Improved survival with palliative surgery and chemotherapy for Mixed adenoneuroendocrine carcinoma of the gastroesophageal junction with liver metastases.

Mixed adenoneuroendocrine carcinomas (MANEC) are characterized by the simultaneous presence of an exocrine glandular component and a neuroendocrine component. They are rare, heterogeneous tumors that present a very variable morphological/clinical profile and prognosis. We present the case of a 69-year-old man with controlled hypertension, who reported progressive dysphagia over the previous 4 months and weight loss. Endoscopy revealed a neoproliferative mass in the cardia with stenosis, and biopsy demonstrated a poorly differentiated adenocarcinoma. The CT scan(Fig.1A)showedmucosalandsubmucosalthickeningof5 cm of the cardia (probable T2–T3), inconclusive lymphadenopathy at the gastrohepatic ligament, but no evidence of distant metastasis. Tumormarkerlevelswere:CEA:18.7 ng/mLandCA19-9:32 U/mL. During surgery, a mass was identified in the esophagogastric junction that infiltrated the hiatus as well as a peripheral single hepatic metastasis in segment III, but no other tumors were found by intraoperative ultrasound. Since the metastasis was solitary and peripheral, we decided to perform hepatic metastasectomy as it did not imply greater risks for the patient. Subsequently, esophagogastrectomy was performed with esophagojejunal intramediastinal Roux-en-Y anastomosis as a palliative method. The macroscopic study of the surgical piece showed circumferential involvement of the esophagogastric junction and free margins (proximal margin 4 cm). The pathology study identified a grade 3 (WHO 2010) MANEC tumor with Ki-67 index >20%. One infiltrated lymph node was isolated from 28 studied. The liver lesion was positive for MANEC tumor with negative HercepTest. The final stage was pT3N3M1 (AJCC/UICC TNM 7th Edition), therefore the patient received 6 cycles of adjuvant chemotherapy with carboplatin and etoposide. After 6 months, CT and SPECT/CT were normal and showed no evidence of recurrence. However, after 14 months, another CT study (Fig. 1B) showed hepatic lesions compatible with metastasis in segments II, VI and VII, therefore another line was initiated with 6 cycles of carboplatin+5-fluorouracil. The patient presented a very favorable response (RECIST criteria), with a decrease in the size of the metastases greater than 50%. The 32-month CT scan showed stable disease with no local recurrence and no growth of the metastases, which are currently smaller than 1 cm (Fig. 1C). MANEC are characterized by a neuroendocrine component, marked by the expression of synaptophysin (75%–90%), chromogranin (60%–70%) and CD56 (50%), and an exocrine glandular component, identified by its structure with positivity for cytokeratins 7 and 20 as well as CEA. The exocrine component generally has an adenocarcinoma histology, but cases of squamous cells have also been described in tumors of the esophagus and anorectal region. In our case, immunohistochemical staining of the liver lesion showed positivity for CDX2, synaptophysin and chromogranin A (Fig. 2A–C). Based on these results, it was concluded that the liver lesion was a metastatic MANEC lesion of the esophagogastric junction (Fig. 2D and E) that also c i r e s p . 2 0 1 8 ; x x ( x x ) : x x x – x x x