Neuroendocrine Carcinoma (neuroendocrine + carcinoma)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Neuroendocrine Carcinoma

  • cell neuroendocrine carcinoma
  • large cell neuroendocrine carcinoma
  • pulmonary large cell neuroendocrine carcinoma
  • small cell neuroendocrine carcinoma


  • Selected Abstracts


    A Study of Moderately Differentiated Neuroendocrine Carcinomas of the Larynx and an Examination of Non-Neoplastic Larynx Tissue for Neuroendocrine Cells

    THE LARYNGOSCOPE, Issue 7 2004
    Jin-Haeng Chung MD
    Abstract Objectives/Hypothesis: To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist. Study Design: Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells. Methods: Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells. Results: Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin. Conclusions: Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC. [source]


    Invasive neuroendocrine carcinoma of the breast

    CANCER, Issue 19 2010
    A distinctive subtype of aggressive mammary carcinoma
    Abstract BACKGROUND: Neuroendocrine carcinoma (NEC) of the breast, a pathologic entity newly defined in the 2003 World Health Organization classification of tumors, is a rare type of tumor that is not well recognized or studied. The purpose of this first case-controlled study is to reveal the clinicopathologic features, therapeutic response, and outcomes of patients with NEC of the breast. METHODS: Seventy-four patients with NEC of the breast who were treated at The University of Texas M. D. Anderson Cancer Center were analyzed; 68 of them had complete clinical follow-up. Two cohorts of invasive mammary carcinoma cases were selected to pair with NEC to reveal demographic, pathologic, and clinical features at presentation, along with therapeutic response to treatment and patient outcomes. RESULTS: NEC was more likely to be estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative. Despite similar age and disease stages at presentation, NEC showed a more aggressive course than invasive ductal carcinoma, with a higher propensity for local and distant recurrence and poorer overall survival. High nuclear grade, large tumor size, and regional lymph node metastasis were significant negative prognostic factors for distant recurrence-free survival; high nuclear grade and regional lymph node metastasis were also significant negative prognostic factors for overall survival. Although endocrine therapy and radiation therapy showed a trend toward improved survival, the small number of cases in this study limited the statistical power to reveal therapeutic benefits in NEC of the breast. CONCLUSIONS: NEC is a distinct type of aggressive mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely different clinical entity. Cancer 2010. © 2010 American Cancer Society. [source]


    High-grade neuroendocrine carcinoma presenting as an abscess: Diagnosis by fine needle aspiration and review of the literature

    DIAGNOSTIC CYTOPATHOLOGY, Issue 9 2008
    Jonathon B. Herbst M.D.
    Abstract Neuroendocrine carcinomas (NEC) comprise about 2% of all carcinomas. Review of the literature indicates only a few cases of NEC presenting as an abscess, all having been diagnosed by tissue biopsy. Here, we report the FNA diagnosis of a high-grade neuroendocrine carcinoma presenting as an abscess of the axilla/chest wall in a 68-year-old man and review the pertinent literature. Diagn. Cytopathol. 2008;36:670,673. © 2008 Wiley-Liss, Inc. [source]


    Fine-needle aspiration of metastatic prostatic neuroendocrine carcinomas: Cytomorphologic and immunophenotypic features

    DIAGNOSTIC CYTOPATHOLOGY, Issue 8 2008
    Guoping Cai M.D.
    Abstract Metastatic prostatic carcinoma may, in rare occasions, present as a neuroendocrine tumor. Its recognition is crucial to avert a wrongful exclusion of prostate as a primary site. We report five cases of metastatic prostatic neuroendocrine carcinoma diagnosed by image-guided fine-needle aspiration biopsy. The aspirate smears showed loosely cohesive or dyscohesive clusters of tumor cells with scanty (three cases) to moderate amount (two cases) of cytoplasm, speckled or coarse chromatin and inconspicuous nucleoli. Nuclear molding and necrosis were focally present in two cases. Immunohistochemically, the tumor cells were positive for synaptophysin or/and chromogranin, but negative for prostatic specific antigen and prostatic specific acid phosphatase. Review of prior prostate biopsies/resections revealed adenocarcinoma with focal neuroendocrine differentiation in all cases, with two cases being newly recognized on retrospective review. Confirming neuroendocrine differentiation in the prior biopsy/resection may help to establish a link between metastasis and prostate primary. Diagn. Cytopathol. 2008; 36: 545,549. © 2008 Wiley-Liss, Inc. [source]


    Synchronous metastases to the liver and pancreas from a primary neuroendocrine carcinoma of the breast diagnosed by fine-needle aspiration

    DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2008
    Maria McIntire M.D.
    Abstract Extrapulmonary neuroendocrine carcinoma is uncommon. Cases of primary neuroendocrine carcinoma of the breast have been reported, though rare. We report the case of a 53-year-old woman who underwent a mastectomy for breast carcinoma and presented three years later with synchronous masses in the head of the pancreas and liver. Fine-needle aspiration of both organs revealed a neuroendocrine carcinoma. The original breast tumor was reviewed and found to express neuroendocrine markers. A diagnosis of a primary neuroendocrine carcinoma of the breast was rendered. Diagn. Cytopathol. 2008;36:54,57. © 2007 Wiley-Liss, Inc. [source]


    Primary cancer of the sphenoid sinus,A GETTEC study,

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2009
    Pierre Olivier Vedrine MD
    Abstract Background. Primary involvement of the sphenoid sinus occurs in 2% of all paranasal sinus tumors and is associated with dismal prognosis. Optimal management remains debatable. Methods. A total of 23 patients were treated for a primary cancer of the sphenoid sinus from 1988 to 2004. Charts were reviewed for patient-, tumor-, and treatment-related parameters. Univariate and multivariate analyses were conducted to identify prognostic factors for locoregional control and survival. Results. Cranial neuropathies were present in 12 patients. Pathologic findings included adenoid cystic carcinoma, adenocarcinoma, lymphoma, squamous cell carcinoma, sarcoma, neuroendocrine carcinoma, melanoma, and malignant hemangiopericytoma. All but 2 patients had stages III to IV cancer. Radiotherapy was performed in 18 patients and chemotherapy in 12. Of 10 patients undergoing surgery, total excision with grossly negative margins was achieved in 4 patients and subtotal resection in 6. Median locoregional control and overall survival were 12 and 41 months, respectively. On multivariate analysis, cranial neuropathy was associated with worse locoregional control and survival. Surgery was rarely complete because of advanced stages at presentation, but it yielded better outcomes than other treatments without surgery in non lymphoma-cases. Conclusion. Early CT and MRI should be performed when facing aspecific, rhinological, or neuro-ophtalmological symptoms. Cranial neuropathies indicate a worse prognosis. Surgery, including debulking surgery, may be preferred to combined modality treatments without surgery. Its apparently favorable impact on prognosis would need to be tested in homogenous histological groups of patients, which is impossible because of the rarity of the disease. Highly conformal radiotherapy (adjuvant or definitive) should be encouraged and optimized with concurrent chemotherapy in advanced stages. Aggressive multidisciplinary management including surgery, chemotherapy, and radiotherapy should be encouraged and adapted on histology and tumor extensions. Progress is still warranted to improve outcomes. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source]


    Primary and secondary small cell neuroendocrine carcinoma of the larynx: A review

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2008
    Alfio Ferlito MD, DPath, FASCP, FDSRCS, FHKCORL, FRCPath, FRCSEd, FRCSGlasg, FRCSI
    Abstract Primary laryngeal small cell neuroendocrine carcinoma (SCNC) is an unusual malignancy accounting for <0.5% of laryngeal carcinomas. To date, approximately 200 cases of primary and 5 of secondary SCNC of the larynx have been reported. This tumor most often presents in the sixth and seventh decades in men who are heavy cigarette smokers. The lesion may be associated with different paraneoplastic syndromes (ectopic adrenocorticotropic hormone syndrome, Schwartz,Bartter syndrome or syndrome of inappropriate secretion of antidiuretic hormone, and Eaton,Lambert myasthenic syndrome) or with ectopic hormone production. The diagnosis is based essentially on the histologic appearance of the tumor, confirmed by immunocytochemical investigations. Concurrent chemoradiotherapy regimens offer potential for long-term survival. This tumor is biologically aggressive, and the extent of the disease is the most significant independent prognostic factor of survival. The survival rate is similar to that with pulmonary SCNC. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source]


    Small cell neuroendocrine carcinoma of the maxillary sinus,A case report and nude mouse transplantable model,

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2002
    Kazuma Noguchi DDS
    Abstract Background A rare case of small cell neuroendocrine carcinoma (SNEC) arising in the maxillary sinus is presented, and a SNEC tumor line serially transplantable in nude mice was established. Tumor marker for SNEC is also discussed. Methods The tumor tissues obtained from operated material were heterotransplanted subcutaneously into nude mice. Histopathologic studies and immunoradiometric assays for NSE and pro-GRP in serum were performed. Results The primary lesion was composed of tumor nests of small cells with hyperchromatic nuclei and was positive for NSE and chromogranin A immunohistochemically. Serum levels of NSE and pro-GRP changed dynamically, reflecting the clinical status. Nude mouse tumor showed similar histologic features to those of original tumor and expressed NSE. Neuroendocrine granules were detected in tumor cells in electron microscopy. Serum NSE level in nude mice was elevated in proportion to the relative tumor weight. Conclusions Serum NSE and pro-GRP were useful tumor markers for extrapulmonary SNEC. A SNEC tumor transplantable in nude mice would provide a valuable model for characterization of this lesion. © 2002 Wiley Periodicals, Inc. [source]


    Poorly differentiated tumours of the anal canal: a diagnostic strategy for the surgical pathologist

    HISTOPATHOLOGY, Issue 1 2007
    B Balachandra
    Poorly differentiated malignancies affecting the anal canal are uncommon but pose diagnostic difficulties because of the wide range of normal cell types that may occur within a limited anatomical region. The range of lesions that may present as poorly differentiated tumours includes squamous cell carcinoma, adenocarcinoma, small and large cell neuroendocrine carcinoma, neuroendocrine carcinoma expressing epithelial cytokeratins and other patterns of mixed differentiation, undifferentiated carcinoma, malignant melanoma, lymphoma and secondary tumours. This review discusses the differential diagnosis of these neoplasms with the aid of short illustrative case studies. [source]


    Metastatic Basal Cell Carcinoma with Neuroendocrine Differentiation or Merkel Cell Carcinoma?

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005
    A. Andea
    We present here a case of basal cell carcinoma (BCC) with neuroendocrine features that has transformed into a high-grade neuroendocrine carcinoma with various morphologic features of Merkel cell carcinoma (MCC). A 54-year-old white female was treated for a BCC of the right thigh. Pathologic examination revealed an otherwise classical BCC that demonstrated granular positivity for chromogranin. Six years later the patient developed a right inguinal lymphadenopathy diagnosed as metastatic BCC with squamous changes. The metastatic BCC showed partial peripheral palisading and a trabecular pattern. Two years later the patient underwent a right nephrectomy due to obstruction of the right ureter by metastatic BCC. After another four years the patient came back with extensive involvement of the appendiceal wall and right ovary by a diffusely infiltrating metastatic basaloid and trabecular carcinoma. This time the tumor had many histologic features of MCC and showed strong positivity for chromogranin and also for CK20 and NSE. Electron microscopy revealed neurosecretory granules. This case is an example of a chromogranin positive basal cell carcinoma of the skin, which transformed during multiple recurrences into a high grade neuroendocrine carcinoma with features of Merkel cell tumor, demonstrating the potential for cross differentiation among skin tumors. [source]


    Merkel cell (primary neuroendocrine) carcinoma of the skin with nodal metastasis showing rhabdomyosarcomatous differentiation

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2002
    María-Teresa Fernández-Figueras
    Background:, We describe a unique case of Merkel cell (primary neuroendocrine) carcinoma of the skin with a lymph node metastasis showing rhabdomyosarcomatous differentiation. Skeletal muscle differentiation has occasionally been described in primary small cell neuroendocrine carcinomas and considered a form of dual differentiation rather than a collision tumor. In the present case, capacity for divergent differentiation appeared late in the course of the tumor, which suggests a clonal origin for both components of the neoplasm. Conclusions:, The coexistence of neural and rhabdomyoblastic types of differentiation, best epitomized by the Triton tumor, has been construed as the product of dual differentiation of cells originated from neural crest-derived ectomesenchyme. Since Merkel cells seem to originate from a pluripotential primitive keratinocyte and not from the neural crest, rhabdomyoblastic differentiation in a metastasis of primary neuroendocrine carcinoma of the skin probably reflects the close proximity between the programs of neural and skeletal muscle differentiation, which would have been sequentially activated in the case we are reporting. [source]


    Multiple cutaneous metastases of neuroendocrine carcinoma derived from the uterine cervix

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2009
    W-J Lee
    [source]


    Significant high expression of cytokeratins 7, 8, 18, 19 in pulmonary large cell neuroendocrine carcinomas, compared to small cell lung carcinomas

    PATHOLOGY INTERNATIONAL, Issue 2 2010
    Ryo Nagashio
    The aim of the present study was to clarify protein profiling in small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC). The proteomic approach was used, and involved cell lysate from two cell lines (N231 derived from SCLC and LCN1 derived from LCNEC), with 2-D gel electrophoresis (2-DE). In the present study, 25 protein spots with greater than twofold quantitative differences between LCN1 and N231 cells on 2-DE gels were confirmed. Within the 25 identified proteins, cytokeratins (CK) 7, 8, 18 and 19 were upregulated in LCN1 cells compared with N231 cells. The expression of CK7, 8, 18, and 19 was further studied on immunohistochemistry with 81 formalin-fixed and paraffin-embedded pulmonary carcinomas, which included 27 SCLC, 30 LCNEC, 14 adenocarcinomas, and 10 squamous cell carcinomas. Although the expression of CK7, 8, 18, and 19 was observed in all histological types, the mean immunostaining scores of CK7, 8, 18, and 19 were significantly higher in LCNEC than in SCLC (P < 0.001, P < 0.001, P < 0.01 and P < 0.001, respectively). These data suggest that the biological characteristics of LCNEC and SCLC may be different and the expression of CK may serve as differential diagnostic markers. [source]


    Cytokeratin 20-positive large cell neuroendocrine carcinoma of the colon

    PATHOLOGY INTERNATIONAL, Issue 8 2005
    Tomoya Kato
    Herein is presented a case of cytokeratin (CK) 20-positive large cell neuroendocrine carcinoma of the colon, in which the tumor was clinically at stage IV and located in the ascending colon. Pathological examination of the resected tumor revealed nested and solid proliferation of large undifferentiated cells with vesicular nucleus and prominent nucleoli. No areas showed differentiation toward adenocarcinoma or squamous cell carcinoma. Tumor cells were immunohistochemically positive for chromogranin A, synaptophysin, CD 56 (focal), and bore electron-dense granules. With these features, the tumor was diagnosed as a large cell neuroendocrine carcinoma of the colon. Liver metastasis and local recurrence progressed, and the patient died of the primary disease 7 months after operation. The autopsy confirmed this diagnosis without detectable tumors in the lungs. Interestingly, more than half of the tumor cells were positive for CK 20, while CK 7 was not expressed. Most neuroendocrine carcinomas do not express CK 20, with the exception of Merkel cell carcinomas, and most colorectal adenocarcinomas express CK 20. To the best of the authors' knowledge, the present case is the first CK 20-positive, CK 7-negative colorectal neuroendocrine carcinoma to be described, suggesting a link between colorectal neuroendocrine carcinoma and conventional adenocarcinoma. [source]


    Anal canal neuroendocrine carcinoma with Pagetoid extension

    PATHOLOGY INTERNATIONAL, Issue 8 2004
    Limei Guo
    A case of anal canal neuroendocrine carcinoma with Pagetoid intraepithelial extension is presented. An 80-year-old man was admitted to hospital with a complaint of pain in the anorectal region. Clinical examination revealed a hard and fixed mass in the anal canal, and subsequent biopsy of the lesion showed it to be a carcinoma. The surgically resected specimen showed a solid tumor measuring 3.4 × 3.2 cm within the area from the surgical anal canal to the anatomical anal canal. Tumor cells proliferated predominantly with compact nests. Many tumor cells had a high nuclear-to-cytoplasmic ratio, dispersed chromatin, and conspicuous nucleoli. Additionally, neoplastic cells focally formed a glandular structure. Some polygonal neoplastic cells were small with round nuclei. A rosette-like arrangement was also focally observed. In addition, tumor cells exhibited Pagetoid extension into the overlying epithelium of the histological anal canal. Both the underlying original neoplastic cells and the Pagetoid spreading tumor cells showed cytoplasmic granules positive for Grimelius staining and immunopositivity for carcinoembryonic antigen, synaptophysin and cytokeratins 7 and 20. These findings are highly suggestive of neuroendocrine differentiation of adenocarcinoma cells. To the best of our knowledge, this is the first case of anal canal neuroendocrine carcinoma with Pagetoid extension into the overlying epithelium of the histological anal canal. [source]


    Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature review

    APMIS, Issue 8 2010
    SALVATORE SQUILLACI
    Squillaci S, Marchione R, Piccolomini M, Colombo F, Bucci F, Bruno M, Bisceglia M. Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature review. APMIS 2010; 118: 543,56. The objectives of this study were to evaluate the frequency of carcinoid tumors of the extrahepatic biliary ducts (EHBDs) and the pathologic progression and the role of surgery in the management of this disease. We describe two cases of malignant carcinoids of the EHBDs, which presented as common bile duct tumors in two adult male patients, aged 52 and 70 years, who were diagnosed histologically on surgical resection specimens. A comprehensive review of the literature has also been performed with a focus on survival data. Microscopically, the tumors presented herein were composed of relatively small rounded cells with a trabecular or nesting pattern. Both cases were diffusely immunopositive for chromogranin and synaptophysin, and one of them was also focally reactive with somatostatin and pancreatic polypeptide. There was no expression in any of these tumors of thyroid transcription factor-1 (TTF-1), gastrin, insulin, glucagon, vasoactive intestinal peptide (VIP) and prolactin. The tumor showed transmural invasion in both cases, with lymph node metastasis and subcapsular liver tissue infiltration in one. Both patients are alive with no evidence of disease 41 months and 59 months, respectively, after surgery. Despite being extremely uncommon, with only 70 cases reported to date, carcinoids should be included in the differential diagnosis of EHBD tumors. This study emphasizes the necessity of complete surgical resection as the gold standard treatment for these lesions, and the importance of a correct pathologic diagnosis for prognostic implications. [source]


    Role of definitive radiotherapy in treating patients with inoperable Merkel cell carcinoma: The Westmead Hospital experience and a review of the literature

    AUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2009
    Clare SL Koh
    ABSTRACT Merkel cell carcinoma (MCC) is an uncommon aggressive primary cutaneous neuroendocrine carcinoma with a propensity to spread to regional lymph nodes and distant sites. The head and neck is the commonest site for presentation (50,60%) and recent evidence suggests patients treated with excision (to achieve a negative microscopic margin) and adjuvant wide-field radiotherapy (RTx) have an improved survival compared with surgery alone. Surgery is often not possible in elderly patients with multiple co-morbidities and in patients with advanced lesions. Definitive RTx therefore remains an option in these inoperable patients, with data to report its benefit. We report the results of eight patients with inoperable MCC treated with RTx alone between 1993 and 2007 at Westmead Hospital, Sydney, Australia, and also review the relevant literature on definitive RTx in the treatment of MCC. The median age at diagnosis was 82.5 years in five women and three men. All patients were Caucasian and none were immunosuppressed. Seven of eight patients were clinically node-positive. The mean duration of follow up was 12 months. A median dose of 50 Gy was prescribed. Seven of eight patients with inoperable MCC achieved in-field control, with most eventually relapsing distantly. Treatment-related toxicity was acceptable. In keeping with our results, other studies also report high rates of in-field locoregional control following RTx alone. These findings highlight the radioresponsiveness of advanced MCC and support a recommendation of moderate-dose RTx alone in select cases. Lower-dose palliative dose fractionation schedules (e.g. 25 Gy in five fractions) may be considered in patients of very poor performance status. [source]


    Merkel cell carcinoma (primary cutaneous neuroendocrine carcinoma): An overview on management

    AUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 3 2006
    Michael J Veness
    SUMMARY Merkel cell carcinoma is an uncommon but aggressive primary cutaneous neuroendocrine (small cell) carcinoma. There is ongoing debate regarding the optimal treatment of this disease. The early literature comprised small institutional studies with inherent weaknesses. Recent data have emerged from larger studies, including those from Australian institutions, that adds support to a multimodality approach as best practice. Despite this, the outcome for patients with unfavourable disease remains poor and in most series 25,30% of patients die as a direct result of Merkel cell carcinoma. The head and neck is the commonest site for presentation (50,60%) and wide excision (2,3 cm) of the primary lesion is usually recommended, although achieving this is often difficult within functional and cosmetic constraints. All clinically node-negative patients should be considered candidates for elective nodal treatment and those with clinical nodal disease should undergo nodal dissection and adjuvant radiotherapy. Recent evidence suggests that patients treated with surgery and adjuvant locoregional radiotherapy experience a better disease-free survival compared with those undergoing surgery alone. The role of platinum-based chemotherapy is evolving. The aim of this article is to discuss relevant issues in the management of a patient with Merkel cell carcinoma. [source]


    Invasive neuroendocrine carcinoma of the breast

    CANCER, Issue 19 2010
    A distinctive subtype of aggressive mammary carcinoma
    Abstract BACKGROUND: Neuroendocrine carcinoma (NEC) of the breast, a pathologic entity newly defined in the 2003 World Health Organization classification of tumors, is a rare type of tumor that is not well recognized or studied. The purpose of this first case-controlled study is to reveal the clinicopathologic features, therapeutic response, and outcomes of patients with NEC of the breast. METHODS: Seventy-four patients with NEC of the breast who were treated at The University of Texas M. D. Anderson Cancer Center were analyzed; 68 of them had complete clinical follow-up. Two cohorts of invasive mammary carcinoma cases were selected to pair with NEC to reveal demographic, pathologic, and clinical features at presentation, along with therapeutic response to treatment and patient outcomes. RESULTS: NEC was more likely to be estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative. Despite similar age and disease stages at presentation, NEC showed a more aggressive course than invasive ductal carcinoma, with a higher propensity for local and distant recurrence and poorer overall survival. High nuclear grade, large tumor size, and regional lymph node metastasis were significant negative prognostic factors for distant recurrence-free survival; high nuclear grade and regional lymph node metastasis were also significant negative prognostic factors for overall survival. Although endocrine therapy and radiation therapy showed a trend toward improved survival, the small number of cases in this study limited the statistical power to reveal therapeutic benefits in NEC of the breast. CONCLUSIONS: NEC is a distinct type of aggressive mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely different clinical entity. Cancer 2010. © 2010 American Cancer Society. [source]


    Genetic alterations in early-stage pulmonary large cell neuroendocrine carcinoma

    CANCER, Issue 6 2004
    Kenzo Hiroshima M.D.
    Abstract BACKGROUND Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are high-grade malignant neuroendocrine tumors. Histologic differentiation between SCLC and LCNEC is difficult in some cases and to the authors' knowledge, genetic alterations associated with LCNEC have not been identified. Therefore, the authors studied genetic alterations found in LCNEC and compared them with those of SCLC and classic large cell carcinoma (CLCC). METHODS Twenty-two patients with UICC TNM Stage I LCNEC, 12 patients with Stage I CLCC, and 11 patients with SCLC with limited disease were studied. All tumors were resected completely. Loss of heterozygosity (LOH) of the tumor cells was detected using fluorescent primers. Methylation status of the p16 gene and expression of the p53 protein, retinoblastoma protein, and p16 protein were evaluated immunohistochemically. RESULTS LOH at TP53 and 13q14 was observed in most patients. The prevalence of LOH at D3S1295, D3S1234, and D5S407 was significantly higher in patients with LCNEC and SCLC than in patients with CLCC. The prevalence of LOH at D5S422 was higher in patients with CLCC and in patients with SCLC than in patients with LCNEC. Expression of the p16 protein was observed more frequently in SCLC than in CLCC or LCNEC. Hypermethylation of the p16 gene was observed more frequently in LCNEC than in SCLC. Patients with allelic losses at D3S1234 and D10S1686 had poorer prognoses compared with patients without allelic losses at these sites. CONCLUSIONS Genetic alterations of LCNEC were akin to those of SCLC. However, allelic losses at 5q and abnormalities in the p16 gene may differentiate LCNEC from SCLC. Cancer 2004. © 2004 American Cancer Society. [source]


    The diagnostic value of on-site cytopathological evaluation and cell block preparation in fine-needle aspiration cytology of liver masses

    CYTOPATHOLOGY, Issue 5 2006
    K. Ceyhan
    Objective:, The aims of this study were to evaluate the typing accuracy of conventional smear (CS), cell block (CB) preparations and combined use of both procedures (CS + CB) for the diagnosis of hepatic malignancies and to determine whether immediate on-site cytopathological evaluation improves the diagnostic yield of liver fine-needle aspiration cytology (FNAC). Methods:, Ultrasound-guided FNABs were performed on 323 consecutive cases with liver masses between December 2002 and December 2004. Histologically and/or clinically correlated 167 cases were included in the study. Preliminary FNAB results, results of CS, CB, and combined use of CS and CB were compared regarding diagnostic sensitivity, specificity, and accuracy for the diagnosis of malignancy. Subtyping accuracies of different methods were also compared. Results:, The sensitivity of on-site cytopathological examination and CS were both 92.8%. The sensitivity of CS + CB was slightly better than that of CB (93.5% versus 84.8%). Specificity of all procedures was achieved 100%. Diagnostic accuracy of on-site cytopathological evaluation, CS, CB, and CS + CB were 93.9%, 93.9%, 87.2%, and 94.5%, respectively. A specific subtype diagnosis of malignant tumours could be rendered accurately on the basis of preliminary diagnosis in 71%, CS in 75.4%, CB in 78.3% and combined approach in 92% of cases. In terms of typing accuracy, 87.5% of HCCs, 93.2% of adenocarcinomas, 92.3% of neuroendocrine carcinomas, 100% of lymphomas and 100% of other malignant tumours were correctly subclassified in the final cytopathological diagnosis. The agreement between preliminary diagnosis and final cytopathological diagnosis was 77.2%. Conclusion:, With use of on-site cytopathological evaluation and combined use of CS and CB, the diagnostic accuracy of liver tumours approaches 100% and also significantly improve diagnostic and subtyping accuracy of liver malignancies. [source]


    Fine-needle aspiration of metastatic prostatic neuroendocrine carcinomas: Cytomorphologic and immunophenotypic features

    DIAGNOSTIC CYTOPATHOLOGY, Issue 8 2008
    Guoping Cai M.D.
    Abstract Metastatic prostatic carcinoma may, in rare occasions, present as a neuroendocrine tumor. Its recognition is crucial to avert a wrongful exclusion of prostate as a primary site. We report five cases of metastatic prostatic neuroendocrine carcinoma diagnosed by image-guided fine-needle aspiration biopsy. The aspirate smears showed loosely cohesive or dyscohesive clusters of tumor cells with scanty (three cases) to moderate amount (two cases) of cytoplasm, speckled or coarse chromatin and inconspicuous nucleoli. Nuclear molding and necrosis were focally present in two cases. Immunohistochemically, the tumor cells were positive for synaptophysin or/and chromogranin, but negative for prostatic specific antigen and prostatic specific acid phosphatase. Review of prior prostate biopsies/resections revealed adenocarcinoma with focal neuroendocrine differentiation in all cases, with two cases being newly recognized on retrospective review. Confirming neuroendocrine differentiation in the prior biopsy/resection may help to establish a link between metastasis and prostate primary. Diagn. Cytopathol. 2008; 36: 545,549. © 2008 Wiley-Liss, Inc. [source]


    The frequency of neuroendocrine cell hyperplasia in patients with pulmonary neuroendocrine tumours and non-neuroendocrine cell carcinomas

    HISTOPATHOLOGY, Issue 3 2009
    Selim M H Rizvi
    Aims:, To evaluate the frequency of neuroendocrine cell hyperplasia (NEH) in resected neuroendocrine tumours and non-neuroendocrine cell carcinomas and to study its relationship to selected clinical parameters. Methods and results:, Random blocks without tumour from resected typical carcinoids (TCs, n = 46), atypical carcinoids (ACs, n = 14), large cell neuroendocrine carcinomas (LCNECs, n = 18), small cell carcinomas (SCLCs, n = 22), adenocarcinomas (ADENOs, n = 26) and squamous cell carcinomas (SCCs, n = 18) were stained for CD56 and evaluated for linear proliferations, cell aggregates (>4 CD56+ cells), and tumourlets (<5 mm with basement membrane invasion). There was a statistically significant difference between the frequency of NEH in all neuroendocrine tumours (TC/AC/LCNEC/SCLC, 35/100, 35%) (P = 0.009) when compared with non-neuroendocrine carcinomas (ADENO/SCC, 6/44, 14%) and in the frequency of NEH in TC (21/46, 46%) versus all other tumours (AC/LCNEC/SCLC/SCC/ADENO, 20/98, 20%) (P = 0.001). There was increased frequency of NEH in peripheral TCs (8/13, 62%) compared with central TCs (14/33, 43%) (P = 0.33). There was no association between smoking history and NEH. Clinical and imaging data showed no evidence of an increased frequency of obliterative bronchiolitis in patients with NEH. Conclusions:, NEH is significantly increased in the background lung of neuroendocrine tumours when compared with non-neuroendocrine carcinomas, supportive data for NEH having neoplastic potential. [source]


    Merkel cell (primary neuroendocrine) carcinoma of the skin with nodal metastasis showing rhabdomyosarcomatous differentiation

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2002
    María-Teresa Fernández-Figueras
    Background:, We describe a unique case of Merkel cell (primary neuroendocrine) carcinoma of the skin with a lymph node metastasis showing rhabdomyosarcomatous differentiation. Skeletal muscle differentiation has occasionally been described in primary small cell neuroendocrine carcinomas and considered a form of dual differentiation rather than a collision tumor. In the present case, capacity for divergent differentiation appeared late in the course of the tumor, which suggests a clonal origin for both components of the neoplasm. Conclusions:, The coexistence of neural and rhabdomyoblastic types of differentiation, best epitomized by the Triton tumor, has been construed as the product of dual differentiation of cells originated from neural crest-derived ectomesenchyme. Since Merkel cells seem to originate from a pluripotential primitive keratinocyte and not from the neural crest, rhabdomyoblastic differentiation in a metastasis of primary neuroendocrine carcinoma of the skin probably reflects the close proximity between the programs of neural and skeletal muscle differentiation, which would have been sequentially activated in the case we are reporting. [source]


    Significant high expression of cytokeratins 7, 8, 18, 19 in pulmonary large cell neuroendocrine carcinomas, compared to small cell lung carcinomas

    PATHOLOGY INTERNATIONAL, Issue 2 2010
    Ryo Nagashio
    The aim of the present study was to clarify protein profiling in small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC). The proteomic approach was used, and involved cell lysate from two cell lines (N231 derived from SCLC and LCN1 derived from LCNEC), with 2-D gel electrophoresis (2-DE). In the present study, 25 protein spots with greater than twofold quantitative differences between LCN1 and N231 cells on 2-DE gels were confirmed. Within the 25 identified proteins, cytokeratins (CK) 7, 8, 18 and 19 were upregulated in LCN1 cells compared with N231 cells. The expression of CK7, 8, 18, and 19 was further studied on immunohistochemistry with 81 formalin-fixed and paraffin-embedded pulmonary carcinomas, which included 27 SCLC, 30 LCNEC, 14 adenocarcinomas, and 10 squamous cell carcinomas. Although the expression of CK7, 8, 18, and 19 was observed in all histological types, the mean immunostaining scores of CK7, 8, 18, and 19 were significantly higher in LCNEC than in SCLC (P < 0.001, P < 0.001, P < 0.01 and P < 0.001, respectively). These data suggest that the biological characteristics of LCNEC and SCLC may be different and the expression of CK may serve as differential diagnostic markers. [source]


    LKB1 protein expression in neuroendocrine tumors of the lung

    PATHOLOGY INTERNATIONAL, Issue 2 2008
    Randa Mahmoud Sobhi Amin
    During a recent investigation of LKB1 gene abnormality in lung lesions, strong expression of LKB1 protein in normal neuroendocrine (NE) cells of the bronchial epithelium was found. Because LKB1 functions as a tumor suppressor gene, the question of whether alteration of LKB1 expression is related to the development of pulmonary NE tumors of various grades was investigated. LKB1 immunohistochemistry was examined in a total of 68 primary pulmonary NE tumors consisting of 30 specimens of small cell lung carcinoma (SCLC), 23 large cell neuroendocrine carcinomas (LCNEC), two atypical carcinoids, and 13 typical carcinoids. Loss or low expression (<20% immunoreactive cells) of LKB1 protein expression was more frequently observed in high-grade NE tumors (SCLC and LCNEC; 45/53, 84.9%) than in typical and atypical carcinoids (3/15; 20%). The difference in LKB1 immunoreactivity between the high-grade NE tumors and the carcinoid group was statistically significant (P < 0.0001). In conclusion, marked reduction of LKB1 expression in high-grade NE tumors of the lung suggests a possible role of LKB1 inactivation in its tumorigenesis. Although a few previous studies indicated rare genetic alterations of LKB1 in SCLC, further studies including analysis of other NE tumors and focusing on epigenetic abnormalities of LKB1 gene are warranted. [source]


    Cytokeratin 20-positive large cell neuroendocrine carcinoma of the colon

    PATHOLOGY INTERNATIONAL, Issue 8 2005
    Tomoya Kato
    Herein is presented a case of cytokeratin (CK) 20-positive large cell neuroendocrine carcinoma of the colon, in which the tumor was clinically at stage IV and located in the ascending colon. Pathological examination of the resected tumor revealed nested and solid proliferation of large undifferentiated cells with vesicular nucleus and prominent nucleoli. No areas showed differentiation toward adenocarcinoma or squamous cell carcinoma. Tumor cells were immunohistochemically positive for chromogranin A, synaptophysin, CD 56 (focal), and bore electron-dense granules. With these features, the tumor was diagnosed as a large cell neuroendocrine carcinoma of the colon. Liver metastasis and local recurrence progressed, and the patient died of the primary disease 7 months after operation. The autopsy confirmed this diagnosis without detectable tumors in the lungs. Interestingly, more than half of the tumor cells were positive for CK 20, while CK 7 was not expressed. Most neuroendocrine carcinomas do not express CK 20, with the exception of Merkel cell carcinomas, and most colorectal adenocarcinomas express CK 20. To the best of the authors' knowledge, the present case is the first CK 20-positive, CK 7-negative colorectal neuroendocrine carcinoma to be described, suggesting a link between colorectal neuroendocrine carcinoma and conventional adenocarcinoma. [source]


    A Study of Moderately Differentiated Neuroendocrine Carcinomas of the Larynx and an Examination of Non-Neoplastic Larynx Tissue for Neuroendocrine Cells

    THE LARYNGOSCOPE, Issue 7 2004
    Jin-Haeng Chung MD
    Abstract Objectives/Hypothesis: To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist. Study Design: Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells. Methods: Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells. Results: Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin. Conclusions: Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC. [source]


    L1 cell adhesion molecule as a predictor for recurrence in pulmonary carcinoids and large-cell neuroendocrine tumors

    APMIS, Issue 2 2009
    HYO SONG KIM
    Pulmonary neuroendocrine tumors are a distinct subset of neoplasms with indolent to aggressive behavior. This study was conducted to evaluate the prognostic role of L1 cell adhesion molecule (L1CAM) in pulmonary neuroendocrine tumors. We retrospectively analyzed L1 expression in 55 cases of completely resected carcinoids and large-cell neuroendocrine carcinomas, by the immunohistochemistry with monoclonal antibody A10-A3 against human L1. L1 immunoreactivity was detected in 34 (61.8%) of 55 specimens. There was a significant correlation between L1 expression and the World Health Organization classification of this tumor (Spearman rank correlation, ,=0.60, p<0.001). With median follow-up of 52.0 months, the 5-year survival rate for patients with low expression of L1 (<20% of tumor cells stained) was significantly better compared with those with high expression of L1 (82.6% vs. 43.7%, p=0.005). L1 was also a significant independent predictor of disease-free survival, and patients with high L1 expression have a higher risk for recurrence compared with those with low L1 expression (hazard ratio, 3.0; 95% confidence interval, 1.2,8.3; p=0.034). L1 expression is significantly associated with aggressiveness and further studies with larger samples are needed to validate potential prognostic value for pulmonary neuroendocrine tumors. [source]


    Composite glandular-endocrine cell carcinomas of the stomach: clinicopathologic and methylation study,

    APMIS, Issue 9 2005
    EUI JIN LEE
    Four cases of very rare composite glandular-endocrine cell carcinoma of the stomach are presented with methylation findings. All but one of the tumors arose in the antrum and two of them were at the early stage. Each composite carcinoma was accompanied by atrophic and metaplastic gastritis in the adjacent mucosa. Three cases showed lymph nodes metastasis, and one of them showed both glandular and neuroendocrine tumor components within the metastatic nodes. Mucin stains were positive in the adenocarcinoma areas while only the neuroendocrine markers were positive in neuroendocrine tumor components. Of all seven markers tested for, p16INK4A methylation was observed in both components of one composite carcinoma and hMLH1 was methylated in the neuroendocrine tumor component within the same tumor. An additional six gastric large cell neuroendocrine carcinomas showed no methylation. Follow up of patients indicated short survival in patients with poorly differentiated neuroendocrine carcinoma components and advanced stages of tumors, while patients with well-differentiated neuroendocrine tumor components and early stages showed long disease-free survival. Our results suggest that hypermethylation of tumor suppressor genes is rare in gastric composite and neuroendocrine carcinomas, and prognosis of gastric composite carcinomas appears to be related to the histopathology of neuroendocrine components and tumor stage. [source]