A Case of Gastric Adenocarcinoma With Pernicious Anemia, Polyneuropathy, and Subacute Combined Degeneration Caused by Autoimmune Gastritis

Dear Editor,

Vitamin B12 deficiency causes pernicious anemia (PA) and neurological diseases such as subacute combined degeneration (SCD) of the spinal cord, peripheral neuropathy, and neuropsychiatric manifestations.¹ The most common cause of severe vitamin B12 deficiency worldwide is autoimmune gastritis (AIG). Individuals with PA have been suggested as having an increased risk of gastric cancer.² Here we report a very rare case of vitamin B12 deficiency caused by AIG with gastric adenocarcinoma, along with hematological and neurological complications.

A 64-year-old male presented with aggravated gait disturbance for 2 weeks. He reported experiencing distal paresthesia and minimally unstable gait 3 years previously. In the month before this presentation, his oral intake was significantly reduced due to abdominal discomfort. The patient had no history of smoking, alcohol consumption, diabetes mellitus, recent immunization, or fever. He reported that he had received blood transfusions several times 3 years previously due to anemia. A physical examination revealed a palpable mass in the left upper abdomen. A neurological examination revealed symmetric distal weakness in the lower extremities (knee extension, medical research council [MRC] grade IV; ankle dorsiflexion, MRC grade III; and toe dorsiflexion, MRC grade II), decreased sensation in all modalities below the T12 level, and absent deep tendon reflex in the lower extremities. The plantar response was flexor. Dysmetria was noted in heel-to-shin and finger-to-nose tests. The patient had difficulty in performing a tandem gait and Romberg tests. Laboratory tests disclosed microcytic hypochromic anemia: hemoglobin, 9.9 g/dL (reference range 13.0–18.2 g/dL); mean corpuscular volume (MCV), 81.4 fL (85.1–98.4 fL); mean corpuscular hemoglobin concentration, 31.3% (32.6%–35.1%); and iron, 51 ug/dL (65–157 µg/dL). Nerve conduction studies indicated axonal sensorimotor polyneuropathy in the lower extremities, and MRI revealed a subtle high-signal area in the posterior portion of the cervical spinal cord (Fig. 1A and B). Abdomen CT indicated a lobulated heterogeneous enhanced gastric mass with shallow ulceration (Fig. 1C). Gastroduodenoscopy revealed erythematous and atrophic mucosal changes in the antrum and body and an ulcerofungating mass from the distal antrum to the duodenal bulb (Fig. 1D). A biopsy confirmed tubular adenocarcinoma. Both the rapid urease test and polymerase chain reaction were negative for Helicobacter pylori. Further laboratory tests revealed the following results: vitamin B12, 93.6 pg/mL (reference range 211–946 pg/mL); thiamin, 28.5 nmol/L (66.5-200 nmol/L); pepsinogen I level, 18.3 µg/L (>70 µg/L); pepsinogen I/II ratio, 0.7 (>3.0); homocysteine, 35.45 µmol/L (5.46–16.2 µmol/L); methylmalonic acid, 0.43 µmol/L (<0.40 µmol/L); and gastrin, 352 pg/mL (13–115 pg/mL). His blood was positive for parietal cell and anti-intrinsic factor antibodies. Serum folate levels were normal. A peripheral blood smear (PBS) indicated a mixed population of microcytic and macrocytic RBCs with increased distribution widths. After the diagnosis of gastric adenocarcinoma, axonal polyneuropathy, and SCD of the spinal cord caused by AIG and thiamine deficiency related to malnutrition, intravenous thiamine and intramuscular cyanocobalamin were initiated. Chemotherapy was administered before surgery for the gastric cancer. The patient was able to walk without assistance after 4 months. Distal paresthesia was mildly improved, but this was aggravated after the third chemotherapy cycle.

Fig. 1. Cervical spine MRI, abdomen CT and gastroscopy of the patient. A and B: A sagittal T2-weighted MRI scan (A) indicating no definite signal change, but an axial T2-weighted image at C4 (B) indicates a high-signal area (arrow) in the posterior column. C: Abdomen CT revealed a lobulated heterogeneous enhanced gastric mass (arrowheads) with perigastric tumor infiltration including into the adjacent omentum and lymph node. D: Gastroscopy demonstrated a mucosal-protruding lesion with friable mucosa and central ulceration with exudate.

Laboratory tests including MCV, PBS, serum cyanocobalamin, methylmalonic acid, and homocysteine are vital in diagnosing vitamin B12 deficiency.³ Macrocytosis is one of the earliest features in a PA diagnosis. In AIG, the loss of parietal cells causes achlorhydria, which affects dietary iron absorption.⁴ AIG is also a common cause of combined iron and vitamin B12 deficiencies.⁵ When coexisting with iron deficiency, the initial complete blood count can show microcytic or normal MCV and mask the macrocytic expression of megaloblastic anemia.⁵,⁶ This may contribute to a delayed diagnosis and altered treatment, as occurred in our patient.

The pathogenesis of gastric cancer accompanied by AIG is thought to begin with chronic inflammation that leads to tissue atrophy and subsequently intestinal metaplasia, which is considered a precursor lesion.⁷ Chronic achlorhydria and the resulting high gastrin levels also stimulate the proliferation and hyperplasia of both neuroendocrine and nonspecialized epithelial cells, promoting the development of gastric carcinoid tumors and carcinomas.⁸,⁹

Early diagnosis is crucial because there is no established treatment for AIG, but this is difficult due to its broad clinical spectrum; for example, a definitive diagnosis was delayed by more than 10 years in several patients.¹⁰ Clinical awareness of AIG and its association with gastric cancer can therefore be the first step in preventing hematological and neurological complications and identifying gastric cancer early.

Availability of Data and Material

The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.