High-grade neuroendocrine carcinoma of the lung: comparative clinicopathological study of large cell neuroendocrine carcinoma and small cell lung carcinoma.
ABSTRACT Large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) are high-grade neuroendocrine carcinomas. In order to clarify the similarities and differences between these cancers, 22 cases each of LCNEC and SCLC were collected and a comparative pathological study was carried out. First, their clinicopathological characteristics were confirmed, which were very similar to those previously reported. The 5 year survival rate of LCNEC and SCLC patients was 38.3% and 29.7%, respectively. The morphological characteristics of LCNEC and SCLC were then reviewed with regard to the morphology previously used to differentiate these cancers. As a result, many morphological indicators, such as tumor cell size, nuclear/cytoplasmic ratio, nuclear molding, rosette formation, prominent nucleoli and karyolysis were confirmed to be significant indicators for distinguishing LCNEC from SCLC. On comparative immunohistochemistry, LCNEC had significantly high staining scores for the expression of keratin 7 and 18, E- and P-cadherins, beta-catenin, villin 1, retinoblastoma protein (pRB), c-met and alpha-enolase. These results might reflect the differentiation or deviation of LCNEC toward an epithelial nature irrespective of neuroendocrine tumor lineage. In conclusion, the present comparative study of LCNEC and SCLC defined the similarities and differences between these cancers, and showed the biologically and clinicopathologically overlapping spectrum of the tumor lineage.
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ABSTRACT: Pulmonary neuroendocrine tumors have a prognostic spectrum including typical carcinoid (TC), atypical carcinoid (AC), small cell carcinoma (SCLC), and large cell neuroendocrine carcinoma (LCNEC). We conducted a retrospective study to compare their clinicopathological characteristics, immunophenotype, preoperative biopsy and frozen section diagnoses, and prognosis. Ninety cases of surgically treated pulmonary neuroendocrine tumors were studied. Immunohistochemical studies were performed using antibodies to chromogranin A, synaptophysin, and CD56. The preoperative biopsy and frozen section diagnoses were reviewed. The 5-year survival rates for TC, AC, SCLC, and LCNEC were 96.6%, 66.7%, 42.4%, and 38.0%, respectively. T stage and pleural status correlated with outcome of SCLC and LCNEC, but N-stage and overall TNM stage did not. In preoperative biopsy, accurate diagnosis was achieved in 5 of 11 TC, 2 of 4 AC, 6 of 15 SCLC, and 0 of 5 LCNEC cases. Using frozen sections, accurate diagnosis was achieved in 8 of 12 TC, 2 of 11 SCLC, and 0 of 11 LCNEC cases. LCNEC was the most difficult to diagnose using either preoperative biopsy or frozen sections. T stage and pleural status can predict outcome of SCLC and LCNEC. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.Journal of Surgical Oncology 12/2013; DOI:10.1002/jso.23497 · 2.84 Impact Factor
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ABSTRACT: In lung tumors, the association between carcinoids and high-grade neuroendocrine tumors (HGNETs) is controver-sial. To understand the phenotypic similarities/differences between lung carcinoids and HGNETs, we comparatively investigated the expression of three kinds of developing neural transcription factors (DNTFs: BRN2, TTF1 and ASCL1) and multiple endocrine neoplasia type 1 (MEN1) as well as RB1 and P53 using 18 carcinoids and 16 HGNETs. The DNTFs were expressed in 10 of the 18 carcinoids and in all the HGNETs, while normal neuroendocrine cells, which are considered the major cell origin of lung carcinoids and small cell carcinomas, did not express DNTFs. Both the DNTF -and DNTF + carcinoids contained typical and atypical carcinoids. All the DNTF -carcinoids examined were formed in the bronchial wall. All the MEN1 -carcinoids examined were classified into the DNTF -carcinoids, while all the HGNETs expressed MEN1. This finding suggests that DNTF -MEN1 -carcinoids are unlikely to be precursors of HGNETs. Although the status of RB1 and P53 between carcinoids and HGNETs were apparently different, the DNTF + carcinoids of two male patients and one female patient revealed mor-phologies resembling HGNET cells and relatively high Ki67 indices. Further investigation of DNTF expression in carcinoids might provide important clues to understand the association between carcinoids and HGNETs. The World Health Organization (WHO) classifies morphologi-cally identifiable lung neuroendocrine (NE) tumors (NETs) into four categories: typical carcinoid (TC), atypical carcinoid (AC), small cell carcinoma (small cell lung cancer, SCLC) and large cell NE carcinoma (LCNEC). 1–3 Carcinoid tumors are histologically and clinicopathologically subclassified as TC (low-grade NET) or AC (intermediate-grade NET) according to mitotic count and the presence/absence of necrotic foci, 3Pathology International 08/2014; 64(8). DOI:10.1111/pin.12183 · 1.59 Impact Factor
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ABSTRACT: Patient: Female, 60 Final Diagnosis: Large-cell neuroendocrine carcinoma Symptoms: Back pain Medication: - Clinical Procedure: Vertebroplasty Specialty: Oncology. Unusual clinical course. An atypical presentation of large-cell neuroendocrine carcinoma was diagnosed from a metastatic nodule on the chest wall. The patient was a 60-year-old female who presented with intractable back pain with an MRI showing an L3 compression fracture and multiple lesions in L3, L5, and the pelvis. The patient had a 40-pack-year smoking history. On admission, a small, non-tender nodule was noted under her left breast on the chest wall. CT and PET scan confirmed diffuse metastases in the lumbar spine, brain, lung, liver, and pancreas, without knowing the primary site. The patient underwent L3 vertebroplasty and removal of the nodule on the chest wall. The pathology report of the nodule showed large cell neuroendocrine carcinoma (LCNEC). Immunohistochemical stains were positive for cytokeratin AE 1/3, TTF-1, CD56, Synaptophysin, and chromogranin. The stains were negative for CK7, Napsin, cytokeratin 20, GATA-3, mammaglobin, and CEA. A pathology diagnosis of metastatic LCNEC was made, with the lung as the most likely original site. Treatment consisted of pain control through an intra-thecal pump and whole brain radiation followed by systemic chemotherapy. This case elucidates the unusual cutaneous metastatic site for LCNECs, which was biopsied to confirm the diagnosis. This is the first case of LCNEC diagnosed by a cutaneous metastasis. In conclusion, it is possible to diagnose LCNEC of the lung at a distant metastatic site with careful histological and immunohistochemical examination, which can spare patients from more harmful biopsies.01/2014; 15:97-102. DOI:10.12659/AJCR.890094