vol 11 (3) ◽  
pp. 676-681 ◽  
Author(s):  
Kishore Kumar ◽  
Rafeeq Ahmed ◽  
Chime Chukwunonso ◽  
Hassan Tariq ◽  
Masooma Niazi ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Tumor Grade ◽  
Small Cell ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Cell Type ◽  
Variable Response ◽  
Ki 67 ◽  
Platinum Based Chemotherapy ◽  
Poorly Differentiated

Neuroendocrine cells are widespread throughout the body and can give rise of neuroendocrine tumors due to abnormal growth of the chromaffin cells. Neuroendocrine tumors divide into many subtypes based on tumor grade (Ki-67 index and mitotic count) and differentiation. These tumors can be further divided into secretory and nonsecretory types based on the production of peptide hormone by tumor cells. Poorly differentiated small-cell-type neuroendocrine tumors are one of the subtypes of neuroendocrine tumors. These tumors are less common; however, they tend to be locally invasive and aggressive in behavior with poor overall median survival. Treatment of the nonsecretory small-cell type is modeled to small-cell lung cancer with a regimen consisting of platinum-based chemotherapy and etoposide with variable response. Here, we present a case of poorly differentiated small-cell neuroendocrine tumor originating from the prostate.

Phase II study of pembrolizumab-based therapy in previously treated extrapulmonary poorly differentiated neuroendocrine carcinomas: Results of Part B (pembrolizumab + chemotherapy).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4148-4148
Author(s):  
Jennifer A. Chan ◽  
Nitya Prabhakar Raj ◽  
Rahul Raj Aggarwal ◽  
Susan Calabrese ◽  
April DeMore ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Type I ◽  
First Line ◽  
Open Label ◽  
Total N ◽  
Poorly Differentiated ◽  
Neuroendocrine Carcinomas

4148 Background: The efficacy of immune checkpoint inhibitor (CPI) therapy has not been established in extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PDNECs). In small cell lung cancer, CPI therapy is approved for use in the first-line and salvage settings. We investigated the efficacy and safety of pembrolizumab (PEM)-based therapy in biomarker-unselected patients (pts) with EP-PDNECs. PEM alone (Part A, N=14) was inactive (ASCO GI 2019; Abstr#363). We now report the results of Part B (PEM plus chemotherapy). Methods: We conducted an open label, multicenter, phase 2 study of PEM-based therapy in pts with EP-PDNECs, excluding Merkel cell carcinoma and well differentiated grade 3 neuroendocrine tumors (NET), with disease progression on first-line systemic therapy. In Part B of this trial, patients were treated with PEM 200 mg IV every 3 week cycle plus dealers’ choice chemotherapy (chemo): weekly irinotecan (IRI, 125 mg/m2 day 1,8 of every 21 day cycle) or weekly paclitaxel (PAC, 80 mg/m2). After PEM/IRI safety lead-in (N=6), 16 additional pts (total N=22) were enrolled. This was based on a primary endpoint of objective response rate (ORR) by RECIST 1.1 and a plan to test Ha ORR 31% vs H0 ORR 10% with 80% power at a type I error rate of 0.05. Secondary endpoints include safety, overall survival (OS), and progression-free survival (PFS). Serial blood samples and baseline tumor biopsies were required in all pts. Results: Preliminary data from Part B are available. Of 22 pts enrolled, male/female 15/7; median age 57 years (range 34-75); ECOG PS 0/1: 10/12; 6 large cell, 8 small cell, 8 NOS. Primary sites of disease: GI 73%, GYN 5%, unknown 23%. Ki67 index (available for 18 pts) median 68% (range 30 to >95%). Chemo choice: 17 IRI (77%) and 5 PAC (23%). PEM/IRI was safe based on lead-in. Median number of cycles of therapy administered was 3 (range 0-13). Treatment-related Gr 3 or 4 AE occurred in 7 (32%) of 22 pts overall: 4 (18%) had at least one Gr 3 AE attributed to PEM (1 pt each with pain, ALT increase, or nausea; 2 with fatigue); 7 (32%) had at least one Gr 3/4 AE attributed to chemo (2 with fatigue, 2 with neutropenia; 1 each with pain, ALT increase, hyponatremia, diarrhea, nausea, and/or acute kidney injury). No grade 5 AE. ORR was 9%: PR in 2 pts (9%), SD 3 pts (14%), PD 13 pts (60%); 4 pts (18%) unevaluable (off study before first scheduled scan). Median PFS 2 mo. At last follow-up, 5 pts (23%) were alive with 1 pt still on treatment. Median OS 4 mo. Of 21 pts off treatment, 76% off for PD, 10% off for AE, 14% off for withdrawal of consent/other therapy. Conclusions: PEM + chemotherapy was not effective in this pretreated, biomarker-unselected population of EP-PDNECs arising in different organs. Biomarker studies are planned (Parts A/B). Clinical trial information: NCT03136055.

scholarly journals Rare Occurrence of a Poorly Differentiated Neuroendocrine Tumor of the Bladder

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Katherine Dowd ◽  
Charles Rotenberry ◽  
Douglas Russell ◽  
Mitchell Wachtel ◽  
Werner de Riese
Keyword(s):  
Cell Carcinoma ◽  
Neuroendocrine Tumor ◽  
Survival Data ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Disease Recurrence ◽  
Small Cell ◽  
Treatment Regimens ◽  
Poorly Differentiated ◽  
Carcinoma Of The Bladder

Neuroendocrine tumors rarely occur in the urinary bladder. They can be carcinomatous, subdivided into small cell and large cell pathology. Small cell carcinoma of the bladder is a rarity that may present at an advanced pathologic stage. No treatment regimens have been standardized for local or metastatic disease. Review of the recent literature shows equivalent survival data for localized disease treated with chemoradiotherapy combined with either bladder sparing surgery or radical cystectomy. Patients with significant comorbidities are an additional challenge. We report a case of poorly differentiated neuroendocrine tumor of the bladder, which could not be classified as small or large cell carcinoma, complicated by significant comorbidities. After management with transurethral resection of the tumor, adjuvant chemotherapy, and radiation, the patient is alive and asymptomatic nearly 1 year after initial TURBT with no evidence of disease recurrence.

Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses

2006 ◽  
Vol 120 (4) ◽  
pp. 289-297 ◽  
Author(s):  
E Babin ◽  
V Rouleau ◽  
P O Vedrine ◽  
B Toussaint ◽  
D de Raucourt ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Neuroendocrine Carcinoma ◽  
Paranasal Sinuses ◽  
Neuron Specific Enolase ◽  
Current Treatment ◽  
Small Cell ◽  
Sinonasal Tract ◽  
Neuroendocrine Neoplasms ◽  
Hormone Production ◽  
Small Cell Neuroendocrine Carcinoma

Introduction: Small cell neuroendocrine carcinoma (SNEC) of the sinonasal tract is a rare disease.Objective: Report a descriptive study of a relatively large cohort of SNEC of the nasal cavity and paranasal sinuses.Method: The medical records of 21 patients presenting with nasal and paranasal SNEC to various French hospitals, from 1989 to 2003, were analysed to determine the clinical features and current treatment of the disease.Results: Patient data were obtained from eight French hospitals. Twelve of the patients were male and nine were female, with a mean age at presentation of 55 years (range: 27 to 79 years). Patients' staging for nasal cavity malignancy was: T1, four; T2, three; T3, one; T4, 13; N0, 18; N2, three; M0, 20; and M1, one. None of the patients suffered from SNEC of the sinonasal tract with ectopic hormone production. Immunohistochemistry proved useful for diagnosis in 20 cases. Twelve cases were positive for cytokeratin, 14 for chromogranin, eight for neuron-specific enolase and 11 for neuron-specific synaptophysin. One patient had an adenocarcinoma and an inverted papilloma associated with neuroendocrine carcinoma. Patients underwent surgery (11 cases), radiotherapy (14 cases) and chemotherapy (12 cases). Recurrence occurred in 10 cases. Five patients had visceral metastases or cervical lymph node involvement. Nine of the patients died within four years of onset of the disease.Conclusion: Small cell neuroendocrine carcinoma of the sinonasal tract is an uncommon neoplasm with aggressive clinical behaviour. Recurrence is frequent and the prognosis is poor. However, the current treatment of these neuroendocrine neoplasms varies widely.

scholarly journals SMARCA4/BRG1-Deficient Sinonasal Carcinoma: Morphologic Spectrum of an Evolving Entity

2021 ◽  
Author(s):  
Aanchal Kakkar ◽  
Subiyathul Farah Ashraf ◽  
Amber Rathor ◽  
Amit Kumar Adhya ◽  
Suresh Mani ◽  
...  
Keyword(s):  
Early Recognition ◽  
Multimodality Treatment ◽  
Large Cell ◽  
Undifferentiated Carcinoma ◽  
Small Cell ◽  
Biological Behavior ◽  
Clinicopathologic Features ◽  
Sinonasal Carcinoma ◽  
Poorly Differentiated Carcinoma ◽  
Poorly Differentiated

Context.— Molecular analysis of poorly differentiated/undifferentiated sinonasal neoplasms has resulted in identification of a growing number of genetically defined tumors. SMARCA4-deficient sinonasal carcinoma is one such recently described entity that emerged from within sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and teratocarcinosarcoma (TCS). Objective.— To identify SMARCA4-deficient sinonasal carcinomas from a large institutional cohort of poorly differentiated/undifferentiated carcinomas and evaluate their clinicopathologic features. Design.— SMARCA4/BRG1 immunohistochemistry was performed on all tumors diagnosed as SNUC, poorly differentiated carcinoma, NEC, and TCS during a 12-year period. SMARCA2/BRM and INSM1 immunostaining was performed in SMARCA4-deficient cases. Results.— Twelve SMARCA4-deficient sinonasal carcinomas were identified among 299 cases. Morphologically, 5 cases were large cell NEC, 2 cases were small cell NEC, and 5 were TCS. SMARCA4 loss was diffuse and complete in 10 cases, while 2 cases showed focal retention. Most cases showed diffuse cytokeratin staining accompanied by weak, usually focal staining for chromogranin and synaptophysin. INSM-1 showed negativity in most cases. All cases showed retained SMARCA2 expression. IDH1/2 mutation was absent in all cases analyzed. Four of 7 patients died of disease, and aggressive multimodality treatment had better outcome. Conclusions.— SMARCA4-deficient sinonasal carcinomas are morphologically akin to sinonasal poorly differentiated NECs and TCS, display cytokeratin positivity and only focal staining for neuroendocrine markers, and have aggressive biological behavior. Inclusion of SMARCA4 in the immunohistochemical panel for diagnostic workup of all sinonasal NEC and TCS phenotypes will facilitate their early recognition. Comprehensive germline and somatic mutational analyses of these tumors are necessary for further insights into their molecular pathogenesis.

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 DPre: computational identification of differentiation bias and genes underlying cell type conversions

2019 ◽  
Author(s):  
Simon Steffens ◽  
Xiuling Fu ◽  
Fangfang He ◽  
Yuhao Li ◽  
Isaac A Babarinde ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Large Cell ◽  
Cell Types ◽  
Supplementary Information ◽  
Computational Techniques ◽  
Cell Type ◽  
Mixed Cell ◽  
Directional Bias ◽  
Differentiated Cells

Abstract Summary Cells are generally resistant to cell type conversions, but can be converted by the application of growth factors, chemical inhibitors and ectopic expression of genes. However, it remains difficult to accurately identify the destination cell type or differentiation bias when these techniques are used to alter cell type. Consequently, there is demand for computational techniques that can help researchers understand both the cell type and differentiation bias. While advanced tools identifying cell types exist for single cell data and the deconvolution of mixed cell populations, the problem of exploring partially differentiated cells of indeterminate transcriptional identity has not been addressed. To fill this gap, we developed driver-predictor, which relies on scoring per gene transcriptional similarity between RNA-Seq datasets to reveal directional bias of differentiation. By comparing against large cell type transcriptome libraries or a desired target expression profile, the tool enables the user to visualize both the changes in transcriptional identity as well as the genes accounting for the cell type changes. This software will be a powerful tool for researchers to explore in vitro experiments that involve cell type conversions. Availability and implementation Source code is open source under the MIT license and is freely available on https://github.com/LoaloaF/DPre. Supplementary information Supplementary data are available at Bioinformatics online.

Immunohistochemical Expression of Estrogen and Progesterone Receptors in Primary Pulmonary Neuroendocrine Tumors

2008 ◽  
Vol 132 (12) ◽  
pp. 1889-1895
Author(s):  
Gabriel Sica ◽  
Patrick L. Wagner ◽  
Nassar Altorki ◽  
Jeffrey Port ◽  
Paul C. Lee ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Neuroendocrine Tumors ◽  
Progesterone Receptors ◽  
Large Cell ◽  
Small Cell ◽  
Neuroendocrine Neoplasms ◽  
Typical Carcinoid ◽  
Combined Small Cell Carcinoma ◽  
Estrogen And Progesterone Receptor

Abstract Context.—Lung and breast carcinomas are among the most prevalent cancers. Advances in cancer therapies can provide survival benefit and be potentially curative, even in metastatic disease. Due to the high prevalence of these carcinomas, it is not unusual to encounter lung nodule(s) in a patient with breast carcinoma, and distinguishing between primary and metastatic disease is critical for management/treatment. Occasionally neuroendocrine differentiation is present in breast carcinoma, making its distinction from pulmonary/nonpulmonary neuroendocrine tumors in the lung difficult. Objective.—To assess estrogen and progesterone receptor expression in the entire spectrum of pulmonary neuroendocrine tumors. Design.—Seventy-one neuroendocrine neoplasms including typical carcinoids (42), atypical carcinoids (7), small cell carcinomas (14), large cell neuroendocrine carcinomas (2), and combined small cell carcinomas (6) were evaluated for estrogen and progesterone receptors. Mammary and non–small cell lung carcinomas were also stained for comparison. Results.—The entire spectrum of neuroendocrine neoplasms demonstrated focal to diffuse estrogen (typical carcinoid, 23; atypical carcinoid, 6; small cell carcinoma, 8; large cell neuroendocrine carcinoma, 2; combined small cell carcinoma, 4) and progesterone (typical carcinoid, 11; atypical carcinoid, 2; small cell carcinoma, 7; large cell neuroendocrine carcinoma, 0; combined small cell carcinoma, 2) expression. There was no correlation between sex and estrogen/progesterone status. Estrogen and progesterone staining were also noted in endothelial cells. Relative to neuroendocrine carcinomas, mammary carcinomas expressed estrogen and progesterone more frequently. Non–small cell carcinomas had greater and similar immunoreactivity for estrogen and progesterone, respectively. Conclusions.—Although estrogen and progesterone receptor staining is frequently associated with breast and gynecologic primaries, it can also be observed in “nontarget” organs. Therefore, presence of estrogen and/or progesterone expression in neuroendocrine tumors involving the lung should not exclude a primary pulmonary neoplasm.

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