Neuroendocrine carcinoma of prostate presenting with ascites.

Prostate cancer is a very common cause of morbidity and mortality in India. The commonest type of prostate carcinoma is adenocarcinoma, most of them are confined to prostate at the time of presentation. Bone is the preferred site for metastasis. The following is a case of neuroendocrine carcinoma of prostate arising in a 36 years old male who presented with ascitis and jaundice to the emergency department. The ascitic tap was positive for malignant cells. CECT done to detect primary showed osteoblastic secondaries in the spine along with lesions in the liver. DRE revealed grade 2 prostatomegaly. A TRUS guided biopsy showed neuroendocrine carcinoma of the prostate. Neuroendocrine carcinoma is a very rare type of prostatic carcinoma, with presentation of the same as ascitis is very uncommon. The following case is presented due to its rarity.

Clinicopathologic features of metastatic small cell carcinoma of the prostate to the liver: a series of four cases.

BACKGROUND: Small cell neuroendocrine carcinoma of the prostate (SCNECP) is a rare, aggressive subtype of prostate carcinoma. Most SCNECP arise from conventional prostate adenocarcinoma (CPAC) treated with androgen deprivation therapy (ADT). CASE PRESENTATIONS: We identified four cases of CPAC treated with ADT, which evolved to SCNECP with liver metastasis. The average interval between the diagnosis of CPAC and SCNECP was 102 months (range: 12 to 168). Histologically, the tumors showed nests of cells with high nuclear:cytoplasmic ratios, granular chromatin, and frequent mitoses. All cases were synaptophysin, chromogranin, and AE1/AE3 positive, with a Ki-67 labeling index ≥70%. NKX3.1 was negative in all but one case and TTF-1 was positive in half. Weak ERG positivity by IHC was seen in one case which also demonstrated the TMPRSS2-ERG gene rearrangement; all other cases were negative for ERG by IHC. Serum prostate specific antigen (PSA) levels were normal to near-normal in all. The median interval between the diagnosis of SCNECP and death was 3.25 months (range: 0.75 to 26). CONCLUSIONS: Our case series highlights the importance of considering a prostate primary, even in the setting of normal PSA levels and loss of prostate markers, when diagnosing neuroendocrine carcinoma in the liver. Further, we emphasize the significance of diagnosing SCNECP that metastasizes to the liver, as it portends a particularly dismal prognosis.

Primary Parotid Merkel Type Small Cell Neuroendocrine Carcinoma with Oligometastasis to the Brain and Adrenal Gland: Case Report and Review of Literature.

Oligometastatic disease is a hypothesized intermediate stage of disease between localized and widespread metastatic cancer. Localized treatment of oligometastatic lesions may offer survival advantages in addition to systemic treatment. In this case report, we describe a patient who presented with small cell neuroendocrine carcinoma "Merkel type" (SNECM) of the parotid gland which had metastasized to the brain and adrenal gland. He was treated with chemotherapy followed by stereotactic radiotherapy and volumetric modulated arc therapy for oligometastasis. He maintains good functional status with low burden of disease at 20-months after diagnosis. SNECM is a rare and aggressive parotid cancer with immunohistochemical and morphologic similarities to Merkel cell carcinoma (MCC). There are only 44 cases of parotid SNECM in the English literature. This is the first case to describe management of oligometastatic SNECM and we review literature on management of both SNECM and metastatic MCC.

Metastasis of Carcinoma to a Cerebral Arteriovenous Malformation.

BACKGROUND: Although carcinoma metastasis to primary intracranial neoplasms has occasionally been reported, metastasis to a cerebral arteriovenous malformation (AVM) has been exceedingly rare, with only 5 cases reported to date. In the present study, we have reported a case of lung carcinoma that had metastasized to a cerebral AVM. To the best of our knowledge, the present report is the first case in which the pathological examination detected the bleeding mechanism of this rare condition, showing destruction of the feeders by the metastatic tumor. CASE DESCRIPTION: A 61-year-old man who had had a tumor shadow in the right middle lung field identified at a medical examination 5 weeks previously had suddenly experienced a disturbance of consciousness. Head computed tomography and computed tomography angiography revealed a right occipital subcortical hemorrhage with abnormal vessels, suggesting a ruptured AVM. Magnetic resonance imaging with gadolinium-based contrast agents did not show any other lesions. Cerebral angiography revealed a Spetzler-Martin grade III AVM in the right occipital lobe. Endovascular feeder embolization and subsequent removal of the AVM were performed. Histopathological examination of the resected mass showed a small cell carcinoma that had metastasized to the AVM. The tumor cells had infiltrated to the vessel walls of the feeders, which might have elicited the bleeding. CONCLUSION: Although rare, clinicians should recognize that undifferentiated carcinomas can metastasize to AVMs and cause bleeding. Because the preoperative diagnosis can be difficult, even using the latest imaging modalities, careful examination of the resected specimen is required to reveal such pathological conditions.

Biological functions of long noncoding RNAs and circular RNAs in small-cell lung cancer.

We aim to discuss comprehensively the role of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in small-cell lung cancer (SCLC) biology and their clinical utility as cancer biomarkers. We searched the scientific literature to select articles related to the role of lncRNAs and circRNAs in SCLC biology or as cancer biomarkers. We identified that a number of lncRNAs and circRNAs can regulate key biological processes involved in SCLC development, including cell proliferation, metastasis and chemoresistance mainly acting as miRNA sponges. Also, the expression of a few lncRNAs and circRNAs predicted survival outcome depicting their utility as prognostic biomarkers. Further investigations on the role of lncRNAs and circRNAs in SCLC tumors may yield novel therapeutic targets for SCLC.

Interferon-Induced Transmembrane Protein 1 (IFITM1) Promotes Distant Metastasis of Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a severe malignancy associated with early and widespread metastasis. To study SCLC metastasis, we previously developed an orthotopic transplantation model using the human SCLC cell line DMS273. In the model, metastatic foci were found in distant tissues such as bone and the adrenal gland, similarly as observed in patients with SCLC. In this study, we evaluated the differentially expressed genes between orthotopic and metastatic tumors in the model. We isolated tumor cells from orthotopic and metastatic sites, and the tumor cell RNA was analyzed using DNA microarray analysis. We found that 19 genes in metastatic tumors were upregulated by more than 4-fold compared with their expression in orthotopic tumors. One of these genes encodes a transmembrane protein, interferon (IFN)-induced transmembrane protein 1 (IFITM1), and immunohistochemical analysis confirmed the higher expression of the protein in metastatic sites than in orthotopic sites. IFITM1 was also detected in some SCLC cell lines and lung tumors from patients with SCLC. The overexpression of IFITM1 in DMS273 cells increased their metastatic formation in the orthotopic model and in an experimental metastasis model. Conversely, the silencing of IFITM1 suppressed metastatic formation by DMS273 cells. We also found that IFITM1 overexpression promoted the metastatic formation of NCI-H69 human SCLC cells. These results demonstrate that IFITM1 promotes distant metastasis in xenograft models of human SCLC.

Worsening of anti-Hu paraneoplastic neurological syndrome related to anti-PD-1 treatment: Case report and review of literature.

We present an illustrative case of a 62-year-old woman with small cell lung cancer who developed progressive worsening of pre-existing anti-Hu antibody associated sensory neuronopathy after treatment with programmed cell death-1 (PD-1) inhibitor, nivolumab. We review the literature and identify 6 reported cases to understand the clinical outcomes of patients with anti-Hu paraneoplastic neurologic syndrome (PNS) treated with anti-PD-1 treatment. The PNS clinical spectrum comprised of encephalitis, a combination of sensory neuronopathy and anti-NMDAR encephalitis, isolated sensory neuronopathy, and encephalomyelitis. Immune checkpoint inhibitor have the potential to worsen pre-existing anti-Hu PNS and may promote the development of anti-Hu PNS.

Expanding the Spectrum of Radiation Necrosis After Stereotactic Radiosurgery (SRS) for Intracranial Metastases From Lung Cancer: A Retrospective Review.

OBJECTIVE: Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN. METHODS: We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes. RESULTS: Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%, P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality. CONCLUSIONS: This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.

Fine-needle aspiration biopsy for suspected uveal metastases.

OBJECTIVE: One indication of fine-needle aspiration biopsy (FNAB) is the diagnostic confirmatory of a clinical suspicion of uveal metastasis. We analyzed our experience in this clinical setting to assess the effectiveness of FNAB technique. DESIGN: Retrospective study. PARTICIPANTS: 28 patients (28 eyes) underwent FNAB biopsy. METHODS: Aspirates were performed using 25-gauge needle and were classified into the following categories: positive, atypical, negative, or nondiagnostic. The electronic medical records provided all clinical data. Subsequent clinical course was considered as the diagnostic standard. RESULTS: Subsequent clinical course was metastatic tumour in 19 cases (68%) and nonmetastatic tumour in other 9 cases, considered as the diagnostic standard. Cytological interpretations for metastases were positive in 19 cases (68%), atypical in 2 cases (7%), negative in 4 cases (14%), and nondiagnostic in 3 cases (11%). The metastasis-positive cases included 9 adenocarcinoma, 3 uveal lymphoma, 3 small cell carcinomas, 3 non-small cell carcinomas, and 1 metastatic paraganglioma. Both of the atypical cases were suggestive for non-Hodgkin lymphoma. The 4 negative cases for metastases included 2 true negative cases, and 2 false negative aspirates that subsequently proved to be metastatic adenocarcinoma. The 3 nondiagnostic cases included 1 schwannoma, 1 low-grade uveal non-Hodgkin lymphoma, and 1 metastatic adenocarcinoma. The overall sensitivity for FNAB was 87.5%, with a specificity of 100%. CONCLUSIONS: FNAB of suspected uveal metastases is a reliable diagnostic technique.

Clinicopathologic features, treatment, prognosis and prognostic factors of neuroendocrine carcinoma of the endometrium: a retrospective analysis of 42 cases from the Kansai Clinical Oncology Group/Intergroup study in Japan.

OBJECTIVE: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. METHODS: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. RESULTS: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. CONCLUSION: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.

Small Cell Carcinoma in the Head and Neck.

OBJECTIVES: Small cell carcinomas in extrapulmonary sites (ESmCCs) are very rare. ESmCCs originating in the head and neck account for approximately 10% of all ESmCCs, and there are few reports about this disease. ESmCCs have an aggressive natural history characterized by widespread metastasis. The aim of this study was to investigate the characteristics and outcomes of patients with ESmCCs of the head and neck. METHODS: The outcomes of 21 patients with ESmCCs of the head and neck treated between January 2001 and December 2015 at the authors' hospital and associated facilities were reviewed. RESULTS: There were 18 men and 3 women, and the median age was 74 years (range, 53-91 years). The tumor site was the larynx in 6 patients; the paranasal sinus in 5; the hypopharynx in 3; the oropharynx in 2; the nasopharynx in 2; and the oral cavity, salivary gland, and primary unknown in 1 patient each. The extent of the disease was staged as follows: stage I or II, 3 cases; stage III, 4 cases; stage IVA, 9 cases; stage IVB, 1 case; and stage IVC, 4 cases. The median observation time was 17 months (range, 1-103 months). Four patients (19%) had distant metastasis at initial treatment, and 13 patients (62%) developed distant metastasis within 3 years. Treatments were administered, including radical surgery (9 patients), radiation therapy (5 patients), chemoradiotherapy (7 patients), and chemotherapy (6 patients). The 1- and 3-year overall survival rates of patients were 56% and 37%, respectively. More than half of the patients died of distant metastasis. CONCLUSIONS: ESmCCs of the head and neck have a poor prognosis, similar to those of carcinomas in many other sites. Control of distant metastasis would contribute to improving the prognosis of ESmCCs of the head and neck. Further studies are required for better understanding these disease entities and their response to treatment modalities.

Small Cell Carcinoma of the Esophagus: A Nationwide Analysis of Treatment and Outcome at Patient Level in Locoregional Disease.

BACKGROUND AND PURPOSE: Small cell carcinoma of the esophagus (SCEC) is a rare subtype of esophageal cancer for which optimal treatment is unknown. We analyzed the impact of treatment factors on outcome in patients with nonmetastasized SCEC. METHODS: Patients with a histologically confirmed SCEC without distant metastases were analyzed in a nationwide multicenter retrospective cohort. All patients received radiotherapy as part of curative treatment between January 2000 and December 2014. Details on treatment and outcome were retrieved from individual charts. Cox regression analysis was used to determine prognostic factors for survival. RESULTS: Fifty-eight patients were analyzed. Median survival was 16 months (95% confidence interval, 11-21 mo). Infield recurrences occurred in 25%, distant metastases in 45%, and brain metastases in 12%. In total, 63% of patients developed a recurrence. Most recurrences (67%) occurred within 1 year. In univariable analyses an increased number of chemotherapy cycles (>3) and lower radiotherapy doses (<45 Gy) were associated with improved survival. T-stage, N-stage, treatment period, type of chemotherapy, prophylactic cranial irradiation, and age were not associated with survival. In multivariable analyses, only the number of chemotherapy cycles was associated with better survival (hazard ratio, 0.78; P=0.006). CONCLUSIONS: SCEC recurs frequently at distant sites after definitive chemoradiotherapy and usually within 1 year after curative treatment. With a dose of 45 to 50 Gy, infield recurrence rate was low. We found a relationship between number of received chemotherapy cycles and survival with best results obtained after at least 4 cycles of chemotherapy.

[SCCOHT/ovarian rhabdoid tumor: A case report]. / SCCOHT/tumeur rhabdoïde ovarienne : à propos d'un cas.

We report the case of a 22-year-old patient with acute abdominopelvic pain. The diagnosis of hypercalcemic small cell carcinoma (SCCOHT)/ovarian rhabdoid tumor has been made. Small cell carcinoma of hypercalcemic type is a rare and aggressive tumor that occurs in young women. The diagnosis of this tumor and the management must be rapid in view of its aggressiveness. Through this observation, we specify the epidemiological, diagnostic, molecular aspects and discussions about its name.

A rare case of small cell carcinoma of lung with intraventricular metastasis.

Our case report involves a Chinese patient who was presented to our hospital with the chief complaint of dizziness and double vision for one week. He was diagnosed with small cell carcinoma of lung in the past. The patient undertook various test at our hospital. His MR scan revealed an intraventricular metastasis from small cell carcinoma of lung which is very rare. We have analyzed the clinical data of this patient and related literature. We report this case to increase the awareness of this rare metastasis of small cell carcinoma of lung.

Primary Esophageal Mixed Sarcomatoid and Small Cell Neuroendocrine Carcinoma With Brain Metastasis: A Challenging Diagnosis on Biopsy.

Mixed carcinomas in the esophagus are highly uncommon neoplasms that represent a diagnostic challenge on small tissue biopsies. We present a case of a primary mixed sarcomatoid-small cell carcinoma of the esophagus that was diagnosed after repeat sampling of the lesion. The components were morphologically distinct and could be further classified by immunohistochemistry. Next-generation sequencing identified mutations in PIK3CA and CDKN2A. The small cell component morphology was also identified in brain metastasis.

The prognostic factors influencing overall survival in uterine cervical cancer with brain metastasis.

BACKGROUND/AIMS: The occurrence of brain metastasis (BM) has increased due to improved overall survival (OS) in uterine cervical cancer. However, research about prognostic factors and therapeutic guidelines for BM in uterine cervical cancer remains scarce due to the rarity of BM in this type of cancer. The present study evaluated the clinical characteristics and prognostic factors influencing OS in patients with BM from uterine cervical cancer. METHODS: A total of 19 BM patients of uterine cervical cancer were analyzed retrospectively from January 1995 to December 2016. RESULTS: The median and mean OS of all patients was 9.6 and 15.4 months. Treatment (vs. palliative care, p < 0.001), fewer than three regimens of chemotherapy before BM (vs. ≥ 3, p < 0.013), and chemotherapy after BM (vs. absence, p < 0.001) significantly increased the OS time. The Karnofsky performance status ≥ 70 (vs. < 70, p = 0.213), single BM (vs. multiple BM, p = 0.157), and small cell carcinoma (vs. others, p = 0.351) had numerically higher OS than others. Dual therapy (vs. single therapy, p = 0.182; vs. no therapy, p = 0.076) were associated with a longer OS time, but the difference did not reach statistical significance. In addition, the graded prognostic assessment (GPA) appeared to be a better prognostic tool than the recursive partitioning analysis. CONCLUSION: The results of the present study suggest active multimodal treatment including neurosurgery, radiotherapy, and chemotherapy for BM of uterine cervical cancer with single BM, good performance status, histology of small cell carcinoma, and a better GPA.

Brachytherapy and survival in small cell cancer of the cervix and uterus.

PURPOSE: Small cell cancer involving the cervix and uterus is considered the same rare disease, but management is controversial and disparate. Patterns of care and outcomes in the United States are unclear. METHODS AND MATERIALS: Clinical data from patients with small cell cancer of the cervix and uterus were abstracted from the National Cancer Database from 2004 to 2014. Patients with missing clinical stage, incomplete followup, or receiving treatment >90 days from diagnosis were excluded. RESULTS: There were 621 cervical and 95 uterine patients with cancer treated from 2004 to 2014. Compared to patients with a cervix primary site, patients with a uterine primary site were older (median age 64 years vs. 47 years), more likely to present with distant metastatic disease (47% vs. 33%), less likely to receive any pelvic radiation (31% vs. 64%), less likely to receive brachytherapy (3% vs. 27%), more likely to have at least a total hysterectomy (58% vs. 28%), and less likely to receive chemotherapy (74% vs. 88%), all p < 0.05. Brachytherapy was associated with improved overall survival (OS) for patients with locally advanced cervical small cell carcinoma (II-IVA, p = 0.03), but only 38% of patients with Stage II-IVA disease received brachytherapy. For the uterine site, hysterectomy (p = 0.001) and external irradiation (p = 0.03) were associated with improved OS in unadjusted Kaplan-Meier analysis, but only chemotherapy and stage were significantly associated with higher OS in multivariable analysis. CONCLUSIONS: Brachytherapy may improve OS for Stage II-IVA small cell cancer of the cervix but appears underutilized. Brachytherapy was not commonly delivered for uterine primaries.

Case of metastatic small cell carcinoma of the oropharynx successfully treated with image-guided volumetric modulated arc therapy (IG-VMAT): pushing the limits of technology to match treatment intent.

Extrapulmonary small cell carcinomas (EPSCC) are a rare subtype of neuroendocrine tumours which have been documented to arise from a multitude of sites and treatment outcomes are disappointing. The most common site involved in the head and neck region is the larynx and the oropharynx as a primary site has been infrequently reported. The patient presented with bilateral neck swelling and an ulcerated lesion was noted in the base of tongue (BOT). A biopsy revealed small cell carcinoma (SCC) and was confirmed with immunohistochemistry. The final diagnosis after workup was SCC of BOT stage IVc. He received induction chemotherapy to which the tumour responded partially, followed by curative intent chemoradiotherapy and adjuvant chemotherapy. The patient achieved a radiological complete response to treatment and almost all treatment-induced toxicities resolved. An aggressive approach to managing EPSCC is possible with modern radiotherapy techniques, with tolerable treatment-induced toxicities.