David Geffen School of Medicine at UCLA Los Angeles, CA
Maxwell M. Wang, BA1, Simi Singh, MD2; 1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2David Geffen School of Medicine at UCLA, Porter Ranch, CA
Introduction: Esophageal neuroendocrine carcinoma (eNEC) is a rare (< 3% of US esophageal cancers) and aggressive malignancy (< 5% 5-year overall survival [OS]) that lacks treatment guidelines. The timing and nature of relapse after successful treatment is not well characterized. We report a case of rapidly extensive recurrence after complete pathologic response (cPR) to definitive chemoradiation (dCRT) and maintenance therapy (MT).
Methods: A 51 year old woman with no medical history presented with 3 weeks of epigastric pain, mild acid reflux, and dysphagia. She denied smoking or alcohol use. Pantoprazole, previously prescribed by her primary care doctor, did not help. Endoscopy revealed a 4 cm, necrotic, mid-esophageal ulcer (Fig 1) with NEC histology (Fig 2). Staging with endoscopic ultrasound, brain MRI, and PET-CT determined T3N2M0 disease (Fig 3).
dCRT (cisplatin/etoposide) was completed in 6 months with symptom resolution. PET-CT revealed resolution of the initial FDG-avid ulcer and lymph nodes (LNs) (Fig 3). Endoscopy with esophageal biopsies was normal, confirming cPR (Fig 1).
After 3 months of atezolizumab for subsequent MT, chest pain occurred. PET-CT showed FDG-avid masses in the liver, bones, thoracic LNs, and subcutaneous tissue (Fig 3). Biopsy of the hepatic lesions confirmed metastatic NEC despite a normal repeat endoscopy (Fig 1). Discussion: This case is unusual given our patient’s atypical demographic for esophageal carcinoma. eNEC’s median age of diagnosis is 62 years with male preference (73%). About 50% and 25% of patients have a smoking and alcohol abuse history, respectively.
Selecting dCRT over radical esophagectomy maximized our patient’s quality of life while accepting a potentially suboptimal OS. Recent data on stage III eNEC patients show a 43 month median OS and 50% 3-year OS for those receiving surgery with neoadjuvant chemotherapy, versus 15 months and 15% for those receiving non-surgical treatment.
Innovative MT was essential given eNEC’s risk for relapse and lack of established protocols. Our trial of atezolizumab is the first reported off-label use of immune checkpoint inhibition in eNEC. Ongoing phase II trials are studying the efficacy of anti-PD-1 monotherapy and dual anti-PD-1/anti-CTLA-4 therapy in eNEC.
Relapse only 4 months after cPR emphasizes eNEC’s insidious and early metastatic course. Given eNEC’s nature, it is imperative that empathic, shared decision-making be an essential component of patient-centered care for this rare malignancy.
Comparison of endoscopy findings at initial presentation (July 2019), cPR after dCRT (December 2019), and recurrence (April 2020). In July, there was a 4 cm, necrotic, half-circumferential, cratered ulcer spanning between 28-34 cm from the incisors. Esophagus was otherwise unremarkable, aside from mild reflux esophagitis at the GE junction. Stomach and duodenum (to the second portion) were unremarkable. In December, there was near complete resolution of the original ulcerated lesion. Biopsies returned as normal squamous mucosa, without intestinal metaplasia, dysplasia, or malignancy. In April, the appearance of the esophagus was generally similar to that in December, aside from mild re-ulceration of the lesion now measuring 1 cm. Biopsies still revealed normal squamous mucosa, with some necrotic debris. A: Necrotic ulcer, approached from the normal, proximal esophagus; B: Direct view of the ulcer in the mid to distal esophagus; C: Former lesion site, approached from the proximal esophagus; D: Former lesion site, exiting toward the distal esophagus; E: Former lesion site, with mild raising and ulceration, F: Unremarkable distal esophagus.
Biopsy histopathology (from July endoscopy) confirming primary esophageal neuroendocrine carcinoma. Homogeneous, small, round, purple/blue cells on H&E staining are characteristic of this high grade, poorly differentiated neuroendocrine malignancy. Immunohistochemistry was positive for specific neuroendocrine markers: synaptophysin, chromogranin, and CD56. The neoplasm was strongly Ki-67 positive (80-90% of cells), reflecting its highly proliferative nature. Staining was negative for adenocarcinoma markers, including mucicarmine and CDX2. Negative staining for CD45, SOX10, and CD30 ruled out hematopoietic, neural crest, or lymphatic tissue origin, respectively.
Comparison of PET-CT findings at initial staging (August 2019), cPR after dCRT (December 2019), and recurrence (April 2020). In August, there were no distant metastases (including a negative brain MRI). Increased FDG activity was confined to the mid-esophageal mass (A, B) and lymph nodes within the gastrohepatic ligament (C). CT demonstrated a 2.6 x 2.2 cm, right lower esophageal, eccentric mass with central necrosis and positive gastrohepatic LNs up to 1.3 cm. Imaging was negative for intrathoracic or cervical lymphadenopathy. In December, there was near complete resolution of abnormal FDG uptake at the esophageal site (D, E), with decreased size and reduced FDG uptake at the gastrohepatic LNs (F). In April, there was interval development of FDG-avid masses within the liver (G), bilateral iliac bones (G), L2/L3 vertebral bodies (H), left scapula, right posterior sacrum, thoracic lymph nodes (I), and right chest wall subcutaneous tissue (J). White arrows indicate areas of abnormal FDG-avidity corresponding to malignant lesions.
Disclosures: Maxwell Wang indicated no relevant financial relationships. Simi Singh indicated no relevant financial relationships.