Extrapulmonary Small Cell Carcinoma Research Articles

SMALL-CELL NEUROENDOCRINE CARCINOMA OF NASOPHARYNX: A CASE REPORT

Extra pulmonary small cell carcinomas are extremely rare, accounting for 0.1-0.4% of all malignancies and 2.5-4% of small cell carcinomas. In the head and neck region, the most common primary sites are the larynx, salivary gland, nasal cavity, paranasal sinus, tonsil, and oral cavity. Small cell carcinomas occurring in nasopharynx are extremely rare, to our best knowledge, only four cases of primary nasopharyngeal small cell carcinoma has been described in English literature. We report another case of nasopharyngeal small cell carcinoma arising in a 46-year-old woman. She accused, for five months, nasal blockage, right hypoacousia, exophthalmos and reduced visual acuity. Cerebral and facial magnetic resonance imaging showed an extensive mass of the nasopharynx with the invasion of sphenoidal body, the diagnosis of disseminated small cell carcinoma of nasopahrynx was established. The patient received three courses of systemic chemotherapy; unfortunately, she died after the third course. The prognosis of such entity is poor and is similar to that for patients with extensive small cell lung cancer.

The small cell carcinoma neuroendocrine type of the larynx—Case report

Abstract Introduction Extrapulmonary small cell carcinoma neuroendocrine type (ESCCNET) is a rare tumor (2.5%-4.0% of all small cell carcinomas), and during the past 30 years, only 160 cases of primary small cell carcinoma of the larynx have been reported worldwide. Aim To report a rare case of small cell carcinoma of the larynx, in a 54-year-old man, including diagnostic work-up, and treatment with chemotherapy (CHT) and radiotherapy (RT), compromised by the patient's nonadherence, and to spread awareness of the need of further research, focused on new therapeutic strategies, in patients with ESCCNET. Case study The patient underwent induction CHT based on cisplatin and etoposide. Partial remission was obtained after the 3rd cycle of CHT, confirmed by the CT scan. The patient refused further CHT. He underwent RT. The residual larynx tumor and elective nodal volume were irradiated. A follow-up laryngological examination and control CT scan, performed two months after the completion of RT, showed a complete remission. Eight months later brain CT revealed multiple metastases. Palliative cranial irradiation and CHT were applied. The patient died in October 2011. Results and discussion ESCCNET, an unusual neoplasm, accounting for 0.5% of all laryngeal carcinomas, is most commonly located in the supraglottic region. In contrast to squamous cell carcinoma of the larynx, a single modality therapy is not advised for ESCCNET, because these tumors are biologically aggressive, and at least 73% of patients have distant metastases. Therefore, RT and CHT in concomitant or sequential fashion offer the best chance of survival. However, in the presented case, the recommended therapy was not fully implemented, due to the patient's noncompliance. Conclusions This report underscores the need for thorough, systemic diagnostic work-up, and emphasizes that the combination of RT and CHT remains the treatment of choice for ESCCNET (while surgery is reserved for persistent and recurrent disease). In addition, it points out that the new therapeutic strategies to improve survival in ESCCNET are needed, such as a prophylactic cranial irradiation that could be explored in future clinical trials.

KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer.

Lung cancer is one of the most lethal cancers. It is mainly classified into 2 groups: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Extrapulmonary small cell carcinomas (EPSCC) are very rare. The Ras oncogene controls most of the cellular functions in the cell. Overall, 21.6% of human cancers contain a Kirsten Ras (KRAS) mutation. SCLC and EPSCC have several similar features but their clinical course is different. We investigated the KRAS mutation status in SCLC and EPSCC. Mutation research. Thirty-seven SCLC and 15 EPSCC patients were included in the study. The pathological diagnoses were confirmed by a second pathologist. KRAS analysis was performed in our medical genetic department. DNA isolation was performed with primary tumor tissue using the QIAamp DNA FFPE Tissue kit (Qiagen; Hilden, Germany) in all patients. The therascreen KRAS Pyro Kit 24 V1 (Qiagen; Hilden, Germany) was used for KRAS analyses. Thirty-four (91.9%) of the SCLC patients were male, while 11 (73.3%) of the EPSCC l patients were female. SCLC was more common in males, and EPSCC in females (p=0.001). A KRAS mutation was found in 6 (16.2%) if SCLC patients. The most common mutation was Q61R (CAA>CGA). Among the 15 EPSCC patients, 2 had a KRAS mutation (13.3%). When KRAS mutant and wild type patients were compared in the SCLC group, no difference was found for overall survival (p=0.6). In previous studies, the incidence of KRAS mutation in SCLC was 1-3%; however, it was 16.2% in our study. Therefore, there may be ethnic and geographical differences in the KRAS mutations of SCLC. As a result, KRAS mutation should not be excluded in SCLC.

Extrapulmonary Small Cell Carcinoma of the Seminal Vesicles and Prostate Demonstrated on 18F-FDG Positron Emission Tomography/Computed Tomography.

Extrapulmonary primary small cell carcinomas arising from the urogenital tract is infrequent. It can rarely arise from the prostate and even more rarely from the seminal vesicles. We present a 79-year-old male who was admitted due to acute renal failure with a history of radical radiotherapy for prostate adenocarcinoma 13 years ago. The prostate specific antigen level was not elevated. An abdominopelvic computed tomography (CT) scan showed markedly enlarged seminal vesicles causing bilateral ureteral obstruction and a mildly enlarged prostate. Further evaluation with fluorine-18-fluorodeoxyglucose (0F-FDG) positron emission tomography/CT demonstrated extensive 18F-FDG uptake in the pelvis with diffuse involvement of both seminal vesicles and the prostate without pathologic uptake in the lungs or elsewhere in the body. Core biopsies of the prostate and both seminal vesicles revealed diffuse involvement by small cell carcinoma. Therapy could not be instituted due to a rapid deterioration in the patient’s clinical condition.

Extrapulmonary small cell carcinoma of lymph node: Pooled analysis of all reported cases.

To study clinical outcomes and management of lymph nodes extrapulmonary small cell carcinoma (LNEPSCC). Herein, we perform a systematic search of published literature in the PubMed and EMBASE databases for studies describing LNEPSCC. For uniformity of reporting, LNEPSCC was staged as limited if it involved either single lymph node station or if surgery with curative intent had been undertaken. The disease was staged extensive if it involved two or more lymph node regions. The systematic literature review yielded eight descriptions (n = 14) involving cervical, submandibular and inguinal lymph nodes. Eleven (64.7%) patients had limited disease (LD) and six (35.3%) had extensive disease (ED) at presentation. Chemotherapy (n = 6, 35.3%) or surgery (n = 4, 23.5%) were the most common form of treatment given to these patients. Complete response was achieved in 12 (70.6%) of the patients. Median (interquartile range) progression free survival and overall survival was 15 (7-42) mo and 22 (12.75-42) mo respectively. Of the three illustrative cases, two patients each had ED at presentation and achieved complete remission with platinum based combination chemotherapy. LNEPSCC is a rare disease with less than 15 reported cases in world literature. Surgical resection with curative intent is feasible in those with LD while platinum based combination chemoradiation is associated with favorable outcomes in patients with ED. Prognosis of LNEPSCC is better than that of small cell lung cancer in general.

Primary small cell carcinoma of kidney in a young female: A rare case report

Small cell carcinomas (SCCs) occur mainly in pulmonary tract while extrapulmonary SCCs (EPSCCs) are rare neoplasms comprising approximately 2.5% of all SCCs. A 23-year-old female presented with complaints of hematuria and a mass in right flank region. She had no other complaints. Examination of the patient revealed lump in the right lumbar region with no other remarkable findings. Contrast-enhanced computed tomography showed a large heterogeneously enhancing necrotic mass involving the right entire kidney. A right radical nephrectomy was performed, and a histological examination revealed mass involving whole right kidney with capsular and lymphatic invasion along with small cell histology. The patient was given adjuvant chemotherapy of etoposide and carboplatin, every 3 weeks. The patient started complaining of bony pain after 1 month of operation, and bone scanning revealed of multiple osteoblastic lesions. Zoledronic acid (4 mg) had been started for bony metastasis. SCC of the kidney is a rare neoplasm of the elderly age group that has aggressive behavior with an increased tendency for locoregional and distant dissemination. Our patient represents the first case of SCC of the kidney to be reported in a young female.

Small Cell Carcinoma of the Upper Urinary Tract: A Case Report and Review of Existing Cases

Primary extra-pulmonary small cell carcinomas (SCC) are rare, with 40% of SCCs of the urinary tract are metastatic on presentation. In these cases, surgical options are limited and prognosis is poor. The literature suggests that neoadjuvant chemotherapy in organ-confined disease improves clinical outcome. However due to rarity of cases, there is limited evidence to guide management of metastatic SCC.

Pancreatic small cell cancer

Small cell carcinoma (SCC) is most commonly associated with lung cancer. Extra-pulmonary SCC can originate in virtually any organ system, with the gastrointestinal tract being the most common site of involvement. We review the clinical presentation, pathogenesis, histology, imaging modalities and optimal therapeutic management of PSCC in light of available evidence.

Extrapulmonary Small Cell Carcinoma - a Case Series of Oropharyngeal and Esophageal Primary Sites Treated with Chemo-Radiotherapy.

The optimal sequence and extent of multimodality therapy remains to be defined for extrapulmonary small cell carcinoma because of its rarity. The purpose of our study was to assess the response to neoadjuvant chemotherapy followed by chemoradiation/radiation in patients with extrapulmonary small cell carcinoma. Four consecutively diagnosed patients were included in this study. The primary tumor site was oropharynx in three patients and esophagus in one. The patients with the limited disease were treated with chemotherapy followed by concurrent chemoradiation (n=2) or radiotherapy (n=1). The patient with the extensive disease with the primary site in vallecula was treated with chemotherapy and palliative radiotherapy to the metastatic site. The median follow-up was 22.5 months (range, 8-24 months). Three patients with the limited disease (base of tongue, n=2; esophagus, n=1) were in complete remission. The patient with the extensive disease died of loco-regional tumor progression at 8 months from the time of diagnosis. The combination of chemotherapy and radiotherapy is the preferred therapeutic approach for patients with extrapulmonary small cell carcinoma. Induction chemotherapy followed by concurrent chemoradiation or radiation provides a good loco-regional control in patients with limited disease.

Extrapulmonary Small Cell Carcinoma (EPSCC): Single-Institution Review of Management and Outcomes

Extrapulmonary Small Cell Carcinoma (EPSCC): Single-Institution Review of Management and Outcomes

Small-Cell Neuroendocrine Carcinoma Originating From the Nasopharynx: Report of a Rare Case

Introduction: Extrapulmonary small-cell carcinoma, neuroendocrine type is uncommon, particularly in the head and neck region. It represents an extremely rare finding when originating from the nasopharynx, and so far only five cases have been reported. Case Presentation: The authors present a case of a female patient with this tumor type, and describe a treatment strategy that combined radiotherapy and chemotherapy. Conclusions: Persistent disease was documented ten months after treatment completion.

Mediastinal small cell carcinoma: a unique clinical entity?

Mediastinal small cell carcinoma (MSCC) is a rare tumor with limited published literature. In view of diagnostic confusion pertaining to this tumor, we investigated its origin, clinical features, management and survival. Clinical data of MSCC patients were retrospectively reviewed. Eligible patients showed pathologically proven small cell carcinoma (SCC) with the primary lesions confined to the mediastinum. Survival information was collected through follow-up studies. Among 25 MSCC patients identified, 22 were classified to have limited disease (LD), while 3 were with extensive disease (ED). The 5 patients (20%) underwent surgery and 20 patients (80%) underwent non-surgical treatment. The 4 patients with LD MSCC received chemotherapy alone, while 13 of them received chemoradiotherapy. Overall median survival time (MST) of all patients was 22 months, and the 1-, 3- and 5-year overall survival rates were 67.4, 16.8, and 8.4%, respectively. The MST of LD and ED patients separately was 23 and 8 months, respectively, with significant difference (P = 0.005). But, the MST of patients who received surgical and non-surgical treatment was 25 and 21 months, respectively, with no significant difference (P = 0.757). The MST of LD patients receiving chemotherapy and chemoradiotherapy was 12 and 29 months, respectively, but somehow did not show significant difference (P = 0.482). Our data suggested that MSCC may be a separate clinical entity like extrapulmonary small cell carcinomas (EPSCCs). Despite, multimodal treatment is currently the main treatment option, but for patients with LD MSCC, chemoradiotherapy is recommended to be preferred treatment modality.

Is there necessary to perform ureterectomy in renal cell carcinoma treatment

Is there necessary to perform ureterectomy in renal cell carcinoma treatment

Prognostic factors in extrapulmonary small cell carcinomas.

e15196 Background: Extra-pulmonary small cell carcinomas (EPSCC) are a heterogeneous group of cancers whose clinicopathological features of EPSCC remain poorly defined. Methods: A retrospective stu...

Comparative genomics of pulmonary and extrapulmonary small cell carcinoma.

e18547 Comparative genomics of pulmonary and extrapulmonary small cell carcinoma Background: Biology of small cell lung cancer (SCLC) is poorly understood in part due to limited opportunities for i...

A population-based study of incidence and patient survival of small cell carcinoma in the United States, 1992-2010.

BackgroundIn contrast to the well-described epidemiology and behavior of small cell lung carcinoma (SCLC), little is known about extrapulmonary small cell carcinoma (EPSCC).MethodsUsing data from the Surveillance, Epidemiology and End Results (SEER) Program (1992–2010), we calculated age-adjusted incidence rates (IRs), IR ratios (IRRs), annual percent change (APC), relative survival (RS), RS ratios (RSRs), and the respective 95% confidence intervals (95% CI) of SCLC and EPSCC according to primary site. We used the SEER historic stage variable that includes localized (confined to the organ of origin), regional (direct extension to adjacent organ/tissue or regional lymph nodes), and distant (discontinuous metastases) stages and combined localized and regional stages into “limited” stage.ResultsThe incidence of SCLC (IR = 76.3/million person-years; n = 51,959) was 22-times that of EPSCC (IR = 3.5; n = 2,438). Of the EPSCC sites, urinary bladder, prostate, and uterine cervix had the highest incidence (IRs = 0.7-0.8); urinary bladder (IRR = 4.91) and stomach (IRR = 3.46) had the greatest male/female disparities. Distant-to-limited stage site-specific IRRs of EPSCC were significantly elevated for pancreas (IRR = 6.87; P < 0.05), stomach, colon/rectum, ovary, and prostate (IRRs = 1.62-2.42; P < 0.05) and significantly decreased for salivary glands, female breast, uterine cervix, and urinary bladder (IRRs = 0.32-0.46). During 1992–2010, significant changes in IRs were observed for EPSCC overall (APC = 1.58), small cell carcinoma of the urinary bladder (APC = 6.75), SCLC (APC = −2.74) and small cell carcinoma of unknown primary site (APC = −4.34). Three-year RS was significantly more favorable for patients with EPSCC than SCLC for both limited (RSR = 2.06; 95% CI 1.88, 2.26) and distant stages (RSR = 1.55; 95% CI 1.16, 2.07). Among limited stage small cell carcinoma, RS was most favorable for salivary glands, female breast, and uterine cervix (RS = 52-68%), whereas RS for nearly all sites with distant stage disease was <10%.ConclusionEPSCC comprises a heterogeneous group of diseases that appears, at least in part, etiologically distinct from SCLC and is associated with more favorable stage-specific patient survival.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1188-y) contains supplementary material, which is available to authorized users.

Extrapulmonary small cell carcinoma in head and neck.

The management of extrapulmonary small cell carcinoma has not been standardised to date. This study reviewed the clinical course, management and survival outcomes of patients with extrapulmonary small cell carcinoma in the head and neck region. Nine patients with extrapulmonary small cell carcinoma in the head and neck were included in this study. Five patients received radical surgery followed by adjuvant chemotherapy or radiotherapy or both. Two other patients were treated with chemotherapy consisting of CPT11 plus cisplatin or CPT11 plus cisplatin plus VP-16 three times. Two other patients received chemoradiotherapy consisting of S-1 or CPT11 plus cisplatin. The median overall survival was 14.5 months, with a three-year survival rate of 23.7 per cent. The prognosis of extrapulmonary small cell carcinoma is generally poor. Further prospective multicentre studies are required for better understanding of disease entities and response to treatment modalities.

Distinct genetic alterations in small cell carcinoma from different anatomic sites.

Small cell carcinoma (SmCC) is a distinct clinicopathological entity first described in the lung. It represents approximately 15% of all bronchogenic carcinoma. Extrapulmonary small cell carcinoma (EPSmCC) morphologically indistinguishable from small cell lung cancer (SCLC) was first reported in 1930. Since its first description, EPSmCC has been reported in virtually all anatomical sites, including: gynecologic organs (ovary and cervix); genitourinary organs (urinary bladder and prostate); the gastrointestinal tract (esophagus); skin (Merkel cell carcinoma) and head and neck region. Regardless of the anatomic sites, all SmCCs have similar, if not identical, histo-pathology features and immunohistochemical profile. SmCC is one of the most aggressive malignancies. The molecular mechanisms underlying its development and progression remain poorly understood. Herein, we reviewed the literature in SmCC in respect to its site of occurrence, clinical features, immunohistochemical characteristics. SmCCs have heterogeneous molecular mutations. Dinstinct genetic alterations associated with SmCC from different body sites were reviewed. Some genetic alterations such as RB1, TP53 are commonly seen in different origins of SmCC. Other genes with site specificity were also summarized, such as bladder SmCC with TERT promoter mutations; prostate SmCC with ERG translocations; ovarian SmCC with SMARCA4 mutations; Merkel cell carcinoma (skin) and cervical SmCC with Merkel cell polyomavirus (MCV or MCPyV) and human papillomavirus (HPV). Further studies are needed to employ a genetically oriented approach for the diagnosis and therapy of SmCC.

PD-L1 expression in small cell neuroendocrine carcinomas

Small cell lung cancer and extrapulmonary small cell carcinomas are the most aggressive type of neuroendocrine carcinomas. Clinical treatment relies on conventional chemotherapy and radiotherapy; relapses are frequent. The PD-1/PD-L1/PD-L2 pathway is a major target of anti-tumour immunotherapy. Aberrant PD-L1 or PD-L2 expression may cause local immune-suppression. Here we investigated expression of PD-1 and its ligands by immunohistochemistry and RNA-seq in small cell carcinomas.PD-L1 and PD-1 protein expression were analysed in 94 clinical cases of small cell carcinomas (61 pulmonary, 33 extrapulmonary) by immunohistochemistry using two different monoclonal antibodies (5H1, E1L3N). RNA expression was profiled by RNA-seq in 43 clinical cases.None of the small cell carcinomas showed PD-L1 protein expression in tumour cells. PD-L1 and PD-1 expression was noticed in the stroma: Using immunohistochemistry, 18.5% of cases (17/92) showed PD-L1 expression in tumour-infiltrating macrophages and 48% showed PD-1 positive lymphocytes (45/94). RNA-seq showed moderate PD-L1 gene expression in 37.2% (16/43). PD-L1 was correlated with macrophage and T-cell markers. The second PD-1 ligand PD-L2 was expressed in 27.9% (12/43) and showed similar correlations.Thus, the PD-1/PD-L1 pathway seems activated in a fraction of small cell carcinomas. The carcinoma cells were negative in all cases, PD-L1 was expressed in tumour-infiltrating macrophages and was correlated with tumour-infiltrating lymphocytes. Patients with stromal PD-L1/PD-L2 expression may respond to anti-PD-1 treatment. Thus, evaluation of the composition of the tumour microenvironment should be included in clinical trials. Besides conventional immunohistochemistry, RNA-seq seems suitable for detection of PD-L1/PD-L2 expression and might prove to be more sensitive.

Patterns of relapse in extrapulmonary small cell carcinoma: retrospective analysis of outcomes from two cancer centres

ObjectivesWe conducted a retrospective review of patients with extrapulmonary small cell carcinomas (EPSCCs) to explore the distribution, treatments, patterns of relapse and outcomes by primary site.SettingWe have reviewed the outcomes...