Small Cell Neuroendocrine Carcinoma of the Prostate on 18 F-DCFPyL and 18 F-FDG PET/CT.

ABSTRACT: A 51-year-old man with newly diagnosed small cell neuroendocrine carcinoma of the prostate was referred for a staging 18 F-DCFPyL PET/CT, which showed a solitary metastasis in the left acetabulum. Subsequent 18 F-FDG PET/CT showed intense uptake throughout the prostate as well as extensive avid pelvic and thoracic nodal disease and redemonstration of the left acetabular metastasis. Despite initial metabolic response to treatment, subsequent 18 F-FDG PET 8 months later revealed significant progression of nodal disease above and below the diaphragm, as well as multiple new sites of metastases.

Increased 68 Ga-FAPI Activity in Primary Small Cell Neuroendocrine Carcinoma of the Gallbladder.

ABSTRACT: Primary small cell neuroendocrine carcinomas are extremely rare heterogeneous neoplasms. We present 68 Ga-FAPI (fibroblast activation protein inhibitor) PET/CT findings of small cell neuroendocrine carcinoma of the gallbladder in a 57-year-old woman. This rare gallbladder small cell neuroendocrine carcinoma demonstrated intense tracer uptake on 68 Ga-FAPI PET/CT. This demonstrates the potential value of 68 Ga-FAPI PET/CT for evaluation of gallbladder small cell neuroendocrine carcinoma.

Primary small cell carcinoma of the gallbladder diagnosed by PET/CT combined with tumour markers: A case report.

Small cell cancer (SCC) of the gallbladder is a rare and highly aggressive malignancy. We report here a case diagnosed by positron emission tomography/computed tomography (PET-CT) combined with tumour markers. A 51-year-old man presented with pain in his neck, shoulder, back, lumbar and right thigh. Ultrasonography showed an isoechoic mass in the gallbladder, and a magnetic resonance image (MRI) scan showed multiple retroperitoneal occupations and multiple vertebral bone destruction with pathological fractures. Blood analysis showed elevated levels of tumour markers including neuron-specific enolase (NSE) and PET/CT images showed extensive distant metastases. A diagnosis of primary SCC of the gallbladder was made following exclusion of the possibility of metastasis from other organs. The use of biomarkers with immunohistochemical findings and PET/CT imaging, will assist clinicians in the identification and understanding of the pathology of this disease.

Metastatic Small Cell Neuroendocrine Carcinoma of Endometrium: Rare Entity, Rare Presentation.

ABSTRACT: Primary small cell neuroendocrine carcinoma of endometrium is very rare and aggressive carcinoma. Most patients present with metastases at the time of diagnosis and have very poor prognosis. Only very few cases are reported in literature. Here we present a case of 67-year-old woman, who on evaluation for mild pain abdomen was subsequently diagnosed to have metastatic small cell neuroendocrine carcinoma of endometrium on PET/CT scan and biopsy.

Small cell neuroendocrine carcinoma with primary orbital involvement - The unseen, and a review of literature.

Neuroendocrine neoplasms are derived from the epithelial lineages mainly of respiratory tract, with predominant neuroendocrine differentiation. There are only a handful of documented cases of paranasal small cell neuroendocrine carcinomas (SNEC) with primary orbital involvement. Here, the authors describe a 33-year-old male patient with rapidly progressive swelling of the right lower lid with proptosis since 4 weeks. On contrast-MRI orbit, an ill-defined multilobulated mass measuring 3.6 × 3.1 cm with intense homogenous enhancement was seen in the right retrobulbar space involving the right ethmoid sinus. On incisional biopsy, a poorly differentiated mass containing numerous small round blue cells and scanty intervening stroma with prominent necrosis and apoptosis was seen. Immunohistochemistry was strongly positive for synaptophysin. He was diagnosed as a case of SNEC and received chemotherapy, with good response till date of 9 months of follow up. The authors present a literature review and describe challenges in management of a primary orbital SNEC.

Complete resolution of paraneoplastic syndrome of inappropriate antidiuretic hormone secretion following thymic small-cell carcinoma thoracoscopic resection.

Thymic neuroendocrine tumours are rare anterior mediastinal neoplasms often associated with paraneoplastic syndromes. A patient presented with intractable hyponatraemia and a DOTATATE-avid mediastinal mass. Following medical optimization, she underwent thoracoscopic thymectomy with en bloc thymic small-cell carcinoma resection. Her symptoms resolved and her sodium levels normalized. In localized disease, curative-intent, minimally invasive thymic neuroendocrine tumour resection is safe and effective following preoperative staging and paraneoplastic syndrome management.

Mismatched Lesions on 18F-FDG PET and 18F-Fluciclovine PET Images in a Patient With Metastatic Prostate Small Cell Carcinoma.

ABSTRACT: A 65-year-old man with fluciclovine-avid metastatic prostate small cell carcinoma with prostate-specific antigen (PSA) 19.4 ng/mL at diagnosis underwent system therapy and subsequent surgery and achieved hormonal response with PSA <0.1 ng/mL. An 18F-fluciclovine PET/CT scan 3 months after surgery was negative for disease. Although PSA remained <0.1 ng/mL, the rising carcinoembryonic antigen prompted an 18F-FDG PET/CT 6 weeks later. It showed multiple hypermetabolic lesions in the prostatectomy bed, liver, and right iliac bone, suggestive of malignant disease. The FDG-avid prostatectomy lesions were further confirmed on MRI. This case demonstrates that FDG PET/CT has a role in suspected metastatic prostate small cell carcinoma with negative fluciclovine PET examination.

Radiological and Histological Correlation in Small Cell Neuroendocrine Carcinoma of the Breast: A Case Report.

BACKGROUND Primary breast small cell neuroendocrine carcinoma is a rare subtype of breast cancer with about 57 cases reported in the literature. This rare type of cancer represents about 0.1% of breast carcinomas. Recently, the World Health Organization defined this type of cancer as a separate entity from other breast cancer types. The diagnosis of this type of cancer in the breast is difficult because the histological pattern is similar to the small cell neuroendocrine carcinoma of other more common primary sites of origin, including the lung. CASE REPORT A 39-year-old woman presented to our hospital with a left breast mass and recurrent mastitis. Physical examination revealed a painless lump in her left breast with a brown-colored discharge from the nipple, and her child refused breastfeeding from the left breast. A high-density well-defined rounded mass was observed upon mammography in the upper lateral aspect of the left breast. This mass lesion appeared hypoechoic with no posterior acoustic shadowing on ultrasound scan. A core-needle biopsy of the mass was performed and the diagnosis of small cell neuroendocrine carcinoma was rendered after histopathologic examination. Positron emission tomography scanning was helpful in the exclusion of primary origin from other organ sites; thus, the primary breast origin of the tumor was confirmed. CONCLUSIONS This case report provides a comprehensive approach to diagnose this type of small cell carcinoma originating primarily in the breast. The suspicion of this type of breast cancer should be raised if there is presence of characteristic histopathologic findings with the exclusion of any primary origin from other organ sites by the help of imaging studies.

A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer.

Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21-1 (CYFRA 21-1) and C-reactive protein (CRP). The model was first validated in two independent cohorts, and showed a good diagnostic performance across a range of lung tumor types, emphasizing its high specificity and positive predictive value. We next tested its utility in two clinically relevant contexts: assessment of lung cancer risk and nodule malignancy. The scores derived from the model were associated with a significantly higher risk of having lung cancer in asymptomatic individuals enrolled in a computed tomography (CT)-screening program (OR = 1.89; 95% CI = 1.20-2.97). Our model also served to discriminate between benign and malignant pulmonary nodules (AUC: 0.86; 95% CI = 0.80-0.92) with very good specificity (92%). Moreover, the model performed better in combination with clinical factors, and may be used to reclassify patients with intermediate-risk indeterminate pulmonary nodules into patients who require a more aggressive work-up. In conclusion, we propose a new diagnostic biomarker panel that may dictate which incidental or screening-detected pulmonary nodules require a more active work-up.

Combined Simultaneous Multiportal Approach via Minimally Invasive Transciliary and Endoscopic Endonasal Approaches for Tumors Invading Both the Skull Base and the Sinonasal Area.

BACKGROUND: A combined transcranial and transfacial approach has long been the gold standard for surgical management of large tumors with sinonasal and skull base involvement. The extended endoscopic endonasal approach for such pathologies has its advantages, but it has flaws as well, such as anatomic limitations and more ponderous skull base reconstruction and thus higher risk of postoperative complications. Our primary technique for surgical treatment of these pathologies has been a combination of transfacial and minimally invasive transciliary supraorbital keyhole approaches. With the aim to further minimize invasiveness, potential complications, and unsatisfactory aesthetic outcomes during surgical treatment of large tumors invading both the sinonasal area and the skull base, we abandoned the transfacial approach and simultaneously combined the transciliary supraorbital keyhole approach with the endoscopic endonasal approach. METHODS: The well-known microscope-assisted minimally invasive approach via a transciliary supraorbital keyhole craniotomy was combined with the endoscopic endonasal approach. RESULTS: Six patients with different histologic types of tumors affecting the sinonasal area and the skull base were operated on. The mean operative time was 3 hours, there were no unexpected intraoperative or postoperative complications, and total tumor removal was achieved in each patient. None of the patients experienced complications associated with the surgery during follow-up. CONCLUSIONS: Our combined simultaneous multiportal approach enables total tumor eradication with reduced operative time and is associated with minimal intraoperative and postoperative complications, low mortality rate, and excellent cosmetic results.

Small Cell Neuroendocrine Carcinoma of Paranasal Sinuses: Radiologic Features in 14 Cases.

PURPOSE: The purpose of this study was to explore the characteristic computed tomography (CT) and magnetic resonance (MR) features of small cell neuroendocrine carcinoma (SNEC) of paranasal sinuses. MATERIALS AND METHODS: Computed tomography (n = 8) and MR (n = 14) images and clinical findings from 14 patients with SNEC of paranasal sinuses were retrospectively reviewed. RESULTS: Eight lesions were located in the ethmoidal sinus, 4 in the maxillary sinus, and 2 in the sphenoid sinus. Small cell neuroendocrine carcinoma of the sphenoid sinus showed bilateral asymmetry patterns. On CT images, bony changes were visible in all 8 cases. On MR, 4 cases contained hemorrhage, and 10 cases contained cystic or necrotic areas. All cases demonstrated marked heterogeneous enhancement, with half showing a "cribriform-like" or "geographic" appearance. The nasal cavity was the most common site invaded by SNEC of paranasal sinuses, followed by the orbits. A time-signal intensity curve examination showed a washout-type pattern in all but 1 case. The mean ± SD apparent diffusion coefficient value was 0.702 ± 0.112 (×10-3 mm2/s). According to the Dulguerov staging system, 9 tumors were staged as N0 (1 T1, 1 T2, 5 T3, and 2 T4). The recurrence rate was 64.3%. CONCLUSIONS: Some characteristics of radiological findings can provide important clues for preoperative diagnosis.

New lung mass in a patient with granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a potentially lethal ANCA-associated small-vessel vasculitis characterized by a typical triad of upper respiratory tract, lung, and kidney involvement. Lung involvement in GPA occurs in 25-80% of cases. The most common radiographic and computed tomography (CT) abnormalities of pulmonary GPA are lung nodules and masses, very often multiple and with cavitation. As there are various clinical presentations, the diagnosis of GPA can be challenging, and the illness is difficult to distinguish from other diseases such as infection or malignancy. Following the improved survival rates in patients with GPA, there is accumulating evidence to suggest an increased occurrence of different types of cancer. Exposure to cyclophosphamide seems to be one of its main causes. We present the case of a patient with chronic GPA who was hospitalized owing to a new infiltrate in the lung, suggesting relapse of the disease, and finally diagnosed with small cell lung cancer. Data regarding lung cancer in GPA patients are limited. While there are some case reports and short case series in the literature, there are no detailed data regarding an association between CYC exposure and lung cancer development in vasculitis. It is necessary to consider the causes of pulmonary masses other than a GPA relapse. Bronchoscopy with biopsy and histopathological examination are crucial in proper differential diagnosis. GPA patients require long-term follow-up to monitor for the development of complications during treatment.

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.

Self-Distinguishing and Stimulus-Responsive Carrier-Free Theranostic Nanoagents for Imaging-Guided Chemo-Photothermal Therapy in Small-Cell Lung Cancer.

Lack of tumor targeting and low drug payload severely impedes various nanoagents further employed in small-cell lung cancer (SCLC). Therefore, how to develop a new targeting ligand and enhance drug payload has been an urgent need for SCLC therapy. Herein, we first sift and verify that capreomycin (Cm) has a high affinity toward CD56 receptors overexpressed on SCLC cells. Motivated by the concept of self-targeted drug delivery, Cm is selected as the specific targeting ligand toward CD56 receptors and chemodrug doxorubicin (Dox) is adopted to be covalently linked via the redox-responsive disulfide linkage. The synthesized self-distinguishing prodrug (Dox-ss-Cm) and FDA-approved photosensitizer indocyanine green (ICG) as structural motifs can be self-assembled into theranostic nanoagents (ICG@Dox-ss-Cm NPs) within an aqueous solution. Such carrier-free nanoagents with high drug payload can exert targeted on-demand drug release under multiple stimuli of intracellular lysosomal acidity, glutathione (GSH), and an external near-infrared (NIR) laser. Besides, our nanoagents can be specifically self-targeted to SCLC sites in vivo and self-distinguishing via SCLC cells in vitro; thus, they decrease the undesirable effects on normal tissues and organs. Further in vitro and in vivo studies uniformly confirm that such nanoagents show highly synergistic effects for SCLC chemo-photothermal therapy (PTT) under the precise guidance of NIR fluorescence (NIRF)/photoacoustic (PA) imaging. Taken together, our work can provide a novel and promising strategy for the targeted treatment of SCLC.