Metastatic LCNEC in the skin must be differen- tiated from Merkel cell carcinoma and primary LCNEC of the skin [9, 18, 21]. Merkel cell carci- noma is a rare primary cutaneous carcinoma. This type of tumor is thought to originate from (or differentiate toward) Merkel cells, which are mechanoreceptors present in the epidermis and skin appendages. The typical histopatho- logical feature of Merkel cell carcinoma is pro- liferation of small round cells containing vesicu- lar chromatin and inconspicuous nucleoli, however, Merkel cell carcinomas with large cell features have been reported . Therefore, differentiation from Merkel cell carcinoma is necessary, and immunohistochemical analyses are usually useful. The characteristic immuno- histochemical characteristics of Merkel cell carcinoma include dot-like expression of cyto- keratin 20 (86.7%) and a lack of expression of TTF-1 (3.3%), although cases of cytokeratin 20-negative/TTF-1-positive Merkel cell carcino- ma have been documented . Recently, it has been documented that approximately 80% of cases of Merkel cell carcinoma harbor a novel polyomavirus, referred to as Merkel cell polyomavirus (MCPyV), and immunodetection with monoclonal antibody against MCPyV large T antigen has been recognized as a useful tool in the evaluation of Merkel cell carcinoma . However, MCPyV-negative Merkel cell carcino- ma does exist, and interestingly, MCPyV- negative Merkel cell carcinomas morphologi- cally have more abundant cytoplasm and more irregularly shaped nuclei than MCPyV-positive cases . Moreover, only a few cases of pri- mary cutaneous LCNEC have been reported, which shows positive immunoreactivity for syn- aptophysin, and lacks chromogranin A and dot- like cytokeratin 20 expression . Histopa- thological and immunohistochemical charac- teristics cannot differentiate primary cutane- ous LCNEC from metastatic LCNEC. Therefore, a combination of clinical history, and analyses of histopathological and immunohistochemical features is needed for correct diagnosis. Table 1. Clinicopathological features of metastatic large cell neuroendocrine carcinoma in the skin
Van der Walt, A, MBChB; FCP(SA); Registrar; Huddle K, MBBCh; FCP(SA); FRCP(UK), Head of Department Department of Internal Medicine, Division of Endocrinology, Chris Hani Baragwanath Academic Hospital; University of Witwatersrand Pather S, MBBCh; FCPath(SA)Anat, Consultant, Department of Anatomical Pathology, Chris Hani Baragwanath Academic Hospital University of Witwatersrand; National Health Laboratory Services Korb A, MBChB; Dip PEC; FCP(SA), Registrar, Department of Internal Medicine Division of Endocrinology, Chris Hani Baragwanath Academic Hospital University; University of Witwatersrand Correspondence to: Andrew van der Walt, e-mail: email@example.com Keywords: neuroendocrine tumour, large cell neuroendocrine carcinoma, ectopic ACTH, Cushing’s syndrome, superior mediastinum
Primary large cell neuroendocrine carcinoma (LCNEC) of the urinary tract is an extremely rare neoplasm. Given its rarity, the risk factors, bio- logical properties, and effective therapeutic strategies for LCNEC have yet to be determined. LCNECs originate almost exclusively in the uri- nary bladder [1-17], although they also have been reported, in rare instances, to occur in the kidney [18-20]. To the best of our knowledge, a primary LCNEC of the ureter has not been reported in the literature. Herein, we report the first case of a primary LCNEC of the ureter and focus on the clinicopathological findings. Materials and methods
Abstract: The incidence of large cell neuroendocrine carcinoma (LCNEC) of the lung is rare, and the treatment methods and prognosis for such patients are still subjects of debate. We report a case of a 78-year-old male LCNEC patient for whom stereotactic body radiation therapy was performed. A four-dimensional computed tomography scan was used for simulation, and radiotherapy was planned using the volumetrically modulated arc technique. A total of 55 Gy was delivered in five daily fractions. The treatment was safely completed, and the patient did not report any discomfort. The only side-effect was an intermittent cough. Currently, the patient has received 18 months of outpatient follow-up care with no evidence of disease. In conclusion, stereotactic body radiation therapy can be a valuable treatment option for early stage LCNEC. Keywords: lung, large cell, neuroendocrine carcinoma, stereotactic ablative radiotherapy, radiation therapy
Combined large cell neuroendocrine carcinoma of the lungs (combined LCNEC) with giant cell carcinoma is extremely rare. A 65-year-old man was found to have an abnormal shadow in his left lung field. Computed tomography revealed a solid, round mass measuring 2.8 × 2.2 cm that was located in the left S9. The patient underwent left lower lobectomy and mediastinal lymph node dissection. Histopathological examination revealed an LCNEC, combined with giant cell carcinoma. The patient received by S-1 (TS-1, an oral fluoropyrimidine)
Case presentation: A 59-year-old Japanese man presented to his previous physician with hematuria. Computed tomography revealed masses in the heart and right kidney, and fluorodeoxyglucose-positron emission tomography showed abnormal uptake in the heart. A cardiac biopsy under transesophageal echocardiographic guidance revealed a metastatic tumor. Subsequently, multiple lung lesions were detected, and a right nephrectomy was performed after these metastases were suspected to have originated from renal carcinoma. Large cell neuroendocrine carcinoma of the kidney was ultimately diagnosed. Pancreatic metastasis was detected on computed tomography postoperatively. Three courses of chemotherapy with carboplatin and irinotecan were administered, and were temporarily effective against the metastatic lesions in the lungs and pancreas. However, our patient ’ s general condition deteriorated with the progression of the lesions, and he died 9 months after his initial examination.
Large cell neuroendocrine carcinoma (LCNEC) of the ovary, a rare tumor that is often accompanied by other epithelial and germ cell tumors, is an extremely malig- nant tumor with an aggressive lethal outcome [1–3]. However, there are also some rare diseases entities re- lated to the histology of pure large cell neuroendocrine carcinoma. According to the World Health Organization (WHO), primary ovarian LCENC is synonymous with undifferentiated type of non-small cell neuroendo- crine carcinoma (NSNEC), possessing the characteristics of a large pleiomorphic nucleus with large round or oval nuclei and a tendency of neuroendocrine differentiation [3–6]. Additionally, assessment of neuroendocrine differ- entiation through immunohistochemical analysis, such as positive immunostaining for chromogranin A (CgA), synaptophysin (Syn) or Neural Cell Adhesion Molecule (NCAM, also the cluster of differentiation CD56), is re- quired to confirm the diagnosis of LCNEC [5–8]. The initial symptoms presented by LCNEC of the ovary are identical to that of epithelial ovarian cancer (EOC), such as presence of an abdominal mass, pain or distention. Anderson Cancer Center reported on a total of 11 cases of NSCNEC from 1990 to 2005, with the most common symptoms being abdominal pain (6/11), ascites (2/11), pelvic mass (1/11), vaginal bleeding (1/11), and abdom- inal distension (1/11) .
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Large cell neuroendocrine carcinoma (LCNEC) of the ovary is a rare tumor and is now included in the World Health Organization tumor classification . Its prognosis is generally very poor even when the diagnosis is made at an early stage. Since Collins et al  described the first case of mixed neuroendocrine and mucinous carcinomas, a few more cases of primary ovarian LCNECs have been reported. The majority of the tumors are associated with other epithelial neoplasms, among which only one case of serous carcinoma has been recently described . Here we present another case of LCNEC of the ovary associated with serous carcinoma with mucin production.
Large cell neuroendocrine carcinoma (LCNC) of the ovary, or ovarian undifferentiated non-small cell carcinoma of neuroendocrine type, is a rare entity that is frequently associated with ovarian surface epithelial tumors. Few cases have been reported in the literature. LCNC is an aggressive tumor with tendency to present at advanced stages and to cause death after a short postoperative duration. We report three cases of LCNC diagnosed histopathologically. Immunohistochemically, the tumor cells were positive for chromogranin A, NSE, CD56, and pancytokeratin. The patients were treated postoperatively with combination chemotherapy. Due to the rarity of LCNC, the general consensus on standard therapy is not established. Although most patients are at stage I, the biological aggressiveness and poor prognosis of the tumors have been reported in previous reports despite extensive surgery and chemotherapy.
16. Russo S, Russo F, Maiello FM, Paolini B, Carrabba A, De Gregorio A. Biphasic large cell neuroendocrine carcinoma – pure mucinous carcinoma of the gallbladder (MANEC): a unique combination. Pathologica. 2012;104:185 – 9. 17. Rindi G. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Lyon, France: The International Agency for Research on Cancer; 2010. p. 13 – 4. 18. Mahipal A, Gupta S. Small-cell carcinoma of the gallbladder: report of a case
Pure large cell neuroendocrine carcinoma (LCNEC) has been first described in 2000 by M. Papotti et al. , who reported two cases of LCNEC, one of which was the pure type and the other is mixed with adenocarcinoma of the gallbladder. Around two- thirds of the histologically proven GBCA are inci- dentally found in cholecystectomy specimens [5, 10]. The determination of GB NETs is often difficult and requires many immunohistochemical expressions of markers as well as other cell type-specific amines and peptides. Our diagnosis of primary GB LCNEC has been based on the typical morphological and
The large cell neuroendocrine carcinomas of the lung (LCNEC) are high-grade tumors and they have simi- lar clinical and biological characteristics of non-small cell lung cancer (NSCLC). We discuss a patient with LCNEC of the lung which early metastasis to chest wall. Sixty-two-year-old male patient had a 1.5 cm solid mass in left upper lob on computered tomogra- phy (CT). The mass was reported by positron emis- sion tomography as malignant. Left upper lobectomy was applied in the same period, when perioperatively frozen-section result was diagnosed NSLC. Histo- pathological examination was revealed a neuroendo- crine carcinoma, which may originate from the gas- trointestinal tract p(T1AN0M0). The octreotide scin- tigraphy, gastroscopy, colonoscopy, abdominal, and chest CT were performed for primary origin, but did not reveal any pathology. Chest wall mass was de- tected postoperative third months and biopsy result was reported as large cell neuroendocrine carcino- ma. Then, chemoradiotherapy was planned. Patient died after one year from diagnosis. Accurate differen- tiation of LCNEC from other types of NSCLC is im- portant, and there is a need for close follow-up in these patients for aggressive and metastatic nature and recurrent disease.
Neuroendocrine neoplasms (NEN) are a heterogeneous group of rare tumors that account for approximately 2% of all malignancies and 0.5% of all newly diagnosed malignancies . Despite being a rare disease, the incidence is on the rise [2, 3]. Although they occur spor- adically, NENs can occur in association with hereditary syndromes. NENs often originate from neuroendocrine cells, which are specialized cells that receive neuronal in- put and synthesize and secrete hormones in response to that stimulus, thereby connecting the nervous and endo- crine systems of the body. Due to this secretory function, neuroendocrine tumors (NETs) can cause a variety of clinical syndromes depending upon the hormone re- leased. Neuroendocrine cells are located throughout the body, most notably in the hypothalamus and pituitary
Thymic large cell neuroendocrine carcinomas (LCNECs) are very rare. We here describe a case in which the tumor could be completely resected. A 55-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor found at a regular health check-up. The patient underwent an extended thymectomy of an invasive thymoma of Masaoka’s stage II that had been suspected preoperatively. The tumor was located in the right lobe of the thymus and was completely resected. Final pathological diagnosis of the surgical specimen was thymic LCNEC. The patient underwent adjuvant chemotherapy with irinotecan and cisplatin in accordance with the diagnosis of a lung LCNEC, and is alive without recurrence or metastasis 16 months after surgery.
resection of thymic carcinomas. Tiffet et al. reported a patient who survived for 67 months without recurrence after complete resection of thymic LCNEC followed by adjuvant radiotherapy . The guideline does not men- tion the effectiveness of chemotherapy after complete re- section of thymic epithelial cancer. Although there is no evidence to support adjuvant therapy for thymic LCNEC, a regimen using cisplatin/carboplatin/etoposide, as for lung small cell carcinoma, seems the most com- mon choice in thymic LCNEC at this time . Nagata et al. reported a case of lung metastasis of thymic LCNEC after four courses of carboplatin/etoposide that achieved complete response . Although such re- sponders were sometimes seen, these all have a major limitation due to the small numbers of patients. Further consideration of radiotherapy and chemotherapy in thymic LCNEC is needed.
with peripheral palisading and the presence of nucleoli in tumor cells. Basaloid carcinoma usually expresses p63 and p40, rarely CD5 and CK5/6, but is negative for neuroen- docrine markers like synaptophysin and chromogranin . Another more challenging issue is the differential diagnosis between primary thymic LCNEC extended to lung parenchyma and a primary pulmonary LCNEC in- vading the mediastinum [1, 2]. Correlations between clin- ical, radiological, and histopathological findings should be carefully done to determine the correct primary site of the tumor. Mostly, pulmonary LCNEC (like SCNEC) is highly associated with heavy tobacco smoking, whereas thymic LCNEC is not. With imaging techniques (CT scan especially), primary lung LCNEC is usually peri- pherally located, rarely central, and invades the medias- tinal structures less often [11 – 13]. Thus, any anterior mediastinal LCNEC invading lung structures radio- logically, suggests at first a locally advanced thymic pri- mary tumor. With immunochemistry, TTF-1 and CK7 positive staining is highly suggestive of lung primary LCNEC. Recently, Weissferdt et al. in a study including 25 cases of pulmonary NETs and 25 cases of thymic NETs, concluded that PAX8+/TTF-1 − immunophenotype appears to be more common in thymic neuroendocrine carcinomas, whereas the reverse (PAX8-/TTF-1+) is true for most pulmonary neuroendocrine carcinomas . However, this study used only carcinoid tumors (low and intermediate grade tumors). Table 1 summarizes some
There are four histological lung tumor types: adenocar- cinoma, squamous cell, and mixed large and small cell carcinoma. Usually, lung cancers have a single histological type; however, there are reports of patients with MPLC with different histology, including our patient. Jung-Legg et al .  reported a synchronous MPLC composed of a small cell carcinoma, bronchial carcinoid, and adenocar- cinoma of the right lung, and Wcisło et al .  described an MPLC composed of an adenocarcinoma, squamous cell carcinoma, and neuroendocrine carcinoma. Yoon et al .  reported a synchronous triple primary lung cancer that included a squamous cell cancer, invasive mucinous, and nonmucinous adenocarcinoma. Our patient’s case is particularly interesting and rare. In a single patient, we identified three primary lung cancers (triple SLC), classi- fied as adenocarcinoma, squamous cell carcinoma, and mixed small and large cell neuroendocrine carcinoma.
the esophagus more frequently present in the middle of the esophagus and stain positive for CD56, synaptophy- sin, and chromogranin A [1, 11]. These tumors are slow growing, but high-grade neuroendocrine tumors of the esophagus have a poor prognosis and a 5-year survival of approximately 25% [1, 11]. The therapeutic strategy for NEC of the esophagus has not been well defined be- cause of the small number of cases . To date, there has only been one case of collision of SCC and NEC of the esophagus treated by ESD .
gallbladder cancers, and 4% of extrahepatic cholangio- carcinomas . The authors of this report expressed the opinion that normal adenocarcinoma developed during a process of growth and dedifferentiation to endocrine cells. Albores et al. reported that neuroendo- crine cells could be detected at sites of intestinal meta- plasia induced by chronic inflammation due to cholelithiasis and congenital anomalies, which might be the initial step in the development of neuroendocrine tumors of the CBD . The process suggested this report was one reason why pure NET and NEC devel- oped. Although pure NET cases without dysplastic intestinal-type epithelium exist, they seem to follow a different developmental process.
SmCC most commonly arises in the lung but may arise at other anatomical sites including the breast. Diagnosing a breast tumour as a primary SmCC may be difficult as the H&E ap- pearance and immunohistochemical staining profile, including immunoreactivity for TTF-1, are nearly identical to that of SmCC arising at other sites [1, 2]. Confident diagnosis of primary SmCC of the breast requires the exclusion of non-mammary primary sites by clinical examina- tion and imaging studies, and/or histopathologi- cal demonstration of an in situ component . The immunohistochemical features of in situ carcinoma co-existing with SmCC of the breast are not well described. Ersahin et al  reported a case of SmCC of the breast with admixed in situ carcinoma in which the invasive carcinoma expressed TTF-1 and neuroendocrine markers, but the in situ component did not express TTF-1 or neuroendocrine markers. There is one previ- ously reported case of TTF-1 expression by in situ carcinoma associated with a primary SmCC of the breast .