Gastric medullary carcinoma (GMC) is a very rare histological variant (1–4% of gastric tumours). Patients diagnosed with GMC are usually male and over the age of 60. It has a better prognosis than gastric adenocarcinoma.1 We present a case of GMC, discussing the therapeutic options.
The patient was an 80-year-old man with hepatitis C treated with ledipasvir/sofosbuvir as his only relevant medical history. In a study for iron deficiency anaemia, with normal tumour markers, a gastroscopy was performed, showing a large ulcerated lesion in the gastric antrum from which biopsies were taken (Fig. 1A). Histological examination of the endoscopic biopsy shows a neoplastic proliferation of epithelial cells arranged in nests, trabeculae and ill-defined tubules with intraepithelial lymphocytosis compatible with GMC. Immunohistochemical study of repair proteins (MLH1, MSH2, MSH6, PMS2) showed normal expression; Epstein-Barr virus study by in situ hybridisation and HER-2 membrane receptor were negative (Fig. 1B).
CT scan of chest, abdomen and pelvis showed a thickening of the gastric wall with no obvious signs of local invasion (Fig. 1C) and a suspicious lymphadenopathy in the coeliac trunk, staged as T3N2M0 according to the 8th edition of the AJCC-TNM classification.
In a multidisciplinary committee for gastrointestinal tumours, it was decided to administer neoadjuvant chemotherapy with four cycles of FOLFOX. After neoadjuvant treatment, a re-staging PET-CT scan showed a decrease in tumour size, with no enlarged lymph nodes or gastric tumour uptake. A laparoscopic subtotal gastrectomy was performed. The post-surgical pathology study showed complete tumour response, with 15 negative isolated lymph nodes and no lymphovascular or perineural invasion. The patient had no major postoperative complications (Clavien I), and chemotherapy treatment was restarted with four more cycles of 5-fluorouracil, with no recurrence in the six months that had elapsed.
The first description of GMC was made by Hirakawa in 1975.2 GMC has been associated with Epstein-Barr virus (90% of patients) and microsatellite instability (6–10% of cases).3 However, the mechanism of viral oncogenesis is unclear. It should be noted that neither of these two aetiopathogenic factors was present in our case, which makes it an even more atypical case of GMC. Lymphoepithelioma-like gastric carcinoma (LELC) has traditionally been considered synonymous with GMC. However, there are histological features that differentiate them: GMC is arranged in syncytial sheets with well-defined peripheral margins and peritumoural lymphocyte arrangement, whereas LELC is arranged in small clusters divided by a large number of intratumoural lymphocytes.2
GMC is normally diagnosed in early stages, usually incidentally during gastroscopy. The most common location of this tumour is at the level of the cardia and gastric body. The clinical signs and symptoms are often non-specific, ranging from asymptomatic patients to severe cases of tumour-related gastric perforation.4 Definitive diagnosis is obtained by histopathology and immunohistochemistry. The differential diagnosis is with lymphoepithelioma-like gastric carcinoma, gastric MALT lymphoma and gastrointestinal stromal tumours.4
Due to its low incidence, treatment is not standardised, but complete tumour resection is the therapeutic option of choice. In small tumours, endoscopic submucosal resection may be valid. In the rest of GMC, as in our case, the treatment tends to be surgical resection.4 There are as yet no conclusive data on the best chemotherapy regimens and their timing.5 The prognosis for GMC is good, with a higher five-year survival rate (72%) than for other gastric cancers (42%).4 Lymphovascular invasion is relatively common, although not in our case. Haematogenous metastases to the liver, although rare, are the main cause of death.6
In conclusion, GMC is a rare histological variant of gastric cancer. The diagnosis can made in the case of typical morphological findings. Testing positive for Epstein-Barr virus or microsatellite instability support the diagnosis, although these abnormalities are not always present. As there are no specific therapeutic regimens for GMC, the usual ones for gastric cancer are adopted. In our case, the administration of neoadjuvant therapy resulted in a complete tumour response in the surgical specimen, which opens up new debates on the need for surgery in GMC.
FundingNo funding was received for preparing this manuscript.
Conflicts of interestThe authors declare that they have no conflicts of interest.
