Primary Large Cell Neuroendocrine Carcinoma Research Articles

Primary pure large cell neuroendocrine carcinoma of the ovary

Neuroendocrine tumors are more common in the female genital tract than in the male genital tract, and most are uterine small cell carcinomas or ovarian carcinoid tumors. Most ovarian tumors are associated with surface epithelial tumors, SertolieLeydig cell tumors, teratoma, small cell carcinoma, pulmonary-type and undifferentiated carcinoma, and nonsmall cell lung cancer [1]. Large cell neuroendocrine carcinoma (LCNEC) of the ovary is unusual and defined as an extremely malignant tumor with an aggressive lethal outcome. For this original and updated review, we searched the databases of PubMed Clinical Queries, MEDLINE, Cochrane Library and UpToDate. We also hand-searched relevant journals and reference lists of identified articles. The keywords used were “ovary”, “pure LCNEC”, and “immunohistochemistry”. We found that only 37 cases of ovarian tumor involving LCNEC associated with surface epithelial stromal tumors and/or teratoma have been reported to date [2e5]. In addition, seven cases of primary LCNEC of the ovary without any associated component have been described [2,3,6e8]. Herein, we present the case of a patient with stage IV primary pure LCNEC of the ovary with liver metastasis and carcinomatosis. A 50-year-old married, Taiwanese female, G3P3, was referred by a clinical oncologist for the evaluation of a pelvic mass. She denied specific systemic disease, a gynecological history, and undergoing major operations previously. She also denied any significant symptoms, such as compression sensation, lower abdominal pain, or abnormal vaginal bleeding. Because of an increased abdominal circumference and a palpable 20-cmmass in the abdomen that had been present for 2 weeks, she was referred by a clinical oncologist and underwent a suboptimal debulking operation with total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial

Primary Large Cell Neuroendocrine Carcinoma of the Renal Pelvis: A Case Report

We report a case of primary large cell neuroendocrine carcinoma of the renal pelvis, diagnosed in a 79-year-old man. The abdominal computed tomography showed a solid, vegetant lesion in the left renal pelvis, conditioning marked hydronephrosis. The patient underwent radical nephroureterectomy. The histological examination showed a large cell neuroendocrine carcinoma associated with a high-grade urothelial carcinoma, with local invasion (pT3). Large cell renal neuroendocrine carcinomas are rare tumors with an aggressive course and a bad prognosis. At present, only five cases were reported in literature.

P1–150 - A Case Report of a Primary Large-Cell Neuroendocrine Carcinoma of the Breast

P1–150 - A Case Report of a Primary Large-Cell Neuroendocrine Carcinoma of the Breast

Clinicopathological features and the impact of the new TNM classification of malignant tumors in patients with pulmonary large cell neuroendocrine carcinoma

The prognosis of patients with large-cell neuroendocrine carcinoma (LCNEC) of the lung is extremely poor and the optimal treatment for these patients has yet to be determined. In this study, we described the clinicopathological characteristics of LCNECs and compared the prognoses of corresponding stages determined by the guidelines of the 6th and 7th editions of the TNM classification of malignant tumors. Clinical data from 42 patients diagnosed with primary LCNEC who underwent treatment at Kitasato University Hospital between 1991 and 2009 were retrospectively analyzed. On follow-up of 42 patients, 22 (52.4%) had confirmed recurrent tumors, including 8 patients with mediastinal lymph node recurrences and 19 with distant metastases. The sites of distant metastases included the brain in 8, bone in 8, liver in 7, lungs in 5 and adrenal glands in 4 patients. For all the patients, the 5-year overall survival rate was 34.7% and the 5-year disease-free survival rate was 32.9%. The 5-year overall survival rates of patients with stage I cancers according to the 6th and 7th staging editions was 51.3% (6th n=18, 7th n=16). Thirteen of 42 patients (31.0%) also had metachronous or synchronous primary cancers. Patients with LCNEC had poor outcomes, even those with stage I tumors classified according to the 7th edition of the TNM classification. Therefore, frequent recurrences in addition to metachronous or synchronous primary cancers in patients with LCNEC should be treated.

A Case of Large Cell Neuroendocrine Carcinoma of the Parotid Gland

Received July 8, 2012 Revised August 22, 2012 Accepted August 27, 2012 Address for correspondence Jin Pyeong Kim, MD Department of Otolaryngology, College of Medicine, Gyeongsang National University, 79 Gangnam-ro, Jinju 660-702, Korea Tel +82-55-750-8178 Fax +82-55-759-0613 E-mail jinpyeong@gnu.ac.kr Large cell neuroendocrine carcinoma is a rare malignant tumor of the parotid gland and has poor prognosis due to its aggressive and rapid growth and easy metastasis. Large cell neuroendocrine carcinoma usually occurs in the lung and intestine. However, a few cases of large cell neuroendocrine carcinoma have been reported in other sites such as the uterine cervix, thymus, urinary bladder, ovary and the ampulla of vater. In large cell neuroendocrine carcinoma of the parotid gland, radical parotidectomy is the first therapeutic step and can be followed by local radiation therapy. We report one case of primary large cell neuroendocrine carcinoma occurring in the parotid gland, and discuss the literature. Korean J Otorhinolaryngol-Head Neck Surg 2013;56:98-101 Key WordsZZLarge cell carcinoma ᆞNeuroendocrine tumors ᆞParotid neoplasms.

“pure” primary large cell neuroendocrine carcinoma of the urinary bladder

“pure” primary large cell neuroendocrine carcinoma of the urinary bladder

A Case of the Large Cell Neuroendocrine Carcinoma of the Urinary Bladder

Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is very rare. Definite treatment strategy has not been established and prognosis of the disease is not clear yet. We report a case of primary LCNEC of the urinary bladder here with some review of the literature. The patient was a 84-year-old man. He underwent transurethral resection of bladder tumor (TURBT). Histological examination revealed a rosette arrangement of the tumor cells by HE staining and immunohistochemical study revealed positive CD 56, synaptophysin, and chromogranin A (LCNEC). After TURBT, he has no sign of recurrence for 8 months. We have to strictly observe the progress because LCNEC is very aggressive.

Unknown primary large cell neuroendocrine carcinoma (LCNEC) in the mediastinum

Unknown primary large cell neuroendocrine carcinoma (LCNEC) in the mediastinum is extremely rare. In this report, we present a case of a 53-year-old man with superior vena cava (SVC) syndrome who developed LCNEC in the middle mediastinum. His chief complaint was facial edema. Chest X-ray revealed an abnormal shadow in the right upper mediastinum. Computed tomography (CT) scan of the chest revealed a 67-mm mass in the middle mediastinum. Tumor invasion caused constriction of the SVC. The patient underwent induction chemoradiotherapy with vinorelbin and cisplatin and concurrent radiation therapy. After induction therapy, the tumor size decreased remarkably and was resected completely. The pathological diagnosis was LCNEC.

A rare case report of a primary large-cell neuroendocrine carcinoma of the breast with coexisting Paget disease

Neuroendocrine carcinomas are malignancies deriving from neuroendocrine cells existing in various sites of the body, most commonly in the lungs and gastrointestinal tract. Primary neuroendocrine carcinomas of the breast are extremely rare, and their diagnosis is confirmed by positive neuroendocrine markers. We describe a case of a 46-year-old woman with a palpable mass in her left breast for the previous 3 months. The tumor was resected and a primary large-cell neuroendocrine tumor of the breast was confirmed by histopathologic examination. Paget disease of the nipple was noted as well.

Neuroendocrine Tumors of the Submandibular Gland

Primary salivary neuroendocrine neoplasms are extremely rare, with only 1 case of carcinoid tumor and 7 cases of primary large-cell neuroendocrine carcinomas having been reported. Salivary small-cell neuroendocrine carcinomas are more frequent, accounting for less than 2% of all salivary malignancies. In addition to a literature review on the subject, the authors describe a rare case of malignant intermediate-grade neuroendocrine tumor of the submandibular gland.

Primary mixed neuroendocrine carcinoma of the bladder with large cell component: a case report and review of the literature

Primary large cell neuroendocrine carcinomas (NECs) of the bladder are rarely encountered, and only a few reports have been documented. Frequently, they are found to be admixed with other histologies. In this report, we describe such a tumor found in a 65-year-old man who underwent radical cystectomy, after initial transurethral resection discovered a small cell NEC pathology. We also reviewed the limited number of neuroendocrine tumors reported containing a large cell component. Given the paucity of these tumors and the resultant difficulty in developing generalized treatment protocols, we promote the use of gene expression models to tailor chemotherapeutic regimens for individual tumors.

Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma

The prognosis for patients with large-cell neuroendocrine carcinoma (LCNEC) of the lung is extremely poor, and an optimal treatment has not yet been established. It has been recently reported that molecular-targeted therapies, such as tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR), are effective in patients with lung carcinoma. In efforts to improve the prognosis of patients with LCNEC, we analyzed gene expression, gene mutations and immunohistochemical (IHC) expression of known molecular targets in LCNECs, and compared the expression to that of lung adenocarcinomas (ACs). Thirteen patients with primary LCNEC and 14 patients with AC were analyzed. We evaluated IHC expression for c-KIT, human epidermal growth factor receptor type 2 (HER2) and vascular endothelial growth factor (VEGF), gene mutations for EGFR, K-ras and c-kit, and gene expression using fluorescence in situ hybridization for EGFR. In cases with LCNEC, the IHC expression of c-KIT, HER2 and VEGF was 76.9, 30.8 and 100%, respectively. There was a significant difference in the IHC expression of c-KIT and HER2 between the LCNEC and AC cases. Two cases of LCNEC had overexpression of HER2, and the frequency of EGFR gene mutations was higher in the the AC group, with only a single EGFR mutation (exon 18) identified in the LCNEC group. Although LCNEC had a higher rate of expression of c-KIT by IHC, no c-kit gene mutations were found. These findings suggest a potential role for anti-VEGF-, anti-c-KIT- and possibly anti-HER2-targeted agents in the treatment of LCNEC.

Primary large cell neuroendocrine carcinoma of the vagina: Cytomorphology of previously unreported case

Squamous carcinoma is the most common malignancy of the vagina. Other malignancies include adenocarcinoma, melanoma, lymphoma, and very rarely, neuroendocrine carcinoma/small-cell carcinoma. Large cell neuroendocrine carcinoma (LCNEC) has not been reported in this location. In this report, we describe a case of LCNEC of the vagina, which is believed to be the first case to date in the English literature. The patient is a 53-year old gravida 3, para 2, African-American woman who had a 4 month history of severe pelvic pain and difficulty voiding and was found to have a firm plate-like mass on the anterior vaginal wall. Thin prep of vaginal swap was interpreted as atypical glandular cells; however, the biopsies showed a large cell neuroendocrine carcinoma which was confirmed by diffuse strong immunoreactivity to AE1/3, CAM5.2, CK7, and CD56 in the tumor cells. Subsequent clinical workup showed that the patient also had numerous metastatic nodules in the bilateral lungs and a vaginal-urethral fistula caused by the tumor. The patient underwent palliative radiation of pelvis for local pain control and then chemotherapy. Although the vaginal tumor increased in size even after radiation, her symptoms were under control and she was doing well for a short period of time. The patient is still alive but developed brain metastasis a year later after initial diagnosis. Despite its rarity, large cell neuroendocrine cell carcinoma should be included in the differential diagnosis when cytomorphology shows features suggestive of neuroendocrine differentiation.

Primary large-cell neuroendocrine carcinoma of the scrotum

Neuroendocrine tumors (NETs) mostly develop from the neural crest cells but a few arise from neuroectoderm. They are common in the lungs and gastrointestinal tract but rare in the genitourinary tract. A 78-year-old man with no family history of malignant or hereditary diseases presented with a 3-month history of a rapidly growing asymptomatic scrotal nodule and swelling in the groin. He had a negative history of sexually transmitted disease and of trauma, fungal infection or chronic irritation in the scrotal area; there was no history of radiotherapy or exposure to chemicals or arsenic. Both the scrotal and groin lesions were excised with a minimum of 1.2 cm of normal skin. Examination of the specimen revealed a confined poorly differentiated large-cell neuroendocrine carcinoma with a metastasis to the inguinal lymph nodes. Three months after the excision we found a local recurrence. The recurrent tumor revealed tumor tissue concurrent with the primary lesion. To the best of our knowledge, there have been no previously published case reports on neuroendocrine tumor of the scrotum.

Primary Large Cell Neuroendocrine Carcinoma of the Kidney

We report a case of a 56-year-old male with a primary large cell neuroendocrine renal carcinoma. Grossly, the left kidney was enlarged by a solid tumor that measured 145 x 125 x 100 mm. Histologically, the tumor consisted of large cells with a moderate to abundant amount of eosinophilic cytoplasm. The nuclei were irregular, some of them with finely or coarsely granular chromatin, others with vesicular chromatin and prominent nucleoli. The tumor cells showed multiple mitotic figures (up to 32 mitoses/10 HPF). In some areas, the tumor cells were arranged in solid sheets; however, the predominant pattern was solid-alveolar, trabecular and cribriform. Large areas of tumor necrosis were found. Immunohistochemically, the tumor cells were positive for synaptophysin, CD56 and CD57. Cytokeratin AE1/AE3, vimentin and CD10 were positive only focally. Chromogranin showed weak cytoplasmic positivity in rare tumor cells. Cytokeratin CAM5.2, cytokeratin 34betaE12, BerEP 4, EMA, TTF-1, cytokeratin 7, cytokeratin 20, calretinin, serotonin, somatostatin, gastrin, calcitonin, glukagon and insulin were negative. Primary large cell neuroendocrine carcinoma of the kidney is a rare tumor. To the best of our knowledge, only 3 cases of a tumor of this type have been reported to date.

Primary large cell neuroendocrine carcinoma of the urinary bladder

Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is rare. It is a type of neuroendocrine carcinoma morphologically distinct from small cell carcinoma. We report here a case of primary LCNEC of the urinary bladder. We observed a very large invasive tumor, which was not able to be detected three months previously by cystoscopy or computed tomography. The tumor cells morphologically and immunohistochemically resembled that of pulmonary LCNEC. With prompt cystoprostatectomy and chemotherapy, the patient is free of disease 16 months after diagnosis. Although LCNEC is usually very aggressive, it may be controlled by early diagnosis and treatment.

Clinical implications of unusual NeuroD and mASH1 expression in a patient with primary large-cell neuroendocrine carcinoma of the duodenum: Report of a case

A 69-year-old woman was referred to our hospital for investigation of tarry stools. Abdominal computed tomography (CT) showed a slightly enhanced heterogeneous mass in the first to second part of the duodenum, adjacent to the gallbladder and head of the pancreas. Endoscopy showed a huge protruding tumor with ulceration in the first part of the duodenum. The preoperative histopathological diagnosis was neuroendocrine carcinoma with expression of synaptophysin. Thus, we performed pancreaticoduodenectomy with gallbladder bed resection. Histopathologically, the tumor was a large-cell neuroendocrine carcinoma (LCNEC) of the duodenum. To our knowledge, this is the first report of duodenal LCNEC arising outside the ampulla of Vater. The patient has been disease-free for 24 months since her operation, without additional therapy. Immunohistochemically, the tumor cells revealed positive expression to NeuroD and faint expression to mASH1 (hASH1): both essential transcriptional factors for normal neural development. The expression patterns of NeuroD and mASH1 suggest a favorable prognosis.

Primary pure large-cell neuroendocrine carcinoma of the ovary

We report a case of a 73-year-old female with a rare simultaneous occurrence of three tumors: ovarian carcinoma, endometrial carcinoma, and breast carcinoma. The ovarian tumor was a primary pure large-cell neuroendocrine carcinoma. Grossly, the left ovary was enlarged by a solid tumor that measured 9×7×7 cm. Histologically, the tumor consisted of large cells with irregular hyperchromatic nuclei and a moderate amount of eosinophilic cytoplasm. In some areas, the tumor cells were arranged in solid sheets; however, the predominant pattern was cribriform and solid-alveolar, with palisaded tumor cells located peripherally. The tumor cells showed multiple mitotic figures (up to 43 mitoses/10 HPF). Large areas of tumor necrosis were found. Immunohistochemically, the tumor cells were positive for EMA, synaptophysin, chromogranin, CD56, and CEA. Cytokeratin 20 was positive focally. Primary large-cell neuroendocrine carcinoma of the ovary is a rare tumor. To the best of our knowledge, only 4 cases of a pure tumor of this type have been reported to date.

A Primary Large Cell Neuroendocrine Carcinoma of the Urinary Bladder in a 19-year-old Man

A Primary Large Cell Neuroendocrine Carcinoma of the Urinary Bladder in a 19-year-old Man Whi-An Kwon, Yun-Sok Ha, Ok-Jun Lee, Yong-June Kim, Seok-Joong Yun, Sang-Cheol Lee, Wun-Jae Kim From the Departments of Urology and Pathology, Chungbuk National University College of Medicine, Cheongju, Korea Primary large cell neuroendocrine carcinomas of the urinary bladder are extremely rare. To date, only six cases of large cell neuroendocrine carcinoma have been reported. We present a case of a 19-year-old man who presented with gross hematuria and who was subsequently found to have a solitary tumor on the dome of the urinary bladder. The patient underwent transurethral resection of the bladder tumor for histological confirmation. A diagnosis of large cell neuroendocrine carcinoma was made based upon immunohistochemical reactivity for synaptophysin and CD56. Based on the pathologic diagnosis, he subsequently had a partial cystectomy. Histologically, the tumor penetrated the perivesical fat. It has now been 6 months since the surgery, and the patient is preparing to receive his 5th cycle of chemotherapy. There is no evidence of tumor recurrence or metastasis. (Korean J Urol 2008;49:647-649) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Primary Large Cell Neuroendocrine Carcinoma of the Breast: Radiologic and Pathologic Findings

Some breast neoplasms are classified as primary neuroendocrine carcinomas because they are positive for neuroendocrine markers. Although neuroendocrine carcinomas can originate from various organs of the body, primary neuroendocrine carcinomas of the breast are extremely rare. The diagnosis of primary neuroendocrine carcinoma of the breast can only be made if nonmammary sites are confidently excluded or if an in situ component can be found. Here we report a primary large-cell neuroendocrine carcinoma (LCNL) involving the left breast. Breast ultrasonography revealed a lobulated, heterogeneous, low-echoic mass in the left breast, and the lesion ap-peared as a well-defined, highly-enhancing mass on a chest computed tomography scan. Ultrasound-guided core needle biopsy was performed on the mass, and primary LCNC was confirmed by histopathologic examination.