Large cell neuroendocrine carcinoma of the ampulla of Vater

BACKGROUND: Neuroendocrine tumors of the ampulla of Vater are extremely rare, and few cases of large cell neuroendocrine carcinoma (LCNEC) of the ampulla have been reported. METHODS: A 48-year-old male with obstructive jaundice was admitted to our hospital. On examination the patient was found to have a periampullary growth and subsequently underwent the Whipple's procedure. RESULTS: Histopathological examination and immunohistochemistry revealed features of LCNEC of the ampulla of Vater. The patient developed multiple liver metastases 6 months after Whipple's procedure. CONCLUSION: LCNEC of the ampulla of Vater is rare and highly aggressive, with a dismal prognosis.     

Intrathoracic manifestations of disseminated prostatic adenocarcinoma

Four cases of disseminated adenocarcinoma of the prostate illustrating the clinical spectrum of intrathoracic involvement in this disease are presented. In two cases the presenting features of prostatic cancer were with lymphangitis carcinomatosa and an isolated pleural effusion, whereas two other cases developed intrathoracic metastases in the setting of previously known locally advanced prostatic cancer. In one this took the form of hilar and mediastinal lymphadenopathy and in the other that of pulmonary nodules. An immuno-cytochemical marker for prostatic specific antigen, a highly sensitive and specific tool for identifying prostatic epithelium, identified the prostate as the primary site of malignancy in the first two cases. Symptomatic and radiological responses were noted in all four cases after bilateral orchidectomy. Pulmonary metastases are common in the advanced stages of prostatic cancer but may also be present at the initial presentation with the disease even when the primary tumour is not clinically apparent. We recommend that (i) immuno-cytochemical stains for prostatic specific antigen are applied to all lung, pleural and mediastinal biopsy specimens showing adenocarcinoma in male patients, and (ii) all males with intrathoracic adenocarcinoma have prostatic aspiration cytology performed if the prostatic specific antigen stain is positive.     

Large cell neuroendocrine carcinoma of the lung: clinical, CT, and pathologic findings in 11 patients.

The purpose of this study was to describe the clinical, computed tomographic (CT), and pathologic findings of large cell neuroendocrine carcinoma (LCNEC) of the lung. CT and pathologic findings as well as clinical features of surgically proven LCNEC of the lung were reviewed retrospectively in 11 consecutive patients (eight men and three women; mean age, 63 years; range, 44-77 years). Chest CT showed peripheral mass or nodule (n = 8) and central mass with distal atelectasis (n = 3). Six tumors were accompanied by mediastinal (n = 3) and hilar (n = 3) lymph node enlargement at CT. On pathologic examination, all resected tumors showed necrosis of variable extent (mean: 38%, range; 10-70%). The areas of intrinsic lipoid pneumonia and tumor emboli in two patients appeared at CT as areas of ground-glass opacity surrounding the tumor. Mediastinal nodal metastases were seen in three (27%) patients. Pathologic staging of 11 patients was IB in six, IIA in one, IIB in one, IIIA in two, and IIIB in one. Follow-up data showed extrathoracic metastases in four patients at mean follow-up period of 15 months. One patient died of distant metastasis 5 months after the surgery. CT findings of LCNEC of the lung are nonspecific and similar to those of other non-small cell lung cancers and extrathoracic metastasis is seen in approximately one third of the patients with follow-up study.     

Large-cell neuroendocrine carcinoma of the distal bile duct

Large-cell neuroendocrine carcinoma (LCNEC) in the distal bile duct is very rare and different from common distal bile duct adenocarcinoma. A 77-year-old man was admitted with obstructive jaundice. Severe stenosis of the distal bile duct was revealed by percutaneous transhepatic cholangiography. Subtotal stomach-preserving pancreaticoduodenectomy was performed. A tumor measuring 1.8 cm in diameter was located in the distal bile duct. Both histopathological and immunohistochemical examination of the resected specimen revealed features of LCNEC of the bile duct. The patient developed multiple liver metastases, lung metastases, and local recurrence and died of disease 3 months after the operation. The clinical behavior of LCNEC in the distal bile duct appears to be highly aggressive with early metastases and a fatal outcome.     

肺大细胞神经内分泌癌

肺大细胞神经内分泌癌是一种高度恶性神经内分泌肿瘤,属于大细胞癌的变异亚型,但其生物学特性类似于小细胞肺癌.肺大细胞神经内分泌癌同时具备神经内分泌形态学特征和神经内分泌分化特征,具有较强的侵袭性,单独手术治疗疗效差,包括辅助化疗在内的多学科治疗有望提高患者的预后.     

Eosinophilic pneumonia and thoracic metastases as an initial manifestation of prostatic carcinoma

We herein report an 80-year-old man with prostatic carcinoma who developed eosinophilic pneumonia and intrathoracic metastases. He presented with shortness of breath, cough, and fever as a chief complaint. Chest X-ray and computed tomography showed bilateral pulmonary nodules, intrathoracic lymphadenopathy, and right-sided consolidation. Positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) showed poor uptake in these nodules and lymph nodes. The patient subsequently received a pelvic computed tomography scan, which revealed a massively enlarged prostate. The serum prostate specific antigen level was elevated to 4,181.2 ng/mL, and a transrectal biopsy revealed prostatic adenocarcinoma. Based on the morphological and immunohistochemical findings, the nodules in the lung and the lymph nodes were diagnosed as secondary neoplasm from the prostate. As for right-sided consolidation, remarkable bronchoalvelar lavage fluid eosinophilia was detected, that was compatible with eosinophilic pneumonia. Eosinophilic pneumonia in this case disappeared and has not recurred by treatment of prostatic carcinoma and steroid therapy for a week, and was regarded to be tumor-associated. Although prostatic carcinoma with an initial manifestation of intrathoracic metastases and eosinophilic pneumonia is uncommon, physicians should suspect the condition. In addition, we should also keep in mind that prostatic carcinoma sometimes shows poor uptake in FDG-PET. PET: Positron emission tomography, FDG: (18)F-flouorodeoxyglucose.     

Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene.

A transgenic mouse model for prostate and mammary cancer has been developed in mice containing a recombinant gene expressing the simian virus 40 early-region transforming sequences under the regulatory control of the rat prostatic steroid binding protein [C3(1)] gene. Male transgenic mice develop prostatic hyperplasia in early life that progresses to adenoma or adenocarcinoma in most animals surviving to longer than 7 months of age. Prostate cancer metastases to lung have been observed. Female animals from the same founder lines generally develop mammary hyperplasia by 3 months of age with subsequent development of mammary adenocarcinoma by 6 months of age in 100% of the animals. The development of tumors correlates with the expression of the transgene as determined by Northern blot and immunohistochemical analyses. The results of these experiments demonstrate that the C3(1) regulatory region used in these experiments is useful for targeting expression to the prostate and mammary gland. To our knowledge, this experimental system is the first reported transgenic mouse model for prostate cancer. These transgenic animals offer the opportunity to study hormone response elements in vivo and the multistage progression from normal tissue to carcinoma in the prostate and mammary glands.     

A case of prostatic adenocarcinoma clinically presenting as supraclavicular and mediastinal lymphadenopathy]

We report a 70-year-old man with prostatic carcinoma presenting as supraclaviculer and mediastinal lymphadenopathy. He had no urinary tract symptoms, and computed tomography and FDG-PET showed no abnormality in the prostate or pelvic lymph nodes. Metastatic prostatic adenocarcinoma was finally diagnosed from the results of immunohistochemical staining for PSA of a biopsy specimen of the mediastinal lymph node, and he was treated by hormonal therapy. There are fears that some other similar cases might be treated with chemotherapy as lung cancer without immunohistochemical staining. Prostatic carcinoma should always be considered in the differential diagnosis of elderly men with supraclaviculer or mediastinal lymph node metastases, since appropriate treatment will lead to a prolonged survival.     

Adenoid cystic/basal cell carcinoma of the prostate:case report

Although most prostate carcinomas belong to the conventional acinar type, unusual variants have been reported. The adenoid cystic/basal cell carcinoma of the prostate is a rare tumor with distinctive histopathologic features. There are quite few publications in the literature concerning the diagnosis, treatment, and prognosis of this neoplasm. METHODS. A 71-year-old man had an increased PSA value (5.11 ng/dL); the prostatic biopsy examination was positive for adenoid cystic/basal cell carcinoma. For this reason we proceeded with radical prostatectomy. The histology examination showed an acinar conventional carcinoma and adenoid cystic/basal cell carcinoma. At eight months the patient did not show any recurrence. CONCLUSIONS. Various histologic and immunohistochemical features are helpful in recognizing the adenoid cystic/basal cell carcinoma of the prostate. Clinically, the only difference from a conventional adenocarcinoma is that the PSA value is usually normal or only slightly increased. This tumor has a biological potential that can result in metastases in some cases; the current treatment consists primarily in the surgical resection. A close, long-term follow-up is strongly recommended.     

Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma

Purpose According to the World Health Organization (WHO) classification of pulmonary large cell neuroendocrine carcinoma (LCNEC), one of the neuroendocrine tumors of the lung, is considered as a variant of non-small cell lung carcinoma. The objective of this study was to investigate the treatment strategy for LCNEC.Methods We retrospectively reviewed the clinical information of 12 patients with LCNEC.Results Three patients with stage I disease underwent curative resection but all relapsed within 20 months. One with stage IIA disease underwent non-curative resection received adjuvant chemoradiotherapy (cisplatin plus etoposide) and is well with no evidence of recurrence. Two with stage IIIB disease received concurrent chemoradiotherapy. Both achieved partial response (PR) but relapsed within 2 months. One elderly patient with stage IIIA disease received vinorelbine alone and did not respond. Of five patients with stage IV disease, three received platinum-based chemotherapy but no patient achieved PR. Of five patients with gefitinib as salvage therapy, one achieved PR.Conclusions The prognosis of LCNEC is poor. To improve the outcome, we must evaluate the effectiveness of adjuvant or neoadjuvant therapy in patients with resectable disease. In addition, the evaluation of systemic and multimodality treatment strategies similar as in small cell lung cancer is worthy of consideration.     

Chemotherapy targeted to cancers through tumoral hormone receptors.

Work on cytotoxic analogs of luteinizing hormone-releasing hormone (LH-RH), somatostatin and bombesin, designed for targeting chemotherapy to peptide receptors on various cancers, is reviewed here as the project is at advanced stages of development and clinical trials are pending. Cytotoxic analogs of LH-RH, AN-152 and AN-207, containing doxorubicin (DOX) or 2-pyrrolino-DOX (AN-201), respectively, target LH-RH receptors and can be used for the treatment of prostatic, breast, ovarian and endometrial cancers and melanomas. AN-201 was also incorporated into the cytotoxic analog of somatostatin, AN-238, which can be targeted to receptors for somatostatin in prostatic, renal, mammary, ovarian, gastric, colorectal and pancreatic cancers as well as glioblastomas and lung cancers, suppressing the growth of these tumors and their metastases. A cytotoxic analog of bombesin AN-215, containing 2-pyrrolino-DOX, was likewise synthesized and successfully tested in experimental models of prostate cancer, small cell lung carcinoma, gastrointestinal cancers and brain tumors expressing receptors for bombesin/gastrin-releasing peptide. This new class of targeted cytotoxic peptide analogs might provide a more effective therapy for various cancers.     

A clinical study of advanced large cell neuroendocrine carcinoma]

Large cell neuroendocrine carcinoma (LCNEC) is a newly recognized clinicopathologic entity. The clinical features of advanced LCNEC are still unclear, because most of the previous reports have described resected cases. The aim of this study was to clarify the clinical characteristics and response to chemotherapy in patients with advanced LCNEC. From June 2002 to July 2004, nine patients (seven men and two women, median age 61) with advanced LCNEC were admitted to our hospital. We reviewed the clinical manifestations, tumor markers, and treatment of these patients. Seven of nine patients (78%) were current or ex-smokers. As for tumor markers, the levels of progastrin-releasing peptide (proGRP) and neuron-specific enolase (NSE) were elevated in six patients (67%) and five patients (56%), respectively. The diagnosis of LCNEC was made based on the resected specimens in 8 patients including resection of brain metastasis in 1 and CT-guided needle biopsy in 1. One patient was stage IIIA, 1 was stage IIIB, 3 were stage IV, and 4 had postoperative recurrence. Treatment included chemotherapy alone in 7 patients, chemotherapy plus whole brain radiation in 1, and postoperative radiotherapy in 1. Of 7 patients treated by chemotherapy alone who had received carboplatin-based chemotherapy. 5 showed partial response, yielding response rate of 71.4%. The proGRP level was frequently elevated in patients with advanced LCNEC and the response rate of LCNEC to carboplatin-based chemotherapy was comparable to that of small cell lung cancer.     

Ectopic ACTH syndrome associated with large-cell neuroendocrine carcinoma of the lung

Although ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a well-known paraneoplastic phenomenon, an association with large-cell neuroendocrine carcinoma of the lung (LCNEC) has not been reported. We describe a 63-year-old man with metastatic LCNEC to the left temporomandibular joint (TMJ) who presented with progressive muscle weakness and bilateral lower leg edema for 2 weeks. He did not have a typical Cushingoid appearance nor used diuretics. His newly noted hypertension, hypokalemia (plasma potassium (K) concentration 1.8 mEq/L) with renal K wasting, and metabolic alkalosis suggested a state of mineralocorticoid excess. His plasma renin activity and aldosterone concentrations were low, but cortisol and ACTH levels were extremely elevated, consistent with ACTH-dependent Cushing's syndrome. Nonsuppressible plasma cortisol level and normal sella turcica on magnetic resonance imaging pointed to EAS. A strongly positive stain for ACTH from the metastatic left TMJ mass supported LCNEC-related EAS. His hypokalemia and hypertension were controlled with spironolactone and K supplementation. This is the first reported case of EAS in LCNEC and should be kept in mind as a cause of hypokalemia in lung cancer patients.     

肺大细胞神经内分泌癌CT表现及临床特征

目的分析肺大细胞神经内分泌癌(LCNEC)的CT表现及临床特征,以提高对该病的认识及诊治水平。 方法回顾性分析我院收治经病理证实的80例LCNEC患者的临床资料、CT征象并复习相关文献。 结果临床症状最常见为咳嗽咳痰,约占71.25%,CT检查示肿瘤平均直径(58.23±33.58)mm,纵隔型5例,中央型23例,周围型52例;肿瘤出现钙化16例,分叶征78例,毛刺征63例,形态不规则72例,胸膜粘连71例,淋巴结肿大60例;肿瘤平扫CT值约(33.63±8.28)Hu,动脉期平均强化幅度约(17.42±9.30)Hu;34例首诊即发现单发或多处转移,其中骨转移16例,颅内转移14例,肾上腺转移7例,肺内转移6例,肝脏转移5例,脾脏转移2例。 结论LCNEC好发于有长期大量吸烟史的老年男性,临床表现及实验室指标均缺乏特异性,确诊主要依靠组织学病理及免疫组织化学检查。其CT表现具有一定的特征性,对于重度吸烟史的老年男性,当CT发现肺内较大结节或不规则肿块并伴有分叶、边界清晰、强化不均及早期转移时应考虑到该病可能。其标准治疗方案存在很大争议,主张早期以手术治疗为主的综合治疗。早诊断、早治疗对于提高LCNEC患者生存率尤为重要。     

Vascular endothelial growth factor and signaling in the prostate: more than angiogenesis

In cloning tyrosine kinase genes in dog prostate cells, a fragment of the vascular endothelial growth factor (VEGF) receptor 1 or Flt-1 was sequenced. To test for a functional protein, Flt-1 antibodies were used to probe immunoprecipitated tyrosine phosphorylated proteins. Western blotting revealed a major 170-180 kDa band and a few bands below 116 kDa in dog prostate and human prostatic carcinoma PC-3 cells, with higher levels in PC-3. Similar results were obtained with human placental membranes used as a source of Flt-1. That the major Flt-1 tyrosine phosphorylated protein was likely VEGF-R1 and part of VEGF signaling pathways was shown by enhanced level of only this protein when PC-3 cells were exposed to VEGF. Accordingly specific cell surface receptor complexes, displaced by VEGF but not EGF and compatible with Flt-1 in size, were revealed by chemical cross-linking after 125I-VEGF binding. Similarly to the prostatic neuroproduct, gastrin-releasing peptide/bombesin, VEGF directly triggered the tyrosine phosphorylation of focal adhesion kinase and stimulated PC-3 cell motility. The titration of prostate tissue sections with VEGF-A antibodies revealed a confined staining in chromogranin A and/or serotonin positive neuroendocrine (NE) cells, including in primary tumors and lymph node metastases. Given that NE differentiation is associated with advanced disease, that NE cells are a significant source of VEGF in prostatic tumors, and that VEGF directly act on prostate cancer cells in vitro, VEGF-A may be more than angiogenic in prostate cancer and hence favor progression by affecting tumor cells.     

Small cell carcinoma of the prostate: an underrecognized entity

Adenocarcinoma is by far the most commonly diagnosed histologic subtype among prostate malignancies. Historically, there has been little awareness of the rare but lethal small cell carcinoma (SCC) in association with prostate cancer. Within the last decade, however, several reports have documented the existence of a neuroendocrine-like tumor arising from cells in the prostate. There is evidence that the development of poorly-differentiated neuroendocrine cells (similar to those found in oat cell carcinomas of the lung) can be seen in the progression of an initially pure adenocarcinoma, possibly due to the totipotential nature of the basal or reserve cells normally present in the prostatic acini. Although pure SCC is rare, admixtures of adenocarcinoma and small cell components may be more prevalent than previously believed. Since effective treatment of a prostatic tumor, or part of a tumor, with an SCC etiology differs from that of pure adenocarcinoma, early recognition of any histologic or clinical changes in the patient with prostate cancer may alter the course of the disease.     

Large cell neuroendocrine carcinoma arising from the left main bronchus

A 67-year-old man was referred to our hospital for a detailed medical examination of a bronchial polyp that was detected during chest computed tomography. Bronchoscopic examination revealed a tumor that almost occluded the main left bronchus. Nd-YAG laser treatment and tumor removal with biopsy forceps were conducted. On the basis of the histopathological and immunohistochemical features, large cell neuroendocrine carcinoma (LCNEC), T2aN0M0, stage IB was diagnosed. After induction chemotherapy with a combination of cisplatin and etoposide, a sleeve resection of the left main bronchus with telescoping bronchial anastomosis was performed. LCNEC typically occurs in the peripheral lung field, but here, we report a rare case of LCNEC arising from the left main bronchus.     

Primary pure large cell neuroendocrine carcinoma of the ovary: A rare case report and review of literature

Introduction:Ovarian large cell neuroendocrine carcinoma (LCNEC), or ovarian non-small cell neuroendocrine carcinoma, which is a newly described tumour in the classification of primary ovarian neoplasms by the World Health Organization, is a rare entity that is frequently associated with a surface epithelial and germ cell neoplasm component. Few cases have been reported in the literature, and only 18 primary pure ovarian LCNEC cases have been reported so far, including our 1 case. Ovarian LCNEC is a highly aggressive tumor with a poor prognosis even at an early stage.Patient concerns:We report a case of a 55-year-old postmenopausal woman who complained of abdominal pain. CT examination revealed a mass in the right adnexial region and CA125 level was elevated.Diagnosis:She underwent a exploratory laparotomy, and diagnosed as LCNEC histopathologically.Interventions:Cytoreductive surgery was administered to the patient, and had accepted 5 cycles of chemotherapy consisting of paclitaxel and cisplatin.Outcomes:Follow-up for 12 months showed no clinical or radiological evidence of disease recurrence.Conclusion:This case is 1 of the ovarian LCNEC which is a rare and extremely malignant tumor. Diagnosis requires histopathology and immunohistochemistry. The treatment includes primary cytoreductive surgery followed by chemotherapy.     

Primary large cell neuroendocrine carcinoma in the common bile duct: First Asian case report

Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases. Herein, we report an unusual case of a pure primary LCNEC of the common bile duct (CBD). A 75-year-old female presented with nausea and jaundice. The patient underwent a CBD excision with lymph node dissection. Upon histological and immunohistochemical examination, the tumor exhibited pure large cell-type neuroendocrine features. Metastases were noted in two of the eight lymph nodes. The patient was administered adjuvant chemotherapy. The patient’s cancer recurred 7 mo after surgery, and the patient died from liver failure 5 mo after recurrence. The prognosis of LCNEC of CBD remains poor despite curative resection and adjuvant chemotherapy. The role of additional therapies, such as multimodal treatment including radiation therapy, must be further studied to improve the prognoses of patients.     

Proliferative disorders of the aging human prostate: involvement of protein hormones and their receptors.

The majority of elderly men is affected by benign and malignant diseases of the prostate. Both proliferative disorders, i.e., benign hyperplasia of the prostate (BPH) and prostate cancer (PCa)-which has recently emerged as the most common male malignancy in industrialized countries-seem to be governed by endocrine factors such as sex steroid hormones, but auto/paracrine factors are involved as well. Age-related changes in levels and ratios of endocrine factors as androgens, estrogens, gonadotropins, and prolactin (PRL) and changes in the balance between auto/paracrine growth-stimulatory and growth-inhibitory factors such as insulin-like growth factors (IGFs), epidermal growth factor (EGF), nerve growth factor (NGF), IGF-binding proteins (IGFBPs), and transforming growth factor beta (TGFbeta) are meant to be responsible for abnormal prostatic growth. We investigated the existence of putative local regulatory circuits involving the protein hormones, human growth hormone (hGH), human placental lactogen (hPL), and hPRL, and their corresponding receptors in prostatic tissue specimens (transurethral resections of the prostate, TURP; n = 11), in the prostatic cancer cell lines PC3, Du145, LnCap, a virus-transformed BPH cell line (BPH-1), and in a normal healthy prostate by RT-PCRs and highly specific and sensitive immunofluorometric assays (IFMA). Neither hPRL nor hGH was detected at the mRNA or protein levels in prostatic tissue and cell lines, with the exception of 2 of 11 prostatic TURP-samples, which showed weak expression of the PL-A/B genes. PRL- and GH-receptors were expressed in all normal and pathological prostatic specimens. Surprisingly, PRL-receptor expression was not detectable in prostatic cancer cell lines. The trophic effects of exogenous hGH, hPL, and hPRL were investigated by cell proliferation assays (WST-I) in prostatic primary cell cultures and PCa cell lines. hGH significantly (p < 0.005) increased cell proliferation up to 138+/-3.2% (1 nM hGH), while hPL and hPRL revealed only moderate effects. Our data suggest that local auto/paracrine networks of protein hormone actions are not involved in the pathology of BPH or prostatic cancer. On the other hand, systemic pituitary-derived hGH can increase the proliferative response of BPH and PCa, acting directly on the target organ prostate, via the hGH-R. In this case, envisaged GH substitution in elderly people must be viewed at with caution because age-related declines in GH/IGF-I could act as a protective mechanism against abnormal cell growth.